Our understanding of the nervous tissues that affect the wing flapping of insects mainly focuses on the brain,but wing flapping is a rhythmic movement related to the central pattern generator in the ventral nerve cord...Our understanding of the nervous tissues that affect the wing flapping of insects mainly focuses on the brain,but wing flapping is a rhythmic movement related to the central pattern generator in the ventral nerve cord.To verify whether the neural activity of the abdominal ganglion of the honeybee(Apis mellifera)affects the flapping-wing flight,we profiled the response characteristics of indirect flight muscles to abdominal ganglion excitation.Strikingly,a change in the neural activity of ganglion 3 or ganglion 4 has a stronger effect on the electrophysiological activity of indirect flight muscles than that of ganglion 5.The electrophysiological activity of vertical indirect flight muscles is affected more by the change in neural activity of the abdominal ganglion than that of lateral indirect flight muscles.Moreover,the change in neural activity of the abdominal ganglion mainly causes the change in the muscular activity of indirect wing muscles,but the activity patterns change relatively little and there is little change in the complicated details.This work improves our understanding of the neuroregulatory mechanisms associated with the flapping-wing flight of honeybees.展开更多
Objective：To investigate the production of nitric oxide（NO） and the expression of inducible nitric oxide synthase （iNOS）, and their possible role in abdominal aortic aneurysm （AAA）. Methods： A total of 28 pati...Objective：To investigate the production of nitric oxide（NO） and the expression of inducible nitric oxide synthase （iNOS）, and their possible role in abdominal aortic aneurysm （AAA）. Methods： A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells （SMCs）. Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel χ^2 test and Kendall correlation. Results ： Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls （P〈0.05） and the patients with occlusive arteries （P〈0.05）. iNOS protein and media NOx （nitrite＋nitrate） also increased in cultured SMCs from human AAA （n=4, P〈0.05）, while plasma NOx decreased in patients with AAA （n= 25） compared to the healthy controls （n=20）. There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall （Kendall coefficient = 0. 5032, P= 0. 0029）. Conclusion： SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.展开更多
The aim of the present study is to address the effect of rapamycin on abdominal aortic aneurysm（AAA） and the potential mechanisms. A clinically relevant AAA model was induced in apolipoprotein E-deficient（ApoE-/-）...The aim of the present study is to address the effect of rapamycin on abdominal aortic aneurysm（AAA） and the potential mechanisms. A clinically relevant AAA model was induced in apolipoprotein E-deficient（ApoE-/-） mice, in which miniosmotic pump was implanted subcutaneously to deliver angiotensin Ⅱ（Ang Ⅱ） for 14 days. Male ApoE-/-mice were randomly divided into 3 groups： saline infusion, Ang Ⅱ infusion, and Ang Ⅱ infusion plus intraperitoneal injection of rapamycin. The diameter of the supra-renal abdominal aorta was measured by ultrasonography at the end of the infusion. Then aortic tissue was excised and examined by Western blotting and histoimmunochemistry. Ang Ⅱ with or without rapamycin treatment was applied to the cultured vascular smooth muscle cells（VSMCs） in vitro. The results revealed that rapamycin treatment significantly attenuated the incidence of Ang Ⅱinduced-AAA in ApoE-/-mice. Histologic analysis showed that rapamycin treatment decreased disarray of elastin fibers and VSMCs hyperplasia in the medial layer. Immunochemistry staining and Western blotting documented the increased phospho-ERKl/2 and ERK1/2 expression in aortic walls in Ang Ⅱ induced-AAA,as well as in human lesions. Whereas in the rapamycintreated group, decreased phospho-ERK1/2 expression level was detected. Moreover, rapamycin reversed Ang Ⅱ-induced VSMCs phenotypic change both in vivo and in vitro. Based on those results, we confirmed that rapamycin therapy suppressed Ang Ⅱ-induced AAA formation in mice, partially via VSMCs phenotypic modulation and down-regulation of ERK1/2 activity.展开更多
Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanis...Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanisms.Using single-cell RNA sequencing,we analyzed the molecular profile of individual cells within control and AAA abdominal aortas.We found cellular heterogeneity,with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells(VSMCs)in AAA.Up-regulated genes in AAA were associated with muscle tissue development and apoptosis.Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA.Additionally,VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation.Similar observations were made in a mouse model of AAA induced by Angiotensin II,further affirming the relevance of our findings to human AAA.The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention.Nicotinamide phosphoribosyltransferase(NAMPT,also named VISFATIN)signaling emerged as a signature event in AAA.NAMPT was significantly downregulated in AAA.NAMPT-extracellular vesicles(EVs)derived from mesenchymal stem cells restored NAMPT levels,and offered protection against AAA.Furthermore,NAMPT-EVs not only repressed injuries,such as cell senescence and DNA damage,but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models,suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment.These findings shed light on the cellular heterogeneity and injuries in AAA,and offered promising therapeutic intervention for AAA treatment.展开更多
基金supported by the National Natural Science Foundation of China,Grant Number:51475258。
文摘Our understanding of the nervous tissues that affect the wing flapping of insects mainly focuses on the brain,but wing flapping is a rhythmic movement related to the central pattern generator in the ventral nerve cord.To verify whether the neural activity of the abdominal ganglion of the honeybee(Apis mellifera)affects the flapping-wing flight,we profiled the response characteristics of indirect flight muscles to abdominal ganglion excitation.Strikingly,a change in the neural activity of ganglion 3 or ganglion 4 has a stronger effect on the electrophysiological activity of indirect flight muscles than that of ganglion 5.The electrophysiological activity of vertical indirect flight muscles is affected more by the change in neural activity of the abdominal ganglion than that of lateral indirect flight muscles.Moreover,the change in neural activity of the abdominal ganglion mainly causes the change in the muscular activity of indirect wing muscles,but the activity patterns change relatively little and there is little change in the complicated details.This work improves our understanding of the neuroregulatory mechanisms associated with the flapping-wing flight of honeybees.
基金Supported by the National Natural Science Foundation of China (No. 39800177)
文摘Objective：To investigate the production of nitric oxide（NO） and the expression of inducible nitric oxide synthase （iNOS）, and their possible role in abdominal aortic aneurysm （AAA）. Methods： A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells （SMCs）. Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel χ^2 test and Kendall correlation. Results ： Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls （P〈0.05） and the patients with occlusive arteries （P〈0.05）. iNOS protein and media NOx （nitrite＋nitrate） also increased in cultured SMCs from human AAA （n=4, P〈0.05）, while plasma NOx decreased in patients with AAA （n= 25） compared to the healthy controls （n=20）. There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall （Kendall coefficient = 0. 5032, P= 0. 0029）. Conclusion： SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.
基金supported by grants from the National Natural Science Foundation of China(No.81570325)the Fundamental Research Funds for the Central Universities
文摘The aim of the present study is to address the effect of rapamycin on abdominal aortic aneurysm（AAA） and the potential mechanisms. A clinically relevant AAA model was induced in apolipoprotein E-deficient（ApoE-/-） mice, in which miniosmotic pump was implanted subcutaneously to deliver angiotensin Ⅱ（Ang Ⅱ） for 14 days. Male ApoE-/-mice were randomly divided into 3 groups： saline infusion, Ang Ⅱ infusion, and Ang Ⅱ infusion plus intraperitoneal injection of rapamycin. The diameter of the supra-renal abdominal aorta was measured by ultrasonography at the end of the infusion. Then aortic tissue was excised and examined by Western blotting and histoimmunochemistry. Ang Ⅱ with or without rapamycin treatment was applied to the cultured vascular smooth muscle cells（VSMCs） in vitro. The results revealed that rapamycin treatment significantly attenuated the incidence of Ang Ⅱinduced-AAA in ApoE-/-mice. Histologic analysis showed that rapamycin treatment decreased disarray of elastin fibers and VSMCs hyperplasia in the medial layer. Immunochemistry staining and Western blotting documented the increased phospho-ERKl/2 and ERK1/2 expression in aortic walls in Ang Ⅱ induced-AAA,as well as in human lesions. Whereas in the rapamycintreated group, decreased phospho-ERK1/2 expression level was detected. Moreover, rapamycin reversed Ang Ⅱ-induced VSMCs phenotypic change both in vivo and in vitro. Based on those results, we confirmed that rapamycin therapy suppressed Ang Ⅱ-induced AAA formation in mice, partially via VSMCs phenotypic modulation and down-regulation of ERK1/2 activity.
基金funded by the National Natural Science Grant of China(No.82072225,82272246)High-level Hospital Construction Project of Guangdong Provincial People’s Hospital(No.DFJHBF202104,No.DFJH201918)+1 种基金Science and Technology Program of Guangzhou,China(No.202206010044)Guangdong Basic and Applied Basic Research Foundation(2021B1515120062).
文摘Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanisms.Using single-cell RNA sequencing,we analyzed the molecular profile of individual cells within control and AAA abdominal aortas.We found cellular heterogeneity,with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells(VSMCs)in AAA.Up-regulated genes in AAA were associated with muscle tissue development and apoptosis.Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA.Additionally,VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation.Similar observations were made in a mouse model of AAA induced by Angiotensin II,further affirming the relevance of our findings to human AAA.The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention.Nicotinamide phosphoribosyltransferase(NAMPT,also named VISFATIN)signaling emerged as a signature event in AAA.NAMPT was significantly downregulated in AAA.NAMPT-extracellular vesicles(EVs)derived from mesenchymal stem cells restored NAMPT levels,and offered protection against AAA.Furthermore,NAMPT-EVs not only repressed injuries,such as cell senescence and DNA damage,but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models,suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment.These findings shed light on the cellular heterogeneity and injuries in AAA,and offered promising therapeutic intervention for AAA treatment.
