UNASSIGNED: In coronavirus disease 2019 (COVID-19), particularly in older people, dysregulated immune response and aberrant repair can result in varied severity secondary pulmonary fibrosis (PF). By detecting some indicators, the occurrence and prognosis of fibrosis can be measured, providing directions for COVID-19 treatment.
UNASSIGNED: The research study lasted for 3 months and involved 88 COVID-19 patients. According to the chest radiological examination, 47 (53.41%) individuals were found to have no PF, while 41 (46.59%) showed PF. Clinical data such as inflammation markers, imaging findings, blood gas analysis, and hospital stay length were collected.
UNASSIGNED: With area under the curve values of 0.7413, 0.7741, and 0.7048, respectively, and the study of the receiver operating characteristic curve demonstrated that mucin 1 (MUC1), carcinoembryonic antigen (CEA), and CXC chemokine receptor 10 (CXCL10) could diagnose the presence of COVID-19 PF. To evaluate the possibility of PF following severe acute respiratory syndrome coronavirus-2 infection, we established particular values for MUC1, CEA, and CXCL10 (1.296 ng/ml, 4.315 ng/ml, and 32.77 ng/ml, respectively). The survival curve for hospital days indicated that the length of hospital stays positively correlated with these three factors (P < 0.01). Transforming growth factor-beta did not correlate significantly with the severity of COVID-19 or PF.
UNASSIGNED: The results of this study suggested that the MUC1, CEA, and CXCL10 can be employed to explore the severity of secondary PF in COVID-19.

OBJECTIVE: The high recurrence rate of idiopathic orbital inflammation (IOI) has been reported. This study aims to determine existing predictive factors for the recurrence of IOI.
METHODS: This was an 11-year retrospective study with at least a 12-month follow-up. Fifty patients with biopsy-proven IOI admitted between 2006 and 2017 at our tertiary hospital were observed. We compared the clinical characteristics, histopathological profile, and biomarker expressions (mast cell, immunoglobulin G4, tumor necrosis factor-alpha, and transforming growth factor-beta) of 16 patients with recurrence (Group I) and 34 patients with no recurrence (Group II). Statistical comparison and multivariate analysis were performed to establish the predictive factors.
RESULTS: We discovered five recurrence predictive factors: presentation of proptosis (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.36-18.03), visual impairment (OR 15, 95% CI 1.58-142.72), extraocular muscle (EOM) restriction (OR 3.86, 95% CI 1.07-13.94), nonanterior involvement (OR 7.94, 95% CI 1.88-33.5), and corticosteroid (CS) alone treatment (OR 7.20, 95% CI 1.87-27.8). On multivariate analysis, nonanterior involvement and CS alone treatment were validated as predictive factors (area under the curve = 0.807 [95% CI 0.69-0.92]). Histopathological profile and biomarker expressions were not associated with recurrence. However, there was a 22-fold higher recurrence risk for granulomatous-type patients given CS alone treatment.
CONCLUSIONS: Unlike the five clinical characteristics mentioned, both histopathology and biomarker variables were not associated with recurrence. CS alone treatment for patients with nonanterior involvement or granulomatous type is proven to increase the risk of recurrence. Therefore, we suggest not giving CS without any combination treatment with other modalities for this group of patients.

We report the clinical presentation and genetic screening of a 31-year-old man with dilatation of the aortic root and ascending aorta and a positive family history for aortic dissection and sudden death. A novel heterozygous variant in a splice acceptor site (c.1600-1G>T) of TGFβR2 gene was identified by using a targeted multi-gene panel analysis. Bioinformatics tools predicted that the c.1600-1G>T variant is pathogenic by altering acceptor splice site at - 1 position affecting pre-mRNA splicing. These data confirm that the diverging splicing in the TGF-β pathway genes may be an important process in aneurismal disease and emphasize the utility of genetic sequencing in the identification of high-risk patients for a more patient\'s management able to improve outcomes and minimize costs for the care of patients with heritable thoracic aortic aneurysm and dissection.
[Box: see text].

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension characterized by the presence of organized thrombi that obstruct pulmonary arteries, ultimately leading to right heart failure and death. Among others, impaired angiogenesis and inflammatory thrombosis have been shown to contribute to the progression of CTEPH. In this review, we summarize the 2-faced nature of angiogenesis in both thrombus formation and resolution in the context of CTEPH and highlight the dual role of angiogenesis and neovascularization in resolving venous thrombi. Furthermore, we discuss relevant in vitro and in vivo models that support the benefits or drawbacks of angiogenesis in CTEPH progression. We discuss the key pathways involved in modulating angiogenesis, particularly the underexplored role of TGFβ (transforming growth factor-beta) signaling in driving fibrosis as an integral element of CTEPH pathogenesis. We finally explore innovative treatment strategies that target angiogenic pathways. These strategies have the potential to pioneer preventive, inventive, or alternative therapeutic options for patients with CTEPH who may not qualify for surgical interventions. Moreover, they could be used synergistically with established treatments such as pulmonary endarterectomy or balloon pulmonary angioplasty. In summary, this review emphasizes the crucial role of angiogenesis in the development of in fibrothrombotic tissue, a major pathological characteristic of CTEPH.

BACKGROUND: Diabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem cell secretome have been shown in several kidney and liver diseases. The current study aims to evaluate the capability of conditioned media derived from human Wharton\'s jelly mesenchymal stem cells (hWJ-MSCs-CM) to alleviate diabetic complications.
METHODS: Twenty Sprague Dawley rats were made diabetic through injection of STZ (60 mg/kg, i.p.). At week 8, diabetic rats were divided into two groups: treated [DM + hWJ-MSCs-CM (500 µl/rat for three weeks, i.p.)] and not treated (DM). At the 11th week, three groups (control, DM, and DM + hWJ-MSCs-CM) were kept in metabolic cages, and urine was collected for 24 h. The serum samples were maintained for measuring fasting blood glucose (FBG) and kidney and liver functional analysis. The left kidney and liver parts were kept at -80 °C to assess apelin and transforming growth factor-beta (TGF-β) expression. The right kidney, pancreas, and liver parts were used for histopathologic evaluation.
RESULTS: DM was detected by higher FBG, microalbuminuria, increased albumin/creatinine ratio, and pancreas, renal, and hepatic structural disturbances. Diabetic hepatopathy was determined by increasing liver enzymes and decreasing total bilirubin. The TGF-β gene expression was significantly upregulated in the diabetic kidney and liver tissues. Apelin gene expression was significantly downregulated in the diabetic liver tissue but did not change in kidney tissue. Administration of hWJ-MSCs-CM improved renal and hepatic functional and structural disturbances. Moreover, CM therapy significantly decreased TGF-β expression and enhanced apelin expression in the kidney and liver tissues.
CONCLUSIONS: Human WJ-MSCs-CM may have protective effects on diabetic renal and hepatic complications. These effects may happen through the regulation of TGF-β and apelin signaling pathways.

The aim of the present study was to compare the circulating transforming growth factor-beta (TGF-β) of clinically normal age-matched and naturally occurring chronic kidney disease (CKD) cats and to determine the correlation between the TGF-β expression and histopathological changes in cats with CKD.
A total of 11 clinically normal age-matched and 27 cats with naturally occurring CKD were included in this study. Circulating TGF-β was quantified by immunoassays. Kaplan-Meier analysis was used to calculate the association between survival time and the concentration of circulating TGF-β. A general linear model was used to compare the circulating TGF-β between groups. Immunohistochemical analyses revealed TGF-β expression in renal tissues from cats with CKD that died during the study (n = 7) and in available archived renal tissue specimens taken at necropsy from cats that had previous CKD with renal lesions (n = 10). Correlations of the TGF-β expression and clinical parameters (n = 7) and histopathological changes (n = 17) were analysed using Spearman\'s rank correlation.
The median survival time of cats with a lower concentration of circulating TGF-β was shorter than that of cats with a higher concentration. The area under the curve of circulating TGF-β for predicting CKD was 0.781, indicating good differentiation. The study indicated a significant difference in circulating TGF-β concentrations between clinically normal cats and those with CKD and demonstrated that TGF-β expression is correlated with tubular atrophy.
The study findings suggest that decreased serum TGF-β and tubular atrophy with TGF-β immunoreactivity may be significant in cats with CKD.

Elevated intraocular pressure (IOP) is a well-recognized risk factor for development of primary open angle glaucoma (POAG), a leading cause of irreversible blindness. Ocular hypertension is associated with excessive extracellular matrix (ECM) deposition in trabecular meshwork (TM) resulting in increased aqueous outflow resistance and elevated IOP. Hence, therapeutic options targeting ECM remodeling in TM to lower IOP in glaucomatous eyes are of considerable importance.
This paper discusses the complex process of ECM regulation in TM and explores promising therapeutic targets. The role of Transforming Growth Factor-β as a central player in ECM deposition in TM is discussed. We elaborate the key regulatory processes involved in its activation, release, signaling, and cross talk with other signaling pathways including Rho GTPase, Wnt, integrin, cytokines, and renin-angiotensin-aldosterone. Further, we summarize the therapeutic agents that have been explored to target ECM dysregulation in TM.
Targeting molecular pathways to reduce ECM deposition and/or enhance its degradation are of considerable significance for IOP lowering. Challenges lie in pinpointing specific targets and designing drug delivery systems to precisely interact with pathologically active/inactive signaling. Recent advances in monoclonal antibodies, fusion molecules, and vectored nanotechnology offer potential solutions.

Background Chewing areca nuts can result in an oral disorder known as oral submucous fibrosis (OSF), which has the potential to be cancerous. Although it is only beginning to spread to European and the North American continents, it is highly prevalent in Southeast Asia. The probability of malignant transformation from OSF is raised by chewing tobacco use. In the current research, our objective was to assess the potential anti-fibrosis effects and the ability to prevent malignant transformation through the application of mangosteen pericarp extract. Methodology The Ethical Approval-IHEC/SDC/OMED-2101/23/085 from the institution was obtained to conduct this ex vivo study. The cytotoxicity effect of mangosteen pericarp extract on both normal and fibrotic buccal mucosal fibroblasts originating from OSF tissues was tested. Cell proliferation and cell migration by scratch wound healing assay was examined. Dual staining was done to determine the mode of cell death. Additionally, real-time PCR was utilized to measure the expression of TGF-β/Smad2/3 signalling, α-SMA, and type I collagen gene expression. Results Mangosteen extract exerted higher cytotoxicity of fibrotic buccal mucosal fibroblasts compared to normal cells. Furthermore, mangosteen-receiving cells exhibited downregulation in the expression of the TGF-β/Smad2 pathway, as well as reduced expression of α-SMA and type I collagen. Conclusion Findings from this study suggest that mangosteen could serve as a promising agent for averting the progression of oral fibrogenesis and halting the malignancy of the oral epithelium in patients with OSF.

The tumor microenvironment (TME) consists of cancer cells surrounded by stromal components including tumor vessels. Transforming growth factor-β (TGF-β) promotes tumor progression by inducing epithelial-mesenchymal transition (EMT) in cancer cells and stimulating tumor angiogenesis in the tumor stroma. We previously developed an Fc chimeric TGF-β receptor containing both TGF-β type I (TβRI) and type II (TβRII) receptors (TβRI-TβRII-Fc), which trapped all TGF-β isoforms and suppressed tumor growth. However, the precise mechanisms underlying this action have not yet been elucidated. In the present study, we showed that the recombinant TβRI-TβRII-Fc protein effectively suppressed in vitro EMT of oral cancer cells and in vivo tumor growth in a human oral cancer cell xenograft mouse model. Tumor cell proliferation and angiogenesis were suppressed in tumors treated with TβRI-TβRII-Fc. Molecular profiling of human cancer cells and mouse stroma revealed that K-Ras signaling and angiogenesis were suppressed. Administration of TβRI-TβRII-Fc protein decreased the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), interleukin-1β (IL-1β) and epiregulin (EREG) in the TME of oral cancer tumor xenografts. HB-EGF increased proliferation of human oral cancer cells and mouse endothelial cells by activating ERK1/2 phosphorylation. HB-EGF also promoted oral cancer cell-derived tumor formation by enhancing cancer cell proliferation and tumor angiogenesis. In addition, increased expressions of IL-1β and EREG in oral cancer cells significantly enhanced tumor formation. These results suggest that TGF-β signaling in the TME controls cancer cell proliferation and angiogenesis by activating HB-EGF/IL-1β/EREG pathways and that TβRI-TβRII-Fc protein is a promising tool for targeting the TME networks.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma that affects B lymphocytes. It can develop in the lymph nodes and can be localized or generalized. Despite DLBCL being considered potentially curable, little research has been conducted on the relationship between the body\'s immune response and DLBCL.
OBJECTIVE: To study the expression and significance of T-regulatory cells (Tregs) interleukin (IL)-35, IL-10, and transforming growth factor-beta (TGF-β) in DLBCL.
METHODS: Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University (Zhejiang Province, China) between January 2017 and June 2022 and treated with standard first-line regimens were reviewed. Three patients were lost to follow-up; thus, 79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy: Incipient (new-onset and treatment-naïve), effectively treated, and relapsed-refractory. Thirty healthy individuals were included in the control group. The expression of peripheral blood T lymphocytes and their associated factors IL-35, IL-10, and TGF-β in the four groups were observed.
RESULTS: In contrast to the successfully treated and normal control groups, both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive (+) Tregs (P < 0.05), whereas the proportion of CD8+ Tregs did not differ substantially between the groups. Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups (P < 0.05). There was no statistically significant distinction in the expression level of TGF-β between the groups (P > 0.05). The correlation between IL-35 and IL-10 concentrations was significantly positive, with a correlation coefficient of 0.531 (P < 0.05). The correlation between IL-35 and TGF-β concentration was significantly positive, with a correlation coefficient of 0.375 (P < 0.05). The correlation between IL-10 and TGF-β concentration was significantly positive, with a correlation coefficient of 0.185 (P < 0.05). The expression concentrations of IL-35, IL-10 and TGF-β were apparently and positively correlated (P < 0.05).
CONCLUSIONS: Tregs IL-35, and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.