Oral submucous fibrosis (OSF) is a potentially malignant disorder characterised by inflammation and progressive fibrosis. Transforming growth factor-β (TGF-β) has been established as a master regulator of fibrosis in various organs; however, lack of systematic review on expression of TGF-β and its isoforms in OSF restrict the understanding of their behaviour in its pathogenesis. Online electronic databases, such as PubMed Medline, Cochrane Library, Embase, and Scopus, were searched from their respective dates of inception till 31st March 2022. Human studies related to TGF-β expression in histopathologically diagnosed OSF cases, with or without malignant transformation, were included and assessed using a Cochrane risk of bias assessment tool: For non randomised studies of interventions (ACROBAT NRSI). The electronic literature search yielded 394 articles. Of those, ten articles met the inclusion criteria and involved total of 579 OSF patients. The risk of bias (RoB) was low to moderate. These studies demonstrated a significant positive expression of TGF-β and its isoforms in OSF compared to that in normal tissue samples. An increased pan TGF-β expression was observed in the early stages of OSF, and an increased expression of TGF-β1 and TGF-β2 were seen in advanced stages of OSF. Stage wise expression of TGF-β3 has not been discussed in the included studies. No significant relationship was observed between epithelial dysplasia and TGF-β expression in OSF. The distinct pattern in the expression of pan TGF-β, TGF-β1 and TGF-β2 in various stages of OSF indicates their different roles in OSF progression. We believe isoform targeted studies exploring stage wise expression of the marker will open new treatment avenues for OSF.

Peritoneal dialysis (PD) is an effective alternative treatment for patients with end-stage renal disease (ESRD) and is increasingly being adopted and promoted worldwide. However, as the duration of peritoneal dialysis extends, it can expose problems with dialysis inadequacy and ultrafiltration failure. The exact mechanism and aetiology of ultrafiltration failure have been of great concern, with triggers such as biological incompatibility of peritoneal dialysis solutions, uraemia toxins, and recurrent intraperitoneal inflammation initiating multiple pathways that regulate the release of various cytokines, promote the transcription of fibrosis-related genes, and deposit extracellular matrix. As a result, peritoneal fibrosis occurs. Exploring the pathogenic factors and molecular mechanisms can help us prevent peritoneal fibrosis and prolong the duration of Peritoneal dialysis.

BACKGROUND: Diabetes mellitus (DM) is among the most common risk factors for cardiovascular disease in the world with prevalence of more than 500 million population in 2021. Cardiac fibrosis with its complex process has been hypothesized as one of the mechanisms explaining development of heart failure in diabetic patients. Recently, the biomolecular mechanism of cardiac fibrosis in the hyperglycemia setting has been focusing around transforming growth factor β-1 (TGFβ-1) as a major factor. However, there is interplay role of several factors including microRNAs (miRNAs) which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus. This narrative review included articles from the PubMed and Science Direct databases published in the last 10 years (2012-2022).
METHODS: In diabetic patients, excessive activation of myofibroblasts occurs and triggers pro-collagen to convert into mature collagen to fill the cardiac interstitial space resulting in a pathological process of extracellular matrix remodeling. The balance between matrix metalloproteinase (MMP) and its inhibitor (tissue inhibitor of metalloproteinase, TIMP) is crucial in degradation of the extracellular matrix. Diabetes-related cardiac fibrosis is modulated by increasing level of TGF-β1 mediated by cellular components, including cardiomyocyte and non-cardiomyocyte cells involving fibroblasts, vascular pericytes smooth muscle cells, endothelial cells, mast cells, macrophages, and dendritic cells. Several miRNAs such as miR-21, miR-9, miR-29, miR-30d, miR-144, miR-34a, miR-150, miR-320, and miR-378 are upregulated in diabetic cardiomyopathy. TGF-β1, together with inflammatory cytokines, oxidative stress, combined sma and the mothers against decapentaplegic (smad) protein, mitogen-activated protein kinase (MAPK), and microRNAs, is interconnectedly involved in extracellular matrix production and fibrotic response. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus.
CONCLUSIONS: Long-term hyperglycemia activates cardiac fibroblast via complex processes involving TGF-β1, miRNA, inflammatory chemokines, oxidative stress, smad, or MAPK pathways. There is increasing evidence of miRNA\'s roles lately in modulating cardiac fibrosis.

The aim of this study is to analyze the latest evidence on the effects of losartan or Ang II receptor antagonists on cartilage repair, with a focus on their clinical relevance.
The PubMed, Embase, and Cochrane Library databases were searched up to November 12th 2021 to evaluate the effects of losartan or Ang II receptor antagonists on cartilage repair in in vitro studies and in vivo animal studies. Study design, sample characteristics, treatment type, duration, and outcomes were analyzed. The risk of bias and the quality of the eligible studies were assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias assessment tool and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES).
A total of 12 studies were included in this systematic review. Of the 12 eligible studies, two studies were in vitro human studies, three studies were in vitro animal studies, one study was an in vitro human and animal study, and six studies were in vivo animal studies. The risk bias and quality assessments were predominantly classified as moderate. Since meta-analysis was difficult due to differences in treatment type, dosage, route of administration, and method of outcome assessment among the eligible studies, qualitative evaluation was conducted for each study.
Both in vitro and in vivo studies provide evidence to demonstrate beneficial effects of Ang II receptor antagonists on osteoarthritis and cartilage defect models across animal species.

Peritoneal fibrosis (PF) is the most important complication of peritoneal dialysis (PD) that may arise among patients receiving continuous ambulatory peritoneal dialysis (CAPD). PF is a complex process, and many factors contribute to the formation of fibrosis. PD solutions with high glucose content, chronic inflammation, inflammatory cytokines, angiogenesis, and mesothelial to mesenchymal transition (MMT) are factors contributing to the fibrosis of the peritoneum. These factors, as well as stress-induced fibrosis, are going to be discussed further in this article. Although most experimental models are promising in preventing or delaying PD-related fibrosis, most of these recommended treatment options require further research. The lack of sufficient data from real PD patients and many inconclusive data make clinicians depend on conservative treatment. New therapeutics are indeed required for the management of patients undergoing PD to prevent the dreaded complication that may arise from continuous PD. Newer PD solutions are needed to improve survival and minimize the complication associated with PD. Recently, newer PD solutions have been shown to improve patient survival and peritoneal viability and reduce this complication that may arise as a result of continuous PD.

OBJECTIVE: To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of recurrent prolapse in the future. Vaginal oestrogen therapy may improve wound healing, hereby possibly improving surgical outcomes.
METHODS: A systematic search of OVID MEDLINE, OVID Embase, and Web of Science was conducted up to January 28, 2020. We included original studies comparing wound healing-related outcomes of oestrogen exposed subjects (female animals and women) to hypo-oestrogenic subjects after vaginal surgery. Data on wound healing-related outcome measures were extracted. For each individual comparison, the standardised mean difference (Hedges\' g; SMD) and 95% confidence interval (CI) were calculated.
RESULTS: Of the 1474 studies reviewed, 14 studies were included for review, and 11 provided data for meta-analysis. Oestrogen improves neovascularisation (SMD: 1.13, 95% CI: 0.67-1.60), microscopic wound closure (SMD: 0.98, 95% CI: 0.66-1.29), collagen synthesis (SMD: 1.08, 95% CI: 0.42-1.74), and tissue strength (SMD: 1.26, 95% CI: 0.53-1.99) in animals. Oestrogen increases granulation (SMD: 1.67, 95% CI: 0.54-2.79) and accelerates macroscopic wound closure (SMD: 1.82, 95% CI: 1.22-2.42) in women and animals. Oestrogen decreases the inflammatory response (SMD: -0.58, 95% CI: -1.14 to -0.02) in women and animals and reduces levels of transforming growth factor (TGF)-β1 (SMD: -1.68, 95% CI: -2.52 to -0.83) in animals. All results were statistically significant.
CONCLUSIONS: Oestrogen therapy has a positive effect on vaginal wound healing. Future studies should determine whether oestrogen therapy has the potential to improve surgical outcomes.

Rheumatoid arthritis (RA) is a complex autoimmune disease that affects about 1% of the world\'s population. The conclusions about the relationship between TGF gene polymorphism and the risk of RA are still inconsistent. Therefore, we performed a meta-analysis to re-evaluate the relationship between TGF-β1 T869C gene polymorphism and the risk of rheumatoid arthritis.
METHODS: We performed a systematic electronic search in PubMed, Embase, Elsevier, Web of Science, Cochrane Library, Medline and China National Knowledge Infrastructure database (up to August 2020). In the subgroup analysis, we divide the research into three groups: Asian, European and Mediterranean, The combined OR and 95%CI of the five models (allele model, homozygous model, heterozygous model, dominant model, recessive model) were calculated, respectively.
RESULTS: 15 case-control studies (14 articles) were involved in this meta-analysis, including 2103 cases and 2143 healthy controls. In the overall analysis, it showed that there may be an significant association between TGF-β1+869T/C polymorphism and RA sensitivity (allele model, T vs. C: OR=1.444, 95% CI=1.171-1.782, P=0.001; homozygous model, TT vs. CC: OR=1.910, 95% CI=1.322-2.761, P=0.001; heterozygous model, CT vs. CC: OR=1.558, 95% CI=1.179-2.059,P=0.002; dominant model, TT+CT vs. CC: OR= 1.742, 95% CI=1.303-2.329, P=0.001; recessive model, TT vs. CT+CC: OR=1.400, 95% CI= 1.058-1.852, P=0.018).However, the results of ethnic subgroup analysis indicated that rs1982073 was not associated with RA risk in Europeans(allele model, T vs. C: OR=0.993, 95% CI=0.849-1.162, P=0.931, I2 <0.1%, P>0.1).
CONCLUSIONS: In summary, our meta-analysis showed that the rs1982073 T allele does not increase RA susceptibility in Europeans.

Silicosis is an occupational fibrotic lung disease caused by inhaling large amounts of crystalline silica dust. Transforming growth factor-β1 (TGF-β1), which is secreted from macrophages, has an important role in the development of this disease. Macrophages can recognize and capture silicon dust, undergo M2 polarization, synthesize TGF-β1 precursors, and secrete them out of the cell where they are activated. Activated TGF-β1 induces cells from different sources, transforming them into myofibroblasts through autocrine and paracrine mechanisms, ultimately causing silicosis. These processes involve complex molecular events, which are not yet fully understood. This systematic summary may further elucidate the location and development of pulmonary fibrosis in the formation of silicosis. In this review, we discussed the proposed cellular and molecular mechanisms of production, secretion, activation of TGF-β1, as well as the mechanisms through which TGF-β1 induces cells from three different sources into myofibroblasts during the pathogenesis of silicosis. This study furthers the medical understanding of the pathogenesis and theoretical basis for diagnosing silicosis, thereby promoting silicosis prevention and treatment.

BACKGROUND: Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear.
METHODS: An 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-β1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7.
CONCLUSIONS: This is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

BACKGROUND: Brucellosis is one of the major public health problems worldwide. Several current studies have provided data that polymorphisms in the interleukin-6 (IL-6), interleukin-10 (IL-10) and transforming growth factor beta1(TGF-β1) gene were associated with the susceptibility to human brucellosis, but the results remain inconsistent.
OBJECTIVE: The aim of present study was to investigate the relationship between IL-6 (-174 G/C), IL-10 (-1082 A/G, -819C/T) and TGF-β1 (codon 10, codon 25) gene polymorphisms and brucellosis.
METHODS: We performed a comprehensive search of the PubMed, EMBASE, Web of Science, OVID-EBMR, and the Cochrane Library up to Oct. 30, 2018. The search was designed using the following key words: \"brucellosis\" or\" \"brucella melitensis\", \"IL-10\" or \"interleukin10\" or \"interleukin-10\", \"IL-6\" or \"interleukin6\" or \"interleukin-6\", \"TGF-β1\" or \"TGF-beta1\" or \"transforming growth factor β1\", \"polymorphism\" and \"single nucleotide polymorphism (SNP)\". Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of association between TGF-β1, IL-10 and IL-6 polymorphisms and brucellosis risk. All the statistical analyses were conducted by Review manager 5.3 software.
RESULTS: A total of 8 studies involving 1308 cases and 902 controls met the inclusion criteria for IL-6, IL-10, TGF-β1 polymorphisms and brucellosis risk. There was a slightly trend of increasing risk of brucellosis in individuals with the G allele compared with individuals with the C allele (OR = 1.07, 95% CI: 0.85-1.33, P = 0.57) in IL-6 polymorphism. However, statistical analysis showed that these differences are not significant. Our results suggested TGF-β1 (codon 25 G/C) GG genotype may be considered as a risk factor for brucellosis (OR = 1.67, 95% CI: 1.12-2.50, P = 0.01). Herein, we failed to find any significant association between IL-10 (-1082 A/G, -819C/T), TGF-β1 (codon 10C/T) gene polymorphism and susceptibility to brucellosis in all gene models.
CONCLUSIONS: IL-6 (-174 G/C), IL-10 (-1082 A/G, -819C/T), and TGF-β1 (codon 10C/T) polymorphisms is not a risk factor for brucellosis infection. TGF-β1 codon 25 GG genotype may be considered as a risk factor for brucellosis.