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Serum testosterone levels and excessive erythrocytosis during the process of adaptation to high altitudes

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Asian Journal of Andrology 2013年第3期15卷 368-374页

作者： Gustavo F Gonzales high altitude research institute and department of biological and physiological sciences Faculty of Sciences and Philosophy Universidad Peruana Cayetano Heredia Lima 31 Peru

Populations living at high altitudes （HAs）, particularly in the Peruvian Andes, are characterized by a mixture of subjects with erythrocytosis （16 g dl-1〈haemoglobin （Hb）≤21 gdl-1） and others with excessive erythrocytosis （EE）（Hb〉21 g dl-1）. Elevated haemoglobin values （EE） are associated with chronic mountain sickness, a condition reflecting the lack of adaptation to HA. According to current data, native men from regions of HA are not adequately adapted to live at such altitudes if they have elevated serum testosterone levels. This seems to be due to an increased conversion of dehydroepiandrosterone sulphate （DH EAS） to testosterone. Men with erythrocytosis at HAs show higher serum androstenedione levels and a lower testosterone/androstenedione ratio than men with EE, suggesting reduced 17beta-hydroxysteroid dehydrogenase （17beta-HSD） activity. Lower 17beta-HSD activity via A4-steroid production in men with erythrocytosis at HA may protect against elevated serum testosterone levels, thus preventing EE. The higher conversion of DHEAS to testosterone in subjects with EE indicates increased 17beta-HSD activity via the A5-pathway. Currently, there are various situations in which people live （human biodiversity） with low or high haemoglobin levels at HA. Antiquity could be an important adaptation component for life at HA, and testosterone seems to participate in this process.

关键词： chronic mountain sickness DHEA haemoglobin high altitudes men oestradiol women

Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

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Neural Regeneration research 2025年第4期20卷 1015-1030页

作者： Ruoyu Huang Qiuyu Pang Lexin Zheng Jiaxi Lin Hanxi Li Lingbo Wan Tao Wang department of Forensic Science School of Basic Medicine and Biological SciencesSuzhou Medicine College of Soochow UniversitySuzhouJiangsu ProvinceChina

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and *** plays a key role in the establishment and maintenance of the central nervous *** brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and *** brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental ***,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system *** hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and *** cholesterol levels are associated with the risk of intracerebral ***,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell *** cholesterol accumulation in the brain has been found after intracerebral *** this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell *** also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

关键词： cell death cholesterol metabolism intracerebral hemorrhage myelination therapeutic target

A new horizon for neuroscience:terahertz biotechnology in brain research

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Neural Regeneration research 2025年第2期20卷 309-325页

作者： Zhengping Pu Yu Wu Zhongjie Zhu Hongwei Zhao Donghong Cui Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina department of Psychiatry Kangci Hospital of JiaxingTongxiangZhejiang ProvinceChina Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied PhysicsChinese Academy of ScienceShanghaiChina National Facility for Protein Science in Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina

Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain *** this article,we review the development of terahertz biotechnology and its applications in the field of *** evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease,cerebrovascular disease,glioma,psychiatric disease,traumatic brain injury,and myelin *** vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric *** the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood,the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic ***,the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical *** review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.

关键词： biological effect brain neuron neuropsychiatry neuroscience non-thermal effect terahertz imaging terahertz radiation terahertz spectroscopy terahertz technology

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang institute of Life sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina department of Neurology and institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

Tetrandrine inhibits Ca2+-activated chloride channel in cultured human umbilical vein endothelial cells

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Acta Pharmacologica Sinica 2004年第3期25卷 73-79页

作者： Qi-zhi FANG1,2,Ning ZHONG1,3,Yi ZHANG1,Zhao-nian ZHOU1,4 1physiological Lab of Hypoxia,Shanghai institute of biologicalsciences,Chinese Academy ofsciences,Shanghai200031,China 3department of Molecular and Cell Biology,University of California at Berkeley,Berkeley,CA 94720,USA 2 Now in Cardiovascularresearch institute,University of Cali- fornia at San Francisco,San Francisco,CA 94143,USA physiological Lab of Hypoxia Shanghai Institute of Biological Sciences Chinese Academy of Sciences Shanghai 200031 China department of Molecular and Cell Biology University of California at Berkeley

AIM: To characterize the electrophysiological and kinetic properties of Ca2+-activated chloride channel (CaCC) in cultured human umbilical vein endothelial cell line (HUVEC), and test the inhibitory effects of tetrandrine (Tet) on CaCC. METHODS: Ca2+-activated Cl- currents (ICl,Ca) were recorded by patch-clamp whole cell configurations. [Ca2+]i was measured via intracellular Fura-2 fluorescence intensities. RESULTS: ICl,Ca was activated by increasing [Ca2+]i via direct elevation of intracellular calcium. ICl,Ca showed an apparent outward rectification properties, and it was activated in a voltage- and calcium-dependent mode. Tet dose-dependently inhibited ICl,Ca, the IC50 was (5.2±0.4) μmol/L (n=8 cells). Tet suppressed both voltage-dependent and calcium-dependent activation of ICl,Ca. The activa- tion time constant was (326±12) ms [in the presence of 10 μmol/L Tet, compared to control (175±17) ms, at +100 mV], and Ca2+ concentration for half maximal activation was (387±61) nmol/L for Tet (compared to control (287±36) nmol/L. CONCLUSIONS: Tet effectively blocked ICl,Ca, and such effects might be due to its inhibitory effects on the activation process of Ca2+-activated chloride channel.

关键词： chloride channels endothelium tetrandrine patch-clamp techniques calcium

Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

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Neural Regeneration research 2025年第1期20卷 199-200页

作者： Srishti Chawla Mikael Molin Thomas Nystrom institute for Biomedicine Sahlgrenska AcademyCentre for Ageing and Health-AgeCapUniversity of GothenburgGothenburgSweden department of Life sciences Chalmers University of TechnologyGothenburgSweden

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and *** biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated *** is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate *** calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

关键词： activation dinuclear conserved

Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural Regeneration research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules MJanssen Daalen Aurélien Patoz Julien FBally Martin Kopp Davide Malatesta Bastiaan RBloem institute of Sport sciences University of LausanneLausanneSwitzerland Radboud University Medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands Radboud University Medical Center Department of Medical BioSciencesNijmegenThe Netherlands research and Development department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation

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National Science Review 2020年第2期7卷 391-402页

作者： Ouzhuluobu Yaoxi He Haiyi Lou Chaoying Cui Lian Deng Yang Gao Wangshan Zheng Yongbo Guo Xiaoji Wang Zhilin Ning Jun Li Bin Li Caijuan Bai Baimakangzhuo Gonggalanzi Dejiquzong Bianba Duojizhuoma Shiming Liu Tianyi Wu Shuhua Xu Xuebin Qi Bing Su high altitude Medical research Center School of Medicine Tibetan University Fukang Obstetrics Gynecology and Children Branch Hospital Tibetan Fukang Hospital State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Chinese Academy of sciences Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational Biology Shanghai Institute of Nutrition and Health Shanghai Institutes for Biological SciencesUniversity of Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Center for Disease Control Tibet Autonomous Region National Key Laboratory of high altitude Medicine High Altitude Medical Research Institute Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Collaborative Innovation Center of Genetics and Development

Structural variants(SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome(ZF1), with a contig N50 length of 24.57 mega-base pairs(Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps(0.25 Mb in total length) in the reference human genome(GRCh38). Markedly, we detected17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid(Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1(1.32%–1.53%) compared to other East Asian genomes(0.70%–0.98%),reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence—a662-bp intronic insertion in the SCUBE2 gene—is enriched and associated with better lung function(the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.

关键词： long-read sequencing Tibetan structural variants genetic adaptation reference genome

Decoding molecular mechanisms:brain aging and Alzheimer's disease

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Neural Regeneration research 2025年第8期20卷 2279-2299页

作者： Mahnoor Hayat Rafay Ali Syed Hammad Qaiser Mohammad Uzair Khalid Al-Regaiey Roaa Khallaf Lubna Abdullah Mohammed Albassam Imdad Kaleem Xueyi Wang Ran Wang Mehwish SBhatti Shahid Bashir Atta-ur-Rahman School of Applied Biosciences(ASAB) National University of Sciences and Technology(NUST)IslamabadPakistan department of Biotechnology Quaid-i-Azam UniversityIslamabadPakistan department of biological sciences Faculty of Basic&Applied SciencesInternational Islamic University Islamabad(IIUI)IslamabadPakistan department of Bioengineering King Fahd University of Petroleum and MineralsDhahranSaudi Arabia department of Physiology College of MedicineKing Saud UniversityRiyadhSaudi Arabia department of Neurology Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia department of Mental Health Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia department of Biosciences Commission on Science and Technology for Sustainable Development in the South(COMSATS University)IslamabadPakistan department of Psychiatry The First Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Mental Health institute of Hebei Medical University ShijiazhuangHebei ProvinceChina department of Neurobiology and Behavior University of CaliforniaIrvineCAUSA Neuroscience Center King Fahad Specialist Hospital DammamDammamSaudi Arabia

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for *** aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's *** these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging *** these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect *** review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

关键词： Alzheimer’s disease brain aging cognitive health dementia molecular mechanisms neuronal activity neuroplasticity neurotransmission