Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detox...Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detoxication） in treating HIV/AIDS patients in the early or middle stage. Methods： Adopted was randomized double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients randomly divided into the ZY-4 group （36 patients） treated with ZY-4 and the control group （36 patients） treated with placebo. The treatment course was six months. The index of OD4^＋, OD8^＋ counts, body weight, clinical symptom scoring were estimated at 4 time points （0, 1, 3 and 6 month in the course）, and also the viral load before and after treatment. The whole course of observation was completed in 63 patients, 30 in the ZY-4 group and 33 in the control group. Results： OD4^＋ count in the ZY-4 group got elevated by 7.70 4±150.96/mm^3 on average, while that in the control group lowered by 27.33 4±85.28 /mm^3 . Fifteen out of the 30 patients in the ZY-4 group had their OD4^＋ count increased, which was evidently much higher than that in the control group （8/33, P〈0. 05）, suggesting that the efficacy of ZY-4 is superior to that of placebo in elevating OD4^＋ count. Moreover, ZY-4 showed actions in elevating OD45RA^＋ and OD8^＋ count, reducing HIV virus load, improving clinical symptom/sign and increasing body weight of patients. No obvious adverse reaction was found in the clinical trial. Conclusion： ZY-4 has an immunity-protective and/or rebuilding function in HIV/AIDS patients in the early and middle stage, and also shows effects in lowering viral load, increasing body weight and improving symptoms and signs to a certain degree.展开更多
Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidati...Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.展开更多
Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterize...Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterized by the infiltration of auto reactive lymphocytes specific to myelin through the blood-brain barrier,which results in the appearance of inflammatory demyelinating lesions caused by the death of the central nervous system myelinating cells,oligodendrocytes(Oh et al.,2018).There is a prevalence sexual with a ratio of three times more affected women than men.展开更多
基金Supported by the Projects of Ministry of Science and Tech-nology for 10th Five-year Plan (2001BA701A18)
文摘Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detoxication） in treating HIV/AIDS patients in the early or middle stage. Methods： Adopted was randomized double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients randomly divided into the ZY-4 group （36 patients） treated with ZY-4 and the control group （36 patients） treated with placebo. The treatment course was six months. The index of OD4^＋, OD8^＋ counts, body weight, clinical symptom scoring were estimated at 4 time points （0, 1, 3 and 6 month in the course）, and also the viral load before and after treatment. The whole course of observation was completed in 63 patients, 30 in the ZY-4 group and 33 in the control group. Results： OD4^＋ count in the ZY-4 group got elevated by 7.70 4±150.96/mm^3 on average, while that in the control group lowered by 27.33 4±85.28 /mm^3 . Fifteen out of the 30 patients in the ZY-4 group had their OD4^＋ count increased, which was evidently much higher than that in the control group （8/33, P〈0. 05）, suggesting that the efficacy of ZY-4 is superior to that of placebo in elevating OD4^＋ count. Moreover, ZY-4 showed actions in elevating OD45RA^＋ and OD8^＋ count, reducing HIV virus load, improving clinical symptom/sign and increasing body weight of patients. No obvious adverse reaction was found in the clinical trial. Conclusion： ZY-4 has an immunity-protective and/or rebuilding function in HIV/AIDS patients in the early and middle stage, and also shows effects in lowering viral load, increasing body weight and improving symptoms and signs to a certain degree.
基金supported by the National Natural Science Foundation of China,Nos.82271444(to JP),82271268(to BZ),and 82001346(to YL)the National Key Research and Development Program of China,No.2022YFE0210100(to BZ)。
文摘Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.
基金supported by a grant from the French Multiple Sclerosis Society(ARSEP,Grant Number:R20163LL)(to AMG)。
文摘Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterized by the infiltration of auto reactive lymphocytes specific to myelin through the blood-brain barrier,which results in the appearance of inflammatory demyelinating lesions caused by the death of the central nervous system myelinating cells,oligodendrocytes(Oh et al.,2018).There is a prevalence sexual with a ratio of three times more affected women than men.
