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MCU-induced mitochondrial calcium uptake promotes mitochondrial biogenesis and colorectal cancer growth

Signal Transduction and Targeted Therapy 2020年第1期5卷 1898-1910页

作者： Yang Liu Mingpeng Jin Yaya Wang Jianjun Zhu Rui Tan Jing Zhao Xiaoying Ji Chao Jin Yongfeng Jia Tingting Ren Jinliang Xing State Key laboratory of Cancer Biology and Department of Physiology and pathophysiology Fourth Military Medical UniversityXi’anChina Department of Pathology Basic Medical CollegeInner Mongolia Medical UniversityHuhhotChina College of Chemistry and Chemical Engineering Xi’an University of Science and TechnologyXi’anChina Department of Cell Biology and Genetics Basic Medicine CollegeShanxi Medical UniversityTaiyuanChina Department of Orthopedics Xijing HospitalFourth Military Medical UniversityXi’anChina Department of General Surgery Tangdu HospitalFourth Military Medical UniversityXi’anChina State Key laboratory of Cancer Biology and experimental Teaching Center of Basic Medicine Fourth Military Medical UniversityXi’anChina

Mitochondrial calcium uniporter(MCU)has an important role in regulating mitochondrial calcium(Ca^(2+))homeostasis.Dysregulation of mitochondrial Ca^(2+)homeostasis has been implicated in various cancers.However,it remains unclear whether MCU regulates mitochondrial Ca^(2+)uptake to promote cell growth in colorectal cancer(CRC).Therefore,in the present study the expression of MCU in CRC tissues and its clinical significance were examined.Following which,the biological function of MCUmediated mitochondrial Ca^(2+)uptake in CRC cell growth and the underlying mechanisms were systematically evaluated using in in vitro and in vivo assays,which included western blotting,cell viability and apoptosis assays,as well as xenograft nude mice models.Our results demonstrated that MCU was markedly upregulated in CRC tissues at both the mRNA and protein levels.Upregulated MCU was associated with poor prognosis in patients with CRC.Our data reported that upregulation of MCU enhanced the mitochondrial Ca^(2+)uptake to promote mitochondrial biogenesis,which in turn facilitated CRC cell growth in vitro and in vivo.In terms of the underlying mechanism,it was identified that MCU-mediated mitochondrial Ca^(2+)uptake inhibited the phosphorylation of transcription factor A,mitochondrial(TFAM),and thus enhanced its stability to promote mitochondrial biogenesis.Furthermore,our data indicated that increased mitochondrial Ca^(2+)uptake led to increased mitochondrial production of ROS via the upregulation of mitochondrial biogenesis,which subsequently activated NF-κB signaling to accelerate CRC growth.In conclusion,the results indicated that MCU-induced mitochondrial Ca^(2+)uptake promotes mitochondrial biogenesis by suppressing phosphorylation of TFAM,thus contributing to CRC cell growth.Our findings reveal a novel mechanism underlying mitochondrial Ca^(2+)-mediated CRC cell growth and may provide a potential pharmacological target for CRC treatment.

关键词： homeostasis colorectal cancer

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Synthesis of PtCu-based nanocatalysts:Fundamentals and emerging challenges in energy conversion

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Journal of Energy Chemistry 2022年第1期31卷 583-606,I0015页

作者： Wenjuan Yan Dongpei Zhang Quanxing Zhang Yu Sun Shuxia Zhang Feng Du Xin Jin State Key laboratory of Heavy Oil Processing Center for Chemical Engineering Experimental TeachingChina University of PetroleumQingdao 266580ShandongChina

Proton exchange membrane fuel cell and direct methanol fuel cells have gained more attention due to high-energy density,remarkable conversion efficiency,and low emission.However,their widely practical application was hindered by the high usage,limited sources,and high price of Pt catalysts.To achieve more cost-effective catalytic systems,PtCu-based multi-metallic nanoparticles are highly efficient for the oxygen reduction reaction(ORR)and methanol oxidation reaction(MOR).The incorporation of non-noble Cu metal can alter the properties of hybrids by forming new facets,planes,edges to promote the cleavage or formation of chemical bonds in catalytic reaction.This is a rapid growing area with numerous contributions from the interdisciplinary areas of nanocatalysis.This paper has summarized the recent progress in the past two years,in synthesizing PtCu-based alloys with various composition and morphologies,and critically discussed the effect of the catalyst preparation method,metal precursor,surfactant,reductant and heating temperature on nanostructure and electronic configuration.The important role of the composition,size,and morphology of PtCu bimetallic catalysts for electro oxidation reactions has been further established for structure-dependency studies.The challenges and perspectives of nanocatalysts for ORR and MOR discussed in this work is to provide further insights into rational design for cost-effective materials for energy.

关键词： PtCu Nanostructure Electrocatalysis Oxidation

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Status of reproductive health knowledge for junior high school students in Guangzhou city

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Journal of Reproduction and Contraception 2016年第1期27卷 41-49页

作者： Hai-ting YANG Lang-jiang YAO Li-ying WU Zhen-wen HUANG Hui-ting WEN Da-ming CHEN Li-zhi WU Jing LI Wei-jie ZHU Department of Developmental and Regenerative Biology College of Life Science and Technology Jinan University Zengcheng experimental Middle School Department of pathophysiology Medical College Jinan University

Objective To understand the status of reproductive health knowledge for junior high school students in Guangzhou city and provide the base data for reproductive health education. Methods A total of l 210 students including 657 boys and 553 girls aged 12 ~15 years were surveyed with anonymous self-administrated questionnaire. The students were from a middle school in suburb of Guangzhou city. The questionnaire contained basic concepts of reproduction, love, sex, contraceptives, abortion and sexually transmitted diseases （STDs）. Analysis consisted of descriptive statistics and Chi square tests for differences between boys and girls. Results The students mostly had experienced menarche （94%） or first spermatorrhea （83.6%）. About 58. 4% of students just knew little about process of puberty, fertilization, and contraception. Far more boys than girls considered that the effect of abortion on physical injury was harmless （30.4% and 9.6%, P〈O.O01）. More than 60% of respon- dents knew the route of transmission of STDs well but were poor understanding of adverse impact of STDs. The majority of the students did not consider sexual relation- ship acceptable at their age, a viewpoint that was more strongly held by girls （61.6%） than boys （45.1%）（P〈0.001）. Just 35.5% of boys would refuse when the lovers required to have a sex activity, far less than girls （76.1%）（P〈0.001）. The rate of sex intercourses among students was 5%, and a slightly higher proportion （46%） had never used contraception among those who had sexual activity. The demands of students on reproductive health were mainly on how to deal with the relationship with lovers （56. 0%）, knowledge on sexual health and menses （41.7%）, sex moral knowledge （48.3%）, contraception （45.0%）, and preventive measures of STDs/acquired immune deficiency syndrome （AIDS）（47. 0%）. Conclusion The reproductive health knowledge for the students was at very low level There were some differences on the knowledge mastered by boys and girls while the sexual opinion of boys was more open

关键词： adolescence junior high school students reproductive health

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Tau hyperphosphorylation induces apoptotic escape and triggers neurodegeneration in Alzheimer's disease

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Neuroscience Bulletin 2014年第2期30卷 359-366页

作者： Jian-Zhi Wang Zhi-Hao Wang Qing Tian Department of Pathology and pathophysiology Key Laboratory of Ministry of Education of China for Neurological DisordersTongji Medical College Huazhong University of Science and Technology

Since abnormal post-translational modifications or gene mutations of tau have been detected in over twenty neurodegenerative disorders, tau has attracted widespread interest as a target protein. Among its various post-translational modifications, phosphorylation is the most extensively studied. It is recognized that tau hyperphosphorylation is the root cause of neurodegeneration in Alzheimer＇s disease （AD）; however, it is not clear how it causes neurodegeneration. Based on the findings that tau hyperphosphorylation leads to the escape of neurons from acute apoptosis and simultaneously impairs the function of neurons, we have proposed that the nature of AD neurodegeneration is the consequence of aborted apoptosis induced by tau phosphorylation. Therefore, proper manipulation of tau hyperphosphorylation could be promising for arresting AD neurodegeneration. In this review, the neuroprotective and neurodegenerative effects of tau hyperphosphorylation and our thoughts regarding their relationship are presented.

关键词： Alzheimer＇s disease microtubule-associated protein tau hyperphosphorylaUon apoptosis neurodegeneration

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Microglial activation and adult neurogenesis after brain stroke

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Neural Regeneration Research 2021年第3期16卷 456-459页

作者： Ijair R.C.dos Santos Michelle Nerissa C.Dias Walace Gomes-Leal laboratory of experimental Neuroprotection and Neuroregeneration Institute of Biological SciencesFederal University of Pará-BrazilBelém-ParáBrazil

The discovery that new neurons are produced in some regions of the adult mammalian brain is a paradigm-shift in neuroscience research.These new-born cells are produced from neuroprogenitors mainly in the subventricular zone at the margin of the lateral ventricle,subgranular zone in the hippocampal dentate gyrus and in the striatum,a component of the basal ganglia,even in humans.In the human hippocampus,neuroblasts are produced even in elderlies.The regulation of adult neurogenesis is a complex phenomenon involving a multitude of molecules,neurotransmitters and soluble factors released by different sources including glial cells.Microglia,the resident macrophages of the central nervous system,are considered to play an important role on the regulation of adult neurogenesis both in physiological and pathological conditions.Following stroke and other acute neural disorders,there is an increase in the numbers of neuroblast production in the neurogenic niches.Microglial activation is believed to display both beneficial and detrimental role on adult neurogenesis after stroke,depending on the activation level and brain location.In this article,we review the scientific evidence addressing the role of microglial activation on adult neurogenesis after ischemia.A comprehensive understanding of the microglial role after stroke and other neural disorders it is an important step for development of future therapies based on manipulation of adult neurogenesis.

关键词： adult neurogenesis hippocampus ischemia microglia neuroinflammation neuroprotection stroke subventricular zone therapy

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Neuroanatomy and morphological diversity of brain cells from adult crayfish Cherax quadricarinatus

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Journal of Oceanology and Limnology 2018年第6期36卷 2368-2378页

作者：段虎金松君李富花张晓军相建海 Key laboratory of experimental Marine Biology Institute of OceanologyChinese Academy of Sciences laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and Technology

As in vertebrates, brains play key roles in rhythmic regulation, neuronal maintenance, diff erentiation and function, and control of the release of hormones in arthropods. But the structure and functional domains of the brain are still not very clear in crustaceans. In the present study, we reveal the structural details of the brain in the redclaw crayfish using hematoxylin-eosin staining and microscopic examination, firstly. The brain of crayfish is consist of three main parts, namely, protocerebrum, deutocerebrum, and tritocerebrum, including some tracts and commissures, briefly. Secondly, at least 9 kinds of brain cells were identified on the basis of topology and cell shapes, as well as antibody labeling. We also provide morphological details of most cell types, which were previously un-described. In general, four types of glia and three types of neurosecretory cells were described except cluster 9/11 and cluster 10 cells. Glia were categorized into another three main kinds:(1) surface glia;(2) cortex glia; and(3) neuropile glia in addition to astrocytes identified by GFAP labelling. And neurosecretory cells were categorized into I, Ⅱ and III types based on morphological observation. Finally, cluster 9/11 and 10 cells derived from the brain of crayfish, could be used for primary culture about 7–9 d under the optimized conditions. There results provide a resource for improving the knowledge of the still incompletely defined neuroendocrinology of this species. Using the crayfish as an animal model, we are easy to carry out further research in manipulating their endocrine system, exploring cellular and synaptic mechanisms so much as larval production on a small scale, such as in a cell or tissue.

关键词： Cherax quadricarinatus brain’s structure brain cells primary culture

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Determination of thyreostats in bovine urine using ultra-high performance liquid chromatography-tandem mass spectrometry

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色谱 2017年第10期35卷 1048-1054页

作者： Lech RODZIEWICZ Jolanta MASLOWIECKA Anna SADOWSKA Halina CAR laboratory of Chemical Examination of Foodstuffs Department of Veterinary Hygiene Department of experimental Pharmacology Medical University of Bialystok

Five thyreostats(TSs),namely tapazole,thiouracil,methylthiouracil,propylthiouracil,and phenylthiouracil,were determined in bovine urine using ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in positive electrospray ionization mode.Extraction and clean-up were achieved using a ChemElut cartridge with tert-butyl methyl ether,without a derivatization step.Separation was achieved on an Acquity UPLC SS T3 column.The mobile phase was acetonitrile and water containing 0.2%(v/v)formic acid.The mass spectrometer was operated in multiple reaction monitoring mode.Urine samples were spiked with TS solution at levels corresponding to 5,10,15,and 20μg/L.The accuracy(internal standard corrected)ranged from 92%to 107%,with a repeatability precision(relative standard deviation,RSD)less than 15%for all five analytes.The RSDs within-laboratory reproducibility was less than 26%.The decision limits(CCα)and detection capabilities(CCβ)were obtained from a calibration curve and were in the ranges of 3.1-6.1μg/L and 4.0-7.4μg/L,respectively.The CCαand CCβvalues were below the recommended concentration,which was set at 10μg/L.The results show that the described method is suitable for the direct detection of TSs in bovine urine.This method can also be used to determine TSs in porcine urine.

关键词： ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) thyreostats (TSs) urine

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A Novel Poly(3-hexylthiophene) Engineered Interface for Electrochemical Monitoring of Ascorbic Acid During the Occurrence of Glutamate-Induced Brain Cytotoxic Edemas

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Research 2024年第1期2023卷 301-313页

作者： Zexuan Meng Yuchan Zhang Lu Yang Shuang Zhao Qiang Zhou Jiajia Chen Jiuxi Sui Jian Wang Lizhong Guo Luyue Chang Jialing He Guixue Wang Guangchao Zang Institute of Life Science and Laboratory of Tissue and Cell BiologyLab Teaching and Management CenterChongqing Medical UniversityChongqing 400016China Key laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing 400030China Jinfeng laboratory Chongqing 401329China Department of pathophysiology Chongqing Medical UniversityChongqingChina

Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements.In this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)detection.The microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing.Subsequently,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA release.We also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA release.This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism.Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.

关键词： release microelectrode Engine

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Homocysteine activates T cells by enhancing endoplasmic reticulum-mitochondria coupling and increasing mitochondrial respiration

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Protein & Cell 2016年第6期7卷 391-402页

作者： Juan Feng Silin Lu Yanhong Ding Ming Zheng Xian Wang Department of Physiology and pathophysiology School of Basic Medical Science Peking University Key Laboratory of Molecular Cardiovascular Science Ministry of Education Beijing 100191 China

Hyperhomocysteinemia （HHcy） accelerates atherosclero- sis by increasing proliferation and stimulating cytokine secretion in Tcells. However, whether homocysteine （Hcy）- mediated T cell activation is associated with metabolic reprogramming is unclear. Here, our in vivo and in vitro studies showed that Hcy-stimulated splenic T-cell activa- tion in mice was accompanied by increased levels of mitochondrial reactive oxygen species （ROS） and calcium, mitochondrial mass and respiration. Inhibiting mitochon- drial ROS production and calcium signals or blocking mitochondrial respiration largely blunted Hcy-induced T-cell interferon y （IFN-v） secretion and proliferation. Hcy also enhanced endoplasmic reticulum （ER） stress in T cells, and inhibition of ER stress with 4-phenylbutyric acid blocked Hcy-induced T-cell activation. Mechanistically, Hcy increased ER-mitochondria coupling, and uncou- pling ER-mitochondria by the microtubule inhibitor nocodazole attenuated Hcy-stimulated mitochondrial reprogramming, IFN-y secretion and proliferation in T cells, suggesting that juxtaposition of ER and mitochon-dria is required for Hcy-promoted mitochondrial function and T-cell activation. In conclusion, Hcy promotes T-cell activation by increasing ER-mitochondria coupling and regulating metabolic reprogramming.

关键词： homocysteine T cell mitochondria,endoplasmic reticulum stress

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On the road to new treatments for multiple sclerosis: targeting dendritic cell migration into the central nervous system

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Neural Regeneration Research 2019年第12期14卷 2088-2090页

作者： Megha Meena Nathalie Cools laboratory of experimental Hematology Vaccine & Infectious Disease Institute (VAXINFECTIO) Faculty of Medicine and Health Sciences University of Antwerp

Distinct migratory pathways and trafficking of dendritic cells to the central nervous system (CNS): The immune system is a host defense mechanism protecting against invaders, such as bacteria and viruses, while maintaining tolerance to self. Nonetheless, a few sites throughout the body are believed to be immunologically inert, such as the testes, the eye and the brain. Indeed, experiments in the mid-20th century gave rise to the concept of the brain as a site of immune privilege. Originally, the immune privilege of the brain was thought to be absolute, attributed by a physical blood-brain barrier (BBB) protecting the CNS from the entry of pathogens and circulating immune cells. These views have changed and currently, the CNS is seen as an immune-specialized site regulated by immunological components into and within the CNS.

关键词： new treatments multiple sclerosis nervous system

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