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Human iP SC-derived mesenchymal stem cells relieve high blood pressure in spontaneously hypertensive rats via splenic nerve activated choline acetyltransferase-positive cells

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Science China Life Sciences 2024年

作者： Zhen Zhang Weijun Huang Xiaoran Zhang Zhecun Wang Manting Xie Bingbing Xie Yiling Wang Xiaoyong Chen Andy Peng Xiang Qiuling Xiang center for stem cell biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education Sun Yat-sen University department of Physiology Zhongshan School of Medicine Sun Yat-sen University department of Vascular Surgery the First Affiliated Hospital Sun Yat-sen University

Despite substantial advancements in modern medicine, the management of hypertension remains a major challenge. stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases, including hypertension. However, the antihypertensive mechanism of mesenchymal stem cells（MSCs） has not been extensively explored. This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis. Our previous study demonstrated that human induced pluripotent stem cellderived mesenchymal stem cells（hiPSC-MSCs） are functional and homogeneous sources for MSC-based therapy. After the injection of hiPSCMSCs, a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats（SHRs）. cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs. The injected hiPSC-MSCs accumulated adjacent to the splenic nerve, potentially contributing to the antihypertensive effects. Furthermore, the hiPSC-MSCs released abundant glutamate, which acts as a neuromodulator to activate the splenic sympathetic nerve. After inhibition of glutamate synthesis by siRNA, the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished. In addition, the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation（SND）, underscoring the critical role of the splenic nerve. Moreover, activation of the splenic nerve resulted in increased release of norepinephrine（NE）, which increased the number of choline acetyltransferase-positive（ChAT+） cells in the spleen and peripheral blood. Consequently, the acetylcholine（ACh） produced by elevated ChAT+cells could act as a vasodilator, lowering blood pressure and mitigating inflammation in end target organs. In summary, our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT+cells. The co

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Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

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BIOcell 2024年第1期48卷 149-162页

作者： PING YANG YUANXIANG LAN ZHONG ZENG YAN WANG HECHUN XIA department of Neurosurgery School of Clinical MedicineNingxia Medical UniversityYinchuanChina Key Laboratory of Ningxia stem cell and Regenerative Medicine General Hospital of Ningxia Medical UniversityYinchuanChina department of Neurosurgery Xi’an International Medical Center HospitalXi’anChina

Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of ***&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in *** primary objective is to provide evidence supporting the clinical application of ***:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after ***,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal *** intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted *** the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional ***,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and ***:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

关键词： Traumatic brain injury Mesenchymal stem cells Oxidative stress Matrix metalloproteinases

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Glial progenitor heterogeneity and plasticity in the adult spinal cord

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Neural Regeneration Research 2024年第12期19卷 2567-2568页

作者： Haichao Wei Jia Qian Wu department of Neurosurgery McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonTXUSA center for stem cell and Regenerative Medicine UT Brown Foundation Institute of Molecular MedicineHoustonTXUSA MD Anderson Cancer center UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous *** progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific ***,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous *** development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.

关键词： functions plasticity thoroughly

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

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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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Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids

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Protein & cell 2024年第4期15卷 285-304页

作者： Yunuo Mao Wei Wang Jingwei Yang Xin Zhou Yongqu Lu Junpeng Gao Xiao Wang Lu Wen Wei Fu Fuchou Tang School of Life Sciences Biomedical Pioneering Innovation CenterDepartment of General SurgeryThird HospitalPeking UniversityBeijing 100871China Beijing Advanced Innovation center for Genomics(ICG) Ministry of Education Key Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Peking-Tsinghua center for Life Sciences Peking UniversityBeijing 100871China Peking University Third Hospital Cancer center Beijing 100871China The Research center of stem cell and Regenerative Medicine School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Colorectal cancer(CRC)is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be ***,we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original *** efficiently identify repurposed drugs for CRC,we developed a robust organoid-based drug screening *** combining the repurposed drug library and computation-based drug prediction,335 drugs were tested and 34 drugs with anti-CRC effects were *** importantly,we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns:differentiation induction,growth inhibition,metabolism inhibition,immune response promotion,and cell cycle *** anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft(PDOX)system in *** found that fedratinib,trametinib,and bortezomib exhibited effective anticancer ***,the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were *** study offers an innovative approach for drug discovery,and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC.

关键词： colorectal cancer organoids drug repurposing patient-derived organoids-based xenograft mechanism of action

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The potent osteo-inductive capacity of bioinspired brown seaweed-derived carbohydrate nanofibrous three-dimensional scaffolds

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Marine Life Science & Technology 2024年第3期6卷 515-534页

作者： Zahra Dadashi Ouranj Saadi Hosseini Atefeh Alipour Shahin Homaeigohar Shahram Azari Leila Ghazizadeh Mohammadali Shokrgozar Sabu Thomas Saeed Irian Hosein Shahsavarani department of cell and Molecular biology Faculty of Biological SciencesKharazmi UniversityTehran 15719-14911Iran Laboratory of Regenerative Medicine and Biomedical Innovations National Cell Bank of IranPasteur Institute of IranTehran 13169-43551Iran department of Nanobiotechnology Pasteur Institute of IranTehran 13169-43551Iran School of Science and Engineering University of DundeeDundee DD14HNUK School of Chemical Sciences Mahatma Gandhi UniversityKottayamKeralaIndia department of cell and Molecular biology Faculty of Life Sciences and BiotechnologyShahid Beheshti UniversityTehran 19839-69411Iran Iranian Biological Resource center Academic Center for EducationCulture and Research(ACECR)Tehran ***Iran

This study aimed to investigate the osteo-inductive capacity of a fucoidan polysaccharide network derived from brown algae on human adipose-derived stem cells(HA-MSCs)for bone *** physiochemical properties of the scaffold including surface morphology,surface chemistry,hydrophilicity,mechanical stiffness,and porosity were thoroughly *** in vitro and in vivo measurements implied a superior cell viability,proliferation,adhesion,and osteo-inductive performance of obtained scaffolds compared to using specific osteogenic induction medium with increased irregular growth of calcium crystallites,which mimic the structure of natural *** scaffold was highly biocompatible and suitable for cell *** examinations,such as quantification of mineralization,alkaline phosphatase,gene expression,and immunocytochemical staining of pre-osteocyte and bone markers confirmed that HAD-MSCs differentiate into osteoblasts,even without an osteogenic induction *** study provides evidence for the positive relationship and synergistic effects between the physical properties of the decellularized seaweed scaffold and the chemical composition of fucoidan in promoting the osteogenic differentiation of ***,the natural matrices derived from brown seaweed offers a sustainable,cost-effective,non-toxic bioinspired scaffold and holds promise for future clinical applications in orthopedics.

关键词： Bone tissue engineering Seaweed-derived scaffold Fucoidans HA-MSCs differentiation Osteoblasts

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Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study

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World Journal of stem cells 2024年第1期16卷 19-32页

作者： ErdinçCivelek Serdar Kabatas Eyüp Can Savrunlu Furkan Diren Necati Kaplan Demet Ofluoğlu Erdal Karaöz department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey center for stem cell&Gene Therapy Research and Practice University of Health Sciences TurkeyGaziosmanpaşa 34255IstanbulTurkey department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalÇorlu 59860TekirdağTurkey department of Physical Medicine and Rehabilitation Ofluoğlu KlinikGöztepe 34728IstanbulTurkey Liv Hospital Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell)Beşiktaş34340IstanbulTurkey department of Histology and Embryology Istinye UniversityFaculty of MedicineZeytinburnu 34010IstanbulTurkey Istinye University Center for Stem Cell and Tissue Engineering Research and PracticeBeşiktaş34340IstanbulTurkey

BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain ***,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve *** To examine the impact of exosomes on the process of functional recovery following a complete radial nerve *** A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife *** cut is located on the left arm,specifically below the *** neurological examination and electrodiagnostic testing reveal evidence of left radial nerve *** sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion *** exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural *** patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic *** The duration of the patient’s follow-up period was 180 *** increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve *** the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the *** assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon *** results indicated that the level of improvement in motor function was classified as M5,denoting an excellent ***,the level of improvement in sensory function was classified as S3+,indicating a good *** is

关键词： Mesenchymal stem cell Exosomes Radial nerve Sural nerve

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Unresolved Excess Accumulation of Myelin-Derived Cholesterol Contributes to Scar Formation after Spinal Cord Injury

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Research 2024年第1期2023卷 17-32页

作者： Bolin Zheng Yijing He Shuai Yin Xu Zhu Qing Zhao Huiyi Yang Zhaojie wang Rongrong Zhu Liming Cheng Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationDepartment of OrthopedicsTongji HospitalSchool of MedicineTongji UniversityShanghai 200092China Frontier Science center for stem cell Research School of Life Science and TechnologyTongji UniversityShanghai 200092China Clinical center for Brain and Spinal Cord Research Tongji UniversityShanghai 200092China

Spinal cord injury triggers complex pathological cascades,resulting in destructive tissue damage and incomplete tissue *** formation is generally considered a barrier for regeneration in the central nervous ***,the intrinsic mechanism of scar formation after spinal cord injury has not been fully ***,we report that excess cholesterol accumulates in phagocytes and is inefficiently removed from spinal cord lesions in young adult ***,we observed that excessive cholesterol also accumulates in injured peripheral nerves but is subsequently removed by reverse ***,preventing reverse cholesterol transport leads to macrophage accumulation and fibrosis in injured peripheral ***,the neonatal mouse spinal cord lesions are devoid of myelin-derived lipids and can heal without excess cholesterol *** found that transplantation of myelin into neonatal lesions disrupts healing with excessive cholesterol accumulation,persistent macrophage activation,and *** internalization suppresses macrophage apoptosis mediated by CD5L expression,indicating that myelin-derived cholesterol plays a critical role in impaired wound *** together,our data suggest that the central nervous system lacks an efficient approach for cholesterol clearance,resulting in excessive accumulation of myelin-derived cholesterol,thereby inducing scar formation after injury.

关键词： healing Spinal impaired

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Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

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Protein & cell 2024年第6期15卷 441-459页

作者： Feifei Liu Yi Lu Xuebao Wang Shuhui Sun Huize Pan Min Wang Zehua Wang Weiqi Zhang Shuai Ma Guoqiang Sun Qun Chu Si Wang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Sports Medicine department Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China State Key Laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Division of Life Sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Advanced Innovation center for Human Brain Protection and National Clinical Research center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint ***,the mechanism underlying human synovial aging remains poorly ***,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged *** delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged ***,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue *** particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged *** human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged *** data indicate an important role of FOXO1 in the regulation of human synovial ***,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

关键词： FOXO1 degeneration inflammation

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Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer:A systematic review

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 197-213页

作者： Eman Al-Balushi Amina Al Marzouqi Shima Tavoosi Amir Hossein Baghsheikhi Arash Sadri Leyla Sharifi Aliabadi Mohammad-Mahdi Salarabedi Syed Azizur Rahman Nabeel Al-Yateem Alireza Mosavi Jarrahi Aram Halimi Mohammad Ahmadvand Wael M Abdel-Rahman College of Health Sciences University of SharjahSharjah 27272United Arab Emirates department of biology Faculty of SciencesUniversity of IsfahanIsfahan 81746-73441Iran department of biology Science and Research BranchIslamic Azad UniversityTehran 11365/4435Iran Students’Scientific Research center Tehran University of Medical SciencesTehran ***Iran cell Therapy and Hematopoietic stem cell Transplantation Research center Research Institute for OncologyHematologyand Cell TherapyTehran University of Medical SciencesTehran ***Iran Student Research Committee School of MedicineShahid Beheshti University of Medical SciencesTehran ***Iran department of Nursing University of SharjahSharjah 27272United Arab Emirates Cancer Research Centre Shahid Beheshti University of Medical SciencesTehran ***Iran department of Medical Laboratory Sciences University of SharjahSharjah 27272United Arab Emirates

BACKGROUND Colorectal cancer(CRC)is the third most frequent and the second most fatal *** search for more effective drugs to treat this disease is ongoing.A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic ***-specific peptidases(USPs),the largest group of the deubiquitinase protein family,have long been implicated in various *** have been numerous studies on the role of USPs in CRC;however,a comprehensive view of this role is *** To provide a systematic review of the studies investigating the roles and functions of USPs in *** We systematically queried the MEDLINE(via PubMed),Scopus,and Web of Science *** Our study highlights the pivotal role of various USPs in several processes implicated in CRC:Regulation of the cell cycle,apoptosis,cancer stemness,epithelial–mesenchymal transition,metastasis,DNA repair,and drug *** findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in *** dysregulation of USPs in CRC contributes to drug resistance through multiple *** Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

关键词： Ubiquitin-specific peptidases Colorectal cancer Deubiquitinase protein family Drug target discovery Biomarker discovery

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