Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation

ABSTRACT Purpose: To delve into the influence of paeoniflorin (PA) on abating primary biliary cholangitis (PBC)-induced liver fibrosis and its causative role. Methods: Our team allocated the mice to control group, PA group, PBC group and PBC+PA group. We recorded the weight change of mice in each group. We used Masson staining for determining liver fibrosis, immunofluorescence staining for measuring tumor necrosis factor-α (TNF-α) expression, quantitative real-time polymerase chain reaction (qRT-PCR) for assaying related gene expression, as well as Western blot for testing related protein expression. Results: The weight of PBC model mice declined. Twenty-four weeks after modeling, the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) in PBC mice reached 100%. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), laminin (LN), procollagen type III (PC III), and malondialdehyde (MDA) contents saliently waxed (p<0.01). Meanwhile, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity patently waned (p<0.01). Liver fibrosis levels were flagrantly higher (p<0.01), and TNF-α, NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-18 (IL-18), and interleukin-1β (IL-1β) protein or gene expression were manifestly up-regulated (p<0.01). PA could restore the weight of PBC mice, strikingly restrain the positive expression of AMA-M2, and down-regulate serum ALP, ALT, AST, HYP, LN, PC III, MDA in PBC mice (p<0.01). PA could also significantly up-regulate SOD and GSH-px levels (p<0.01), down-regulate IL-1β, IL-18, caspase-1, NLRP3, and TNF-α protein or gene expression in PBC mice (p<0.01) and inhibit liver fibrosis levels (p<0.01). Conclusions: PA can reduce PBC-induced liver fibrosis in mice and may function by curbing the formation of NLRP3.

Regulatory effect of hsa-miR-150-5p on malignant behaviors of glioblastoma U-251MG cells by targeting HIF1α / 中国肿瘤生物治疗杂志

@#Objective: To explore the effect and possible mechanisms of has-miR-150-5p targeting HIF1α to regulate malignant biological behaviors of glioblastoma (GBM) U-251MG cells. Methods: Real-time quantitative PCR (RT-PCR) was used to detect the expression of miR-150-5p and hypoxia inducible factor 1 (HIF1α) in U-251MG cells. Luciferase report assay was carried out to verify the biological relationship between miR-150-5p and HIF1α and their biological functions in U-251MG cells. The protein expressions of miR150-5pand HIF1α in U-251MG cells were detected by western blotting. The ability of cell migration was detected by wound healing test and cell invasion ability was detected by transwell test. Results: After miR-150-5p mimic transfection, the mRNA expression of HIF1α was significantly reduced in U-251MG cells (P<0.01). Bioinformatics prediction and luciferase reporter assay demonstrated that miR-150-5p down-regulated HIF1α through directly binding to HIF1α 3’-untranslated region (3’-UTR) (all P<0.05). In U-251MG cells, miR-150-5p over-expression significantly inhibited HIF1α expression, cell invasion and migration (all P<0.05). Conclusion: miR150-5p inhibits cell invasion and metastasis through negative regulation of HIF1α, indicating that miR-150-5p and HIF1α were both potential therapeutic targets for glioblastoma.

Trend analysis of serum uric acid levels in health check-up subjects of Tianjin municipality 2007-2015 / 中华全科医师杂志

Objective To assess the changing trend of serum uric acid (SUA) levles in health check-up subjects of Tianjin municipality 2007-2015.Method Data were collected from 266 043 subjects receiving annual health check-up from 2007 to 2015 in Tianjin municipality.Changing trends of SUA levels and incidence of hyperuricemia were analyzed during the 9 year period.Results From 2007 to 2015 SUA levels in males were increased from (347 ± 73) μmol/L to (373-± 78) μmol/L,while in females were increased from(253 ± 59) μmol/L to (267-± 61) μmol/L.The trend test showed that both for men and woinen the incidence of hypemricemia was increased in each year (men:x2 =270.30,women:x2 =15.10,both P =0.00).The incidence of hyperuricemia by each year was increased more markedly in men than that in women (x2 level:194.80-1 877.00,all P =0.00).The incidence of hyperuricemia in young adults (20-39) was higher than that in middle-ages (40-59),and the latter was higher than that in elderly (＞ 60).For the 7-year (2009-2015) incidence of hyperuricemia in young and middle-aged men,the trend test showed statistical siganificance (x2 level:14.11-233.90,all P =0.00).By contrast,the incidence hyperuricemia in women was increased with aging,and for the 9-year incidence of hyperuricemia in young women,the trend test showed statistical siganificance (x2 level:115.30-480.20,all P =0.00).Conclusion The incidence rates of hyperuricemia are high in Tianjin health check-up subjects,especiallly in young males and old females.There is a time trend of increasing incidence of hyperuricemia in the young and middle-aged subjects.The results indicate that the prevention and control of hyperuricemia in Tianjin are of clinical and social significance.