目的探索珠海地区NRXN1和NLGN1基因多态性与儿童孤独症易感性的关系,为孤独症的防治提供科学依据。方法采用病例对照的研究方法,选取2011-2016年就诊于珠海市妇幼保健院的123例珠海地区的孤独症患儿和506例健康对照。采用口腔拭子采集...目的探索珠海地区NRXN1和NLGN1基因多态性与儿童孤独症易感性的关系,为孤独症的防治提供科学依据。方法采用病例对照的研究方法,选取2011-2016年就诊于珠海市妇幼保健院的123例珠海地区的孤独症患儿和506例健康对照。采用口腔拭子采集口腔上皮细胞以提取DNA,采用Sequenom Mass Arrayplat form分型技术对NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544进行基因分型。结果NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因型分布在孤独症组和健康对照组比较,差异无统计学意义;但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824存在基因与基因间的交互作用(预测准确率为0.480,交叉验证一致性为10/10,P=0.040)。结论NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因多态性可能与孤独症易感性没有关联,但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824之间的交互作用可能是孤独症易感性的影响因素。展开更多
脆性X综合征(fragile X syndrome,FXS)是导致精神发育迟滞最为常见的原因之一,然而现代医学至今未取得很好的疗效。临床实践及科学研究表明,针刺疗法对精神发育迟滞具有较为明显的治疗效果,但迄今对其治疗作用机制的研究尚不成熟。鉴于...脆性X综合征(fragile X syndrome,FXS)是导致精神发育迟滞最为常见的原因之一,然而现代医学至今未取得很好的疗效。临床实践及科学研究表明,针刺疗法对精神发育迟滞具有较为明显的治疗效果,但迄今对其治疗作用机制的研究尚不成熟。鉴于此,该文将围绕目前对FXS的研究现状,对NLGN-3蛋白作为针刺治疗FXS作用机制靶目标的可行性进行阐述。展开更多
Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine,with its precise underlying causes remaining incompletely understood.In this study,we provide evidence that circular RNA ...Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine,with its precise underlying causes remaining incompletely understood.In this study,we provide evidence that circular RNA circNlgn plays a pivotal role in promoting the development of colitis.Colitis patients produce significant higher levels of circNign.Transgenic mice expressing circNlgn exhibit heightened susceptibility to colitis development and progression,primarily attributed to the presence of the protein isoform Nlgn173 encoded by circNign.Nlgn173 undergoes translocation into cellnuclei,where it interacts with actin,impeding the binding of actin-related protein 2 and 3(Arp2/3)complex to actin molecules.Consequently,this leads to a reduction in actin polymerization.Mechanistically,Nlgn173 enhances tyrosine-53 phosphorylation of nuclear actin,diminishing its capacity to interact with the Arp2/3 complex and causing a decrease in filamentous actin levels.These alterations in actin dynamics result in inhibited cell cycle progression,increased apoptosis,and decreased proliferation of colonic epithelial cells,thereby exacerbating colitis development and progression.In contrast,the silencing of circNign or the targeted inhibition of Nlgn173 translation and nuclear translocation leads to the promotion of nuclear actin polymerization,enhanced cell survival,and reduced apoptosis and ultimately improves the outcome of colitis in vivo.Interestingly,nuclear actin polymerization is highly related with expression of PIAS3,which modulates signal transducer and activator of transcription 3 and NF-kB activity in colitis.Strategies such as circNlgn knockdown and targeting nuclear actin polymerization of the colonic epithelium may explore a novel avenue for acute ulcerativecolitisclinical intervention.展开更多
Objective To study the effects of arsenic exposure on1neurological function including voluntaryymotor ability,anxiety,and short-term memory ability of rats,as well as its impact on the expression levels of synaptic fu...Objective To study the effects of arsenic exposure on1neurological function including voluntaryymotor ability,anxiety,and short-term memory ability of rats,as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1(NLGN1),glutamate receptor 2A(NR2A),and postsynaptic density protein 95(PSD95).Methods Forty 3-week-old male specific pathogen free(SPF)grade Wistar rats[weighing(453.97±35.68)g]were selected and divided into four groups using a random number table:O(control group)and 2,10,and 50 mg/L arsenic exposure groups,with 10 rats in each group.They were given deionized water and 2,10,and 50 mg/L sodium arsenite solutions for 12 weeks,respectively.The open field experiment and Y-maze experiment were used to test the voluntary motor ability,anxiety,and short-term memory ability of rats.Nissl staining was used to observe the pathological damage of the hippocampus in the brain.Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1,NR2A,and PSD95 in the hippocampus,respectively.Results The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group,the movement distances in the central area in the 2,10,and 50 mg/L arsenic exposure groupswere reduced compared to the control group,and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group(P<0.05).The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group(P<0.05).The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures,tightly arranged cells,appearing blue purple in color and clear visible nuclei.However,the number of Nissl bodies decreased,intercellular gaps increased,disordered arrangement increased,cytoplasmic staining was lighter,and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2,10 and 50 mg/L arsenic exposure groups.The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1,NR2A,and PSD95 in the hippocampal tissues of the four groups(F=13.85,44.94,4.63,P<0.05).The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group(0.65±0.07,0.69±0.03 vs 1.00±0.04,0.51±0.11,0.51±0.13 vs 1.00±0.07,P<0.05),and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group(0.51±0.09 vs 1.00±0.05,P<0.05).Conclusion Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1,NR2A,and PSD95.展开更多
文摘目的探索珠海地区NRXN1和NLGN1基因多态性与儿童孤独症易感性的关系,为孤独症的防治提供科学依据。方法采用病例对照的研究方法,选取2011-2016年就诊于珠海市妇幼保健院的123例珠海地区的孤独症患儿和506例健康对照。采用口腔拭子采集口腔上皮细胞以提取DNA,采用Sequenom Mass Arrayplat form分型技术对NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544进行基因分型。结果NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因型分布在孤独症组和健康对照组比较,差异无统计学意义;但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824存在基因与基因间的交互作用(预测准确率为0.480,交叉验证一致性为10/10,P=0.040)。结论NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因多态性可能与孤独症易感性没有关联,但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824之间的交互作用可能是孤独症易感性的影响因素。
文摘脆性X综合征(fragile X syndrome,FXS)是导致精神发育迟滞最为常见的原因之一,然而现代医学至今未取得很好的疗效。临床实践及科学研究表明,针刺疗法对精神发育迟滞具有较为明显的治疗效果,但迄今对其治疗作用机制的研究尚不成熟。鉴于此,该文将围绕目前对FXS的研究现状,对NLGN-3蛋白作为针刺治疗FXS作用机制靶目标的可行性进行阐述。
基金supported by the grants from Canadian Institutes of Health Research(PJT-155962 and PJT-166107)to B.B.Y.
文摘Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine,with its precise underlying causes remaining incompletely understood.In this study,we provide evidence that circular RNA circNlgn plays a pivotal role in promoting the development of colitis.Colitis patients produce significant higher levels of circNign.Transgenic mice expressing circNlgn exhibit heightened susceptibility to colitis development and progression,primarily attributed to the presence of the protein isoform Nlgn173 encoded by circNign.Nlgn173 undergoes translocation into cellnuclei,where it interacts with actin,impeding the binding of actin-related protein 2 and 3(Arp2/3)complex to actin molecules.Consequently,this leads to a reduction in actin polymerization.Mechanistically,Nlgn173 enhances tyrosine-53 phosphorylation of nuclear actin,diminishing its capacity to interact with the Arp2/3 complex and causing a decrease in filamentous actin levels.These alterations in actin dynamics result in inhibited cell cycle progression,increased apoptosis,and decreased proliferation of colonic epithelial cells,thereby exacerbating colitis development and progression.In contrast,the silencing of circNign or the targeted inhibition of Nlgn173 translation and nuclear translocation leads to the promotion of nuclear actin polymerization,enhanced cell survival,and reduced apoptosis and ultimately improves the outcome of colitis in vivo.Interestingly,nuclear actin polymerization is highly related with expression of PIAS3,which modulates signal transducer and activator of transcription 3 and NF-kB activity in colitis.Strategies such as circNlgn knockdown and targeting nuclear actin polymerization of the colonic epithelium may explore a novel avenue for acute ulcerativecolitisclinical intervention.
文摘Objective To study the effects of arsenic exposure on1neurological function including voluntaryymotor ability,anxiety,and short-term memory ability of rats,as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1(NLGN1),glutamate receptor 2A(NR2A),and postsynaptic density protein 95(PSD95).Methods Forty 3-week-old male specific pathogen free(SPF)grade Wistar rats[weighing(453.97±35.68)g]were selected and divided into four groups using a random number table:O(control group)and 2,10,and 50 mg/L arsenic exposure groups,with 10 rats in each group.They were given deionized water and 2,10,and 50 mg/L sodium arsenite solutions for 12 weeks,respectively.The open field experiment and Y-maze experiment were used to test the voluntary motor ability,anxiety,and short-term memory ability of rats.Nissl staining was used to observe the pathological damage of the hippocampus in the brain.Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1,NR2A,and PSD95 in the hippocampus,respectively.Results The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group,the movement distances in the central area in the 2,10,and 50 mg/L arsenic exposure groupswere reduced compared to the control group,and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group(P<0.05).The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group(P<0.05).The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures,tightly arranged cells,appearing blue purple in color and clear visible nuclei.However,the number of Nissl bodies decreased,intercellular gaps increased,disordered arrangement increased,cytoplasmic staining was lighter,and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2,10 and 50 mg/L arsenic exposure groups.The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1,NR2A,and PSD95 in the hippocampal tissues of the four groups(F=13.85,44.94,4.63,P<0.05).The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group(0.65±0.07,0.69±0.03 vs 1.00±0.04,0.51±0.11,0.51±0.13 vs 1.00±0.07,P<0.05),and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group(0.51±0.09 vs 1.00±0.05,P<0.05).Conclusion Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1,NR2A,and PSD95.
