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Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

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Journal of Sport and Health Science 2024年第4期13卷 548-558,F0003页

作者： Hugo de Luca Correa Lysleine Alves Deus Dahan da Cunha Nascimento Nicholas Rolnick Rodrigo Vanerson Passos Neves Andrea Lucena Reis Thais Branquinho de Araujo Carmen Tzanno-Martins Fernanda Silveira Tavares Luiz Sinesio Silva Neto Claudio Avelino Rodrigues Santos Paolo Lucas Rodrigues-Silva Fernando Honorato Souza Vitoria Marra da Motta Vilalva Mestrinho Rafael Lavarini dos Santos Rosangela Vieira Andrade Jonato Prestes Thiago dos Santos Rosa Post-graduate program of Physical Education Catholic University of BrasıliaBrasılia 71966-700Brazil The Human Performance Mechanic Lehman CollegeNew YorkNY 10011USA Clinical Group Home Dialysis Center and RenalClass Sao Paulo 01239-040Brazil Department of Medicine Catholic University of BrasıliaBrasılia 71966-700Brazil Faculty of Medicine Federal University of TocantinsTocantins 77001-090Brazil Embrapa Genetic Resources and Biotechnology Brasılia 70770-917Brazil Graduate program of genomic sciences and Biotechnology Brasılia 71966-700Brazil

Background:Hemodialysis(HD) per se is a risk factor for *** the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training *** aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this ***:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of 70 years old),and HD ***,RE+BFR significantly increases D-dimer after 4 *** with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.

关键词： Blood-flow restriction Chronic kidney disease Coagulation Hemodialysis Vascular occlusion exercises

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Response to Commentary by Dr. Matthew J. Clarkson on

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Journal of Sport and Health Science 2024年第5期13卷 670-671页

作者： Hugo de Luca Corrêa Lysleine Alves Deus Dahan da Cunha Nascimento Nicholas Rolnick Rodrigo Vanerson Passos Neves Andrea Lucena Reis Thais Branquinho de Araújo Carmen Tzanno-Martins Fernanda Silveira Tavares Luiz Sinésio Silva Neto Cláudio Avelino Rodrigues Santos Paolo Lucas Rodrigues-Silva Fernando Honorato Souza Vitória Marra da Motta Vilalva Mestrinho Rafael Lavarini dos Santos Rosangela Vieira Andrade Jonato Prestes Thiago dos Santos Rosa Post-graduate program of Physical Education Catholic University of BrasıliaBrasılia 71966-700Brazil The Human Performance Mechanic Lehman CollegeNew YorkNY 10011USA Clinical Group Home Dialysis Center and RenalClass Sao Paulo 01239-040Brazil Department of Medicine Catholic University of BrasıliaBrasılia 71966-700Brazil Faculty of Medicine Federal University of TocantinsTocantins 77001-090Brazil Embrapa Genetic Resources and Biotechnology Brasılia 70770-917Brazil g Graduate program of genomic sciences and Biotechnology Brasılia 71966-700Brazil

Dear editor:We sincerely thank Matthew *** for his insightful commentary1 on our recent publication in the Journal of Sport and Health Science.2 Clarkson's pioneering work in the development and application of blood flow restriction (BFR) exercise protocols has undeniably laid the groundwork for subsequent investigations in this field,including our own.(3-6)His commentary not only highlights the relevance and timeliness of our study but also offers valuable perspectives on refining safety considerations for intradialytic BFR exercise among hemodialysis patients.

关键词： patients application flow

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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic Surgery Research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic Surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

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MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

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Research 2024年第2期2023卷 239-257页

作者： Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song Juan Carlos Izpisua Belimonte Jing Qu Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of genomic and Precision Medicine Beijng Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of sciences Beijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Bejing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ ***,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell *** answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell *** found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence *** uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence *** together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

关键词： CRISPR/Cas9 homeostasis Mitochondrial

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Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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Journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn Gabriel A.Zayas Eduardo E.Rodriguez Laura M.Jensen Raluca G.Mateescu Peter J.Hansen Department of Animal sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of Applied Systems Biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef *** Genome-wide association studies(GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PEBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PEBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PEBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were *** In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations

关键词： Beef cattle Fertility GWAS QTL

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Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression

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Signal Transduction and Targeted Therapy 2024年第1期9卷 279-294页

作者： Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu Dongxin Lin Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Cancer genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China CAMS Oxford Institute Chinese Academy of Medical SciencesBeijing 100006China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

Epithelial-mesenchymal transition(EMT)and proliferation play important roles in epithelial cancer formation and progression,but what molecules and how they trigger EMT is largely *** we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma(ESCC)from mice and humans to decipher these critical *** investigating spatiotemporal gene expression patterns and cell–cell interactions,we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT *** aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions,which expands to the whole epithelial layer and strengthens along the cancer development and *** analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressedΔNP63 due to TP53 mutation,the culprit in human ESCC *** results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.

关键词： esophageal TP53 squamous

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Tumor initiation and early tumorigenesis:molecular mechanisms and interventional targets

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2900-2935页

作者： Shaosen Zhang Xinyi Xiao Yonglin Yi Xinyu Wang Lingxuan Zhu Yanrong Shen Dongxin Lin Chen Wu Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Key Laboratory of Cancer genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Changping Laboratory 100021 BeijingChina Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China CAMS Oxford Institute Chinese Academy of Medical Sciences100006 BeijingChina

Tumorigenesis is a multistep process,with oncogenic mutations in a normal cell conferring clonal advantage as the initial ***,despite pervasive somatic mutations and clonal expansion in normal tissues,their transformation into cancer remains a rare event,indicating the presence of additional driver events for progression to an irreversible,highly heterogeneous,and invasive ***,researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution,independently of inducing ***,clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into ***,the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully *** this review,we summarize the genetic,epigenetic,and external driver events,and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution.A deeper understanding of the earliest molecular events holds promise for translational applications,predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

关键词： alterations mechanisms restrain

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Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1344-1362页

作者： Zi-Ling Hu Yu-Xuan Wang Zi-Yue Lin Wen-Shuo Ren Bo Liu Hui Zhao Qiong Qin Five Year program of Ophthalmology and Optometry 2019 Beijing Tong Ren HospitalCapital Medical UniversityBeijing 100054China Four Year program of Traditional Chinese Pharmacy 2020 School of Traditional Chinese MedicineCapital Medical UniversityBeijing 100069China School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Beijing Key Laboratory of TCM Collateral Disease Theory Research Beijing 100069China Five Year program of Ophthalmology and Optometry 2021 School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Biochemistry&Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual *** evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological *** factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative *** functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been *** the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD *** the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.

关键词： Nrf2 upstream regulators retinal pigment epithelia age-related macular degeneration oxidative stress

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Comparative transcriptome analysis between rhesus macaques(Macaca mulatta) and crab-eating macaques(M. fascicularis)

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Zoological Research 2024年第2期45卷 299-310页

作者： Yu-Xiang Mao Yamei Li Zikun Yang Ning Xu Shilong Zhang Xuankai Wang Xiangyu Yang Qiang Sun Yafei Mao Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science&Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology Shanghai 201210China University of Chinese Academy of sciences Beijing 100049China Key Laboratory of Genetic Evolution&Animal Models Chinese Academy of SciencesKunmingYunnan 650201China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200030China Zhiyuan College Shanghai Jiao Tong UniversityShanghai 200240China Center for genomic Research International Institutes of MedicineFourth Affiliated HospitalZhejiang UniversityYiwuZhejiang 322000China

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

关键词： Crab-eating macaques Rhesus macaques Comparative transcriptomics Biomedical models Nonhuman primates RNA-seq Duplicated genes

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High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

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Science China(Life sciences) 2024年第8期67卷 1635-1647页

作者： Feng-Qi Liu Qing-Yuan Qu Ying Lei Qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu Qiu-Sha Huang Hai-Xia Fu Yuan Kong Yue-Ying Li Qian-Fei Wang Xiao-Jun Huang Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China Collaborative Innovation Centre of Hematology Peking UniversityBeijing 100044China CAS Key Laboratory of genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of sciences Beijing 100049China Peking-Tsinghua Center for Life sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100074China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the *** soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP *** the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T *** contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell *** a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune ***-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of *** conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of *** may offer novel targets to develop personalized immunotherapies.

关键词： immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow

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