Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism.

BACKGROUND: Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis. AIM: To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. METHODS: To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected. RESULTS: The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1. CONCLUSION: YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Reciprocal Regulation Between O-GlcNAcylation and ß-Catenin Facilitates Cell Viability and Inhibits Apoptosis in Liver Cancer.

Abnormal expression of O-Linked ß-N-acetylglucosamine (O-GlcNAc) and ß-catenin is a general feature of cancer and contributes to transformed phenotypes. In this study, we identified the interaction between O-GlcNAc and ß-catenin, and explored their effects on the progression of liver cancer. Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased ß-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7. In addition, overexpression of ß-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination. Moreover, the O-GlcNAcylation of ß-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells. Knockdown of ß-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression. In conclusion, this study revealed that the reciprocal regulation between O-GlcNAcylation and ß-catenin facilitated the proliferation of liver cancer.

Prognostic value and clinicopathological significance of serum- and tissue-based cytokeratin 18 express level in breast cancer: a meta-analysis.

Cytokeratin 18 (CK18), a type I cytokeratin of the intermediate filament family, has been associated with the prognosis of cancer patients for decades. However, its exact role in predicting the clinical outcome of breast cancer remains controversial. To comprehensively investigated the prognostic value of CK18 in breast cancer, a systematically meta-analysis was conducted to explore the association between CK18 expression and overall survival. Literature collection was conducted by retrieving electronic databases Pubmed, Cochrane Library, Web of Science, EMBASE, and OVID completely (up to January 1, 2017). Nine relevant studies with 4857 cases assessing the relationship between CK18 high expression and the outcome of breast cancer patients were enrolled in our analysis. The results indicated that the high level of CK18 expression was significantly associated with overall survival of breast cancer patients via a specimen-depended manner. Reports which used serum to detect the expression of CK18 predicted a poor outcome of breast cancer (HR = 1.24, 95%CI: 1.11-1.38, P<0.0001), while studies which used tissue as specimen indicated a reverse result (HR = 0.71, 95%CI: 0.60-0.84, P<0.00001). Moreover, overexpression of CK18 was highly relevant to advanced clinicopathological parameters of breast cancer, such as progesterone receptor, human epidermal growth factor receptor-2, tumor size, tumor stage, nodal status, and tumor grade. Taken together, the present study demonstrated that CK18 might be served as a novel biomarker to predict clinicopathological features and the outcome of breast cancer.

Effect of Aidi Injection plus TACE on Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials.

We aim to conduct a meta-analysis of studies on the effect of Aidi injection combined with TACE in the treatment of hepatocellular carcinoma (HCC). China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Allied and Complementary Medicine Database (AMED), EMBASE, Web of Science, PubMed, and Cochrane Library databases to October 1, 2017, were searched to collect the studies. The data analysis was performed using RevMan 5.3 software. Totally 20 clinical trials with 774 (the experimental group: 447 cases; the control group: 327 cases) HCC patients were finally included in this meta-analysis. Meta-analysis results showed that Aidi injection combined with TACE can, to some extent, enhance the clinical effect and improve the overall survival. Meanwhile, it can increase HCC patients' quality of life. Additionally, Aidi injection plus TACE can reduce adverse events including leukopenia, gastrointestinal reaction, and liver damage in HCC patients (all P < 0.05). Therefore, Aidi injection plus TACE may significantly enhance the clinical effect, suggesting that the combination of TCM and western medicine is promising. The exact outcome needs rigorously designed performances, multicenter, and large randomized controlled trials.

Tumor necrosis factor-308 polymorphism with the risk and prognosis of non-Hodgkin lymphomas: a meta-analysis study.

BACKGROUND: Tumor necrosis factor-308 (TNF-308) was implied to be associated with the development of non-Hodgkin lymphoma (NHL). The aim of this meta-analysis study was to investigate the association of TNF-308A polymorphism with the susceptibility to, and prognosis of, NHL. METHODS: PubMed, Web of Science, Elsevier, HighWire, Scopus, and Google Scholar were searched up to May 2015. The association of TNF-308 polymorphism with the risk of NHL and prognosis was assessed by odds ratio and hazard ratio, respectively. RESULTS: Overall, TNF-308G>A polymorphism increased the risk of NHL, B-cell lymphomas (BCL), and T-cell lymphomas and decreased the risk of follicular lymphomas. In stratified analysis, increased risk of BCL and diffuse large B-cell lymphomas (DLBCL) were observed in Caucasians and population-based studies, whereas decreased risk of NHL, BCL, and DLBCL were detected in Asians and hospital-based studies. Furthermore, pooled results of 1,192 patients with NHL from five studies suggested that TNF-308A was correlated with shorter progression-free survival and overall survival in patients with NHL, BCL, and DLBCL. CONCLUSION: Current evidence indicated that TNF-308A polymorphism was significantly associated with the risk and prognosis of NHL. Future studies should further confirm these associations in other NHL subtypes and ethnicities.