Avian influenza viruses(AIVs)represent an ongoing threat to global health due to their capacity for genetic evolution,zoonotic transmission,and pandemic emergence.This review highlights recent progress in understandin...Avian influenza viruses(AIVs)represent an ongoing threat to global health due to their capacity for genetic evolution,zoonotic transmission,and pandemic emergence.This review highlights recent progress in understanding the molecular mechanisms underlying AIV infection,including viral immune evasion strategies and host-virus interactions.It discusses recent outbreaks involving reassortant strains such as H5N1 and H9N2,and examines their public health co-nsequences.Advancements in antiviral therapy,including resistance patterns,and the development of next-generation vaccines such as messenger RNA and universal influenza vaccines are reviewed.The integration of genomic surveillance,artificial intelligence-driven prediction,and One Health approaches is emphasized as essential for pandemic preparedness.This comprehensive overview aims to provide researchers and policymakers with actionable insights for controlling the evolving threat of avian influenza.展开更多
Helicobacter pylori(H.pylori)infection is one of the most prevalent bacterial infections affecting mankind.About half of the world’s population is infected with it.It causes several upper gastrointestinal diseases,in...Helicobacter pylori(H.pylori)infection is one of the most prevalent bacterial infections affecting mankind.About half of the world’s population is infected with it.It causes several upper gastrointestinal diseases,including gastric cancer(GC).It has been identified as a major risk factor for GC.GC is one of the most common cancers affecting humans and the third leading cause of cancer-related deaths worldwide.H.pylori infection causes an inflammatory response that progresses through a series of intermediary stages of precancerous lesions(gastritis,atrophy,intestinal metaplasia,and dysplasia)to the final development of GC.Among infected individuals,approximately 10%develop severe gastric lesions such as peptic ulcer disease,1%-3%progress to GC,and 0.1%develop mucosa-associated lymphoid tissue followed by the development of lymphoma.The bacterium has many virulence factors,including cytotoxin-associated gene A,vacuolating cytotoxin A,and the different outer membrane proteins that cause cancer by different mechanisms.These virulence factors activate cell signaling pathways such as PI3-kinase/Akt,JAK/STAT,Ras,Raf,and ERK signaling that control cell proliferation.Uncontrolled proliferation can lead to cancer.In addition,the repair of DNA damage may also be impaired by H.pylori infection.Reduced DNA repair in combination with increased DNA damage can result in carcinogenic mutations.The accurate identification of pathogenetic pathways is imperative for the development of targeted diagnostic markers and personalized treatments.This scoping review aims to update the readers on the role of H.pylori in the development of GC.It will focus on the molecular mechanisms underpinning gastric carcinogenesis in H.pylori infection.It will highlight the interaction between bacterial virulence factors and host cellular pathways,providing insights into potential therapeutic targets and preventive strategies.展开更多
Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in...Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.展开更多
Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the ...Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surfacemarkers and allow aberrant differentiation of progenies.It facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance. Based on the current information, present review discusses and summarizes the recent advancements on the molecular mechanisms that derive epithelial plasticity and its major role in generating a subset of tumor cells with stemness properties and pathophysiological spread of tumor. This paper further highlights the critical need to examine the regulation of EMT and CSC pathways in identifying the novel probable therapeutic targets.These improved therapeutic strategies based on the co-administration of inhibitors of EMT, CSCs as well as differentiated tumor cells may provide improved antineoplastic response with no tumor relapse.展开更多
BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains el...BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.展开更多
BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion ar...BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion are from complex biological processes.However,the molecular mechanisms underlying the basis of microarray data profile,followed by peritoneal adhesion formation,are largely unknown.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis.We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods.We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.RESULTS In total,446 expressed genes were altered in peritoneal adhesion.We found that several hub genes(e.g.,tumor necrosis factor,interleukin 1 beta,interleukin 6,CX-C motif chemokine ligand 1,C-X-C motif chemokine ligand 2)were marked as significant biomarkers.Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway.According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies,TLR4,myeloid differentiation primary response protein 88(MyD88),and nuclear factor kappa B(NF-κB)played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion.The results of the microarray analysis were verified by the animal experiments.These findings may extend our understanding of the molecular mechanisms of PPA.CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.展开更多
Primary liver cancer is the fifth most common malignan- cy in the world and is a leading cause of cancer-related mortality.Available treatment for hepatocellular carcino- ma(HCC),the commonest primary liver cancer,is ...Primary liver cancer is the fifth most common malignan- cy in the world and is a leading cause of cancer-related mortality.Available treatment for hepatocellular carcino- ma(HCC),the commonest primary liver cancer,is rarely curative and there is a need to develop therapy that is more effective.Specific and powerful gene silencing that can be achieved by activating RNA interference(RNAi) has generated enthusiasm for exploiting this pathway for HCC therapy.Many studies have been carried out with the aim of silencing HCC-related cellular oncogenes or the hepatocarcinogenic hepatitis B virus(HBV)and hepatitis C virus(HCV).Proof of principle studies have demonstrated promising results,and an early clinical trial assessing RNAi-based HBV therapy is currently in progress.Although the data augur well,there are several significant hurdles that need to be overcome before the goal of RNAi-based therapy for HCC is realized.Particu- larly important are the efficient and safe delivery of RNAi effecters to target malignant tissue and the limitation of unintended harmful non-specific effects.展开更多
There is little or no research initiated on enlightening Nigerians about the pathogenesis,targets for drug development and repositioning for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Coronav...There is little or no research initiated on enlightening Nigerians about the pathogenesis,targets for drug development and repositioning for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Coronavirus disease 2019(COVID-19)is a viral infection causing symptoms like dry cough,sore throat,nasal congestion,tiredness,fever,loss of taste,and smell etc.The disease was first reported in Wuhan,China,in December 2019.The infection is caused by SARS-CoV-2,which is the third introduction of a highly pathogenic coronavirus into the human population.Coronaviruses are viruses with a positive RNA envelope assigned toα,β,γ,andδgenera.Moreover,SARS-CoV-2 belongs to theβgenus.The four structural proteins ofβcoronavirus are membrane(M),envelope(E),spike(S),and nucleocapsid(N)protein,mediation of coronavirus host infection is established by spike(S)protein.Therefore,the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic.It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor,viral RNA synthesis and replication,3CLpro,RdRp,and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection.Furthermore,the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development.Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19,and mRNA-1273 targeting spike protein is the promising vaccine.However,as patient management and drug repositioning are taking place,it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection,to develop novel therapeutics.展开更多
文摘Avian influenza viruses(AIVs)represent an ongoing threat to global health due to their capacity for genetic evolution,zoonotic transmission,and pandemic emergence.This review highlights recent progress in understanding the molecular mechanisms underlying AIV infection,including viral immune evasion strategies and host-virus interactions.It discusses recent outbreaks involving reassortant strains such as H5N1 and H9N2,and examines their public health co-nsequences.Advancements in antiviral therapy,including resistance patterns,and the development of next-generation vaccines such as messenger RNA and universal influenza vaccines are reviewed.The integration of genomic surveillance,artificial intelligence-driven prediction,and One Health approaches is emphasized as essential for pandemic preparedness.This comprehensive overview aims to provide researchers and policymakers with actionable insights for controlling the evolving threat of avian influenza.
文摘Helicobacter pylori(H.pylori)infection is one of the most prevalent bacterial infections affecting mankind.About half of the world’s population is infected with it.It causes several upper gastrointestinal diseases,including gastric cancer(GC).It has been identified as a major risk factor for GC.GC is one of the most common cancers affecting humans and the third leading cause of cancer-related deaths worldwide.H.pylori infection causes an inflammatory response that progresses through a series of intermediary stages of precancerous lesions(gastritis,atrophy,intestinal metaplasia,and dysplasia)to the final development of GC.Among infected individuals,approximately 10%develop severe gastric lesions such as peptic ulcer disease,1%-3%progress to GC,and 0.1%develop mucosa-associated lymphoid tissue followed by the development of lymphoma.The bacterium has many virulence factors,including cytotoxin-associated gene A,vacuolating cytotoxin A,and the different outer membrane proteins that cause cancer by different mechanisms.These virulence factors activate cell signaling pathways such as PI3-kinase/Akt,JAK/STAT,Ras,Raf,and ERK signaling that control cell proliferation.Uncontrolled proliferation can lead to cancer.In addition,the repair of DNA damage may also be impaired by H.pylori infection.Reduced DNA repair in combination with increased DNA damage can result in carcinogenic mutations.The accurate identification of pathogenetic pathways is imperative for the development of targeted diagnostic markers and personalized treatments.This scoping review aims to update the readers on the role of H.pylori in the development of GC.It will focus on the molecular mechanisms underpinning gastric carcinogenesis in H.pylori infection.It will highlight the interaction between bacterial virulence factors and host cellular pathways,providing insights into potential therapeutic targets and preventive strategies.
基金the Brain Research Trust,the Wellcome Trust,the UK Medical Research Council and the AnEUploidy grant from Framework Programme 6 from the European Union Commission for funding
文摘Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.
基金supported by Funding was provided by grants from the Changsha Chinese Medicine Foundation(Grant No.B202314)the Natural Science Foundation of Hunan Province,China(Grant No.2024JJ8224)+1 种基金Changsha Municipal Natural Science Foundation(Grant No.kq2403187)Hunan Province Children’s Safe Medication Clinical Medical Technology Demonstration Base(Grant No.2023SK4083).
文摘Pediatric congenital heart disease(CHD)pharmacotherapy faces three fundamental barriers:developmental pharmacokinetic complexity,anatomic-genetic heterogeneity,and evidence chain gaps.Traditional agents exhibit critical limitations:digoxin’s narrow therapeutic index(0.5–0.9 ng/mL)is exacerbated by ABCB1 mutations(toxicity risk increases 4.1-fold),furosemide efficacy declines by 35%in neonates due to NKCC2 immaturity,andβ-blocker responses vary by CYP2D6 polymorphisms(poor metabolizers require 50–75%dose reduction).Novel strategies demonstrate transformative potential—CRISPR editing achieves 81%reversal of BMPR2-associated pulmonary vascular remodeling,metabolically matured cardiac organoids replicate adult myocardial energy metabolism for drug screening,and SGLT2 inhibitors activate triple mechanisms(calcium overload mitigation,mitophagy,fibrosis reversal).However,clinical translation requires overcoming developmental barriers:age-dependent enzyme expression(infant CYP2D6=30–60%adult activity),post-Fontan hepatotoxicity(bosentan trough concentrations elevates 1.8-fold),and AI model limitations(32%error in complex CHD).Future integration of placental transfer models,disease-specific organoids,and multi-omics mapping of FOXO/CRIM1 pathways will shift paradigms from symptom control to curative repair.
文摘Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surfacemarkers and allow aberrant differentiation of progenies.It facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance. Based on the current information, present review discusses and summarizes the recent advancements on the molecular mechanisms that derive epithelial plasticity and its major role in generating a subset of tumor cells with stemness properties and pathophysiological spread of tumor. This paper further highlights the critical need to examine the regulation of EMT and CSC pathways in identifying the novel probable therapeutic targets.These improved therapeutic strategies based on the co-administration of inhibitors of EMT, CSCs as well as differentiated tumor cells may provide improved antineoplastic response with no tumor relapse.
基金Supported by Construction of Engineering Laboratory of Jilin Development and Reform Commission(grant no.3J115AK93429)Jilin Provincial Science and Technology Department Medical Health Project(grant no.3D5195001429)
文摘BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.
基金Supported by the National Natural Science Foundation of China,No.81704084,No.81603529,and No.81673982the Science and Technology Projects of Jiangsu Provincial Bureau of Traditional Chinese Medicine,No.YB2017002 and No.YB2015002+4 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions,No.16KJB360002the Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX18_1541the Qing Lan Projectthe Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine(ZYX03KF63)Jiangsu Government Scholarship for Overseas Studies and China Scholarship Council
文摘BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion are from complex biological processes.However,the molecular mechanisms underlying the basis of microarray data profile,followed by peritoneal adhesion formation,are largely unknown.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis.We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods.We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.RESULTS In total,446 expressed genes were altered in peritoneal adhesion.We found that several hub genes(e.g.,tumor necrosis factor,interleukin 1 beta,interleukin 6,CX-C motif chemokine ligand 1,C-X-C motif chemokine ligand 2)were marked as significant biomarkers.Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway.According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies,TLR4,myeloid differentiation primary response protein 88(MyD88),and nuclear factor kappa B(NF-κB)played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion.The results of the microarray analysis were verified by the animal experiments.These findings may extend our understanding of the molecular mechanisms of PPA.CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.
基金The Cancer Association of South Africa,theSixth Research Framework Programme of the European UnionProject RIGHT,LSHB-CT-2004-005276South African NationalResearch Foundation and Poliomyelitis Research Foundationsupport research
文摘Primary liver cancer is the fifth most common malignan- cy in the world and is a leading cause of cancer-related mortality.Available treatment for hepatocellular carcino- ma(HCC),the commonest primary liver cancer,is rarely curative and there is a need to develop therapy that is more effective.Specific and powerful gene silencing that can be achieved by activating RNA interference(RNAi) has generated enthusiasm for exploiting this pathway for HCC therapy.Many studies have been carried out with the aim of silencing HCC-related cellular oncogenes or the hepatocarcinogenic hepatitis B virus(HBV)and hepatitis C virus(HCV).Proof of principle studies have demonstrated promising results,and an early clinical trial assessing RNAi-based HBV therapy is currently in progress.Although the data augur well,there are several significant hurdles that need to be overcome before the goal of RNAi-based therapy for HCC is realized.Particu- larly important are the efficient and safe delivery of RNAi effecters to target malignant tissue and the limitation of unintended harmful non-specific effects.
文摘There is little or no research initiated on enlightening Nigerians about the pathogenesis,targets for drug development and repositioning for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Coronavirus disease 2019(COVID-19)is a viral infection causing symptoms like dry cough,sore throat,nasal congestion,tiredness,fever,loss of taste,and smell etc.The disease was first reported in Wuhan,China,in December 2019.The infection is caused by SARS-CoV-2,which is the third introduction of a highly pathogenic coronavirus into the human population.Coronaviruses are viruses with a positive RNA envelope assigned toα,β,γ,andδgenera.Moreover,SARS-CoV-2 belongs to theβgenus.The four structural proteins ofβcoronavirus are membrane(M),envelope(E),spike(S),and nucleocapsid(N)protein,mediation of coronavirus host infection is established by spike(S)protein.Therefore,the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic.It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor,viral RNA synthesis and replication,3CLpro,RdRp,and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection.Furthermore,the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development.Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19,and mRNA-1273 targeting spike protein is the promising vaccine.However,as patient management and drug repositioning are taking place,it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection,to develop novel therapeutics.
