Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can r...Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. Methods Sixty-five unrelated cases （35 men and 30 women） who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography （CT） scan or magnetic resonance imaging （MRI）. The differential diagnosis of organic acidurias and fatty acid IS-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA （T8993G, T8993C, T9176C, A8344G, A3243G） were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 （26.2%） of the patients. The diagnosis was confirmed by autopsy in 6 （9.2%） patients. Results The patients had various forms of metabolic encephalomyopathy. Filly-nine （90.8%） of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty （30.8%） patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases （7.7%）. Of these, the A8344G mutation was detected in 2 patients. The T8993G T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） families by DNA sequencing. A G604C mutat展开更多
Angiotensin Ⅱ(Ang Ⅱ) is involved in endothelium injury during the development of hypertension. Tribulus terrestris(TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present ...Angiotensin Ⅱ(Ang Ⅱ) is involved in endothelium injury during the development of hypertension. Tribulus terrestris(TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats(SHRs) and its protective effects against Ang Ⅱ induced injury in human umbilical vein endothelial cells(HUVECs). SHRs were administered intragastrically with TT(17.2 or 8.6 g·kg^(-1)·d^(-1)) for 6 weeks, using valsartan(13.5 mg·kg^(-1)·d^(-1)) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang Ⅱ, endothelin^(-1)(ET^(-1)), superoxide dismutase(SOD) and malonaldehyde(MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10–6 mol·L^(-1) Ang Ⅱ. Cell Apoptosisapoptosis, intracellular reactive oxygen species(ROS) was assessed. Endothelial nitric oxide synthase(eN OS), ET^(-1), SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang Ⅱ, ET^(-1), NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang Ⅱ-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mR NA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.展开更多
基金This study was supported by grants from Peking University Center for Human Disease Genomics (No. 2001-2) and the National Natural Science Foundation of China (No. 30471832).
文摘Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. Methods Sixty-five unrelated cases （35 men and 30 women） who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography （CT） scan or magnetic resonance imaging （MRI）. The differential diagnosis of organic acidurias and fatty acid IS-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA （T8993G, T8993C, T9176C, A8344G, A3243G） were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 （26.2%） of the patients. The diagnosis was confirmed by autopsy in 6 （9.2%） patients. Results The patients had various forms of metabolic encephalomyopathy. Filly-nine （90.8%） of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty （30.8%） patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases （7.7%）. Of these, the A8344G mutation was detected in 2 patients. The T8993G T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） families by DNA sequencing. A G604C mutat
基金supported by Shandong Province‘Taishan Scholar’Construction Project Funds(No.2012-55)the National Natural Science Foundation of China(No.81573916)
文摘Angiotensin Ⅱ(Ang Ⅱ) is involved in endothelium injury during the development of hypertension. Tribulus terrestris(TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats(SHRs) and its protective effects against Ang Ⅱ induced injury in human umbilical vein endothelial cells(HUVECs). SHRs were administered intragastrically with TT(17.2 or 8.6 g·kg^(-1)·d^(-1)) for 6 weeks, using valsartan(13.5 mg·kg^(-1)·d^(-1)) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang Ⅱ, endothelin^(-1)(ET^(-1)), superoxide dismutase(SOD) and malonaldehyde(MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10–6 mol·L^(-1) Ang Ⅱ. Cell Apoptosisapoptosis, intracellular reactive oxygen species(ROS) was assessed. Endothelial nitric oxide synthase(eN OS), ET^(-1), SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang Ⅱ, ET^(-1), NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang Ⅱ-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mR NA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.
