Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the pac...Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into capsids.The present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying mechanism.Methods:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression levels.We analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated cells.We knocked down ISG15 and then monitored HBsAg and HBeAg expression levels.We analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated cells.We used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg expression.HBV virus was collected from HepAD38.7 cell culture medium.Results:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell lines.ISG15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 cells.Dopamine-treated cells activated the JAK/STAT pathway,which upregulated ISG15 expression.In the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 axis.Conclusions:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.展开更多
AIM： To investigate the antiviral effect of beta-L- enantiomer of 2;3＇-didehydro-2＇,3″-dideoxyadenosine （13-L-D4A） on 2.2.15 cells transfected with the hepatitis B virus （HBV） genome.METHODS： Lamivudine （3TC...AIM： To investigate the antiviral effect of beta-L- enantiomer of 2;3＇-didehydro-2＇,3″-dideoxyadenosine （13-L-D4A） on 2.2.15 cells transfected with the hepatitis B virus （HBV） genome.METHODS： Lamivudine （3TC） as a positive control. Then, HBV DNA in treated 2.2.15 cells and the Hepatitis B surface antigen （HBsAg） in the culture supernatants were detected to determine the inhibitory effect of β-L- D4A. At the same time, 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） was used to detect the survival ratio of 2.2.15 cells.RESULTS： β-L-D4A has a dose-dependent inhibitory effect on HBV DNA replication; this effect was apparent when the concentration was above 1 mol/L. When β-L- D4A was at the highest concentration, 100 mol/L, the HBsAg inhibition ratio was above 50%. The Therapeutic index （TI） of β-L-D4A was above 2.1.CONCLUSION： β-L-D4A has a dose-dependent inhibitory effect on the replication of HBV DNA and the secretion of HBsAg at low toxicity,展开更多
Background： Higher hepatitis B surface antigen （HBsAg） facilitates hepatitis C virus （HCV） clearance inpatients with hepatitis B virus （HBV）/HCV co-infection. We investigated the effect of exogenous HBsAgon the...Background： Higher hepatitis B surface antigen （HBsAg） facilitates hepatitis C virus （HCV） clearance inpatients with hepatitis B virus （HBV）/HCV co-infection. We investigated the effect of exogenous HBsAgon the inhibition of HCV replication mediated by natural killer （NK） cells.展开更多
乳腺癌是目前全球发病率最高的恶性肿瘤之一,其中三阴性乳腺癌(triple-negative breast cancer,TNBC)占浸润性乳腺癌的10%~20%。TNBC是一种高度异质性和侵袭性的恶性肿瘤,与其他乳腺癌亚型相比,TNBC治疗手段相对匮乏,预后较差,临床上亟...乳腺癌是目前全球发病率最高的恶性肿瘤之一,其中三阴性乳腺癌(triple-negative breast cancer,TNBC)占浸润性乳腺癌的10%~20%。TNBC是一种高度异质性和侵袭性的恶性肿瘤,与其他乳腺癌亚型相比,TNBC治疗手段相对匮乏,预后较差,临床上亟待寻找可用于精准治疗及提高预后的新靶点。人滋养层细胞表面抗原2(trophoblast cell surface antigen 2,Trop2)在三阴性乳腺癌及多种恶性肿瘤中高表达,其通过细胞表面受体信号在肿瘤细胞的增殖、黏附、侵袭、转移中发挥重要作用,以其为靶点的抗体偶联药物(antibody-drug conjugate,ADC)在临床上中具有广阔的应用前景。本文对靶向Trop2的ADC治疗TNBC的临床研究进展予以综述,为靶向Trop2的ADC在TNBC治疗中的临床应用和提高患者生存预后方面提供参考。展开更多
Aim: We aimed to elucidate whether beta2-glycoprotein I (β2GPI) cooperation with hepatitis B surface antigen (HBsAg) promoted hepatocellular carcinogenesis enhanced by the lipopolysaccharide (LPS) via activation of n...Aim: We aimed to elucidate whether beta2-glycoprotein I (β2GPI) cooperation with hepatitis B surface antigen (HBsAg) promoted hepatocellular carcinogenesis enhanced by the lipopolysaccharide (LPS) via activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and expression of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), and alpha fetal protein (AFP) in liver cancer cells. Methods: Liver cancer cells (SMMC-7721) were transiently transfected with β2GPI and/or HBsAg and were subjected to LPS treatment. TNF-α, IL-1β, and AFP expression were measured in all groups by ELISA. NF-κB activation was assessed by non-radioactive electrophoretic mobility shift assay (EMSA) and was quantified in all groups. Results: Cells transfected with β2GPI and/or HBsAg induced activation of NF-κB, with the highest activation seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Non-transfected cells treated with LPS exhibited lower activation compared to either β2GPI- or HBsAg-transfected cells with LPS treatment. In addition, cells transfected with β2GPI and/or HBsAg induced significantly increased expression of TNF-α, IL-1β and AFP, with the highest levels again seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Conclusion: These observations suggest that the activity of NF-κB induced by β2GPI and HBsAg was enhanced by LPS. Expression of TNF-α, IL-1β and AFP increased in β2GPI and HBsAg cotransfected liver cancer cells.展开更多
基金supported by a grant from the National Natural Science Foundation of China(82170612)Guangzhou Science and Technology Program Key Projects(2023B01J1007)National Natural Science Foundation of China(No.81870597).
文摘Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into capsids.The present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying mechanism.Methods:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression levels.We analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated cells.We knocked down ISG15 and then monitored HBsAg and HBeAg expression levels.We analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated cells.We used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg expression.HBV virus was collected from HepAD38.7 cell culture medium.Results:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell lines.ISG15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 cells.Dopamine-treated cells activated the JAK/STAT pathway,which upregulated ISG15 expression.In the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 axis.Conclusions:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.
基金Grants from the National Natural Science Foundation of China, Key Program, No. 30330680
文摘AIM： To investigate the antiviral effect of beta-L- enantiomer of 2;3＇-didehydro-2＇,3″-dideoxyadenosine （13-L-D4A） on 2.2.15 cells transfected with the hepatitis B virus （HBV） genome.METHODS： Lamivudine （3TC） as a positive control. Then, HBV DNA in treated 2.2.15 cells and the Hepatitis B surface antigen （HBsAg） in the culture supernatants were detected to determine the inhibitory effect of β-L- D4A. At the same time, 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） was used to detect the survival ratio of 2.2.15 cells.RESULTS： β-L-D4A has a dose-dependent inhibitory effect on HBV DNA replication; this effect was apparent when the concentration was above 1 mol/L. When β-L- D4A was at the highest concentration, 100 mol/L, the HBsAg inhibition ratio was above 50%. The Therapeutic index （TI） of β-L-D4A was above 2.1.CONCLUSION： β-L-D4A has a dose-dependent inhibitory effect on the replication of HBV DNA and the secretion of HBsAg at low toxicity,
基金supported by grants from the National S&T Major Projects for Infectious Diseases Control(2012ZX10002-003and 2013ZX10002-004)the National Major S&T Special Project for “Significant New Drugs Development”(2012ZX09303-019)Peking University People’s Hospital Research and Development Fund(RDB2015-20)
文摘Background： Higher hepatitis B surface antigen （HBsAg） facilitates hepatitis C virus （HCV） clearance inpatients with hepatitis B virus （HBV）/HCV co-infection. We investigated the effect of exogenous HBsAgon the inhibition of HCV replication mediated by natural killer （NK） cells.
文摘Aim: We aimed to elucidate whether beta2-glycoprotein I (β2GPI) cooperation with hepatitis B surface antigen (HBsAg) promoted hepatocellular carcinogenesis enhanced by the lipopolysaccharide (LPS) via activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and expression of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), and alpha fetal protein (AFP) in liver cancer cells. Methods: Liver cancer cells (SMMC-7721) were transiently transfected with β2GPI and/or HBsAg and were subjected to LPS treatment. TNF-α, IL-1β, and AFP expression were measured in all groups by ELISA. NF-κB activation was assessed by non-radioactive electrophoretic mobility shift assay (EMSA) and was quantified in all groups. Results: Cells transfected with β2GPI and/or HBsAg induced activation of NF-κB, with the highest activation seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Non-transfected cells treated with LPS exhibited lower activation compared to either β2GPI- or HBsAg-transfected cells with LPS treatment. In addition, cells transfected with β2GPI and/or HBsAg induced significantly increased expression of TNF-α, IL-1β and AFP, with the highest levels again seen in the doubly β2GPI- and HBsAg-transfected cells treated with LPS. Conclusion: These observations suggest that the activity of NF-κB induced by β2GPI and HBsAg was enhanced by LPS. Expression of TNF-α, IL-1β and AFP increased in β2GPI and HBsAg cotransfected liver cancer cells.
