Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

[Changes in Wnt pathway inhibiting factors in nitrosamine-induced esophageal precancerosis lesions and effect of gexia zhuyu decoction].

OBJECTIVE: To discuss the changes in Wnt pathway inhibiting factors in esophageal precancerosis lesions induced by methyl benzyl nitrosamine (MBNA) and the effect of Gexia Zhuyu decoction. METHOD: Wistar rats were subcutaneously injected with MBNA (3.5 mg x kg(-1) for twice per week to establish the model. Since the 1st day after the model establishment, they were orally administered with Gexia Zhuyu decoction (16, 8 mg x kg(-1)). At the 10th week, esophageal tissues were collected to observe the pathological changes of esophageal mucosa, detect SFRP1, sFRP4, Axin1, Axin2 and GSK-3ß mRNA levels.by fluorescent quantitation PCR analysis and ß-catenin protein level by Western blotting. RESULT: Being induced by MBNA, rats in the model group showed slight atypical hyperplasia in the histopathological examination. Compared with the normal group, Gexia Zhuyu decoction dose high and low groups showed no significant pathomorphological and histological changes. The model group showed lower gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and higher ß-catenin protein expression level (P < 0.01) than the normal control group. The Gexia Zhuyu decoction low dose group showed higher gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and lower ß-catenin protein expression level (P < 0.01) than the normal control group. CONCLUSION: Up-regulated ß-catenin protein level and down-regulated Wnt pathway could enhance Wnt pathway activity of MBNA-induced esophageal precancerous lesions. Gexia Zhuyu decoction could down-regulate the ß-catenin protein level and up-regulate the transcription level of Wnt pathway inhibiting factors, but could not block MBNA-induced esophageal precancerosis lesions.

Clinical evaluation of serum concentrations of intercellular adhesion molecule-1 in patients with colorectal cancer.

AIM: To investigate the correlation between the serum soluble intercellular adhesion molecule-1 (sICAM-1) and the clinicopathologic features and to evaluate the possible prognostic significance of sICAM-1 concentration in colorectal cancer. METHODS: A total of 56 patients (mean age 57.3 years) having transitional cell carcinoma of the colorectal and 25 control patients (mean age 42.6 years) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery. Sera were obtained by centrifugation, and stored at -80 degrees C until assay. Serum concentrations of ICAM-1 were measured with enzyme-linked immunoassay. Differences between the two groups were analyzed by Student's t-test. RESULTS: No significant increase of serum sICAM-1 could be demonstrated in the Dukes A(1) patients (352.63+/-61.82 mug/L) compared to the control group (345.72+/-49.81 microg/L, P>0.05), Dukes A(1) patients (352.63+/-61.82 microg/L) compared to Dukes A(2,3) patients (491.17+/-86.36 microg/L, P<0.05). Furthermore, the patients with Dukes B had significantly higher serum concentrations of sICAM-1 than those of the control group (496.82+/-93.04 microg/L vs 345.72+/-49.81 microg/L, P<0.01). Compared with Dukes A(2,3), B colorectal cancer patients, patients with more advanced clinical stage (Dukes C and D) had higher levels of sICAM-1 (743.68+/-113.74 microg/L vs 491.17+/-86.36 microg/L and 496.82+/-93.04 microg/L, P<0.001). The difference was statistically significant in sICAM-1 levels between patients with positive lymph node status and those without lymph node involvement (756.25+/-125.57 microg/L vs 445.62+/-69.18 microg/L, P<0.001). Patients with poorly differentiated colorectal cancer had a higher level of sICAM-1 than those with differentiated and highly differentiated cancer (736.49+/-121.97 microg/L vs 410.23+/-67.47 microg/L, P<0.001). CONCLUSION: In this study, serum ICAM-1 levels were found to be related to tumor presence, clinical stages, and grade. Increased ICAM-1 in patients with colorectal cancer which should be considered when the diagnostic and/or prognostic usefulness of soluble ICAM-1 is to be evaluated. sICAM-1 should prove useful for monitoring malignant disease stage and for evaluating the effectiveness of various therapeutic approaches for colorectal carcinomas.