UNASSIGNED: A combination of genetic and environmental factors contribute to the highly common, complex, and varied endocrine condition known as polycystic ovary syndrome (PCOS) in women. PCOS primarily affects women between the ages of 15 and 35 who are in the early to late stages of pregnancy. Thus, this study aimed to evaluate the serum levels of irisin, subfatin, and adropin in PCOS with and without obesity compared to the control group.
UNASSIGNED: The present cross-sectional study was conducted in 2022 at Al-Nahrain University/Department of Chemistry (Baghdad, Iraq). The serum levels of irisin, subfatin, and adropin were measured with the enzyme-linked immunosorbent assay (ELISA) method. Body mass index, lipid profile, insulin, fasting glucose, follicle-stimulating hormone, and luteinizing hormone levels were also evaluated. The data were analyzed using one-way analysis of variance (ANOVA) by GraphPad Prism software version 8.0.2. A P<0.05 was considered statistically significant.
UNASSIGNED: The study population comprised PCOS patients (n=90, divided into 45 obese and 45 normal weight) and healthy women (n=30). According to the results, the serum levels of irisin were significantly higher (P<0.001) in obese and normal-weight PCOS patients than controls. While adropin and subfatin were significantly lower in PCOS than controls (P<0.001). Moreover, there are higher levels of serum insulin, fasting glucose, and luteinizing hormone in PCOS women than in healthy women.
UNASSIGNED: According to the findings, PCOS patients had a higher level of irisin than the controls. In addition, decreased subfatin and adropin levels were observed in PCOS patients compared with healthy women. Further research is required to confirm these results in the future.

Inflammatory bowel disease (IBD), including Crohn\'s disease and ulcerative colitis, showed a wide spectrum of intestinal and extra-intestinal manifestations, which rendered the patients physically inactive and impaired their quality of life. It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients. Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an anti-inflammatory biomarker in assessing the physical activity of IBD patients. In addition, experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis. Furthermore, irisin produces changes in the diversity of the microbiota. Therefore, endogenous or exogenous irisin, via its anti-inflammatory effects, will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Acute pancreatitis (AP) entails pancreatic inflammation, tissue damage and dysregulated enzyme secretion, including pancreatic lipase (PL). The role of irisin, an anti-inflammatory and anti-apoptotic cytokine, in AP and exocrine pancreatic stress is unclear. We have previously shown that irisin regulates PL through the PPARγ-PGC1α-FNDC5 pathway. In this study, we investigated irisin and irisin\'s pathway on AP in in vitro (AR42J-B13) and ex vivo (rat primary acinar) models using molecular, biochemical and immunohistochemistry methodology. Pancreatitis induction (cerulein (cer)) resulted in a significant up-regulation of the PPARγ-PGC1α-FNDC5 axis, PL expression and secretion and endoplasmic reticulum (ER) stress unfolded protein response (UPR) signal-transduction markers (CHOP, XBP-1 and ATF6). Irisin addition in the cer-pancreatitis state resulted in a significant down-regulation of the PPARγ-PGC1α-FNDC5 axis, PPARγ nucleus-translocation and inflammatory state (TNFα and IL-6) in parallel to diminished PL expression and secretion (in vitro and ex vivo models). Irisin addition up-regulated the expression of pro-survival UPR markers (ATF6 and XBP-1) and reduced UPR pro-apoptotic markers (CHOP) under cer-pancreatitis and induced ER stress (tunicamycin), consequently increasing cells viability. Irisin\'s pro-survival effect under cer-pancreatitis state was abolished under PPARγ inhibition. Our findings suggest irisin as a potential therapeutic option for AP via its ability to up-regulate pro-survival UPR signals and activate the PPARγ-PGC1α-FNDC5 pathway.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy of the gastrointestinal tract with a single therapeutic option and a lack of effective clinical therapeutic biomarkers. Extracellular matrix (ECM) remodeling plays a pro-carcinogenic role in a variety of malignancies, but its role in esophageal squamous carcinoma remains to be elucidated. In this study, we examined the expression levels of ECM remodeling markers in 71 pairs of esophageal squamous carcinoma tissues and normal tissues adjacent to the carcinoma using immunohistochemical staining, and analyzed their relationship with clinicopathological features and prognosis. The results suggested that extracellular matrix remodeling markers (integrin αV, fibronectin, MMP9) were abnormally highly expressed in esophageal squamous carcinoma tissues. There was a statistically significant difference between the positive expression of ECM remodeling and the TNM stage of esophageal squamous carcinoma, and there was no statistically significant correlation with age, gender and carcinoembryonic antigen expression, differentiation degree, T stage, and lymph node metastasis. Overall survival rate and overall survival time were significantly lower in patients with positive ECM remodeling expression, which was an independent risk factor for poor prognosisof esophageal squamous carcinoma.

BACKGROUND: Group B Streptococcus (GBS) is a commensal of healthy adults and an important pathogen in newborns, the elderly and immunocompromised individuals. GBS displays several virulence factors that promote colonisation and host infection, including the ST-17 strain-specific adhesin Srr2, previously characterised for its binding to fibrinogen. Another common target for bacterial adhesins and for host colonization is fibronectin, a multi-domain glycoprotein found ubiquitously in body fluids, in the extracellular matrix and on the surface of cells.
RESULTS: In this study, fibronectin was identified as a novel ligand for the Srr2 adhesin of GBS. A derivative of the ST-17 strain BM110 overexpressing the srr2 gene showed an increased ability to bind fibrinogen and fibronectin, compared to the isogenic wild-type strain. Conversely, the deletion of srr2 impaired bacterial adhesion to both ligands. ELISA assays and surface plasmon resonance studies using the recombinant binding region (BR) form of Srr2 confirmed a direct interaction with fibronectin with an estimated Kd of 92 nM. Srr2-BR variants defective in fibrinogen binding also exhibited no interaction with fibronectin, suggesting that Srr2 binds this ligand through the dock-lock-latch mechanism, previously described for fibrinogen binding. The fibronectin site responsible for recombinant Srr2-BR binding was identified and localised in the central cell-binding domain of the protein. Finally, in the presence of fibronectin, the ability of a Δsrr2 mutant to adhere to human cervico-vaginal epithelial cells was significantly lower than that of the wild-type strain.
CONCLUSIONS: By combining genetic and biochemical approaches, we demonstrate a new role for Srr2, namely interacting with fibronectin. We characterised the molecular mechanism of this interaction and demonstrated that it plays a role in promoting the adhesion of GBS to human cervico-vaginal epithelial cells, further substantiating the role of Srr2 as a factor responsible for the hypervirulence of GBS ST-17 strains. The discovery of the previously undescribed interaction between Srr2 and fibronectin establishes this adhesin as a key factor for GBS colonisation of host tissues.

Cellular senescence plays a role in the development of aging-associated degenerative diseases. Cell therapy is recognized as a candidate treatment for degenerative diseases. To achieve the goal of cell therapy, the quality and good characteristics of cells are concerned. Cell expansion relies on two-dimensional culture, which leads to replicative senescence of expanded cells. This study aimed to investigate the effect of cell culture surface modification using fibronectin (FN) and vitronectin (VN) in adipose-derived stem cells (ADSCs) during long-term expansion. Our results showed that ADSCs cultured in FN and VN coatings significantly enhanced adhesion, proliferation, and slow progression of cellular senescence as indicated by lower SA-β-gal activities and decreased expression levels of genes including p16, p21, and p53. The upregulation of integrin α5 and αv genes influences phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), and AKT proteins. FN and VN coatings upregulated AKT and MDM2 leading to p53 degradation. Additionally, MDM2 inhibition by Nutlin-3a markedly elevated p53 and p21 expression, increased cellular senescence, and induced the expression of inflammatory molecules including HMGB1 and IL-6. The understanding of FN and VN coating surface influencing ADSCs, especially senescence characteristics, offers a promising and practical point for the cultivation of ADSCs for future use in cell-based therapies.

BACKGROUND: Recently, many studies have been devoted to discovering nutrients for exercise-like effects. Resistance exercise and the intake of essential amino acids (EAAs) are known to be factors that can affect muscle mass and strength improvement. The purpose of this study was to investigate changes in muscle quality, myokines, and inflammation in response to resistance exercise and EAA supplementation.
METHODS: Thirty-four males volunteered to participate in this study. They were assigned to four groups: (1) placebo (CO), (2) resistance exercise (RE), (3) EAA supplementation, and (4) RE + EAA supplementation. Body composition, muscle quality, myokines, and inflammation were measured at baseline and four weeks after treatment.
RESULTS: Lean body fat had decreased in both RE and RE + EAA groups. Lean body mass had increased in only the RE + EAA group. In all groups except for CO, irisin, myostatin A, and TNF-α levels had decreased. The grip strength of the right hand and trunk flexion peak torque increased in the RE group. The grip strength of the left hand, trunk flexion peak torque, and knee flexion peak torque of the left leg were increased in RE + EAA.
CONCLUSIONS: RE, EAA, and RE + EAA could effectively improve the muscle quality, myokine, and inflammation factors of young adult males. This finding highlights the importance of resistance exercise and amino acid intake.

Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-β1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-β1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-β1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.

OBJECTIVE: To investigate the effect of tofacitinib, a pan-Janus kinase (JAK) inhibitor, on transforming growth factor-beta 1 (TGF-β1)-induced fibroblast to myofibroblast transition (FMT) and to explore its mechanism. To provide a theoretical basis for the clinical treatment of connective tissue disease-related interstitial lung disease (CTD-ILD).
METHODS: (1) Human fetal lung fibroblast 1 (HFL-1) were cultured in vitro, and 6 groups were established: DMSO blank control group, TGF-β1 induction group, and TGF-β1 with different concentrations of tofacitinib (0.5, 1.0, 2.0, 5.0 μmol/L) drug intervention experimental groups. CCK-8 was used to measure the cell viability, and wound-healing assay was performed to measure cell migration ability. After 48 h of combined treatment, quantitative real-time PCR (RT-PCR) and Western blotting were used to detect the gene and protein expression levels of α-smooth muscle actin (α-SMA), fibronectin (FN), and collagen type Ⅰ (COL1). (2) RT-PCR and enzyme-linked immunosorbnent assay (ELISA) were used to detect the interleukin-6 (IL-6) gene and protein expression changes, respectively. (3) DMSO carrier controls, 1.0 μmol/L and 5.0 μmol/L tofacitinib were added to the cell culture media of different groups for pre-incubation for 30 min, and then TGF-β1 was added to treat for 1 h, 6 h and 24 h. The phosphorylation levels of Smad2/3 and signal transducer and activator of transcription 3 (STAT3) protein were detected by Western blotting.
RESULTS: (1) Tofacitinib inhibited the viability and migration ability of HFL-1 cells after TGF-β1 induction. (2) The expression of α-SMA, COL1A1 and FN1 genes of HFL-1 in the TGF-β1-induced groups was significantly up-regulated compared with the blank control group (P < 0.05). Compared with the TGF-β1 induction group, α-SMA expression in the 5.0 μmol/L tofacitinib intervention group was significantly inhi-bited (P < 0.05). Compared with the TGF-β1-induced group, FN1 gene was significantly inhibited in each intervention group at a concentration of 0.5-5.0 μmol/L (P < 0.05). Compared with the TGF-β1-induced group, the COL1A1 gene expression in each intervention group did not change significantly. (3) Western blotting results showed that the protein levels of α-SMA and FN1 in the TGF-β1-induced group were significantly higher than those in the control group (P < 0.05), and there was no significant difference in the expression of COL1A1. Compared with the TGF-β1-induced group, the α-SMA protein level in the intervention groups with different concentrations decreased. And the differences between the TGF-β1-induced group and 2.0 μmol/L or 5.0 μmol/L intervention groups were statistically significant (P < 0.05). Compared with the TGF-β1-induced group, the FN1 protein levels in the intervention groups with different concentrations showed a downward trend, but the difference was not statistically significant. There was no difference in COL1A1 protein expression between the intervention groups compared with the TGF-β1-induced group. (4) After TGF-β1 acted on HFL-1 cells for 48 h, the gene expression of the IL-6 was up-regulated and IL-6 in culture supernatant was increased, the intervention with tofacitinib partly inhibited the TGF-β1-induced IL-6 gene expression and IL-6 in culture supernatant. TGF-β1 induced the increase of Smad2/3 protein phosphorylation in HFL-1 cells for 1 h and 6 h, STAT3 protein phosphorylation increased at 1 h, 6 h and 24 h, the pre-intervention with tofacitinib inhibited the TGF-β1-induced Smad2/3 phosphorylation at 6 h and inhibited TGF-β1-induced STAT3 phosphorylation at 1 h, 6 h and 24 h.
CONCLUSIONS: Tofacitinib can inhibit the transformation of HFL-1 cells into myofibroblasts induced by TGF-β1, and the mechanism may be through inhibiting the classic Smad2/3 pathway as well as the phosphorylation of STAT3 induced by TGF-β1, thereby protecting the disease progression of pulmonary fibrosis.

Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1, a member of the glutathione S-transferase superfamily, as uniquely required for dissemination and metastasis, but dispensable for primary tumour growth. Gstt1 is expressed in latent disseminated tumour cells (DTCs), is retained within a subpopulation of slow-cycling cells within existing metastases, and its inhibition leads to complete regression of macrometastatic tumours. This distinct Gstt1high population is highly metastatic and retains slow-cycling phenotypes, epithelial-mesenchymal transition features and DTC characteristics compared to the Gstt1low population. Mechanistic studies indicate that in this subset of cancer cells, Gstt1 maintains metastases by binding and glutathione-modifying intracellular fibronectin, in turn promoting its secretion and deposition into the metastatic microenvironment. We identified Gstt1 as a mediator of metastasis, highlighting the importance of heterogeneity and its influence on the metastatic tumour microenvironment.