Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Er...Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.展开更多
Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy(LVH) in type 2 diabetic rats. Methods Type 2 diabetic mellitus(DM) model rats were established by intraperitoneally injecting with 3...Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy(LVH) in type 2 diabetic rats. Methods Type 2 diabetic mellitus(DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy(LVH) by ultrasound examination, and randomly assigned into three groups: untreated(DM-LVH, n=7), treated with insulin(DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3(DM-LVH+VD, n=6). Healthy male rats were used as the controls group(n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later. Results In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group(P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased(all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group(P<0.05), whereas the other parameters were significantly decreased(all P<0.05). Conclusion 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.展开更多
建立了一种简单、实用的光诱导一锅法高选择性N-甲基喹喔啉酮类化合物和苯乙酮类化合物合成一系列3-烷基化喹唑啉-2(1H)-酮类化合物的方法。该方法在室温条件下,以玫瑰红作为光催化剂,在18 W 460 nm的蓝色LED下照射8 h,通过直接C3-H活...建立了一种简单、实用的光诱导一锅法高选择性N-甲基喹喔啉酮类化合物和苯乙酮类化合物合成一系列3-烷基化喹唑啉-2(1H)-酮类化合物的方法。该方法在室温条件下,以玫瑰红作为光催化剂,在18 W 460 nm的蓝色LED下照射8 h,通过直接C3-H活化的方案,较好收率获得一系列相应的3-烷基化喹喔啉-2(1H)-酮类化合物,最高产率可达到76%。反应体系具有经济实用性和底物适用范围广的特点,为3-烷基化喹喔啉-2(1H)-酮类化合物类化合物的合成提供了一种简便经济的方法。展开更多
基金supported by the National Natural Science Foundation of China(U22A20272,82173807,82170497)。
文摘Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.
基金Supported by the Research Fund for Public Health of the Health and Family Planning Commission of Wuhan Municipality(WG13B12)
文摘Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy(LVH) in type 2 diabetic rats. Methods Type 2 diabetic mellitus(DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy(LVH) by ultrasound examination, and randomly assigned into three groups: untreated(DM-LVH, n=7), treated with insulin(DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3(DM-LVH+VD, n=6). Healthy male rats were used as the controls group(n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later. Results In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group(P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased(all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group(P<0.05), whereas the other parameters were significantly decreased(all P<0.05). Conclusion 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.
文摘建立了一种简单、实用的光诱导一锅法高选择性N-甲基喹喔啉酮类化合物和苯乙酮类化合物合成一系列3-烷基化喹唑啉-2(1H)-酮类化合物的方法。该方法在室温条件下,以玫瑰红作为光催化剂,在18 W 460 nm的蓝色LED下照射8 h,通过直接C3-H活化的方案,较好收率获得一系列相应的3-烷基化喹喔啉-2(1H)-酮类化合物,最高产率可达到76%。反应体系具有经济实用性和底物适用范围广的特点,为3-烷基化喹喔啉-2(1H)-酮类化合物类化合物的合成提供了一种简便经济的方法。
