Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The pr...Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.展开更多
AIM:To investigate the diversity of Helicobacter pylori(H.pylori)genotypes and correlations with disease outcomes in an Iranian population with different gastroduodenal disorders.METHODS:Isolates of H.pylori from pati...AIM:To investigate the diversity of Helicobacter pylori(H.pylori)genotypes and correlations with disease outcomes in an Iranian population with different gastroduodenal disorders.METHODS:Isolates of H.pylori from patients with different gastroduodenal disorders were analyzed after culture and identification by phenotypic and genotypic methods.Genomic DNA was extracted with the QIAamp DNA mini kit(Qiagen,Germany).After DNA extraction,genotyping was done for cagA,vacA(s and m regions),iceA(iceA1,iceA2)and babA with specific primers for each allele using polymerase chain reaction(PCR).All patients’pathologic and clinical data and their relation with known genotypes were analyzed by using SPSS version 19.0 software.2test and Fisher’s exact test were used to assess relationships between categorical variables.The level of statistical significance was set at P<0.05.RESULTS:A total of 71 isolates from 177 patients with different gastroduodenal disorders were obtained.Based on analysis of the cagA gene(positive or negative),vacA s-region(s1or s2),vacA m-region(m1or m2),iceA allelic type(iceA1and iceA2)and babA gene(positive or negative),twenty different genotypic combinations were recognized.The prevalence of cagA,vacA s1,vacA s2,vacA m1,vacA m2,iceA1,iceA2,iceA1+iceA2and babA were 62%,78.9%,19.7%,21.1%,78.9%,15.5%,22.5%,40.8%and 95.8%,respectively.Interestingly,evaluation of PCR results for cagA in 6 patients showed simultaneous existence of cagA variants according to their size diversities that proposed mixed infection in these patients.The most prevalent genotype in cagA-positive isolates was cagA+/vacAs1m2/iceA1+A2/babA+and in cagA-negative isolates was cagA-/vacAs1m2/iceA-/babA+.There were no relationships between the studied genes and histo-pathological findings(H.pylori density,neutrophil activity,lymphoid aggregation in lamina propria and glandular atrophy).The strains which carry cagA,vacAs1/m1,iceA2and babA genes showed significant associations with severe active chronic gastritis(P=0.011,0.025,0.020 and 0.031,respectively).The vacAs1genotype had significant correlation with the presence of the cagA gene(P=0.013).Also,babA genotype showed associations with cagA(P=0.024).In the combined genotypes,only cagA+/vacAs1m1/iceA2/babA+genotype showed correlation with severe active chronic gastritis(P=0.025).CONCLUSION:This genotyping panel can be a useful tool for detection of virulent H.pylori isolates and can provide valuable guidance for prediction of the clinical outcomes.展开更多
This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting roles.Our data showed that Gal1 was highly expressed in human and ...This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting roles.Our data showed that Gal1 was highly expressed in human and mouse HCC.The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival.The roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by AAV9.Prior to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor load.The treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body weight.Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing.Within the tumors,silencing Gal1 inhibited translational initiation,elongation,and termination.Furthermore,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas CD8-dependent.Overall,Gal1 silencing has a promising potential for HCC treatment.展开更多
Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treat...Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treatment of metabolic disease may require a long-term strategy of taking multiple medications,which can be costly and have side effects.Attempts to expand the therapeutic use of vaccination to prevent or treat metabolic diseases have attracted significant interest.A growing body of evidence indicates that Bacillus Calmette-Guerin(BCG)offers protection against non-infectious diseases.The non-specific effects of BCG occur likely due to the induction of trained immunity.In this regard,understanding how BCG influences the development of chronic metabolic health including liver diseases would be important.This review focuses on research on BCG,the constellation of disorders associated with metabolic health issues including liver diseases and diabetes as well as how BCG affects the gut microbiome,immunity,and metabolism.展开更多
The incidence of hepatocellular carcinoma(HCC)has been increasing for decades.This disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer mort...The incidence of hepatocellular carcinoma(HCC)has been increasing for decades.This disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer mortality.While several surgical interventions and loco-regional treatment options are available,up to 80%of patients present with advanced disease not amenable to standard therapies.Indeed,traditional cytotoxic chemotherapeutic agents are notoriously ineffective and essentially play no role in the management of affected patients.This has led to an enormous need for more effective sys-temic therapeutic options.In recent years,immunotherapy has emerged as a potentially viable and exciting new alternative for the treatment of HCC.Although the current immunotherapeutic options remain imperfect,various strategies can be employed to further improve their efficacy.New findings have revealed epigenetic modulation can be effective as a new approach for improving HCC immuno-therapy.Studying the gut microbiome(gut-liver axis)can also be an interesting subject in this regard.Here,we explore the latest insights into the role of immunotherapy treating HCC,both mono and in combination with other agents.We also focus on the impact of epigenetic drugs and the microbiome in the overall effectiveness of HCC immunotherapy.展开更多
文摘Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.
基金Supported by Gastroenterology and Liver Diseases Research Center,Shahid Beheshti University of Medical Sciences,Tehran,IranIran National Science Foundation,INSF+3 种基金and a PhD grant from the Faculty of Medical Sciences,Tarbiat Modares University,Tehran,IranGrants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology(MEXT) of Japan,No.22390085,22659087,24406015 and24659200Special Coordination Funds for Promoting Scienceand Technology from the MEXT of Japana Research Fundat the Discretion of the President,Oita University
文摘AIM:To investigate the diversity of Helicobacter pylori(H.pylori)genotypes and correlations with disease outcomes in an Iranian population with different gastroduodenal disorders.METHODS:Isolates of H.pylori from patients with different gastroduodenal disorders were analyzed after culture and identification by phenotypic and genotypic methods.Genomic DNA was extracted with the QIAamp DNA mini kit(Qiagen,Germany).After DNA extraction,genotyping was done for cagA,vacA(s and m regions),iceA(iceA1,iceA2)and babA with specific primers for each allele using polymerase chain reaction(PCR).All patients’pathologic and clinical data and their relation with known genotypes were analyzed by using SPSS version 19.0 software.2test and Fisher’s exact test were used to assess relationships between categorical variables.The level of statistical significance was set at P<0.05.RESULTS:A total of 71 isolates from 177 patients with different gastroduodenal disorders were obtained.Based on analysis of the cagA gene(positive or negative),vacA s-region(s1or s2),vacA m-region(m1or m2),iceA allelic type(iceA1and iceA2)and babA gene(positive or negative),twenty different genotypic combinations were recognized.The prevalence of cagA,vacA s1,vacA s2,vacA m1,vacA m2,iceA1,iceA2,iceA1+iceA2and babA were 62%,78.9%,19.7%,21.1%,78.9%,15.5%,22.5%,40.8%and 95.8%,respectively.Interestingly,evaluation of PCR results for cagA in 6 patients showed simultaneous existence of cagA variants according to their size diversities that proposed mixed infection in these patients.The most prevalent genotype in cagA-positive isolates was cagA+/vacAs1m2/iceA1+A2/babA+and in cagA-negative isolates was cagA-/vacAs1m2/iceA-/babA+.There were no relationships between the studied genes and histo-pathological findings(H.pylori density,neutrophil activity,lymphoid aggregation in lamina propria and glandular atrophy).The strains which carry cagA,vacAs1/m1,iceA2and babA genes showed significant associations with severe active chronic gastritis(P=0.011,0.025,0.020 and 0.031,respectively).The vacAs1genotype had significant correlation with the presence of the cagA gene(P=0.013).Also,babA genotype showed associations with cagA(P=0.024).In the combined genotypes,only cagA+/vacAs1m1/iceA2/babA+genotype showed correlation with severe active chronic gastritis(P=0.025).CONCLUSION:This genotyping panel can be a useful tool for detection of virulent H.pylori isolates and can provide valuable guidance for prediction of the clinical outcomes.
基金The authors thank the Genomics Shared Resource(GSR)core facility at the University of California,Davis Health,Dr.Clifford G Tepper,Stephanie Liu,Ryan Davis,for helping in performing spatial RNA sequencing,and William Amato for his assistance in the quantification of immunohistochemistry slides.This manuscript is supported by grants funded by the USA National Institutes of Health(NIH)T32 CA108459e15,R01CA222490,R50CA243787.BioRender was used to draw mice figures in schematic experimental design.
文摘This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting roles.Our data showed that Gal1 was highly expressed in human and mouse HCC.The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival.The roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by AAV9.Prior to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor load.The treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body weight.Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing.Within the tumors,silencing Gal1 inhibited translational initiation,elongation,and termination.Furthermore,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas CD8-dependent.Overall,Gal1 silencing has a promising potential for HCC treatment.
基金This study is supported by grants funded by the USA National Institutes of Health(R01CA222490).
文摘Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treatment of metabolic disease may require a long-term strategy of taking multiple medications,which can be costly and have side effects.Attempts to expand the therapeutic use of vaccination to prevent or treat metabolic diseases have attracted significant interest.A growing body of evidence indicates that Bacillus Calmette-Guerin(BCG)offers protection against non-infectious diseases.The non-specific effects of BCG occur likely due to the induction of trained immunity.In this regard,understanding how BCG influences the development of chronic metabolic health including liver diseases would be important.This review focuses on research on BCG,the constellation of disorders associated with metabolic health issues including liver diseases and diabetes as well as how BCG affects the gut microbiome,immunity,and metabolism.
基金This study was supported by grants funded by the National In-stitutes of Health U01CA179582 and R01CA222490.
文摘The incidence of hepatocellular carcinoma(HCC)has been increasing for decades.This disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer mortality.While several surgical interventions and loco-regional treatment options are available,up to 80%of patients present with advanced disease not amenable to standard therapies.Indeed,traditional cytotoxic chemotherapeutic agents are notoriously ineffective and essentially play no role in the management of affected patients.This has led to an enormous need for more effective sys-temic therapeutic options.In recent years,immunotherapy has emerged as a potentially viable and exciting new alternative for the treatment of HCC.Although the current immunotherapeutic options remain imperfect,various strategies can be employed to further improve their efficacy.New findings have revealed epigenetic modulation can be effective as a new approach for improving HCC immuno-therapy.Studying the gut microbiome(gut-liver axis)can also be an interesting subject in this regard.Here,we explore the latest insights into the role of immunotherapy treating HCC,both mono and in combination with other agents.We also focus on the impact of epigenetic drugs and the microbiome in the overall effectiveness of HCC immunotherapy.