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Clinical applications of stem cell-derived exosomes

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Signal Transduction and Targeted Therapy 2024年第2期9卷 621-651页

作者： Fei Tan Xuran Li Zhao Wang Jiaojiao Li Khawar Shahzad Jialin Zheng Department of ORL-HNS Shanghai Fourth People’s Hospitaland School of MedicineTongji UniversityShanghaiChina Plasma Medicine and Surgical Implants Center Tongji UniversityShanghaiChina the royal college of surgeons in ireland DublinIreland The royal college of surgeons of England LondonUK Center for Translational Neurodegeneration and Regenerative Therapy Tongji Hospital affiliated to Tongji University School of MedicineShanghaiChina Shanghai Frontiers Science Center of Nanocatalytic Medicine Tongji UniversityShanghaiChina

Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery,it nevertheless comes with inescapable drawbacks that might limit its clinical *** to stem cells,stem cell-derived exosomes possess numerous advantages,such as non-immunogenicity,non-infusion toxicity,easy access,effortless preservation,and freedom from tumorigenic potential and ethical *** can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or *** a thorough search and meticulous dissection of relevant literature from the last five years,we present this comprehensive,up-to-date,specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived *** derived from stem cells(e.g.,embryonic,induced pluripotent,hematopoietic,mesenchymal,neural,and endothelial stem cells)are capable of treating numerous diseases encountered in orthopedic surgery,neurosurgery,plastic surgery,general surgery,cardiothoracic surgery,urology,head and neck surgery,ophthalmology,and obstetrics and *** diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses,and cell-specific molecular signaling *** this review,we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical *** recommend that future research combines wisdoms from surgeons,nanomedicine practitioners,and stem cell researchers in this relevant and intriguing research area.

关键词： viable stem capable

ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam Jochen H.M.Prehn Hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and college of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF2 azadipyrromethene fluorophores

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Frontiers of Chemical Science and Engineering 2020年第1期14卷 97-104页

作者： Dan Wu Gonzalo Duran-Sampedro Donal F.O’Shea Department of Chemistry Royal College of Surgeons in Ireland(RCSI)Dublin 2Ireland

Bis-alkylsulfonic acid and polyethylene glycol(PEG)-substituted BF2 azadipyrromethenes have been synthesized by an adaptable and versatile *** four synthetic stages were required to produce the penultimate fluorophore compounds,containing either two alcohol or two terminal alkyne *** final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous *** acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide,and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated *** fluorophores exhibited excellent near-infrared(NIR)photophysical properties in methanol and aqueous *** cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both *** simple synthesis,with potential for last-step structural modifications,makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells.

关键词： NIR-fluorophores live cell imaging NIRAZA

Acetabular cup size trends in total hip arthroplasty

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World Journal of Orthopedics 2024年第1期15卷 39-44页

作者： Daniel Patrick McKenna Alex Price Timothy McAleese Darren Dahly Paul McKenna May Cleary Department of Trauma and Orthopaedics University Hospital WaterfordWaterford X91 ER8EIreland Department of Epidemiology and Public Health University College CorkCork T12 XF62Ireland

BACKGROUND Total hip arthroplasty(THA)is a common procedure for end stage *** learning curve for THA is complex and *** of the most difficult skills to master is acetabular *** wish to identify if experience in arthroplasty leads to preservation of more bone *** To investigate if increasing surgeon experience will predict an ever decreasing acetabular cup *** A retrospective case series of four attending orthopaedic surgeons was *** uncemented elective total hip arthroplasties since appointment were selected for *** size of acetabular cup used was noted and logistic regression was used to identify if a trend to smaller cups *** A total of 1614 subjects were included with a mean age of 64 *** cups were on average 0.18mm smaller per year(95%confidence interval-0.25 to-0.11,Psurgeons had a more pronounced trend to smaller cups for male subjects than their female *** We found increasing surgeon experience to be associated with an ever-decreasing acetabular cup *** acetabular cup size may act as a surrogate marker of surgical proficiency by virtue of decreased acetabular reaming.

关键词： Hip Arthroplasty Acetabulum Cup Learning

Can we protect the brain via preconditioning?Role of microRNAs in neuroprotection

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Neural Regeneration Research 2016年第3期11卷 388-389页

作者： Sean Quinlan Eva M.Jimenez-Mateos Department of Physiology and Medical Physics Royal College of Surgeons in Ireland

Preconditioning stimulus：Preconditioning is an adaptive response,whereby a small dose of a harmful substance protects the brain from a subsequent damaging insult（Dirnagl et al.,2009）.The concept of preconditioning was first described in an ischemic heart model,it was observed that brief ischemic episodes protect against a subsequent ischemic insult（Murry et al., 1986）.

关键词： subsequent protect harmful brief targeting synaptic stimulus epileptic targeted RNA

Gastrointestinal tolerability of organic infant formula compared to traditional infant formula: A systematic review

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World Journal of Clinical Pediatrics 2024年第1期13卷 125-140页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Reem Elbeltagi Mohamed Basiony Hamza Department of Pediatric Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityDr.Sulaiman Al Habib Medical GroupManama 26671ManamaBahrain Medical Microbiology Section Department of PathologySalmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12ManamaBahrain Medical Microbiology Section Department of PathologyIrish Royal College of SurgeonBusaiteen 15503MuharraqBahrain Department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527AlghrabiaEgypt Department of Pulmonology University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityDr.Sulaiman Al Habib Medical GroupManama 26671ManamaBahrain Department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503MuharraqBahrain Department of Pediatric Faculty of MedicineTanta UniversityTanta 31511AlgahrbiaEgypt

BACKGROUND Infants'nutrition significantly influences their growth,development,and overall *** the increasing demand for organic infant formula driven by the perception of health benefits and growing awareness of natural feeding options,it is crucial to conduct a comparative analysis of the gastrointestinal tolerability between organic and traditional infant *** To provide a concise and precise analysis of the gastrointestinal tolerability of organic infant formula compared to traditional infant *** to limited direct comparisons,the review synthesizes available literature on each formula type,presenting insights into their potential effects on infants'digestive *** An extensive literature search was conducted,compiling studies on organic and traditional infant formulas,their compositions,and reported effects on gastrointestinal *** searched academic databases such as PubMed and Google Scholar and specialized nutrition,paediatrics,and infant health journals using relevant keywords till October 1,*** Although specific comparative studies are scarce and formula heterogeneity is a significant limitation,this systematic review provides an in-depth understanding of organic infant formulas'composition and potential *** scientific evidence directly comparing gastrointestinal tolerability is limited,organic formulas strive to use carefully selected organic ingredients to imitate breast milk *** benefits include improved lipid profiles,higher methionine content,and decreased antibiotic-resistant bacteria *** the gastrointestinal tolerability of organic and traditional infant formulas is crucial for parents and healthcare providers to make informed *** Despite limitations in direct comparisons,this systematic review provides insights into the composition and potential benefits of organic infant *** emphasizes the need for further research to eluci

关键词： Organic infant formula Traditional infant formula Gastrointestinal tolerability Formula ingredients Digestive health Infant nutrition Organic farming

Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via retinoblastoma pathway

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World Journal of Gastroenterology 2004年第1期10卷 17-21页

作者： ChristianGulmann HelenHegarty AntoinetteGrace MaryLeader ElaineKay Stephen Patchett Department of Pathology Beaumont Hospital and Royal College of Surgeons in IrelandDublinIreland Department of Gastroenterology Beaumont HospitalDublinIreland

AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb)tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences. METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour. RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional) decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections) to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections. CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis. It may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.

关键词：胃癌眼癌肿瘤病理学细胞周期免疫组织化学

Metabolomic changes in children with autism

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World Journal of Clinical Pediatrics 2024年第2期13卷 171-197页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Reem Elbeltagi Department of Pediatric Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of Pediatric University Medical CenterDr.Sulaiman Al Habib Medical GroupManamaBahrainManama 26671Bahrain Medical Microbiology Section Department of PathologySalmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12Bahrain Medical Microbiology Section Department of PathologyIrish Royal College of SurgeonBahrainBusaiteen 15503MuharraqBahrain Department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527AlghrabiaEgypt Department of Chest Disease University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of Chest Disease University Medical CenterDr.Sulaiman Al Habib Medical GroupManamaManama 26671Bahrain Department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503MuharraqBahrain

BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive *** profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with *** To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book *** A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January *** criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with *** criteria were applied to ensure the relevance and quality of included *** The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing *** metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment *** profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with *** Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving *** research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic *** advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.

关键词： Autism spectrum disorder Metabolic dysregulations Metabolomic changes Children Mitochondrial dysfunction Oxidative stress Amino acids

Microphallus early management in infancy saves adulthood sensual life:A comprehensive review

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World Journal of Clinical Pediatrics 2024年第2期13卷 16-37页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Majed A Shaikh Reem Elbeltagi Department of Pediatric Faculty of MedicineTanta UniversityTanta 31511Egypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of Pediatric University Medical CenterSulaiman Al Habib Medical GroupManama 26671Bahrain Department of Medical Microbiology Section and Pathology Salmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12Bahrain Department of Medical Microbiology Section and Pathology Irish Royal College of SurgeonBusaiteen 15503Bahrain Department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527Egypt Department of Pulmonology University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain Department of Pulmonology University Medical CenterSulaiman Al Habib Medical GroupManama 26671Bahrain Department of Pediatrics Ibn Al Nafees HospitalManama 54533Bahrain Department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503Bahrain

Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected *** article comprehensively reviews micropenis,its etiology,epidemiology,and various treatment *** conducted a thorough literature review to collect relevant information on micropenis and microphallus,as well as related *** primary databases were PubMed,Medline,and Google *** searched for articles published in English between 2000 and *** analysis included 67 review articles,56 research studies,11 case reports,one guideline,and one *** search terms included"microphallus","micropenis","congenital hypogonadotropic hypogonadism","androgen insensitivity syndrome","pediatric management of micropenis","testosterone therapy",and"psychosocial implications of micropenis".We focused on diagnosing micropenis and related conditions,including hormonal assessments,medical and surgical treatment options,psychosocial and psychological well-being,sexual development of adolescents,and sociocultural influences on men's perceptions of penile ***,we explored parenting and family dynamics in cases of micropenis and disorders of sex development,implications of hormonal treatment in neonates,and studies related to penile augmentation procedures and their *** article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with *** procedures,such as penile lengthening and girth enhancement,and non-surgical approaches like hormonal therapy are *** significance of psychological support,education,and lifestyle modifications is *** management and comprehensive care are crucial for individuals with micropenis,from infancy to adolescence and beyond.A multidisciplinary approach involving urologists,endocrinologists,and mental health professionals is *** assessment of treatment e

关键词： Microphallus Micropenis Hypogonadism Children Adults Sensual life Testosterone therapy