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Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

World Journal of Clinical Cases 2024年第9期12卷 1585-1596页

作者： Osman Boyalı Serdar Kabatas ErdinçCivelek Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Turkey center for Stem Cell&Gene Therapy research and Practice University of Health Sciences TurkeyIstanbul 34360Turkey Department of Physical medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Turkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey center for regenerative medicine and Stem Cell research&Manufacturing(LivMedCell) Liv HospitalIstanbul 34340Turkey Department of Histology and Embryology Istinye UniversityFaculty of Medicineİstanbul 34010Turkey center for Stem Cell and Tissue Engineering research and Practice Istinye UniversityIstanbul 34340Turkey

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and *** in motor functions constitute the main body of CP *** symptoms surface in early childhood and patients are affected for the rest of their ***,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal ***,none of these methods can provide full symptom *** has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and *** To analyze the efficacy and safety of MSCT in CP *** Our sample consists of four CP patients who cannot stand or walk without external *** of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)*** utilized the Modified Ashworth Scale(MAS)to measure *** We found significant improvements in MAS scores after the intervention on both *** months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=***,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity

关键词： Cerebral palsy Mesenchymal stem cell Transplantation Wharton’s jelly Muscle spasticity

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Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2732-2747页

作者： Bo Xiao Yuqi Liang Ga Liu Lingshuang Wang Zhan Zhang Libin Qiu Haiting Xu Sean Carr Xiaoxiao Shi Rui LReis Subhas CKundu Zhenghua Zhu Department of Gastroenterology the First Affiliated Hospital of Nanchang UniversityNanchang 330006China College of Sericulture Textileand Biomass SciencesSouthwest UniversityChongqing 400715China Department of Neurology School of MedicineEmory UniversityAtlantaGA 30322USA Atlanta Veterans Affairs Medical center DecaturGA 30033USA Department of Surgery School of MedicineEmory UniversityAtlantaGA 30322USA Bs research Group I3Bs—Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkBarcoGuimaraes 4805-017Portugal

The progression of ulcerative colitis(UC)is associated with immunologic derangement,intestinal hemorrhage,and microbiota *** traditional medications mainly focus on mitigating inflammation,it remains challenging to address multiple ***,a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO_(2) nanospheres with Cu_(2)O *** resulting CaO_(2)–Cu_(2)O possessed a desirable diameter(291.3 nm)and a uniform size *** could be efficiently internalized by colonic epithelial cells and macrophages,scavenge intracellular reactive oxygen/nitrogen species,and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 *** nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen *** administration of CaO_(2)–Cu_(2)O could stanch the bleeding,repair the disrupted colonic epithelial layer,and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation,anti-oxidation,wound healing,and ***,it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria(e.g.,Odoribacter and Bifidobacterium)and decreasing the abundances of harmful bacteria(e.g.,Prevotellaceae and Helicobacter).Our gas-driven CaO_(2)–Cu_(2)O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

关键词： Nanomotor Anti-inflammation Blood coagulation Immune regulation Hematopexis Microbiota rebalance Ulcerative colitis Rectal administration

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Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

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Nano research 2024年第2期17卷 858-865页

作者： Xiaowan Fan Tao Zhang Xin Ding Yushuo Gu Qing Li Wei Jiang Kelong Fan Nanozyme Medical center Academy of Medical ScienceZhengzhou UniversityZhengzhou 450001China Department Central-China Branch of National Center for Cardiovascular DiseasesHean Cardiovascular Disease CenterFuwai Central-China HospitalCentral China Fuwai Hospital of Zhengzhou UniversityZhengzhou 450046China Application center for Precision medicine the Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide PharmaceuticalsInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 101408China Department of General Surgery Strategic Support Force Medical CenterBeijing 100101China Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Parkinson’s disease(PD)is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory ***-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing ***,traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and ***,Cu-doping zeolite imidazolate framework-8(ZIF-8)nanozyme is designed to simulate Cu/Zn superoxide dismutase(SOD)by biomimetic *** nanozyme composite is then integrated into thermosensitive hydrogel(poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid)(PLGA-PEG-PLGA))to form an effective antioxidant system(Cu-ZIF@Hydrogel).The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion,prolonging nanozyme retention time,and modulating antioxidant activity,thus significantly improving the bioavailability of *** the cellular and animal levels of PD,we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve ***,the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion ***,the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

关键词： bioinspired nanozyme thermosensitive hydrogel Parkinson’s disease oxidative stress neuroinflammatory

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Imaging Carotid Plaque Burden in Living Mice via Hybrid Semiconducting Polymer Nanoparticles-Based Near-Infrared-II Fluorescence and Magnetic Resonance Imaging

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research 2024年第3期2023卷 71-81页

作者： Li Xu Zhe Li Yuan Ma Lingling Lei Renye Yue Hui Cao Shuangyan Huan Wei Sun Guosheng Song State Key Laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical EngineeringEngineeringHunan UniversityChangsha 410082China. Key Laboratory of Targeted Intervention of cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjingMedical University Department of Cardiology The First Affiliated Hospital of Nanjing Medical UniversityNanjing Medical UniversityNanjing 210029JiangsuChina.

The majority of atherothrombotic events (e.g., cerebral or myocardial infarction) often occur as a result of plaque rupture or erosion in the carotid, and thereby it is urgent to assess plaque vulnerability and predict adverse cerebrovascular events. However, the monitoring evolution from stable plaque into life-threatening high-risk plaque in the slender carotid artery is a great challenge, due to not enough spatial resolution for imaging the carotid artery based on most of reported fluorescent probes. Herein, copolymerizing with the small molecules of acceptor-donor-acceptor-donor-acceptor (A-D-A′-D-A) and the electron-donating units (D′), the screened second near-infrared (NIR-II) nanoprobe presents high quantum yield and good stability, so that it enables to image slender carotid vessel with enough spatial resolution. Encouragingly, NIR-II nanoprobe can effectively target to intraplaque macrophage, meanwhile distinguishing vulnerable plaque in carotid atherosclerosis in living mice. Moreover, the NIR-II nanoprobe can dynamically monitor the fresh bleeding spots in carotid plaque, indicating the increased risk of plaque instability. Besides, magnetic resonance imaging is integrated with NIR-II fluorescence imaging to provide contrast for subtle structure (e.g., narrow lumen and lipid pool), via incorporating ultrasmall superparamagnetic iron oxide into the NIR-II nanoprobe. Thus, such hybrid NIR-II/magnetic resonance imaging multimodal nanoprobe provides an effective tool for assessing carotid plaque burden, selecting high-risk plaque, and imaging intraplaque hemorrhage, which is promising for reducing cerebral/ myocardial infarction-associated morbidity and mortality.

关键词： enough conducting Infrared

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Spinal cord injury regenerative therapy development:integration of design of experiments

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Neural Regeneration research 2025年第9期20卷 2571-2573页

作者： Yuji Okano Hideyuki Okano Yoshitaka Kase Division of CNS Regeneration and Drug Discovery International Center for Brain Science(ICBS)Fujita Health UniversityKutsukake-ChoToyoake-ShiAichiJapan Department of Extended Intelligence for medicine The Ishii-Ishibashi LaboratoryKeio University School of MedicineShinanomachiShinjuku-KuTokyoJapan Keio University regenerative medicine research center Kawasaki-kuKawasaki-shiJapan

Spinal cord injury(SCI)can cause motor and sensory paralysis,and autonomic nervous system disorders including malfunction of urination and defecation,thereby significantly impairing the quality of *** continue to explo re new stem cell strategies for the treatment of paralysis by transpla nting human induced pluripotent stem cell-derived neural ste m/progenitor cells(hiPSCNS/PCs)into spinal cord injured tissues.

关键词： Spinal paralysis injury

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Enhancing Generic Reaction Yield Prediction through Reaction Condition-Based Contrastive Learning

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research 2024年第3期 685-702页

作者： Xiaodan Yin Chang-Yu Hsieh Xiaorui Wang Zhenxing Wu Qing Ye Honglei Bao Yafeng Deng Hongming Chen Pei Luo Huanxiang Liu Tingjun Hou Xiaojun Yao Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyMacao 999078China Innovation Institute for Artificial Intelligence in medicine of Zhejiang University College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China. Faculty of Applied Sciences Macao Polytechnic UniversityMacao 999078China. CarbonSilicon AI Technology Co.Ltd HangzhouZhejiang 310018China center of Chemistry and Chemical Biology Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510530China.

Deep learning(DL)-driven efficient synthesis planning may profoundly transform the paradigm for designing novel pharmaceuticals and ***,the progress of many DL-assisted synthesis planning(DASP)algorithms has suffered from the lack of reliable automated pathway evaluation *** a critical metric for evaluating chemical reactions,accurate prediction of reaction yields helps improve the practicality of DASP algorithms in the real-world ***,accurately predicting yields of interesting reactions still faces numerous challenges,mainly including the absence of high-quality generic reaction yield datasets and robust generic yield *** compensate for the limitations of high-throughput yield datasets,we curated a generic reaction yield dataset containing 12 reaction categories and rich reaction condition ***,by utilizing 2 pretraining tasks based on chemical reaction masked language modeling and contrastive learning,we proposed a powerful bidirectional encoder representations from transformers(BERT)-based reaction yield predictor named *** achieved comparable or even superior performance to the best previous models on 4 benchmark datasets and established state-of-the-art performance on the newly curated *** found that reaction-condition-based contrastive learning enhances the model’s sensitivity to reaction conditions,and Egret is capable of capturing subtle differences between reactions involving identical reactants and products but different reaction ***,we proposed a new scoring function that incorporated Egret into the evaluation of multistep synthesis *** results showed that yield-incorporated scoring facilitated the prioritization of literature-supported high-yield reaction pathways for target *** addition,through meta-learning strategy,we further improved the reliability of the model’s prediction for reaction types with limited data and lower data *** r

关键词： synthesis generic holds

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Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

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Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of Biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial Biotechnology research Group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran Novel Diagnostics and Therapeutics research Group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem Cell and regenerative medicine research Group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer *** tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the *** on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against *** discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"***,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer *** understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to ***-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in ***,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： Cancer stem cells(CSCs) Carcinoma Cell cycle heterogeneity Quiescence Therapy resistance Therapy tolerance Tumor dormancy

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Loss of GATA6-mediated up-regulation of UTX promotes pancreatic tumorigenesis and progression

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Genes & Diseases 2024年第2期11卷 921-934页

作者： Hui-Qing Zhang Fanyang Kong Xiangyu Kong Tingting Jiang Muyuan Ma Shaojiang Zheng Junli Guo Keping Xie The Third Department of Medical Oncology Jiangxi Cancer HospitalNanchangJiangxi 330006China Departments of Gastroenterology Changhai HospitalSecond Military Medical UniversityShanghai 200433China center for Pancreatic Cancer research The South China University of Technology School of MedicineGuangzhouGuangdong 510006China Hainan Clinical Medical research center of the First Affiliated Hospital Hainan Women and Children's Medical CenterHainan Medical UniversityHaikouHainan 570102China Key Laboratory of Tropical cardiovascular Diseases research of Hainan Province Key Laboratory of Emergency and Trauma of Ministry of EducationHainan Medical UniversityHaikouHainan 571199China

Ubiquitously transcribed tetratricopeptide repeat on chromosome X(UTX),also known as lysine(K)-specific demethylase 6A(KDM6A),functions as a tumor suppressor gene or oncogene depending on the tumor type and ***,its tumor-suppressive mechanisms remain largely ***,we investigated the clinical significance and biological effects of UTX expression in pancreatic ductal adenocarcinoma(PDA)and determined the potential mechanisms of its *** expression and its association with clinicopathologic characteristics of PDA patients were analyzed using *** mRNA and protein expression and their regulation in PDA cell lines were measured using quantitative polymerase chain reaction and Western blot *** biological functions of UTX in PDA cell growth,migration,and invasion were determined using gain-and loss-of-function assays with both in vitro and in vivo animal *** expression was reduced in human PDA cell lines and *** UTX expression was associated with poor differentiation and prognosis in *** UTX expression inhibited PDA proliferation,migration,and invasion in vitro and PDA growth and metastasis in vivo,whereas knockdown of UTX expression did the ***,UTX expression was trans-activated by GATA6 ***6-mediated PDA progression could be blocked,at least partially,by silencing UTX *** conclusion,loss of GATA6-mediated UTX expression was evident in human PDA and restored UTX expression suppressed PDA growth and ***,UTX is a tumor suppressor in PDA and may serve as a prognostic biomarker and therapeutic target.

关键词： Growth Invasion Metastasis Pancreatic cancer UTX

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Vaspin alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence

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Emergency and Critical Care medicine 2024年第1期4卷 4-15页

作者： Haiying Rui Huaxiang Yu Dan Zou Kai Chi Ping Xu Xiaoshuai Song Lulu Liu Xuting Wu Jinxin Wang Li Xue Department of Emergency medicine and Chest Pain center Qilu Hospital of Shandong UniversityJinanShandongChina Shandong Provincial Clinical research center for Emergency and Critical Care medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityQilu Hospital of Shandong UniversityJinanShandongChina Key Laboratory of Emergency and Critical Care medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinanShandongChina The Key Laboratory of cardiovascular Remodeling and Function research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinanShandongChina.

Background:Visceral adipose tissue-derived serine protease inhibitor(vaspin),a secretory adipokine,protects against insulin *** studies have demonstrated that serum vaspin levels are decreased in patients with coronary artery disease and that vaspin protects against myocardial ischemia-reperfusion injury and ***,it remains unclear whether vaspin exerts specific effects on pathological cardiac ***:An in vivo study was conducted using a cardiac hypertrophy model established by subcutaneous injection of isoproterenol(ISO)in C57BL/6 and vaspin-ko *** was administered intraperitoneally to mice,for further study.H9c2 cells and neonatal rat ventricular myocytes(NRVMs)were treated with ISO to induce *** vaspin fusion protein,the proteasome inhibitor MG132,and chloroquine diphosphate were used for further mechanistic ***:Here,we provide the first evidence that vaspin knockdown results in markedly exaggerated cardiac hypertrophy,fibrosis,and cardiomyocyte senescence in mice treated with ***,the administration of exogenous recombinant human vaspin protected NRVMs in vitro against ISO-induced hypertrophy and ***,vaspin significantly potentiated the ISO-induced decrease in *** rapamycin and chloroquine diphosphate regulated autophagy in vivo and in vitro,respectively,and participated in vaspin-mediated ***,the PI3K-AKT-mTOR pathway plays a critical role in vaspin-mediated autophagy in cardiac tissues and *** data showed that vaspin downregulated the p85 and p110 subunits of PI3K by linking p85 and p110 to NEDD4L-mediated ubiquitination ***:Our results show,for the first time,that vaspin functions as a critical regulator that alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence,providing potential preventive and therapeutic targets for pathological cardiac hyper

关键词： Autophagic flux Myocardial senescence Pathological cardiac hypertrophy Ubiquitination Vaspin

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Kdm6a-CNN1 axis orchestrates epigenetic control of traumainduced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair

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Bone research 2024年第2期12卷 314-333页

作者： Chengjun Li Tian Qin Jinyun Zhao Yuxin Jin Yiming Qin Rundong He Tianding Wu Chunyue Duan Liyuan Jiang Feifei Yuan Hongbin Lu Yong Cao Jianzhong Hu Department of Sports medicine Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceXiangya Road 87Changsha 410008China National Clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China Department of Spine Surgery and Orthopaedics Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China

Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory *** extensive investigations into vascular senescence associated with aging and degenerative diseases,the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress,particularly its involvement in senescence-induced inflammation,remain insufficiently *** this study,we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury(SCI).Lysine demethylase 6A(Kdm6a),commonly known as UTX,emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells(SCMECs).Upregulation of UTX induces senescence in SCMECs,leading to an amplified release of proinflammatory factors,specifically the senescenceassociated secretory phenotype(SASP)components,thereby modulating the inflammatory ***,the deletion of UTX in endothelial cells shields SCMECs against senescence,mitigates the release of proinflammatory SASP factors,and promotes neurological functional recovery after *** forms an epigenetic regulatory axis by binding to calponin 1(CNN1),orchestrating trauma-induced SCMECs senescence and SASP secretion,thereby influencing neuroinflammation and neurological functional ***,local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion,reinstating a local regenerative microenvironment and enhancing functional repair after *** conclusion,targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion,alleviate neuroinflammation,and provide a novel treatment strategy for SCI repair.

关键词： inflammation epigenetic neurological

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