BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify th...BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.展开更多
Correction of genetic errors, commonly known as gene editing, holds promise to treat diseases with unmet medical needs. However, gene therapy trials do encounter unwanted outcomes, because of an incomplete understandi...Correction of genetic errors, commonly known as gene editing, holds promise to treat diseases with unmet medical needs. However, gene therapy trials do encounter unwanted outcomes, because of an incomplete understanding of the disease states, and gene therapy processes, among others. This situation encourages a concept that healthcare professionals receiving laboratory research training will not only identify inadequacies in basic biomedical knowledge of gene therapies but also provide tangible refinements. To this end, we have undertaken the PharmD student training in gene editing in a basic research laboratory setting. As a model, MYC gene was chosen for knockout using CRISPR-Cas9 method in HT29 and OVCAR8 cells. Students were involved in the design of MYC-specific gRNAs, subcloning into Cas9-carrying plasmid, and selection of knockout clones from the transfected cells. Subsequently, genomic DNA isolation and sequencing, analysis of clonal DNA sequences using online bioinformatics tools, western blotting, cell proliferation and cell division cycle experiments, were performed to characterize the MYC knockout clones. Results presented in this communication suggest that healthcare professionals who received laboratory training gain a better understanding of the disease states and mechanisms, gene therapy protocols, limitations of gene therapies, ability to critically evaluate the literature and confidence in the oversight of gene therapies in the clinic.展开更多
Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p ...Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.展开更多
AIM:To identify the genes induced and regulated by the MYC protein in generating tumors from liver stem cells.METHODS:In this study,we have used an immortal porcine liver stem cell line,PICM-19,to study the role of c-...AIM:To identify the genes induced and regulated by the MYC protein in generating tumors from liver stem cells.METHODS:In this study,we have used an immortal porcine liver stem cell line,PICM-19,to study the role of c-MYC in hepatocarcinogenesis.PICM-19 cells were converted into cancer cells(PICM-19-CSCs)by overexpressing human MYC.To identify MYC-driven differential gene expression,transcriptome sequencing was carried out by RNA sequencing,and genes identified by this method were validated using real-time PCR.In vivo tumorigenicity studies were then conducted by injecting PICM-19-CSCs into the flanks of immunodeficient mice.RESULTS:Our results showed that MYC-overexpressing PICM-19 stem cells formed tumors in immunodeficient mice demonstrating that a single oncogene was sufficient to convert them into cancer cells(PICM-19-CSCs).By using comparative bioinformatics analyses,we have determined that>1000 genes were differentially expressed between PICM-19 and PICM-19-CSCs.Gene ontology analysis further showed that the MYCinduced,altered gene expression was primarily associated with various cellular processes,such as metabolism,cell adhesion,growth and proliferation,cell cycle,inflammation and tumorigenesis.Interestingly,six genes expressed by PICM-19 cells(CDO1,C22orf39,DKK2,ENPEP,GPX6,SRPX2)were completely silenced after MYC-induction in PICM-19-CSCs,suggesting that the absence of these genes may be critical for inducingtumorigenesis.CONCLUSION:MYC-driven genes may serve as promising candidates for the development of hepatocellular carcinoma therapeutics that would not have deleterious effects on other cell types in the liver.展开更多
Objective:To study the effects of recombinant antisense c-myc adenovirus (rAS-c-myc-Ad) on SGG 7901 human gastric carcinoma cell line in for and in nude mice. Methods:The effects of rAS-c-myc-Ad and LacZ-Ad on SGG 790...Objective:To study the effects of recombinant antisense c-myc adenovirus (rAS-c-myc-Ad) on SGG 7901 human gastric carcinoma cell line in for and in nude mice. Methods:The effects of rAS-c-myc-Ad and LacZ-Ad on SGG 7901 gastric carcinoma cells were observed with X-galstaining, MTT, DNA gradient degradation test, TUNEL, flow cytometry, PCR and western blot. The therapeutic effects of rAS-c-myc-Ad on the implanted ax 7901 cells in nude mice were also ob served.Results: rAS-c-myc-Ad significantly inhibited the growth of SGG 7901 cells and induced their apoptosis. After the treatment of rAS-c-myc-Ad, the prolifetion rate of the cells was decreased by 44’ l% in de and SGC 7901 cells failed to form caxcinoma ther they were implanted into nude mice. Injection of rAS-c-myc-Ad into the carcinoma subcutaneously implanted to the nude mice significantly inhibited the growth of the implanted carcinoma with an inhibition rate of 68. 9%. Conclusion: rAS-c- myc- Ad significantly inhibits the growth of SGG 7901 human gastric carcinoma cells in vitro and in nude展开更多
文摘BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.
文摘Correction of genetic errors, commonly known as gene editing, holds promise to treat diseases with unmet medical needs. However, gene therapy trials do encounter unwanted outcomes, because of an incomplete understanding of the disease states, and gene therapy processes, among others. This situation encourages a concept that healthcare professionals receiving laboratory research training will not only identify inadequacies in basic biomedical knowledge of gene therapies but also provide tangible refinements. To this end, we have undertaken the PharmD student training in gene editing in a basic research laboratory setting. As a model, MYC gene was chosen for knockout using CRISPR-Cas9 method in HT29 and OVCAR8 cells. Students were involved in the design of MYC-specific gRNAs, subcloning into Cas9-carrying plasmid, and selection of knockout clones from the transfected cells. Subsequently, genomic DNA isolation and sequencing, analysis of clonal DNA sequences using online bioinformatics tools, western blotting, cell proliferation and cell division cycle experiments, were performed to characterize the MYC knockout clones. Results presented in this communication suggest that healthcare professionals who received laboratory training gain a better understanding of the disease states and mechanisms, gene therapy protocols, limitations of gene therapies, ability to critically evaluate the literature and confidence in the oversight of gene therapies in the clinic.
文摘Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.
基金Supported by Departmental funds to Dr.Aravalli RN
文摘AIM:To identify the genes induced and regulated by the MYC protein in generating tumors from liver stem cells.METHODS:In this study,we have used an immortal porcine liver stem cell line,PICM-19,to study the role of c-MYC in hepatocarcinogenesis.PICM-19 cells were converted into cancer cells(PICM-19-CSCs)by overexpressing human MYC.To identify MYC-driven differential gene expression,transcriptome sequencing was carried out by RNA sequencing,and genes identified by this method were validated using real-time PCR.In vivo tumorigenicity studies were then conducted by injecting PICM-19-CSCs into the flanks of immunodeficient mice.RESULTS:Our results showed that MYC-overexpressing PICM-19 stem cells formed tumors in immunodeficient mice demonstrating that a single oncogene was sufficient to convert them into cancer cells(PICM-19-CSCs).By using comparative bioinformatics analyses,we have determined that>1000 genes were differentially expressed between PICM-19 and PICM-19-CSCs.Gene ontology analysis further showed that the MYCinduced,altered gene expression was primarily associated with various cellular processes,such as metabolism,cell adhesion,growth and proliferation,cell cycle,inflammation and tumorigenesis.Interestingly,six genes expressed by PICM-19 cells(CDO1,C22orf39,DKK2,ENPEP,GPX6,SRPX2)were completely silenced after MYC-induction in PICM-19-CSCs,suggesting that the absence of these genes may be critical for inducingtumorigenesis.CONCLUSION:MYC-driven genes may serve as promising candidates for the development of hepatocellular carcinoma therapeutics that would not have deleterious effects on other cell types in the liver.
基金Supported by National 863 High Science and Technology Foundation of China, No.Z20-01-02
文摘Objective:To study the effects of recombinant antisense c-myc adenovirus (rAS-c-myc-Ad) on SGG 7901 human gastric carcinoma cell line in for and in nude mice. Methods:The effects of rAS-c-myc-Ad and LacZ-Ad on SGG 7901 gastric carcinoma cells were observed with X-galstaining, MTT, DNA gradient degradation test, TUNEL, flow cytometry, PCR and western blot. The therapeutic effects of rAS-c-myc-Ad on the implanted ax 7901 cells in nude mice were also ob served.Results: rAS-c-myc-Ad significantly inhibited the growth of SGG 7901 cells and induced their apoptosis. After the treatment of rAS-c-myc-Ad, the prolifetion rate of the cells was decreased by 44’ l% in de and SGC 7901 cells failed to form caxcinoma ther they were implanted into nude mice. Injection of rAS-c-myc-Ad into the carcinoma subcutaneously implanted to the nude mice significantly inhibited the growth of the implanted carcinoma with an inhibition rate of 68. 9%. Conclusion: rAS-c- myc- Ad significantly inhibits the growth of SGG 7901 human gastric carcinoma cells in vitro and in nude
