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MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

Neural Regeneration Research 2025年第5期20卷 1431-1444页

作者： Yuehua Cui Xiaokuang Ma Jing Wei Chang Chen neha Shakir Hitesch Guirram Zhiyu Dai Trent Anderson Deveroux Ferguson Shenfeng Qiu Basic Medical Sciences University of Arizona College of Medicine-PhoenixPhoenixAZUSA Department of Medicine University of Arizona College of Medicine-PhoenixPhoenixAZUSA

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse *** have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine *** investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing *** found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection *** findings are further corroborated by increased synaptic activity and transient generation of immature silent *** MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and *** data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult *** findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

关键词： aging circuit connectivity cortical circuits molecular mechanisms neural regeneration neurodegeneration synapses

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Readmission rate and early complications in patients undergoing total knee arthroplasty:A retrospective study

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World Journal of Orthopedics 2024年第8期15卷 713-721页

作者： Tushar Jethi Deepak Jain Rajnish garg Harpal Singh Selhi Department of Orthopedics Fortis Hospital LudhianaLudhiana 141123PunjabIndia Department of Orthopedics Dayanand Medical College&HospitalLudhiana 141001PunjabIndia Department of Orthopedic Surgery Dayanand Medical College&HospitalLudhiana 141001PunjabIndia

BACKGROUND Total knee arthroplasty(TKA)can improve pain,quality of life,and functional *** uncommon,postoperative complications are extremely consequential and thus must be carefully tracked and communicated to patients to assist their decision-making before *** of the risk factors for complications and readmissions after TKA,taking into account common causes,temporal trends,and risk variables that can be changed or left unmodified,will benefit this *** To assess readmission rates,early complications and their causes after TKA at 30 days and 90 days *** This was a prospective and retrospective study of 633 patients who underwent TKA at our hospital between January 1,2017,and February 28,*** the 633 patients,28 were not contactable,leaving 609 who met the inclusion *** inpatient and outpatient hospital records were retrieved,and observations were noted in the data collection *** Following TKA,the 30-day and 90-day readmission rates were determined to be 1.1%(n=7)and 1.8%(n=11),*** unplanned visit rate at 30 days following TKA was 2.6%(n=16)and at 90 days was 4.6%(n=28).At 90 days,the unplanned readmission rate was 1.4%(n=9).Reasons for readmissions included medical(27.2%,n=3)and surgical(72.7%,n=8).Unplanned readmissions and visits within 90 days of follow-up did not substantially differ by age group(P=0.922),body mass index(BMI)(P=0.633),unilateral vs bilateral TKA(P=0.696),or patient comorbidity status(30-day P=0.171 and 90-day P=0.813).Reoperation rates after TKA were 0.66%(n=4)at 30 days and 1.15%(n=8)at 90 *** average length of stay was 6.53 *** In this study,there was a low readmission rate following *** was no significant correlation between readmission rate and patient factors such as age,BMI,and co-morbidity status.

关键词： Total knee arthroplasty Length of stay Readmission Rates Causes Risk factors Prospective Retrospective Follow-up Reoperation

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Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population

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World Journal of Methodology 2024年第3期14卷 90-105页

作者： Navneet Kaur Gitanjali Goyal Ravinder garg Chaitanya Tapasvi Umit Demirbaga Department of Biochemistry Guru Gobind Singh Medical College and HospitalFaridkot 151203PunjabIndia Department of Biochemistry All India Institute of Medical SciencesBathinda 151005PunjabIndia Department of Medicine Guru Gobind Singh Medical College and HospitalBaba Farid University of Health SciencesFaridkot 151203PunjabIndia Department of Radiodiagnosis Guru Gobind Singh Medical College and HospitalBaba Farid University of Health SciencesFaridkot 151203India Department of Computer Engineering Bartin UniversityBartin 74100Türkiye Department of Medicine University of CambridgeCambridge CB20QQUnited Kingdom European Bioinformatics Institute Wellcome GenomeCambridge CB101SDUnited Kingdom

BACKGROUND Hepatitis C virus(HCV)infection progresses through various phases,starting with inflammation and ending with hepatocellular *** are several invasive and non-invasive methods to diagnose chronic HCV *** invasive methods have their benefits but are linked to morbidity and ***,it is important to analyze the potential of non-invasive methods as an *** wave elastography(SWE)is a non-invasive imaging tool widely validated in clinical and research studies as a surrogate marker of liver *** fibrosis determination by invasive liver biopsy and non-invasive SWE agree closely in clinical studies and therefore both are gold *** To analyzed the diagnostic efficacy of non-invasive indices[serum fibronectin,aspartate aminotransferase to platelet ratio index(APRI),alanine aminotransferase ratio(AAR),and fibrosis-4(FIB-4)]in relation to *** have used an Artificial Intelligence method to predict the severity of liver fibrosis and uncover the complex relationship between non-invasive indices and fibrosis *** We have conducted a hospital-based study considering 100 untreated patients detected as HCV positive using a quantitative Real-Time Polymerase Chain Reaction *** performed statistical and probabilistic analyses to determine the relationship between non-invasive indices and the severity of *** also used standard diagnostic methods to measure the diagnostic accuracy for all the *** The results of our study showed that fibronectin is a highly accurate diagnostic tool for predicting fibrosis stages(mild,moderate,and severe).This was based on its sensitivity(100%,92.2%,96.2%),specificity(96%,100%,98.6%),Youden’s index(0.960,0.922,0.948),area under receiver operating characteristic curve(0.999,0.993,0.922),and Likelihood test(LR+>10 and LR-200),AAR(>1),APRI(>3),and FIB-4(>4)were all strongl

关键词： Hepatitis C virus Non-invasive biomarkers Shear wave elastography Fibronectin Bayesian network Machine learning Liver fibrosis

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Overlap in oncogenic and pro-inflammatory pathways associated with areca nut and nicotine exposure

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Cancer Pathogenesis and Therapy 2024年第3期2卷 187-194页

作者： Krati garg Anuj Kumar Vidisha Kizhakkethil Pramod Kumar Shalini Singh Department of Biochemical Engineering and Biotechnology Indian Institute of Technology(IIT)DelhiDelhi 110016India Division of Molecular Biology ICMR-National Institute of Cancer Prevention and Research(ICMR-NICPR)Indian Council of Medical ResearchNoidaUttar Pradesh 201301India Department of Biotechnology Vellore Institute of Technology(VIT)VelloreTamil Nadu 632024India ICMR-National Institute of Cancer Prevention&Research(ICMR-NICPR) Indian Council of Medical ResearchNoidaUttar Pradesh 201301India

Background:Betel nut/areca nut/Areca catechu is one of the most commonly used psychoactive substance,and is also a major preventable cause of *** other psychoactive substances,such as nicotine,the mechanisms underlying addiction to areca nuts and related oncogenesis remain *** reports suggest a possible overlap in the mechanisms of action of nicotine and areca nuts in the human ***,this study aimed to investigate the interactome of human proteins associated with areca nut exposure and the intricate similarities and differences in the effects of the two psychoactive substances on ***:A list of proteins associated with areca nut use was obtained from the available literature using terms from Medical Subject Headings(MeSH).Protein-protein interaction(PPI)networks and functional enrichment were *** results obtained for both psychoactive substances were ***:Given the limited number of common proteins(36/226,16%)in the two sets,a substantial overlap(612/1176 nodes,52%)was observed in the PPI networks,as well as in Gene *** nuts mainly affect signaling pathways through three hub proteins(alpha serine/threonine-protein kinase,tumor protein 53,and interleukin-6),which are common to both psychoactive substances,as well as two unique hub proteins(epidermal growth factor receptor and master regulator of cell cycle entry and proliferative metabolism).Areca nut-related proteins are associated with unique pathways,such as extracellular matrix organization,lipid storage,and metabolism,which are not found in nicotine-associated ***:Areca nuts affect regulatory mechanisms,leading to systemic toxicity and *** nuts also affect unique pathways that can be studied as potential markers of exposure,as well as targets for anticancer therapeutic agents.

关键词： Cancer Areca nut Nicotine Interactome Cell signaling

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Aging impairs the osteocytic regulation of collagen integrity and bone quality

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Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna Bons Christina D.King Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck Institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly *** molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by *** hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material *** examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses *** control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)*** relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical *** effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

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