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Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi Wang Mengke Zhao Dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing Liu Stem Cell Clinical Research Center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem Cell and precision medicine DalianLiaoning ProvinceChina Institute(College)of Integrative medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)

Mechanism by which Rab5 promotes regeneration and functional recovery of zebrafish Mauthner axons

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Neural Regeneration Research 2025年第6期20卷 1816-1824页

作者： Jiantao Cui Yueru Shen Zheng Song Dinggang Fan Bing Hu Center for Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo;however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase(PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.

关键词： axonal regeneration Mauthner cell nerve regeneration Rab5 zebrafish

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru C.Guo division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada Faculty of medicine–The University of British Columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science Core Collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

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World Journal of Clinical Oncology 2025年第1期16卷 1-4页

作者： Emad Qayed Department of medicine Division of Digestive DiseasesEmory University School of MedicineAtlantaGA 30303United States

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with *** propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse *** study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

关键词： Gastric cancer Overt bleeding Systemic therapy Endoscopic therapy Hemostasis

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu Department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical precision medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina Department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

Rising incidence of acute hepatitis A among adults and clinical characteristics in a tertiary care center of Pakistan

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World Journal of Virology 2025年第1期14卷 73-82页

作者： Yumna Shahid Amna Subhan Butt Iqra Jamali Faisal Wasim Ismail division of Gastroenterology Department of MedicineAga Khan University HospitalKarachi 74800Pakistan Department of medicine Aga Khan University HospitalKarachi 74800Pakistan

BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among ***,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among *** To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)*** This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May *** aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were *** compare the trend patients admitted with acute hepatitis during 2019-2023 were also *** regarding clinical and laboratory parameters were *** yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among *** A total of 396 patients were found to have acute hepatitis during our study *** was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV ***,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute *** trends showed increasing occurrence of HAV infection among adults over last 5 *** patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV ***,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in *** An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.

关键词： Acute hepatitis Hepatitis A virus Hepatitis E virus Acute liver failure Hepatotropic virus Vaccination

Advancements in diabetic retinopathy:Insights and future directions

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World Journal of Methodology 2025年第2期15卷 21-26页

作者： Chun-Yao Cheng Wen-Rui Hao Tzu-Hurng Cheng Department of Ophthalmology Cathay General HospitalTaipei 10633TaiwanChina division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561TaiwanChina division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002TaiwanChina Department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328TaiwanChina

This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive *** their review,Morya et al discussed the pathophysiology of diabetic retinopathy and explored novel treatment *** editorial highlights the importance of these advancements and emphasizes the need for continued research and innovation for the enhanced management of diabetic *** also reflects upon the implications of the authors’review findings for clinical practice and future research directions,underscoring the potential of emerging therapies for improving patient outcomes and providing a deeper understanding of disease mechanisms.

关键词： Diabetic retinopathy Pathophysiology Novel treatments Review analysis Clinical implications

Enhancing the outcomes of diabetic vitrectomy with pharmacological adjuvants

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World Journal of Methodology 2025年第2期15卷 15-20页

作者： Chun-Yao Cheng Wen-Rui Hao Tzu-Hurng Cheng Department of Ophthalmology Cathay General HospitalTaipei 10633TaiwanChina division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei City 23561TaiwanChina division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002TaiwanChina Department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung City 404328TaiwanChina

This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic ***,they synthesized current knowledge and evaluated the efficacy of various adjunctive therapies in improving the outcomes of diabetic retinopathy and managing associated ***,we highlight the key roles of pharmacological adjuvants in optimizing surgical techniques,minimizing intraoperative challenges,and enhancing postoperative *** further discuss the potential implications of this approach for clinical practice and future research directions in this evolving ***,this editorial underscores the importance of incorporating pharmacological adjuvants into standard diabetic vitrectomy care to improve surgical outcomes and thus patients’quality of life.

关键词： Diabetic vitrectomy Pharmacological adjuvants Surgical outcomes Diabetic retinopathy Clinical implications

Improving postoperative outcomes in patients with pancreatic cancer:Inflammatory and nutritional biomarkers

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World Journal of Clinical Oncology 2025年第1期16卷 59-64页

This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic *** et al evaluated the ability of seven biomarkers to predict postoperative recovery and long-term *** biomarkers were albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,nutritional risk index,and geriatric nutritional risk *** PNI was found to be a strong predictor of both overall and recurrence-free survival,underscoring its clinical relevance in managing patients with pancreatic cancer.

关键词： Pancreatic cancer Prognostic nutritional index Systemic immune-inflammation index Postoperative recovery Prognosis