To research into the significance of HLA-DRB1 alleles in the immune response to hepatitis B vaccine, HLA-DRB1 alleles of 84 cases with Hepatitis B vaccine non or hypo-responses were detected with polymerase chain reaction sequence-specific primer(PCR-SSP), and were compared with 78 cases with medium or hyper-responses. According to the research, the allelic frequencies of HLA-DRB1*12, 14, 15 in non or hypo-responders group is 4.76%, 23.8% and 7.14% respectively, and in medium or hyper-responders group 23.1%, 5.13% and 24.4%, which shows significant differences between the two groups (P<; 0.05); while the allelic frequencies of HLA-DRB1*07, 09, 11, 13 show no significant differences between the two groups(P >; 0.05). Thus, there may exist certain relevance between different allelic frequencies of HLA-DRB1 and hepatitis B vaccine immune response. Therefore, the analysis of allelic frequencies of HLA-DRB1 will have great effect on the hepatitis B vaccine immune response system.
c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125's protection against DN. To test the role of NRF2 in SP600125's effect, streptozotocin-induced C57BL/6 wild-type (WT) and Nrf2-knockout (KO) diabetic mice were treated in the presence or absence of SP600125, for 24 weeks. To explore the mechanism by which SP600125 activates NRF2, mouse mesangial cells (MMCs) were treated with high glucose (HG), in the presence or absence of either SP600125 or JNK siRNA. SP600125 significantly attenuated the diabetes-induced renal oxidative stress, inflammation, fibrosis, pathological change and dysfunction in the WT, but not the Nrf2 KO mice. SP600125 inactivated JNK, inhibited kelch-like ECH-associated protein 1 expression, preserved NRF2 protein and facilitated its nuclear translocation in the kidneys of the WT mice, the effects of which were similarly produced by either SP600125 or JNK siRNA in HG-treated MMCs. Further, both SP600125 and JNK siRNA alleviated HG-induced mesangial oxidative stress and expression of inflammatory and fibrotic genes. The present study demonstrates that NRF2 is required for SP600125's protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced Keap1 expression.
The involvement of Circular RNA SMARCA5 (cSMARCA5) in several types of cancer has been reported; however, its role in hepatocellular carcinoma (HCC) is unclear. The presented research aimed to explore the expression level of cSMARCA5 in HCC tissues and evaluate the association between cSMARCA5, prognosis, and radiotherapy resistance for patients with HCC.This study was designed as a case controlled study and enrolled 106 HCC patients. HCC and paired non-tumor samples were collected from HCC patients. Gene expression was analyzed by RT-qPCR. The association between the expression level of cSMARCA5 and prognosis value and radiotherapy resistance for patients with HCC was analyzed by Kaplan-Meier survival curve and Multivariate Cox analysis.Compared to paracancerous tissue, cSMARCA5 demonstrated higher expression in the tumor tissues (p<0.0001).Higher expression of cSMARCA5 is a risk factor in 3-year overall survival (OS) for HCC patients (HR=1.798, 95%CI: 1.165~3.231, p=0.0321). Multivariate analysis showed that higher expression of cSMARCA5 was related to PVTT (HR=2.136, 95%CI: 1.130~5.218), AFP (>400ng/ml) (HR=2.335, 95%CI: 1.247~5.661), tumor size (>5cm) (HR=3.017, 95%CI: 1.477~5.659), poor histopathologic grading (HR=3.344, 95%CI: 2.175~6.143), and multiple tumor number (HR=2.875, 95%CI: 1.453~3.884). We also found that radiotherapy resistance was related to AFP (>400ng/ml) (OR=2.125, 95%CI: 1.015~3.348), tumor size (>5cm) (OR=2.857, 95%CI: 1.665~4.978), poor histopathologic grading (OR=2.463, 95%CI: 1.389~4.446), multiple tumor number (OR=2.332, 95%CI: 1.538~3.887), and high expression of cSMARCA5 (OR=3.574, 95%CI: 1.663~5.932).CircRNA-SMARCA5 is significantly increased in HCC tissues and promotes radiotherapy resistance. More importantly, higher expression level of cSMARCA5 is related to a poorer 3-year OS for patients with HCC.
A case-control study was carried out to explore the clonality of the T cell receptor Vbeta repertoires in complementarity determining region 3 in CD8(+) T lymphocyte of patients infected with HBV. The enrollment included 20 patients and 20 healthy donors. Multiple PCR amplification was applied to amplify many pieces of the T cell receptor Vbeta gene in complementarity determining region 3. High resolution agarose gel electrophoresis was employed to detect the clonality. By statistics, the percentage of monoclonal TCR Vbeta9 and Vbeta14 in CD8(+) T cell in patients' group were significantly higher than those in normal controls, 70.0 % vs 25.0 %, 85.0 % vs 30.0 % (p<; 0.01). The results showed that persons infected with HBV have the cloning changes of the T cell receptor Vbeta repertoire in CD8(+) T cell.
Objective Clinical significance of DNA ploid variability in goiter and thyroid cancer.Methods DNA ploid and cell cycle are analyzed by flow cytometry among 34 goiters(22 nodular goiters,12 diffuse goiters) and 29 thyroid cancers(20 differentiated thyroid cancers,9 undifferentiated thyroid cancers).Results DNA heteroploid percentage of thyroid cancer group(differentiated and undifferentiated thyroid cancers) is much highter than that of goiter group(nodular and diffuse goiters)(P0.05),and the numbers of DNA euploid cells at stage S in thyroid cancer groupl differentiated and undifferentiated thyroid cancers is also much highter than that of goiter group(nodular and diffuse goiters)(P0.05).There are no differences of DNA heteroploid percentage between undifferentiated and differentiated thyroid cancer group(P0.05),and some differences of the numbers of DNA euploid cells at stage S between undifferentiated and differentiated thyroid cancer group(P0.05)were observed.Conclusions DNA ploid and cell cycle would be availability to the early diagnosis of thyroid cancer.
Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling has been found in several types of human cancer, including hepatocellular carcinoma (HCC). NVP-BEZ235 is a novel, orally bioavailable dual PI3K/mTOR inhibitor that has exhibited promising activity against HCC in preclinical models. Autophagy is a cellular lysosomal degradation pathway essential for the regulation of cell survival and death to maintain homeostasis. This process is negatively regulated by mTOR signaling and often counteracts the efficacy of certain cancer therapeutic agents. In this study, we explored the role of autophagy in apoptosis induced by NVP-BEZ235 in two HCC cell lines, Hep3B and PLC/PRF/5, and identified the mechanism of combinatorial treatment. NVP-BEZ235 was effective in inhibiting the growth of the two HCC cell lines possibly though induction of apoptosis. NVP-BEZ235 also potently increased the expression of LC3-II and decreased the expression of p62, indicating induction of autophagy. When NVP-BEZ235 was used in combination with Atg5 siRNA or the autophagy inhibitor 3-methyladenine (3-MA), enhancement of the inhibitory effects on the growth of HCC cells was detected. In addition, enhanced induction of apoptosis was observed in cells exposed to the combination of NVP-BEZ235 and Atg5 siRNA or 3-MA. Thus, induction of autophagy by NVP-BEZ235 may be a survival mechanism that counteracts its anticancer effects. Based on these data, we suggest a strategy to enhance the anticancer efficacy of BEZ235 by blockade of autophagy. Thus, our study provides a rationale for the clinical development of combinations of NVP-BEZ235 and autophagy inhibitors for the treatment of HCC and other malignancies.
HCV genotypes were classified by non-structural region 5 (NS5) of HCV genome polymerase chain reaction (PCR) product restriction endonuclease technique. Resutls, The result of HCV genotyping suggested that 45 cases belong to type II, 28 type III. In type II of hepatitis C virus infection, 31 patients had chronic hepatitis and 14 liver cirrhosis; In type III of HCV infection, 26 suffered from chronic hepatitis and 2 liver cirrhosis. The incidence rate of cirrhosis in HCV type II patients was much highter than that in HCV type III patients. All patients were treated with interferon-alpha 2b (IFN-alpha2b).
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