Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ...Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectivel...BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.展开更多
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
基金supported by the Fundamental Research Program of Shanxi Province of China,No.20210302124277the Science Foundation of Shanxi Bethune Hospital,No.2021YJ13(both to JW)。
文摘Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金Supported by the National High Level Hospital Clinical Research Funding,No.2023-NHLHCRF-BQ-32 and No.2023-NHLHCRFYYPPLC-ZR-13the Elite Medical Professionals Project of China-Japan Friendship Hospital,No.ZRJY2024-GG01.
文摘BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.
