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PMC11278699_p10
|
PMC11278699
|
sec[1]/sec[7]/p[0]
|
2.8. 16S rRNA Sequencing of the Colon Microbiota
| 3.466797 |
biomedical
|
Study
|
[
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[
0.9853515625,
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The colon contents were transported to Beijing Biomarker Technology Co., Ltd. (Beijing, China), on dry ice, with 5 biological replicates per group. Microbial sequencing (16S length) was completed by a company using the PacBio sequencing platform, and all microbiome data analysis was completed on the Biomarker Microbial Diversity analysis cloud platform ( www.biocloud.net ), accessed on 18 January 2024.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278699_p11
|
PMC11278699
|
sec[1]/sec[8]/p[0]
|
2.9. Statistical Analysis
| 2.867188 |
biomedical
|
Study
|
[
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All the experimental results are from at least three independent experiments, and all the data are expressed as the mean ± standard error of the mean (S.E.M.). All the data were statistically significant according to one-way analysis of variance (ANOVA) and Student’s t -test in IBM SPSS Statistics 27. p < 0.05 was considered to indicate statistical significance. All figures and graphics were produced using GraphPad Prism 8.0 statistical software (GraphPad Software Inc., San Diego, CA, USA).
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278699_p12
|
PMC11278699
|
sec[2]/sec[0]/p[0]
|
3.1. L. casei IB1 Alleviated DSS-Induced Colitis in Mice
| 4.109375 |
biomedical
|
Study
|
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To survey the alleviating effect of L. casei IB1 on colitis in mice, experimental colitis models were generated in mice induced with 3% DSS in their water for 7 days . Compared to that of the CON group, the body weight of the DSS group was significantly lower ( p < 0.05) . However, compared with those in the DSS group, after the oral administration of L. casei IB1, the weight loss of the mice in the MID group and the HIGH group was alleviated to some extent ( p < 0.05). Compared with that in the CON group, the DAI in the DSS group was significantly greater ( p < 0.05) . In contrast, after treatment with L. casei IB1, the DAI scores of DSS-treated mice in the MID and HIGH groups were significantly greater than those of DSS-treated mice ( p < 0.05). The colon length of the DSS treatment group was significantly shorter than that of the CON group ( p < 0.05) . Compared with DSS, the oral administration of L. casei IB1 efficiently prevented DSS-induced colon shortening ( p < 0.05).
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278699_p13
|
PMC11278699
|
sec[2]/sec[1]/p[0]
|
3.2. Effect of L. casei IB1 on DSS-Induced Colon Histopathology
| 4.125 |
biomedical
|
Study
|
[
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To observe the effect of L. casei IB1 on DSS-induced colon histopathology, we performed HE staining and PAS staining of colon tissue. As shown in Figure 3 A–D, the colonic epithelial cells of the CON group were neatly arranged, the structure was complete, the villi were neat, the crypts were neatly arranged, there was a large number of goblet cells, and there was almost no inflammatory cell infiltration. After 7 days of DSS induction, compared with those in the CON group, the morphology of intestinal epithelial cells in the colon tissue of mice in the DSS group changed, the crypts were destroyed, the mucosal structure was unclear, the lamina propria and submucosa were infiltrated by a large number of inflammatory cells, and a large amount of connective tissue hyperplasia had occurred. In contrast, after treatment with L. casei IB1, compared to the DSS group, colon tissue injury was reduced in the MID and HIGH groups, the crypt structure was orderly, the mucosal structure was intact, and a large number of goblet cells were recovered ( p < 0.01). Therefore, our results showed that L. case i IB1 had a certain preventive effect on DSS-induced colon injury.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278699_p14
|
PMC11278699
|
sec[2]/sec[2]/p[0]
|
3.3. Effect of L. casei IB1 on Serum Cytokine Levels
| 4.082031 |
biomedical
|
Study
|
[
0.99951171875,
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[
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0.0003788471221923828,
0.00007730722427368164
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The levels of serum cytokines (TNF-α, IL-1β, IL-6 I, and L-10) were measured by ELISA. As shown in Figure 4 A–D, compared with those in the CON group, the levels of the cytokines TNF-α, IL-1β, and IL-6 were significantly increased in the DSS group ( p < 0.05), while the concentration of IL-10 was significantly decreased ( p < 0.05). These results suggested that DSS treatment increased the secretion of proinflammatory cytokines and correspondingly reduced the level of anti-inflammatory cytokines. After treatment with L. casei IB1, the levels of the cytokines TNF-α, IL-1β, and IL-6 were significantly lower than those in the DSS group ( p < 0.01), while the levels of the anti-inflammatory cytokine IL-10 were significantly increased ( p < 0.01). The results showed that L. casei IB1 had anti-inflammatory effects on intestinal tissues.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278699_p15
|
PMC11278699
|
sec[2]/sec[3]/p[0]
|
3.4. L. casei IB1 Upregulated Tight Junction Proteins to Improve Colonic Barrier Dysfunction in DSS-Induced Colitis Mice
| 4.089844 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.99951171875,
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0.00006651878356933594
] |
Intestinal epithelial tight junction (TJ) proteins play important roles in maintaining intestinal barrier integrity. To study the changes in TJ proteins in DSS-induced colitis, Western blotting was used to detect changes in Claudin1, Claudin2, and Occludin in colon tissue. As shown in Figure 5 A–C and Figure S1 , after DSS induction, the protein levels of Occludin, Claudin1, and Cluaudin2 in the DSS group were significantly lower than those in the CON group ( p < 0.01). Compared to the DSS group, the levels of the Occludin, Claudin1, and Claudin2 proteins increased after the oral administration of L. casei IB1, among which, those in the MID group and HIGH group increased most significantly ( p < 0.01).
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278699_p16
|
PMC11278699
|
sec[2]/sec[3]/p[1]
|
3.4. L. casei IB1 Upregulated Tight Junction Proteins to Improve Colonic Barrier Dysfunction in DSS-Induced Colitis Mice
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
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0.99951171875,
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0.00040268898010253906,
0.0000743865966796875
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In addition, the protein expression of ZO-1 and Occludin in colon tissue was detected by immunofluorescence to further evaluate the colonic barrier. As shown in Figure 6 A–C, similar to the Western blot results, the expression of tight junction proteins in the DSS group was significantly lower than that in the CON group ( p < 0.01). After treatment with IB1, the protein expression levels of ZO-1 and Occludin increased ( p < 0.05). These results indicate that L. casei IB1 improves DSS-induced intestinal barrier damage by upregulating TJ proteins.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278699_p17
|
PMC11278699
|
sec[2]/sec[4]/p[0]
|
3.5. L. casei IB1 Inhibits the Inflammatory Response by Inhibiting the NF-κB- and MAPK-Mediated Signaling Pathways
| 4.140625 |
biomedical
|
Study
|
[
0.99951171875,
0.0003230571746826172,
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[
0.9990234375,
0.00019979476928710938,
0.0004658699035644531,
0.00008296966552734375
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To study the potential anti-inflammatory mechanism of L. casei IB1, we examined the effects of IB1 on the NF-κB and MAPK signaling pathways. These signaling pathways are important key regulators of the inflammatory process and play an important part in intestinal inflammation. As shown in Figure 7 A–D and Figure S2 , after DSS treatment, the expression of key proteins in the NF-κB and MAPK signaling pathways in the DSS group increased compared with that in the CON group ( p < 0.01). Compared with that in the DSS group, the expression of the phosphorylated proteins P65 and P38 decreased after the oral administration of L. casei IB1 ( p < 0.01). Interestingly, after the oral administration of L. casei IB1, only the protein levels of phosphorylated ERK and JNK in the MID group and the HIGH group decreased significantly, and there was no significant difference in the LOW group. These results suggest that L. casei IB1 may alleviate intestinal inflammation by inhibiting the activation of NF-κB and MAPK.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278699_p18
|
PMC11278699
|
sec[2]/sec[5]/p[0]
|
3.6. Effects of L. casei IB1 on Microbial Diversity in the Colon
| 4.175781 |
biomedical
|
Study
|
[
0.99951171875,
0.0005273818969726562,
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[
0.9990234375,
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To explore the relationship between intestinal inflammation and intestinal microbial diversity, we collected the colonic contents of the mice and performed 16S rRNA sequencing. The colon microbiota diversity is shown in Figure 8 A. There were 223 common OTUs in the colon of each experimental group. As shown in Figure 8 B–E, the ACE and Chao1 indices measure species richness. The Simpson and Shannon indices are used to measure species diversity. There was no significant difference in the Chao1 index between the groups. Compared with that of the control group, the ACE index of the DSS group decreased significantly ( p < 0.05). Compared to the DSS group, the ACE index of the LOW group and HIGH group increased significantly ( p < 0.05). There was no significant difference in the Simpson index between the CON and DSS groups. Compared to the DSS group, those of the LOW and MID groups decreased significantly ( p < 0.05). However, compared with those of the CON group, the Shannon indices of the DSS group increased significantly ( p < 0.05), and the diversity of the microbial community significantly improved after the oral administration of L. casei IB1, which was similar to the CON group. The results showed that the oral administration of L. casei IB1 could regulate intestinal homeostasis. To further study the similarity between microbial communities, we performed beta diversity analysis based on weighted UniFrac to perform principal coordinate analysis (PCoA) and nonmetric multidimensional scaling (NMDS). As shown in Figure 8 F–G, there was a clear clustering separation between the DSS group and the CON group, indicating that the bacterial community composition differed between the two groups. However, after treatment with L. casei IB1, the bacterial colony composition overlapped with that of the CON group.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278699_p19
|
PMC11278699
|
sec[2]/sec[6]/p[0]
|
3.7. L. casei IB1 Changed the Structural Composition of Colon Microorganisms
| 4.226563 |
biomedical
|
Study
|
[
0.99951171875,
0.0003769397735595703,
0.00023126602172851562
] |
[
0.99951171875,
0.0002505779266357422,
0.0003857612609863281,
0.00008022785186767578
] |
As shown in Figure 9 , the microbial flora of the five groups of colonic contents mainly consisted of five phyla, namely, Firmicutes , Bacteroidetes , Proteobacteria , Verrucomicrobiota , and Patescibacteria, and nine genera, namely, Lachnospiraceae_NK4A136_group , unclassified Muribaculaceae , unclassified Clostridia_UCG_014 , Bacteroides , uncultured Rumen_bacterium , Faecalibacterium , Escherichia_Shigella , Akkermansia , and Alistipes . At the phylum level, the contents of Verrucomicrobia , Firmicutes , Bacteroidetes , Proteobacteria , and Patescibacteria in the CON group were 51.80%, 41.37%, 1.32%, 0.78%, and 4.17%, respectively. Compared with those in the CON group, the contents of Firmicutes , Bacteroidetes , and Patescibacteria in the DSS group decreased to 31.82%, 31.69%, and 0.06%, respectively, while the contents of Proteobacteria and Verrucomicrobiota increased to 20.69% and 12.67%, respectively. After treatment with L. casei IB1, the contents of Proteobacteria and Verrucomicrobia in the LOW group decreased to 3.38% and 0.62%, those in the MID group decreased to 2.42% and 1.72%, and those in the HIGH group decreased to 1.94% and 4.04%, respectively. At the genus level, the abundance of Faecalibaculum decreased after DSS treatment, while that of Escherichia_Shigella increased. Interestingly, after treatment with L. casei IB1, the abundance of Faecalibacterium increased, while the disruption of Escherichia_Shigella normalized.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278699_p20
|
PMC11278699
|
sec[2]/sec[6]/p[1]
|
3.7. L. casei IB1 Changed the Structural Composition of Colon Microorganisms
| 4.175781 |
biomedical
|
Study
|
[
0.99951171875,
0.0003905296325683594,
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[
0.9990234375,
0.00021851062774658203,
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] |
LEfSe and linear discriminant analysis (LDA) were used to analyze and compare the intestinal flora of each group to better understand the indicator bacteria of each group. As shown in Figure 10 A,B, there were 21, 24, 11, 7, and 6 significant differences between the CON group, DSS group, LOW group, MID group, and HIGH group, respectively. The relative abundances of Muribaculaceae , Bacteroidota , Lactobacillaceae , Saccharimonadaceae and Prevotella in the CON group were greater than those in the DSS group. However, the bacterial diversity that affected the DSS group’s microbiome was distributed in different units. The abundance of potential pathogenic bacteria, such as Escherichia_Shigella at the genus level and Enterobacteriaceae at the family level, increased in the DSS group. After treatment with L. casei IB1, the abundance of potential pathogenic bacteria decreased to the lowest level. In the LOW group, the relative abundances of Clostridia at the class level and Erysipelatoclostridium and Alistipes at the genus level were greater. In the MID group, the relative abundances of Firmicutes at the phylum level and uncultured_rumen_bacterium and Turicibacter at the genus level were greater. In contrast, the relative abundances of unclassified _Clostridia _UCG _014 and Faecalibaculum at the genus level in the HIGH group were greater. In summary, treatment with L. casei IB1 alleviated DSS-induced colitis in mice by reducing the abundance of potential pathogenic bacteria and increasing the relative abundance of probiotics.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278699_p21
|
PMC11278699
|
sec[3]/p[0]
|
4. Discussion
| 4.265625 |
biomedical
|
Study
|
[
0.99951171875,
0.0005202293395996094,
0.0001634359359741211
] |
[
0.99853515625,
0.0003304481506347656,
0.0009393692016601562,
0.00013935565948486328
] |
Recently, great progress has been made in the use of probiotics for the treatment of IBD. Probiotics mainly regulate the intestinal barrier and the balance of the intestinal flora to alleviate IBD. At present, the DSS-induced colitis mouse model is a useful tool for studying the efficacy and mechanism of probiotics in relieving acute IBD . The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating the intestinal flora balance, and modulating the intestinal immune response . As one of the representative bacteria for probiotic-assisted therapy in IBD, multiple strains of Lactobacillus have been proven to alleviate intestinal damage and strengthen the intestinal immunological barrier, epithelial cell barrier, and mucus barrier . Lactic acid bacteria are recognized as safe for use in food fermentation and dietary supplementation and are also thought to potentially colonize the human gastrointestinal tract . Therefore, we used a DSS-induced mouse colitis model to study the effect of L. casei IB1 on colitis in C57BL/6 mice. After 7 days of 3% DSS treatment, the mice showed severe damage, and the clinical symptoms were weight loss, diarrhea, and rectal bleeding . In addition, we confirmed that DSS significantly increased the DAI. On the contrary, the symptoms of colitis in mice treated with L. casei IB1 were significantly alleviated. Compared with the DSS group, treatment with L. casei IB1 significantly increased the colon length of the mice. Histopathological evaluation of the colon tissue revealed that L. casei IB1 treatment significantly reduced colonic mucosal damage, crypt injury, inflammatory cell infiltration, and local ulcers, thereby restoring the integrity of the intestinal epithelium. Goblet cells are glandular cells that secrete mucus, lubricate the surface of the epithelium, and protect the epithelium. They can perform lubrication and physical barrier functions to prevent pathogenic microorganisms from invading the host . In this study, compared with that in the DSS group, the number of goblet cells increased after treatment with L. casei IB1, especially in the MID and HIGH groups. These results confirmed the therapeutic potential of L. casei IB1.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278699_p22
|
PMC11278699
|
sec[3]/p[1]
|
4. Discussion
| 4.148438 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.9990234375,
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Cytokines have a wide range of biological activities. They modulate cell differentiation and growth by binding to corresponding receptors and regulating immune responses . Previous studies have shown that the levels of proinflammatory factors increase and the levels of anti-inflammatory factors decrease in patients with ulcerative colitis and DSS-induced colitis in animal models . Inflammatory factors such as IL-6, IL-10, and TNF-α are the main immune response factors involved in the inflammatory response in IBD . Some researchers believe that blocking IL-1β and IL-6 may be an important direction for the treatment of UC . The concentration of cytokines in serum represents the systemic inflammatory response . In this study, we measured the serum levels of pro-inflammatory factors (TNF-α, IL-1β, IL-6) and the anti-inflammatory factor IL-10 using ELISA. Compared to the DSS group, the levels of pro-inflammatory factors were significantly decreased, while the level of IL-10 was markedly increased after treatment with L. casei IB1. These results suggest that L. casei IB1 may mitigate colitis by reducing proinflammatory factor levels and increasing anti-inflammatory factor levels.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278699_p23
|
PMC11278699
|
sec[3]/p[2]
|
4. Discussion
| 4.082031 |
biomedical
|
Study
|
[
0.99951171875,
0.00023865699768066406,
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[
0.99951171875,
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The integrity of the gut barrier is mainly supported by the tight junctions of epithelial cells. The integrity of the intestinal barrier can prevent pathogens from entering the blood . Studies have shown that DSS intervention can reduce the concentration of related tight junction proteins . ZO-1, occludin, and claudin-1 are important epithelial TJ proteins . In this study, Western blotting and immunofluorescence were used to detect related TJ proteins. Compared with those in the DSS group, the levels of related TJ proteins were greater after treatment with L. casei IB1, and the increase in the middle and high groups was the most significant. The results suggested that L. casei IB1 alleviated colitis by improving the expression of TJ proteins.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278699_p24
|
PMC11278699
|
sec[3]/p[3]
|
4. Discussion
| 4.113281 |
biomedical
|
Study
|
[
0.99951171875,
0.00017499923706054688,
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[
0.998046875,
0.0004787445068359375,
0.0013360977172851562,
0.00008237361907958984
] |
The NF-κB and MAPK signaling pathways are involved in the pathogenesis of IBD . Therefore, the inhibition of NF-κB and MAPK activation is considered to be an important target for the treatment of IBD . The MAPK pathway, which includes the JNK, ERK, and p38 proteins, can regulate different physiological processes (apoptosis, proliferation, and differentiation) in cells and is closely linked to intestinal mucosal injury . These results suggest that L. casei IB1 may alleviate DSS-induced colitis by inhibiting MAPK and NF-κB signaling pathway-related proteins.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278699_p25
|
PMC11278699
|
sec[3]/p[4]
|
4. Discussion
| 4.179688 |
biomedical
|
Study
|
[
0.99951171875,
0.000324249267578125,
0.00013709068298339844
] |
[
0.9990234375,
0.0002340078353881836,
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0.00009846687316894531
] |
The intestinal microflora plays a very important role in maintaining human health, and the stability of the microbial community is conducive to the health of the host . Intestinal microbial imbalances have been shown to be related to various diseases . The gut microbiota has been identified as a key factor in the pathogenesis of IBD . Therefore, the use of probiotics to prevent or treat IBD is a potential treatment strategy. In this study, 16S rRNA sequencing was used to explore the mechanism of action of L. casei IB1 on the intestinal microflora in DSS-induced colitis mice. As with previous studies , a wide range of gut microbiota disorders were observed, including a decrease in the number of OTUs and a disorder of β-diversity. The Chao1 and ACE indices measure species richness, that is, the number of species. The Shannon and Simpson indices are used to measure species diversity. The ACE and Chao1 indices decreased under the influence of DSS, while the Simpson and Shannon indices increased. However, these effects were reversed after treatment with L. casei IB1. Through PCoA and NMDS cluster analysis, it could be seen that the CON group and DSS group were obviously separated and, after treatment with L. casei IB1, the LOW group, MID group, and HIGH group overlapped with the CON group. In summary, L. casei IB1 alleviates colitis by regulating the abundance and diversity of microorganisms.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278699_p26
|
PMC11278699
|
sec[3]/p[5]
|
4. Discussion
| 4.425781 |
biomedical
|
Study
|
[
0.99951171875,
0.0005593299865722656,
0.00017249584197998047
] |
[
0.99853515625,
0.00043010711669921875,
0.0009908676147460938,
0.00021123886108398438
] |
In UC patients, intestinal microbial diversity changes significantly, and intestinal microbial abundance decreases. When intestinal inflammation occurs, the proportion of Firmicute s that maintain intestinal health decreases and the abundance of Proteobacteria increases . Consistent with the above reports, in our study, the proportion of Firmicutes was reduced and the abundance of Proteobacteria was increased in DSS-induced colitis mice. Escherichia_Shigella is a common pathogen that often increases in patients with colitis , and Alistipes has been shown to have the opposite relationship with a variety of inflammatory factors . Bacteroides can produce succinic acid, which aggravates the inflammatory response in patients with ulcerative colitis . Some studies have found that Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis . Faecalibaculum was reported to protect the intestinal epithelial barrier by producing butyric acid . Consistent with the above report, our study found that after treatment with IB1, the abundance of Faecalibaculum was upregulated, which may have led to the production of more butyric acid to mitigate colitis. Escherichia Shigella and Bacteroides exhibited a higher relative abundance in IBD individuals and further led to severe colitis . Consistent with the above reports, the abundances of Escherichia Shigella and Bacteroides in the DSS group increased at the genus level compared with those in the CON group. However, after treatment with L. casei IB1, the proportions of Bacteroides and Escherichia Shigella decreased and the proportions of Faecalibacterium and Alistipes increased. The intestinal environment in vivo is more complex than the cell culture environment in vitro. There are interactions among microorganisms, microbial immune cells, and microbial intestinal epithelial cells in the intestinal tract . IB1 may protect the intestinal barrier by interacting with other bacteria or influencing immune cells. It has been reported that the intestinal symbiotic flora can reduce the susceptibility of mice to experimental colitis through T-cell-derived IL-10 . Therefore, L. casei IB1 promoted the growth of beneficial bacteria in the intestine tract, especially beneficial microorganisms related to butyric acid production, and inhibited harmful microorganisms related to intestinal diseases. In this study, IB1 alleviated DSS-induced colitis in mice to a certain extent by improving the intestinal barrier, inhibiting the inflammatory response, and reshaping the intestinal microbiome structure. Further research is needed to investigate the mechanism of IB1 in the prevention and treatment of IBD.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278699_p27
|
PMC11278699
|
sec[4]/p[0]
|
5. Conclusions
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.00030350685119628906,
0.0001055002212524414
] |
[
0.99658203125,
0.0006546974182128906,
0.0025730133056640625,
0.00014460086822509766
] |
In summary, L. casei IB1 can effectively improve DSS-induced colitis in mice. Its effects include alleviating the clinical symptoms caused by DSS, inhibiting the expression of proinflammatory factors, improving the expression of anti-inflammatory factors and tight junction proteins, inhibiting the activation of the MAPK and NF-κB signaling pathways, promoting the growth of beneficial microorganisms in the intestine, and inhibiting the growth of harmful microorganisms in the intestine. This study provides a potential therapeutic strategy for the future treatment of IBD patients.
|
[
"Jianlong Lao",
"Shuping Yan",
"Yanhong Yong",
"Yin Li",
"Zhaohai Wen",
"Xiaoyong Zhang",
"Xianghong Ju",
"Youquan Li"
] |
https://doi.org/10.3390/microorganisms12071379
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p0
|
PMC11278711
|
sec[0]/p[0]
|
1. Introduction
| 4.070313 |
biomedical
|
Review
|
[
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] |
[
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] |
Glaucoma is a complex disease of ocular disorders causing a characteristic pattern of loss of retinal ganglion cells and damage to their axons, which damage the optic nerve head . The global prevalence of glaucoma in the population aged 40 to 80 years is estimated at 3.54%, with a total of 76.0 million in 2020 and 111.8 million in 2040 people worldwide . Several risk factors are implicated in glaucoma, such as elevated intraocular pressure (IOP), older age (>60 years old), thinner central cornea thickness, exfoliation syndrome, diabetes, and high blood pressure . However, vascular dysregulation has come to light as a critical pathophysiological mechanism involved in glaucoma development and progression .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p1
|
PMC11278711
|
sec[0]/p[1]
|
1. Introduction
| 4.273438 |
biomedical
|
Study
|
[
0.99951171875,
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] |
[
0.88623046875,
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0.0004024505615234375
] |
Considerable interest has emerged in Endothelin-1 (ET-1), a potent key modulator of ocular blood flow . ET-1 has been characterized as a powerful vasoconstrictor, as it contributes to the basal constrictive tone of systemic vessels and may contribute to autoregulation of ocular blood flow and ocular vessel tone, especially in the choroid and optic nerve head . ET-1 is a 21 amino acid peptide made by vascular endothelium throughout the body, including tissues relevant to glaucoma (non-pigmented ciliary epithelium, ciliary body muscle, and iris) . Several studies have investigated the role of plasma and aqueous humor ET-1 levels, with most of them finding ET-1 plasma concentrations significantly elevated in glaucoma patients, and aqueous humor ET-1 levels to show great heterogeneity between studies and groups . Findings from animal studies are also noteworthy as intravitreal injection of ET-1 in rats resulted in a dose-dependent and sustained reduction of optic nerve head blood flow , and ΕΤ-1 induced contraction in human trabecular meshwork cell cultures .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p2
|
PMC11278711
|
sec[0]/p[2]
|
1. Introduction
| 4.023438 |
biomedical
|
Review
|
[
0.99365234375,
0.0041351318359375,
0.002079010009765625
] |
[
0.008148193359375,
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] |
Although research interest is increasing to shed light on the pathophysiological mechanisms involved in ET-1 levels with the risk of glaucoma disease, the detailed picture of this connection is still obscure, especially among various types of glaucoma. This systematic review and meta-analysis summarizes the existing evidence on the role of ET-1 levels in both plasma and aqueous humor among glaucoma patients compared to healthy controls. In parallel, it also focuses individually on patients with each type of glaucoma, providing an up-to-date, comprehensive view of this relationship.
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p3
|
PMC11278711
|
sec[1]/sec[0]/p[0]
|
2.1. Literature Search
| 4.144531 |
biomedical
|
Study
|
[
0.9990234375,
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] |
[
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0.00014400482177734375
] |
This study was designed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement . The protocol has been prospectively registered in PROSPERO . PubMed, Cochrane Library, and ScienceDirect databases were searched up to 4 April 2024 for articles examining the role of Endothelin-1 plasma and aqueous humor levels on different types of glaucoma. The following search terms were used with an indicative search query to implement these criteria: “Endothelin-1” or “ET-1”. The keywords listed below were used to identify the outcome variables of interest: “Glaucoma”, “Primary open-angle Glaucoma”, “POAG”, “Angle-Closure Glaucoma”, “ACG”, “Normal Tension Glaucoma”, “NTG”, “Pseudoexfoliative Glaucoma”, or “PEXG”. Based on predefined selection criteria, two researchers independently evaluated the articles for eligibility. Any discrepancies were resolved through repeated reviewing and consensus among the authors. Database searches were rerun before final analyses and any appropriate further studies were retrieved for inclusion.
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278711_p4
|
PMC11278711
|
sec[1]/sec[1]/p[0]
|
2.2. Study Selection and Data Extraction
| 4.039063 |
biomedical
|
Study
|
[
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] |
[
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0.0003516674041748047,
0.005077362060546875,
0.00010132789611816406
] |
All original observational studies (cohort, cross-sectional, and case-control) were included based on the following criteria for the included study design: (i) all studies were conducted in human adults (>18 years old); (ii) studies included soluble plasma and/or aqueous humor concentrations of ET-1 in patients with any type of glaucoma and healthy controls; (iii) studies included information about the diagnostic methods and the method of laboratory analysis of ET-1. We excluded from the analysis: (i) all reviews, systematic reviews, and meta-analyses; (ii) non-English language studies; (iii) animal studies; (iv) studies where the levels of ET-1 were unavailable (even after contacting the corresponding author). After the completion of screening, the following information was extracted from the included studies: (i) first author’s name; (ii) year of publication and title; (iii) study type/design; (iv) sample size (overall and per group); (v) study location (country); (vi) age and sex for the whole sample and each subgroup included.
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278711_p5
|
PMC11278711
|
sec[1]/sec[2]/p[0]
|
2.3. Quality Assessment and Publication Bias
| 4.113281 |
biomedical
|
Study
|
[
0.99951171875,
0.0003113746643066406,
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] |
[
0.9990234375,
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] |
The quality assessment and risk of bias assessment for the 23 studies meeting the eligibility criteria were conducted by the Newcastle–Ottawa Quality Assessment Scale (NOS) criteria, adapted for case-control, cross-sectional, and cohort studies respectively . NOS assessment is based on three main domains: (i) The selection of participants, (ii) the comparability of the groups, and (iii) the ascertainment of either the exposure or outcome of interest. The maximum score is 9 for case-control and 10 for cross-sectional studies. We assigned scores of 0–3, 4–6, and 7–9 (or 7–10 for cross-sectional design) for low, moderate, and high quality, respectively. Also, publication bias was examined with funnel plot assessment, to evaluate the asymmetry of the values between the two groups under comparison. Outlier studies were removed using Egger’s test which is a statistical tool for quantifying funnel plot asymmetry. Study quality was not used as a criterion for outlier removal.
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p6
|
PMC11278711
|
sec[1]/sec[3]/p[0]
|
2.4. Statistical Analysis
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.0003192424774169922,
0.00012600421905517578
] |
[
0.998046875,
0.0003421306610107422,
0.0013284683227539062,
0.0001023411750793457
] |
The acquisition of data was achieved through either direct extraction or indirect calculation, following the methodology of Wan et al. formula in order to estimate mean and standard deviation (SD) in the case of data reported as median and interquartile range (IQR) . To estimate differences, the standardized mean differences (SMD) of the compared groups and their 95% CIs were estimated using random effect models. The examination of statistical heterogeneity was carried out through Q statistic, based on the χ 2 test ( p = 0.05 as the significance threshold) and I 2 was used to quantify the proportion of variance due to between-study heterogeneity. A sensitivity analysis was performed in the analysis of ET-1 levels (both in plasma and aqueous humor) when comparing SMDs between glaucoma patients and control subjects through a leave-one-out strategy. Moreover, a subgroup analysis was conducted between different types of glaucoma and control subjects when the included studies had at least two studies with the same comparison groups. A meta-analysis was conducted using RevMan 5.4 software (The Cochrane Collaboration, Oxford, UK).
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p7
|
PMC11278711
|
sec[2]/sec[0]/p[0]
|
3.1. Search Results
| 3.914063 |
biomedical
|
Review
|
[
0.99853515625,
0.0007243156433105469,
0.0008788108825683594
] |
[
0.414306640625,
0.002025604248046875,
0.5830078125,
0.0005574226379394531
] |
A total of 281 studies was initially identified with 23 being eligible for inclusion in the systematic review and meta-analysis after the application of exclusion and inclusion criteria . Most of the studies included were case-control ( n = 16, 69.6%), and the rest of them were cross-sectional studies ( n = 7, 30.4%). There was a total sample size of n = 2597 subjects ( Table 1 ) .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p8
|
PMC11278711
|
sec[2]/sec[1]/p[0]
|
3.2. Quality Assessment
| 3.994141 |
biomedical
|
Study
|
[
0.99951171875,
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] |
[
0.998046875,
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] |
The overall quality was found high for 19 studies (82.6%) and moderate for the remaining 4 (17.3%). Case-control studies displayed an average score of 7.3 out of 9, with 13 (81.3%) being of high quality. The same figure was 7.9 out of 10 for cross-sectional studies with 6 of them (85.7%) being of high quality ( Supplementary Table S1 ).
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278711_p9
|
PMC11278711
|
sec[2]/sec[2]/sec[0]/sec[0]/p[0]
|
Plasma ET-1 Levels between Glaucoma Patients vs. Healthy Controls
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.0002715587615966797,
0.00017023086547851562
] |
[
0.99853515625,
0.0002167224884033203,
0.0013179779052734375,
0.0000787973403930664
] |
From the studies included in the meta-analysis, 17 studies examined plasma ET-1 levels between glaucoma patients and healthy controls. A total of 1743 subjects were included in the analysis. The meta-analysis showed significantly higher plasma ET-1 levels for glaucoma patients, by a pooled SMD of 1.21 (95% CI: 0.59–1.82, p < 0.001) . Although substantial heterogeneity (I 2 = 96%, p < 0.001) was observed among studies, the sensitivity analysis confirmed the results. It showed higher ET-1 levels for glaucoma patients by a pooled mean difference of 0.42 pg/mL of ET-1 (95% CI: 0.26–0.59, p < 0.001), after funnel plot evaluation and 8 outlier studies removals, with moderate heterogeneity among studies (I 2 = 70%, p < 0.001) .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278711_p10
|
PMC11278711
|
sec[2]/sec[2]/sec[0]/sec[1]/p[0]
|
Plasma ET-1 Levels between POAG Patients vs. Healthy Controls
| 4.136719 |
biomedical
|
Study
|
[
0.99951171875,
0.00027251243591308594,
0.00017499923706054688
] |
[
0.9990234375,
0.00021755695343017578,
0.0008845329284667969,
0.00007063150405883789
] |
From the studies included in the meta-analysis, 13 studies examined plasma ET-1 levels between POAG patients and healthy controls, with a total of 1297 subjects (686 POAG patients vs. 601 healthy controls). The meta-analysis showed significantly higher plasma ET-1 levels in POAG patients, by a pooled SMD of 0.87 (95% CI: 0.09–1.65, p < 0.03), with a substantial heterogeneity among studies (I 2 = 97%, p < 0.001) . The sensitivity analysis confirmed the results showing higher ET-1 levels for POAG patients by a pooled mean difference of 0.44 pg/mL ET-1 (95% CI: −0.07–0.95, p < 0.001), after funnel plot evaluation and 5 outlier studies removals, with a moderate heterogeneity (I 2 = 74%, p = 0.09) .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278711_p11
|
PMC11278711
|
sec[2]/sec[2]/sec[0]/sec[2]/p[0]
|
Plasma ET-1 Levels between NTG Patients vs. Healthy Controls
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.00028514862060546875,
0.00017154216766357422
] |
[
0.9990234375,
0.0002219676971435547,
0.0007529258728027344,
0.000072479248046875
] |
In the present analysis, six studies investigating plasma ET-1 levels between NTG patients and healthy controls were included, with a total of 427 subjects (187 NTG patients vs. 601 healthy controls). The meta-analysis showed significantly higher plasma ET-1 levels in NTG patients, by a pooled SMD of 0.86 (95% CI: 0.27–1.46, p = 0.05), with a substantial heterogeneity among studies (I 2 = 87%, p < 0.001) . The sensitivity analysis confirmed the results showing higher ET-1 levels for NTG patients by a pooled MD of 0.39 pg/mL ET-1 (95% CI: 0.19–0.59, p < 0.001), after funnel plot evaluation and one outlier study removal, with a low heterogeneity among studies (I 2 = 48%, p < 0.001) .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278711_p12
|
PMC11278711
|
sec[2]/sec[2]/sec[0]/sec[3]/p[0]
|
Plasma ET-1 Levels between ACG Patients vs. Healthy Controls
| 4.105469 |
biomedical
|
Study
|
[
0.99951171875,
0.00023496150970458984,
0.00019025802612304688
] |
[
0.9990234375,
0.0001786947250366211,
0.0008983612060546875,
0.00006270408630371094
] |
Two studies were identified investigating plasma ET-1 levels between NTG patients and healthy controls, with a total of 108 subjects (41 ACG patients vs. 67 healthy controls). The analysis showed significantly higher plasma ET-1 levels, by a pooled SMD of 1.03 (95% CI: 0.43–1.63, p < 0.001) and low (I 2 = 48%, p < 0.16) heterogeneity among studies . Moreover, the analysis showed a pooled MD of 1.78 pg/mL ET-1 (95% CI: 0.26–3.30, p = 0.02), with moderate heterogeneity among studies (I 2 = 72%, p = 0.02) .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278711_p13
|
PMC11278711
|
sec[2]/sec[2]/sec[0]/sec[4]/p[0]
|
Plasma ET-1 Levels between PEXG Patients vs. Healthy Controls
| 4.085938 |
biomedical
|
Study
|
[
0.99951171875,
0.0002486705780029297,
0.0001951456069946289
] |
[
0.99951171875,
0.00019097328186035156,
0.00047779083251953125,
0.00005692243576049805
] |
Among studies included in the meta-analysis, two studies identified examining plasma ET-1 levels between PEXG patients and healthy controls, with a total of 89 subjects (36 PEXG patients vs. 53 healthy controls). No significant difference in plasma ET-1 levels was observed between the PEXG patients and healthy controls [SMD: 0.31 (95% CI: −0.68–1.31, p = 0.54)] .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p14
|
PMC11278711
|
sec[2]/sec[2]/sec[1]/sec[0]/p[0]
|
Aqueous Humor ET-1 Levels between Glaucoma Patients vs. Healthy Controls
| 4.144531 |
biomedical
|
Study
|
[
0.99951171875,
0.00028061866760253906,
0.00015747547149658203
] |
[
0.99853515625,
0.0002334117889404297,
0.0009260177612304688,
0.00007867813110351562
] |
From the studies included in the meta-analysis, nine of them examining aqueous humor ET-1 levels between glaucoma patients and healthy controls, with a total of 1166 subjects (685 glaucoma patients vs. 481 healthy controls). The meta-analysis showed significantly higher aqueous humor ET-1 levels for glaucoma patients, by a pooled SMD of 2.07 (95% CI: 0.81–3.34, p < 0.001), with a substantial (I 2 = 87%) heterogeneity among studies . The sensitivity analysis confirmed the results showing higher aqueous humor ET-1 levels for glaucoma patients by a pooled mean difference of 1.98 pg/mL ET-1 (95% CI: 1.36–2.60, p < 0.001), after funnel plot evaluation and 5 outlier studies removals, with moderate heterogeneity among studies (I 2 = 73%, p < 0.001) .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p15
|
PMC11278711
|
sec[2]/sec[2]/sec[1]/sec[1]/p[0]
|
Aqueous Humor ET-1 Levels between POAG Patients vs. Healthy Controls
| 4.121094 |
biomedical
|
Study
|
[
0.99951171875,
0.00028514862060546875,
0.00017261505126953125
] |
[
0.99853515625,
0.0002104043960571289,
0.0011339187622070312,
0.00007665157318115234
] |
Five studies were identified investigating aqueous humor ET-1 levels between POAG patients and healthy controls with a total of 900 subjects (531 POAG patients vs. 369 healthy controls). The meta-analysis showed significantly higher aqueous ET-1 levels in POAG patients, by a pooled SMD of 2.70 (95% CI: 0.67–4.73, p < 0.001), with a substantial heterogeneity among studies . The sensitivity analysis confirmed the results showing higher aqueous humor ET-1 levels for POAG patients by a pooled mean difference of 1.47 pg/mL ET-1 (95% CI: 1.04–1.90, p = 0.03), after funnel plot evaluation and two outlier studies removals, with moderate heterogeneity among studies (I 2 = 73%, p = 0 < 0.01) .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278711_p16
|
PMC11278711
|
sec[2]/sec[2]/sec[1]/sec[2]/p[0]
|
Aqueous Humor ET-1 Levels between PEXG Patients vs. Healthy Controls
| 4.011719 |
biomedical
|
Study
|
[
0.99951171875,
0.0003666877746582031,
0.0002694129943847656
] |
[
0.951171875,
0.0004973411560058594,
0.047821044921875,
0.0002598762512207031
] |
Among the studies reviewed, four studies were examining aqueous humor ET-1 levels between PEXG patients and healthy controls, with a total of 175 subjects (83 PEXG patients vs. 92 healthy controls). The analysis showed significantly higher plasma ET-1 levels, by a pooled SMD of 2.03 (95% CI: 1.00–3.07, p < 0.001), and high heterogeneity among studies was detected . After a sensitivity analysis, a pooled MD of 2.57 pg/mL ET-1 (95% CI: 1.01–4.14, p = 0.001) confirmed the results showing higher aqueous humor ET-1 levels in PEXG patients compared to healthy controls, with moderate heterogeneity (I 2 = 71%, p = 0.06) among studies .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p17
|
PMC11278711
|
sec[3]/p[0]
|
4. Discussion
| 4.035156 |
biomedical
|
Review
|
[
0.994140625,
0.0036067962646484375,
0.0021209716796875
] |
[
0.012908935546875,
0.0010929107666015625,
0.9853515625,
0.0004925727844238281
] |
This systematic review and meta-analysis have provided a comprehensive evaluation of the role of ET-1 levels in both plasma and aqueous humor among patients with various types of glaucoma compared to healthy controls. Elevated ET-1 has been characterized as a potential causal risk factor for glaucoma development and progression, as several studies in the last two decades have investigated the role of ET-1 levels both in plasma and aqueous humor . However, the absence of concrete data for the exact relationship of ET-1 levels in each type of glaucoma prompted us to elucidate the exact role it serves among different groups since the last systematic review and meta-analysis by Li S. et al., 2016 included only six studies .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p18
|
PMC11278711
|
sec[3]/p[1]
|
4. Discussion
| 4.296875 |
biomedical
|
Study
|
[
0.99951171875,
0.0003082752227783203,
0.00013387203216552734
] |
[
0.998046875,
0.0002808570861816406,
0.00153350830078125,
0.00011867284774780273
] |
The significantly elevated levels of ET-1 in the plasma of glaucoma patients observed in our analysis suggest a systemic alteration in vascular regulation among these patients. This aligns with the hypothesis that vascular dysregulation, characterized by an imbalance between vasoconstrictors and vasodilators, may play a crucial role in the development and progression of glaucoma . The substantial heterogeneity observed across studies could be attributed to variations in study populations, methodologies, and definitions of glaucoma, which highlights the complexity of this disease and the multifactorial nature of its vascular components . Interestingly, our findings also revealed significantly higher levels of ET-1 in the aqueous humor of glaucoma patients. This suggests a localized effect of ET-1 within the ocular environment, which may contribute to the impaired ocular blood flow and increased IOP observed in glaucoma patients . The role of ET-1 in regulating ocular blood flow and vessel tone, particularly in the choroid and optic nerve head, provides a plausible mechanism by which elevated ET-1 levels may exacerbate glaucomatous damage .
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278711_p19
|
PMC11278711
|
sec[3]/p[2]
|
4. Discussion
| 4.710938 |
biomedical
|
Review
|
[
0.9970703125,
0.0015840530395507812,
0.0011539459228515625
] |
[
0.365478515625,
0.0021648406982421875,
0.63134765625,
0.00119781494140625
] |
Understanding the complexities of trabecular meshwork and its pivotal role in regulating IOP in various glaucoma subtypes is crucial for developing targeted therapies . Several factors such as changes in extracellular matrix metabolism and antioxidant defense system are known to impair aqueous humor outflow . Interestingly, the intravitreal delivery of ET-1 into rat eyes reduced Electroretinography response indicating impaired retinal function and the subsequent decreased blood flow to the retina . Another study supported that mitochondrial dysfunction is a significant contributor to ET-1-induced damage of retinal ganglion cells in the context of POAG, since ET-1 downregulated mitochondrial electron transport chain components, underlining the key mechanism behind the neurodegenerative changes observed in POAG . Moreover, excessive ET-1 in the aqueous humor can lead to abnormal accumulation of extracellular matrix in trabecular meshwork cultured human cells that restricts aqueous humor outflow, thereby increasing IOP . Such tissue-engineered cultures can replicate the morphology and gene expression patterns of specific ocular regions, such as the trabecular meshwork and Schlemm’s canal, providing physiologically relevant models for studying the disease and testing treatments . Recent treatment studies have shed light on these complex interactions and mechanisms within the trabecular meshwork. Particularly, oral administration of macitentan, a dual endothelin receptor antagonist, effectively attenuated the vasoconstriction caused by intravitreal ET-1 and reduced ET-1 induced retinal ganglion cell loss in rats treated with macitentan. Furthermore, intravitreal injection of Magnesium Acetyltaurate (MgAT) provided significant neuroprotective effects against ET-1 induced damage in the retina by suppressing the neuroinflammatory reaction and offering a way to protect against glaucoma-related retinal damage and preserve vision by addressing both vascular dysfunction and oxidative stress . Finally, there is a clear need to extend the development of targeted therapies beyond animal models to include human clinical trials, ensuring that treatments addressing ET-1’s role in glaucoma can be effectively translated into therapeutic options that mitigate disease progression.
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278711_p20
|
PMC11278711
|
sec[3]/p[3]
|
4. Discussion
| 4.140625 |
biomedical
|
Study
|
[
0.99951171875,
0.00026416778564453125,
0.00015997886657714844
] |
[
0.99560546875,
0.0002689361572265625,
0.00390625,
0.00010758638381958008
] |
The analysis across different types of glaucoma revealed that elevated ET-1 levels were not uniform across all forms. Notably, significant elevations were observed in POAG, NTG, and ACG patients, but not in PEXG plasma ET-1 levels compared to healthy controls. This may indicate that the pathophysiological mechanisms involving ET-1 may vary among different types of glaucoma, suggesting the need for type-specific therapeutic approaches. Moreover, the heterogeneity observed in our analyses, particularly in the aqueous humor ET-1 levels, underscores the complexity of glaucoma as a group of diseases and the intricate role of vascular factors in its pathogenesis . The findings of this meta-analysis can be better understood within its limitations, since the considerable heterogeneity among studies indicates differences in studies’ population and the research environment of each work. Future studies should aim to elucidate the mechanisms by which ET-1 contributes to the vascular dysregulation in glaucoma and explore potential therapeutic interventions targeting ET-1 signaling pathways.
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278711_p21
|
PMC11278711
|
sec[4]/p[0]
|
5. Conclusions
| 4 |
biomedical
|
Review
|
[
0.990234375,
0.006519317626953125,
0.003246307373046875
] |
[
0.004329681396484375,
0.00164794921875,
0.99365234375,
0.0005965232849121094
] |
This systematic review and meta-analysis demonstrate that elevated levels of ET-1 in both plasma and aqueous humor are significantly associated with glaucoma, supporting the hypothesis that vascular dysregulation plays a crucial role in its pathogenesis. The findings indicate that ET-1’s impact varies across different types of glaucoma, suggesting the necessity for type-specific research and treatment strategies. Ultimately, understanding the role of ET-1 in glaucoma could lead to novel approaches to treatment and improve outcomes for patients with this challenging ocular disease.
|
[
"Stamatios Lampsas",
"Stylianos A. Kandarakis",
"Dionysios G. Vakalopoulos",
"Aikaterini Lampsa",
"Evangelos Oikonomou",
"Gerasimos Siasos",
"George D. Kymionis"
] |
https://doi.org/10.3390/medicina60071117
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p0
|
PMC11278723
|
sec[0]/p[0]
|
1. Introduction
| 4.117188 |
biomedical
|
Study
|
[
0.99755859375,
0.0002720355987548828,
0.0020389556884765625
] |
[
0.806640625,
0.007717132568359375,
0.185302734375,
0.0003387928009033203
] |
Free amino acids are crucial compounds in many foods and are frequently considered as a main factor in food quality. In tomato fruits, the total amount of free amino acids increases significantly during ripening on the vine . Such an increase is not seen in tomatoes that have ripened off the vine , which may account for their different taste . Similarly, in grape , melon ( Cucumis melo ) and sunberry ( Physalis minima ) , the level of free amino acids increases during ripening while it remains unaffected in jujube fruits ( Ziziphus jujuba ) and decreases in apple and strawberry . Wheat grown under sulphur starvation contains high amounts of free amino acids in the grains. Pastries made out of such wheat flowers have a reduced loaf volume, a dark crust and crumb, and contain significant amounts of the neurotoxin acrylamide . The content of free amino acids is also a critical factor for sugar beet quality, where this parameter is referred to as α-amino nitrogen. Free amino acids are one of the most important factors preventing sugar crystallisation and thereby reduce yield. A low content is therefore mandatory for the high quality of sugar beets .
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p1
|
PMC11278723
|
sec[0]/p[1]
|
1. Introduction
| 3.546875 |
biomedical
|
Study
|
[
0.99560546875,
0.0001844167709350586,
0.004055023193359375
] |
[
0.7822265625,
0.2034912109375,
0.01372528076171875,
0.0004153251647949219
] |
Free amino acids also play a fundamental role for the taste of many foods prepared via fermentation. For instance, the content of soluble nitrogen compounds, particularly free amino acids, is a major factor of soy sauce quality . During cheese production, the content of free amino acids increases from approximately 50–200 mg/100 g to more than 1000 mg/100 g , which has been suggested as a good indicator of cheese ripening . Therefore, the quantification of the total amino acid level can be informative for a wide variety of samples.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p2
|
PMC11278723
|
sec[0]/p[2]
|
1. Introduction
| 4.167969 |
biomedical
|
Review
|
[
0.99853515625,
0.0004525184631347656,
0.0009899139404296875
] |
[
0.339599609375,
0.00835418701171875,
0.6513671875,
0.0005779266357421875
] |
A number of techniques have been used to determine free amino acids in food and other sample types. Free amino acids are often analysed using so-called amino acid analysers . Although reliable, disadvantages include low sensitivity and a long run time of typically more than 30 min for one sample. Frequently used alternatives are based on high-performance liquid chromatography in the reversed-phase (RP) or hydrophilic interaction (HILIC) mode with a precolumn derivatisation step to enhance the binding of the amino acids to the stationary phase and improve their detection sensitivity. Commonly used derivatisation reagents include phenyl isothiocyanate (PITC) , o-phthaldialdehyde (OPA) alone or in combination with fluorenylmethyloxycarbonyl chloride (FMOC-Cl) , 6-aminoquinoline- N -hydroxy-succinimidyl carbamate (AQC) , dansyl chloride and Sanger’s reagent (1-fluoro-2,4-dinitrophenylbenzene, DNFB) . These methods are highly sensitive and allow the quantification of individual amino acids. However, they are time consuming, and require special equipment and a high degree of standardisation to allow the reliable assignment of all peaks.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p3
|
PMC11278723
|
sec[0]/p[3]
|
1. Introduction
| 4.316406 |
biomedical
|
Study
|
[
0.99951171875,
0.0002453327178955078,
0.00024580955505371094
] |
[
0.99169921875,
0.0006618499755859375,
0.007354736328125,
0.00011146068572998047
] |
Alternatively, spectroscopic methods can be used for the quantification of free amino acids. Using OPA, a highly sensitive method for the quantification of the free amino acids using spectrofluorimetry has been developed . This method is simple and has superior sensitivity. Disadvantages include the instability of the formed isoindoles and the moderately uniform response of the different proteinogenic amino acids. Another well-known reagent is 2,4,6-trinitrobenzene sulphonate (TNBS) which gives, depending on the reaction conditions, an orange coloured reaction product with an absorption maximum at 420 nm or a derivative with an absorption maximum at 340 nm . The latter has the disadvantage that the absorption maximum overlaps with that of picric acid, a side product of the reaction , while the former originates from an unstable complex. Similarly, amino acids can be derivatised with DNFB under alkaline conditions to stable 2,4-dinitrophenyl derivatives, which can be extracted using ethyl acetate and measured at 420 nm . However, DNFB hydrolyses rapidly under alkaline conditions to 2,4-dinitrophenol, which absorbs in the same range as the 2,4-dinitrophenyl amino acid derivatives . Thus, it remains to be investigated how efficient extraction with ethyl acetate can discriminate between the amino acid derivatives and the by-product.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p4
|
PMC11278723
|
sec[0]/p[4]
|
1. Introduction
| 4.4375 |
biomedical
|
Study
|
[
0.99853515625,
0.00047707557678222656,
0.0007653236389160156
] |
[
0.7431640625,
0.0021991729736328125,
0.25439453125,
0.000476837158203125
] |
The most widely used reagent for the spectrophotometric quantification of amino acids is ninhydrin. This reagent reacts with primary amino groups to form Ruhemann’s purple, a colourful compound that can be measured using spectrophotometry at 570 nm. In contrast to the other spectroscopic methods described above, all primary amino compounds give the same dye because the final reaction product contains only the primary amino nitrogen of the amino acid. Thus, in theory, all primary amino compounds should give the same response. The ninhydrin reaction has been used for a long time, but there are several variations in its implementation. Typical reagents consist of ninhydrin dissolved in a mixture of an aqueous buffer and an organic solvent including 2-methoxyethanol, phenol, sulfolane and dimethyl sulfoxide (DMSO). As a buffer system, acetic acid/lithium acetate with a molar ratio of 0.325/1 is frequently used . Interestingly, Sun et al. showed that lithium acetate has no advantage over the significantly cheaper sodium acetate . Surprisingly, they provided evidence that the reaction works very well in the range of pH 8–9. In addition, an agent must be added that reduces a small quantity of ninhydrin to hydrindantin, which is required for an efficient reaction. All proposed compounds have disadvantages: tin(II)-chloride forms insoluble precipitates, cyanide and sodium borohydride are highly toxic and ascorbic acid increases the blank significantly. Instead of a reducing agent, pure hydrindantin can be added . This has the advantages that it is not toxic and the blank is kept low. Finally, the reaction must be heated to induce the formation of Ruhemann’s purple. A wide range of different temperatures and incubation times have been reported. The most frequently used temperature was 100 °C for 10 to 30 min , but also lower temperatures including 90 °C for 15 min , 80 °C for 30 min and even a temperature as low as 60 °C for 30 min have been reported.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278723_p5
|
PMC11278723
|
sec[0]/p[5]
|
1. Introduction
| 4.027344 |
biomedical
|
Study
|
[
0.99755859375,
0.0002913475036621094,
0.002025604248046875
] |
[
0.99951171875,
0.00021147727966308594,
0.0002472400665283203,
0.00004112720489501953
] |
Although the ninhydrin reaction has been used for decades, a variety of reaction conditions are used and no standard procedure has been established. Many of the protocols used seem to be based on tradition rather than experimental evidence. Thus, we decided to investigate the factors affecting the formation of Ruhemann’s purple in a systematic way. Based on the literature, an important factor to be investigated is the type and concentration of the acetate buffer, particularly the cation of the salt and the acetic acid to acetate ratio. Among the proposed solvents, only sulfolane and DMSO are a good choice with respect to work safety and thus we focused on those. All previously used reducing agents have disadvantages and thus we decided to use hydrindantin instead because it is commercially available, simple to use and non-toxic. Furthermore, we investigated the impact of the ninhydrin and hydrindantin concentrations and the reaction conditions, particularly temperature and reaction time on dye formation.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p6
|
PMC11278723
|
sec[1]/sec[0]/p[0]
|
2.1. Buffer Composition
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
0.0002620220184326172,
0.00042700767517089844
] |
[
0.99951171875,
0.0001709461212158203,
0.00021564960479736328,
0.00004416704177856445
] |
In previous publications, acetic acid in combination with lithium or sodium acetate was used as a buffer system but no reasons for the selection of these cations were given . To investigate the impact of the cation, reactions in the presence of lithium, sodium, potassium, magnesium, calcium and barium acetate were performed. Since preliminary experiments had indicated that a ratio of acetic acid to acetate of 2/1 (mol/mol) is best , this ratio was used for all acetates tested. Asparagine was used as a representative amino acid during the optimisation procedure since it is one of the most abundant free amino acids in many sample types, including food and plant extracts. As indicated in Figure 1 A, the type of acetate had only a minor impact, since the absorption measured for all reactions containing asparagine was very similar. The same also applied to the blank reactions. The ratio of the asparagine reaction and the blank was highest for the three alkaline metal acetates and for magnesium, indicating that these acetates are equally suitable. Among them, potassium acetate has by far the highest solubility with 25 mol salt per kg water , allowing the preparation of buffers with a high capacity. In addition, it is one of the cheapest acetates. Thus, we selected potassium acetate for the further experiments.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p7
|
PMC11278723
|
sec[1]/sec[0]/p[1]
|
2.1. Buffer Composition
| 4.117188 |
biomedical
|
Study
|
[
0.9990234375,
0.00024187564849853516,
0.0008916854858398438
] |
[
0.99951171875,
0.00020813941955566406,
0.000225067138671875,
0.00003820657730102539
] |
As stated above, preliminary experiments showed that an acetic acid to lithium acetate ratio of 2/1 gave the best results. To test whether this also applies for the acetic acid/potassium acetate buffer system, the concentration of potassium acetate was kept at 0.5 mol L −1 while the concentration of acetic acid varied between 0 and 1.8 mol L −1 . As for lithium acetate, a broad optimum in the range of approximately 0.7 to 1.4 mol L −1 acetic acid was observed. This corresponds to a ratio of acetic acid to potassium acetate of 1.4/1 to 2.8/1. This result was surprising, since in most previous publications buffer systems with a significantly lower ratio of acetic acid to acetate, typically in the range of 0–0.96/1, were used . However, our data with acetic acid/potassium acetate and acetic acid/lithium acetate clearly indicate that an acid to salt ratio of approximately 2/1 is most suitable, which corresponds to the results of Fisher et al. . It is worthy to note that the pH of the buffer system depended strongly on the conditions, including buffer concentration and DMSO content ( Supplementary Table S1 ). Therefore, in this manuscript, we always refer to the acetic acid to acetate ratio rather than the pH.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p8
|
PMC11278723
|
sec[1]/sec[0]/p[2]
|
2.1. Buffer Composition
| 4.113281 |
biomedical
|
Study
|
[
0.99853515625,
0.0002944469451904297,
0.0009775161743164062
] |
[
0.99951171875,
0.00021064281463623047,
0.00017595291137695312,
0.00004285573959350586
] |
Since the colour appeared different at distinct acid to potassium acetate ratios, spectra were recorded for all samples in the range of 300 nm to 700 nm . This showed that the samples have two maxima, one at 404 nm and one at 570 nm. The intensities of both maxima increased with the acetic acid concentration up to approximately 1 mol L −1 . Importantly, the wavelength of the maxima did not change. In sharp contrast, the wavelength of the minimum shifted from 490 nm in the absence of acetic acid to approximately 460 nm in the presence of acetic acid concentrations of more than 1 mol L −1 . Also, the absorbance of the minimum decreased considerably. This explains the different colour and shows that a wavelength of 570 nm is suitable for measurement.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278723_p9
|
PMC11278723
|
sec[1]/sec[0]/p[3]
|
2.1. Buffer Composition
| 3.923828 |
biomedical
|
Study
|
[
0.998046875,
0.00020384788513183594,
0.0018491744995117188
] |
[
0.99755859375,
0.002109527587890625,
0.0001760721206665039,
0.00006312131881713867
] |
A high buffer concentration is desirable to neutralise acids or bases present in the sample. However, high salt concentrations may impact on colour development and cause the precipitation of some compounds. To investigate this in more detail, the concentration of acetic acid varied between 0.5 mol L −1 and 3 mol L −1 and that of potassium acetate correspondingly between 0.25 mol L −1 and 1.5 mol L −1 . Only slight differences in the absorption were observed and the optimum was in the range of 0.75 mol L −1 to 1 mol L −1 potassium acetate and 1.5 mol L −1 to 3 mol L −1 acetic acid .
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p10
|
PMC11278723
|
sec[1]/sec[1]/p[0]
|
2.2. Type and Amount of Organic Solvent
| 3.482422 |
biomedical
|
Study
|
[
0.99560546875,
0.00028228759765625,
0.0040283203125
] |
[
0.96435546875,
0.03509521484375,
0.0004439353942871094,
0.0002321004867553711
] |
Ninhydrin is poorly water-soluble and thus an organic solvent must be added to the reaction. In the literature, 2-methoxyethanol, phenol, DMSO and sulfolane were used. Since the first two are toxic, they were excluded from further investigations. Thus, reactions were prepared with different amounts of DMSO and sulfolane. A major difference in reagent preparation using these two solvents was that ninhydrin and hydrindantin were perfectly soluble in DMSO while they were poorly soluble in sulfolane, making heating and incubation in an ultrasonic bath necessary.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p11
|
PMC11278723
|
sec[1]/sec[1]/p[1]
|
2.2. Type and Amount of Organic Solvent
| 4.097656 |
biomedical
|
Study
|
[
0.9990234375,
0.0002510547637939453,
0.0007066726684570312
] |
[
0.99951171875,
0.0002541542053222656,
0.00018990039825439453,
0.00004482269287109375
] |
Using DMSO, an optimum of colour development was observed at a content of 35 to 45% ( v / v ) organic solvent in potassium acetate buffer . However, the overall impact of the solvent on dye formation was small. Similarly, the sulfolane content had little impact on the reaction and only a small increase in the absorbance was observed for higher solvent contents . However, the blank also increased in the same way and thus the amount of Ruhemann’s purple formed seems to be quite independent of the sulfolane content in the range of 32 to 50% ( v / v ) in potassium acetate buffer. The absorption was higher for reactions with DMSO than sulfolane, which has already been reported previously .
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p12
|
PMC11278723
|
sec[1]/sec[1]/p[2]
|
2.2. Type and Amount of Organic Solvent
| 2.544922 |
biomedical
|
Study
|
[
0.99169921875,
0.0007510185241699219,
0.00771331787109375
] |
[
0.83935546875,
0.15869140625,
0.0008606910705566406,
0.0009179115295410156
] |
Since colour development was higher in DMSO, ninhydrin and hydrindantin are readily soluble in this solvent and because of its significantly lower cost than sulfolane, DMSO was used for the further experiments.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278723_p13
|
PMC11278723
|
sec[1]/sec[2]/p[0]
|
2.3. Ninhydrin and Hydrindantin Concentration
| 4.066406 |
biomedical
|
Study
|
[
0.99853515625,
0.0003476142883300781,
0.0012254714965820312
] |
[
0.99951171875,
0.0002378225326538086,
0.0001270771026611328,
0.000038683414459228516
] |
A (final) ninhydrin concentration between 10 and 30 g L −1 has been suggested in the literature and ratios of hydrindantin to ninhydrin of 1:100 to 4:100 were used . To investigate the optimal reaction conditions, the ninhydrin concentration varied from 3 g L −1 to 30 g L −1 , while the hydrindantin to ninhydrin ratio was kept at 3.75:100 in these reactions . Interestingly, the curve did not pass through the origin and at the lowest tested concentration of 3 g L −1 only a small amount of Ruhemann’s purple was formed. At higher concentrations, a plateau of the colour formation was reached. However, the blank increased significantly with the ninhydrin concentration and thus the corrected values (colour developed in the reaction with asparagine minus blank) were calculated as well . This showed that the minimum concentration of ninhydrin where the plateau of colour development was reached was 20 g L −1 . This concentration was used for subsequent experiments.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278723_p14
|
PMC11278723
|
sec[1]/sec[2]/p[1]
|
2.3. Ninhydrin and Hydrindantin Concentration
| 3.849609 |
biomedical
|
Study
|
[
0.99609375,
0.0002892017364501953,
0.00374603271484375
] |
[
0.99560546875,
0.004024505615234375,
0.00016927719116210938,
0.00008028745651245117
] |
In the next step, the ninhydrin concentration was kept at 20 g L −1 while the concentration of hydrindantin varied from 0.1125 to 1.125 g L −1 , corresponding to a hydrindantin to ninhydrin ratio of 0.56:100 to 5.6:100. The highest absorption was obtained at a concentration of approximately 0.8 g L −1 (corresponding to a hydrindantin to ninhydrin ratio of 4:100).
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11278723_p15
|
PMC11278723
|
sec[1]/sec[2]/p[2]
|
2.3. Ninhydrin and Hydrindantin Concentration
| 4.066406 |
biomedical
|
Study
|
[
0.9990234375,
0.0002390146255493164,
0.0006985664367675781
] |
[
0.9990234375,
0.0009331703186035156,
0.00014638900756835938,
0.000056684017181396484
] |
To this end, the reaction conditions were optimised and the optimal composition was found to be 1.6 mol L −1 acetic acid, 0.8 mol L −1 potassium acetate, 20 g L −1 ninhydrin and 0.8 g L −1 hydrindantin in DMSO/aqueous acetate buffer 40/60 ( v / v ) (all values refer to the final concentration). In the following experiments a mixture of the 200 µL sample and 800 µL reagent was used. Thus, the reagent must consist of 2 mol L −1 acetic acid, 1 mol L −1 potassium acetate, 25 g L −1 ninhydrin and 1 g L −1 hydrindantin in DMSO/acetate buffer 50/50 ( v / v ) to establish the required composition of the final reaction. As shown during optimisation, the optima are very broad and thus the reaction can tolerate small deviations from the optimal conditions.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p16
|
PMC11278723
|
sec[1]/sec[3]/p[0]
|
2.4. Reaction Conditions
| 2.550781 |
biomedical
|
Other
|
[
0.9794921875,
0.0008606910705566406,
0.019439697265625
] |
[
0.1551513671875,
0.8310546875,
0.0126495361328125,
0.0009322166442871094
] |
For colour development, the reaction mixtures must be heated. In the literature, different conditions have been described. Moore and Stein heated the solution for 20 min in a boiling water bath , Rosen for 15 min and Fisher et al. only for 5 min .
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p17
|
PMC11278723
|
sec[1]/sec[3]/p[1]
|
2.4. Reaction Conditions
| 4.09375 |
biomedical
|
Study
|
[
0.99951171875,
0.00028967857360839844,
0.0003249645233154297
] |
[
0.99951171875,
0.00033855438232421875,
0.0002467632293701172,
0.000058591365814208984
] |
To identify the most suitable reaction time, mixtures containing asparagine or water as a blank and the optimised reagent were heated in a block thermostat to 100 °C and samples were taken after the indicated times . The best results were obtained after 30 min, but it was recognised that the colour declined upon prolonged incubation, which makes the assay less convenient since precise timing is required. Thus, a reaction temperature of 90 °C was also assayed in the same way. Here, the best results were obtained after 45 min and a broad optimum ranging from approximately 30 min to at least 60 min was observed . Therefore, incubation at 90 °C for 45 min is preferable because small deviations from the optimal time have little impact on the result.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278723_p18
|
PMC11278723
|
sec[1]/sec[4]/p[0]
|
2.5. Response of Different Amino Acids
| 3.960938 |
biomedical
|
Study
|
[
0.99951171875,
0.0002453327178955078,
0.0004296302795410156
] |
[
0.9990234375,
0.0006451606750488281,
0.0003352165222167969,
0.00008195638656616211
] |
We used asparagine, a hydrophilic uncharged amino acid, for the optimisation of the procedure. To investigate whether the identified conditions are also suitable for other amino acids, we repeated the procedure focusing on the most significant factors: the ratio of acetic acid to potassium acetate, the concentrations of ninhydrin and hydrindantin, and the reaction time. We tested these conditions with glutamic acid, arginine, and leucine, representatives for acidic, basic, and hydrophobic amino acids, respectively.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278723_p19
|
PMC11278723
|
sec[1]/sec[4]/p[1]
|
2.5. Response of Different Amino Acids
| 4.101563 |
biomedical
|
Study
|
[
0.99951171875,
0.00025963783264160156,
0.00045371055603027344
] |
[
0.99951171875,
0.00024008750915527344,
0.00028061866760253906,
0.000048279762268066406
] |
Regarding the acetic acid to potassium acetate ratio, arginine and leucine showed, similar to asparagine, increased colour development at a higher acid content . In contrast, the colour development of glutamic acid was relatively independent of the acid to salt ratio. This showed that the previously established ratio is suitable for all tested amino acids. For the ninhydrin and hydrindantin concentrations, essentially the same results as for asparagine were obtained for the tested amino acids . Interestingly, glutamic acid, arginine and leucine reacted quicker than asparagine . Nevertheless, the previously suggested incubation time of 45 min is suitable for all of these amino acids. These data indicate that the aforementioned reaction conditions are appropriate.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278723_p20
|
PMC11278723
|
sec[1]/sec[4]/p[2]
|
2.5. Response of Different Amino Acids
| 3.476563 |
biomedical
|
Other
|
[
0.9970703125,
0.00033593177795410156,
0.00243377685546875
] |
[
0.40087890625,
0.59716796875,
0.0014715194702148438,
0.0007157325744628906
] |
Since the same reaction product, Ruhemann’s purple, is obtained from all primary amines, all proteinogenic amino acids should give the same response except for proline, which does not react because of its secondary amino group, and lysine, which has two primary amino groups and should therefore respond twice as strongly.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278723_p21
|
PMC11278723
|
sec[1]/sec[4]/p[3]
|
2.5. Response of Different Amino Acids
| 4.089844 |
biomedical
|
Study
|
[
0.99951171875,
0.0002751350402832031,
0.0002918243408203125
] |
[
0.99951171875,
0.00015926361083984375,
0.00026726722717285156,
0.00005251169204711914
] |
To investigate this in more detail, the responses of all proteinogenic amino acids as well as cysteine and ammonium (in form of ammonium sulphate) were investigated using the optimised reagent and reaction conditions. The response was expressed relative to that of asparagine ( Table 1 ). The majority of the proteinogenic amino acids gave a response highly similar to that of asparagine. As expected, proline gave only a very slight response. The response of lysine was roughly twice as high as that of asparagine. Cysteine gave a significantly lower response, which is in agreement with previous reports describing that the ninhydrin reaction proceeds differently for this amino acid .
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278723_p22
|
PMC11278723
|
sec[1]/sec[4]/p[4]
|
2.5. Response of Different Amino Acids
| 4.054688 |
biomedical
|
Study
|
[
0.99951171875,
0.00015842914581298828,
0.00038814544677734375
] |
[
0.9990234375,
0.0008392333984375,
0.0002142190933227539,
0.00006079673767089844
] |
Except for these expected deviations, the other amino acids showed a very similar response, and thus the method is suitable to estimate the level of free amino acids in samples, particularly since cysteine, proline and lysine are usually scarce among the free amino acids. However, it must be mentioned that other compounds with primary amino acids and ammonia also react with ninhydrin to Ruhemann’s purple. The reactivity of ammonia was similar to that of most amino acids ( Table 1 ).
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p23
|
PMC11278723
|
sec[1]/sec[5]/p[0]
|
2.6. Validation of the Method
| 3.21875 |
biomedical
|
Study
|
[
0.99609375,
0.0005741119384765625,
0.0034580230712890625
] |
[
0.97998046875,
0.0190277099609375,
0.000614166259765625,
0.00029754638671875
] |
The ninhydrin reaction using the optimised reaction conditions showed a highly linear response, exceeding an absorption of 2 .
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p24
|
PMC11278723
|
sec[1]/sec[5]/p[1]
|
2.6. Validation of the Method
| 4.15625 |
biomedical
|
Study
|
[
0.99951171875,
0.00033402442932128906,
0.00021898746490478516
] |
[
0.998046875,
0.001140594482421875,
0.0005044937133789062,
0.00009083747863769531
] |
The limits of detection and quantification were defined as the 3 and 10-fold standard deviation (SD) of the blank and were determined according to Section 4.2.2.1 of the ICH guideline Q2 (R2) on the Validation of Analytical Procedures . Measuring 20 independent blank reactions gave an average absorption at 570 nm of 0.2391 with a SD of 0.0070. Using the slope of the calibration curve, this corresponds to a LOD and LOQ of 0.03 mmol L −1 and 0.1 mmol L −1 , respectively.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p25
|
PMC11278723
|
sec[1]/sec[5]/p[2]
|
2.6. Validation of the Method
| 4.09375 |
biomedical
|
Study
|
[
0.99951171875,
0.000278472900390625,
0.00035691261291503906
] |
[
0.99951171875,
0.00022077560424804688,
0.00033211708068847656,
0.00005537271499633789
] |
The inter-day and intra-day repeatability were assessed using tomato juice, an aqueous extract of potato tubers and, as an example of a sample rich in free amino acids, soy sauce. As indicated in Table 2 , Table 3 and Table 4 , the results were highly reproducible with intra-day and inter-day relative standard deviations (RSDs) in the range of 0.5% to 2.4% and 1.7% to 2.1%, respectively. Also, the regression parameters of the calibration curves were highly similar between the different days, and all Pearson correlation coefficients exceeded 0.999 ( Table 5 ). This shows that the developed method is highly reproducible.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p26
|
PMC11278723
|
sec[1]/sec[5]/p[3]
|
2.6. Validation of the Method
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
0.00025200843811035156,
0.0003821849822998047
] |
[
0.99951171875,
0.0003681182861328125,
0.0002951622009277344,
0.000057816505432128906
] |
The accuracy of the method was determined according to Section 3.3.1.2 of the ICH guideline Q2(R2) on the Validation of Analytical Procedures . Tomato juice and soy sauce samples were spiked with asparagine at two different levels. Subsequently, the amino acid concentrations were determined in the unspiked and spiked samples ( Table 6 ). Very good recovery rates in the range of 100% to 105% were obtained, showing that the method is very accurate.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p27
|
PMC11278723
|
sec[2]/sec[0]/p[0]
|
3.1. Chemicals and Reagents
| 1.369141 |
biomedical
|
Other
|
[
0.99072265625,
0.00153350830078125,
0.0079803466796875
] |
[
0.2010498046875,
0.79345703125,
0.00202178955078125,
0.003326416015625
] |
Ninhydrin (purity > 99%) and barium acetate (purity > 99%) were purchased from Merck (Darmstadt, Germany). Hydrindantin (purity > 97%) and all proteinogenic amino acids (all with a purity of >99%) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Lithium acetate, sodium acetate, potassium acetate, magnesium acetate, calcium acetate and ammonium sulphate (all with a purity of >99%) as well as acetic acid (purity > 99.5%), 2-propanol (purity > 99.8%) and DMSO (purity > 99.8%) were purchased from Carl Roth (Karlsruhe, Germany).
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p28
|
PMC11278723
|
sec[2]/sec[0]/p[1]
|
3.1. Chemicals and Reagents
| 3.644531 |
biomedical
|
Study
|
[
0.99853515625,
0.0004892349243164062,
0.0011739730834960938
] |
[
0.5849609375,
0.4130859375,
0.0008606910705566406,
0.0009489059448242188
] |
Ninhydrin reagent sufficient for 24 reactions was prepared by dissolving 550 mg ninhydrin and 22 mg hydrindantin in 11 mL DMSO and mixing the solution with 11 mL acetate buffer (98.1 g potassium acetate and 111 mL glacial acetic acid dissolved in water to a final volume of 500 mL). The reagent was used directly after preparation.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p29
|
PMC11278723
|
sec[2]/sec[1]/p[0]
|
3.2. Analytical Procedure for Quantification of Total Amino Acids
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.0003039836883544922,
0.00019025802612304688
] |
[
0.99853515625,
0.0012378692626953125,
0.00034427642822265625,
0.00010597705841064453
] |
An aliquot of the sample or standard of 200 µL was mixed with 800 µL reagent in 1.5 mL reaction tubes. The tubes were centrifuged for 10 s using a Biofuge Pico centrifuge (Heraeus, Hanau, Germany) to ensure that no drops of the mixture remained in the caps of the tubes. Subsequently, the tubes were incubated in a dry block thermostat (Biosan, Riga, Latvia) at 90 °C for 45 min. Next, the tubes were cooled in water and exactly 500 µL of the reaction mixture was transferred to a 3 mL cuvette; 2.5 mL of a mixture of 2-propanol/water = 1/1 ( v / v ) was added and the contents were mixed well. The absorption at 570 nm was measured using a Specord 200 Plus spectrophotometer (Analytik Jena, Jena, Germany). The same instrument was also used to record the UV/VIS spectra shown in Figure 1 C. A step-by-step protocol is included in the Supplementary Data section (Supplementary Methods S1) .
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278723_p30
|
PMC11278723
|
sec[2]/sec[1]/p[1]
|
3.2. Analytical Procedure for Quantification of Total Amino Acids
| 2.191406 |
biomedical
|
Study
|
[
0.99072265625,
0.0008339881896972656,
0.008209228515625
] |
[
0.77490234375,
0.2171630859375,
0.00638580322265625,
0.0014905929565429688
] |
During the optimisation of the reaction conditions, different variations in the reagent and procedure were used. The details are stated in the figure legends.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278723_p31
|
PMC11278723
|
sec[2]/sec[2]/p[0]
|
3.3. Response of Different Amino Acids
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.00028014183044433594,
0.00023818016052246094
] |
[
0.9990234375,
0.000579833984375,
0.0002472400665283203,
0.00006562471389770508
] |
Solutions containing 2.5 mmol L −1 of the compound to be tested (amino acids and ammonia) were prepared and aliquots of 200 µL were reacted with 800 µL of the freshly prepared ninhydrin reagent as described above. Each time, a blank and 2.5 mmol L −1 asparagine standard were included, and all reactions were made in quadruplicate. The absorptions (ABS) were measured at 570 nm. The response of each compound was calculated using the formula (1) R e s p o n s e i n % = A B S c o m p o u n d − A B S b l a n k A B S a s p a r a g i n e − A B S b l a n k × 100
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278723_p32
|
PMC11278723
|
sec[3]/p[0]
|
4. Conclusions
| 4.273438 |
biomedical
|
Study
|
[
0.99951171875,
0.0003561973571777344,
0.0001531839370727539
] |
[
0.998046875,
0.00036978721618652344,
0.00148773193359375,
0.00016057491302490234
] |
The ninhydrin reaction has been frequently used for the determination of the total content of free amino acids in foods, plants, and other types of samples. Recently, mostly acetic acid/lithium acetate buffers at a ratio of 0–0.96/1 (mol/mol) have been used. Surprisingly, we found that a significantly higher acetic acid to acetate ratio of 2/1 gives better results with respect to the signal intensity and a more uniform dye production from different amino acids. In addition, although an acetic acid/lithium acetate buffer system was used in most previous protocols, we found that lithium, sodium, potassium and magnesium acetate are equally suitable. Due to its superior solubility in water, potassium acetate was used for the preparation of the buffer. DMSO was found to be the most suitable organic solvent because the colour development was most intense and ninhydrin and hydrindantin were readily soluble in this reagent, simplifying reagent preparation. Concentrations of 20 g L −1 and 0.8 g L −1 were found to be optimal for ninhydrin and hydrindantin, respectively. In contrast to previous publications, where samples were incubated at 100 °C for 5 to 20 min, we found that 90 °C for 45 min is more suitable because the obtained dye is more stable at that temperature. The optimised procedure was perfectly linear and highly sensitive, with an LOD and LOQ of 0.03 and 0.1 mmol L −1 , respectively. Furthermore, the developed method was highly reproducible and accurate as indicated by the intra-day and inter-day RSDs in the range of 0.5% to 2.4% and 1.7% to 2.1%, as well as recovery rates for spiked samples in the range of 100–105%.
|
[
"Amelie Charlotte Stauß",
"Carolin Fuchs",
"Paulina Jansen",
"Sarah Repert",
"Kimberley Alcock",
"Sandra Ludewig",
"Wilfried Rozhon"
] |
https://doi.org/10.3390/molecules29143262
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278736_p0
|
PMC11278736
|
sec[0]/p[0]
|
1. Introduction
| 3.267578 |
biomedical
|
Other
|
[
0.99609375,
0.0030727386474609375,
0.0009226799011230469
] |
[
0.00980377197265625,
0.8193359375,
0.166748046875,
0.004016876220703125
] |
Infective endocarditis (IE) is a condition that has not seen a substantial reduction in mortality rates despite the progress made in current developments in antibiotic discovery, the use of advanced imaging techniques such as transesophageal echocardiography for early diagnosis, and the implementation of treatment efforts in recent years .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p1
|
PMC11278736
|
sec[0]/p[1]
|
1. Introduction
| 3.099609 |
biomedical
|
Other
|
[
0.99658203125,
0.002593994140625,
0.000972747802734375
] |
[
0.0173797607421875,
0.8232421875,
0.1552734375,
0.00420379638671875
] |
IE, while still relatively rare, appears to be on the rise. This severe form of sepsis affects up to 40–50% of patients, who may require valve surgery. With a mortality rate of 20–25% per year, the disease remains a significant concern. However, the classic clinical syndromes of acute or subacute endocarditis have shifted, and the current forms are less pronounced .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p2
|
PMC11278736
|
sec[0]/p[2]
|
1. Introduction
| 1.942383 |
biomedical
|
Other
|
[
0.99267578125,
0.002353668212890625,
0.004734039306640625
] |
[
0.07196044921875,
0.912109375,
0.01343536376953125,
0.002536773681640625
] |
Notably, high-income countries have experienced profound epidemiological changes, with a growing number of cases involving prosthetic valves.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p3
|
PMC11278736
|
sec[0]/p[3]
|
1. Introduction
| 3.855469 |
biomedical
|
Review
|
[
0.9990234375,
0.0006337165832519531,
0.00029015541076660156
] |
[
0.2296142578125,
0.207275390625,
0.560546875,
0.002471923828125
] |
Prosthetic valve infective endocarditis (PVE) was initially identified in the 1950s and has been the focus of numerous studies reporting extremely high mortality rates among these patients. PVE is a serious condition that can arise following cardiac valve replacement surgery, and it is associated with elevated mortality rates, which can range from 18% to 59% .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p4
|
PMC11278736
|
sec[0]/p[4]
|
1. Introduction
| 3.945313 |
biomedical
|
Review
|
[
0.9990234375,
0.0006861686706542969,
0.0002799034118652344
] |
[
0.30712890625,
0.024993896484375,
0.66650390625,
0.0012521743774414062
] |
PVE is a severe and potentially life-threatening complication of valve replacement surgery, with an incidence of 10–30% of all IE cases. Patients with prosthetic heart valves are considered to be at high risk of developing IE, with an incidence rate of 0.3–1.2%. Approximately one-third of all endocarditis cases are attributed to PVE, due to the growing number of valve replacement procedures being performed. The rise in transcatheter aortic valve implantations (TAVIs) has further contributed to the prevalence of this condition .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278736_p5
|
PMC11278736
|
sec[0]/p[5]
|
1. Introduction
| 2.564453 |
biomedical
|
Other
|
[
0.9970703125,
0.0011186599731445312,
0.0018291473388671875
] |
[
0.060302734375,
0.9072265625,
0.0300140380859375,
0.0022449493408203125
] |
Research suggests that the mitral and aortic valves are most commonly affected, while the tricuspid valve is least commonly affected .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p6
|
PMC11278736
|
sec[0]/p[6]
|
1. Introduction
| 2.783203 |
biomedical
|
Other
|
[
0.99658203125,
0.002239227294921875,
0.0013141632080078125
] |
[
0.0149688720703125,
0.978515625,
0.0048980712890625,
0.0015878677368164062
] |
Bacteria are the primary cause of prosthetic valve endocarditis (PVE), although fungal species can also lead to IE .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p7
|
PMC11278736
|
sec[0]/p[7]
|
1. Introduction
| 3.167969 |
biomedical
|
Other
|
[
0.99853515625,
0.0010194778442382812,
0.0005764961242675781
] |
[
0.0804443359375,
0.90625,
0.011474609375,
0.0018987655639648438
] |
S. aureus , E. faecalis , and Coagulase-negative Staphylococci are the most commonly implicated bacteria in the pathogenesis of IE .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p8
|
PMC11278736
|
sec[0]/p[8]
|
1. Introduction
| 3.890625 |
biomedical
|
Other
|
[
0.8583984375,
0.1397705078125,
0.0018520355224609375
] |
[
0.017669677734375,
0.9541015625,
0.012603759765625,
0.0154876708984375
] |
Surgical management of patients diagnosed with PVE typically targets cases in which significant vegetation, prosthetic valve infections, valve dysfunction, or advanced cardiac insufficiency are identified through sonography. Frequently, when antibiotics fail to alleviate septic symptoms, such as fever, chills, fatigue, and low blood pressure that persist for over a week, surgical intervention involving a prosthetic valve is usually warranted .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p9
|
PMC11278736
|
sec[0]/p[9]
|
1. Introduction
| 2.373047 |
biomedical
|
Other
|
[
0.9892578125,
0.00910186767578125,
0.00185394287109375
] |
[
0.00893402099609375,
0.984375,
0.00388336181640625,
0.002910614013671875
] |
The outcome of PVE is often determined by the time of presentation. Early-onset PVE occurs less than one year after surgery, while late-onset takes place at more than a year after surgical treatment.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p10
|
PMC11278736
|
sec[0]/p[10]
|
1. Introduction
| 3.828125 |
biomedical
|
Other
|
[
0.97705078125,
0.0221405029296875,
0.0005855560302734375
] |
[
0.0394287109375,
0.8994140625,
0.05340576171875,
0.007648468017578125
] |
Patients diagnosed with PVE may experience a variety of complications, including persistently positive blood cultures, septic shock, or even death. It is crucial to understand that persistent infection and heart failure are the most significant predictive factors of mortality in hospitalized patients with PVE. Complications associated with PVE are often challenging to manage, and the complexity of the condition typically requires specialized knowledge and expertise to effectively address the associated issues .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278736_p11
|
PMC11278736
|
sec[0]/p[11]
|
1. Introduction
| 2.916016 |
biomedical
|
Other
|
[
0.99755859375,
0.0016632080078125,
0.0006642341613769531
] |
[
0.28759765625,
0.69873046875,
0.0100860595703125,
0.003582000732421875
] |
S. aureus is still associated with high mortality rates in patients with PVE, as well as early complications such as congestive heart failure. The postoperative mortality rates in this category remained high, indicating virulence of the infectious pathogen. The prognosis for these individuals is challenging to evaluate because it can fluctuate significantly depending on the specific infectious agent present .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p12
|
PMC11278736
|
sec[0]/p[12]
|
1. Introduction
| 2.109375 |
biomedical
|
Other
|
[
0.984375,
0.01093292236328125,
0.00458526611328125
] |
[
0.0046234130859375,
0.98828125,
0.005207061767578125,
0.0020618438720703125
] |
Two important innovations in the management of PVE have been suggested in recent years: a multimodal approach and a team of experts that constitutes the endocarditis team .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278736_p13
|
PMC11278736
|
sec[0]/p[13]
|
1. Introduction
| 2.501953 |
biomedical
|
Other
|
[
0.99267578125,
0.005672454833984375,
0.0016651153564453125
] |
[
0.0078887939453125,
0.9794921875,
0.01082611083984375,
0.001678466796875
] |
Several studies support the importance of multidisciplinary therapy for IE (infectious disease specialists, cardiac surgeons, cardiologists, neurologists, and anesthesiologists) that are bound to guide medical therapy .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278736_p14
|
PMC11278736
|
sec[0]/p[14]
|
1. Introduction
| 3.808594 |
biomedical
|
Other
|
[
0.8779296875,
0.11944580078125,
0.0024242401123046875
] |
[
0.01406097412109375,
0.95947265625,
0.01904296875,
0.007572174072265625
] |
The primary responsibility of the endocarditis team is to evaluate the most vulnerable or severely impaired patients, as there is still considerable debate regarding the optimal timing and postoperative care for these patients. The decision to perform surgery must consider various factors, including the location and severity of the infection, the patient’s preoperative condition and comorbidities, and the feasibility of early surgical intervention. The treatment of PVE is among the most difficult, often resulting in a high mortality rate .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278736_p15
|
PMC11278736
|
sec[0]/p[15]
|
1. Introduction
| 3.601563 |
biomedical
|
Other
|
[
0.99072265625,
0.00832366943359375,
0.001033782958984375
] |
[
0.01230621337890625,
0.767578125,
0.2164306640625,
0.0037384033203125
] |
Patients with PVE are more likely to experience complications and unfavorable outcomes than those with native valve endocarditis, despite having a similar incriminating agent. Thus, it is essential to diagnose PVE accurately and initiate prompt treatment to mitigate its detrimental effects. The significance of the multimodal approach for the diagnosis and management of PVE has become increasingly recognized .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278736_p16
|
PMC11278736
|
sec[1]/sec[0]/p[0]
|
2.1. Study Design
| 3.699219 |
biomedical
|
Study
|
[
0.99853515625,
0.0012063980102539062,
0.0004787445068359375
] |
[
0.9990234375,
0.00039505958557128906,
0.0002276897430419922,
0.0001455545425415039
] |
This was an observational, population-based cohort study that utilized data from the electronic records of individuals who were admitted to the Infectious Diseases Department of the “Dr. Carol Davila” Central Military Emergency University Hospital in Bucharest between 1 January 2017 and 31 December 2022. The study was conducted in accordance with ethical guidelines and approved by the Ethics Committee of the “Dr. Carol Davila” Central Military Emergency University Hospital in Bucharest . Informed consent was obtained from all the patients included in the study.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278736_p17
|
PMC11278736
|
sec[1]/sec[1]/p[0]
|
2.2. Setting
| 2.533203 |
biomedical
|
Study
|
[
0.982421875,
0.0158233642578125,
0.0017271041870117188
] |
[
0.98828125,
0.0096588134765625,
0.0007171630859375,
0.0015211105346679688
] |
PVE was diagnosed according to the modified Duke criteria . All patients who were diagnosed with PVE between 1 January 2017 and 31 December 2022 were included in the study. The follow-ups for PVE and survival ended on 31 December 2023 and February 2024, respectively.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278736_p18
|
PMC11278736
|
sec[1]/sec[2]/p[0]
|
2.3. Study Population
| 3.865234 |
biomedical
|
Study
|
[
0.9228515625,
0.076171875,
0.0009760856628417969
] |
[
0.990234375,
0.0062255859375,
0.0007648468017578125,
0.00299835205078125
] |
We included all patients (n = 78) who were diagnosed with PVE between 2017 and 2022 at the “Dr. Carol Davila” Central Military Emergency University Hospital in Bucharest. The exclusion criteria were other types of implantable cardiovascular devices, three consecutive negative blood cultures, and no obvious vegetation on transesophageal ultrasound examination. Three sets of blood cultures were obtained from each patient with a minimum interval of 30 min between each set and a maximum of 24 h. Blood cultures were collected, and patients were administered empirical broad-spectrum antibiotic therapy.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p19
|
PMC11278736
|
sec[1]/sec[2]/p[1]
|
2.3. Study Population
| 2.933594 |
clinical
|
Other
|
[
0.276123046875,
0.72119140625,
0.0024623870849609375
] |
[
0.046112060546875,
0.8193359375,
0.003108978271484375,
0.1314697265625
] |
Following the receipt of blood culture results at an average interval of 3–5 days, antibiotic therapy was directed using an antibiogram. The decision to administer combined therapy, comprising medical treatment and surgery, was made by a multidisciplinary team that included an infectious disease specialist, cardiologist, and cardiovascular surgeon.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p20
|
PMC11278736
|
sec[1]/sec[3]/p[0]
|
2.4. Statistical Analysis
| 4.089844 |
biomedical
|
Study
|
[
0.99951171875,
0.0004737377166748047,
0.0002472400665283203
] |
[
0.9990234375,
0.0004916191101074219,
0.0003161430358886719,
0.00007897615432739258
] |
Frequency tables and descriptive statistics (mean and standard deviation) were used to analyze patient information, and two non-parametric statistical tests, the Mann–Whitney test and Kruskal–Wallis test, were applied to reveal gender and age differences in patients’ medical characteristics. These non-parametric tests have the main advantage of not making any assumptions about the shape of the population distribution from which the sample was drawn. The results of the Kruskal–Wallis test are expressed as p -values. The p -value represents the probability of obtaining differences as large or larger than those observed in our data, if the null hypothesis is true. If the p -value is less than the predefined significance level of 0.05, we reject the null hypothesis and conclude that there are significant differences between at least two groups.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p21
|
PMC11278736
|
sec[1]/sec[3]/p[1]
|
2.4. Statistical Analysis
| 1.62207 |
biomedical
|
Study
|
[
0.978515625,
0.001605987548828125,
0.02001953125
] |
[
0.5166015625,
0.4775390625,
0.00399017333984375,
0.0020904541015625
] |
SPSS software Version 26 was used to conduct the statistical analyses.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p22
|
PMC11278736
|
sec[1]/sec[4]/p[0]
|
2.5. Objective
| 4.054688 |
biomedical
|
Study
|
[
0.9833984375,
0.015960693359375,
0.0005903244018554688
] |
[
0.99072265625,
0.007659912109375,
0.000759124755859375,
0.0007958412170410156
] |
The objective of this study was to evaluate patients with PVE by comparing the treatment outcomes of early- and late-onset IE episodes following prosthetic valve replacement surgery. The goal was to provide a comprehensive assessment of the efficacy of these methods. The findings from this assessment will be used to improve the quality of care for individuals who have undergone prosthetic valve replacement surgery for IE.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278736_p23
|
PMC11278736
|
sec[2]/p[0]
|
3. Results
| 2.761719 |
biomedical
|
Study
|
[
0.9921875,
0.006439208984375,
0.0014829635620117188
] |
[
0.99755859375,
0.0019063949584960938,
0.0002073049545288086,
0.0004398822784423828
] |
This study included a total of 78 patients. The patient distribution per year was as follows: 23 in 2017, 20 in 2018, 10 in 2019, 13 in 2020, and 12 in 2021. With regard to age, the majority of patients fell within the range of 61 to 80 years (74.4%). Of the patients, 14.2% were aged between 41 and 60 years and 3.84% were aged between 21 and 40 years. Only 7.6% of patients were aged >80 years. The participants were aged between 25 and 95 years, with a mean age of 66 years.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p24
|
PMC11278736
|
sec[2]/p[1]
|
3. Results
| 2.392578 |
biomedical
|
Study
|
[
0.69677734375,
0.300048828125,
0.00336456298828125
] |
[
0.87255859375,
0.07366943359375,
0.0032711029052734375,
0.05059814453125
] |
Upon admission, fever was the most common symptom that was present in all patients. In terms of hospitalization, the majority of the patients (66.4%) required hospitalization for 31–43 days, while 33.6% required more than 46 days.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278736_p25
|
PMC11278736
|
sec[2]/p[2]
|
3. Results
| 3.599609 |
biomedical
|
Study
|
[
0.60498046875,
0.392333984375,
0.00249481201171875
] |
[
0.96630859375,
0.0195159912109375,
0.0024242401123046875,
0.011749267578125
] |
The shortest hospital stay was 3 days, whereas the longest was 94 days, with an average hospital stay of 34.8 days. Evolutionarily, 27 patients (34.7%) were admitted to the ICU with an average duration of 11 days. For patients who were only treated with antibiotics, the length of hospital stay varied between a minimum of 5 days and a maximum of 94 days, with an average stay of 62.4 days. For patients who underwent surgical intervention in addition to antibiotic treatment, the minimum duration of hospitalization was 3 days, whereas the maximum duration was 73 days, with an average stay of 51.2 days.
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278736_p26
|
PMC11278736
|
sec[2]/sec[0]/p[0]
|
3.1. Analysis of the Distribution of Etiological Agents in Patients with PVE
| 3.675781 |
biomedical
|
Study
|
[
0.998046875,
0.0017137527465820312,
0.0002942085266113281
] |
[
0.998046875,
0.0015573501586914062,
0.00025773048400878906,
0.00027632713317871094
] |
Microorganisms were detected in the blood cultures of all 78 patients using serological methods. The most prevalent microorganism identified was S. aureus (38.5%), followed by E. faecalis (26.9%). These data are shown in Table 1 .
|
[
"Corina-Ioana Anton",
"Cosmin Alexandru Buzilă",
"Silviu Marcel Stanciu",
"Săndica Bucurică",
"Daniela Anghel",
"Alexia Teodora Ștefan",
"Ion Ștefan",
"Adrian Streinu-Cercel"
] |
https://doi.org/10.3390/microorganisms12071442
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |