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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PMC11276800_p4
|
PMC11276800
|
sec[1]/sec[0]/p[1]
|
2.1. Musashi RBPs
| 4.230469 |
biomedical
|
Study
|
[
0.99951171875,
0.0002541542053222656,
0.0001653432846069336
] |
[
0.99853515625,
0.00023937225341796875,
0.00116729736328125,
0.00008755922317504883
] |
Padial-Molina et al. investigated the nuclear and cytoplasmic expression of Musashi-1 in different cell types involved in bone formation in an experimental model of rat femur bone fracture. Osteoblasts demonstrated both nuclear and cytoplasmic Musashi-1 expression, which was absent in mature chondrocytes. Over a 14-day period of callus formation, there was a gradual increase in Musashi-1 expression in MSCs, osteoblasts, and osteocytes as compared to the control. After 14 days of healing, Musashi-1 was detected at a much higher level in bone fracture callus as compared to fibrous connective tissues of the unfractured bone. In addition, Musashi-1 was predominantly found in the nucleus of MSCs and immature chondrocytes of the fibrocartilage callus. RUNX2 and POSTN (periostin) followed an almost identical expression pattern to that of Musashi-1 in MSCs, osteoblasts, and chondrocytes, suggesting an interrelated function between Musashi-1, RUNX-2, and POSTN during the bone healing process.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p5
|
PMC11276800
|
sec[1]/sec[0]/p[2]
|
2.1. Musashi RBPs
| 4.183594 |
biomedical
|
Study
|
[
0.99951171875,
0.00017881393432617188,
0.00015652179718017578
] |
[
0.99853515625,
0.00028443336486816406,
0.0009579658508300781,
0.00007772445678710938
] |
O’Valle et al. detected high Musashi-1 levels in the nucleus and cytoplasm of MSCs derived from bone grafts after maxillary sinus surgery in humans. Musashi-1 was also found in the nucleus and cytoplasm of osteoclasts and osteoblasts, but it was exclusively localized in the nucleus of osteocytes. No Musashi-1 expression was detected in adipocytes. Although RUNX2 expression remained unchanged in both native and grafted bone, POSTN expression was increased in grafted bone and correlated with the expression of Musashi-1, suggesting an interrelated function of the two genes to regulate osteogenesis during bone regeneration.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276800_p6
|
PMC11276800
|
sec[1]/sec[0]/p[3]
|
2.1. Musashi RBPs
| 4.167969 |
biomedical
|
Study
|
[
0.99951171875,
0.00019669532775878906,
0.00019407272338867188
] |
[
0.9990234375,
0.00019657611846923828,
0.0008916854858398438,
0.0000635981559753418
] |
Padial-Molina et al. characterized the expression of Musashi-1 during the osteogenic differentiation of MSCs from the oral cavity, in relation to RUNX2. MSCs derived from dental pulp exhibited the highest expression of cell stemness markers such as MYC , SOX2 , POU5F1 , and NANOG after xenografting. An investigation of Musashi-1 mRNA expression in MSCs of different origins showed that Musashi-1 was significantly elevated in MSCs from the dental follicle but not from the alveolar bone or tooth germ after 14 days of differentiation. After 28 days of differentiation, Musashi-1 was detected in MSCs from grafted bone. Similar to the findings of O’Valle et al. , POSTN expression was increased in grafted bone, while RUNX2 expression remained unchanged.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276800_p7
|
PMC11276800
|
sec[1]/sec[0]/p[4]
|
2.1. Musashi RBPs
| 4.53125 |
biomedical
|
Study
|
[
0.99951171875,
0.000354766845703125,
0.00021398067474365234
] |
[
0.99609375,
0.00048351287841796875,
0.0029888153076171875,
0.00021123886108398438
] |
Suo et al. detected a gradual increase in Musashi-2 expression during the differentiation of bone-marrow-derived MSCs into osteoblasts. However, Musashi-2 expression gradually decreased following the induction of adipocyte differentiation. These findings indicate that Musashi-2 may play a vital role in determining the differentiation fate of bone-marrow-derived MSCs towards either osteoblasts or adipocytes. Musashi-2 was detected in the growth plate, periosteum, and cancellous bone but not in compact bone. Musashi-2 knockdown resulted in significant reductions in trabecular bone thickness and bone mass and a markedly shortened femur infiltrated with adipocytes. Bone-marrow-derived MSCs lacking Musashi-2 showed significantly -decreased expression of Col1α1 , Atf4 , Alp , and Bsp and increased expression of Cebpα and Cebpβ during osteogenic and adipogenic differentiation, respectively. RNA sequencing techniques confirmed these results, suggesting that the Musashi-2 knockout might promote osteoblast differentiation and suppress adipogenic differentiation. Musashi-2 overexpressed in bone-marrow-derived MSCs was found to bind to the peroxisome proliferator-activated receptor γ (PPARγ) mRNA, promoting the differentiation into osteoblast lineage cells, whereas the enrichment of Cebpα transcript by Musashi-2 influenced adipocyte differentiation from MSCs.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276800_p8
|
PMC11276800
|
sec[1]/sec[1]/p[0]
|
2.2. ZFP36L1
| 4.214844 |
biomedical
|
Study
|
[
0.99951171875,
0.00024580955505371094,
0.00015413761138916016
] |
[
0.99853515625,
0.0002142190933227539,
0.00098419189453125,
0.00009196996688842773
] |
Liu et al. investigated the role of the RBP ZFP36L1 in adipogenic differentiation of bone-marrow-derived MSCs in aplastic anemia (AA) in the presence of levamisole. Levamisole is an adipogenic differentiation suppressor that acts through improving the bone microenvironment. MSCs from AA patients exhibited increased expression of adipogenic markers such as PPARγ, PLIN1, LPL, and FABP4, along with a greater number of lipid droplets as compared to controls. The induction of adipogenic differentiation led to decreased ZFP36L1 expression in AA MSCs, and levamisole treatment restored ZFP36L1 expression. ZFP36L1 knockdown enhanced the expression of adipogenic differentiation markers PPARγ , PLIN1 , LPL , and FABP4 and increased lipid droplet formation in AA MSCs, while ZFP36L1 overexpression downregulated the adipogenic differentiation markers and decreased lipid droplet formation. Mechanistically, Liu et al. . found that ZFP36L1 could downregulate PPRAGC1B to mediate the effects of levamisole. The associated mechanisms are shown in Figure 1 .
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p9
|
PMC11276800
|
sec[1]/sec[2]/p[0]
|
2.3. PUM RBPs
| 4.269531 |
biomedical
|
Study
|
[
0.99951171875,
0.0001844167709350586,
0.00014913082122802734
] |
[
0.9990234375,
0.0003490447998046875,
0.000621795654296875,
0.00008654594421386719
] |
The human PUF family proteins, PUM1 and PUM2, are RBPs that bind to a PUM recognition element (PRE) in the 3′-UTR of target mRNAs. Lee et al. reported that PUM2 can bind to the 3′UTR region of the JAK2 and RUNX2 mRNA to mediate the crosstalk between osteogenic and adipogenic differentiation. PUM2 overexpression downregulated JAK2 and RUNX2, but it did not affect the colony-forming ability of bone-marrow-derived MSCs. Instead, PUM2 overexpression induced PPARγ and ALP expression and promoted adipogenic differentiation. CRISPR/CAS-9-mediated PUM2 silencing prevented fat accumulation and enhanced bone formation in zebrafish embryos.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p10
|
PMC11276800
|
sec[1]/sec[2]/p[1]
|
2.3. PUM RBPs
| 4.183594 |
biomedical
|
Study
|
[
0.99951171875,
0.0001806020736694336,
0.00015997886657714844
] |
[
0.99853515625,
0.00029850006103515625,
0.0011014938354492188,
0.00008571147918701172
] |
Yoon et al. detected reduced PUM1 expression during MSC senescence. PUM1 modulated the activity of nuclear factor κβ (NF-κB) by post-transcriptionally targeting the mRNA translation of Toll-like receptor 4 (TRL4). PUM1 overexpression rescued the proliferation and colony-forming ability of MSCs treated with H 2 O 2 . Additionally, PUM1 was found to be downregulated in damaged cartilage tissues from patients with osteoarthritis (OA). Injections of a lentiviral vector carrying PUM-1 protected the knee cartilage integrity in a mouse model of medial meniscus damage-induced osteoarthritis.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p11
|
PMC11276800
|
sec[1]/sec[3]/p[0]
|
2.4. ELAVL1
| 4.261719 |
biomedical
|
Study
|
[
0.99951171875,
0.00024199485778808594,
0.00016021728515625
] |
[
0.9990234375,
0.0002849102020263672,
0.0004279613494873047,
0.00010651350021362305
] |
The RBP embryonic lethal abnormal version like-1 (ELAVL-1) was predominantly localized in the nucleus in MSCs undergoing osteogenic differentiation, where it promoted differentiation . Selective ELAVL1 knockdown in mouse bone-marrow-derived MSCs altered alizarin red staining and the transcript levels of RUNX2 , Col1a1 , and Fabp4 but not OSX. ELAVL1 silencing also reduced the expression of a number of genes involved in adipogenesis. RNA-sequencing of bone-marrow-derived MSCs during differentiation showed that ELAVL1 knockdown upregulated genes associated with extracellular matrix (ECM) formation and collagen synthesis at the transcriptional level. However, the effect of ELAVL1 overexpression on osteogenic and adipogenic differentiation was not evaluated.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276800_p12
|
PMC11276800
|
sec[2]/p[0]
|
3. RBPs Involved in Osteoblastogenesis
| 4.296875 |
biomedical
|
Study
|
[
0.99951171875,
0.0001773834228515625,
0.0001798868179321289
] |
[
0.9892578125,
0.0015401840209960938,
0.00899505615234375,
0.00016617774963378906
] |
Bone remodeling commences with MGS differentiation to mononuclear osteoblasts, a process under the control of transcriptional factors such as RUNX2 . Osteoblasts regulate bone metabolism, mineralization, and the synthesis of ECM proteins such as osteocalcin and alkaline phosphatase. In addition, osteoblast-derived signaling molecules facilitate intercellular interaction with osteoclasts. Osteoblast-derived RANKL plays a role in abnormal bone remodeling and mineralization in osteoarthritis . Recent studies have indicated that RBPs are involved in the post-transcriptional regulation of osteoblastogenesis.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p13
|
PMC11276800
|
sec[2]/sec[0]/p[0]
|
3.1. ZFP36L1
| 4.265625 |
biomedical
|
Study
|
[
0.99951171875,
0.00022423267364501953,
0.00017392635345458984
] |
[
0.9990234375,
0.0002639293670654297,
0.0008087158203125,
0.00009268522262573242
] |
Tseng et al. reported that the RBP ZFP36L1 promoted osteoblastogenesis but inhibited adipogenic differentiation. Lower mRNA levels of ZFP36L1 were detected in the femur and MSCs of aged mice compared to younger controls. ZFP36L1 knockdown in MC3T3-E1 preosteoblasts inhibited their differentiation into osteoblasts, as evidenced by decreased levels of osteocalcin and osteopontin. However, ZFP36L1 knockdown upregulated adipogenic differentiation markers, including PPARγ-2, aP2, and adiponectin. ZFP36L1 overexpression in C3H10T1/2 cells enhanced osteoblastogenesis but reduced PPARγ2 expression and decreased lipid droplet formation. These findings support the binding of ZFP36L1 to the PPARγ-2 mRNA as a key factor directing osteoblast and adipocyte lineage differentiation.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p14
|
PMC11276800
|
sec[2]/sec[1]/p[0]
|
3.2. BICC1
| 4.40625 |
biomedical
|
Study
|
[
0.99951171875,
0.0003249645233154297,
0.00021898746490478516
] |
[
0.998046875,
0.0002875328063964844,
0.001720428466796875,
0.00014030933380126953
] |
Mesner et al. investigated the associations of the RBP Bicaudal C homolog-1 (BICC1) with quantitative trait loci related to osteoblastogenesis. The results identified BICC1 as a genetic determinant of osteoblastogenesis and bone mineral density. Linkage data analysis identified Bmd43 and Bmd42 as regulators of bone mineral density. BICC1 was found to be localized in close proximity to Bmd43 , and the two proteins showed a correlated expression. The absence of BICC1 was associated with reduced bone mineral density in the femoral bones of mice, but the bone in the medullary region was not altered. In addition, a correlation was observed between trabecular bone volume and bone fraction volume in BICC1 knockdown mice. High BICC1 expression was detected in primary calvarial osteoblasts during differentiation, with relatively lower levels observed at the midpoint of differentiation. siRNA-mediated BICC1 knockdown results indicated that BICC1 regulated the activity of alkaline phosphatase and the expression of osteogenic markers during bone formation. BICC1 was found to target polycystic kidney disease 2 (PKD2) to inhibit osteoblastogenesis. BICC1 knockdown reduced alizarin activity, which was rescued by PKD2 overexpression.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276800_p15
|
PMC11276800
|
sec[2]/sec[2]/p[0]
|
3.3. RBM3
| 4.226563 |
biomedical
|
Study
|
[
0.99951171875,
0.00018131732940673828,
0.00016760826110839844
] |
[
0.9990234375,
0.00028896331787109375,
0.0005440711975097656,
0.00007671117782592773
] |
Kim et al. reported that the RBP RBM3 facilitates osteoblast differentiation through extracellular-signal-regulated kinase (ERK) phosphorylation. RBM3 was expressed during the osteoblastic differentiation of MC3T3E1 cells. RBM3 overexpression upregulated early osteogenic differentiation markers such as RUNX2 and osteocalcin, while RBM3 knockdown decreased the expression of RUNX2. Conversely, RUNX2 knockdown did not affect RBM3 expression. RBM3 overexpression enhanced the phosphorylation of ERK and p38 kinase (p38) but suppressed the phosphorylation of c-Jun N-terminal kinase (JNK).
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276800_p16
|
PMC11276800
|
sec[2]/sec[3]/p[0]
|
3.4. Sam68
| 4.179688 |
biomedical
|
Study
|
[
0.99951171875,
0.00019872188568115234,
0.00014674663543701172
] |
[
0.99853515625,
0.0002532005310058594,
0.00133514404296875,
0.00009226799011230469
] |
Richard et al. found that the elimination of the RBP Sam68 prevented bone loss in aging mice. Sam68 was highly expressed in the metaphysis of long bones and cartilage, and it was localized in the nucleus of proliferating osteoblasts. Mouse embryos deficient in Sam68 showed no significant developmental abnormalities—no tumor formation or immunogenic reactions. Sam68-deficient aging mice exhibited no cortical bone thinning or trabecular bone loss, and the bone mineral density of the femur and vertebrae showed significant improvement over control mice. In line with this, aging Sam68-deficient mice showed a distinct pattern of bone structure preservation, as evidenced by the results from ALP and TRAP staining and mineral deposition assessment.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p17
|
PMC11276800
|
sec[2]/sec[3]/p[1]
|
3.4. Sam68
| 4.191406 |
biomedical
|
Study
|
[
0.99951171875,
0.00019752979278564453,
0.00014150142669677734
] |
[
0.99853515625,
0.00029277801513671875,
0.0010023117065429688,
0.00008690357208251953
] |
Sun et al. detected high Sam68 expression in the synovial tissue of rheumatoid arthritis (RA) patients, which was predominantly localized in fibroblast-like synoviocytes (FLS). TNFα stimulated Sam68 expression and induced its translocation from the cytoplasm to the nucleus. Sam68 knockdown in FLS suppressed TNFα, IL-6, and MMP-1 expression and inhibited cell proliferation, migration, and invasion. These findings underscore the important function of Sam68 in regulating FLS pathophysiology in RA in the presence of TNFα.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p18
|
PMC11276800
|
sec[2]/sec[4]/p[0]
|
3.5. SAMD4
| 4.300781 |
biomedical
|
Study
|
[
0.99951171875,
0.0002532005310058594,
0.00016057491302490234
] |
[
0.9990234375,
0.0003020763397216797,
0.0005130767822265625,
0.00011903047561645508
] |
Niu et al. found that the insertion of a PiggyBac transposon allele at the sterile alpha motif domain containing protein 4 (SAMD4) locus reduced the expression of the RBP SAMD4, resulting in a smaller body size and a shortened lifespan in mice. SAMD4 deficiency was associated with atypical skull development, decreased osteogenesis, and delayed ossification of the tibia. SAMD4-deficient mouse osteoblasts displayed decreased expression of osteoblast differentiation markers and ALP activity, highlighting the regulatory role of SAMD4 in osteoblastogenesis. Mechanistically, SAMD4 was shown to bind to the mitogen-inducible gene 6 (MIG6) mRNA and impair its translation.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276800_p19
|
PMC11276800
|
sec[2]/sec[4]/p[1]
|
3.5. SAMD4
| 3.326172 |
biomedical
|
Study
|
[
0.99755859375,
0.0006895065307617188,
0.0017538070678710938
] |
[
0.490478515625,
0.4580078125,
0.049896240234375,
0.0017108917236328125
] |
A schematic diagram illustrating the regulation of osteoblastogenesis by RBPs is presented in Figure 2 .
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p20
|
PMC11276800
|
sec[3]/p[0]
|
4. RBPs Involved in Osteoclastogenesis
| 3.976563 |
biomedical
|
Review
|
[
0.99853515625,
0.0007610321044921875,
0.0005869865417480469
] |
[
0.1138916015625,
0.006195068359375,
0.87939453125,
0.0006923675537109375
] |
Monocyte colony stimulating factor and RANKL stimulate multinuclear osteoclast differentiation from the fusion of macrophage/monocyte precursors in the bone microenvironment. This process perpetuates a dynamic equilibrium of bone formation and resorption during bone remodeling. Excessive osteoclast activity can disrupt the bone microarchitecture and increase bone fragility, leading to osteoporosis or osteoarthritis. Here, we discuss the molecular mechanisms by which RBPs regulate osteoclastogenesis, as illustrated below.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276800_p21
|
PMC11276800
|
sec[3]/sec[0]/p[0]
|
4.1. CPEB RBPs
| 4.371094 |
biomedical
|
Study
|
[
0.99951171875,
0.0002541542053222656,
0.0002410411834716797
] |
[
0.99169921875,
0.00042629241943359375,
0.0075836181640625,
0.00015532970428466797
] |
The CPEB family of RBPs, which include CPEB1, 2, 3, and 4, are widely expressed in warm-blooded mammals . Arasaki et al. detected elevated CPEB4 expression in RAW264.7 cells undergoing osteoclastic differentiation induced by RANKL. RANKL stimulated CPEB4 translocation from the cytoplasm to the nucleus through activation of the PI3K-Akt signaling pathway. CPEB4 deletion led to the decreased expression of osteoclastic differentiation markers such as Acp5 , Nfatc1 , Ctsk , and RANK . Yang et al. found that CPEB4 was upregulated in metastatic tumors compared to the non-metastatic tumors of human osteosarcoma. CPEB4 overexpression increased M2-like polarization of activated RAW264.7 macrophages, as evidenced by enhanced CD206 and Arg1 expression. Supernatants from activated RAW264.7 macrophages overexpressing CPEB4 increased U2OS and MG-63 cell invasion and migration, highlighting the role of macrophage-derived CPEB4 in human osteosarcoma tumorigenesis. In addition, CPEB1 was implicated in the malignant progression of human osteosarcoma .
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11276800_p22
|
PMC11276800
|
sec[3]/sec[1]/p[0]
|
4.2. Musashi2
| 4.144531 |
biomedical
|
Study
|
[
0.99951171875,
0.00017702579498291016,
0.0001544952392578125
] |
[
0.9990234375,
0.0002918243408203125,
0.0007162094116210938,
0.0000852346420288086
] |
Fujiwara et al. found that Musashi-2, but not Musashi-1, was significantly upregulated during RANKL-induced osteoclastic differentiation. Musashi-2 knockdown decreased the number of TRAP-positive cells and downregulated the osteoclast markers Nfatc1 , Ctsk , and Acp5. The Western blotting results revealed that Musashi-2 promoted osteoclastogenesis through Numb-independent mechanisms.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276800_p23
|
PMC11276800
|
sec[3]/sec[2]/p[0]
|
4.3. Tristetraprolin
| 4.289063 |
biomedical
|
Study
|
[
0.99951171875,
0.0002627372741699219,
0.00015020370483398438
] |
[
0.9990234375,
0.00038123130798339844,
0.0005426406860351562,
0.00013256072998046875
] |
Mice deficient in the RBP tristetraprolin (TTP) exhibited increased alveolar bone loss over time, along with amplified inflammatory cell infiltration in the periodontal epithelium and maxillary tissues . TTP-deficient maxillae showed an increased number of osteoclasts around the bone perimeter, and these osteoblasts were larger in size compared to wildtype control, and they exhibited increased resorptive function. Elevated levels of tumor necrosis factor-α (TNFα), a master modulator of osteoclastogenesis, were detected in the serum of TTP-deficient mice. It was postulated that TTP targets TNFα to suppress osteoclastogenesis and bone resorption.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p24
|
PMC11276800
|
sec[3]/sec[3]/p[0]
|
4.4. IMP2
| 4.183594 |
biomedical
|
Study
|
[
0.99951171875,
0.00019443035125732422,
0.00014770030975341797
] |
[
0.9990234375,
0.00034165382385253906,
0.0005202293395996094,
0.00009381771087646484
] |
Liu et al. demonstrated that IMP2, an insulin-like growth factor 2 mRNA-binding protein, can regulate osteoclast function and adhesion. IMP2-deficit mice showed more immature bone structures and a thicker hypertrophic chondrocyte layer in the femoral metaphysis compared to wildtype mice. IMP2-deficient osteoclasts displayed impaired resorptive activity and reduced adhesion to the bone surface owing to defects in the CD44-osteopontin signaling pathway .
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p25
|
PMC11276800
|
sec[3]/sec[4]/p[0]
|
4.5. Mex3B
| 4.3125 |
biomedical
|
Study
|
[
0.99951171875,
0.00026226043701171875,
0.0001499652862548828
] |
[
0.9990234375,
0.0004925727844238281,
0.0004439353942871094,
0.0001481771469116211
] |
The RBP Mex3B can inhibit osteoclastogenesis by negatively regulating the level of the dendritic-cell-specific transmembrane protein (DC-STAMP) mRNA . Mex3B-deficient mice exhibited reduced bone density, decreased trabecular bone volume, and enlarged osteoclasts in the tibia and femur. Bone-marrow-derived macrophages deficient in Mex3B exhibited increased DC-STAMP mRNA level and enhanced osteoclastic differentiation upon RANKL stimulation. In addition, Mex3B overexpression suppressed osteoclastic differentiation of RAW264.7 macrophages. The results from qPCR assays indicated that Mex3B regulated the transcription of the DC-STAMP gene or the stability of the nascent transcript.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p26
|
PMC11276800
|
sec[3]/sec[5]/p[0]
|
4.6. QKI
| 4.316406 |
biomedical
|
Study
|
[
0.99951171875,
0.00026726722717285156,
0.00015747547149658203
] |
[
0.99853515625,
0.00029969215393066406,
0.0009741783142089844,
0.00012230873107910156
] |
The femoral metaphysis of mice lacking the RBP QKI showed decreased bone mineral density and cancellous bone formation . QKI-deficient mice showed elevated levels of intraosseous inflammatory cytokines such as TNFα, a suppressor of osteoblastogenesis and a promoter of osteoclastogenesis. Mechanistically, QKI downregulation enhanced osteoclastogenesis by activating the MAPK and NF-κB signaling pathways. Rauwel et al. investigated the role of QKI5 in HCMV-mediated osteoclastogenesis and bone resorption. HCMV infection upregulated QKI5 and induced its translocation from the cytoplasm to the nucleus to interact with the immediate early 2 viral gene, leading to the downregulation of the CSF-1F and RANK mRNA. QKI5 knockdown exacerbated HCMV-mediated osteoclastogenesis, while QKI5 overexpression inhibited osteoclastogenesis and protected against bone destruction in a mouse model of calvarial bone erosion.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276800_p27
|
PMC11276800
|
sec[4]/p[0]
|
5. RBPs Associated with Bone Diseases
| 2.431641 |
biomedical
|
Other
|
[
0.99609375,
0.0020542144775390625,
0.00200653076171875
] |
[
0.00792694091796875,
0.96826171875,
0.0219268798828125,
0.001766204833984375
] |
Bone diseases such as osteoporosis, osteosarcoma, and osteoarthritis are quite common, but their etiology is not fully understood. Identifying new target molecules for therapeutic intervention is critical for improving the clinical outcome of patients with bone diseases.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p28
|
PMC11276800
|
sec[4]/sec[0]/p[0]
|
5.1. RBPs Associated with Diabetic Osteoporosis
| 3.789063 |
biomedical
|
Study
|
[
0.99951171875,
0.0002313852310180664,
0.0003180503845214844
] |
[
0.4892578125,
0.12396240234375,
0.385498046875,
0.0013294219970703125
] |
Diabetic osteoporosis is a life-limiting complication of diabetes mellitus (DM). Epidemiological data show that DM is a major risk factor for osteoporotic fracture . High glucose suppresses osteocalcin expression to inhibit osteoblast differentiation and bone formation, contributing to diabetic osteopenia . A number of RBPs have been implicated in the pathogenesis of diabetic osteoporosis as illustrated below.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p29
|
PMC11276800
|
sec[4]/sec[0]/sec[0]/p[0]
|
5.1.1. ELAVL1
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.00017023086547851562,
0.00014972686767578125
] |
[
0.9990234375,
0.0002999305725097656,
0.0005807876586914062,
0.00008243322372436523
] |
Ren et al. detected elevated levels of ELAVL1 and divalent metal transporter 1 (DMT1) in the femur of DM mice. ELAVL1 knockdown in DM mice increased osteogenesis and prevented bone loss. In addition, ELAVL1 knockdown in MC3T3-E1 preosteoblasts enhanced osteoblastic differentiation and mineralization. Mechanistic studies suggest that ELAVL1 may function through regulating DMT1.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p30
|
PMC11276800
|
sec[4]/sec[0]/sec[1]/p[0]
|
5.1.2. PCBP1
| 4.136719 |
biomedical
|
Study
|
[
0.99951171875,
0.0001609325408935547,
0.00015842914581298828
] |
[
0.9990234375,
0.0002849102020263672,
0.0006399154663085938,
0.00007927417755126953
] |
Ma et al. found that high glucose upregulated the RBP PCBP1, reduced the viability of hFOB1.19 osteoblasts, and caused mitochondria atrophy. PCBP1 overexpression enhanced OPG and OCN expression and increased calcium deposition, while PCBP1 knockdown showed opposite effects. Mechanistically, PCBP1 may function through suppressing ferroptosis upon high glucose stimulation.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p31
|
PMC11276800
|
sec[4]/sec[1]/p[0]
|
5.2. RBPs Associated with Osteosarcoma
| 3.019531 |
biomedical
|
Other
|
[
0.99853515625,
0.0004742145538330078,
0.0009655952453613281
] |
[
0.401123046875,
0.476806640625,
0.11993408203125,
0.0023212432861328125
] |
Osteosarcoma is a common bone disease, with an estimated incidence rate of 9 per million individuals. Due to the lack of diagnostic tests and limited treatment options, the survival rate and prognosis of osteosarcoma patients are extremely poor. A number of RBPs have been implicated in the pathogenesis of osteosarcoma as illustrated below.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p32
|
PMC11276800
|
sec[4]/sec[1]/sec[0]/p[0]
|
5.2.1. HuR
| 4.1875 |
biomedical
|
Study
|
[
0.99951171875,
0.00027370452880859375,
0.0002536773681640625
] |
[
0.97119140625,
0.0005731582641601562,
0.027862548828125,
0.0002079010009765625
] |
Liu et al. detected high expression of the RBP HuR in stage T2 osteosarcoma (OS) tissues and various OS cell lines, including MG63, SAOS2, U2OS, and SJSA-1. HuR knockdown decreased SJSA-1 cell proliferation, migration, and epithelial–mesenchymal transition (EMT). Mechanistically, HuR may function through targeting AGO2. Similarly, Pan et al. showed that HuR was highly expressed in human OS tissues, and HuR knockdown decreased MG63 OS cell viability and EMT. Mechanistic investigation suggested that HuR may promote OS progression by disrupting the interaction between miR-142-3p and HMGA-1. Xu et al. reported that HuR knockdown repressed SAOS2 OS cell migration, invasion, and stemness through inhibiting YAP.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p33
|
PMC11276800
|
sec[4]/sec[1]/sec[1]/p[0]
|
5.2.2. LIN28A
| 4.085938 |
biomedical
|
Study
|
[
0.99951171875,
0.00015234947204589844,
0.0002009868621826172
] |
[
0.9990234375,
0.00036597251892089844,
0.0003972053527832031,
0.00006562471389770508
] |
Wang et al. detected high expression of the RBP LIN28A in human OS tissues compared to adjacent tissues. LIN28A knockdown in MG63 OS cells decreased cell viability and migration and increased apoptosis. LIN28A was found to associate with the long noncoding RNA (lncRNA) MALAT1 and increase its stability and expression.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p34
|
PMC11276800
|
sec[4]/sec[1]/sec[2]/p[0]
|
5.2.3. PTBP-1
| 4.1875 |
biomedical
|
Study
|
[
0.99951171875,
0.0001914501190185547,
0.0001556873321533203
] |
[
0.9990234375,
0.00033783912658691406,
0.0004837512969970703,
0.00008243322372436523
] |
Zhou et al. reported that the LncRNA ZMIZ1-AS1 was upregulated in human OS tissues, which was controlled by the transcription of SOX-2 and MYC in response to the hippo signal pathway. ZMIZ1-AS1 promoted OS cell proliferation, migration, and invasion by recruiting the RBP PTBP1 to stabilize the ZMIZ1 mRNA. PTBP1 or ZMIZ1 overexpression rescued the suppressive effects of ZMIZ1-AS1 knockdown on OS cellular processes.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p35
|
PMC11276800
|
sec[4]/sec[2]/sec[0]/p[0]
|
5.3.1. ZFP36L1
| 4.203125 |
biomedical
|
Study
|
[
0.99951171875,
0.0002086162567138672,
0.0001537799835205078
] |
[
0.9990234375,
0.0002760887145996094,
0.0008349418640136719,
0.00009125471115112305
] |
Son et al. found that the RBP ZFP36L1 was upregulated in human and mouse osteoarthritis (OA) chondrocytes and cartilage. Although ZFP36L1 overexpression alone in mouse knee-joint tissue did not modulate OA symptoms, ZFP36L1 silencing significantly reduced cartilage destruction and osteophyte formation in OA mice. Mechanistically, ZFP36L1 may function through directly targeting members of the heat shock protein 70 family such as HSPA1A and HSPA1B. HSPA1A overexpression reduced OA symptoms after surgical destabilization of the medial meniscus.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276800_p36
|
PMC11276800
|
sec[4]/sec[2]/sec[1]/p[0]
|
5.3.2. GNL3
| 4.019531 |
biomedical
|
Study
|
[
0.99951171875,
0.00019252300262451172,
0.00018739700317382812
] |
[
0.9990234375,
0.0006971359252929688,
0.00030803680419921875,
0.00010502338409423828
] |
The RBP GNL3 was found to be upregulated in the synovial tissue and fluid of OA patients . RNA sequencing revealed elevated GNL3, PTN, and IL-24 levels in human OA lesions. GNL3 knockdown studies identified IL-24 and PTN as target genes for GNL3 .
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276800_p37
|
PMC11276800
|
sec[4]/sec[2]/sec[2]/p[0]
|
5.3.3. TDP-43
| 4.082031 |
biomedical
|
Study
|
[
0.99951171875,
0.0001780986785888672,
0.00013816356658935547
] |
[
0.9990234375,
0.0002655982971191406,
0.0008563995361328125,
0.0000845789909362793
] |
Chang et al. found that the RBP TDP-43 and its binding partner G3BP1 were downregulated in the degenerated cartilage of OA patients. TDP-43 concentration in human OA synovial fluid was positively correlated with IL-1β. In addition, an intra-articular injection of recombinant TDP-43 improved cartilage degradation and subchondral bone remodeling in a rat model of post-traumatic knee OA.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p38
|
PMC11276800
|
sec[4]/sec[2]/sec[3]/p[0]
|
5.3.4. SND1
| 4.203125 |
biomedical
|
Study
|
[
0.99951171875,
0.00020384788513183594,
0.00014221668243408203
] |
[
0.9990234375,
0.00027823448181152344,
0.0008015632629394531,
0.00009655952453613281
] |
Lv et al. found that an IL-1β treatment of rat primary chondrocytes upregulated the RBP SND1 and induced ferroptosis. SND1 knockdown suppressed chondrocyte ferroptosis induced by IL-1β, which could be abolished by HSPA5 knockdown. In a rat model of OA with surgical destabilization of the medial meniscus, SND1 knockdown upregulated HSPA5, suppressed ferroptosis, and alleviated cartilage tissue damage. Mechanistically, SND1 bound to the 3′UTR of the HSPA5 mRNA and destabilized the HSPA5 mRNA.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p39
|
PMC11276800
|
sec[4]/sec[3]/sec[0]/p[0]
|
5.4.1. PTBP1
| 4.023438 |
biomedical
|
Study
|
[
0.99951171875,
0.00011408329010009766,
0.00015234947204589844
] |
[
0.998046875,
0.0008616447448730469,
0.00084686279296875,
0.00010538101196289062
] |
Yu et al. reported that the LncRNA SNHGI interacted with the RBP PTBP1 to upregulate DNMT1, which, in turn, suppressed osteogenic differentiation of bone-marrow-derived MSCs and contributed to osteoporosis.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p40
|
PMC11276800
|
sec[4]/sec[3]/sec[1]/p[0]
|
5.4.2. HuR
| 4.277344 |
biomedical
|
Study
|
[
0.99951171875,
0.00028014183044433594,
0.00018298625946044922
] |
[
0.99267578125,
0.00037360191345214844,
0.0068817138671875,
0.00016105175018310547
] |
Liu et al. reported that HuR was downregulated in the bone tissue of ovariectomized (OVX) mice. HuR silencing suppressed osteoblastic differentiation of MC3T3-E1 preosteoblasts, as evidenced by decreased Runx2 and Osterix expression and reduced ALP activity. Mechanistically, HuR stabilized the LRP6 mRNA and promoted its translation through binding to the 3′UTR of the LRP mRNA, leading to the activation of the Wnt pathway. In OVX mice, injection of HuR-overexpressing bone-marrow-derived MSCs alleviated OA symptoms and enhanced femoral bone formation. Chen et al. found that the circular RNA circStage-1 was downregulated in human and rat osteoporotic bone tissues. CircStag-1 overexpression promoted osteogenic differentiation of bone-marrow-derived MSCs. Mechanistically, circStag1 interacted with HuR and promoted its translocation from the nucleus to the cytoplasm, where HuR stabilized and enhanced LRP5/6 and β-catenin, thereby activating the Wnt pathway and stimulating osteogenic differentiation.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276800_p41
|
PMC11276800
|
sec[4]/sec[4]/sec[0]/p[0]
|
RBFOX2
| 4.148438 |
biomedical
|
Study
|
[
0.99951171875,
0.00015592575073242188,
0.00014793872833251953
] |
[
0.9990234375,
0.00046706199645996094,
0.0005292892456054688,
0.0000889897346496582
] |
Cho et al. found that the RBP RBFOX2 was localized in the cytoplasm in calcific tendons and the nucleus in normal tendons of human subscapularis. RBFOX2 regulated CHD2 and MBNL1 mRNA splicing in the nucleus. Thus, the cytoplasmic localization of RBFOX2 in calcific tendons may have affected overall mRNA splicing and gene expression, contributing to the development of calcific tendinopathy.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11276800_p42
|
PMC11276800
|
sec[5]/p[0]
|
6. Summary and Perspectives
| 4.089844 |
biomedical
|
Review
|
[
0.98681640625,
0.008148193359375,
0.005237579345703125
] |
[
0.0028228759765625,
0.0040130615234375,
0.9921875,
0.000911712646484375
] |
This review article discusses RBPs involved in bone development and bone-related diseases, along with their mechanisms of action. Through interacting with target RNA molecules, RBPs regulate the osteogenic differentiation of bone-marrow-derived MSCs and the formation of osteoclasts by the fusion and differentiation of macrophages, thereby modulating bone homeostasis and contributing to bone pathology ( Table 1 ). Current evidence supports RBPs as potential targets for developing novel therapies to treat various bone diseases. However, research on RBPs in bone pathology is still at an early stage, and establishing RBPs as reliable targets is a work in progress.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p43
|
PMC11276800
|
sec[5]/p[1]
|
6. Summary and Perspectives
| 4.066406 |
biomedical
|
Study
|
[
0.99951171875,
0.00028443336486816406,
0.0003075599670410156
] |
[
0.626953125,
0.010101318359375,
0.362548828125,
0.0006122589111328125
] |
Future work may utilize advanced technologies such as CLIP sequencing, CRISPR-Cas9-based gene editing, co-immunoprecipitation, and molecular imaging to further the understanding of RBPs and their mechanisms of action in bone biology and pathophysiology. In particular, the intricate regulatory interactions of RBPs with various RNA molecules, including mRNA, miRNA, lncRNA, and circRNA, warrant comprehensive investigation. These interactions need rigorous validation to mitigate false positives, which could be addressed using techniques such as cellular thermal shift assays and microscale thermophoresis. The dynamic nucleocytoplasmic shuttling of RBPs at various stages of bone diseases could be another focal point of the research .
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276800_p44
|
PMC11276800
|
sec[5]/p[2]
|
6. Summary and Perspectives
| 4.175781 |
biomedical
|
Study
|
[
0.99951171875,
0.0003783702850341797,
0.0003478527069091797
] |
[
0.69873046875,
0.002986907958984375,
0.297607421875,
0.0004954338073730469
] |
The aggregation of RBPs is a pathological hallmark of neurodegenerative diseases such as ALS and FTD . In these disease, the RNA-mediated phase transition of RBPs is a key mechanism leading to the deposition of RBP aggregates in degenerating lesions. To date, there have been few reports on RBP aggregation in bone tissues. In future research, molecular dynamics simulations, thermal aggregation assays, protein chromatography, and X-ray scattering techniques can be used to investigate RBP aggregation in bone biology and pathology. Using nomogram models to analyze microarray and RNA-seq data in the public domain may identify new RBP diagnostic markers or therapeutic targets for bone diseases. The interactions between the RBP-RNA network and cell components such as ribosomes, the ubiquitin–proteasome system, and the cytoskeleton can be investigated using genome-wide transcriptome analysis. Overall, a systematic approach to screen and identify altered RBPs in disease-affected bone tissue could help identify novel molecular entities for therapeutic intervention.
|
[
"Hafiz Muhammad Umer Farooq",
"Lihuizi Yang",
"Mengru Cao",
"Zhihao Chen",
"Airong Qian",
"Kai Dang"
] |
https://doi.org/10.3390/ijms25147735
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p0
|
PMC11276812
|
sec[0]/p[0]
|
1. Introduction
| 4.152344 |
biomedical
|
Other
|
[
0.99462890625,
0.00447845458984375,
0.0009355545043945312
] |
[
0.048828125,
0.54052734375,
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0.0083770751953125
] |
Contact dermatitis is an inflammatory reaction of the skin to a substance that either irritates the skin (irritant contact dermatitis (ICD)) or triggers an allergic response (allergic contact dermatitis (ACD)) after repeated exposure . ICD is a nonimmunologic and nonspecific inflammatory response to direct cutaneous injury caused by contact with an irritating substance . Symptoms characterizing a severe skin reaction include erythema (redness), edema (swelling), vesiculation (fluid-filled bumps or blisters), and the development of scaling, crusting, and cracks or fissures. Sensory symptoms include burning and/or itching and hypersensitivity (enhanced itching or pain) to certain mechanical or thermal cutaneous stimuli.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p1
|
PMC11276812
|
sec[0]/p[1]
|
1. Introduction
| 4.152344 |
biomedical
|
Review
|
[
0.99755859375,
0.0016345977783203125,
0.0007824897766113281
] |
[
0.0703125,
0.00331878662109375,
0.92578125,
0.0007262229919433594
] |
In humans, ICD represents up to 7% of all dermatological cases and 80% of contact dermatitis-associated occupational skin disorders . The development of ICD is caused by exposure to an irritant, leading to a disrupted skin barrier and increased penetration of irritants . This triggers an inflammatory response with dysregulation of proinflammatory cytokines and chemokines and immunologic activation . The clinical manifestation of ICD can vary significantly based on several factors, including the strength, amount, duration, frequency, and concentration of irritants, as well as environmental factors and underlying skin conditions . Therefore, one challenge posed by ICD lies in its heterogeneous nature. It encompasses a spectrum of conditions with diverse clinical manifestations and underlying causes. Examples include acute, delayed acute, and cumulative (chronic) ICD, each presenting unique challenges in both clinical treatment and experimental investigation . In the treatment of ICD, avoidance of irritants is a major factor, and moisturizers are commonly employed to enhance the regeneration of the skin barrier compared to untreated irritated skin .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p2
|
PMC11276812
|
sec[0]/p[2]
|
1. Introduction
| 4.171875 |
biomedical
|
Study
|
[
0.99951171875,
0.0002560615539550781,
0.0004074573516845703
] |
[
0.94091796875,
0.002017974853515625,
0.056884765625,
0.00021445751190185547
] |
Sodium lauryl sulfate (SLS, or sodium dodecyl sulfate (SDS)) is an irritant, anionic, surface-active detergent that causes ICD. It is commonly applied as an emulsifier in cosmetics (soaps), detergents, foods (oils), and pharmaceutical vehicles and therefore has a wide application . It is utilized for studying cutaneous irritation in humans and animals . Among the various irritants used to induce experimental ICD models, SLS stands out due to its ability to disrupt the skin barrier and trigger inflammatory responses similar to those observed in clinical settings . To accurately compare models and clinical settings, it is essential to assess symptomology ; consequently, both sensory analyses in humans and fitting valid behavioral analyses in rodents must be applied. Behavioral analysis to assess the effects of raw cosmetic or cleanser products is rarely the focus of such studies , though these products could potentially lead to detrimental effects, as in the case of SLS inducing ICD. Considering that chemicals in washing and cleansing products are often applied to the face, it is crucial to investigate these in combination with other chemicals and factors, as real-life scenarios involve co-application and mechanical and thermal stimulation . Moreover, variations in skin sensitivity and recovery rates depending on the irritated anatomical region underscore the need for standardized testing protocols when assessing the effectiveness of treatments . Therefore, a uniformly applied model and protocols are of high importance.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p3
|
PMC11276812
|
sec[0]/p[3]
|
1. Introduction
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.0001556873321533203,
0.00015234947204589844
] |
[
0.99853515625,
0.0006771087646484375,
0.0009293556213378906,
0.00007325410842895508
] |
Inducing painful and pruritic models on the cheeks of mice offers a valid system for investigating acute and chronic itch and pain through behavioral analysis . This approach allows for the inclusion of responses to injected chemicals and pruritogens in models that induce itch and pain through different pathways to differentiate underlying mechanisms and pathology . We have recently established mechanical and thermal testing protocols specifically for the cheek . For example, in a model of ACD on the cheek, mice exhibited enhanced itch-like scratching in response to pruritogens and an algogen, which typically elicited only pain-like wiping behavior of normal skin without inducing scratching . This approach enables more precise and comprehensive investigation of models like the SLS-induced ICD model and better representation of clinical settings.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p4
|
PMC11276812
|
sec[0]/p[4]
|
1. Introduction
| 4.015625 |
biomedical
|
Study
|
[
0.99951171875,
0.00036525726318359375,
0.00036525726318359375
] |
[
0.99951171875,
0.0002963542938232422,
0.00017392635345458984,
0.00006604194641113281
] |
This study aimed to determine whether ICD produced by SLS elicited excessive site-directed scratching and/or wiping behaviors occurring spontaneously or in response to chemical, mechanical, or thermal stimuli.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276812_p5
|
PMC11276812
|
sec[1]/sec[0]/p[0]
|
2.1. Behavioral Responses to Mechanical Stimulation
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.0003829002380371094,
0.00026416778564453125
] |
[
0.99951171875,
0.00018262863159179688,
0.0002906322479248047,
0.00006413459777832031
] |
After mechanical stimulation, differences in the mean DSs (discomfort scores) revealed significant main effects of treatment, force, and time of testing and an interaction between treatment, group, time, and force. The mean DSs significantly increased with bending forces for both the control and SLS groups on each day after the irritant removal. The control mice exhibited no consistent change in mean DS for both mechanical stimuli across all days. Compared with day 0, the mean DS in the SLS group was significantly greater on day 1 as a reaction to an innocuous vFF (von Frey filament) applied with a 0.23 mN force (allodynia) and to each of the typically aversive vFFs applied with forces of 2 to 20 mN (hyperalgesia). The SLS-group mice had a significantly greater mean DS than the control mice in response to each filament , but only on day 1. No differences between groups were found on subsequent days for any filament.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p6
|
PMC11276812
|
sec[1]/sec[1]/p[0]
|
2.2. Behavioral Responses to Heat Stimulation
| 4.125 |
biomedical
|
Study
|
[
0.9990234375,
0.0004563331604003906,
0.00037384033203125
] |
[
0.99951171875,
0.00018477439880371094,
0.00025463104248046875,
0.00005716085433959961
] |
Significant main effects of treatment, temperature, and day of testing were found in response to thermal stimulation. For both the control and SLS groups, before and each day after the irritant removal, the mean DS was higher after 52 °C compared to 38 °C. For the innocuous temperature of 38 °C, no change in the mean DS was observed in the control or SLS groups on any day. However, after noxious heat of 52 °C, a significant difference in the mean DS was only found on days 1 and 2 (hyperalgesia) compared with day 0 in the SLS group and in a comparison of the SLS and the control group .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276812_p7
|
PMC11276812
|
sec[1]/sec[2]/p[0]
|
2.3. Spontaneous Behavior
| 2.632813 |
biomedical
|
Study
|
[
0.99609375,
0.0009822845458984375,
0.0028228759765625
] |
[
0.99560546875,
0.0033512115478515625,
0.0006723403930664062,
0.0002086162567138672
] |
ICD mice exhibited an increased mean number of spontaneous wipes but not scratching bouts on days 1 and 2 in comparison to the control mice . No differences were significant between days 1 and 2 for either the SLS or the control groups.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p8
|
PMC11276812
|
sec[1]/sec[3]/p[0]
|
2.4. Behavioral Responses to Pruritogens and an Algogen
| 4.105469 |
biomedical
|
Study
|
[
0.99951171875,
0.00027108192443847656,
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] |
[
0.99951171875,
0.00020778179168701172,
0.0002658367156982422,
0.0000521540641784668
] |
When responses to an injection of saline were compared, the control mice exhibited significantly more bouts of scratching and wipes in response to both the algogen bradykinin and the pruritogens histamine, BA, and BAM8-22 . After SLS application, significantly more scratching was evoked by each pruritogen and the algogen in comparison with saline . Only BK led to significantly higher wiping numbers in comparison to saline injection . SLS-treated mice exhibited more scratching but not wiping in comparison to the control mice . However, they also showed significantly more scratching in response to saline. This increased response to saline may have contributed to the greater response to each pruritogen and bradykinin.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276812_p9
|
PMC11276812
|
sec[1]/sec[4]/p[0]
|
2.5. Severity of Inflammation of Cheek Skin
| 3.921875 |
biomedical
|
Study
|
[
0.9990234375,
0.0007123947143554688,
0.0003337860107421875
] |
[
0.99755859375,
0.0016689300537109375,
0.0004494190216064453,
0.00017535686492919922
] |
Cheek skin was photographed on each day in each group. For all the groups, after treatment, a roundly shaped area of hair removal surrounding the treatment area was left by the removal of the PEEK cups. The control mice showed no indications of redness, scaling, or swelling at all time points. In contrast, SLS led to an erythema of the skin on day 1 and day 2, and a slight scaling was seen on day 1 and was more pronounced on day 2 .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276812_p10
|
PMC11276812
|
sec[1]/sec[4]/p[1]
|
2.5. Severity of Inflammation of Cheek Skin
| 4.117188 |
biomedical
|
Study
|
[
0.99951171875,
0.00043892860412597656,
0.0002448558807373047
] |
[
0.99951171875,
0.00028514862060546875,
0.0002982616424560547,
0.00007337331771850586
] |
The erythema and scaling were scored, and skin-fold thickness was measured. The control mice had no erythema, scaling, nor increased thickness of the skin after treatment with distilled water. The erythema score and skin thickness showed an increase on day 1 and day 2 in the SLS group, whereas the scaling score increased significantly only on day 2 . In comparison with the control group, SLS mice had significantly higher values of erythema and skin thickness on both day 1 and day 2, but a significantly higher scaling score only on day 2 .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p11
|
PMC11276812
|
sec[1]/sec[5]/p[0]
|
2.6. High-Frequency Ultrasound Imaging of Skin Layers
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.00037407875061035156,
0.0002930164337158203
] |
[
0.99951171875,
0.00022292137145996094,
0.0002758502960205078,
0.00006401538848876953
] |
Ultrasound images of each mouse’s cheek were acquired on each day (day 0, day 1, and day 2) for each group and condition. Exemplary ultrasound images for the control group showed similar features, such as skin thickness and smoothness, across all days. There was no difference displayed in overall skin thickness or each skin-layer thickness between each day in the control group and day 0 in the different groups. The SLS group showed an increased overall skin thickness on day 1—more so on day 2 . This was also indicated by an increase in the thickness of each layer on day 2 . The highest increase was seen in the epidermis and dermis, especially on the second day. The increase in dermal thickness even reached significance on the first day.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p12
|
PMC11276812
|
sec[2]/p[0]
|
3. Discussion
| 3.914063 |
biomedical
|
Study
|
[
0.99951171875,
0.00021183490753173828,
0.00036454200744628906
] |
[
0.9990234375,
0.0005307197570800781,
0.00022590160369873047,
0.00006848573684692383
] |
In this study, we successfully developed an ICD model using 5% SLS dissolved in acetone applied consistently to the cheeks of mice using occlusion via PEEK cups. This approach allowed precise administration of SLS and facilitated rapid induction of the model, reducing suffering and pain.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p13
|
PMC11276812
|
sec[2]/p[1]
|
3. Discussion
| 4.070313 |
biomedical
|
Study
|
[
0.99951171875,
0.00017774105072021484,
0.00029349327087402344
] |
[
0.9990234375,
0.00027632713317871094,
0.00047969818115234375,
0.00005632638931274414
] |
SLS-induced ICD increased pain-like spontaneous behavior. In contrast, SLS did not increase the incidence of itch-like spontaneous behavior. These results are consistent with previous findings in humans that SLS-treated skin was accompanied by inflammatory pain sensation but little or no spontaneous itching , and, in one study in mice, no spontaneous scratching was observed . However, in a clinical setting, most forms of ICD are accompanied by frequent pruritus . Therefore, the SLS-induced ICD model in mice may not be an accurate representation for studying spontaneous itch.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276812_p14
|
PMC11276812
|
sec[2]/p[2]
|
3. Discussion
| 2.333984 |
biomedical
|
Other
|
[
0.9951171875,
0.0003955364227294922,
0.0045623779296875
] |
[
0.365478515625,
0.619140625,
0.01397705078125,
0.0013360977172851562
] |
Symptomology and behavioral analysis are important aspects in assessing murine models. In assessing the side effects of cosmetic raw products such as triclosan, an antibacterial compound used in many cosmetic products, other authors have uncovered behavioral impairments .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p15
|
PMC11276812
|
sec[2]/p[3]
|
3. Discussion
| 4.347656 |
biomedical
|
Study
|
[
0.99951171875,
0.00040531158447265625,
0.0001653432846069336
] |
[
0.998046875,
0.00028586387634277344,
0.0015935897827148438,
0.00016546249389648438
] |
We also found that SLS mice exhibited allodynia and hyperalgesia on day 1 after punctate mechanical stimuli and hyperalgesia to heat. These findings are consistent with those obtained in humans, where 1% and 2% SLS produced temporary hyperalgesia to heat and mechanical stimuli that disappeared within 2–3 days . This finding aligns with previous studies highlighting the temporal dynamics of inflammatory responses, demonstrating that cytokine activation and peaking occur within the first 24 h and that gene activation decreases by 96 h . In human models, full recovery without treatment is expected within 2–4 weeks , although the inflammatory peak subsides and signs of skin inflammation, such as visual scoring and transepidermal water loss, decrease in the days following induction . In our SLS-induced ICD model, no significant differences were observed beyond the initial rection regarding mechanical and thermal stimulation. However, visual signs of inflammation and ultrasound analysis continued to progress. In accordance with our findings of uncoupled symptomatology, stimulation, and visual skin inflammation, a study on human volunteers applying higher concentrations of SLS on the arm led to the recovery of functional parameters and visual skin inflammation, while only reactions to chemical skin provocation persisted . It is known that ICD is heterogeneous regarding underlying mechanisms, inflammation processes, time course, and other factors and that it can develop differently based on region and irritant .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p16
|
PMC11276812
|
sec[2]/p[4]
|
3. Discussion
| 4.179688 |
biomedical
|
Study
|
[
0.99951171875,
0.00023043155670166016,
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[
0.9990234375,
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Despite the nociceptive effects of SLS on spontaneous and stimulus-evoked behavior, injections of each pruritogen and the algogen bradykinin elicited more scratching in the controls but not more wiping behavior. This ICD reaction to SLS is different from that caused by the irritant response to the hapten SADBE, which in unsensitized mice led to increased spontaneous scratching and wiping but with little or no allodynia or hyperalgesia to mechanical and thermal stimulations . In contrast, mice that had been sensitized to the hapten in a model of SADBE-induced ACD exhibited greater than normal scratching in reaction to histamine-independent pruritogens and bradykinin . The present finding that ICD from 5% SLS caused increased itching after stimulation with histamine stands in contrast to the effects of SADBE-induced ACD, as well as the dry skin model or atopic dermatitis, and is suggestive of differences between the models in underlying biological mechanisms and potentially different options for treatment .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276812_p17
|
PMC11276812
|
sec[2]/p[5]
|
3. Discussion
| 2.658203 |
biomedical
|
Other
|
[
0.99755859375,
0.0005164146423339844,
0.0019073486328125
] |
[
0.255615234375,
0.71435546875,
0.028106689453125,
0.0017843246459960938
] |
It is well established that ICD can co-occur with ACD and atopic dermatitis because these patients may be more susceptible to inflammation and have a lower threshold for developing ICD . This observation suggests a valuable area for further investigation in future animal studies to enhance treatment approaches.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276812_p18
|
PMC11276812
|
sec[2]/p[6]
|
3. Discussion
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.00022208690643310547,
0.0001379251480102539
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[
0.99853515625,
0.0002887248992919922,
0.0010023117065429688,
0.00008016824722290039
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Additionally, our study uncovered differences in reactivity to histamine-dependent and -independent pruritogens which may indicate differences in the involvement of TRPV1 and TRPA1 in downstream signaling, respectively . Though histamine has not been demonstrated to have a role in the development of ICD, antihistamines may relieve symptoms and are therefore regarded as a symptomatic treatment option . Similarly, in a murine study, topical antihistamines treated inflammation and improved the skin barrier in ICD .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276812_p19
|
PMC11276812
|
sec[2]/p[7]
|
3. Discussion
| 4.15625 |
biomedical
|
Study
|
[
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[
0.9990234375,
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It is known that irritants lead to inflammation initiated by varying mechanisms and mediators. The ICD reactions induced may differ based on the type and concentration of the irritant, the host, the environment, and the application procedure . For example, follicular spongiosis was observed after ICD caused by croton oil, benzalkonium chloride, and dithranol but not SLS . Previously, in allergic reactions, increased mRNA expression of different proteins, namely, the chemokine interferon-γ-inducible protein-10 (CXCL10) and the related CXC chemokine receptor 3-activating chemokines (CXCR3) macrophage migration inhibitory factor (MIF) and IP-9, was identified. This was not observed in irritation reactions induced by SLS . Similarly, in our previous study on SADBE-induced ICD, a proinflammatory milieu with cell invasion and increases in IL-1β, TNF-α, and CXCR3 was detected .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p20
|
PMC11276812
|
sec[2]/p[8]
|
3. Discussion
| 3.845703 |
biomedical
|
Study
|
[
0.99951171875,
0.0001195669174194336,
0.0003814697265625
] |
[
0.9853515625,
0.0093536376953125,
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] |
The missing combination of itch and pain and only increased itch after chemical stimulation, as well as the uncoupled sensory symptoms on the first day versus inflammation on the second day, make the 5% SLS model less attractive as a model of pruritic diseases where both itch and pain are present. But the model could be used to study the interaction of itch and pain signaling. Further studies are needed to apply different dosages of SLS and directly compare and contrast itch- and pain-like behaviors for different ICD models.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276812_p21
|
PMC11276812
|
sec[2]/p[9]
|
3. Discussion
| 4.15625 |
biomedical
|
Study
|
[
0.99951171875,
0.0002880096435546875,
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[
0.99755859375,
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] |
Our research highlights the importance of understanding how different irritants elicit distinct inflammatory and sensory pathways, which could inform the structural and immunological characterization of allergenic proteins. The establishment of a standardized model and protocols is paramount for consistent research outcomes. By elucidating the specific sensory and inflammatory mechanisms in ICD, our work contributes to the broader goal of developing targeted treatments for allergic and irritant skin conditions. This model also provides a valuable tool for studying the interplay between itch and pain signaling, offering insights that could lead to better management of pruritic diseases. Therefore, the results of our study can be applied in several critical areas. Investigating whether spontaneous scratching and/or wiping behaviors are heightened in SLS-induced ICD models is essential for understanding symptomatology, refining models for comparative research, distinguishing between skin reaction types, assessing therapeutic strategies, comparing irritants, and guiding clinical applications.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p22
|
PMC11276812
|
sec[2]/p[10]
|
3. Discussion
| 4.035156 |
biomedical
|
Study
|
[
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[
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In conclusion, while our study provides valuable insights into the sensory and inflammatory mechanisms of SLS-induced ICD, further refinements are necessary to enhance the model’s fidelity to clinical pruritic conditions. This could involve optimizing dosages, exploring additional sensory endpoints, and incorporating advanced molecular and immunological analyses. Such advancements hold promise for developing more effective therapeutic strategies tailored to the comprehensive treatment of allergic and irritant skin disorders.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p23
|
PMC11276812
|
sec[3]/sec[0]/p[0]
|
4.1. Animals
| 4.085938 |
biomedical
|
Study
|
[
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[
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C57/BL6 mice (purchased from Charles River Laboratories), 6–8 weeks old and weighing 20–25 g, were housed in groups of four under a 12 h light/dark cycle with unrestricted access to standard laboratory food and water. Approved by the Institutional Animal Care and Use Committee of Yale University School of Medicine, the experimental procedures adhered to the guidelines of the National Institutes of Health (NIH) and the International Association for the Study of Pain (IASP). Experimenters who were blinded to the experimental conditions conducted and assessed all the experiments. A group size of N = 8–10 per group was aimed for based on previous combined behavioral and morphological aspects of other models, and the same chemicals analyses were applied to determine significant differences. A loss was accounted for in each experimental part in case of illness, cup replacement, or other unforeseen cases; therefore, N = 12 mice per group were included in each experimental part . In the stimulus-evoked experiments, N = 12 mice in the SLS group and N = 12 mice in the control group were tested. For assessment of spontaneous behavior, N = 12 mice in the SLS group and N = 12 mice in the control group were tested. Assessment of chemically evoked behavior was performed on N = 5 × 12 = 60 mice in the SLS group and N = 5 × 12 = 60 mice in the control group. Skin inflammation was assessed for N = 12 mice in the SLS group and N = 12 mice in the control group. Ultrasound imaging was conducted with N = 12 mice in the SLS group and N = 12 mice in the control group before treatment with the vehicle and with N = 10 mice after treatment on days 1 and 2 in the control group.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p24
|
PMC11276812
|
sec[3]/sec[1]/p[0]
|
4.2. Model of Irritant Contact Dermatitis
| 4.105469 |
biomedical
|
Study
|
[
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[
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] |
To induce the SLS ICD model, first, the mice were acclimated to the housing facility for 7 days, followed by 5 days of habituation to handling, the testing environment, and the wearing of an Elizabethan collar around the abdomen. The cheek skin was shaved (1 × 1 cm area) under brief anesthesia with isoflurane (2% in pure oxygen). Two days later, filter paper soaked in 5% SLS (Sigma, St. Louis, MO, USA) in distilled water or the vehicle (distilled water) alone was topically applied to the shaved cheek skin by means of a Finn chamber under brief anesthesia with 2% isoflurane and a flow rate of 300 mL/min of oxygen . Cyanoacrylate was applied as a thin layer on the rim of the chamber to affix the cup to the skin. The Finn chamber (Yale Medical School Machine shop, New Haven, CT, USA) consisted of a polyether ether ketone (PEEK) cup (Trident Plastics, Warminster, PA, USA). The cup was a 8 mm diameter disk with a 1.5 mm wide rim around the edge of the disk and was 0.2–0.3 mm deep and could accommodate the thickness of a 5 mm diameter soaked filter paper. PEEK is a biocompatible plastic used in medical applications in orthopedic surgery and in dental implants, among other uses .
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276812_p25
|
PMC11276812
|
sec[3]/sec[1]/p[1]
|
4.2. Model of Irritant Contact Dermatitis
| 4.097656 |
biomedical
|
Study
|
[
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[
0.99755859375,
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] |
To prevent the mice from removing the PEEK cup while allowing locomotion, feeding, and drinking, an Elizabethan collar was placed around the abdomen. In the mouse’s home cage, the wire food rack was removed for 24 h and wet chow was placed in a single cup and on the floor to prevent the mouse from being trapped on one side of the cage without access to drinking water. After the PEEK cup was in place for 24 h, the animal was brought back to the laboratory, where the collar, the PEEK cup, and any remaining glue were removed under brief anesthesia . The SLS ICD model was used to simulate acute inflammatory responses in the mice, allowing for the study of skin irritation and subsequent behavioral and physiological changes. This methodology provides a controlled way to induce and analyze inflammatory responses, offering insights into the dynamics of irritant-induced dermatitis.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p26
|
PMC11276812
|
sec[3]/sec[2]/p[0]
|
4.3. Behavioral Responses after Mechanical Stimuli and Heat Stimuli
| 4.246094 |
biomedical
|
Study
|
[
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[
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Mechanical and heat stimuli were delivered to the treated cheek as previously described before (day 0) and 1 h (day 1), 24 h (day 2), 48 h (day 3), and 72 h (day 4) after irritant removal. Each mouse was placed in a meshed chamber of 4.5 cm length, 3.5 cm width, and 5 cm height. The mechanical stimuli were delivered using nylon filaments with micrometric (µm) tip diameters that exerted bending forces in millinewtons (mN): specifically, 67 (0.23), 100 (2), 100 (10), and 100 (20). Heat stimuli were administered using a probe comprising a chip resistor (2 × 3 mm) and a thermocouple, delivering either 38 °C for warmth or 52 °C for noxious heat. The stimulus temperature was maintained at the probe–skin interface via electronic circuitry. The duration of stimulus application was 1 s unless it was ended by the animal’s withdrawal. Each stimulus was applied 5 times in ascending order of intensity and then 5 times in descending order. During testing, the mice were video-recorded from the side with a mirror positioned to allow for a two-sided view. Behavioral responses to each stimulus were documented post-stimulation and later verified or corrected upon reviewing the video recordings. The operator conducting the experiments was blinded to the experimental treatment. Each behavioral reaction to a stimulus was categorized by discomfort scores (DSs): “no reaction” (=0); “looking” or turning the head or body towards the stimulus (=1); “withdrawal” by turning the head or body away or pulling backward (=2); rapid “flinching” (=3); “biting” with a quick turn of the head towards the object (=4); “shaking” with a short, rapid body movement (=5); “jumping aside” (=6); “jumping in the air” (=7); and audible squeaking (=8). When observing two immediate behaviors, only the one with the highest score was documented. Each wipe directed at the stimulated cheek was counted and added to the DS. The mean score from ten presentations of the same stimulus was then calculated . Mechanical and heat stimuli were applied to assess changes in sensitivity and pain responses in the treated cheek. This testing helped to determine the extent of sensory alterations, hyperalgesia, and allodynia to mechanical and thermal stimuli, providing quantitative data on the impacts of ICD analyzed by behavioral signs.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p27
|
PMC11276812
|
sec[3]/sec[3]/p[0]
|
4.4. Spontaneous Behaviors and Behaviors Evoked by Chemical Injection
| 4.113281 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.99951171875,
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] |
Spontaneous behaviors directed toward the cheek were recorded after 1 h (day 1) and 24 h (day 2) after irritant removal, as described previously . Each mouse was individually placed in a separate plastic container measuring 9 × 9 × 13 cm 3 , each containing a small amount of bedding. A camcorder positioned above both containers recorded both mice simultaneously. Four mirrors were placed and angled around the container, giving a full view of each mouse. The recording was performed inside a sound-proof room after the mice were placed in the container. After a period of 15 min to allow the mice to acclimate to the recording container, spontaneous behavior was recorded for 1 h. Next, each mouse was taken out of the container and received an intradermal injection into the previously treated cheek (SLS or control) of 5 μL of one of 5 chemicals with a 0.3 mL insulin syringe with a 31-gauge needle, as described previously, e.g., . All injections were conducted within 10 s; then, the mouse was again placed in the container for recording of behavior for 30 min without the experimenter being present in the sound-proof room. Each of the following chemicals were given to a different group of 12 mice: saline (5 µL), histamine (5 μg/5 μL), BAM8-22 (1 μg/5 μL), β-alanine (45 μg/5 μL), and bradykinin (2.65 μg/5 μL).
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p28
|
PMC11276812
|
sec[3]/sec[3]/p[1]
|
4.4. Spontaneous Behaviors and Behaviors Evoked by Chemical Injection
| 4.089844 |
biomedical
|
Study
|
[
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[
0.9990234375,
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The video recordings were subsequently analyzed to record the numbers of scratching bouts with the ipsilateral hindlimb as itching sensations and the numbers of wipes with the ipsilateral forelimb directed to the treated cheek as painful sensations. The investigator was kept blinded to the experimental conditions . Spontaneous behaviors and responses to chemical injections were recorded to evaluate itch- and pain-related behaviors. This allowed for a comprehensive understanding of how different stimuli affect behavior and sensory perception in ICD inflamed skin and the altered underlying mechanisms regarding histamine-dependent and -independent itching as well as pain.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p29
|
PMC11276812
|
sec[3]/sec[4]/p[0]
|
4.5. Scoring the Severity of Visually Evident Inflammation
| 4.109375 |
biomedical
|
Study
|
[
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[
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For each experimental group, pictures of the mice’s cheeks were taken in a standardized setup of lighting and camera setting with a color picker and a scale in each picture before (day 0) and 1 h (day 1) and 24 h (day 2) after the irritant removal . At each time point, the erythema and scaling (desquamation) were separately rated to assess the severity of inflammation on the following scale: 0, none; 1, slight; 2, moderate; 3, marked; and 4, very marked . Additionally, the cheek skin-fold thickness was measured under brief anesthesia with 2% isoflurane in pure oxygen; the measurements were taken three times using a micrometer (Mitutoyo, Tokyo, Japan), and the means were calculated.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p30
|
PMC11276812
|
sec[3]/sec[4]/p[1]
|
4.5. Scoring the Severity of Visually Evident Inflammation
| 3.898438 |
biomedical
|
Study
|
[
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Visual scoring of erythema and scaling, along with measurement of skin-fold thickness, was conducted to quantify the severity of inflammation. These assessments helped correlate visible inflammation with underlying pathological changes, offering a clear metric for evaluating the inflammatory response.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276812_p31
|
PMC11276812
|
sec[3]/sec[5]/p[0]
|
4.6. High-Frequency Ultrasound Imaging of Cheek Skin
| 4.136719 |
biomedical
|
Study
|
[
0.99951171875,
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[
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] |
For the acquisition of ultrasound images, a different group of mice were briefly anesthetized before (day 0) and 1 h (day 1) and 24 h (day 2) after the irritant removal, positioned on a thermoregulated platform. The skin of the cheek was evenly coated with ultrasound gel. Using a high-frequency ultrasound scanner (VisualSonics Vevo 770) in B mode and a 55 MHz transducer (RMV 708), we imaged the superficial skin layers to achieve the optimal spatial resolution. We measured the overall thickness of different skin layers—the stratum corneum, epidermis, dermis, and hypodermis—based on their distinct order, appearance, and echogenicity. Light structures were identified as hyperechoic (white), while darker areas were classified as hypoechoic (gray), using ImageJ. The investigators were kept blinded to the experimental condition . High-frequency ultrasound imaging was utilized to measure the thickness of various skin layers, providing detailed structural information. This noninvasive technique allows for precise monitoring of skin changes over time, supporting the evaluation of inflammation and its progression.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276812_p32
|
PMC11276812
|
sec[3]/sec[6]/p[0]
|
4.7. Statistical Analysis
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
0.0003218650817871094,
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[
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0.00006449222564697266
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Behavioral analyses for each type of spontaneous, site-directed behavior (number of scratching bouts or wipes) involved a mixed-design analysis of variance (ANOVA). This included 2 treatment groups (SLS and control) across 2 testing days with repeated measures (before and 1 h after irritant removal). DS values obtained after stimulation with each vFF and heat stimulus were separately analyzed using a three-way ANOVA: 2 treatment groups (SLS, control) × 4 mechanical stimuli (0.23 mN, 2 mN, 10 mN, and 20 mN) × 2 days post-irritant removal. The effects of force and temperature on responses to mechanical and heat stimuli were analyzed separately using a mixed-design ANOVA: 2 treatment groups (SLS and control) × 4 forces or 2 temperatures × 5 testing days with repeated measures over force or temperature and days of testing. Additionally, erythema score, scaling score, and skin-fold thickness were analyzed with a two-way ANOVA: 2 treatment groups (SLS and control) × 3 testing days with repeated measures. Thickness measurements of different skin layers and power Doppler evaluation of high-frequency ultrasound imaging were analyzed with a one-way ANOVA: 2 treatment groups (SLS and control) × 3 testing days. Bonferroni corrections for family-wise error rates were applied to account for multiple comparisons in each statistical analysis following each ANOVA. A p -value < 0.05 was considered statistically significant. The results are presented as means ± SEMs and SDs for categorical variables.
|
[
"Nathalie M. Malewicz-Oeck",
"Zhe Zhang",
"Steven G. Shimada",
"Robert H. LaMotte"
] |
https://doi.org/10.3390/ijms25147718
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p0
|
PMC11276824
|
sec[0]/p[0]
|
1. Introduction
| 3.558594 |
biomedical
|
Other
|
[
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[
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Chronic spontaneous urticaria (CSU) and atopic dermatitis (AD) are two prevalent dermatological conditions that significantly impact the quality of life of affected individuals . These chronic inflammatory skin disorders not only present considerable challenges in diagnosis and management but also necessitate a deeper understanding of their underlying pathophysiology for effective treatment strategies.
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p1
|
PMC11276824
|
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|
1. Introduction
| 4.425781 |
biomedical
|
Study
|
[
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[
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Urticaria is categorized based on its duration as either acute (less than 6 weeks) or chronic (at least 6 weeks), and its potential to have a triggering factor is either inducible or spontaneous. CSU affects approximately 0.02–2.7% of the population with no evident distinction between children and adults. However, it has a slightly elevated occurrence among patients in fifth and sixth decade of life . In the pathogenesis of CSU, the activation and degranulation of mast cells in the skin trigger the release of histamine and other mediators. This cascade leads to sensory nerve activation (itch), vasodilation (erythema), plasma extravasation (edema), and cellular recruitment, manifesting with such symptoms as itchy wheals (hives) and angioedema . Additionally, beyond the release of histamine from dermal mast cells, nonlesional skin in CSU patients exhibits the upregulation of adhesion molecules, infiltration of eosinophils, altered cytokine expression , and sometimes a mild to moderate increase in mast cell numbers .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p2
|
PMC11276824
|
sec[0]/p[2]
|
1. Introduction
| 4.414063 |
biomedical
|
Review
|
[
0.9951171875,
0.002834320068359375,
0.0019102096557617188
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[
0.032562255859375,
0.0023040771484375,
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AD, the most common chronic inflammatory skin disease, affects up to 20% of children worldwide. It persists in adulthood in a minority of cases, affecting up to 3% of the adult population . There has been an increased prevalence of AD over the past decades, not only in developed countries but also in developing ones . The diagnosis of AD is primarily based on clinical presentation and patient history, excluding erythematous and eczematous conditions. While diagnosing AD is generally straightforward in infants and young children, it can become particularly challenging in severe cases and adult populations . In infants, skin lesions typically manifest between 2 and 6 months of age. These lesions may present as papules and papulovesicles, which can coalesce into large plaques that exude fluid and form crusts . Although some infants may initially present with flexural disease, which affects areas such as the antecubital and popliteal fossae, wrists, and ankles, this form of the disease typically emerges after the first year of life. In contrast, adult-onset AD exhibits a more heterogeneous presentation, characterized by greater variability in lesion morphology and distribution, with a notable predilection for the head, neck, hands, and feet. Persistent itching leads to scratching and further contributes to skin thickening and lichenification over time .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p3
|
PMC11276824
|
sec[0]/p[3]
|
1. Introduction
| 4.410156 |
biomedical
|
Study
|
[
0.99951171875,
0.00020778179168701172,
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[
0.994140625,
0.0023860931396484375,
0.003505706787109375,
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The epidermis, crucial as a physical and functional barrier, exhibits significant defects in AD skin. Compromised skin barrier function increases permeability and water loss, making the skin more vulnerable to allergens and pollutants. Immune cells like dendritic cells (DCs) and type 2 innate lymphoid cells (ILC2s) are activated by alarmins released by damaged skin cells, such as interleukins (IL)-33, IL-25, and thymic stromal lymphopoietin (TSLP). These activated immune cells produce cytokines such as IL-5 and IL-13, further activating eosinophils and Th2 cells, exacerbating inflammation . Nonlesional skin in AD patients exhibits an overt increase in the proportion of Th2 cells .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p4
|
PMC11276824
|
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|
1. Introduction
| 4.058594 |
biomedical
|
Study
|
[
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[
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As mentioned, the pathogenesis of AD and CSU remains incompletely understood, with various mechanisms involved. In the immune response, there is a particular emphasis on the role of the Th2 pathway. Th2 cells are characterized by the production of cytokines, including IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13 along with ILC2 cells, which also produce IL-4, IL-5, and IL-13. These Th2 and ILC2 cells share many functional similarities and are key factors in the development of AD and contribute to the chronicity of CSU .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p5
|
PMC11276824
|
sec[0]/p[5]
|
1. Introduction
| 4.144531 |
biomedical
|
Study
|
[
0.99951171875,
0.00022208690643310547,
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[
0.99951171875,
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] |
In our study, we aim to investigate the concentration of IL-5 receptor (IL-5R) within the context of CSU and AD. IL-5 is a well-known pro-inflammatory cytokine secreted by various cell types, such as Th2 lymphocytes, ILC2s, mast cells, and eosinophils. IL-5 influences target cells through the IL-5R, and its functions include promoting eosinophil proliferation, activation, viability, and migration out of the bloodstream towards the site of inflammation . Additionally, IL-5 can increase the expression of IL-2Rα on B cells, boost IgA production, and promote the proliferation and differentiation of both B cells and cytotoxic T cells. IL-5 does not directly participate in IgE production but can stimulate mast cells to release histamine . Several factors that downregulate and upregulate IL-5R expression are presented in Figure 3 .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p6
|
PMC11276824
|
sec[0]/p[6]
|
1. Introduction
| 3.863281 |
biomedical
|
Review
|
[
0.9970703125,
0.0019245147705078125,
0.0010843276977539062
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[
0.01136016845703125,
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Over the past decade, therapeutic approaches for atopic dermatitis and chronic spontaneous urticaria have mostly focused on alleviating symptoms and decreasing inflammation rather than addressing the underlying cause. However, the emergence of novel biological agents targeting IL-5 and IL-5R, such as mepolizumab, reslizumab, and benralizumab, has introduced new therapeutic options .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p7
|
PMC11276824
|
sec[1]/p[0]
|
2. Results
| 3.796875 |
biomedical
|
Study
|
[
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[
0.99951171875,
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] |
The obtained results show that the mean IL-5R serum concentration was significantly higher in patients with CSU than in the control group ( p = 0.038). The values and differences in serum concentrations of IL-5R in patients and the control group are shown in Table 1 .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p8
|
PMC11276824
|
sec[1]/p[1]
|
2. Results
| 4.09375 |
biomedical
|
Study
|
[
0.99951171875,
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[
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In the AD group, 3/15 (20%) of participants had severe AD, and 12/15 (80%) had a moderate degree of disease severity according to the SCORAD index. Furthermore, we found relationships between the mean IL-5R serum concentration and the severity of AD: there was a significant positive correlation between IL-5R level and the SCORAD index ( p = 0.047). On the contrary, no significant correlation was found between the IL-5R concentration and the activity of CSU measured with the UAS7 scale. All patients with CSU and AD reported skin pruritus of average to moderate intensity, which was assessed with the use of the VAS. Nevertheless, the mean serum IL-5R concentration did not correlate with the intensity of itching sensations in the examined patients. The data on the disease severity in patients with CSU and AD are shown in Table 2 .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276824_p9
|
PMC11276824
|
sec[2]/p[0]
|
3. Discussion
| 4.296875 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.6904296875,
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] |
The involvement of eosinophils in the inflammatory infiltrate associated with AD has been well documented. It has been observed that both the number of eosinophils and the levels of eosinophil granule proteins in the peripheral blood are elevated in the majority of patients with AD, and these parameters seem to correlate with the activity of the disease . Whenever systemic eosinophilic inflammation is identified as a clinically pertinent observation, it is reasonable to consider that inhibiting IL-5 or its receptor might represent a putative therapeutic approach. Mepolizumab, reslizumab, and benralizumab constitute humanized monoclonal antibodies that inhibit IL-5 signalling. While mepolizumab and reslizumab bind directly to IL-5, benralizumab targets the IL-5 receptor alpha (IL-5Rα), subsequently inducing antibody-dependent cell-mediated cytotoxicity . Clinical trials indicate that reslizumab treatment does not elicit meaningful responses in patients lacking elevated eosinophil levels, implying that the effectiveness of IL-5 inhibition predominantly results from the reduction in eosinophil counts .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p10
|
PMC11276824
|
sec[2]/p[1]
|
3. Discussion
| 4.175781 |
biomedical
|
Study
|
[
0.99560546875,
0.00417327880859375,
0.00031256675720214844
] |
[
0.9853515625,
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0.0006356239318847656
] |
In a randomized, double-blind, placebo-controlled, parallel-group study, 18 patients diagnosed with AD were administered two single intravenous doses of 750 mg of mepolizumab. In comparison, 22 patients received a placebo treatment. The results indicated a significant reduction in peripheral blood eosinophil counts among the treatment group compared to the placebo group. However, the treatment did not achieve clinical success as determined by the physician’s global assessment, the objective SCORAD, itch scoring metrics, and the atopy patch test (APT) . The findings from recent research indicate that anti-IL-5 therapies might not yield efficacy in treating AD due to their failure to decrease eosinophil levels in the skin substantially. Alternatively, it is hypothesized that eosinophils may not play a critical role in the pathogenesis of AD. To further explore these possibilities, forthcoming studies should consider administering increased doses of anti-IL-5 and subsequently assess the infiltration of eosinophils into lesional skin areas .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276824_p11
|
PMC11276824
|
sec[2]/p[2]
|
3. Discussion
| 4.304688 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.99609375,
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Elevated levels of serum-soluble IL-5 α (s-IL-5Rα) are observed prior to the onset of AD in pediatric populations. A substantial correlation was identified between eczema phenotypes and s-IL-5Rα. Following adjustments for multiple comparisons, it was observed that children with late-onset AD exhibited significantly elevated levels of s-IL-5Rα in comparison to individuals who had never experienced AD . In a study by Taha et al., acute and chronic skin lesions demonstrated a marked elevation in the quantity of IL-5Rα and GM-CSFRα mRNA-positive cells compared to uninvolved AD skin and normal skin. Chronic skin lesions exhibited a significantly higher prevalence of IL-5Rα and GM-CSFRα mRNA-positive cells in comparison to acute AD skin . It has been observed that the rs2522411 SNP and the T-A haplotype in the IL-5 gene, along with serum IL-5 levels, exhibit a strong association with the extrinsic (allergic) type of AD, as opposed to the intrinsic (nonallergic) type of AD. IL-5 is crucial in the proliferation and survival of eosinophils, and thus, IL-5 plays an important role in allergic type of AD. Furthermore, the correlation between the rs6771148 SNP and the T-C-T haplotype in the IL-5Rα gene with blood eosinophil counts and serum ECP (eosinophil cationic protein) levels suggests a role for the IL-5Rα gene in the regulation of eosinophils in the peripheral blood .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p12
|
PMC11276824
|
sec[2]/p[3]
|
3. Discussion
| 4.492188 |
biomedical
|
Study
|
[
0.9990234375,
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] |
[
0.9033203125,
0.0009407997131347656,
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0.0005006790161132812
] |
CSU is predominantly regarded as a disease driven by mast cell activation. Emerging evidence suggests that eosinophils may also play a role in the manifestation of symptoms. In a study by Di Lorenzo et al., an increase in both blood eosinophil counts and serum ECP levels was found in patients presenting with acute urticaria . Another study showed increased EDN (eosinophil-derived neurotoxin) levels in patients with CSU . As EDN is secreted predominantly by eosinophils, this biomarker may serve as a direct indicator of exacerbations in eosinophilic inflammation . Although numerous allergic and inflammatory conditions are frequently correlated with an increase in peripheral blood eosinophils, the situation may be reversed in CSU, where a reduction in peripheral blood eosinophils, or eosinopenia, is often observed in many patients. Potential mechanisms for this phenomenon may involve the depletion of blood eosinophils due to their recruitment into the skin during active phases of the disease, and their immunological destruction within the bloodstream. The incidence of eosinopenia was significantly elevated in patients with CSU compared to that observed in the general population. Eosinopenia was detected in approximately 10% of patients with CSU compared to 5% of the general population. Eosinopenia in patients with CSU is associated with elevated disease activity, type IIb autoimmunity, and suboptimal response to therapeutic interventions .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p13
|
PMC11276824
|
sec[2]/p[4]
|
3. Discussion
| 4.144531 |
biomedical
|
Study
|
[
0.99462890625,
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[
0.99560546875,
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] |
A 24-week repeated-measures study was conducted to evaluate the clinical efficacy of benralizumab in CSU. The values of UAS7 and CUQoLTS (Chronic Urticaria Quality-of-Life Questionnaire Total Score) were significantly correlated after administration compared to the baseline. Significant improvement was observed in the CUQoLTS components, specifically in the pruritus/wheal scores and the urticarial interference with physical activities, sleep, and leisure time. The findings of this study advocate for the administration of benralizumab in treating unresponsive CSU to standard glucocorticoid-antihistamine therapy (SGAH). The improvements related to benralizumab in UAS7 and CUQoLTS are comparable to those reported for omalizumab in the treatment of CSU, as indicated in prior research
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p14
|
PMC11276824
|
sec[2]/p[5]
|
3. Discussion
| 4.183594 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.9990234375,
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The role of IL-5 in AD and CSU is well documented, with numerous lines of evidence supporting its significant contribution to the pathogenesis of these diseases. In our study, there was a significant association between IL-5R serum concentrations in patients with CSU compared to healthy individuals, suggesting that anti-IL-5 therapies may be successful in that group. In summary, the presented pilot study is one of the reports to assess an increased serum level of IL-5R in adult patients with CSU and AD compared to a healthy control group. Moreover, the IL-5R level was found to be correlated to AD severity measured by the SCORAD index. In contrast, this molecule was irrelevant to CSU activity by UAS7 and itch intensity by VAS in examined patients. Therefore, our results support the concept of a systemic and inflammatory component in CSU and AD and might be useful in the investigations of the complex, multi-pronged, and intertwined etiology of these diseases. Nevertheless, further studies on a larger cohort of patients should be conducted to clarify whether IL-5R may be a potential biomarker of CSU and AD, prognostic tool prior to exacerbations, or new effective targeted therapies in the era of personalized medicine. We suggest that future clinical trials should take into account markers, such as peripheral blood eosinophil counts and QoL questionnaires assessed before and after the treatment.
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p15
|
PMC11276824
|
sec[2]/p[6]
|
3. Discussion
| 3.419922 |
biomedical
|
Study
|
[
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[
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The current study has several limitations. The primary limitation of our pilot study is the small patient group that was examined. Thus, for additional validation, we believe a more extensive examination ought to be carried out. Moreover, the current study employed a cross-sectional design, which provides data from only one point in time, possibly neglecting changes over time or causal connections that might develop throughout the prolonged course of the disease.
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p16
|
PMC11276824
|
sec[3]/sec[0]/p[0]
|
4.1. Examined Groups
| 3.914063 |
biomedical
|
Study
|
[
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[
0.998046875,
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This pilot study included 45 participants (35 females and 10 males) aged 20 to 56 (average age: 30.91 ± 8.65 years). The study group was composed of two subgroups: 15 subjects diagnosed with CSU, based on the medical history and complex physical examination before participation in our study, and 15 subjects diagnosed with AD according to criteria defined by Hanifin and Rajka . The control group consisted of 15 healthy volunteers with a negative medical history of chronic skin diseases. The demographic data are shown in Table 3 .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p17
|
PMC11276824
|
sec[3]/sec[0]/p[1]
|
4.1. Examined Groups
| 2.941406 |
biomedical
|
Study
|
[
0.9736328125,
0.0257415771484375,
0.0007638931274414062
] |
[
0.9658203125,
0.03131103515625,
0.0008273124694824219,
0.0022220611572265625
] |
The exclusion criteria for all subjects were as follows: lack of consent, age under 18 years or over 70 years, treatment with long-acting antihistamines or systemic corticosteroids (up to 14 days prior to the study), females during pregnancy, significant comorbidities, and an unstable period of the skin disease. The study protocol was approved by the local ethical committee , and all participants signed informed consent.
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p18
|
PMC11276824
|
sec[3]/sec[1]/p[0]
|
4.2. Blood Collection and Biochemical Analysis
| 4.054688 |
biomedical
|
Study
|
[
0.99951171875,
0.00031065940856933594,
0.00018656253814697266
] |
[
0.99951171875,
0.0003724098205566406,
0.0002372264862060547,
0.00006639957427978516
] |
Peripheral blood samples (5 mL) were collected to the coagulation activator tubes (Saerstedt AG & Co., Nümbrecht, Germany) from all patients with CSU, AD, and the healthy controls. Then, the serum was separated after centrifugation at room temperature at 1700 rpm for 16 min. and kept at a temperature of −70 °C in an Eppendorf tube (AG, Hamburg, Germany) until further analysis. Single measurements of the serum concentrations of IL-5R were performed with the human enzyme-linked immunosorbent assay (ELISA) kits, following manufacturers’ instructions (Wuhan EIAAB Science Co., Ltd., Darmstadt, Germany).
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276824_p19
|
PMC11276824
|
sec[3]/sec[2]/p[0]
|
4.3. Disease Severity
| 4.136719 |
biomedical
|
Study
|
[
0.9990234375,
0.0008692741394042969,
0.00014638900756835938
] |
[
0.99853515625,
0.0007009506225585938,
0.0008511543273925781,
0.00013911724090576172
] |
The Urticaria Activity Score (UAS) was used to assess disease activity in patients with urticaria. The questionnaire analyses the number of wheals and the intensity of pruritus in a recommended 7-day monitoring period (UAS7), with once-daily documentation (resulting in a summary score from 0 to 42 points) in patients with CSU . The Scoring Atopic Dermatitis (SCORAD) index was used to assess the severity of AD. Based on the estimated score, patients can be subdivided into mild (<25 points), moderate (25–50 points), or severe (>50 points) AD . Additionally, the Visual Analogue Scale (VAS) was applied to evaluate the difference in intensity of pruritus observed in subsequent weeks. Patients with CSU and AD were asked to assess the intensity of the itch, from 0 points (no itching) to 10 points (worst imaginable itch). The results were ranked as follows: 0–2.9 points—mild pruritus; 3–6.9 points—moderate pruritus; 7–8.9 points—severe pruritus; and 9–10 points—very severe pruritus .
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276824_p20
|
PMC11276824
|
sec[3]/sec[3]/p[0]
|
4.4. Statistical Analysis
| 3.019531 |
biomedical
|
Study
|
[
0.998046875,
0.0003521442413330078,
0.0015697479248046875
] |
[
0.97119140625,
0.0271759033203125,
0.0014123916625976562,
0.00027751922607421875
] |
Statistical analysis was performed using the Statistica 13.3 software package (StatSoft, Kraków, Poland). To determine the significance of the results, the Bartlett test, the U Mann–Whitney test, the χ 2 test, and the Spearman correlation coefficient test were used. A p -value less than 0.05 was considered statistically significant.
|
[
"Krzysztof Gomułka",
"Maciej Tota",
"Julia Laska",
"Karina Gojny",
"Łukasz Sędek"
] |
https://doi.org/10.3390/ijms25147598
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057639_p0
|
39057639
|
sec[0]/p[0]
|
1. Introduction
| 4.007813 |
biomedical
|
Other
|
[
0.998046875,
0.0016803741455078125,
0.0001856088638305664
] |
[
0.2423095703125,
0.476318359375,
0.264404296875,
0.01678466796875
] |
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare disease caused by the abnormal development of the left coronary artery (LCA). It typically manifests in infancy with heart failure (HF), myocardial ischemia and dilated cardiomyopathy (DCM) . In most cases, the left ventricle (LV) function improves following corrective surgery. However, postoperative data suggest that some myocardial ischemia and fibrosis may persist .
|
[
"Asmaa Carla Hagău",
"Horațiu Suciu",
"Anca Voichița Popoiu",
"Iolanda Muntean"
] |
https://doi.org/10.3390/jcdd11070219
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057639_p1
|
39057639
|
sec[0]/p[1]
|
1. Introduction
| 4.101563 |
biomedical
|
Clinical case
|
[
0.9033203125,
0.0960693359375,
0.00077056884765625
] |
[
0.265625,
0.10235595703125,
0.006885528564453125,
0.625
] |
Several imagistic techniques are being used to detect myocardial abnormalities. However, in recent years, advanced echocardiographic techniques such as speckle tracking have become more popular for assessing the myocardium even in the intensive care unit . Because of its high sensitivity and low inter-observer variability compared to conventional echocardiography, this method can detect early myocardium abnormalities based on coronary artery vascularization territories, despite a normal ejection fraction (EF) calculated with the standard echocardiography methods. In this case, we aim to present global and regional myocardial function changes in the case of ALCAPA in an infant patient using speckle-tracking echocardiography.
|
[
"Asmaa Carla Hagău",
"Horațiu Suciu",
"Anca Voichița Popoiu",
"Iolanda Muntean"
] |
https://doi.org/10.3390/jcdd11070219
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057639_p2
|
39057639
|
sec[1]/p[0]
|
2. Case Presentation
| 2.753906 |
clinical
|
Clinical case
|
[
0.2264404296875,
0.76025390625,
0.01354217529296875
] |
[
0.0026645660400390625,
0.006191253662109375,
0.0024204254150390625,
0.98876953125
] |
We present the case of a two-month-old infant admitted to our intensive care unit with severe HF.
|
[
"Asmaa Carla Hagău",
"Horațiu Suciu",
"Anca Voichița Popoiu",
"Iolanda Muntean"
] |
https://doi.org/10.3390/jcdd11070219
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057639_p3
|
39057639
|
sec[1]/p[1]
|
2. Case Presentation
| 4.164063 |
biomedical
|
Clinical case
|
[
0.68017578125,
0.318603515625,
0.0014562606811523438
] |
[
0.1343994140625,
0.0243377685546875,
0.0078582763671875,
0.83349609375
] |
Physical examination revealed low cardiac output and acute HF symptoms (pale skin with cold extremities, respiratory distress, tachycardia, a 4/6 holosystolic murmur at the left side of the sternal border, hepatomegaly). Laboratory tests indicated elevated serum creatinine levels, suggesting an acute pre-renal failure due to severely reduced systemic output. Moreover, significantly elevated NT-proBNP, Troponin T hs and Lactate levels were observed (60,477 pg/mL, 138 pg/mL and 6.3 mmol/L). Chest radiography revealed cardiomegaly, and the electrocardiogram revealed septal ischemia with a characteristic ALCAPA QR pattern in lateral leads. A transthoracic echocardiography revealed severe dilatation of the LV compressing the right cavities and severe mitral valve regurgitation with a dilated mitral annulus. The origin of the LCA from the pulmonary artery was visualised using two-dimensional and three-dimensional techniques. Color Doppler revealed retrograde flow from the pulmonary artery into the LCA .
|
[
"Asmaa Carla Hagău",
"Horațiu Suciu",
"Anca Voichița Popoiu",
"Iolanda Muntean"
] |
https://doi.org/10.3390/jcdd11070219
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057639_p4
|
39057639
|
sec[1]/p[2]
|
2. Case Presentation
| 4.21875 |
biomedical
|
Study
|
[
0.9990234375,
0.000614166259765625,
0.00012767314910888672
] |
[
0.99853515625,
0.00067138671875,
0.0005564689636230469,
0.00022792816162109375
] |
Using the Simpson method, LV EF was calculated using conventional echocardiography (18.3%). The speckle-tracking analysis assessed the regional myocardial function of individual segments and global longitudinal strain (GLS). Longitudinal strain measurements of the LV were low in all views (two-chamber: −5.6%, three-chamber: −3.6% and four-chamber: −4.6%), with impaired GLS (−4.4%). The analysis revealed hypokinetic anterior, anterolateral, and inferior LV regions with a hypokinetic septum, corresponding to territories supplied by both the LCA and the right coronary artery (RCA) .
|
[
"Asmaa Carla Hagău",
"Horațiu Suciu",
"Anca Voichița Popoiu",
"Iolanda Muntean"
] |
https://doi.org/10.3390/jcdd11070219
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
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