In the study, the antitumor effect was observed by employing HAC-tumor-bearing mice treated with direct moxibustion on point Guanyuan(CV 4) (Group M), subcutaneous administration of liposome encapsulated immunomodulat...In the study, the antitumor effect was observed by employing HAC-tumor-bearing mice treated with direct moxibustion on point Guanyuan(CV 4) (Group M), subcutaneous administration of liposome encapsulated immunomodulators called IMC(Group IMC), and combination of these two methods(Group M + IMC). Parameters reflecting biological characteristics of tumor cells, including 5 kinds of lectins, mitotic cycle, expression of C-erbB-2 oncogene and counts of AgNORs were further investigated. The results showed that treatment with combination of moxibustion and IMC could significantly lower three lectins (ConA, LCA, RCA) among these five lectins (BSL, ConA, LCA,RCA, WGA), significantly reduce the expression of C-erbB-2 oncogene, the counts of AgNORs ane the percentage of phase S in HAC tumor cells (compared with Group IMC). Moxibustion or IMC alone did render a certain degree of influence on the above-mentioned parameters, although most of changes were not statistically significant. The above-mentioned results indicated that the antitumor efficacy achieved by treatment with combination of moxibustion and IMC was mainly through its influence on biological characteristics of the tumor cells, namely, its reducing effect on DNA synthesis or on the proliferating rate of tumor cells and its influence on other biological characteristics of tumor展开更多
Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate...Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytom-etry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by in-vestigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of im-munohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.展开更多
Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,live...Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver cancer.Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver complications.However,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver events.Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV DNA.Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.展开更多
Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).How...Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.展开更多
寄生虫病是一种在全球范围内广泛流行的传染性疾病,对人类和家畜的健康造成了严重威胁。寄生虫入侵宿主后,会激活机体免疫系统。宿主通过先天免疫反应和获得性免疫反应来对抗寄生虫感染,并通过多种调节机制来保护自身,以防止过度的免疫...寄生虫病是一种在全球范围内广泛流行的传染性疾病,对人类和家畜的健康造成了严重威胁。寄生虫入侵宿主后,会激活机体免疫系统。宿主通过先天免疫反应和获得性免疫反应来对抗寄生虫感染,并通过多种调节机制来保护自身,以防止过度的免疫反应。调节性B细胞(regulatory B cells, Bregs)是一类在寄生虫感染过程中具有免疫抑制功能的B细胞亚群。其在自身免疫性疾病、癌症和过敏反应中研究较为广泛。目前,越来越多的研究表明,寄生虫感染可诱导Bregs的产生,并且Bregs可以通过分泌抑炎细胞因子白细胞介素10(interleukin-10,IL-10)抑制炎症反应,从而减轻寄生虫感染对宿主的伤害。然而,关于Bregs增殖的信号通路以及激活机制目前还不清楚,仍需要进一步的探究。作者简要介绍了不同类型的Bregs及其表型,并对Bregs在疟原虫(Plasmodium)、血吸虫(Schistosoma)、利什曼原虫(Leishmania)、弓形虫(Toxoplasma)和锥虫(Trypanosoma)感染过程中发挥的免疫调节作用进行总结,以期为寄生虫的治疗和预防策略提供新的见解。展开更多
Immunomodulators,particularly the thiopurines and to a lesser extent methotrexate,were standard of care for inflammatory bowel diseases,including Crohn’s disease and ulcerative colitis,for>40 years.While there has...Immunomodulators,particularly the thiopurines and to a lesser extent methotrexate,were standard of care for inflammatory bowel diseases,including Crohn’s disease and ulcerative colitis,for>40 years.While there has been a renaissance in available therapies with the advent of biologics and small molecules,an impetus remains for the ongoing use of thiopurines and methotrexate.This is particularly true for the maintenance of remission and when used in combination therapy with infliximab to suppress anti-biologic antibodies.This article summarizes the data behind immunomodulator use in Crohn’s disease,focusing on the beneficial role these drugs still have while acknowledging their clinical limitations.展开更多
The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic st...The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.展开更多
Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,whi...Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.展开更多
Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essent...Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.展开更多
文摘In the study, the antitumor effect was observed by employing HAC-tumor-bearing mice treated with direct moxibustion on point Guanyuan(CV 4) (Group M), subcutaneous administration of liposome encapsulated immunomodulators called IMC(Group IMC), and combination of these two methods(Group M + IMC). Parameters reflecting biological characteristics of tumor cells, including 5 kinds of lectins, mitotic cycle, expression of C-erbB-2 oncogene and counts of AgNORs were further investigated. The results showed that treatment with combination of moxibustion and IMC could significantly lower three lectins (ConA, LCA, RCA) among these five lectins (BSL, ConA, LCA,RCA, WGA), significantly reduce the expression of C-erbB-2 oncogene, the counts of AgNORs ane the percentage of phase S in HAC tumor cells (compared with Group IMC). Moxibustion or IMC alone did render a certain degree of influence on the above-mentioned parameters, although most of changes were not statistically significant. The above-mentioned results indicated that the antitumor efficacy achieved by treatment with combination of moxibustion and IMC was mainly through its influence on biological characteristics of the tumor cells, namely, its reducing effect on DNA synthesis or on the proliferating rate of tumor cells and its influence on other biological characteristics of tumor
基金This work was supported by grants from the National Natural Science Foundation of China(52072005 and 51872279).
文摘Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytom-etry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by in-vestigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of im-munohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.
文摘Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver cancer.Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver complications.However,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver events.Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV DNA.Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.
基金This work was supported by the National Natural Science Foundation of China(No.82173668)Scientific Research Project of High-Level Talents(No.C1034335,China)in Southern Medical University of ChinaThousand Youth Talents Program(No.C1080094,China)from the Organization Department of the CPC Central Committee,China.
文摘Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.
文摘寄生虫病是一种在全球范围内广泛流行的传染性疾病,对人类和家畜的健康造成了严重威胁。寄生虫入侵宿主后,会激活机体免疫系统。宿主通过先天免疫反应和获得性免疫反应来对抗寄生虫感染,并通过多种调节机制来保护自身,以防止过度的免疫反应。调节性B细胞(regulatory B cells, Bregs)是一类在寄生虫感染过程中具有免疫抑制功能的B细胞亚群。其在自身免疫性疾病、癌症和过敏反应中研究较为广泛。目前,越来越多的研究表明,寄生虫感染可诱导Bregs的产生,并且Bregs可以通过分泌抑炎细胞因子白细胞介素10(interleukin-10,IL-10)抑制炎症反应,从而减轻寄生虫感染对宿主的伤害。然而,关于Bregs增殖的信号通路以及激活机制目前还不清楚,仍需要进一步的探究。作者简要介绍了不同类型的Bregs及其表型,并对Bregs在疟原虫(Plasmodium)、血吸虫(Schistosoma)、利什曼原虫(Leishmania)、弓形虫(Toxoplasma)和锥虫(Trypanosoma)感染过程中发挥的免疫调节作用进行总结,以期为寄生虫的治疗和预防策略提供新的见解。
文摘Immunomodulators,particularly the thiopurines and to a lesser extent methotrexate,were standard of care for inflammatory bowel diseases,including Crohn’s disease and ulcerative colitis,for>40 years.While there has been a renaissance in available therapies with the advent of biologics and small molecules,an impetus remains for the ongoing use of thiopurines and methotrexate.This is particularly true for the maintenance of remission and when used in combination therapy with infliximab to suppress anti-biologic antibodies.This article summarizes the data behind immunomodulator use in Crohn’s disease,focusing on the beneficial role these drugs still have while acknowledging their clinical limitations.
文摘The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.
基金Supported by Science and Technology Department Project of Jilin Province,China,No.20230101163JCthe Outstanding Youth Fund Project of Jilin Provincial Department of Education,China,No.JJKH20241324KJ.
文摘Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.
文摘Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.
