Primary liver cancer is an important cause of cancer death, and hepatocellular carcinoma （HCC） accounts for 70%-85% of total liver cancer worldwide. Chronic hepatitis B virus （HBV） infection contributes to 〉 75% ...Primary liver cancer is an important cause of cancer death, and hepatocellular carcinoma （HCC） accounts for 70%-85% of total liver cancer worldwide. Chronic hepatitis B virus （HBV） infection contributes to 〉 75% of HCC cases. High serum viral load is the most reliable indicator of viral replication in predicting development of HCC. HBV genotype C is closely associated with HCC in cirrhotic patients aged 〉 50 years, whereas genotype B is associated with development of HCC in non-cirrhotic young patients and postoperative relapse of HCC. Different HBV subgenotypes have distinct patterns of mutations, which are clearly associated with increased risk of HCC. Mutations accumulate during chronic HBV infection and predict occurrence of HCC. Chronic inflammation leads to increased frequency of viral mutation via cellular cytidine deaminase induction. Mutations are negatively selected by host immunity, whereas some immuno-escaped HBV mutants are active in hepatocarcinogenesis. Inflammatory pathways contribute to the inflammation-necrosis-regeneration process, ultimately HCC. Their hallmark molecules can predict malignancy in HBV-infected subjects. Continuing inflammation is involved in hepatocarcinogenesis and closely related to recurrence and metastasis. HBV load, genotype C, viral mutations and expression of inflammatory molecules in HBV-related HCC tissues are significantly associated with poor prognosis. Imbalance between intratumoral CD8^＋T cells and regulatory T cells or Thl and Th2 cytokines in peritumoral tissues can predict prognosis of HBV-related HCC. These factors are important for developing active prevention and surveillance of HBV-infected subjects who are more likely to develop HCC, or for tailoring suitable treatment to improve survival or postpone postoperative recurrence of HCC.展开更多
Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepa...Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8<sup>+</sup> T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.展开更多
Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-infl...Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia(VaD).Methods:The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table,including sham,four-vessel occlusion(4-VO),4-VO+EA,4-VO+non-EA,sham+EA,4-VO+lipopolysaccharide(LPS),4-VO+LPS+EA,and 4-VO+TAK-242 groups.The VaD model was established by the 4-VO method.Seven days later,rats were treated with EA at 5 acupoints of Baihui(DV 20),Danzhong(RN 17),Geshu(BL 17),Qihai(RN 6)and Sanyinjiao(SP 6),once per day for 3 consecutive weeks.Lymphocyte subsets,lymphocyte transformation rates,and inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)were measured to assess immune function and inflammation in VaD rats.Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus.The levels of TLR4,MyD88,IL-6,and TNF-αwere detected after EA treatment.TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.Results:Compared with the 4-VO group,EA notably improved immune function of rats in the 4-VO+EA group,inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats,reduced the expressions of serum IL-6 and TNF-α(all P<0.05 or P<0.01),and led to neuronal repair in the hippocampus.There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups,nor between the 4-VO+TAK-242 and 4-VO+EA groups(P>0.05).Conclusions:EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway.Thus,EA may be a promising alternative therapy for the treatment of VaD.展开更多
Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function ...Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function are maintained through multidimensional mechanisms that can proficiently remove foreign pathogenic microorganisms while effectively maintaining local symbiotic microbial homeostasis.The basic immune mechanisms of the insect gut,such as the dual oxidase-reactive oxygen species(Duox-ROS)system and the immune deficiency(Imd)-signaling pathway,are involved in the maintenance of microbial homeostasis.This paper reviews the role of physical defenses,the Duox-ROS and Imd signaling pathways,the Janus kinase/signal transducers and activators of transcription signaling pathway,and intestinal symbiotic flora in the homeostatic maintenance of the insect gut microbiome.展开更多
基金Supported by National Natural Science Foundation of China,No. 81025015 and No. 30921006
文摘Primary liver cancer is an important cause of cancer death, and hepatocellular carcinoma （HCC） accounts for 70%-85% of total liver cancer worldwide. Chronic hepatitis B virus （HBV） infection contributes to 〉 75% of HCC cases. High serum viral load is the most reliable indicator of viral replication in predicting development of HCC. HBV genotype C is closely associated with HCC in cirrhotic patients aged 〉 50 years, whereas genotype B is associated with development of HCC in non-cirrhotic young patients and postoperative relapse of HCC. Different HBV subgenotypes have distinct patterns of mutations, which are clearly associated with increased risk of HCC. Mutations accumulate during chronic HBV infection and predict occurrence of HCC. Chronic inflammation leads to increased frequency of viral mutation via cellular cytidine deaminase induction. Mutations are negatively selected by host immunity, whereas some immuno-escaped HBV mutants are active in hepatocarcinogenesis. Inflammatory pathways contribute to the inflammation-necrosis-regeneration process, ultimately HCC. Their hallmark molecules can predict malignancy in HBV-infected subjects. Continuing inflammation is involved in hepatocarcinogenesis and closely related to recurrence and metastasis. HBV load, genotype C, viral mutations and expression of inflammatory molecules in HBV-related HCC tissues are significantly associated with poor prognosis. Imbalance between intratumoral CD8^＋T cells and regulatory T cells or Thl and Th2 cytokines in peritumoral tissues can predict prognosis of HBV-related HCC. These factors are important for developing active prevention and surveillance of HBV-infected subjects who are more likely to develop HCC, or for tailoring suitable treatment to improve survival or postpone postoperative recurrence of HCC.
文摘Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8<sup>+</sup> T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.
基金the National Natural Science Foundation of China(No.81960811)the Major Research Project of Innovation Group of Guizhou Provincial Department of Education(No.2018KY023)。
文摘Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia(VaD).Methods:The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table,including sham,four-vessel occlusion(4-VO),4-VO+EA,4-VO+non-EA,sham+EA,4-VO+lipopolysaccharide(LPS),4-VO+LPS+EA,and 4-VO+TAK-242 groups.The VaD model was established by the 4-VO method.Seven days later,rats were treated with EA at 5 acupoints of Baihui(DV 20),Danzhong(RN 17),Geshu(BL 17),Qihai(RN 6)and Sanyinjiao(SP 6),once per day for 3 consecutive weeks.Lymphocyte subsets,lymphocyte transformation rates,and inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)were measured to assess immune function and inflammation in VaD rats.Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus.The levels of TLR4,MyD88,IL-6,and TNF-αwere detected after EA treatment.TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.Results:Compared with the 4-VO group,EA notably improved immune function of rats in the 4-VO+EA group,inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats,reduced the expressions of serum IL-6 and TNF-α(all P<0.05 or P<0.01),and led to neuronal repair in the hippocampus.There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups,nor between the 4-VO+TAK-242 and 4-VO+EA groups(P>0.05).Conclusions:EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway.Thus,EA may be a promising alternative therapy for the treatment of VaD.
文摘Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function are maintained through multidimensional mechanisms that can proficiently remove foreign pathogenic microorganisms while effectively maintaining local symbiotic microbial homeostasis.The basic immune mechanisms of the insect gut,such as the dual oxidase-reactive oxygen species(Duox-ROS)system and the immune deficiency(Imd)-signaling pathway,are involved in the maintenance of microbial homeostasis.This paper reviews the role of physical defenses,the Duox-ROS and Imd signaling pathways,the Janus kinase/signal transducers and activators of transcription signaling pathway,and intestinal symbiotic flora in the homeostatic maintenance of the insect gut microbiome.
