id
stringlengths 11
17
| article_id
stringlengths 8
11
| path
stringlengths 11
60
| section_title
stringlengths 1
1.33k
| educational_score
float64 0
5.16
| domain
stringclasses 4
values | document_type
stringclasses 5
values | domain_scores
listlengths 0
3
| document_type_scores
listlengths 0
4
| text
stringlengths 1
110k
| authors
listlengths 0
8.02k
| article_url
stringlengths 3
63
| license_type
stringclasses 1
value | license_url
stringclasses 15
values | language
stringclasses 45
values | language_score
float64 0
1
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
39057216_p52
|
39057216
|
sec[3]/p[15]
|
4. Discussion
| 4.085938 |
biomedical
|
Study
|
[
0.99951171875,
0.00020492076873779297,
0.0004246234893798828
] |
[
0.99951171875,
0.00015473365783691406,
0.0004246234893798828,
0.000041961669921875
] |
The data revealed that the two tested EOs, O. majorana and R. officinalis , exhibited a varied level of activation and inhibition of the detoxification enzymes, α-esterase and GST, over time post-treatment. The increased activity of detoxification enzymes following xenobiotic treatment may represent a direct adaptive response aimed at neutralizing toxic compounds and detoxifying insecticides, thereby enhancing survival rates . Furthermore, Ref. suggested that the induction of detoxification enzymes is associated with increased tolerance of insects to insecticides.
|
[
"Fatma S. Ahmed",
"Walid S. Helmy",
"Nawal Abdulaziz Alfuhaid",
"Moataz A. M. Moustafa"
] |
https://doi.org/10.3390/insects15070483
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057216_p53
|
39057216
|
sec[3]/p[16]
|
4. Discussion
| 4.105469 |
biomedical
|
Study
|
[
0.99951171875,
0.00018405914306640625,
0.0004858970642089844
] |
[
0.99951171875,
0.00020575523376464844,
0.00018513202667236328,
0.00004082918167114258
] |
However, in the current work, the most common effect of both tested EOs on α-esterase and GST was inhibition. Insects utilize such detoxification enzymes as α-esterase and GST to metabolize the secondary metabolites of plants, thereby protecting themselves from oxidative damage . This suggests that the mortality of A. ipsilon larvae following exposure to R. officinalis and O. majorana EOs might be a consequence of the reduced activity of α-esterase and GST. Our findings suggest that α-esterase and GST play a part in the detoxification process of O. majorana and R. officinalis in A. ipsilon larvae. However, further research, at the molecular level, could provide more precise insights.
|
[
"Fatma S. Ahmed",
"Walid S. Helmy",
"Nawal Abdulaziz Alfuhaid",
"Moataz A. M. Moustafa"
] |
https://doi.org/10.3390/insects15070483
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057216_p54
|
39057216
|
sec[3]/p[17]
|
4. Discussion
| 4.121094 |
biomedical
|
Study
|
[
0.9990234375,
0.00024044513702392578,
0.0007190704345703125
] |
[
0.99951171875,
0.00013494491577148438,
0.0003190040588378906,
0.00003820657730102539
] |
Our current results align with those of , who observed varied levels in the activity of AChE, carboxylesterase, and GST in the cereal weevil, Sitophilus zeamais , in response to Melaleuca alternifolia EO over time post-treatment. However, the varied level recorded in their study in the EO-treated insects was consistently lower than that recorded in the untreated insects at all time intervals, presenting a contrasting result with ours. This variation between our study and theirs could be attributed to the different concentrations used; they used a lethal concentration (LC 50 ), while we used sublethal ones (LC 10 and LC 30 ). Additionally, they employed a fumigation method to treat their insects, whereas we used the leaf dipping technique. This latter point suggests a potential future comparative study testing the same EOs using different bioassay methods to identify the most efficient bioassay method for these EOs against A. ipsilon larvae.
|
[
"Fatma S. Ahmed",
"Walid S. Helmy",
"Nawal Abdulaziz Alfuhaid",
"Moataz A. M. Moustafa"
] |
https://doi.org/10.3390/insects15070483
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057216_p55
|
39057216
|
sec[3]/p[18]
|
4. Discussion
| 4.105469 |
biomedical
|
Study
|
[
0.99951171875,
0.00030994415283203125,
0.00037407875061035156
] |
[
0.986328125,
0.00033402442932128906,
0.01322174072265625,
0.00010955333709716797
] |
Furthermore, the inhibition trend of detoxification enzymes by the tested EOs in the current work highlights the potential of using these EOs to enhance the toxicity of synthetic insecticides as previously suggested by . In accordance with this suggestion, reported that various plant EOs have been shown to inhibit detoxification enzymes such as GST and cytochrome P450 monooxygenases of Aedes aegypti and Anopheles gambiae , both pyrethroid-susceptible and pyrethroid-resistant strains, increasing the efficacy of pyrethroids against the resistant populations of these pests. Additionally, lemongrass EO was found to synergize the toxic effect of certain insecticides on Bemisia tabaci adults . These findings suggest that EOs could be valuable synergistic agents in conventional insecticides. Future research should focus on exploring the precise mechanisms of enzyme inhibition by these EOs, synergistic effects in various pest management scenarios, and ensuring environmental safety. Large-scale field trials are also recommended to assess the practicality and long-term benefits of integrating EOs with traditional insecticides in pest control programs across urban, public health, and agricultural settings.
|
[
"Fatma S. Ahmed",
"Walid S. Helmy",
"Nawal Abdulaziz Alfuhaid",
"Moataz A. M. Moustafa"
] |
https://doi.org/10.3390/insects15070483
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057216_p56
|
39057216
|
sec[3]/p[19]
|
4. Discussion
| 4.1875 |
biomedical
|
Study
|
[
0.99951171875,
0.00024771690368652344,
0.00037479400634765625
] |
[
0.99951171875,
0.00016832351684570312,
0.00024771690368652344,
0.00004965066909790039
] |
The molecular docking results indicated that terpinene-4-ol and α-pinene, the major constituents of O. majorana and R. officinalis EOs, respectively, exhibited favorable energy scores (S); −4.51 and −4.29 Kcal/mol, respectively, which closely resemble the score of the diethyl hydrogen phosphate (DPF) ligand (−4.67). This alignment with the toxicity assay data further supports the observation that O. majorana is more toxic than R. officinalis to A. ipsilon larvae. Additionally, the molecular docking results reinforce our earlier hypothesis, initially derived from the biochemical analysis of detoxification enzymes, regarding the involvement of the detoxification enzyme α-esterase in the response of A. ipsilon larvae to both tested EOs.
|
[
"Fatma S. Ahmed",
"Walid S. Helmy",
"Nawal Abdulaziz Alfuhaid",
"Moataz A. M. Moustafa"
] |
https://doi.org/10.3390/insects15070483
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057216_p57
|
39057216
|
sec[4]/p[0]
|
5. Conclusions
| 4.140625 |
biomedical
|
Study
|
[
0.9990234375,
0.0002353191375732422,
0.0007448196411132812
] |
[
0.99951171875,
0.00013363361358642578,
0.00032806396484375,
0.00004035234451293945
] |
This study indicates that the Na+-K+ pump may be a primary target for Rosmarinus officinalis . Additionally, the Mg 2+ /Ca 2+ -ATPase and Ca 2+ pumps may also be targeted by this EO. However, while Origanum marjoram may influence these pumps, they might not be its primary targets. Furthermore, the findings regarding detoxification enzymes suggest that α-esterase and GST play roles in the detoxification process of these EOs in A. ipsilon larvae. Overall, O. majorana and R. officinalis EOs can be promising insecticides in organic farming and IPM programs for A. ipsilon management. Additionally, in silico studies could serve as a powerful tool to validate and enhance the understanding of the toxicity and biochemical data. To conclude, our research provided good insights; however, a more granular understanding of our results can be achieved through subsequent research employing advanced molecular and electrophysiological methods.
|
[
"Fatma S. Ahmed",
"Walid S. Helmy",
"Nawal Abdulaziz Alfuhaid",
"Moataz A. M. Moustafa"
] |
https://doi.org/10.3390/insects15070483
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p0
|
PMC11276877
|
sec[0]/p[0]
|
1. Introduction
| 3.912109 |
biomedical
|
Study
|
[
0.99951171875,
0.00039267539978027344,
0.00020575523376464844
] |
[
0.5166015625,
0.408447265625,
0.07305908203125,
0.0019683837890625
] |
Candidiasis is one of the most common opportunistic fungal infections, especially in the healthcare environment. This disease can be caused by different species of Candida ; however, infections with Candida albicans are the most common . C. albicans is a commensal organism that can be found in different parts of the human body such as the gastrointestinal and reproductive tracts, mouth, and skin without causing damage to the host . However, in response to some stimuli, such as certain types of immunodeficiency, a disturbance in the microbiota balance, or the presence of lesions in the epithelium, this fungus can become an important human pathogen .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p1
|
PMC11276877
|
sec[0]/p[1]
|
1. Introduction
| 3.699219 |
biomedical
|
Other
|
[
0.9970703125,
0.0019216537475585938,
0.0007824897766113281
] |
[
0.03070068359375,
0.60302734375,
0.364013671875,
0.0024776458740234375
] |
The most common forms of candidiasis are vulvovaginal, oral, and esophageal, and in more severe cases, this pathogen can reach the bloodstream and spread to other organs . According to the World Health Organization (WHO), patients with invasive candidiasis can be hospitalized for weeks, sometimes even months, with a mortality rate ranging from 20% to 50%. In light of these reports, the WHO has designated this species as a priority fungal pathogen for public health development and action .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p2
|
PMC11276877
|
sec[0]/p[2]
|
1. Introduction
| 3.804688 |
biomedical
|
Study
|
[
0.99951171875,
0.000354766845703125,
0.00016760826110839844
] |
[
0.51416015625,
0.2464599609375,
0.2374267578125,
0.00196075439453125
] |
C. albicans has several well-characterized virulence factors which can contribute to pathogenesis . These include the ability of C. albicans to transition between different morphological forms , its production of adhesins , its metabolic plasticity, its secretion of enzymes, and its ability to form biofilms . Among these, the last one is a major concern in clinical practice .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276877_p3
|
PMC11276877
|
sec[0]/p[3]
|
1. Introduction
| 3.941406 |
biomedical
|
Study
|
[
0.99951171875,
0.00042128562927246094,
0.00012242794036865234
] |
[
0.751953125,
0.08709716796875,
0.1591796875,
0.0017137527465820312
] |
Biofilms are microbial communities strongly adhered to a surface and surrounded by an extracellular matrix . In the clinical setting, these communities pose an important threat to human health due to their intrinsic high resistance to antimicrobials and to the immune system . Biofilms are closely associated with the long-term use of many medical devices such as catheters, pacemakers, and implants , and C. albicans is considered one of the most common microorganisms causing device-associated infections .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p4
|
PMC11276877
|
sec[0]/p[4]
|
1. Introduction
| 3.933594 |
biomedical
|
Review
|
[
0.99853515625,
0.0010175704956054688,
0.00037741661071777344
] |
[
0.12408447265625,
0.1190185546875,
0.7548828125,
0.0018968582153320312
] |
Azoles are the most used antifungal class in the treatment of candidiasis. Among the advantages of this group of antifungals is the possibility of oral administration, the low costs of treatment, their limited toxicity, and their broad spectrum of action . However, C. albicans biofilms present an intrinsic resistance to azoles, demanding the use of other more toxic and/or expensive antifungals to treat biofilm-associated infections and reinforcing the need to develop better antifungal therapies .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276877_p5
|
PMC11276877
|
sec[0]/p[5]
|
1. Introduction
| 4.085938 |
biomedical
|
Review
|
[
0.998046875,
0.0012369155883789062,
0.0007500648498535156
] |
[
0.084228515625,
0.006023406982421875,
0.9091796875,
0.0007519721984863281
] |
In the last two decades, antimicrobial peptides (AMPs) have been attracting increasing attention in the development of new therapeutic strategies to treat infectious diseases . AMPs are small molecules present in several organisms and are an effective part of their innate immune response against pathogens . In general, they are cationic, amphipathic, and have a broad spectrum of activity against various microorganisms . Their main mechanism of action is the physical damage of microbial membranes in a receptor-independent way, which is less prone to the development of antimicrobial resistance . However, among the obstacles in the clinical development of therapies using AMPs is the toxicity of some AMPs to mammalian cells . A strategy to overcome this problem is the use of AMPs in combination with other antifungals, reducing their working concentrations to safe levels and avoiding the problem of resistance development .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276877_p6
|
PMC11276877
|
sec[0]/p[6]
|
1. Introduction
| 4.09375 |
biomedical
|
Study
|
[
0.99951171875,
0.00030231475830078125,
0.00015842914581298828
] |
[
0.9990234375,
0.0002987384796142578,
0.00041556358337402344,
0.00007218122482299805
] |
In this context, we evaluated the combined in vitro and in vivo action of the scorpion venom-derived antimicrobial peptide ToAP2 and NDBP-5.7 with Fluconazole or Amphotericin B against C. albicans biofilms.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p7
|
PMC11276877
|
sec[1]/sec[0]/p[0]
|
2.1. Synergism between ToAP2 with Antifungals in Different Stages of Biofilm Formation
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
0.0002872943878173828,
0.0002391338348388672
] |
[
0.99951171875,
0.00016820430755615234,
0.0003597736358642578,
0.00005412101745605469
] |
The impact of combining ToAP2 with either Amphotericin B or fluconazole was assessed during both the early and mature phases of biofilm formation using the SynergyFinder Plus package version 3.10.3 . Our results revealed no significant synergistic effect in the combinations of the peptide with Amphotericin B during both phases of biofilm formation . The mean synergy score was 3.16 ( p -value = 4.95 × 10 −1 ) for the initial phase and 10.52 ( p -value = 7.32 × 10 −2 ) for mature biofilms .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276877_p8
|
PMC11276877
|
sec[1]/sec[0]/p[1]
|
2.1. Synergism between ToAP2 with Antifungals in Different Stages of Biofilm Formation
| 4.199219 |
biomedical
|
Study
|
[
0.99951171875,
0.00033402442932128906,
0.00019633769989013672
] |
[
0.9990234375,
0.00023257732391357422,
0.0005974769592285156,
0.00007522106170654297
] |
In contrast, the combinations of ToAP2 with fluconazole exhibited a synergistic effect in both phases of biofilm formation. Specifically, combining ToAP2 at concentrations of 12.5 μM or higher with any of the tested concentrations of fluconazole (1.62, 3.25, 6.5 μM) resulted in a reduction of over 50% in the biofilm . The highest synergy score (44.19 ± 2.02; p -value = 8.60 × 10 −23 ) was observed at concentrations of 12.5 μM of ToAP2 and 0.52 μM of fluconazole . Similarly, in the mature biofilm, the highest score was achieved with the combination of 100 μM ToAP2 and 0.52 μM fluconazole (synergy score: 59.27 ± 9.46; p -value = 7.72 × 10 −4 ) . The synergy scores reflect the average excess response resulting from drug interactions. According to this, a synergy score less than −10 indicates an antagonistic interaction between the drugs. Scores from −10 to 10 suggest an additive interaction, while scores greater than 10 indicate a synergistic interaction . Additionally, combining 100 μM of ToAP2 with any concentration of fluconazole resulted in a biofilm reduction of more than 50% .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p9
|
PMC11276877
|
sec[1]/sec[1]/p[0]
|
2.2. ToAP2 Increases the Damage to Membranes of C. albicans Biofilm Cells in the Presence of Fluconazole
| 4.105469 |
biomedical
|
Study
|
[
0.99951171875,
0.0003306865692138672,
0.0002541542053222656
] |
[
0.99951171875,
0.00015807151794433594,
0.0003306865692138672,
0.000056803226470947266
] |
We evaluated biofilm damage using both scanning electron and atomic force microscopy. In Figure 2 , treatment with 100 µM ToAP2 peptide or with 1.08 µM Amphotericin B resulted in noticeable regions of wrinkling on the biofilm surface which are indicated by white arrows in the image. On the other hand, the untreated control showed smooth, intact cell surfaces . In contrast, the biofilms treated with 100 µM of another AMP, NDBP-5.7, showed few effects on biofilm structure , while those treated with 52 µM Fluconazole exhibited mostly no significant difference in comparison to the untreated control . The white arrow in Figure 2 C highlights an area of cell collapse. Interestingly, biofilm damage was increased when ToAP2 (100 µM) was combined with Amphotericin B or with fluconazole .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p10
|
PMC11276877
|
sec[1]/sec[1]/p[1]
|
2.2. ToAP2 Increases the Damage to Membranes of C. albicans Biofilm Cells in the Presence of Fluconazole
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.0002942085266113281,
0.0001780986785888672
] |
[
0.99951171875,
0.00016307830810546875,
0.0004258155822753906,
0.00006651878356933594
] |
The AFM analysis not only confirmed the combinatory effects observed in the SEM images but also provided a more detailed assessment of the impact of NDBP-5.7 on C. albicans biofilms. The AFM figures once again showed significant changes, including cell collapse and roughening of the membranes in all the treated samples, except for those treated with 52 µM Fluconazole, similar to the results seen from SEM. The evaluation of the membrane roughness by AFM revealed a statistically significant increase in the average surface roughness of the biofilms treated with both ToAP2 and NDBP-5.7 in comparison to the control . In contrast, the treatments with Fluconazole or Amphotericin B alone did not alter the surface roughness of the biofilms relative to the control.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p11
|
PMC11276877
|
sec[1]/sec[2]/p[0]
|
2.3. ToAP2 Combined with Fluconazole Reduces the Viability of C. albicans Biofilm in Different Materials
| 4.078125 |
biomedical
|
Study
|
[
0.99951171875,
0.0002880096435546875,
0.00018775463104248047
] |
[
0.99951171875,
0.00017845630645751953,
0.0003325939178466797,
0.000058710575103759766
] |
In addition to the assays performed in the 96-well plates, we extended our evaluation of the antifungal activity of ToAP2 to the biofilms formed in clinical materials such as intravenous infusion and intravenous catheter tubes (PU catheters). The treatment of the C. albicans biofilms in infusion tubes with 50, 25, or 12.5 µM of ToAP2 alone or with 52 µM of Fluconazole alone did not impact the viability of those biofilms. However, a significant reduction in biofilm viability was observed when the biofilms were treated with the same concentrations of ToAP2 in the presence of Fluconazole compared to the control . The treatment of the PU catheters with ToAP2 or ToAP2 with fluconazole yielded effects consistent with those observed in the intravenous infusion model .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p12
|
PMC11276877
|
sec[1]/sec[3]/p[0]
|
2.4. ToAP2 Alters Expression of Genes Related to C. albicans Virulence Factors
| 4.203125 |
biomedical
|
Study
|
[
0.99951171875,
0.0003459453582763672,
0.00017631053924560547
] |
[
0.99951171875,
0.0002396106719970703,
0.00037407875061035156,
0.00008344650268554688
] |
We analyzed the effects of ToAP2 on C. albicans cells regarding the modulation in the expression of diverse genes associated with fungal pathogenesis . In the analysis of planktonic cells , there was a significant upregulation of the transcripts of genes related to fungal cell adhesion to the surface of host cells and biofilm formation such as HWP1, which encodes a cell wall protein involved in hyphae formation and the ALS family genes (ALS1, ALS3, and ALS5), which encode adhesion surface glycoproteins , as well as fungal efflux pump-mediated resistance (CDR1, CDR2, and MDR1) . Interestingly, we observed a downregulation of transcript accumulation for ERG11, a key gene in the ergosterol biosynthesis pathway and, in turn, in azole drug resistance .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p13
|
PMC11276877
|
sec[1]/sec[3]/p[1]
|
2.4. ToAP2 Alters Expression of Genes Related to C. albicans Virulence Factors
| 4.011719 |
biomedical
|
Study
|
[
0.99951171875,
0.00021028518676757812,
0.00027251243591308594
] |
[
0.99951171875,
0.000286102294921875,
0.0002434253692626953,
0.00005429983139038086
] |
Although the accumulation of transcripts for most of the evaluated genes was not affected by the ToAP2 treatment in the C. albicans biofilms , an upregulating effect was observed in the ALS1 and ALS5 genes at both concentrations of ToAP2 tested (25 µM and 50 µM).
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p14
|
PMC11276877
|
sec[2]/p[0]
|
3. Discussion
| 4.28125 |
biomedical
|
Study
|
[
0.99951171875,
0.0003762245178222656,
0.0001392364501953125
] |
[
0.9970703125,
0.0003199577331542969,
0.002269744873046875,
0.00013208389282226562
] |
The ability of C. albicans to form biofilms on medical devices is a significant source of nosocomial infections associated with elevated morbidity and mortality. This is exacerbated by the high intrinsic resistance of biofilms to antifungals, such as azoles and Amphotericin B, compared to planktonic cells . Additionally, many available antifungals are known for their toxicity to mammalian cells, especially at higher concentrations, limiting their clinical utility . To address this issue and also mitigate the development of antimicrobial resistance, combined antifungal therapies have been proposed . While we have previously observed a synergistic effect in planktonic cells , the combination of ToAP2 and Amphotericin B demonstrated a distinct impact on biofilms. An assessment of these combinations during the adhesion phase showed minimal differences in comparison to the effects of individual drugs. In the mature biofilms, although certain combinations displayed increased antifungal activity, no statistically significant difference was observed compared to individual compounds, suggesting a neutral effect on the biofilm. These findings suggest a potential similarity in the mechanisms of action of ToAP2 and Amphotericin against biofilms .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p15
|
PMC11276877
|
sec[2]/p[1]
|
3. Discussion
| 4.152344 |
biomedical
|
Study
|
[
0.99951171875,
0.0003352165222167969,
0.0001456737518310547
] |
[
0.99853515625,
0.0002334117889404297,
0.0010023117065429688,
0.00008827447891235352
] |
On the other hand, the outcomes of combining ToAP2 with Fluconazole appear promising, as this exhibited a synergistic inhibitory effect in both phases of biofilm formation. Remarkably, in the presence of 25 and 12.5 µM of the peptide, even minimal concentrations of Fluconazole were able to reduce the viability of the biofilm in the adhesion phase to less than 50%. In previous work, we demonstrated that these concentrations show very low cytotoxicity against human erythrocytes and murine peritoneal macrophages . In addition, there was also a marked reduction in the mature biofilms when 25, 50, and 100 µM of ToAP2 was used with different Fluconazole concentrations. This finding is particularly interesting considering the intrinsic resistance of C. albicans biofilms to Fluconazole . This suggests a potential avenue for the development of combined therapies with this antifungal, which is especially noteworthy as Fluconazole belongs to one of the main classes of antifungals used in the clinical settings against candidiasis.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p16
|
PMC11276877
|
sec[2]/p[2]
|
3. Discussion
| 4.21875 |
biomedical
|
Study
|
[
0.99951171875,
0.0003237724304199219,
0.00021350383758544922
] |
[
0.9990234375,
0.00016558170318603516,
0.0006241798400878906,
0.00007867813110351562
] |
SEM and AFM analysis of biofilms treated with ToAP2 and Fluconazole revealed significant structural alterations, suggesting that the peptide also targets the cell membrane—a well-stablished mechanism of action for various AMPs . Similarly, in a study with the peptide P-113, the authors showed that this peptide induced protuberances in the C. albicans biofilm filaments . Interestingly, Fluconazole alone exhibited no discernible impact on biofilm morphology. However, when combined with ToAP2, we observed a notable reduction in biofilm size alongside morphological changes (cell shrinkage and increased cell roughness), as is evident in both SEM and AFM images. Notably, ToAP2, when administered alone, induced structural changes like the ones observed with amphotericin treatment. The SEM analysis of the C. albicans biofilm treated with another peptide, NDBP-5.7, did not reveal any major structural changes, but the AFM analysis revealed an increase in the biofilm surface roughness. The combination of ToAP2 and Fluconazole also revealed an increase in the biofilm roughness. Alone, neither Amphotericin B nor Fluconazole induced changes in the biofilm roughness in comparison to the untreated control.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p17
|
PMC11276877
|
sec[2]/p[3]
|
3. Discussion
| 4.003906 |
biomedical
|
Study
|
[
0.99951171875,
0.00019633769989013672,
0.000152587890625
] |
[
0.9912109375,
0.0004019737243652344,
0.008209228515625,
0.00011008977890014648
] |
These results demonstrate the great potential of the combination of Fluconazole and ToAP2 in eliminating biofilms on surfaces such as intravenous catheters, which are closely associated with systemic candidiasis. Cools et al. found similar results with the combination of caspofungin and the peptide HsLin06_18, which significantly reduced C. albicans biofilms in intravenous catheters. Additionally, Raman et al. showed that catheters loaded with different polymers containing a β peptide were able to inhibit the growth of C. albicans biofilms.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p18
|
PMC11276877
|
sec[2]/p[4]
|
3. Discussion
| 4.265625 |
biomedical
|
Study
|
[
0.99951171875,
0.00033402442932128906,
0.00017881393432617188
] |
[
0.9990234375,
0.00023543834686279297,
0.000457763671875,
0.00008827447891235352
] |
Our findings also suggest that the combined therapeutic potential of Fluconazole and ToAP2 can be leveraged in developing biotechnological tools for coating surfaces to prevent C. albicans biofilms. Interestingly, in the presence of ToAP2, the expression of various genes associated with C. albicans virulence was altered, as assessed by qRT-PCR. In planktonic cells, genes related to adhesion (HWP1, ALS1, and ALS3) and efflux pumps (CDR1 and MDR1) showed increased expression at different tested concentrations. This phenomenon might imply a response by C. albicans to counteract the adverse effects of the therapeutic agent. Conversely, the expression of the ERG11 gene, associated with the ergosterol synthesis pathway, was reduced, suggesting that the peptide targets the plasma membrane, as demonstrated in previous studies . A similar alteration in the expression of ERG11 and ERG5 along with an increase in the accumulation of CDR1 transcripts were observed in the presence of the AMP MAF-1A after two hours of interaction with C. albicans .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276877_p19
|
PMC11276877
|
sec[2]/p[5]
|
3. Discussion
| 4.101563 |
biomedical
|
Study
|
[
0.99951171875,
0.0002346038818359375,
0.0002002716064453125
] |
[
0.99951171875,
0.0001513957977294922,
0.00039196014404296875,
0.00005364418029785156
] |
In the evaluation of gene expression in the C. albicans biofilms, only the ALS1 and ALS5 genes showed a significant increase in expression. This observation aligns with previous works suggesting that the upregulation of specific adhesin genes plays a significant role in the biofilm formation and pathogenesis of C. albicans . Contrasting with our results, Maione et al. observed a significant reduction in the expression of ERG11 and ALS5 in C. albicans biofilm in the presence of the WMR peptide. This difference may be related to the biofilm’s exposure time to the peptide, with the researchers maintaining the biofilm’s contact with the peptide for 24 h while our analysis was performed 1 h after the treatment.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p20
|
PMC11276877
|
sec[2]/p[6]
|
3. Discussion
| 4.164063 |
biomedical
|
Study
|
[
0.99951171875,
0.0003981590270996094,
0.00013709068298339844
] |
[
0.99658203125,
0.0004489421844482422,
0.0028858184814453125,
0.00013172626495361328
] |
In conclusion, the ToAP2 peptide not only impacts C. albicans biofilms independently but also in combination with clinically used antifungals. Its effects extend beyond direct implications for C. albicans cell viability, encompassing significant changes in biofilm morphology at subinhibitory concentrations across various medical devices. The synergistic action with Fluconazole is particularly noteworthy, presenting a promising avenue for novel therapeutic approaches and the coating of medical devices. This is especially relevant since Fluconazole, a widely employed antifungal in candidiasis treatment, lacks efficacy against C. albicans biofilms.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276877_p21
|
PMC11276877
|
sec[3]/sec[0]/p[0]
|
4.1. Synthesis of Peptides
| 4.101563 |
biomedical
|
Study
|
[
0.99951171875,
0.0001550912857055664,
0.0002396106719970703
] |
[
0.9990234375,
0.0007777214050292969,
0.00022280216217041016,
0.00006729364395141602
] |
The AMPs ToAP2 (FFGTLFKLGSKLIPGVMKLFSKKKER, 3 KDa, net charge: +6) and NDBP-5.7 (ILSAIWSGIKSLF-NH2, 1.43 KDa, net charge: +1) were chemically synthesized by Biomatik using an Fmoc/t-butyl on solid support strategy. The peptide sequences were derived from scorpion gland cDNA libraries and purification and characterization took place as described previously .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276877_p22
|
PMC11276877
|
sec[3]/sec[1]/p[0]
|
4.2. C. albicans Culture Conditions
| 4.085938 |
biomedical
|
Study
|
[
0.99951171875,
0.0003066062927246094,
0.0001577138900756836
] |
[
0.99755859375,
0.0019073486328125,
0.00030231475830078125,
0.00011163949966430664
] |
C. albicans SC 5314 was used in all the experiments. Aliquots from frozen stocks in 30% glycerol were plated on Sabouraud dextrose agar for 24 h at 30 °C. After growth, a colony was selected and inoculated in Sabouraud dextrose broth at 30 °C (200 rpm) for 24 h. After growth, the cells were washed three times with sterile phosphate buffer (PBS) and counted using a hemocytometer, then the cultures were diluted to appropriate cell densities according to each experiment.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p23
|
PMC11276877
|
sec[3]/sec[2]/p[0]
|
4.3. Antimicrobial Activity of ToAP2 in Combination with Other Antifungals
| 4.261719 |
biomedical
|
Study
|
[
0.99951171875,
0.00036525726318359375,
0.00015687942504882812
] |
[
0.99853515625,
0.0003924369812011719,
0.000774383544921875,
0.00010627508163452148
] |
The antifungal activity of ToAP2 against C. albicans SC 5314 biofilms was performed as previously described . An inoculum of 1 × 10 5 C. albicans cells in 100 μL of RPMI 1640 medium was added to 96-well polystyrene microplates and incubated at 37 °C for 4 or 24 h (early and mature phases respectively). After that, biofilms were washed three times with PBS to remove non-adherent cells, received fresh medium with different concentrations of ToAP2 combined with Amphotericin B or Fluconazole, and the plates were incubated at 37 °C for 24 h. Cell viability was evaluated using the Alamar Blue (ThermoFisher, Waltham, MA, USA) reagent and fluorescence was read using a SpectraMax ® M plate reader (Molecular Devices, LLC, San Jose, CA, USA), with excitation at 550 nm and emission at 585 nm. To capture the combinatorial multidose–response effects, drug synergism was assessed using SynergyFinder Plus R package . Fluorescence intensity readings were normalized to the average of the control wells on the same plate to determine relative cell viability values. All cell viability data were transformed to inhibition values. Synergism analysis was performed applying the Zero Interaction Potency (ZIP) model, which captures drug interaction relationships by comparing the change in the potency of the dose–response curves between individual drugs and their combinations . Plots to visualize synergy maps for two-drug combinations were produced in R using the package SynergyFinder Plus 3.10.3. The summary synergy scores represent the average excess response due to drug interactions. In general, a synergy score less than −10 indicates antagonistic interaction between the drugs. Scores from −10 to 10 suggest an additive interaction, while scores greater than 10 indicate a synergistic interaction .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p24
|
PMC11276877
|
sec[3]/sec[3]/p[0]
|
4.4. Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM)
| 4.136719 |
biomedical
|
Study
|
[
0.99951171875,
0.0002880096435546875,
0.000164031982421875
] |
[
0.9990234375,
0.0004067420959472656,
0.0003554821014404297,
0.00006783008575439453
] |
SEM images were made as previously described . To generate C. albicans biofilms, 10 6 yeast cells were inoculated in RPMI medium on 24-well plates containing sterile coverslips and incubated at 37 °C for 24 h. After biofilm formation, the coverslips were gently washed with PBS and the biofilms were treated for 24 h with ToAP2 (100 µM), NDBP-5.7 (100 µM), Amphotericin B (1.08 µM), Fluconazole (52 µM), or with combinations of ToAP2 and the two antifungals. An untreated group was used as a control. After the treatments, the samples were fixed with 2.5% glutaraldehyde in sodium-cacodylate buffer, washed with ultrapure water, and air-dried at room temperature. Samples for SEM analysis were coated with Au/Pd before analysis and imaged using an FEI Quanta 400 SEM in high vacuum, at 10 KeV accelerating voltage. Samples for AFM were scanned without metal coating using a TT-AFM from AFM Workshop in vibrating mode, using a 50 × 50 × 17 µm scanner using ACT probes with resonant frequency of approximately 300 kHz (Applied NanoStructures, Inc., Mountain View, CA, USA). Micro-roughness was evaluated using the Gwyddion 2.40 software.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p25
|
PMC11276877
|
sec[3]/sec[4]/p[0]
|
4.5. Effect of the ToAP2 Peptide on Biofilms in Different Clinical Devices
| 4.09375 |
biomedical
|
Study
|
[
0.99951171875,
0.0003619194030761719,
0.00013947486877441406
] |
[
0.9990234375,
0.0003306865692138672,
0.00040912628173828125,
0.00008589029312133789
] |
The action of the ToAP2 peptide on an in vitro catheter model of C. albicans biofilms was performed as previously described . Before the inoculum, fragments of intravenous catheters and tubes for intravenous infusion (1 cm) were incubated in 24-well plates with fetal bovine serum for 12 h. After that, the catheters were incubated in the presence of 5 × 10 6 cells of C. albicans for another 24 h at 37 °C in RPMI medium for biofilm formation. The fragments were then transferred to new plates, washed carefully with PBS, and incubated for another 24 h in the presence of ToAP2, Fluconazole, or combinations of the two molecules. Biofilm viability was assessed using the viability reagent Alamar Blue in a SpectraMax ® M plate reader, and untreated groups were used as growth control.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p26
|
PMC11276877
|
sec[3]/sec[5]/p[0]
|
4.6. Evaluation of C. albicans Gene Expression in Response to AMP Treatment
| 4.085938 |
biomedical
|
Study
|
[
0.99951171875,
0.00028133392333984375,
0.00017631053924560547
] |
[
0.99951171875,
0.000377655029296875,
0.0002655982971191406,
0.000064849853515625
] |
Control and AMP-treated C. albicans cells were subjected to gene expression analysis by qRT-PCR. An inoculum of 2 × 10 7 planktonic cells of C. albicans , treated or untreated with 25 and 50 µM of ToAP2, was incubated at 37 °C with shaking (200 rpm) for 1 h. Following the treatment, fungal cells were washed with PBS and subjected to total RNA extraction.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276877_p27
|
PMC11276877
|
sec[3]/sec[5]/p[1]
|
4.6. Evaluation of C. albicans Gene Expression in Response to AMP Treatment
| 4.101563 |
biomedical
|
Study
|
[
0.99951171875,
0.00031256675720214844,
0.0001577138900756836
] |
[
0.9990234375,
0.0005278587341308594,
0.0003261566162109375,
0.00007593631744384766
] |
The conditions used for biofilm formation and AMP treatment were as described before . Briefly, stock cells from C. albicans were thawed and cultured in Sabouraud dextrose broth for 18 h at 30 °C with shaking at 200 rpm. Then, cells were washed with PBS and centrifuged . An inoculum of 1 × 10 6 cells/mL of C. albicans in 100 µL of RPMI 1640 medium was added to 96-well microplates. Plates were then incubated for 24 h at 37 °C to promote full biofilm formation. After the incubation time, biofilms were washed with PBS to remove non-adherent cells. RPMI medium with different concentrations of ToAP2 was added and incubated for 1 h at 37 °C. Then, biofilms were washed and detached from the plates for total RNA extraction to perform sessile cell gene expression evaluation by qRT-PCR.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p28
|
PMC11276877
|
sec[3]/sec[5]/p[2]
|
4.6. Evaluation of C. albicans Gene Expression in Response to AMP Treatment
| 3.955078 |
biomedical
|
Study
|
[
0.99951171875,
0.00013840198516845703,
0.00014853477478027344
] |
[
0.9912109375,
0.0079498291015625,
0.0007653236389160156,
0.0002048015594482422
] |
Total RNA was extracted from C. albicans planktonic and biofilm cells using mirVana™ miR Isolation Kit (Invitrogen, Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturer’s specifications.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276877_p29
|
PMC11276877
|
sec[3]/sec[5]/p[3]
|
4.6. Evaluation of C. albicans Gene Expression in Response to AMP Treatment
| 4.105469 |
biomedical
|
Study
|
[
0.99951171875,
0.00023639202117919922,
0.00017845630645751953
] |
[
0.9990234375,
0.0003724098205566406,
0.00029587745666503906,
0.0000661611557006836
] |
RNA samples were quantified using a NanoDrop One c instrument (Thermo Fisher Scientific, Waltham, MA, USA), and their quality was analyzed by electrophoresis on agarose gels. RNA samples were subjected to DNase treatment (Promega, Madison, WI, USA) and were stored at −20 °C. For cDNA synthesis, total RNA was reverse transcribed from 1 µg of total RNA using High-Capacity cDNA Reverse Transcription kit (Applied Biosystems, Waltham, MA, USA) according to the manufacturer’s instructions. The qPCR reactions were performed in triplicate using Fast SYBR Green Master Mix ® (Applied Biosystems) and carried out in the 7500 Fast Real-Time PCR System (Applied Biosystem). The genes evaluated were Hwp1, Als1, Als3, Als5, Mdr1, Cdr1, Cdr2, Erg6, Erg11, and the housekeeping control Act1 ( Table 1 ). Changes in transcript abundance in stimulated samples were compared to non-stimulated control group using the 2 −∆∆Ct method .
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276877_p30
|
PMC11276877
|
sec[3]/sec[6]/p[0]
|
4.7. Statistical Analysis
| 3.908203 |
biomedical
|
Study
|
[
0.99951171875,
0.00017881393432617188,
0.0001647472381591797
] |
[
0.9990234375,
0.0006656646728515625,
0.00043964385986328125,
0.00007772445678710938
] |
For the analysis, three independent experiments were performed in technical triplicate. The multiple group comparisons were conducted with a one-way analysis of variance (ANOVA) followed by Tukey’s post-test. Synergism between the antifungal drugs and AMP combinations was evaluated using the ZIP model from SynergyFinder Plus package 3.10.3 in the R environment. For the qPCR experiments, comparisons were conducted using Student’s t -test. A p -value < 0.05 was considered to indicate a statistically significant difference. Statistical analyses were carried out with GraphPad Prism software, version 8.
|
[
"Jhones do Nascimento Dias",
"Fabián Andrés Hurtado Erazo",
"Lucinda J. Bessa",
"Peter Eaton",
"José Roberto de Souza de Almeida Leite",
"Hugo Costa Paes",
"André Moraes Nicola",
"Ildinete Silva-Pereira",
"Patrícia Albuquerque"
] |
https://doi.org/10.3390/ijms25147769
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276889_p0
|
PMC11276889
|
sec[0]/p[0]
|
1. Introduction
| 3.896484 |
biomedical
|
Study
|
[
0.99951171875,
0.0002779960632324219,
0.0004398822784423828
] |
[
0.56689453125,
0.036468505859375,
0.395751953125,
0.0006308555603027344
] |
The process of wound healing is complex and begins immediately after an injury or tissue damage occurs. It consists of several overlapping phases, which are generally known and well described in the current literature . Despite the many studies that have been conducted to date, many unresolved questions remain. Thus, further investigation of wound healing is crucial, both in vivo and in vitro. Animal experiments are necessary to address research questions and develop wound therapies, since it is challenging to recruit enough patients with comparable wounds to show statistical significance. Thus, using only clinical research, it would be impossible to gain new insights within an acceptable time frame .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276889_p1
|
PMC11276889
|
sec[0]/p[1]
|
1. Introduction
| 3.921875 |
biomedical
|
Study
|
[
0.99951171875,
0.0001323223114013672,
0.00045037269592285156
] |
[
0.8994140625,
0.0389404296875,
0.06121826171875,
0.00029659271240234375
] |
Small mammals, including rabbits, guinea pigs, rats, and mice, are often used in wound healing studies, as they are relatively inexpensive and easy to handle . However, small mammals differ from humans in a number of ways, including anatomy and physiology . Regarding wound healing studies, one main difference between small mammals and humans is the thickness of their skin, especially the epidermis of fur-bearing animals, which is only 1–3 cell layers thick. Small mammals have a relatively thin epidermis and dermis, which means that their wounds heal more quickly than in humans. Another important difference is that wounds in these small mammals heal more through wound contraction than re-epithelialization .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276889_p2
|
PMC11276889
|
sec[0]/p[2]
|
1. Introduction
| 4.203125 |
biomedical
|
Study
|
[
0.99951171875,
0.00029587745666503906,
0.0003769397735595703
] |
[
0.9775390625,
0.0004706382751464844,
0.022003173828125,
0.00013303756713867188
] |
In contrast to small mammals, there are a number of significant similarities between humans and pigs, including in terms of the anatomy and physiology of their skin . In fact, Sullivan et al. showed a concordance of 78% between human wound healing studies and swine studies versus 53% between humans and small mammal studies. For instance, human and swine wound healing processes have similar wound closure mechanisms; they share the same number of healing phases, and both use re-epithelialization as the main strategy to close partial-thickness wounds . The domestic pig also has a skin surface area similar to humans when compared to their body size. Additionally, both humans and domestic pigs have reduced hair density, comparable skin thickness , and similar biochemical dermal collagen . Furthermore, they have similar vascularization of the hair follicles. Of course, there are also differences that should be considered; for instance, the absence of cutaneous eccrine glands in the common integument, or poor vascularization of the cutaneous glands and parts of the subepidermal plexus. Furthermore, domestic pigs present reduced variation in their skin phototype, whereas humans have a wide variety of skin tones; recently, many works have reported differences in wound healing outcomes for Fitzpatrick skin types IV–VI, especially for scarring and chronic wounds . Despite these contrasts, a wound model using domestic pigs is still reliable and showed better concordance with human studies , especially regarding translational relevance .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276889_p3
|
PMC11276889
|
sec[0]/p[3]
|
1. Introduction
| 4.195313 |
biomedical
|
Study
|
[
0.9990234375,
0.00033974647521972656,
0.00039267539978027344
] |
[
0.91259765625,
0.0015888214111328125,
0.0855712890625,
0.00023066997528076172
] |
There are four main categories of wound models in pigs . These include incisional wounds, partial-thickness excisional wounds, full-thickness excisional wounds, and burn wounds. For research purposes, depending on the object to be examined and the research question, one must select the most suitable. Partial-thickness excisions, a widely studied wound type, remove the epidermis and different amounts of dermis, often leaving the bases of the sebaceous glands and hair follicles intact. These excisions are frequently made with a dermatome. They closely mimic partial-thickness burns after debridement or donor sites created from split-thickness skin grafting . However, one of the limitations of wound healing experiments in pigs to date is the lack of standardization . There has been no agreed protocol for these experiments so far, which makes it difficult to compare results across studies. Together, the reduced standardization and the challenges of comparing wound regeneration results call for an increased number of animals to achieve more reliable outcomes, although this raises ethical concerns, especially considering the importance of abiding by the 3R principles . Since the study of wound healing requires holistic analyses that include both local and systemic responses, the use of animal models remains a necessity . However, several factors should be considered during the experimental design in order to achieve a higher level of standardization, including animal characteristics (e.g., age and weight) and the wounds created (e.g., size, depth, and positioning). Additionally, qualitative and quantitative histological examinations set the basis for a solid understanding of the wound healing process and how different treatments can influence it. Therefore, in order to achieve a highly standardized model, it is mandatory to understand in depth the results of histomorphology analysis and how different methods can influence it.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p4
|
PMC11276889
|
sec[0]/p[4]
|
1. Introduction
| 3.998047 |
biomedical
|
Study
|
[
0.99951171875,
0.00022733211517333984,
0.00034332275390625
] |
[
0.99951171875,
0.000232696533203125,
0.00035762786865234375,
0.000052034854888916016
] |
The work reported in this study presents a thorough analysis of the histomorphology characteristics of a porcine excision wound model. For this reason, different parameters were considered, such as sampling preparation and position, as well as the reproducibility and standardization of the wounds and how different morphological aspects dictate the healing process.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p5
|
PMC11276889
|
sec[1]/sec[0]/p[0]
|
2.1. Animals and Wounds
| 3.009766 |
biomedical
|
Study
|
[
0.966796875,
0.031951904296875,
0.0013952255249023438
] |
[
0.9755859375,
0.01727294921875,
0.0007610321044921875,
0.00647735595703125
] |
A total of 11 female domestic pigs were included in the study. The animals were between three and five months old. The starting weight was 24–57 kg, with an average of 38.2 kg. After surgery, no animal experienced discomfort, severe pain, or adverse side effects. There was no evidence of infection or marked inflammation. None of the animals died or had to be euthanized for ethical reasons due to clinical complications. Protective bandages were applied to avoid any complications with regard to the wound dressing (e.g., detachment or dislocation) during the 7-day observation period.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p6
|
PMC11276889
|
sec[1]/sec[1]/sec[0]/p[0]
|
2.2.1. General
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.0004172325134277344,
0.00015473365783691406
] |
[
0.9990234375,
0.0005450248718261719,
0.0004482269287109375,
0.00009965896606445312
] |
A histopathologist used the scoring approach we have employed in former studies and used predetermined scoring criteria to undertake a blinded analysis of the H&E-stained wound sections, assessing new epidermis and new dermis . To evaluate as precisely as possible the extent of new epidermis (i.e., “% re-epithelialization”), a total of 16–21 adjacent 100× microscopic fields, depending on the width of the wound, were examined using a light microscope covering the entire wound area, and the percentage of new epidermis per microscopic field was assigned to each 5% increment, creating a “new epidermis heatmap” from 0 to 100%. A global re-epithelialization percentage per histological section was calculated for each wound by averaging each microscopic field .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p7
|
PMC11276889
|
sec[1]/sec[1]/sec[0]/p[1]
|
2.2.1. General
| 4.121094 |
biomedical
|
Study
|
[
0.99951171875,
0.000354766845703125,
0.0001615285873413086
] |
[
0.9990234375,
0.0006122589111328125,
0.0004680156707763672,
0.00008606910705566406
] |
Quantitative manual morphometry was used to determine the wound width (wound length per histological section) and areas of newly formed tissues. The edges of the wound were defined by the thinnest detectable presence of new dermis (granulation tissue). On the wound’s surface, one straight line was drawn, or two or more were drawn and linked, to determine the approximate wound width . By physically outlining the newly healed tissues, new dermal and new epidermal areas were created. By dividing the area by the measured wound width, the standardized thickness of the new epidermis and dermis were obtained.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276889_p8
|
PMC11276889
|
sec[1]/sec[1]/sec[1]/p[0]
|
2.2.2. Dermatome Samples
| 4 |
biomedical
|
Study
|
[
0.99951171875,
0.00038504600524902344,
0.0002434253692626953
] |
[
0.9990234375,
0.0007829666137695312,
0.00024318695068359375,
0.00009864568710327148
] |
The skin samples taken by dermatome showed consistent and comparable thickness and morphology . The mean cross-sectional area of all dermatome skin samples was 2905 pixels with a SD of ±278.6 pixels . This standardized deviation was calculated to be 9.6% of the average dermatome cross-sectional area.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276889_p9
|
PMC11276889
|
sec[1]/sec[1]/sec[2]/p[0]
|
2.2.3. Sampling Procedure Effects and Wound Sample Position
| 4.109375 |
biomedical
|
Study
|
[
0.9990234375,
0.0007138252258300781,
0.000270843505859375
] |
[
0.99951171875,
0.0002827644348144531,
0.00023448467254638672,
0.00007981061935424805
] |
Our first evaluation, which was carried out within the wound itself, examined the possible effect of removing the dressing material before fixation for histology, as there might be an effect concerning the re-epithelialization measured, most notably, the mechanical detachment of the fragile new epithelium. Therefore, we divided the wound area (marked for orientation with a biopsy punch) in two halves: in the right half, the dressing was left in place on the wound, whereas in the left half, the dressing was removed prior to fixation. The entire area was then excised, immersed in NBF, and sent for histopathology, as described above. Cuttings were taken from different locations for histological analysis . No significant differences were observed in the samples examined concerning the wound healing re-epithelialization parameter .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p10
|
PMC11276889
|
sec[1]/sec[1]/sec[2]/p[1]
|
2.2.3. Sampling Procedure Effects and Wound Sample Position
| 4.117188 |
biomedical
|
Study
|
[
0.99951171875,
0.00043129920959472656,
0.00021898746490478516
] |
[
0.99951171875,
0.0001742839813232422,
0.00040841102600097656,
0.0000730752944946289
] |
Further, to explore possible topographical differences in wound healing within the wound, several sagittal and parasagittal or oblique cut positions were selected within the 3 × 3 cm square wound beds for histopathology. Furthermore, we wanted to evaluate whether a cutting position, such as position A (the center of the wound) in Figure 4 A, is representative of the entire wound. According to the histopathology scoring analysis, the healing parameter for re-epithelialization was quite consistent, with lower re-epithelialization grades in the middle of the wound bed and expectedly high scores in the sections closest to the edge of the wound . Quantitative manual morphometry evaluations supported the findings by demonstrating a consistent re-epithelialization process . In order to determine how this selected cutting location compared to the mean value, the results from sampling position A were highlighted with a red dot in the scatter plot figures. This alternative sampling method was also used to examine other healing parameters. Despite the presence of some outliers, the morphological characterization of the thickness of the new epidermis and the thickness of the new dermis/granulation tissue exhibited similarly consistent results.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p11
|
PMC11276889
|
sec[1]/sec[1]/sec[3]/p[0]
|
2.2.4. Body Mass Influence on the Dermal Tissue and Residual Dermal Tissue
| 4.160156 |
biomedical
|
Study
|
[
0.99951171875,
0.0003399848937988281,
0.0002391338348388672
] |
[
0.99951171875,
0.0001615285873413086,
0.0004897117614746094,
0.0000699758529663086
] |
Manual measurements were performed to assess the thickness of the unwounded dermis and the reminiscent dermal tissue under the wound bed. Intact dermal tissues on each side of the wound bed were measured in triplicate. The measurements start at the basal lamina and extend to the first cells of the hypodermis. To quantify the thickness of the residual dermis, a triplicate measurement was performed, starting at the interface between the more basophilic new dermal tissue and the residual dermis extending to the beginning of the hypodermis. The measurements obtained for the intact and residual dermis differed significantly. The difference between the two measurements was then compared to the thickness of the dermis present on the excised dermatome samples, with no apparent statistical significance. This result indicates that the missing dermis on the wound bed has roughly the same thickness as the dermis present in the excised dermatome samples. To understand how the body mass of the analyzed animals correlates to these two dermal characteristics, Pearson’s correlation was calculated for the body weight vs. the tissue thickness for the residual dermis and for the intact dermis. A very strong positive relationship was found for the comparison to the reminiscent dermis , and a strong positive relationship was observed for the intact dermis ( r = 0.82; p = 0.001).
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276889_p12
|
PMC11276889
|
sec[1]/sec[1]/sec[4]/p[0]
|
2.2.5. Wound Position Effects
| 4.113281 |
biomedical
|
Study
|
[
0.99951171875,
0.0002834796905517578,
0.00025153160095214844
] |
[
0.99951171875,
0.0002884864807128906,
0.00036454200744628906,
0.00005996227264404297
] |
A map displaying the mean residual thickness of the dermis under the wound for each wound site position was created using the results obtained for all 11 animals . For each flank of each animal, a heat map was established using a color gradient, with the lowest values denoted by red, the middle values by orange, the high values by light green, and the highest values by dark green. A trend for the dermis thickness is apparent in this “heat map” created from the results obtained. While the dermis tissue is evidently thicker closer to the caudal section of the animal, the residual dermis thickness appears to be thinner at the regions closer to the cranium of the animal. Opposing wounds exhibited similar dermis thicknesses. As a final step, the mean value for each donor site position was determined and ranked using the same color scheme. To provide perspective on how the dermis thickness in this position is comparable to those at the other wound sites, the corresponding color scheme was applied on an illustration .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p13
|
PMC11276889
|
sec[1]/sec[1]/sec[5]/p[0]
|
2.2.6. Influence of the Residual Dermis under the Wound on Healing Parameters
| 4.089844 |
biomedical
|
Study
|
[
0.99951171875,
0.00039505958557128906,
0.0002505779266357422
] |
[
0.99951171875,
0.000186920166015625,
0.000324249267578125,
0.00005817413330078125
] |
Pearson’s correlation tests were conducted to determine whether the variance in residual dermis thickness had an impact on the wound donor site healing process. Thus, 56 measurements of wounds created at different dorsal positions were analyzed after seven days of treatment. The residual dermis thickness and the re-epithelialization process showed a significant and strong positive correlation , whereas for the regeneration of new dermal tissue, a significant and strong negative correlation was found when compared to the thickness of the residual dermis .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p14
|
PMC11276889
|
sec[2]/sec[0]/p[0]
|
3.1. Animal Selection and Wound Setting
| 3.964844 |
biomedical
|
Study
|
[
0.9990234375,
0.0003364086151123047,
0.0005345344543457031
] |
[
0.5048828125,
0.02484130859375,
0.4697265625,
0.0006327629089355469
] |
In vivo wound models remain the most reliable models for studying the intricate processes involved in skin wound regeneration . There are several reasons why pig models are particularly well suited for studying wound healing. First, pig skin is structurally very similar to human skin. This similarity allows pigs to be used to study the mechanisms of wound healing, particularly in the areas of immune response and inflammation, vascular contributions, cell proliferation and migration, and extracellular matrix remodeling. Second, pigs have a similar immune system to humans, which means that their responses to infection and inflammation are also similar . This makes pigs ideal for studying the role of the immune system in wound healing. Finally, pigs are large animals, making them easier to handle than mice or rats. This facilitates performing surgical procedures and monitoring the healing process over time.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p15
|
PMC11276889
|
sec[2]/sec[0]/p[1]
|
3.1. Animal Selection and Wound Setting
| 2.457031 |
biomedical
|
Study
|
[
0.98828125,
0.00971221923828125,
0.0022430419921875
] |
[
0.9619140625,
0.034454345703125,
0.0017862319946289062,
0.0017824172973632812
] |
Based on the data collected, it can be concluded that the surgery and postoperative phases were well tolerated by the animals. There were no severe side effects, signs of pain, or other intolerance. The minimal influence of the protective bandages on the applied wound dressings suggests that the bandages were effective in protecting the wounds.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p16
|
PMC11276889
|
sec[2]/sec[1]/p[0]
|
3.2. Histological Assessment
| 4.078125 |
biomedical
|
Study
|
[
0.99951171875,
0.00019943714141845703,
0.0001844167709350586
] |
[
0.99658203125,
0.0021762847900390625,
0.0011148452758789062,
0.00009208917617797852
] |
The use of a scoring scale introduces potential imprecision in the assessment of dermis and epidermis healing, enabling only broad, significant differences to be observed and necessitating intra-observer and inter-observer validations. The use of quantitative manual morphometry provides a measure of healing for each tissue and tissue sub-compartment, enabling comparisons between different treatments with low magnitude effects, various time points in longitudinal studies, different studies with the same design, etc. The pathologist’s evaluation of the percentage of epithelialization was highly predictive of the corresponding variable measured by interval quantitative morphometry on the epidermis.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276889_p17
|
PMC11276889
|
sec[2]/sec[2]/p[0]
|
3.3. Dermatome Samples
| 4.082031 |
biomedical
|
Study
|
[
0.99951171875,
0.0003726482391357422,
0.00021767616271972656
] |
[
0.9990234375,
0.0006585121154785156,
0.0003216266632080078,
0.00008356571197509766
] |
The standard deviation of the excised cross-sectional skin areas was calculated to be 9.6% of the average dermatome cross-sectional area, confirming the reproducibility and performance of the wound-making procedure with a battery-assisted dermatome. Hence, the data from the dermatome samples suggest that using a dermatome for wound setting is a consistent and reliable way of taking skin samples and setting relatively standard wounds. This dataset demonstrates that the dermatome is capable of setting wounds of consistent size, morphology, and depth .
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p18
|
PMC11276889
|
sec[2]/sec[3]/p[0]
|
3.4. Sampling and Histology within the Wound
| 3.927734 |
biomedical
|
Study
|
[
0.99951171875,
0.0003142356872558594,
0.00036454200744628906
] |
[
0.99853515625,
0.0008664131164550781,
0.00043702125549316406,
0.00007241964340209961
] |
The results of the intra-wound sectioning positions seem to be quite consistent, with lower re-epithelialization scores in the middle regions/center of the wound bed and expectedly high scores in the sections closest to the edge of the wound. According to the morphological evaluations, this represents a consistent re-epithelialization process. However, it should be noted that there are some outliers present. The cross-sectioning located in the middle of the donor site seems to be representative of the entire wound. However, it is possible that preparing two or three step sections could increase the representativeness of the sampling.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p19
|
PMC11276889
|
sec[2]/sec[3]/p[1]
|
3.4. Sampling and Histology within the Wound
| 4.113281 |
biomedical
|
Study
|
[
0.99951171875,
0.00035691261291503906,
0.0002086162567138672
] |
[
0.99853515625,
0.0007147789001464844,
0.00043702125549316406,
0.00007623434066772461
] |
Furthermore, no significant differences were observed in the samples concerning the re-epithelialization healing parameter, regardless of whether the dressing material was removed before or after NBF fixation for histology. This suggests that removing the dressing material before fixation for histology can be done if needed and does not induce any significant mechanical artifacts, even in very immature epidermis. However, if it is necessary to remove it beforehand, one should do so very carefully, as this could unnecessarily injure the fragile epidermis and, as a result, significantly alter the epidermal data.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p20
|
PMC11276889
|
sec[2]/sec[4]/p[0]
|
3.5. Body Mass Influence on the Dermal Tissue and Residual Dermal Tissue
| 4.105469 |
biomedical
|
Study
|
[
0.99951171875,
0.0002663135528564453,
0.00023686885833740234
] |
[
0.99951171875,
0.00015354156494140625,
0.0002884864807128906,
0.00005561113357543945
] |
In the present study, we investigated the thickness of the dermis in relation to the body mass of the animals. Our results showed that the thickness of the dermis positively correlated with the body mass of the animals. Moreover, integrating these results with those obtained for the relationship of the residual dermis thickness on the new dermis to new epidermis parameters, notably re-epithelialization suggests that the body mass of the animals may play an indirect role in the regeneration of the epidermis after wounding due to thicker residual dermis leading to faster subsequent re-epithelialization. Further studies are needed to confirm this finding and to elucidate the underlying mechanisms.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p21
|
PMC11276889
|
sec[2]/sec[4]/p[1]
|
3.5. Body Mass Influence on the Dermal Tissue and Residual Dermal Tissue
| 3.039063 |
biomedical
|
Other
|
[
0.99658203125,
0.0005278587341308594,
0.0029449462890625
] |
[
0.285400390625,
0.708984375,
0.00489044189453125,
0.0006451606750488281
] |
Consequently, if possible, to avoid any confounding factors, it is highly recommended to use age-matched and, more importantly, weight-matched individual pigs in experiments comparing several treatment modalities.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276889_p22
|
PMC11276889
|
sec[2]/sec[5]/p[0]
|
3.6. Position Effects
| 3.908203 |
biomedical
|
Study
|
[
0.99951171875,
0.00025343894958496094,
0.0003905296325683594
] |
[
0.99462890625,
0.00460052490234375,
0.0004570484161376953,
0.00014638900756835938
] |
The mean residual thickness of the dermis under the wounds at different positions on the animal varies along the back of the pig. The heat map shows a trend for dermis thickness, with thicker dermis toward the caudal section and thinner dermis toward the cranial section. This provides perspective on how the dermis thickness at each position compares to the other positions. This finding is crucial in comparing wound dressings. It suggests that wounds should be compared in opposite lateral areas rather than in very different cranial and caudal areas along the back of the pig, since the dermis is thinner in the cranial area than in the caudal region.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p23
|
PMC11276889
|
sec[2]/sec[6]/p[0]
|
3.7. Influence of the Residual Dermis under the Wound on Healing Parameters
| 4.113281 |
biomedical
|
Study
|
[
0.99951171875,
0.0002732276916503906,
0.00024437904357910156
] |
[
0.99951171875,
0.00015056133270263672,
0.0004546642303466797,
0.00005245208740234375
] |
Commonly, the rate of wound closure (% of re-epithelialization) is the major healing parameter explored in publications aiming to analyze the skin regeneration process . However, in order to improve the standardization of the model and to better understand how the remaining tissue influences other healing parameters, we decided to include an analysis of the role of the residual tissue in skin regeneration in this study. The results of the Pearson’s correlation test evaluating the underlying dermis and the advent of new epithelium development showed a significant and strong positive correlation between residual dermis thickness and the re-epithelialization process. This indicates that wounds with a thicker residual dermis underneath the wounded area tend to achieve faster wound closure.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p24
|
PMC11276889
|
sec[2]/sec[6]/p[1]
|
3.7. Influence of the Residual Dermis under the Wound on Healing Parameters
| 4.0625 |
biomedical
|
Study
|
[
0.99951171875,
0.00032806396484375,
0.0002994537353515625
] |
[
0.99951171875,
0.0001862049102783203,
0.00028228759765625,
0.00005561113357543945
] |
In examining the correlation between the thickness of the residual dermis and the thickness of the newly formed dermis, once again, a significant and strong correlation was obtained; however, this time, the correlation showed a negative effect. This suggests that the regeneration of the new dermis is based on the thickness of the residual dermis in a negative proportional relationship. It is noteworthy that no qualitative substantial difference in vascular density was observed upon histopathological evaluation. However, since vascularization density was not quantitatively examined in this study, subtle variations may not have been detected.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p25
|
PMC11276889
|
sec[2]/sec[6]/p[2]
|
3.7. Influence of the Residual Dermis under the Wound on Healing Parameters
| 4.117188 |
biomedical
|
Study
|
[
0.99951171875,
0.00031876564025878906,
0.00025153160095214844
] |
[
0.9990234375,
0.0002865791320800781,
0.0006804466247558594,
0.00005602836608886719
] |
This phase of the study suggests that the thickness of the residual dermis is an important factor in wound healing. In the same way that the thickness of the damaged tissue has a direct impact on the healing outcome , the thickness of the dermal tissue under the wound bed influences the regeneration process. A thicker remaining dermis provides a more suitable environment for keratinocyte proliferation, offering better healing support . Thus, wounds with thicker remaining dermis tend to close faster (i.e., have higher re-epithelialization rates) than wounds presenting thinner ones. For the regeneration of the dermal tissue, on the other hand, the opposite was observed, where the thickness of the residual dermis negatively impacted dermal regeneration. This negative influence was rather expected but important, since a positive influence would create hyper-granulation, a less desirable healing outcome.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276889_p26
|
PMC11276889
|
sec[2]/sec[7]/p[0]
|
3.8. Comparable Studies
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.00027251243591308594,
0.00026416778564453125
] |
[
0.99951171875,
0.00019824504852294922,
0.000476837158203125,
0.00005602836608886719
] |
Partial-thickness excisional wounds in pigs performed with a dermatome have been the subject of several prior studies. Table 1 outlines the important elements, including wound size, wound number, pig strain, and wound depth, to show how our study differs from these earlier studies. We may better comprehend the distinctive contributions and constraints of our study, as well as how it fits into the overall body of knowledge on partial-thickness wounds in pigs and their standardization, by contrasting and comparing these elements. Furthermore, none of these studies have performed a comparable complete histological analysis. The histological analysis performed in our study provides a comprehensive examination of the healing process and tissue regeneration following partial-thickness excisional wounds.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p27
|
PMC11276889
|
sec[2]/sec[8]/p[0]
|
3.9. Limitations
| 3.865234 |
biomedical
|
Study
|
[
0.9990234375,
0.0002605915069580078,
0.0005536079406738281
] |
[
0.99951171875,
0.0003540515899658203,
0.0003094673156738281,
0.000052034854888916016
] |
One limitation of this study might be the young age of the pigs and their faster wound healing compared to older pigs. Additionally, in our experiments, only female animals were considered; therefore, potential variability in the healing outcomes for gilts and barrows could not be observed. Moreover, as with all animal experiments, it is also possible that the results of this study may not be fully applicable to humans, as there are differences between pigs and humans. Another limitation might be that the study was limited to a single type of wound, and it is not clear whether the results would be the same for other types of wounds. Our experiment studying the influence of the residual dermis was based on six sites that received the exact same treatment on a single animal.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276889_p28
|
PMC11276889
|
sec[3]/sec[0]/p[0]
|
4.1. Animal Wound Model Development
| 4.210938 |
biomedical
|
Study
|
[
0.9931640625,
0.0066375732421875,
0.00029397010803222656
] |
[
0.99365234375,
0.0046844482421875,
0.0006413459777832031,
0.0009608268737792969
] |
The experiments were approved by the Animal Care and Use Committee (Veterinary University of Vienna, Austrian Ministry for Science and Research). For this model, we used female pigs (domestic pig— Sus domesticus ) aged 3–5 months and weighing approximately 24–57 kg. Anesthesia and analgesia were performed on the animals by a trained veterinarian. The animal received oxygen via facemask and anesthesia with 1–2% sevoflurane (SEVOrane ® , AbbVie GmbH, Vienna, Austria). Furthermore, via an intravenous line placed in the ear, analgesics and, if needed, additional anesthesia were administered. After anesthesia and pain management were completed, the dorsum of the animal was cleaned, and the hair was clipped. Then, the planned positioning of the wounds was marked. In total, there were 12 wounds, 6 on each side of the vertebral column. The midline (spine) and cranial height (caudal angle of the scapula) were marked where the wounds would begin. The distance to the spine or midline was 3 cm laterally. The distance between the wounds was 4 cm to ensure that they did not influence each other . After disinfection with Octenisept ® (Schülke & Mayr GmbH, Norderstedt, Germany), the 12 dermatome wounds, each 3 cm × 3 cm with a depth of 1.2 mm, were set on the dorsum lateral to the spine of the pigs using a battery-operated dermatome . The upper skin excised with the dermatome was stored as a sample for further investigation of its thickness in neutral buffered formalin (NBF) in biopsy cassettes. In order to stop initial bleeding from the dermatome wounds, compression was applied. After sufficient hemostasis was achieved, the study dressings (epicite hydro , QRSkin GmbH, Wuerzburg, Germany) were applied to the wounds and fixed in place with staples to prevent dislocation. A protective dressing was then applied and fixed to the area with staples. For analgesia, a transdermal opioid pain patch (Fentanyl 50 µg/h, Gebro Pharma GmbH, Fieberbrunn, Austria) was applied to the animal’s gluteal region. Finally, a protective bodysuit was put on to protect the bandages and wounds from alterations. No neck collarette was used. After the surgical procedure was completed, the animals were placed into their pen for recovery. For the next seven days, the animals were monitored for any signs of pain, discomfort, or distress, and if needed, treated accordingly. Seven days after sustaining the injuries, the animals were anesthetized and euthanized using a 1 mol/L dose of potassium chloride (1 M-Kaliumchlorid-Lösung, Fresenius Kabi AG, Bad Homburg vor der Höhe, Germany). Once the veterinarian confirmed the animals’ deaths with certainty, the protective body suits and protective bandages and staples were removed. The study doctor then carried out a macroscopic evaluation of the wounds, paying particular attention to infection or other abnormalities, followed by exact photographic documentation of the wounds and wound dressings. The wound areas were marked for orientation with a biopsy punch for mapping studies of the wounds. On some wounds, the wound dressings were partially removed for evaluation of the influence of manipulation of the wound before histological assessment. The wounds were then excised epifascially in toto for further histological investigation by a veterinary pathologist. The skin samples, including the samples of microtome-excised superficial skin taken on day 1, were sent to the pathology laboratory (TPL Path Labs GmbH, now StageBio, Freiburg, Germany).
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p29
|
PMC11276889
|
sec[3]/sec[1]/sec[0]/p[0]
|
4.2.1. General
| 4.191406 |
biomedical
|
Study
|
[
0.99951171875,
0.0005345344543457031,
0.0001728534698486328
] |
[
0.9990234375,
0.0004138946533203125,
0.0004680156707763672,
0.00010085105895996094
] |
Tissues were fixed with NBF for a maximum of 72 h and routinely trimmed according to the standard protocol, embedded in paraffin, cut at a nominal thickness of 3 µm, and stained with hematoxylin and eosin (H&E) using standard operating procedures. A histopathologist then conducted an analysis of the slides, blinded to the treatment modalities. He concentrated the analysis on the width of each wound and the process of repair of primarily two tissues: the epidermal tissue (analyzing the epidermal area, the percentage of re-epithelialization, and the standard thickness of epidermis) and the dermal tissue (analyzing the new granulation tissue area and the thickness scoring for the new dermis on each harvested tissue sample). Additionally, Zen 3.3 blue edition software (Zeiss Microscopy, Jena, Germany) was used to conduct hand measurements of the morphological characteristics of the new epidermis (percent coverage and average “standard” thickness) and the average thickness of the new and preexisting dermis. The standard thicknesses of the new epidermis and the new dermis were calculated by dividing the new epidermis or new dermis/granulation tissue areas, respectively, by the measured wound length per section (wound width)—see Figure 1 C,D.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276889_p30
|
PMC11276889
|
sec[3]/sec[1]/sec[1]/p[0]
|
4.2.2. Sampling and Histology within the Wound
| 4.09375 |
biomedical
|
Study
|
[
0.9990234375,
0.0005292892456054688,
0.00024819374084472656
] |
[
0.99951171875,
0.0002186298370361328,
0.00021314620971679688,
0.0000718235969543457
] |
Each wound site was sampled, including an approximately 0.5 cm-wide edge of normal preexisting skin adjacent to the wound sites. In the current study, we evaluated the dermatome-induced intra-wound healing process occurring within the wound to examine any changes in healing parameters. An overview of the wound bed at several locations was made possible by macroscopic investigation. Based on this observation, an apparently uneven process of re-epithelialization was suspected. To test this hypothesis, a sampling strategy was designed to examine the influence of within-wound positional locations on healing degree status. This was carried out by choosing several allocations of histological cuts (i.e., the map of suggested slices forwarded to the trimming laboratory before paraffin embedding) within the wound sites . Furthermore, a punch biopsy was conducted cranially outside the wound to permit wound site orientation by the pathologist.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276889_p31
|
PMC11276889
|
sec[3]/sec[1]/sec[2]/p[0]
|
4.2.3. Statistical Analysis
| 3.667969 |
biomedical
|
Study
|
[
0.99951171875,
0.00018084049224853516,
0.0002868175506591797
] |
[
0.998046875,
0.0012722015380859375,
0.0004496574401855469,
0.00008273124694824219
] |
The results of the quantitative variables of the study were expressed as the mean ± standard deviation (SD), and significant differences were calculated using Student’s t -test, with significance indicated by p < 0.05. Pearson’s correlation analysis was used to analyze the relationship between the different quantitative healing parameters. The results are expressed in terms of Pearson’s correlation coefficients and p -values. Data analysis was performed using GraphPad Prism 9 (GraphPad Software, La Jolla, CA, USA).
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276889_p32
|
PMC11276889
|
sec[4]/p[0]
|
5. Conclusions
| 4.207031 |
biomedical
|
Study
|
[
0.9990234375,
0.0007853507995605469,
0.00017392635345458984
] |
[
0.998046875,
0.0003921985626220703,
0.0015354156494140625,
0.00016832351684570312
] |
In conclusion, our study has contributed significantly to the field of wound healing by designing and characterizing a standardized porcine model for wound healing evaluation. We implemented a unique approach by performing histological analyses over the complete wound length, in contrast to previous studies, which have only described/analyzed selected punch biopsies. This method provided unprecedented insights into the complex process of wound healing and allowed us to identify the impact of various factors on wound healing. Another important conclusion with potential clinical relevance of this study suggests that a wound’s ability to heal is significantly influenced by the thickness of the residual dermis under the wounded area. In comparison to wounds with thinner residual dermis, wounds with thicker residual dermis typically healed more quickly (i.e., re-epithelialize more rapidly). This is probably because the thicker dermis offers a better physical and/or chemical environment for the regeneration of new epidermal tissue, perhaps better supplying the necessary growth factors through a better vascular network. This hypothesis could be tested in further studies. The clinical significance of this study lies in its introduction of a new parameter, residual dermis thickness, which has the potential to enhance wound healing by informing and directing treatment options, ultimately resulting in improved patient outcomes.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276889_p33
|
PMC11276889
|
sec[4]/p[1]
|
5. Conclusions
| 4.058594 |
biomedical
|
Study
|
[
0.99951171875,
0.00025916099548339844,
0.00012481212615966797
] |
[
0.99658203125,
0.00043702125549316406,
0.0027313232421875,
0.00010645389556884766
] |
Additionally, our findings prove that the current porcine wound model is a reproducible tool for evaluating dermal and epidermal wound healing. This model could serve as a useful platform for future research on novel wound dressings and local wound healing therapies. Overall, our study adds to the current understanding of wound healing and provides a foundation for further investigation in this area. By providing insights into the underlying mechanisms of wound healing, this research may pave the way for the development of more effective therapies and treatments for wound healing in both humans and animals. Furthermore, the development of a standardized porcine model for wound healing evaluation will enable researchers to better understand the complexities of wound healing and ultimately improve outcomes for patients suffering from wounds.
|
[
"Alexandru-Cristian Tuca",
"Ives Bernardelli de Mattos",
"Martin Funk",
"Danijel Markovic",
"Raimund Winter",
"Thomas Lemarchand",
"Daniela Kniepeiss",
"Stephan Spendel",
"Bernd Hartmann",
"Christian Ottoman",
"Lars-Peter Kamolz"
] |
https://doi.org/10.3390/ijms25147658
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p0
|
PMC11276901
|
sec[0]/p[0]
|
1. Introduction
| 1.53125 |
other
|
Other
|
[
0.25048828125,
0.001956939697265625,
0.74755859375
] |
[
0.00684356689453125,
0.9892578125,
0.003513336181640625,
0.0002963542938232422
] |
Urbanization has transformed city landscapes, and the expansion of built-up areas often reduces urban green spaces (UGSs), which can play an important role in promoting physical activity, social interactions, and public health. Increasing mental health issues have spurred research into the benefits of UGS .
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p1
|
PMC11276901
|
sec[0]/p[1]
|
1. Introduction
| 3.681641 |
biomedical
|
Study
|
[
0.91796875,
0.000591278076171875,
0.08123779296875
] |
[
0.99853515625,
0.0005364418029785156,
0.0006895065307617188,
0.0000426173210144043
] |
Building on research by Bressane et al. , which found significant associations between nature engagement and reduced mental health issues in Brazilian cities, this study delves into whether simply having urban green space in the neighborhood is enough to significantly impact residents’ mental well-being. Although recognized for their benefits, a deeper understanding of how UGS suitability affects mental well-being is limited. Makram et al. found that neighborhoods with higher NatureScores—an indicator of urban greenness—have significantly lower mental health issues. However, most research overlooks the suitability of green spaces for recreational use, limiting urban planning strategies. Recent findings highlight the multifaceted benefits of green spaces, such as improved sleep and lower blood pressure .
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p2
|
PMC11276901
|
sec[0]/p[2]
|
1. Introduction
| 1.770508 |
biomedical
|
Other
|
[
0.87744140625,
0.0014019012451171875,
0.1212158203125
] |
[
0.1063232421875,
0.85498046875,
0.0374755859375,
0.0010251998901367188
] |
Although research in developed nations highlights the mental health benefits of green spaces, similar studies are lacking in developing countries . The socio-economic and environmental contexts in the Global South differ significantly from those in developed nations, potentially altering the relationship between nature exposure and mental health.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p3
|
PMC11276901
|
sec[0]/p[3]
|
1. Introduction
| 3.613281 |
biomedical
|
Study
|
[
0.923828125,
0.0007534027099609375,
0.07550048828125
] |
[
0.9990234375,
0.0005564689636230469,
0.00019359588623046875,
0.00004696846008300781
] |
In the context of Brazilian metropolitan regions, the study aims to determine if higher intensity, frequency, and duration of nature activities correlate with lower depression, anxiety, and stress levels, moderated by UGS suitability. The present study hypothesizes that accessibility to UGSs with suitable infrastructure for visitation and physical activities, like leisure or recreation, provides more significant benefits. Higher nature engagement is expected to negatively correlate with mental health issues, moderated by green space suitability. By addressing these aspects, this study aims to deepen the understanding of the role of UGS in promoting mental health and to guide the creation of urban environments conducive to well-being. Confirming the hypothesis could offer important insights for healthier city design.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p4
|
PMC11276901
|
sec[1]/sec[0]/p[0]
|
2.1. Impact of UGS on Mental Health
| 3.822266 |
biomedical
|
Study
|
[
0.828125,
0.00087738037109375,
0.171142578125
] |
[
0.97900390625,
0.001171112060546875,
0.0199432373046875,
0.00009554624557495117
] |
Research consistently indicates that exposure to UGSs is associated with enhanced psychological well-being. For instance, a study by White et al. utilized a large-scale longitudinal dataset to examine the effects of green space exposure on mental well-being. The findings revealed that individuals residing in areas with greater green space reported higher levels of life satisfaction and lower levels of mental distress compared to those in less green areas. The study underscores the potential of green spaces to foster a sense of well-being among urban residents. A recent study by Helbich et al. further supports this notion, revealing that residential green space is positively associated with lower risks of depression, particularly in women and lower-income groups. This large-scale, cross-sectional study utilized high-resolution satellite imagery to assess green space exposure, providing robust evidence for the psychological benefits of urban greenery.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p5
|
PMC11276901
|
sec[1]/sec[0]/p[1]
|
2.1. Impact of UGS on Mental Health
| 3.921875 |
biomedical
|
Review
|
[
0.96630859375,
0.00511932373046875,
0.0287017822265625
] |
[
0.006290435791015625,
0.0010013580322265625,
0.99267578125,
0.00020587444305419922
] |
UGSs also play a crucial role in stress reduction. A systematic review by Bowler et al. analyzed various studies assessing the impact of natural environments on stress. The review found that interaction with green spaces, whether through passive viewing or active engagement, significantly reduced physiological markers of stress, such as cortisol levels, and self-reported stress measures. This body of evidence suggests that urban green spaces can serve as a natural antidote to the high stress levels prevalent in urban settings. A more recent meta-analysis by Twohig-Bennett and Jones confirmed these findings, indicating that exposure to natural environments significantly reduces stress and improves overall mood. This comprehensive review of over 140 studies strengthens the argument for integrating green spaces into urban planning to mitigate stress and enhance mental health.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p6
|
PMC11276901
|
sec[1]/sec[0]/p[2]
|
2.1. Impact of UGS on Mental Health
| 3.935547 |
biomedical
|
Study
|
[
0.99853515625,
0.0003509521484375,
0.0012111663818359375
] |
[
0.90576171875,
0.0008144378662109375,
0.09344482421875,
0.00017178058624267578
] |
Beyond general well-being and stress reduction, UGSs have been linked to the alleviation of specific mental health disorders. A notable study by van den Berg et al. explored the relationship between green space and depression. The researchers found that individuals with more access to green spaces were less likely to experience depressive symptoms. This association was particularly pronounced in socioeconomically disadvantaged populations, indicating that green spaces could serve as an equalizer in mental health disparities. Recent evidence from a longitudinal study by Wendelboe-Nelson et al. supports these findings, demonstrating that increased exposure to green space is associated with a lower incidence of major depressive disorder. This study followed participants over a five-year period, providing strong evidence for the long-term mental health benefits of urban greenery.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p7
|
PMC11276901
|
sec[1]/sec[0]/p[3]
|
2.1. Impact of UGS on Mental Health
| 4.015625 |
biomedical
|
Review
|
[
0.98095703125,
0.0010747909545898438,
0.017913818359375
] |
[
0.2022705078125,
0.002079010009765625,
0.79541015625,
0.0002467632293701172
] |
The mechanisms through which urban green spaces impact mental health are multifaceted. Attention Restoration Theory of Kaplan and Kaplan posits that natural environments facilitate cognitive recovery from mental fatigue, thereby enhancing mental functioning. Additionally, the Biophilia Hypothesis, proposed by Wilson , suggests an innate human affinity for nature, which can inherently improve mental health outcomes. These theoretical frameworks provide a basis for understanding the psychological benefits derived from urban green spaces. A recent study by Markevych et al. proposed an integrated conceptual model that combines these theories with empirical findings, suggesting that green spaces impact mental health through multiple pathways, including social cohesion, physical activity, and environmental stress reduction. This model underscores the complex interplay of factors contributing to the mental health benefits of urban green spaces.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p8
|
PMC11276901
|
sec[1]/sec[1]/p[0]
|
2.2. Quality and Accessibility of UGS
| 2.261719 |
other
|
Study
|
[
0.41845703125,
0.0008711814880371094,
0.58056640625
] |
[
0.9384765625,
0.046661376953125,
0.0142974853515625,
0.000408172607421875
] |
The quality of UGS encompasses aspects such as maintenance, safety, amenities, biodiversity, and aesthetic value. High-quality green spaces are more likely to be used by residents and provide greater health benefits. Proper maintenance and perceived safety are essential for the utilization of urban green spaces. A study by Van Dillen et al. found that well-maintained and safe green spaces significantly enhance their use and contribute to improved mental health and well-being. The study emphasized that neglect and safety concerns could deter individuals from using these spaces, thereby negating potential health benefits.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p9
|
PMC11276901
|
sec[1]/sec[1]/p[1]
|
2.2. Quality and Accessibility of UGS
| 1.580078 |
other
|
Other
|
[
0.09088134765625,
0.0007395744323730469,
0.908203125
] |
[
0.2025146484375,
0.77783203125,
0.0188751220703125,
0.0009250640869140625
] |
The presence of amenities such as playgrounds, benches, walking paths, and sports facilities can significantly enhance the attractiveness and usability of green spaces. Kaczynski and Henderson reported that the availability of diverse recreational facilities in urban parks is positively associated with physical activity levels among residents. This highlights the importance of incorporating various amenities to cater to different user preferences and promote active lifestyles.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p10
|
PMC11276901
|
sec[1]/sec[1]/p[2]
|
2.2. Quality and Accessibility of UGS
| 1.852539 |
other
|
Study
|
[
0.2607421875,
0.0009293556213378906,
0.73828125
] |
[
0.810546875,
0.1700439453125,
0.0184783935546875,
0.0009360313415527344
] |
Biodiversity and aesthetic appeal also play crucial roles in the perceived quality of green spaces. Fuller et al. demonstrated that higher biodiversity in urban parks is associated with greater psychological benefits, including reduced stress and improved mood. The study suggested that biodiversity enhances the restorative experience of green spaces, making them more beneficial for mental health.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p11
|
PMC11276901
|
sec[1]/sec[1]/p[3]
|
2.2. Quality and Accessibility of UGS
| 1.868164 |
other
|
Study
|
[
0.08477783203125,
0.0005373954772949219,
0.91455078125
] |
[
0.9482421875,
0.04913330078125,
0.002414703369140625,
0.00040602684020996094
] |
Accessibility refers to the ease with which residents can reach and use green spaces. It is influenced by factors such as proximity, connectivity, and socio-economic barriers. Proximity to green spaces is a key determinant of their use. A study by Schipperijn et al. found that the likelihood of using urban green spaces decreases as the distance from one’s residence increases. This study highlighted the need for equitable distribution of green spaces within urban areas to ensure all residents have easy access. Additionally, the study emphasized the importance of connectivity, such as pedestrian and cycling paths, to facilitate access.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p12
|
PMC11276901
|
sec[1]/sec[1]/p[4]
|
2.2. Quality and Accessibility of UGS
| 2.164063 |
other
|
Review
|
[
0.08642578125,
0.0023670196533203125,
0.9111328125
] |
[
0.08270263671875,
0.0635986328125,
0.8525390625,
0.0011854171752929688
] |
Socio-economic factors can significantly affect access to green spaces. Rigolon reviewed disparities in green space access and found that lower-income and minority communities often have less access to high-quality green spaces. This inequity can exacerbate health disparities, as these communities might not benefit from the mental and physical health advantages provided by green spaces. An inclusive design that considers the needs of diverse populations, including children, the elderly, and people with disabilities, is crucial for enhancing accessibility. A study by Byrne et al. highlighted that inclusive design can promote greater use and enjoyment of green spaces by all community members. The study recommended incorporating features such as accessible paths, sensory gardens, and age-appropriate amenities.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p13
|
PMC11276901
|
sec[1]/sec[2]/p[0]
|
2.3. Brazilian Context
| 3.853516 |
biomedical
|
Study
|
[
0.984375,
0.00036263465881347656,
0.0155029296875
] |
[
0.96142578125,
0.0011749267578125,
0.037109375,
0.00009173154830932617
] |
A few recent studies have further explored the effect of UGSs on mental well-being in the Brazilian context. Bressane et al. conducted a primary survey in Brazil assessing the association between contact with nature and symptoms of anxiety, stress, and depression. They found that frequent contact with nature significantly reduced the likelihood of these mental health issues, emphasizing the mental health benefits of regular interaction with natural environments. In turn, Bressane et al. found specific patterns and frequencies of nature contact that are most beneficial for mental health, providing insights for urban planning and public health strategies. Bressane et al. investigated how the naturalness of green spaces impacts public well-being. Their study highlighted that more natural green spaces, with higher biodiversity and less human intervention, provided greater mental health benefits, supporting the design of healthier urban environments.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p14
|
PMC11276901
|
sec[1]/sec[2]/p[1]
|
2.3. Brazilian Context
| 3.376953 |
biomedical
|
Study
|
[
0.9912109375,
0.0004673004150390625,
0.00812530517578125
] |
[
0.97021484375,
0.00144195556640625,
0.0279693603515625,
0.00015556812286376953
] |
As highlighted in this literature review, while many studies such as those by White et al. and Helbich et al. have established the general benefits of UGSs on mental health in developed countries, there is a notable gap in research within developing countries. This study fills this gap by examining the intensity, frequency, and duration of nature activities and their correlation with mental health outcomes in Brazil, thus providing valuable insights into a different socio-economic and environmental context.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p15
|
PMC11276901
|
sec[1]/sec[2]/p[2]
|
2.3. Brazilian Context
| 3.894531 |
biomedical
|
Study
|
[
0.97900390625,
0.00039458274841308594,
0.0205230712890625
] |
[
0.99755859375,
0.00036525726318359375,
0.002227783203125,
0.00004857778549194336
] |
Furthermore, this study addresses the critical but often overlooked moderating role of UGS suitability. The literature review points out that the quality and accessibility of green spaces are crucial for maximizing their mental health benefits . By investigating how the quality and infrastructure of green spaces influence mental health benefits, this study offers practical implications for urban planning. Findings from similar contexts, such as the study by Wendelboe-Nelson et al. , which highlighted the long-term mental health benefits of green space, support the significance of this research. The use of a diverse sample from Brazilian metropolitan cities further ensures the generalizability of the findings in previous studies conducted in other regions, making this study a valuable addition to the existing body of literature on the benefits of urban green spaces and their role in promoting mental health.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p16
|
PMC11276901
|
sec[2]/sec[0]/p[0]
|
3.1. Study Area
| 2.828125 |
biomedical
|
Study
|
[
0.84326171875,
0.0010547637939453125,
0.15576171875
] |
[
0.99658203125,
0.0029125213623046875,
0.0003235340118408203,
0.00010770559310913086
] |
This study explores the UGS–mental well-being relationship within metropolitan cities in Brazil, a country with the highest anxiety rate in the world and the third highest rate of depression in Latin America . In Brazil, UGSs are diverse, ranging from public parks to community gardens . Rapid urban growth in this country often reduces access to these environments . Brazilian cities, where complex social, economic, and environmental factors shape public health outcomes, face unique challenges in maintaining mental health through green spaces . Rapid urbanization and rich biodiversity create a stark contrast, leading to nature disconnection, urban heat island effects, environmental degradation, and adverse mental health impacts .
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p17
|
PMC11276901
|
sec[2]/sec[1]/p[0]
|
3.2. Experimental Design
| 2.744141 |
biomedical
|
Study
|
[
0.9423828125,
0.0010280609130859375,
0.056793212890625
] |
[
0.99853515625,
0.0011701583862304688,
0.0001691579818725586,
0.00006103515625
] |
The survey questionnaire was designed to assess participants’ interaction with nature and their mental health. The variables analyzed include intensity of nature engagement, indicating the physical activity level; duration of nature engagement; frequency of nature engagement; UGS suitability, indicating the accessibility to UGS in the neighborhood with suitable infrastructure for visitation and physical activities; and mental well-being scores, encompassing depression, anxiety, and stress levels. The analysis also controls for sociodemographic factors, including gender, age, income, and education.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p18
|
PMC11276901
|
sec[2]/sec[2]/p[0]
|
3.3. Survey Sections
| 4.015625 |
biomedical
|
Study
|
[
0.95751953125,
0.0008463859558105469,
0.041717529296875
] |
[
0.9990234375,
0.00039196014404296875,
0.0003268718719482422,
0.00004380941390991211
] |
The first section of the survey provided demographic details of participants, including gender, age, income, education, and place of residence. The second section recorded the weekly frequency of engagement with nature, ranging from “less than once” to “more than three times”. The duration of weekly nature interactions was measured in 30 min intervals, from “30 min” to “over 240 min”. In this same section, participants were also asked about the types of activities undertaken during these interactions, categorized by intensity levels: low, moderate, or high. Activities included observing, walking, fishing, meditating, camping, horseback riding, running, cycling, swimming, and others. This categorization was based on physical exertion levels, referencing standards by Haskell et al. and Ainsworth et al. , being that low-intensity activities, observing, meditating, walking (minimal physical effort, promoting relaxation and mindfulness); moderate-intensity activities, fishing, camping, horseback riding (moderate physical exertion, more engaging than low-intensity activities); and high-intensity activities, running, cycling, swimming (vigorous, significantly demanding, higher energy expenditure). In the third section, the participants specified whether they have access to UGSs in the neighborhood (within a 300 m radius), with the response options: “yes, with suitable infrastructure for visitation and physical activities”, “yes, but with unsuitable infrastructure for visitation and physical activities”, or “no, there are no UGS in my neighborhood”. The final section included the Depression, Anxiety, and Stress Scale (DASS-21), a validated tool for assessing psychological health . The DASS-21 utilizes a four-point Likert-type scale to gauge symptoms of depression, anxiety, and stress.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p19
|
PMC11276901
|
sec[2]/sec[3]/p[0]
|
3.4. Data Collection
| 1.867188 |
other
|
Study
|
[
0.2431640625,
0.0010738372802734375,
0.755859375
] |
[
0.97802734375,
0.02130126953125,
0.00043463706970214844,
0.0002579689025878906
] |
Data were collected from a diverse group of respondents in a metropolitan region in Brazil using a dual recruitment strategy. The survey was disseminated via social media and email to educational institutions, leveraging their demographic diversity. Special efforts targeted underrepresented groups, such as older adults and individuals from lower socioeconomic backgrounds, through partnerships with local organizations and public libraries. Reminders were sent to boost participation rates among less active online communities. This strategy aimed to ensure a representative sample of the urban population in Brazil. Previous research has shown the efficacy of using varied channels, including schools and word of mouth, to engage urban populations and enhance participation rates . Collaborations with local organizations and public libraries were specifically chosen to engage underrepresented groups, addressing potential biases and ensuring diverse socioeconomic representation .
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276901_p20
|
PMC11276901
|
sec[2]/sec[4]/p[0]
|
3.5. Data Analysis
| 4.105469 |
biomedical
|
Study
|
[
0.9990234375,
0.00037384033203125,
0.0008211135864257812
] |
[
0.99951171875,
0.00016498565673828125,
0.0003783702850341797,
0.00004315376281738281
] |
Correlations between activity intensity, duration, frequency, and mental health scores were computed, considering the quality of nearby green spaces. This method effectively elucidates how combinations of independent variables (nature contact dimensions) relate to multiple dependent variables (mental health outcomes), providing a comprehensive view of these interactions. Multiple regression analyses determined the impact of activity intensity, duration, and frequency on mental health scores, controlling for sociodemographic variables and green space quality. Interaction effects between green space quality and activity intensity, duration, and frequency on mental health outcomes were also examined. Analyses of variance (ANOVA) compared mean mental health scores across different activity intensity and frequency levels and UGS suitability categories . To ensure the reliability of the scale’s grouping, a robustness check was conducted by calculating Cronbach’s alpha, which resulted in a value of 0.789, indicating satisfactory internal consistency. While a value of 0.8 is traditionally considered good, a Cronbach’s alpha above 0.7 is generally acceptable for most research purposes . A test power (1 − β) of 0.8 was adopted, indicating an 80% probability of detecting significant effects and minimizing Type II errors . The significance level (α) was set at 0.05, the standard threshold for determining statistical significance while controlling for the false discovery rate. The minimum detectable effect size (rho) was set at 5%.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p21
|
PMC11276901
|
sec[2]/sec[5]/p[0]
|
3.6. Ethical Considerations
| 1.384766 |
biomedical
|
Other
|
[
0.875,
0.0019893646240234375,
0.12310791015625
] |
[
0.080810546875,
0.91748046875,
0.0010805130004882812,
0.0007872581481933594
] |
The study complied with Brazilian ethical standards for human research, as confirmed by approval from the ethical review board . Participant anonymity and confidentiality were maintained throughout the research process.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276901_p22
|
PMC11276901
|
sec[3]/p[0]
|
4. Results
| 2.462891 |
biomedical
|
Study
|
[
0.931640625,
0.0009236335754394531,
0.06768798828125
] |
[
0.99755859375,
0.002197265625,
0.000148773193359375,
0.00007039308547973633
] |
This study included a diverse group of 2136 participants, with 59.6% female. Educational attainment was high: 83.5% held a university degree, 16.2% completed high school, and 0.3% had only elementary education. Age distribution was 15.7% young adults (18–25 years), 55.2% adults (26–45 years), and 29.1% middle-aged adults (46–65 years). Income distribution was 16.2% in the lower-income bracket (up to 2 minimum wages), 21.9% in the lower-middle income bracket (2–4 minimum wages), 37% in the middle-income bracket (4–10 minimum wages), and 17.7% in the upper-middle income range (10–20 minimum wages).
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p23
|
PMC11276901
|
sec[3]/p[1]
|
4. Results
| 4.058594 |
biomedical
|
Study
|
[
0.998046875,
0.000396728515625,
0.00159454345703125
] |
[
0.99951171875,
0.00012171268463134766,
0.00022602081298828125,
0.00003081560134887695
] |
Regarding depression, anxiety, and stress scores, stratified by activity intensity, duration, frequency, and UGS suitability, the data revealed that individuals engaging in high-intensity activities (mean depression score = 4.75, SD = ±3.92), for longer durations (mean anxiety score = 2.55, SD = ±3.05), and with greater frequency (mean stress score = 5.32, SD = ±4.17) tend to exhibit lower scores of depression, anxiety, and stress. Notably, those with access to suitable UGSs show lower mental health scores (mean depression = 6.21, anxiety = 2.85, stress = 6.85) compared to individuals without nearby UGSs (mean depression = 6.52, anxiety = 3.27, stress = 6.95) or those with access to inadequate spaces (mean depression = 7.37, anxiety = 2.93, stress = 6.30).
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p24
|
PMC11276901
|
sec[3]/p[2]
|
4. Results
| 2.4375 |
biomedical
|
Study
|
[
0.9912109375,
0.0007867813110351562,
0.0081634521484375
] |
[
0.998046875,
0.0015392303466796875,
0.0003571510314941406,
0.00010699033737182617
] |
Table 1 and Table 2 present the correlation and multiple regression analysis, respectively, between activity intensity, duration, frequency, and mental health scores, including the quality of green spaces within a 300 m radius.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276901_p25
|
PMC11276901
|
sec[3]/p[3]
|
4. Results
| 3.921875 |
biomedical
|
Study
|
[
0.99072265625,
0.0003428459167480469,
0.00887298583984375
] |
[
0.99951171875,
0.00023221969604492188,
0.00034117698669433594,
0.000027298927307128906
] |
Significant negative correlations between activity variables (intensity: r = −0.261, duration: r = −0.221, frequency: r = −0.211) and depression scores reinforce the notion that greater nature engagement is associated with better mental well-being. Similar results were found for anxiety (intensity: r = −0.120, duration: r = −0.157, frequency: r = −0.155) and stress (intensity: r = −0.176, duration: r = −0.176, frequency: r = −0.185). The moderate correlation between UGS suitability and mental scores (depression: r = −0.107, anxiety: r = −0.067, stress: r = −0.084) suggests that the quality of nearby UGSs can enhance these benefits.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p26
|
PMC11276901
|
sec[3]/p[4]
|
4. Results
| 4.078125 |
biomedical
|
Study
|
[
0.998046875,
0.0003578662872314453,
0.0016574859619140625
] |
[
0.99951171875,
0.00013339519500732422,
0.00036263465881347656,
0.000034928321838378906
] |
For depression scores, significant negative coefficients were found for activity intensity (−0.627, p < 0.001), duration (−0.098, p = 0.002), and frequency (−0.212, p = 0.001). Additionally, UGS suitability within the neighborhood also showed a significant negative coefficient (−0.258, p = 0.010), suggesting that the quality of nearby green spaces plays an important role in reducing depression. Regarding anxiety scores, significant negative coefficients were also observed for activity intensity (−0.319, p = 0.001), duration (−0.094, p = 0.006), and frequency (−0.238, p = 0.001). UGS suitability also showed a significant negative coefficient (−0.368, p = 0.001), reinforcing the importance of high-quality green spaces. Concerning stress scores, as with depression and anxiety, significant negative coefficients were found for activity intensity (−0.278, p = 0.005), duration (−0.123, p = 0.001), and frequency (−0.213, p = 0.003). However, UGS suitability was not significant for stress (−0.166, p = 0.500), which may indicate that other factors, beyond this suitability, could moderate the effects of stress.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11276901_p27
|
PMC11276901
|
sec[3]/p[5]
|
4. Results
| 4.058594 |
biomedical
|
Study
|
[
0.99755859375,
0.000293731689453125,
0.0020236968994140625
] |
[
0.99951171875,
0.0001837015151977539,
0.00025200843811035156,
0.00003081560134887695
] |
The apparent discrepancy between low correlations and highly significant regression coefficients may arise from the nature of these statistical analyses. Correlations only measure the strength and direction of a linear relationship between two variables without accounting for the influence of other variables. In contrast, multiple regression analysis considers the simultaneous effects of multiple predictors on the outcome variable, allowing for the control of confounding factors. In our study, while individual correlations between nature engagement variables and mental health scores are moderate, the regression models show significant coefficients. This indicates that when controlling for other variables such as sociodemographic factors and UGS suitability, the combined effect of nature engagement on mental health outcomes becomes more pronounced.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p28
|
PMC11276901
|
sec[3]/p[6]
|
4. Results
| 2.478516 |
biomedical
|
Study
|
[
0.9716796875,
0.0009140968322753906,
0.027435302734375
] |
[
0.99853515625,
0.0012264251708984375,
0.0002162456512451172,
0.00007623434066772461
] |
Table 3 presents the results of the ANOVA, conducted to determine if there are significant differences in mean scores of depression, anxiety, and stress among different levels of engagement with nature, stratified by accessibility to suitable UGS within a 300 m radius of the respondents’ residences.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.