ABSTRACT
Objective·To investigate the prevalence of pre-existing direct-acting antiviral agents (DAAs) resistance associated variants (RAVs) in genotype 1 hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients.Methods·All NS3 and NSSB HCV sequences in genotype 1 HCV/HIV co-infected patients were retrieved from NCBI GenBank database.And sequences were aligned and analyzed using software MEGA 5.0.Results·In total,the overall prevalence of DAAs RAVs in NS3 region was high (26.06％ and 38.18％,respectively),no matter in genotype 1a or genotype 1b.In genotype 1a,the high prevalence of RAVs mainly presented in the position Q80 (8.45％).In genotype lb,S122 RAV was most observed (36.36％).It is worth noting that,RAVs in NS5B region were rare observed (0.77％) in this study,especially as no RAV was detected in any sequence of genotype 1a patients.Conclusion·The prevalence of pre-existing RAVs is high in NS3 region but rare in NS5B region in HCV/HIV co-infected patients,suggesting that NS5B inhibitors based combination regions are a better choice for HCV/HIV co-infected patients.
ABSTRACT
To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.
ABSTRACT
This paper was aimed to investigate the protective effects of luteolin (Lut) against acetaminophen（APAP）-induced damage in L02 liver cells. CCK-8 was used to detect the cell activation of L02 cells treated by different Lut. The concentration and time of APAP induced L02 cell damage was screened. The effect of Lut on APAP induced apoptosis of L02 cells was detected by cell morphological observation, CCK-8 assay and flow cytometry. The contents of MDA, GSH and SOD activity in cell supernatant were detected by colorimetric assay. The expression of apoptosis-related genes Bax, Bcl-2 and caspase-3 was detected by RT-PCR. The results showed that Lut in 2.5-40 μmol•L⁻¹ range does not affect the activity of L02 cells; 12 mmol•L⁻¹ APAP incubated with L02 cell 12 h to establish damage model. Compared with the model group, the cell status of Lut group was significantly improved, the cell body was increased, the adherence ability was recovered, and the apoptosis rate was obviously decreased. MDA content decreased significantly (P<0.05, P<0.01), GSH and SOD activity significantly increased (P<0.05, P<0.01), at the same time, it could up-regulate expression of Bcl-2 mRNA and down-regulate the expression of Bax and caspase-3 mRNA. In conclusion,Lut has protective effect on APAP induced L02 cell injury, and its mechanism may be related to the reduction of oxidative stress and inhibition of apoptosis.
ABSTRACT
Objective: To evaluate the effects of ethanol extract of Hedyotis Diffusae Herba (EEHDH) on chronic ulcerative colitis (UC) and the inhibition on intestinal tissue abnormalities hyperplasia. Methods: The C57 mice were randomly divided into five groups: normal, DSS, low-, mid-, and high-dose (2.5, 10.0, and 20.0 g/kg) EEHDH groups. The DSS-induced UC model was employed. The body weight, hematochezia, and stool property were recorded to evaluate the change of physiology daily. The pathology changes of colonic mucosa tissue of mice were evaluated by HE staining, and the expression changes of inflammatory factors IL-6 and TNF-α in serum and tissues were detected by ELISA and real-time PCR, as well as immunohistochemistry was used to analyze the positive rate of Ki67 of the nuclear antigen in epithelial cells of colonic tissues. Results: Compared to the model group, the treatment with mid- and high-dose EEHDH has a relatively slower weight loss and a faster recovery when the stimulation is gone; Meanwhile the symptoms of diarrhea and hematochezia are significantly improved, the pathological damage and intestinal tissue dysplasia are alleviated; The inflammatory factors IL-6, TNF-α, and the positive rate of Ki67 are significantly decreased. Conclusion: EEHDH could attenuate DSS-induced UC and decrease pathological injury, inflammation invasion, and abnormalities hyperplasia, by inhibiting the expression of inflammatory cytokines, such as IL-6 and TNF-α, which indicates that EEHDH is of great value in the treatment of UC and colitis-associated cancer.