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Repair of the damaged meniscus is a scientific challenge owing to the poor self-healing potential of the white area of the meniscus. Tissue engineering provides a new method for the repair of meniscus injuries. In this study, we explored the superiority of 2% hyaluronic acid chitin hydrogel in temperature sensitivity, in vitro degradation, biocompatibility, cell adhesion, and other biological characteristics, and investigated the advantages of hyaluronic acid (HA) and Transforming Growth Factor β1 (TGF-β1) in promoting cell proliferation and a matrix formation phenotype. The hydrogel loaded with HA and TGF-β1 promoted cell proliferation. The HA + TGF-β1 mixed group showed the highest glycosaminoglycan (GAG) content and promoted cell migration. Hydroxypropyl chitin (HPCH), HA, and TGF-β1 were combined to form a composite hydrogel with a concentration of 2% after physical cross-linking, and this was injected into a rabbit model of a meniscus full-thickness tear. After 12 weeks of implantation, the TGF-β1 + HA/HPCH composite hydrogel was significantly better than HPCH, HA/HPCH, TGF-β1 + HPCH, and the control group in promoting meniscus repair. In addition, the new meniscus tissue of the TGF-β1 + HA/HPCH composite hydrogel had a tissue structure and biochemical content similar to that of the normal meniscus tissue. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease (ESRD), causing an urgent need for preventive strategies for DKD. Astragaloside I (ASI), a bioactive saponin extracted from Astragalus membranaceus (Fisch.) Bunge has been demonstrated to possess a variety of biological activities. This study investigates the therapeutic potential of ASI in DKD and the underlying molecular mechanism using db/db mice in vivo and high glucose (HG)-induced SV40-MES-13 cells in vitro. The results indicated that ASI significantly ameliorated renal dysfunction and mitigated the pathological alterations in the renal tissues of db/db mice. Moreover, ASI was found to reduce the levels of renal fibrosis makers and suppress the activation of TGF-β1/Smad2/3 pathway in both db/db mice and HG-induced SV40-MES-13 cells. Furthermore, ASI downregulated HDAC3 expression, upregulated Klotho expression, and enhanced Klotho release. ASI is directly bound to HDAC3, and the beneficial effects of ASI on Klotho/TGF-β1/Smad2/3-mediciated renal fibrosis in DKD were reversed by the HDAC3 agonist ITSA-1. In conclusion, ASI attenuates renal fibrosis in DKD, and may act through concurrently inhibiting HDAC3 and TGF-β1, thereby regulating HDAC3-mediciated Klotho/TGF-β1/Smad2/3 pathway. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-β (TGF-β) superfamily play key roles in the homeostasis of pancreatic β-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-β1, TGF-β3 and the risk to GDM in Chinese women.Methods: This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-β1 (rs4803455) and TGF-β3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test.Results: An increased frequency of TGF-β3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054-1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650-0.919). But there were no significant differences in the distribution of TGF-β1 rs4803455 and TGF-β3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE).Conclusions: The AA and AG genotype of TGF-β3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population. [ABSTRACT FROM AUTHOR]

Corilagin is a polyphenol that can be extracted from many medicinal plants and shows multiple pharmacological effects. We aimed to investigate the role of corilagin on miR-21-regulated hepatic fibrosis, especially miR-21-regulated TGF- β 1/Smad signaling pathway, in hepatic stellate LX2 cell line and Sprague–Dawley rats. The mRNA or protein levels of miR-21, Smad7, connective tissue growth factor (CTGF), α -smooth muscle actin (α -SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), collagen type I alpha 1 (COL1A1), Smad2, Smad3, Smad2/3, p-Smad2, p-Smad3, p-Smad2/3, and transforming growth factor- β 1 (TGF- β 1) in LX2 cells and liver tissues were determined. Furthermore, gain-of and loss-of function of miR-21 in miR-21-regulated TGF- β 1/Smad signaling pathway were analyzed in LX2 cells. Liver tissues and serum were collected for pathological analysis, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Corilagin treatment reduced mRNA or protein levels of miR-21, CTGF, α -SMA, TIMP-1, TGF- β 1, COL1A1, p-Smad2, p-Smad3, and p-Smad2/3 both in vitro and in vivo. While corilagin increased mRNA and protein levels of Smad7 and MMP-9. After gain-of and loss-of function of miR-21, the downstream effectors of miR-21-regulated TGF- β 1/Smad signaling pathway in LX2 cells changed accordingly, and the changes were inhibited by corilagin. Simultaneously, administration of corilagin not only ameliorated pathological manifestation of liver fibrosis but also reduced levels of α -SMA and COL1A1 in liver tissues and TGF- β 1, ALT levels in serum. Corilagin is able to potentially prevent liver fibrosis by blocking the miR-21-regulated TGF- β 1/Smad signaling pathway in LX2 cells and CCl4-induced liver fibrosis rats, which may provide a novel therapeutic strategy for liver fibrosis. [ABSTRACT FROM AUTHOR]

Mitochondrial abnormalities and a defective expression of neurotrophic factors contribute to neuronal damage in Huntington's disease (HD). HD patients showed a reduction in transforming growth factor-β1 (TGF-β1) levels in the peripheral blood and in cortical neurons. 3-n-butylphthalide (NBP) is first isolated from the seeds of celery, treats ischemic stroke in China. NBP could attenuate cognitive and motor impairments in the experimental models of Parkinson's disease and Alzheimer's disease, reduce mitochondrial oxidative stress and increase the expression of TGF-β1 in rats with focal cerebral ischemia. To our knowledge, the effect of NBP on Huntington's disease has not been reported. We proposed the hypothesis that whether NBP could protect mitochondria and regulate TGF-β1 and its downstream signaling in a HD animal model, further prevents motor dysfunction. Malonic acid is a reversible inhibitor of mitochondrial enzyme complex-II, induces energy crisis and free radical generation. In this study, we used intrastriatal injections of malonic acid in rats to mimic mitochondrial abnormalities and the other HD like symptoms. We found that treatment with NBP significantly attenuated malonic acid-induced motor and cognitive dysfunction in locomotor behaviour test, rotarod test, novel object recognition test and morris water maze test, prevented neurotoxicity and mitochondrial damage, activated TGF-β1/Akt/Wnt/β-Catenin pathway in striatum, but didn't regulate mitochondrial fusion and fission. The above effect was partly reversed by a PI3K/Akt inhibitor. Our data support NBP as a potential candidate for the treatment of HD. [ABSTRACT FROM AUTHOR]

The proliferation and migration of hepatic stellate cells (HSCs) profoundly impact the pathogenesis of liver inflammation and fibrogenesis. As a perennial herb native to China, Bupleurum falcatum is administered for its anti-inflammatory, antipyretic, and antihepatotoxic effects. Saikosaponin a (SSa) and Saikosaponin d (SSd) are the major active components of triterpene saponins in Bupleurum falcatum. This study analyzes how SSa and SSd affect rat HSC-T6 cell line proliferation and migration. Experimental results indicate that, in addition to suppressing HSC-T6 proliferation, wound healing activity and cell migration in a time- and dose-dependent manner, SSa and SSd significantly induce apoptosis. Additionally, SSa and SSd decreased the expressions of extracellular matrix-regulated kinase 1/2 (ERK1/2), platelet-derived growth factor receptor 1 (PDGFR1), and subsequently transforming growth factor-β1 receptor (TGF-β1R), α-smooth muscle actin, TGF-β1 and connective tissue growth factor. They also decreased phosphorylation of p38 (p-p38) and ERK1/2 (p-ERK1/2) of HSC-T6. Furthermore, both SSa and SSd can block PDGF-BB and TGF-β1-induced cell proliferation and migration of HSC-T6. These results suggest that SSa and SSd may inhibit proliferation and activation of HSC-T6, and the modulated mechanisms warrant further study. [ABSTRACT FROM AUTHOR]

Abstract: Epidemiological evidence has shown two polymorphisms (namely RS#1800468G>A and RS#1800471G>C) of transforming growth factor-beta 1 (TGF-β1) gene may be involved in the cancer development. However, their role in the carcinogenic process of esophageal squamous cell carcinoma (ESCC) has been less well elaborated. We conducted a hospital-based case-control study including 391 ESCC cases and 508 controls without any evidence of tumors to evaluate the association between these two polymorphisms and ESCC risk and prognosis for Zhuangese population by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS)-PCR techniques. We found that individuals with the genotypes with RS#1800471 C allele (namely RS#1800471-GC or -CC) had an increased risk of ESCC than those without above genotypes (namely RS#1800471-GG, adjusted odds ratio 3.26 and 5.65, respectively). Further stratification analysis showed that this polymorphism was correlated with tumor histological grades and TNM (tumor, node, and metastasis) stage, and modified the serum levels of TGF-β1. Additionally, RS#1800471 polymorphism affected ESCC prognosis (hazard ratio, 3.40), especially under high serum levels of TGF-β1 conditions. However, RS#1800468 polymorphism was not significantly related to ESCC risk. These findings indicated that TGF-β1 RS#1800471G>C polymorphism may be a genetic modifier for developing ESCC in Zhuangese population. [Copyright &y& Elsevier]

Abstract: Quercetin''s protective effects on the glomerulosclerosis of diabetic nephropathy (DN) in rat mesangial cells were investigated. The cell cycles, type IV collagen and laminin, TGF-β1 mRNA, Smad 2/3 and Smad 7, and activities of cell antioxidases were measured. Compared with the high glucose group, quercetin may decrease the cell percentages of G0/G1 phase, Smad 2/3 expression, laminin and type IV collagen, and TGF-β1 mRNA level significantly. The antioxidant capacity, the cell percentages of S phase and Smad 7 expression was significantly increased by quercetin. These results suggest that quercetin is a protective agent against glomerulosclerosis in DN. [Copyright &y& Elsevier]

Aims. Based on a case–control study, we investigated the relationship between +869T/C and +915G/C gene polymorphisms in transforming growth factor-β1 (TGF-β1), protein levels and essential hypertension (EH) in the Kazakh and Han Chinese populations selected from the Boertonggu countryside of Shawan region in the Xinjiang Uygur Autonomous Region of China ( n=1600). The polymorphisms of TGF-β1 and the blood levels were detected using polymerase chain reaction–restriction fragment length polymorphism assays and sandwich ELISA, respectively. Major findings. An association was found between +869C-allele with higher risk of EH in these two populations. We also found that the CG haplotype of the two polymorphisms was associated with EH in the Kazakh EH patients. The levels of TGF-β1 in the blood were positively correlated with diastolic blood pressure both in the Kazakh and Han EH patients. Levels of the TGF-β1 protein in the Kazakh EH patients were significantly higher than those in the Han EH patients. Principal conclusion. These results suggest that the TGF-β1 +869 C allele is potentially a genetic factor of EH in these two ethnicities, the CG haplotype can be a genetic marker of EH in the Kazakh Chinese and the high concentration of TGF-β1 is possibly associated with EH, especially in the Kazakh population. [ABSTRACT FROM AUTHOR]

Background: To date there is no information on the expression of mediators associated with tissue remodeling in Asian patients with chronic rhinitis with (CRSwNP) or without (CRSsNP) nasal polyps. Objectives: To study the expression of TGF-β1, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), collagen, and regulatory T cells in Chinese patients with CRSwNP and CRSsNP. Methods: Thirty-six male and female subjects (12 patients with CRSwNP, 12 patients with CRSsNP, and 12 control subjects), age 17 to 60 years, were recruited into the study. Samples were collected from polyp and sinusoidal mucosal, ethmoidal mucosal, or inferior turbinate in the respective groups and assessed for TGF- β1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 by immunoassay; collagen by histochemistry; and forkhead box P3 (FOXP3) mRNA by real-time PCR. Results: Patients with CRSwNP showed significantly lower concentrations of TGF-β1, TIMP-1, TIMP-4, FOXP3, and collagen compared with patients with CRSsNP. Although there were no significant differences between the concentrations of MMP-7 and MMP-9 in patients with CRSwNP and CRSsNP, these were significantly increased compared with control patients. MMP-2 and TIMP-2 concentrations were not significantly different in any patient group, whereas TIMP-3 was not detectable. Conclusion: Chronic rhinosinusitis with nasal polyps is characterized by a relative lack of TGF-ß expression versus CRSsNP. This finding may be causal for decreased collagen, TIMP-1/4, and FOXP3 expression in CRSwNP versus CRSsNP. TGF-ß serves as a main switch for different remodeling patterns in sinus disease. [Copyright &y& Elsevier]

This study examined the association of cytokine gene polymorphisms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for IFN-γ (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/ A), TNF-α (-308 G/A), and TGF-β1 (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with IFN-γ intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-α low- producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-γ and TNF-α genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-γ and low producing TNF-α), moderate, and low (low-producing IFN-γ and high producing TNF-α,) risk groups. The incidence of IHDD was significantly different among these groups (P= 0.022); 88.9% (odds ratio, OR = 24.0) in high, 56.5% (OR = 3.9) in moderate, and 25.0% (OR = 1) in low risk groups. SNP of IFN-γ and TNF-α, genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Transforming growth factor-β 1 (TGF-β1), TGF-β2, osteoprotegerin (OPG), and leptin are important cytokines in the regulation of bone remodeling. We investigated the relationship of TGF-β1 and TGF-β2 concentrations with those of OPG and leptin in Chinese females. Methods: The serum concentrations of TGF-β1, TGF-β2, OPG, and leptin were measured by ELISA in 459 healthy Chinese females aged 25–80 y. Results: The mean values (±SD) of the serum concentrations of TGF-β1, TGF-β2, OPG, and leptin in Chinese females were 29.7±1.69 μg/l, 13.7±3.86 μg/l, 3.81±1.96 pmol/l, and 10.5±2.01 μg/l, respectively. Further, the serum TGF-β1 concentrations of postmenopausal women were significantly lower than those of perimenopausal and premenopausal women (24.3±1.59 vs 33.4±1.69 and 37.6±1.64, respectively), while the TGF-β2 concentrations of postmenopausal women were significantly higher than those of perimenopausal and premenopausal women (14.6±3.91 vs 13.5±3.93 and 11.7±2.68, respectively). The serum TGF-β1 concentration was found to be significantly negatively correlated with age (r =−0.335, P =0.000) and the TGF-β2 concentration, to be significantly positively correlated with age (r =0.230, P =0.000). The TGF-β1 concentration was found to be significantly negatively correlated with both TGF-β2 (r =−0.261, P =0.000) and OPG (r =−0.313, P =0.000) concentrations; a significantly positive correlation was found between the TGF-β1 and leptin concentrations (r =0.164, P =0.000) and between TGF-β2 and OPG concentrations (r =0.432, P =0.000). Conclusion: These results provide age-related reference values of TGF-β1 and TGF-β2 in Chinese adult women, and reveal the relationships between these cytokines. [Copyright &y& Elsevier]

Abstract: The TGF-β signaling pathway plays a very important role in the control of cell proliferation and differentiation that is involved in colorectal carcinogenesis. The associations between polymorphisms of TGF-β1 and its receptors genes and the colorectal cancer risk were assessed in a population-based case-control study (206 cases and 838 controls). We could not observe any variant in the G-800A, codon25 and codon263 of TGF-β1 and A-364G of TGFβR2 in Chinese population. However, the results revealed that -509CT and TT genotypes were significantly associated with decrease risk for colorectal cancer (adjusted OR=0.58, 95% CI 0.40–0.84 and adjusted OR=0.44, 95% CI 0.29–0.68, respectively). Moreover, the linkage disequilibrium analysis revealed that TGF-β1 C-509T and codon10 polymorphisms were in strong linkage disequilibrium, and the −509C/+29C was associated with a significantly increased risk of colorectal cancer (OR=1.32, 95% CI=1.05–1.66). Our findings indicate that the distributions of polymorphisms in TGF-β1 and its receptors genes vary greatly among different ethnic groups, and these polymorphisms might contribute to the colorectal cancer susceptibility. [Copyright &y& Elsevier]

Background: Gastric cancer (GC) is one of the most prevalent malignancy around the world. Primary tumor cells are enabled to invade and migrate into adjacent normal tissues to form secondary tumors. Epithelial-mesenchymal transitions (EMT) plays a pivotal role in facilitating tumor progression. Abundant evidence suggested that the transforming growth factor-β1 (TGF-β1) triggered the process of EMT. Nonetheless, the precise molecular mechanisms underlying EMT requires further elucidation, and there still lacks effective specific therapeutic target. In our recent research, we demonstrated that the interferon (IFN)-induced transmembrane protein 2 (IFITM2) promoted the growth and metastasis of GC. However, it remains unclear whether IFITM2 involves in TGF-β1 mediated EMT in GC., Methods and Results: In the present research, we investigated the functional role of IFITM2 in EMT process and TGF-β1 signaling pathway in two GC cell lines. We noticed that silencing IFITM2 can effectively inhibit TGF-β1 signaling mediated EMT by regulating down stream small mother against decapentaplegic (SMAD) 2/3 and transcription factors.This finding was further determined in both tumor tissues from GC patients and normal tissues adjacent to cancer. Our data demonstrated the key role of IFITM2 in TGF-β1 signaling and EMT in GC., Conclusion: The findings enriched our understanding of the underlying mechanism in EMT during the progression of GC. In addition, IFITM2 would be a potential target for treating GC and other malignant tumors., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

• 119 active components in GXV and 169 potential targets shared between GXV and VR were identified. • GXV produces marked anti-apoptosis and anti-fibrosis effects in VR though Caspase-3 and TGF-β1. • Our study deepens the understanding of the molecular mechanisms of GXV in treating VR. Guanxin V (GXV) has been widely used to treat ventricular remodeling (VR) in clinical practice in China. However, the underlying mechanisms are currently still lack. A systematic pharmacology-based strategy was utilized for predicting the synergistic pharmacological mechanisms of GXV in VR. The active compounds of GXV were selected and then the potential targets of these compounds contained in GXV and VR were successively identified. Then, after networks were constructed, DAVID was applied to functional enrichment. Moreover, the key findings were validated though molecular docking and molecular biology experiments. A total of 119 active components in GXV and 169 potential targets shared between GXV and VR were obtained. The results of functional enrichment indicated that several biological processes and signaling pathways, mainly cell apoptosis and fibrosis. Finally, we discovered GXV produced marked anti-apoptosis and anti-fibrosis effects in VR though Caspase-3 and TGF-β1. GXV could relieve and reverse VR through anti-apoptosis and anti-fibrosis effects predicted by systematic pharmacology and validated by molecular docking and molecular experiments. Our study deepens the understanding of the molecular mechanisms of GXV in treating VR. [ABSTRACT FROM AUTHOR]

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., Method: 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, I 2 <0.1%, P>0.1)., Conclusion: In summary, our meta-analysis showed that the rs1982073 T allele does not increase RA susceptibility in Europeans., (Copyright © 2021. Published by Elsevier B.V.)

Macroangiopathy is a complication of Type II Diabetes Mellitus (T2DM), which is mainly caused by fibrosis of blood vessels. Using T2DM rat models, we investigated whether the traditional Chinese medicine, Di-Dang Decoction (DDD), exhibited anti-fibrotic actions on great vessels. T2DM rats were randomly divided into non-intervention group, early-, middle-, late-stage DDD intervention groups and control groups, including pioglitazone group and aminoguanidine group. After administration of DDD to T2DM rats at different times, we detected the amount of extracellular matrix (ECM) deposition in the thoracic aorta. The results showed that early-stage intervention with DDD could effectively protect great vessels from ECM deposition. Considering that TGF-β1 is the master regulator of fibrosis, we further validated at the molecular level that, compared to middle- and late-stage intervention with DDD, early-stage intervention with DDD could significantly decrease the expression levels of factors related to the activated TGF-β1/Smad signalling pathway, as well as the expression levels of downstream effectors including CTGF, MMP and TIMP family proteins, which were directly involved in ECM remodelling. Therefore, early-stage intervention with DDD can reduce macrovascular fibrosis and prevent diabetic macroangiopathy., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background: Abnormal renal metabolism is closely related to the development of chronic kidney disease. It is well known that renal inflammation plays an important role in the occurrence and development of tubulointerstitial damage in the renal tubules. The purpose of the experiment was to observe the bioactivity of Alpina oxyphylla extract (AOE) on renal injury in diabetic nephropathy (DN) rats induced by streptozotocin (STZ)., Methods: Thirty male Wistar rats were randomly divided into five group (n = 6): (1) intact control (non-diabetic, ND); (2) intact diabetic (STZ), (3) diabetic rats treated with gliclazide 5 mg/kg (STZ-gli), (4) diabetic rats treated with AOE 400 mg/kg (AOE 400), (5) diabetic rats treated with AOE 800 mg/kg (AOE 800). The diabetic nephropathy rat model was established by single intraperitoneal injected 50 mg/kg STZ. Fasting blood glucose (FBG) and body weight was observed at 1、3、6 weeks. After 6 weeks, the renal function parameters of five groups and 24 h urinary protein were detected. Expression of transforming growth factor-beta1 (TGF-β1) and myeloid differentiation factor 88 (MyD88) were assessed by Western Blot., Results: The STZ group showed hyperglycemia, proteinuria, renal function damage, and the levels of 24 h urinary protein, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Scr), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and interleukin-6 (IL-6) in the STZ group increased significantly compared with the ND group. The expression of TGF-β1 in STZ group was increase (p < 0.01), and the expression of MyD88 was significantly lower than in ND group (p < 0.05). The treatment of DN rats with AOE attenuated DN-associated in the serum biochemical index and the expression of TGF-β1., Conclusions: AOE can effectively protect kidney tissues of diabetic nephropathy, and probably through regulating level of TGF-β1/MyD88.

A major obstacle to effective cancer immunotherapy is the tumor immune microenvironment. Natural killer (NK) cell resistance has been suggested as a primary cause of poor prognosis in hepatocellular carcinoma (HCC), which seemingly correlates with CNOT7 overexpression. CNOT7, a cytoplasmic mRNA deadenylase that is highly expressed in HCC, may regulate cytokine transforming growth factor-β1 (TGF-β1) secretion by controlling nuclear factor-κB subunit p65 trafficking. CNOT7 depletion suppresses TGF-β1 secretion in HCC and promotes interferon-γ (IFN-γ) secretion by NK cells, and we previously demonstrated that CNOT7 depletion reversed IFN-γ resistance in HCC cells. Therefore, we hypothesized that CNOT7 depletion might reverse NK cell resistance by influencing the tumor immune microenvironment of HCC. To test this hypothesis, we examined the correlation between CNOT7, STAT1, TGF-β1 and IFN-γ expression with hepatitis B virus-related cirrhosis and HCC with hepatitis B virus-related cirrhosis. We found that modulation of CNOT7 expression alters TGF-β1 secretion in HCC and IFN-γ secretion in NK cells. We also examined the effects of NK cells in HepG2 cells with CNOT7 knockdown, which showed that NK cell surface CD107a expression is up-regulated and caspase-3 expression is significantly enhanced in CNOT7-deficient HepG2 cells. Overall, our results show that knockdown of CNOT7 expression reverses NK cell resistance in HCC cells. Therefore, CNOT7 depletion has potential as a new adjuvant therapy in immunotherapy for HCC., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Transforming growth factor (TGF)-β1 contributed to angiotensin II (Ang II)-mediated collagen accumulation after myocardial infarction (MI). The present study aimed to investigate the association of genetic variant of TGF-β1 gene with the risk of MI. The present study recruited a total of 530 MI patients and 651 healthy controls. The genomic DNA was extracted and subjected into polymerase chain reaction (PCR) and Sanger sequencing. The present study indicated that TGF-β1 -913G/C polymorphism was associated with increased risk for MI under the co-dominant, dominant and allelic models. The increased risk effect was also evident among the females, younger subjects (age < 60 years), smokers, non-drinkers and individuals with hypertension. Additionally, the present study observed significant differences among cases and controls in terms of total cholesterol (TC). In conclusion, TGF-β1 -913G/C polymorphism is associated with increased risk for MI. TGF-β1 -913G/C polymorphism may be a potential prognostic biomarker for MI., (© 2019 The Author(s).)

Nicousamide has been shown to exert renal protective effects against diabetic nephropathy and has moved to a phase II clinical trial in China for diabetic nephropathy indication. To expand its clinical indications, 5/6-nephrectomised rats were used to mimic glomerular and vascular sclerosis and tubulointerstitial scarring, with subsequent progression towards end-stage renal disease. Adult Wistar rats underwent 5/6 nephrectomy to induce the development of chronic kidney disease, with a sham operation performed as a control. The nephrectomised animals were treated orally with either saline, nicousamide (7.5,15, or 45 mg/kg), benazepril (4 mg/kg), or losartan (10 mg/kg) daily for 20 weeks. At 8, 16, and 20 weeks of treatment, blood pressure was measured in each animal, and blood and urine samples were collected for biochemical analysis, while kidney remnants were collected for histological examination. Levels of fibronectin and transforming growth factor beta 1 (TGF-β1) were measured in kidneys by immunohistochemistry. Renin activity in the plasma was measured by an enzyme-linked immunosorbent assay. The results showed that nicousamide treatment significantly reduced systemic hypertension, proteinuria, and blood urea nitrogen (P < 0.05), effectively alleviated glomerular sclerosis scores and tubulointerstitial injuries in a dose-dependent manner (P < 0.01), and markedly decreased fibronectin and TGF-β1 levels in kidney tissues of the 5/6-nephrectomised animals. In vitro studies suggested that nicousamide could moderately inhibit the renin activity and strongly block the TGF-β1 internalisation into fibroblast cells. In summary, nicousamide may protect from renal failure through dual targeting, which involves a TGF-β1-dependent mechanism and inhibition of renin activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Asian Sand Dust-Particulate Matter (ASD-PM) aerosol brings large amounts of wind-eroded soil particles containing high concentrations of metallic components caused by industrialization and vehicles. Proinflammatory and cytotoxic cytokines trigger local inflammatory responses and cause a systematically high incidence of cardiovascular and other diseases. Tenascin C (Tn-C) is known to be expressed in damaged tissue or in a developmental stage of tissue. In this study, we examined the expression of Tn-C and Fibronectin in human cancer-cell lines and in liver tissue of mice treated with ASD-PM to investigate the inflammatory and cell-damage effects of ASD-PM. In our in vivo study, mice were intratracheally instilled with saline suspensions of ASD-PM particles. Instillation of these particles was repeated twice a week for 12 weeks and the liver tissues were stained with hematoxylin, eosin, and Masson's trichrome, and we carried out an IF. Tn-C expression in liver tissues was detected by RT-PCR and western blot analysis. In the results, the expression of Tn-C increased in a dose-dependent manner in both RNA and Immunofluorescence assay (IF). In our in vitro study, A549 and Hep3B cell lines were incubated in culture media with Transforming Growth Factor-Beta1(TGF-β1) and ASD-PM. Immunofluorescence microscopy images showed a two times stronger expression of fluorescence in the ASD-treated group than in that treated with TGF-β1. They also showed a stronger expression of Tn-C in proportion to the concentration of ASD-PM. We confirmed that ASD-PM when inhaled formally migrated to other organs and induced Tn-C expression. ASD-PM containing metals causes expression of Tn-C in liver tissue in proportion to the concentration of ASD-PM.

Genetic alterations, together with environmental risk factors during infancy and childhood, contribute significantly to the etiology of autism spectrum disorder (ASD), a heterogeneous neurodevelopmental condition characterized by impairments in social interaction and restricted, repetitive behaviors. Mounting evidence points to a critical contribution of immunological risk factors to the development of ASD. By affecting multiple neurodevelopmental processes, immune system dysfunction could act as a point of convergence between genetics and environmental factors in ASD. Previous studies have shown altered cytokine levels in individuals with ASD, but research in Asian populations are limited. Here, we measured the plasma levels of 11 candidate cytokines in ASD and typically developing (TD) children. The cohort included 41 TD children and 87 children with ASD, aged 1-6 years. We found that as compared to the TD group, children with ASD had higher plasma levels of Eotaxin, TGF-β1 and TNF-α. The increase in TGF-β1 level was most significant in males, while the increase in Eotaxin was most significant in females. Eotaxin level negatively correlated with the social affect score (SA) in ADOS, while TNF-α level positively correlated with total development quotient (DQ), measured using GMDS. These pilot findings suggest potentially important roles of Eotaxin, TGF-β1 and TNF-α in ASD in the Chinese population. Autism Res 2018, 11: 989-999. © 2018 International Society for Autism Research, Wiley Periodicals, Inc., Lay Summary: Alteration of immune system function is an important risk factor for autism spectrum disorder (ASD). Here we found that the levels of cytokines, including Eotaxin, TGF-β1 and TNF-α, are elevated in Chinese children with ASD, as compared to typically developing children. The change in TGF-β1 level was most prominent in boys, while that of Eotaxin was more significant in girls. These results provide evidence for changes in cytokine profile in Chinese children with ASD., (© 2018 International Society for Autism Research, Wiley Periodicals, Inc.)

Ethnopharmacological Relevance: Polyporus umbellatus (Pers.) Fries (Polyporaceae, Zhuling ) has been commonly used in medicine for a wide range of ailments related to the edema, scanty urine, vaginal discharge, urinary dysfunction, as well as jaundice and diarrhea., Aim of the Review: The present paper reviewed the traditional uses, propagation, phytochemistry, pharmacology, pharmacokinetics and quality control of Polyporus umbellatus., Materials and Methods: All the available information on Polyporus umbellatus was collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Splinker, Google Scholar, etc.)., Results: Phytochemical studies showed the presence of many valuable secondary metabolites such as steroids, polysaccharides, anthraquinones and nucleosides. Crude extracts and isolated compounds showed a wide spectrum of pharmacological activities including diuretic, nephroprotective, anti-cancer, immuno-enhancing, hepatoprotective, anti-inflammatory and antioxidative activities. The pharmacokinetic studies demonstrated that the ergosterol and ergone had a high distribution and absorption in the plasma and the two main components of Polyporus umbellatus were mainly excreted by faeces. The determination of multiple chemical components was successfully applied to the quality control of Polyporus umbellatus., Conclusions: Modern phytochemical, pharmacological and metabonomic investigations showed that the crude extracts and isolated compounds from Polyporus umbellatus possess many kinds of biological functions, especially in the diuretic activities and the treatment of kidney diseases as well as anti-cancer, immuno-enhancing and hepatoprotective activities. The pathways of the distribution, absorption, metabolism and excretion of main steroidal compounds were clarified by pharmacokinetic studies. Most of the pharmacological studies were conducted using crude and poorly characterized extracts of Polyporus umbellatus in animals especially in case of diuretic activities and the treatment of kidney diseases. Thus, more bioactive components especially diuretic compounds should be identified using bioactivity-guided isolation strategies and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from Polyporus umbellatus need to be evaluated integrating pharmacological, pharmacokinetic, bioavailability-centered and physiological approaches. In addition, more experiments including in vitro, in vivo and clinical studies should be encouraged to identify any side effects or toxicity. These achievements will further expand the existing therapeutic potential of Polyporus umbellatus and provide a beneficial support to its future further clinical use in modern medicine., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

This study examined the association of cytokine gene polymorphisms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for IFN-gamma (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/A), TNF-alpha (-308 G/A), and TGF-beta1 (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with IFN-gamma intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-alpha low-producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-gamma and TNF-alpha genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-gamma and low producing TNF-alpha), moderate, and low (low-producing IFN-gamma and high producing TNF-alpha) risk groups. The incidence of IHDD was significantly different among these groups (P = 0.022): 88.9% (odds ratio, OR = 24.0) in high, 56.5% (OR = 3.9) in moderate, and 25.0% (OR = 1) in low risk groups. SNP of IFN-gamma and TNF-alpha genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients.