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Neural Regeneration Research 2024年第8期19卷 1645-1646页

作者： Dmitry Lim Alexei Verkhratsky Department of Pharmaceutical Sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Achucarro Center for Neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain&Department of NeurosciencesUniversity of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Department of Stem Cell Biology State Research Institute Centre for Innovative MedicineVilniusLithuania Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina

Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and *** hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.

关键词： Alzheimer homeostasis cortex

Leaf C:N:P stoichiometric homeostasis of a Robinia pseudoacacia plantation on the Loess Plateau

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Journal of Forestry Research 2023年第4期34卷 929-937页

作者： Zhuoxia Su Bingqian Su Shenglin Mao Zhouping Shangguan State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau Northwest A&F UniversityYangling 712100ShaanxiPeople’s Republic of China

homeostasis is the adaptability of a species to a changing ***,the ecological stoichiometric homeostasis of Robinia pseudoacacia *** diff erent climatic regions is poorly understood but could provide insights into its adaptability in the loess hilly *** study sampled 20 year-old *** plantations at 10 sites along a north–south transect on the Loess *** in the ecological stoichiometric characteristics of leaf and soil carbon,nitrogen,and phosphorus were analysed and homeostatic characteristics of leaf ecological stoichiometric parameters in diff erent climates were identifi *** aff ecting leaf stoichiometry were *** results show that *** leaves were rich in nitrogen and defi cient in phosphorous during tree growth and *** and phosphorous levels in the soils of the loess region were lower than the average in soils in the rest of *** ecological stoichiometric parameters of *** leaves in two diff erent climates were considered“strictly homeostasis”.Precipitation,available phosphorus,and soil C:P were the main factors aff ecting the variation of C:N:P stoichiometry of *** *** in the loess hilly region has strong ecologically homeostatic characteristics and suggests that it is well-adapted to the area.

关键词： Loess Plateau Robinia pseudoacacia Ecological stoichiometry homeostasis

Metabolism of tissue macrophages in homeostasis and pathology

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Cellular & Molecular Immunology 2022年第3期19卷 384-408页

作者： Stefanie K.Wculek Gillian Dunphy Ignacio Heras-Murillo Annalaura Mastrangelo David Sancho Immunobiology Laboratory Centro Nacional de Investigaciones Cardiovasculares(CNIC)Melchor Fernández Almagro 3Madrid28029Spain

Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy and structural *** emerging field of immunometabolism highlights the importance of cellular metabolism for the maintenance and activities of immune *** are embryo-or adult bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome,atherosclerosis,fibrosis or *** metabolism has largely been studied in ***,different organs contain diverse macrophage populations that specialize in distinct and often tissue-specific *** context specificity creates diverging metabolic challenges for tissue macrophage populations to fulfill their homeostatic roles in their particular microenvironment and conditions their response in pathological ***,we outline current knowledge on the metabolic requirements and adaptations of macrophages located in tissues during homeostasis and selected diseases.

关键词： Tissue macrophages metabolism homeostasis pathology tissue regeneration

Copper homeostasis and cuproptosis in health and disease

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Signal Transduction and Targeted Therapy 2022年第12期7卷 4352-4367页

作者： Liyun Chen Junxia Min Fudi Wang The Fourth Affiliated Hospital The First Affiliated HospitalInstitute of Translational MedicineSchool of Public HealthState Key Laboratory of Experimental HematologyZhejiang University School of MedicineHangzhouChina The First Affiliated Hospital Basic Medical SciencesSchool of Public HealthHengyang Medical SchoolUniversity of South ChinaHengyangChina

all cell *** the accumulation of intracellular copper can induce oxidative stress and perturbing cellular function,copper homeostasis is tightly *** studies identified a novel copper-dependent form of cell death called cuproptosis,which is distinct from all other known pathways underlying cell *** occurs via copper binding to lipoylated enzymes in the tricarboxylic acid(TCA)cycle,which leads to subsequent protein aggregation,proteotoxic stress,and ultimately cell ***,we summarize our current knowledge regarding copper metabolism,copper-related disease,the characteristics of cuproptosis,and the mechanisms that regulate *** addition,we discuss the implications of cuproptosis in the pathogenesis of various disease conditions,including Wilson’s disease,neurodegenerative diseases,and cancer,and we discuss the therapeutic potential of targeting cuproptosis.

关键词： homeostasis metabolism diseases

Runx1 is a key regulator of articular cartilage homeostasis by orchestrating YAP,TGFβ,and Wnt signaling in articular cartilage formation and osteoarthritis

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Bone Research 2022年第4期10卷 882-892页

作者： Yan Zhang Tao Zuo Abigail McVicar Hui-Lin Yang Yi-Ping Li Wei Chen Department of Pathology University of Alabama at BirminghamBirminghamAL 35294USA Key Laboratory of Biomedical Information Engineering of Ministry of Education Biomedical Informatics and Genomics CenterSchool of Life Science and TechnologyXi’an Jiaotong UniversityXi’an 710049 ShaanxiP.R.China Department of Orthopaedics the First Affiliated Hospital of Soochow UniversityOrthopaedic Institute of Soochow University899 Pinghai RoadSuzhou 215031 JiangsuP.R.China Division in Cellular and Molecular Medicine Department of Pathology and Laboratory MedicineTulane University School of MedicineTulane UniversityNew OrleansLA 70112USA

Runt-related transcription factor 1(Runx1)plays a key role in cartilage formation,but its function in articular cartilage formation is *** generated non-inducible and inducible Runx1-deficient mice(Runx1^(f/f)Col2α1-Cre and Runx1^(f/f)Col2α1-CreER mice)and found that chondrocyte-specific Runx1-deficient mice developed a spontaneous osteoarthritis(OA)-like phenotype and showed exacerbated articular cartilage destruction under OA,characterized by articular cartilage degradation and cartilage ossification,with decreased Col2α1 expression and increased Mmp13 and Adamts5 ***-sequencing analysis of hip articular cartilage from the Runx1^(f/f)Col2α1-Cre mice compared to that from wild-type mice and subsequent validation analyses demonstrated that Runx1 is a central regulator in multiple signaling pathways,converging signals of the Hippo/Yap,TGFβ/Smad,and Wnt/β-catenin pathways into a complex network to regulate the expression of downstream genes,thereby controlling a series of osteoarthritic pathological ***-sequencing analysis of mutant knee joints showed that Runx1’s role in signaling pathways in articular cartilage is different from that in whole knee joints,indicating that Runx1 regulation is *** analysis confirmed that Runx1 deficiency decreased the levels of YAP and p-Smad2/3 and increased the levels of activeβ-*** of Runx1 dramatically increased YAP expression in ***-associated virus-mediated Runx1 overexpression in the knee joints of osteoarthritic mice showed the protective effect of Runx1 on articular cartilage damaged in *** results notably showed that Runx1 is a central regulator of articular cartilage homeostasis by orchestrating the YAP,TGFβ,and Wnt signaling pathways in the formation of articular cartilage and OA,and targeting Runx1 and its downstream genes may facilitate the design of novel therapeutic approaches for OA.

关键词： cartilage homeostasis protective

SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3780-3793页

作者： Kai Yang Shiyun Liu Han Yan Wenju Lu Xiaoqian Shan Haixia Chen Changlei Bao Huazhuo Feng Jing Liao Shuxin Liang Lei Xu Haiyang Tang Jason X-J.Yuan Nanshan Zhong Jian Wang State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangdong Key Laboratory of Vascular DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Guangzhou National Laboratory Guangzhou International Bio IslandGuangzhouGuangdongChina Department of Pulmonary and Critical Care Medicine The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner Mongolia Autonomous RegionChina Department of Pathology The Affiliated Cancer Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina School of Medicine Southern University of Science and TechnologyShenzhenGuangdongChina Section of Physiology Division of PulmonaryCritical Care and Sleep MedicineDepartment of MedicineUniversity of California San DiegoLa JollaCAUSA

Exposure to the spike protein or receptor-binding domain(S-RBD)of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular *** this study,angiotensin-converting enzyme 2 humanized inbred(hACE2 Tg)mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular *** show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration([Ca^(2+)]i)via acute activation of TRPV4,and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel(SOCC)key component Orai1 in cultured human pulmonary arterial endothelial cells(PAECs).In mechanism,S-RBD interacts with ACE2 to induce formation of clusters involving Orai1,Piezo1 and TRPC1,facilitate the channel activation of Piezo1 and SOCC,and lead to elevated *** effects are blocked by Kobophenol A,which inhibits the binding between S-RBD and ACE2,or intracellular calcium chelator,*** of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBDinduced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated[Ca^(2+)]*** to prototypic strain,Omicron variants(BA.5.2 and XBB)of S-RBD induces significantly less severe cell *** analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda *** summary,this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering[Ca^(2+)]i through upregulation of Piezo1 and *** inhibition of ACE2-Piezo1/SOCC-[Ca^(2+)]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases.

关键词： ACE2 elevated homeostasis

Interoceptive regulation of skeletal tissue homeostasis and repair

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骨研究:英文版 2023年第3期11卷 481-496页

作者： Yao Xiao Changhao Han Yunhao Wang Xinshu Zhang Rong Bao Yuange Li Huajiang Chen Bo Hu Shen Liu Department of Orthopaedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital600 Yishan RdShanghai 200233PR China Spine Center Department of OrthopedicsChangzheng HospitalNaval Medical UniversityShanghai 200003PR China

Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone *** hypothalamus,located in the central nervous system(CNS),plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system,neuropeptide release,and neuroendocrine *** mechanisms control the differentiation of mesenchymal stem cells into osteoblasts(OBs),the activation of osteoclasts(OCs),and the functional activities of bone *** nerves extensively innervate skeletal tissues,facilitating the transmission of interoceptive signals to the *** review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological *** findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

关键词： system homeostasis maintain

Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc

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Bone Research 2022年第1期10卷 165-177页

作者： Sheng Chen Xiaohao Wu Yumei Lai Di Chen Xiaochun Bai Sheng Liu Yongchao Wu Mingjue Chen Yuxiao Lai Huiling Cao Zengwu Shao Guozhi Xiao Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Department of Orthopedic Surgery Rush University Medical CenterChicagoIL 60612USA Research Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Cell Biology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Centre for Translational Medicine Research and Development Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Intervertebral disc(IVD) degeneration(IVDD) is the main cause of low back pain with major social and economic burdens;however, its underlying molecular mechanisms remain poorly defined. Here we show that the focal adhesion protein Kindlin-2 is highly expressed in the nucleus pulposus(NP), but not in the anulus fibrosus and the cartilaginous endplates, in the IVD tissues. Expression of Kindlin-2 is drastically decreased in NP cells in aged mice and severe IVDD patients. Inducible deletion of Kindlin-2 in NP cells in adult mice causes spontaneous and striking IVDD-like phenotypes in lumbar IVDs and largely accelerates progression of coccygeal IVDD in the presence of abnormal mechanical stress. Kindlin-2 loss activates Nlrp3 inflammasome and stimulates expression of IL-1β in NP cells, which in turn downregulates Kindlin-2. This vicious cycle promotes extracellular matrix(ECM) catabolism and NP cell apoptosis. Furthermore, abnormal mechanical stress reduces expression of Kindlin-2, which exacerbates Nlrp3 inflammasome activation, cell apoptosis, and ECM catabolism in NP cells caused by Kindlin-2 deficiency. In vivo blocking Nlrp3 inflammasome activation prevents IVDD progression induced by Kindlin-2 loss and abnormal mechanical stress. Of translational significance, adeno-associated virus-mediated overexpression of Kindlin-2 inhibits ECM catabolism and cell apoptosis in primary human NP cells in vitro and alleviates coccygeal IVDD progression caused by mechanical stress in rat. Collectively, we establish critical roles of Kindlin-2 in inhibiting Nlrp3 inflammasome activation and maintaining integrity of the IVD homeostasis and define a novel target for the prevention and treatment of IVDD.

关键词： Kindlin homeostasis prevention

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4082-4114页

作者： Junjun Jing Zhuoxuan Wu Jiahe Wang Guowen Luo Hengyi Lin Yi Fan Chenchen Zhou State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengdu 610041China Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengdu 610041China

The past decade has seen significant advances in our understanding of Hedgehog(HH)signaling pathway in various biological *** signaling pathway exerts its biological effects through a complex signaling cascade involved with primary *** signaling pathway has important functions in embryonic development and tissue *** plays a central role in the regulation of the proliferation and differentiation of adult stem ***,it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence,malignant progression,poor prognosis and even increased *** the integrative nature of HH signaling pathway has opened up the potential for new therapeutic targets for cancer.A variety of drugs have been developed,including small molecule inhibitors,natural compounds,and long non-coding RNA(LncRNA),some of which are approved for clinical *** review outlines recent discoveries of HH signaling in tissue homeostasis and cancer and discusses how these advances are paving the way for the development of new biologically based therapies for ***,we address status quo and limitations of targeted therapies of HH signaling *** from this review will help readers understand the function of HH signaling in homeostasis and cancer,as well as opportunities and challenges of therapeutic targets for cancer.

关键词： homeostasis therapies targeted

Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution

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Journal of Traditional Chinese Medicine 2022年第1期42卷 96-101页

作者： ZHANG Huixiang WANG Limei GUO Jipeng WANG Jiai ZHANG Qianqian WANG Yutao LIU Xun ZHANG Lihuan SHI Lanlan WU Hongxiang CAO Xue Institute of Neuroscience Basic Medical CollegeKunming Medical UniversityKunming 650500China Department of Laboratory Animal Science Kunming Medical UniversityKunming 650500China Department of Laboratory Animal Science Kunming Medical UniversityState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanYunnan UniversityKunming 650500Chin Faculty of Rehabilitation Medicine Kunming Medical UniversityKunming 650500China School of Electrical and Information Technology Yunnan Minzu UniversityKunming 650500China School of Medicine Kunming UniversityKunming 650214China Basic Medical College Kunming Medical UniversityKunming 650500China Department of Anatomy Histology and EmbryologyBasic Medical CollegeKunming Medical UniversityKunming 650500China

OBJECTIVE:Yang-deficiency constitution(YADC)is a common unbalanced constitution that predisposes individuals to certain ***,not all people with YADC manifest develop *** calls for delineation of the underlying molecular *** studies suggested that the gut microbiota and gene differential expression should be ***:In the present study,we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution(BC)counterparts,based on 16 S r RNA gene sequence ***,YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis,functional clustering and pathway enrichment ***:The levels of harmful gut microbiota(Prevotellaceae,LDA score>4.0,P=0.0141)and beneficial gut microbiota(Ruminococcaceae,LDA score>4.0,P=0.0025,Faecalibacterium,LDA score>4.0,P=0.0484)were both elevated in healthy YADC ***,we found that the specific metabolic pathway with 2,6-Dichloro-p-hydroquinone 1,2-Dioxygenase(Pcp A)as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon ***:Both beneficial and harmful factors had been detected in healthy YADC individuals,functionally,they may have triggered homeostasis to maintain the health of individuals with *** homeostasis may be maintained by beneficial and harmful factors from gut flora and *** studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.

关键词： Yang deficiency physical constitution theory health promotion gastrointestinal microbiome genes hydrocarbons aromatic homeostasis