Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage.

Interleukin-10 gene promoter polymorphism and susceptibility to liver cirrhosis.

BACKGROUND/AIMS: Liver cirrhosis is the end-stage of various liver diseases, which has a poor prognosis and determined by deterioration of hepatic functional capacity and consecutive development of hepatic complications. We investigated the role of IL-10-592 A/C, IL-10-819 C/T and IL-10-1082 A/G gene polymorphisms on the development of liver cirrhosis. METHODOLOGY: A 1:2 matched case-control study was conducted, including 266 patients from 302 Military Hospital. Genotyping of IL-10-592 A/C, IL-10-819 C/T and IL-10-1082 A/G were performed in a 384-well plate format on the Sequenom MassARRAY platform. RESULTS: Multivariate regression analyses showed that subjects carrying the IL-10-592 CC variant had a significant increased risk of liver cirrhosis (OR: 1.83, 95% Cl: 1.10-3.03), and IL-0-592 A/C showed a significant increased risk in recessive model (OR: 1.97, 95% CI: 1.15-3.45). We found those carrying IL-10-592 CC genotype had a heavy increased risk of liver cirrhosis in those with positive chronic hepatitis B, with an OR (95% CI) of 2.46 (1.35-4.42), and a significant interaction was observed between the IL-10-592 A/C genotype and chronic hepatitis B infection (P = 0.036). Those carrying IL-10-819 C/T and IL-10-1082 A/G variants had non-significant increased risk of liver cirrhosis. CONCLUSIONS: Our study demonstrates that IL-10-592A/C gene polymorphism would enhance the risk for liver cirrhosis, and this gene variant has interaction with chronic hepatitis B infection in Asian population.

Risk factors related to low-level viraemia in chronic hepatitis B patients receiving entecavir treatment.

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-α in NAs-suppressed chronic hepatitis B patients.

Objective: The aim of this study was to explore the profile of cytokine changes during the combination therapy with pegylated interferon alpha (PEG-IFN-α) and its relationship with HBsAg loss in nucleos(t)ide analogs (NAs)-suppressed chronic hepatitis B patients. Methods: Seventy-six patients with chronic hepatitis B with HBsAg less than 1,500 IU/ml and HBV DNA negative after receiving ≥ 1-year NAs therapy were enrolled. Eighteen patients continued to take NAs monotherapy (the NAs group), and 58 patients received combination therapy with NAs and PEG-IFN-α (the Add-on group). The levels of IFNG, IL1B, IL1RN, IL2, IL4, IL6, IL10, IL12A, IL17A, CCL2, CCL3, CCL5, CXCL8, CXCL10, TNF, and CSF2 in peripheral blood during treatment were detected. Results: At week 48, 0.00% (0/18) in the NAs group and 25.86% (15/58) in the Add-on group achieved HBsAg loss. During 48 weeks of combined treatment, there was a transitory increase in the levels of ALT, IL1RN, IL2, and CCL2. Compared to the NAs group, CXCL8 and CXCL10 in the Add-on group remain higher after rising, yet CCL3 showed a continuously increasing trend. Mild and early increases in IL1B, CCL3, IL17A, IL2, IL4, IL6, and CXCL8 were associated with HBsAg loss or decrease >1 log, while sustained high levels of CCL5 and CXCL10 were associated with poor responses to Add-on therapy at week 48. Conclusions: The serum cytokine change profile is closely related to the response to the combination therapy with PEG-IFN-α and NAs, and may help to reveal the mechanism of functional cure and discover new immunological predictors and new therapeutic targets.

Anti-fibrotic effects of the Masson pine pollen aqueous extract on hepatic fibrosis rat model.

AIM: To observe the antifibrotic effects of Masson Pine Pollen aqueous extract. METHODS: Adult Sprague-Dawley rats were randomly divided into control (CG), hepatic fibrosis model (MG), MPPAE low dose (LG), MPPAE high dose (HG), and MPP original powder (MPPOP; OG) groups. Each group was treated with specific protocols and sacrificed 8 weeks later. Multiple indicators such as serum transaminase, HE staining of the liver tissue, and relevant indexes to fibrosis were determined. RESULTS: Severe hyperplasia of fibrous connective tissues was observed in livers of the MG group rats, while aspartate transaminase and alanine transaminase levels and collagen content obviously increased, superoxide dismutase and glutathione peroxidase activities and MMPs expression decreased, malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine concentrations increased, while mRNA expressions of hepatic stellate cell (HSC)-related cytokines such as transforming growth factor-ß1 and platelet-derived growth factor, transcription factors such as nuclear factor-κB p65, and signaling protein α-smooth muscle actin were all increased significantly. CONCLUSIONS: MPPAE effectively inhibited the fibrotic process in this CCl4-induced hepatic fibrosis rat model. It may be associated with synergic functions of antioxidant activity, inhibitory activity on HSC proliferation, collagen synthesis, and MMPs expression induction.

[Study of the subcellular location of the human gene 6 transactivated by nonstructeral protein 5a of hepatitis C virus].

OBJECTIVE: To found the subcellular location of the human gene 6 transactivated by nonstructural protein 5A of hepatitis C virus (NS5ATP6). METHODS: Green fluorescent protein (GFP) expression vector pEGFP- NS5ATP6 was established. The pEGFP- NS5ATP6 was transfected into HepG2 cells, and analyze the subcellular location of the proteins expressed by NS5ATP6 through Green fluorescent microscopy after 24 hours. RESULTS: The pEGFP- NS5ATP6 gene was successful cloned, NS5ATP6 can express protein in cells and subcellularly located in cell plasma. CONCLUSION: NS5ATP6 can express protein, and the protein expressed by NS5ATP6 subcellularly located in cell plasma.

[Efficacy and safety of Fufang Biejia Ruangan tablet in patients with chronic hepatitis B complicated with hepatic fibrosis].

OBJECTIVE: To study the clinical therapeutic effects and safety of Fufang Biejia Ruangan tablet (FBRt) in patients with chronic hepatitis B complicated with hepatic fibrosis. METHODS: Totally 420 patients were randomly divided into two groups, FBRt group (300 cases) were treated with Fufang Biejia Ruangan tablets and control group (120 cases) were treated with He Luo Shu Gan capsule, the patients in both groups were treated for 6 months. RESULTS: The cure rate and total effective rate of FBRt group were significantly higher than those of control group (55.67 percent and 81.67 percent vs. 15.8 percent and 60.00 percent, P less than 0.01). CONCLUSION: Fufang Biejia Ruangan tablet could alleviate clinical symptoms and hepatic fibrosis. Fufang Biejia Ruangan tablet is effective and safe in treatment of patients with chronic hepatitis B complicated with liver fibrosis.

[Analysis on factors related to X-ray outcomes in 93 SARS patients].

OBJECTIVE: To study the related factors of the X-ray outcomes in recovered SARS patients. METHODS: The X-ray results of 93 patients with SARS were studied retrospectively. The possible related factors analyzed were age, sex, body temperature at onset, range of the lesion, glucocorticoid administration time. The data were analyzed by chi square test. RESULTS: Among all the patients with abnormal X-ray result, 19 were male (54.29%), 16 (45.71%) were female, P > 0.01; 7 (58.33%) were above the age of 45; 28 (34.57%) were below the age of 45, P > 0.01; hyperpyrexia (>/= 39), 26 (50.00%), below 39, 9 (21.95%); multiple-lesion, 22 (52.38%), mono-lesion, 13 (25.49%), P < 0.01; glucocorticoid administration time within 5 days, 22 (38.60%) after 5 days, 12 (33.33%), P > 0.01; within 7 days, 21 (30.00%), after 7 days, 14 (60.87%), P < 0.01. CONCLUSION: The X-ray results of SARS were closely related to the severity of the disease (hyperpyrexia and bilateral lung field lesion). There was no significant correlation between X-ray result and the age or sex of the patients. Early use of glucocorticoid (within 5 days after onset), had no remarkable influence on the X-ray result. It was noted, however, the incidence of residual lesion in lung obviously increased if glucocorticoid was administered after 7 days of onset.