Objective: To investigate the effect of activated protein C (APC) on inflammatory responses in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). Methods: The second passage of co...Objective: To investigate the effect of activated protein C (APC) on inflammatory responses in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). Methods: The second passage of collagenase digested HUVEC was divided into the following groups: serum free medium control group (SFM control), phosphate buffer solution control group (PBS control), LPS group with final concentration of 1 μg/ml (LPS group), APC group with final concentration of 7 μg/ml, Pre-APC group (APC pretreatment for 30 min prior to LPS challenge), and Post-APC group (APC administration 30 min after LPS challenge). Supernatant was harvested at 0, 4, 8, 12 and 24 h after LPS challenge. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) levels were analyzed with ELISA. Cells were harvested at 24 h after LPS challenge, and total RNA was extracted. Mes-senger RNA levels for IL-6 and IL-8 were semi-quantitatively determined by RT-PCR. Results: Compared with control group, IL-6 and IL-8 levels steadily increased 4 to 24 h after LPS stimulation. APC treatment could increase LPS-induced IL-6 and IL-8 production. The mRNA levels of IL-6 and IL-8 exhibited a similar change. Conclusion: APC can further increase the level of IL-6 and IL-8 induced by LPS. The effect of these elevated cytokines is still under investigation.展开更多
Fizzy-related protein homolog 1 (FZR1) mainly functions as a specific activator of the anaphase-promotingcomplex/cyclosome (APC/C) in the cell cycle and controls the G0 and G1 phases of the cell cycle. We highlightrec...Fizzy-related protein homolog 1 (FZR1) mainly functions as a specific activator of the anaphase-promotingcomplex/cyclosome (APC/C) in the cell cycle and controls the G0 and G1 phases of the cell cycle. We highlightrecent work that has studied the role of FZR1 in tumorigenesis, growth, differentiation, and genome stability throughcell-cycle control. We summarize the current state of knowledge regarding FZR1 structure, function, and the distinctways of APC/C dysregulation in solid tumors and hematologic malignancies. We also discuss novel approaches fortargeting the FZR1 as a cancer therapy and research area for future work.展开更多
Chronic hepatitis B(CHB)is consistently challenging to conquer with numerous complications and fatalities.Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus(HBV)replication,there is an u...Chronic hepatitis B(CHB)is consistently challenging to conquer with numerous complications and fatalities.Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus(HBV)replication,there is an urgent need for novel and more effective treatment modalities.Current strategies predominantly emphasize immune activation but still face challenges in sufficiently eliciting T cell responses.Taking into account the targeted delivery of nanoparticles to the liver and spleen via intravenous injection,we have proposed a dual-pronged therapeutic strategy based on antigen-presenting cells(APCs)-derived exosomes.Specifically,exosomes targeted to the spleen can activate specific immune responses,while those targeted to the liver can modulate or reverse the liver’s immunosuppressive microenvironment.After immunization,exosome formulations exhibit the remarkable ability to effectively activate APCs,thereby triggering the proliferation of CD8^(+)T cells.Simultaneously,they also play an immunoregulatory role by converting M2 macrophages into M1 macrophages.This two-pronged therapeutic strategy precisely addresses the issues of T cell dysfunction and immune suppression,both characteristic features of CHB patients.When combined with Aluminum(Alum)-adjuvanted vaccine,these exosome formulations not only demonstrate a high level of cellular immune response but also secrete specific antibodies comparable to those induced by Alum adjuvant.This combined approach effectively enhances both cellular and humoral immunity,offering a promising avenue for the development of therapeutic hepatitis B vaccines based on exosome formulations.展开更多
文摘Objective: To investigate the effect of activated protein C (APC) on inflammatory responses in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). Methods: The second passage of collagenase digested HUVEC was divided into the following groups: serum free medium control group (SFM control), phosphate buffer solution control group (PBS control), LPS group with final concentration of 1 μg/ml (LPS group), APC group with final concentration of 7 μg/ml, Pre-APC group (APC pretreatment for 30 min prior to LPS challenge), and Post-APC group (APC administration 30 min after LPS challenge). Supernatant was harvested at 0, 4, 8, 12 and 24 h after LPS challenge. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) levels were analyzed with ELISA. Cells were harvested at 24 h after LPS challenge, and total RNA was extracted. Mes-senger RNA levels for IL-6 and IL-8 were semi-quantitatively determined by RT-PCR. Results: Compared with control group, IL-6 and IL-8 levels steadily increased 4 to 24 h after LPS stimulation. APC treatment could increase LPS-induced IL-6 and IL-8 production. The mRNA levels of IL-6 and IL-8 exhibited a similar change. Conclusion: APC can further increase the level of IL-6 and IL-8 induced by LPS. The effect of these elevated cytokines is still under investigation.
基金supported by the National Key Scientific Research Project(2017YFC1001903)Provincial and Ministerial Level Projects(cstc2016shmstzx10006)the Guizhou Provincial Science&Technology Program(QKHZC[2020]4Y154).
文摘Fizzy-related protein homolog 1 (FZR1) mainly functions as a specific activator of the anaphase-promotingcomplex/cyclosome (APC/C) in the cell cycle and controls the G0 and G1 phases of the cell cycle. We highlightrecent work that has studied the role of FZR1 in tumorigenesis, growth, differentiation, and genome stability throughcell-cycle control. We summarize the current state of knowledge regarding FZR1 structure, function, and the distinctways of APC/C dysregulation in solid tumors and hematologic malignancies. We also discuss novel approaches fortargeting the FZR1 as a cancer therapy and research area for future work.
基金supported by National Key Research and Development Program of China(Nos.2023YFC2307704,and 2021YFC2302603)National Natural Science Foundation of China(Nos.82341405,and 32030062)+1 种基金CAS Project for Young Scientists in Basic Research(No.YSBR-083)IPE Project for Frontier Basic Research(No.QYJC-2022-012).
文摘Chronic hepatitis B(CHB)is consistently challenging to conquer with numerous complications and fatalities.Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus(HBV)replication,there is an urgent need for novel and more effective treatment modalities.Current strategies predominantly emphasize immune activation but still face challenges in sufficiently eliciting T cell responses.Taking into account the targeted delivery of nanoparticles to the liver and spleen via intravenous injection,we have proposed a dual-pronged therapeutic strategy based on antigen-presenting cells(APCs)-derived exosomes.Specifically,exosomes targeted to the spleen can activate specific immune responses,while those targeted to the liver can modulate or reverse the liver’s immunosuppressive microenvironment.After immunization,exosome formulations exhibit the remarkable ability to effectively activate APCs,thereby triggering the proliferation of CD8^(+)T cells.Simultaneously,they also play an immunoregulatory role by converting M2 macrophages into M1 macrophages.This two-pronged therapeutic strategy precisely addresses the issues of T cell dysfunction and immune suppression,both characteristic features of CHB patients.When combined with Aluminum(Alum)-adjuvanted vaccine,these exosome formulations not only demonstrate a high level of cellular immune response but also secrete specific antibodies comparable to those induced by Alum adjuvant.This combined approach effectively enhances both cellular and humoral immunity,offering a promising avenue for the development of therapeutic hepatitis B vaccines based on exosome formulations.
