RESUMO
Background: Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI). Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms. Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined. Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1ß, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI. Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.
RESUMO
BACKGROUND: PRC1 (Protein regulator of cytokinesis 1) regulates microtubules organization and functions as a novel regulator in Wnt/ß-catenin signaling pathway. Wnt/ß-catenin is involved in development of liver fibrosis (LF). We aim to investigate effect and mechanism of PRC1 on liver fibrosis. METHODS: Carbon tetrachloride (CCl4)-induced mice LF model was established and in vitro cell model for LF was induced by mice primary hepatic stellate cell (HSC) under glucose treatment. The expression of PRC1 in mice and cell LF models was examined by qRT-PCR (quantitative real-time polymerase chain reaction), western blot and immunohistochemistry. MTT assay was used to detect cell viability, and western blot to determine the underlying mechanism. The effect of PRC1 on liver pathology was examined via measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hydroxyproline, as well as histopathological analysis. RESULTS: PRC1 was up-regulated in CCl4-induced mice LF model and activated HSC. Knockdown of PRC1 inhibited cell viability and promoted cell apoptosis of activated HSC. PRC1 expression was regulated by Wnt3a signaling, and PRC1 could regulate downstream ß-catenin activation. Moreover, PRC1 could activate glioma-associated oncogene homolog 1 (GLI1)-dependent osteopontin expression to participate in LF. Adenovirus-mediated knockdown of PRC1 in liver attenuated LF and reduced collagen deposition. CONCLUSIONS: PRC1 aggravated LF through regulating Wnt/ß-catenin mediated GLI1-dependent osteopontin expression, providing a new potential therapeutic target for LF treatment.
RESUMO
ABSTRACT Background: The Montreal Cognitive Assessment (MoCA) is used for screening mild cognitive impairment (MCI), and the Beijing version (MoCA-BJ) is widely used in China. We aimed to develop a computerized tool for MoCA-BJ (MoCA-CC). Methods: MoCA-CC used person-machine interaction instead of patient-to-physician interaction; other aspects such as the scoring system did not differ from the original test. MoCA-CC, MoCA-BJ and routine neuropsychological tests were administered to 181 elderly participants (MCI = 96, normal controls [NC] = 85). Results: A total of 176 (97.24%) participants were evaluated successfully by MoCA-CC. Cronbach's α for MoCA-CC was 0.72. The test-retest reliability (retesting after six weeks) was good (intraclass correlation coefficient = 0.82; P < 0.001). Significant differences were observed in total scores (t = 9.38, P < 0.001) and individual item scores (t = 2.18-8.62, P < 0.05) between the NC and MCI groups, except for the score for "Naming" (t = 0.24, P = 0.81). The MoCA-CC total scores were highly correlated with the MoCA-BJ total scores (r = 0.93, P < 0.001) in the MCI participants. The area under receiver-operator curve for the prediction of MCI was 0.97 (95% confidence interval = 0.95-1.00). At the optimal cut-off score of 25/26, MoCA-CC demonstrated 95.8% sensitivity and 87.1% specificity. Conclusion: The MoCA-CC tool developed here has several advantages over the paper-pencil method and is reliable for screening MCI in elderly Chinese individuals, especially in the primary clinical setting. It needs to be validated in other diverse and larger populations.
