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Mesenchymal stem cell therapy for liver fibrosis need“partner”:Results based on a meta-analysis of preclinical studies

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World Journal of Gastroenterology 2024年第32期30卷 3766-3782页

作者： Yan Xu Xue-Song Wang Xiao-Lei Zhou Wen-Ming Lu Xing-Kun Tang Yu Jin Jun-Song Ye Subcenter for stem cell Clinical Translation First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina School of Rehabilitation Medicine Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina Ganzhou Key Laboratory of stem cell and Regenerative Medicine Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina Department of Medical Genetics School of MedicineTongji UniversityShanghai 200092China Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of EducationGannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina

BACKGROUND The efficacy of mesenchymal stem cells(MSCs)in treating liver fibrosis has been demonstrated in several clinical ***,their low survival and liver implantation rates remain *** recent years,a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver *** has inspired new ways of thinking about treating liver *** To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver *** Data sources included four electronic databases and were constructed until January *** subjects,interventions,comparators,outcomes,and study design principle were used to screen the literature,and the quality of the literature was evaluated to assess the risk of *** randomised controlled trials were selected,and the final 13 studies were included in the final *** A total of 13 studies were included after *** analysis showed that MSCs combined with drug therapy significantly improved liver function,promoted the repair of damaged liver tissues,reduced the level of liver fibrosis-related indexes,and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment,promoting the homing of MSCs,and regulating the relevant signaling pathways,and the treatment efficacy was superior to MSCs ***,the combined treatment statistics showed no amelioration in serum albumin levels(standardized mean difference=0.77,95%confidence interval:-0.13 to 1.68,P=0.09).CONCLUSION In conclusion,MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic ***,due to the different drugs,the treatment mechanism and effect also ***,more randomized controlled trials are needed to compare the therapeutic effic

关键词： drugs alone partner

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Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF:not just ICSI failure

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Asian Journal of Andrology 2024年第2期26卷 175-182页

作者： Jian-Fang Che Hui-Xia Wu Si-Cong Zeng Yue-Ren Wu Jing Dai De-Hua Cheng Fei Gong Guang-Xiu Lu Ge Lin Can Dai School of Medicine Hunan Normal UniversityChangsha 410013China Reproductive and Genetic Hospital of CITIC-Xiangya Changsha 410008China Clinical Research Center for Reproduction and Genetics in Hunan Province Changsha 410078China National Engineering and Research Center of Human stem cell Changsha 410205China

Phospholipase C zeta(PLC)is a key sperm-borne oocyte-activating factor that triggers Ca^(2+)oscillations and the subsequent block to polyspermy following gamete *** in PLCZ1,the gene encoding PLCζ,cause male infertility and intracytoplasmic sperm injection(ICSI)fertilization failure;and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate(FR).However,in conventional in vitro fertilization(cIVF),whether and how sperm PLCζ affects fertilization remain ***,we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei(PN)*** staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca^(2+) *** with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live ***,we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CiTiC-Xiangya(Changsha,China)between February 2019 and January *** found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total *** optimal cutoff value below which males were likely to experience low FR(total FR≤30%)after clVF was 56.7%for the proportion of spermatozoa expressing *** study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the widermale population and not onlymen with IcsI failure.

关键词： conventional IVF gene variants PLCζ polyspermy

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Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China(Life Sciences) 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Tenth People’s Hospital School of MedicineTongji UniversityShanghai 200072China Frontier Science Center for stem cell Research Tongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Shanghai Institute of stem cell Research and Clinical Translation Shanghai 200120China

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription,the epigenome and ***,previous studies using knockdown(KD)or knockout(KO)models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles,as well as compensatory effects among TET family members,which has made the understanding of the enzymatic role of TET not accurate *** solve this problem,we successfully generated mice catalytically inactive for specific Tet members(Tetm/m).We observed that,compared with the reported KO mice,mutant mice exhibited distinct developmental defects,including growth retardation,sex imbalance,infertility,and perinatal ***,Tetm/mmouse embryonic stem cells(mESCs)were successfully established but entered an impaired developmental program,demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA ***,Tet3,traditionally considered less critical for m ESCs due to its lower expression level,had a significant impact on the global hydroxymethylation,gene expression,and differentiation potential of ***,there were common regulatory regions between Tet1 and Tet3 in pluripotency *** summary,our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

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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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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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PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

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Zoological Research 2024年第5期45卷 1037-1047页

作者： Chun-Xue Niu Jia-Wei Li Xiao-Li Li Lin-Lin Zhang Yan Lang Zhen-Bo Song Chun-Lei Yu Xiao-Guang Yang Hai-Feng Zhao Jia-Ling Sun Li-Hua Zheng Xue Wang Ying Sun Xiao-Hong Han Guan-Nan Wang Yong-Li Bao National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal UniversityChangchunJilin 130117China China International Joint Research Center for Human stem cell Bank Northeast Normal UniversityChangchunJilin 130117China Jilin Institute for Drug Control ChangchunJilin 130022China

Serine protease 50(PRSS50/TSP50)is highly expressed in *** study investigated its role in testicular development and ***,PRSS50 knockdown was observed to impair DNA synthesis in *** further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male ***,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic *** analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−*** together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.

关键词： PRSS50(TSP50) Meiotic progression Sperm quality MKP3 ERK

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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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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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Deer antler stem cell niche: An interesting perspective

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World Journal of stem cells 2024年第5期16卷 479-485页

作者： Claudia Cavallini Elena Olivi Riccardo Tassinari Chiara Zannini Gregorio Ragazzini Martina Marcuzzi Valentina Taglioli Carlo Ventura National Laboratory of Molecular Biology and stem cell Engineering National Institute of Biostructures and Biosystems-Eldor LabBologna 40128Italy Eldor Lab Bologna 40128Italy Department of Medical and Surgical Sciences(DIMEC) University of BolognaBologna 40138Italy

In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident ***,in particular,have garnered significant interest for their potential to serve as natural scaffolds for *** this editorial,we provide commentary on the study by Wang et al,in a recently published issue of World J stem cells,which investigates the use of a decellularized xenogeneic extracellular matrix(ECM)derived from antler stem cells for repairing osteochondral defects in rat knee *** focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities,thanks to the establishment of a favorable microenvironment(niche).stem cell differen-tiation heavily depends on exposure to intrinsic properties of the ECM,including its chemical and protein composition,as well as the mechanical forces it can ***,these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and *** interest in mechanobiology,often conceptualized as a form of“structural memory”,is steadily gaining more validation and momen-tum,especially in light of findings such as these.

关键词： Extracellular matrix Antler stem cells stem cell niche Regenerative medicine Decellularized scaffolds cell memory

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Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

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Neural Regeneration Research 2024年第4期19卷 872-880页

作者： Mou Gao Qin Dong Zhijun Yang Dan Zou Yajuan Han Zhanfeng Chen Ruxiang Xu Department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of China Department of Neurosurgery Chinese PLA General Hospital Zhongsai stem cell Genetic Engineering Co. Ltd. Department of Neurology Fu Xing HospitalCapital Medical University

stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head *** previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell ***,the neural regeneration efficiency of induced neural stem cells remains *** this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem *** found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem ***,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived *** predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem *** H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 ***,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem ***,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury *** results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

关键词： closed head injury Ctbp2 induced neural stem cell lncRNA H19 miR-325-3p neurogenesis

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