AIM: To examine the expression of activin A, a member of the transforming growth factor (TGF-β) superfamily, recently has been reported to beoverexpressed in liver cirrhosis, in the course of carbon tetrachloride-induced rat hepatic fibrosis.

METHODS: Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeks after carbon tetrachloride injections, the rats were killed in group (6-10 rats each time) for study. The activin A messenger RNA expression and its protein localization were assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry.

RESULTS: The normal rat liver expressed activin A mRNA and protein, and its expression was transiently decreased and became undetectable after carbon tetrachloride injections for 2 or 3 weeks and then increased gradually. After injection of carbon tetrachloride for 6 and 7 weeks, activin A mRNA and protein expressions were significantly enchanced in rat liver. Compared with that of the normal rat liver. Activin A mRNA expression levels in rats receiving carbon tetrachloride injections for 6 and 7 weeks were 1.6 and 2.2 times that of those in normal rat liver respectively (0.456 ± 0.094 vs 0.286 ± 0.0670, P < 0.01; 0.620 ± 0.134 vs 0.286 ± 0.0670, P < 0.01). Immunohistochemistry showed that activin A expressed in hepatocytes of normal liver, and its expression was decreased in rats receiving carbon tetrachloride for 2 or 3 weeks. Compared with normal liver, activin A expression distribution mode changed in fibrotic liver, being increased significantly in hepatocytes around fibrotic areas.

CONCLUSION: Activin A expression was increased in late stage of hepatic fibrosis, and this may be involved in hepatic fibrosis formation in this period.

Expression changes of activin A in the development of hepatic fibrosis

The tripartite-motif (TRIM) family represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. TRIM family is involved in a variety of cellular signaling transductions and biological processes. TRIM family also contributes to cancer initiation, progress, and therapy resistance, exhibiting oncogenic and tumor-suppressive functions in different human cancer types. Moreover, TRIM family members have great potential to serve as biomarkers for cancer diagnosis and prognosis. In this review, we focus on the specific mechanisms of the participation of TRIM family members in tumorigenesis, and cancer development including interacting with dysregulated signaling pathways such as JAK/STAT, PI3K/AKT, TGF-β, NF-κB, Wnt/β-catenin, and p53 hub. In addition, many studies have demonstrated that the TRIM family are related to tumor resistance; modulate the epithelial-mesenchymal transition (EMT) process, and guarantee the acquisition of cancer stem cells (CSCs) phenotype. In the end, we havediscussed the potential of TRIM family members for cancer therapeutic targets. 

/pdf/trim-family-contribute-to-tumorigenesis-cancer-development-g730r4qu.pdf

TRIM family contribute to tumorigenesis, cancer development, and drug resistance

Oxidative stress is a key driver in the development and progression of several diseases, including metabolic associated fatty liver disease (MAFLD). This condition includes a wide spectrum of pathological injuries, extending from simple steatosis to inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Excessive buildup of lipids in the liver is strictly related to oxidative stress in MAFLD, progressing to liver fibrosis and cirrhosis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of redox homeostasis. NRF2 plays an important role for cellular protection by inducing the expression of genes related to antioxidant, anti-inflammatory, and cytoprotective response. Consistent evidence demonstrates that NRF2 is involved in every step of MAFLD deve-lopment, from simple steatosis to inflammation, advanced fibrosis, and ini-tiation/progression of hepatocellular carcinoma. NRF2 activators regulate lipid metabolism and oxidative stress alleviating the fatty liver disease by inducing the expression of cytoprotective genes. Thus, modulating NRF2 activation is crucial not only in understanding specific mechanisms underlying MAFLD progression but also to characterize effective therapeutic strategies. This review outlined the current knowledge on the effects of NRF2 pathway, modulators, and mechanisms involved in the therapeutic implications of liver steatosis, inflammation, and fibrosis in MAFLD.

Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease

NLRP3 Inflammasome in Atherosclerosis: Putting Out the Fire of Inflammation

Oral squamous cell carcinoma (OSCC) is one of the main types of head and neck squamous cell carcinoma. Although progress has been made in treating OSCC, it remains a threat to human health, and novel therapeutic strategies are needed to extend the lifespan of patients with OSCC. The present study, evaluated whether bone marrow stromal antigen 2 (BST2) and STAT1 were potential therapeutic targets in OSCC. Small interfering RNA (siRNA) or overexpression plasmids were used to regulate BST2 or STAT1 expression. Western blotting and reverse transcription-quantitative PCR were performed to assess changes in the protein and mRNA expression levels of signaling pathway components. The effects of BST2 and STAT1 expression changes on the migration, invasion and proliferation of OSCC cells were assessed using the scratch test assay, Transwell assay and colony formation assay in vitro, respectively. Cell-derived xenograft models were used to evaluate the impact of BST2 and STAT1 on the occurrence and development of OSCC in vivo. Finally, it was demonstrated that BST2 expression was significantly upregulated in OSCC. Furthermore, it was demonstrated that high expression of BST2 in OSCC contributed to the metastasis, invasion and proliferation of OSCC cells. Moreover, it was demonstrated that the promoter region of BST2 was regulated by the transcription factor STAT1, and that the STAT1/BST2 axis could affect the behavior of OSCC via the AKT/ERK1/2 signaling pathway. In vivo studies also demonstrated that STAT1 downregulation inhibited OSCC growth by down-regulating BST2 expression via the AKT/ERK1/2 signaling pathway.

/pdf/bst2-regulated-by-the-transcription-factor-stat1-can-promote-23k43zly.pdf

BST2 regulated by the transcription factor STAT1 can promote metastasis, invasion and proliferation of oral squamous cell carcinoma via the AKT/ERK1/2 signaling pathway

Abstract Salvianolic acid A (SA-A), a water-soluble compound extracted from traditional Chinese herb Radix Salvia miltiorrhiza, has anti-fibrotic effects on carbon tetrachloride (CCl4)-induced liver fibrosis. However, the underlying molecular mechanism remains unclear. Thus, this study aimed to elucidate the molecular mechanism underlying the anti-fibrotic effects of SA-A on CCl4-induced liver fibrosis in mice. All mice (except control group) were intraperitoneally administered CCl4 dissolved in peanut oil to induce liver fibrosis. Treatment groups were then gavaged with SA-A (20 or 40 mg/kg). The liver function index; liver fibrosis index; and superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were determined. Furthermore, histopathological changes in liver tissues were observed via hematoxylin–eosin and Masson's trichrome staining. The expression of α-smooth muscle actin (α-SMA) and collagen I was detected using immunofluorescence, and the mRNA levels of inflammatory factors were determined using quantitative polymerase chain reaction. Finally, western blotting and immunofluorescence were used to determine the expression levels of proteins related to Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways. The results showed that SA-A could ameliorate CCl4-induced liver injury and liver fibrosis, improve morphology, and alleviate collagen deposition in the fibrotic liver. Moreover, SA-A could regulate the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways; increase the levels of SOD and GSH-Px; and decrease MDA level in the fibrotic liver. Collectively, our study findings indicate that SA-A is effective in preventing liver fibrosis in mice by inhibiting inflammation and oxidative stress via regulating the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways.

Salvianolic acid A suppresses CCl4-induced liver fibrosis through regulating the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways

https://doi.org/10.1016/j.apsb.2022.04.010

In situ synthesis and unidirectional insertion of membrane proteins in liposome-immobilized silica stationary phase for rapid preparation of microaffinity chromatography

Salvianolic acid B suppresses hepatic stellate cell activation and liver fibrosis by inhibiting the NF-κB signaling pathway via miR-6499-3p/LncRNA-ROR.

Breast cancer is the most common cancer in women. Novel mechanisms and targets are urgently needed to understand and treat this disease due to the complexity of breast cancer. In this study, we evaluated the expression level of tripartite motif-containing (TRIM) 35 in various breast cancer cell lines by qPCR and immunoblot. Cell proliferation assay and flow cytometry were performed upon overexpression and depletion of TRIM35. Xenograft tumor model was applied to validate the findings observed in vitro. The correlation between TRIM35 and outcomes of breast cancer patients was investigated by analyzing The Cancer Genome Atlas (TCGA) database. We observed differential expression of TRIM35 in various breast cancer cell lines. Overexpression of TRIM35 significantly inhibited cell proliferation and promoted cell apoptosis. On the contrary, depletion of TRIM35 exerted the opposite effects on cell proliferation and apoptosis. Mechanistically, TRIM35 reduced PDK1 by ubiquitination, resulting in the degradation of PDK1. Overexpression of TRIM35 significantly suppressed ZR7530 cell line-derived xenograft tumor growth by inducing apoptosis. Finally, a lower level of TRIM35 was associated with a poor prognosis in patients. In conclusion, TRIM35 functions as a tumor suppressor to suppress breast cancer proliferation by inactivating AKT signaling through the increased ubiquitination of PDK1, resulting in the promotion of apoptosis.

Rong Wang Zhi Rong Wang

Papers

Salvianolic acid A suppresses CCl4-induced liver fibrosis through regulating the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways

In situ synthesis and unidirectional insertion of membrane proteins in liposome-immobilized silica stationary phase for rapid preparation of microaffinity chromatography

Salvianolic acid B suppresses hepatic stellate cell activation and liver fibrosis by inhibiting the NF-κB signaling pathway via miR-6499-3p/LncRNA-ROR.

TRIM35 functions as a novel tumor suppressor in breast cancer by inducing cell apoptosis through ubiquitination of PDK1.

Gomisin D alleviates liver fibrosis through targeting PDGFRβ in hepatic stellate cells.