Background Cardiovascular disease has become a major cause of death worldwide.Atherosclerosis is the pathological basis of many cardiovascular diseases.It is well established that hemodynamics also play an important r...Background Cardiovascular disease has become a major cause of death worldwide.Atherosclerosis is the pathological basis of many cardiovascular diseases.It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development.In the process of inflammatory reaction,the damage of vascular endothelial cells is the initial link,and various factors can cause damage of endothelial cells.The change of shear stress is considered to be one of the important factors.In the body,vascular endothelial cells are constantly exposed to blood flow.Flow conditions critically regulate endothelial cell functions in the vasculature.Shear stress not only influences the endothelial cell morphology,migration,differentiation and proliferation,but also regulates the expression of proteins in the endothelial cells.Reduced shear stress resulting from disturbed blood flow can drive the development of vascular inflammatory lesions and promote the formation of atherosclerosis.In the present study,the objective of our study is the comprehensive identification of CX3CR1/NF-κB signaling pathway involved in low shear stress(LSS)-induced inflammation in HUVECs through protein profiling and cell function experiment.Methods Human umbilical vein endothelial cell was cultured onglass slides and placed in a parallel plate flow chamber.M199 culture medium was used for low laminar shear stress at 4.14 dyn/cm2,2 h for the testing group,CX3CR1 sh-RNA and NF-κB inhibitor PDTC are used to block the effects of CX3CR1 and P65.The expression levels of the protein were determined by western blot analysis.Mononuclear cell adhesion assays and scratch assays are used to detect cell adhesion and migration.Results Western blotting analyses revealed that compared with the controls,there is a significant increase in the expression of CX3CR1,nucleusP65,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)and Interleukin-6(IL-6),while the expression of cytosolic P65 and IκB was significantly reduced in human umbilical vein endothelial cells(HUVECs)treated with LSS.CX3CR1 Sh-RNA was use to reveal its effect on LSS-induced inflammation.Further,specific NF-κB P65 inhibitors(PDTC)were used to reveal the downstream NF-κB P65 exclusively involved in LSS-induced inflammation in HUVECs,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.Monocyte adhesion assay and scratch test revealed LSS promotes adhesion of monocytes and migration of cells,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.LSS is involved in the expression of adhesion moleculesand chemokines,which are important for the initiation of endothelial inflammation-related atherosclerosis.Conclusions The activation of CX3CR1/NF-κB signaling pathway induced by low shear stress in endothelial cells may lead to the future therapeutic targets of atherosclerotic inflammation.展开更多
Introduction: Low bodyweight type 2 DM is a distinct clinical entity having many inherent peculiarities seen in India and developing countries, constituting 11% to 25% of type 2 diabetic subjects. Our study aimed at a...Introduction: Low bodyweight type 2 DM is a distinct clinical entity having many inherent peculiarities seen in India and developing countries, constituting 11% to 25% of type 2 diabetic subjects. Our study aimed at assessing the prevalence of inflammatory markers like hsCRP, adiponectin and NF-κB expression in peripheral blood mononuclear cells in subjects with type 2 DM in relation to BMI. Materials and Methods: 57 consecutive type 2 diabetics were recruited for study, classified as Low Bodyweight (A = BMI < 18.5), Standard weight (B = BMI 18.5 - 24.99) and Obese (C = BMI ≥ 25). Group D comprised 14 healthy controls. They were evaluated for clinical parameters, FBG, 2hrPPBG, HbA1c, lipid profile and above mentioned inflammatory markers. Results: Serum hsCRP was significantly higher in all group of diabetics as compared to Group D but was lowest in Group A. Adiponectin levels were highest in Group D, similar in Groups B and C but lowest in Group A. NF-κB expression, though higher in diabetic subjects than controls (OD = 0.041 ± 0.006), was least in Group A (OD = 0.045 ± 0.005). Discussion and Conclusion: Our study revealed that Indians with type 2DM are in a pro-inflamematory state. Low bodyweight type 2 diabetics had the least pro-inflammatory load. This further supported the earlier observation of lesser macrovascular disease load and testifying that Low Bodyweight type2DM constitutes a distinct entity.展开更多
目的研究低频脉冲电刺激对脑卒中后吞咽障碍患者吞咽功能影响,以及对神经源性基因同源蛋白(Notch)/核转录因子-κB(NF-κB)信号通路的影响。方法选择2021年6月至2023年1月在河北省退役军人总医院治疗的脑卒中后吞咽障碍患者120例,其中男...目的研究低频脉冲电刺激对脑卒中后吞咽障碍患者吞咽功能影响,以及对神经源性基因同源蛋白(Notch)/核转录因子-κB(NF-κB)信号通路的影响。方法选择2021年6月至2023年1月在河北省退役军人总医院治疗的脑卒中后吞咽障碍患者120例,其中男性58例,女性62例;年龄45~68岁,平均年龄56.82岁;病程2~8周,平均病程4.61周。随机将患者分为2组,即研究组(常规训练+脉冲电刺激)、对照组(常规训练),每组60例。两组患者均进行营养脑神经细胞、降低颅内压、控制脑水肿和改善脑组织循环等常规治疗,且均进行吞咽康复训练;研究组加用低频脉冲电刺激治疗。治疗前和治疗结束后,应用洼田饮水试验对两组患者的吞咽功能进行检测。参考《摄食、吞咽障碍康复实用技术》评价患者临床疗效。评价治疗前后美国国立卫生院卒中量表(NIHSS)评分。检测治疗前后血液组织中Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达。结果治疗后,两组洼田饮水试验评分均降低,研究组比对照组更低[(2.23±0.64)分vs(3.02±0.81)分。P<0.01]。治疗后,研究组总有效率高于对照组患者(93.33%vs 75.00%。P<0.05)。治疗后,两组NIHSS评分均降低,研究组比对照组更低[(10.32±1.85)分vs(7.18±2.31)分。P<0.05]。治疗后,两组患者Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达均有降低(0.86±0.09 vs 1.42±0.12、0.74±0.11 vs 1.39±0.09、0.86±0.09 vs 1.52±0.14、0.79±0.07 vs 1.52±0.10。P<0.05),且研究组Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达低于对照组(0.86±0.09 vs 1.12±0.10、0.74±0.11 vs 1.04±0.12、0.86±0.09 vs 1.02±0.08、0.79±0.07 vs 1.04±0.11。P<0.05)。结论低频脉冲电刺激对脑卒中后吞咽障碍患者临床症状改善明显,且可能通过Notch/NF-κB信号通路改善患者症状。展开更多
基金supported by a project grant from the National Natural Science Foundation of China ( 31860261)
文摘Background Cardiovascular disease has become a major cause of death worldwide.Atherosclerosis is the pathological basis of many cardiovascular diseases.It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development.In the process of inflammatory reaction,the damage of vascular endothelial cells is the initial link,and various factors can cause damage of endothelial cells.The change of shear stress is considered to be one of the important factors.In the body,vascular endothelial cells are constantly exposed to blood flow.Flow conditions critically regulate endothelial cell functions in the vasculature.Shear stress not only influences the endothelial cell morphology,migration,differentiation and proliferation,but also regulates the expression of proteins in the endothelial cells.Reduced shear stress resulting from disturbed blood flow can drive the development of vascular inflammatory lesions and promote the formation of atherosclerosis.In the present study,the objective of our study is the comprehensive identification of CX3CR1/NF-κB signaling pathway involved in low shear stress(LSS)-induced inflammation in HUVECs through protein profiling and cell function experiment.Methods Human umbilical vein endothelial cell was cultured onglass slides and placed in a parallel plate flow chamber.M199 culture medium was used for low laminar shear stress at 4.14 dyn/cm2,2 h for the testing group,CX3CR1 sh-RNA and NF-κB inhibitor PDTC are used to block the effects of CX3CR1 and P65.The expression levels of the protein were determined by western blot analysis.Mononuclear cell adhesion assays and scratch assays are used to detect cell adhesion and migration.Results Western blotting analyses revealed that compared with the controls,there is a significant increase in the expression of CX3CR1,nucleusP65,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)and Interleukin-6(IL-6),while the expression of cytosolic P65 and IκB was significantly reduced in human umbilical vein endothelial cells(HUVECs)treated with LSS.CX3CR1 Sh-RNA was use to reveal its effect on LSS-induced inflammation.Further,specific NF-κB P65 inhibitors(PDTC)were used to reveal the downstream NF-κB P65 exclusively involved in LSS-induced inflammation in HUVECs,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.Monocyte adhesion assay and scratch test revealed LSS promotes adhesion of monocytes and migration of cells,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.LSS is involved in the expression of adhesion moleculesand chemokines,which are important for the initiation of endothelial inflammation-related atherosclerosis.Conclusions The activation of CX3CR1/NF-κB signaling pathway induced by low shear stress in endothelial cells may lead to the future therapeutic targets of atherosclerotic inflammation.
文摘Introduction: Low bodyweight type 2 DM is a distinct clinical entity having many inherent peculiarities seen in India and developing countries, constituting 11% to 25% of type 2 diabetic subjects. Our study aimed at assessing the prevalence of inflammatory markers like hsCRP, adiponectin and NF-κB expression in peripheral blood mononuclear cells in subjects with type 2 DM in relation to BMI. Materials and Methods: 57 consecutive type 2 diabetics were recruited for study, classified as Low Bodyweight (A = BMI < 18.5), Standard weight (B = BMI 18.5 - 24.99) and Obese (C = BMI ≥ 25). Group D comprised 14 healthy controls. They were evaluated for clinical parameters, FBG, 2hrPPBG, HbA1c, lipid profile and above mentioned inflammatory markers. Results: Serum hsCRP was significantly higher in all group of diabetics as compared to Group D but was lowest in Group A. Adiponectin levels were highest in Group D, similar in Groups B and C but lowest in Group A. NF-κB expression, though higher in diabetic subjects than controls (OD = 0.041 ± 0.006), was least in Group A (OD = 0.045 ± 0.005). Discussion and Conclusion: Our study revealed that Indians with type 2DM are in a pro-inflamematory state. Low bodyweight type 2 diabetics had the least pro-inflammatory load. This further supported the earlier observation of lesser macrovascular disease load and testifying that Low Bodyweight type2DM constitutes a distinct entity.
文摘目的研究低频脉冲电刺激对脑卒中后吞咽障碍患者吞咽功能影响,以及对神经源性基因同源蛋白(Notch)/核转录因子-κB(NF-κB)信号通路的影响。方法选择2021年6月至2023年1月在河北省退役军人总医院治疗的脑卒中后吞咽障碍患者120例,其中男性58例,女性62例;年龄45~68岁,平均年龄56.82岁;病程2~8周,平均病程4.61周。随机将患者分为2组,即研究组(常规训练+脉冲电刺激)、对照组(常规训练),每组60例。两组患者均进行营养脑神经细胞、降低颅内压、控制脑水肿和改善脑组织循环等常规治疗,且均进行吞咽康复训练;研究组加用低频脉冲电刺激治疗。治疗前和治疗结束后,应用洼田饮水试验对两组患者的吞咽功能进行检测。参考《摄食、吞咽障碍康复实用技术》评价患者临床疗效。评价治疗前后美国国立卫生院卒中量表(NIHSS)评分。检测治疗前后血液组织中Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达。结果治疗后,两组洼田饮水试验评分均降低,研究组比对照组更低[(2.23±0.64)分vs(3.02±0.81)分。P<0.01]。治疗后,研究组总有效率高于对照组患者(93.33%vs 75.00%。P<0.05)。治疗后,两组NIHSS评分均降低,研究组比对照组更低[(10.32±1.85)分vs(7.18±2.31)分。P<0.05]。治疗后,两组患者Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达均有降低(0.86±0.09 vs 1.42±0.12、0.74±0.11 vs 1.39±0.09、0.86±0.09 vs 1.52±0.14、0.79±0.07 vs 1.52±0.10。P<0.05),且研究组Notch、Hes1、p-NF-κBp65/NF-κBp65、Bax蛋白表达低于对照组(0.86±0.09 vs 1.12±0.10、0.74±0.11 vs 1.04±0.12、0.86±0.09 vs 1.02±0.08、0.79±0.07 vs 1.04±0.11。P<0.05)。结论低频脉冲电刺激对脑卒中后吞咽障碍患者临床症状改善明显,且可能通过Notch/NF-κB信号通路改善患者症状。
基金Funds from National Natural Sciences Foundation (No.30771986,30772356)Beijing Natural Sciences Foundation (No.7092016, 7062010)Science and Technology NewStar Funds of Beijing (No.2004B27, 2005A29)
