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The proteome of distal nerves: implication in delayed repair and poor functional recovery

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Neural Regeneration Research 2022年第9期17卷 1998-2006页

作者： Song Guo Raymond M.Moore M.Cristine Charlesworth kenneth L.Johnson Robert J.Spinner Anthony J.Windebank Huan Wang Department of Neurologic Surgery Mayo ClinicRochesterMNUSA Biomedical Statistics and Informatics Mayo ClinicRochesterMNUSA Proteomics Core Mayo ClinicRochesterMNUSA Department of Neurology Mayo ClinicRochesterMNUSA

Chronic denervation is one of the key factors that affect nerve *** axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for *** of these factors/proteins have been individually *** better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair *** rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week *** the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting ***-five micrograms of protein from each sample were fractionated in SDS-PAGE ***-MS/MS analysis was applied to the *** expression levels of nerves on the surgery side were compared to those on the contralateral *** protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially *** the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve *** Pathway Analysis(IPA)software was used for pathway *** results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were *** experimental group also had more beneficial proteins that were d

关键词： chronic axotomy chronic denervation delayed repair distal nerve functional recovery nerve regeneration peripheral nerve prolonged denervation proteome sciatic nerve sciatic nerve transection

Power regulation of kinematic control inputs for forward flying Drosophila

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Acta Mechanica Sinica 2014年第6期30卷 809-818页

作者： kenneth MacFarlane Imraan Faruque J.Sean Humbert 3181 Glenn L Martin Hall University of MarylandCollege Park MD 20742 USA

The choices of insect wing kinematic programs is not well understood,particularly the mechanism by which an insect selects a distortion to achieve flight control.A methodology to evaluate prospective kinematic control inputs is presented based on the reachable states when control actuation was constrained to a unit of *** method implements a computationally-derived reduced order model of the insect’s flight dynamics combined with calculation of power *** kinematic inputs are evaluated based on this criterion for a Drosophila size insect in forward *** bias is shown to be the dominant control input using this power normalized evaluation measure.

关键词： Flight control Control Drosophila Power

The emerging roles of microRNAs in the molecular responses of metabolic rate depression

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分子细胞生物学报:英文版 2011年第3期3卷 167-175页

作者： Kyle K.Biggar kenneth B.Storey Institute of Biochemistry and Department of Biology Carleton University1125 Colonel By DriveOttawaONCanada K1S 5B6

Metabolic rate depression is an important survival strategy for many animal species and a common element of hibernation,torpor,estivation,anoxia and *** of the molecular mechanisms that regulate reversible transitions to and from hypometabolic states have identified principles of regulatory *** control mechanisms are conserved among biologically diverse organisms and include the coordinated reduction of specific groups of key regulatory enzymes or proteins in the cell,a process likely driven by microRNA target repression/*** present review focuses on a growing area of research in hypometabolism and mechanisms involving the rapid and reversible control of translation facilitated by *** analysis draws primarily from current research on three animal models:hibernating mammals,anoxic turtles and freeze-tolerant frogs(with selected examples from multiple other sources).Here,we demonstrate a link between metabolic rate depression,a well-documented response to periods of environmental stress,and microRNA ***-based expression profiles and PCR-driven studies have revealed that specific microRNAs are induced in response to environmental *** members of this group decrease pro-apoptotic signaling,reduce muscle wasting and reduce protein translation,whereas other members contribute to cell cycle arrest and mitogen-activated protein kinase *** of the same microRNAs are frequently deregulated in numerous disease pathologies and,hence,the hypometabolism model could provide a novel approach for the treatment of stroke and heart attack in humans.

关键词： microRNA metabolism metabolic rate depression protein translation muscle atrophy cell cycle apoptosis

Chronotropic incompetence is more frequent in obese adolescents and relates to systemic inflammation and exercise intolerance

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Journal of Sport and Health Science 2023年第2期12卷 194-201页

作者： Wouter M.A.Franssen Charly Keytsman Nastasia Marinus kenneth Verboven Bert O.Eijnde Lisa van Ryckeghem Paul Dendale Renate Zeevaert Guy Massa Dominique Hansen Rehabilitation Research Centre(REVAL) Faculty of Rehabilitation SciencesHasselt UniversityHasselt 3500Belgium Biomedical Research Institute(BIOMED) Faculty of Medicine and Life SciencesHasselt UniversityHasselt 3500Belgium ADLON Sports Medical Center Hasselt 3500Belgium Heart Centre Hasselt Jessa HospitalHasselt 3500Belgium Department of Pediatric Endocrinology and Diabetology Jessa HospitalHasselt 3500Belgium

Background:Adults with obesity may display disturbed cardiac chronotropic responses during cardiopulmonary exercise testing,which relates to poor cardiometabolic health and an increased risk for adverse cardiovascular *** is unknown whether cardiac chronotropic incompetence(CI)during maximal exercise is already present in obese adolescents and,if so,how that relates to cardiometabolic ***:Sixty-nine obese adolescents(body mass index standard deviation score=2.23±0.32,age=14.1±1.2 years;mean±SD)and 29lean adolescents(body mass index standard deviation score=-0.16±0.84,age=14.0±1.5 years)performed a maximal cardiopulmonary exercise testing from which indicators for peak performance were *** resting heart rate and peak heart rate were used to calculate the maximal chronotropic response ***(lipid profile,glycemic control,inflammation,and leptin)was studied in fasted blood samples and during an oral glucose tolerance test within obese *** analyses were applied to examine associations between the presence of CI and blood or exercise capacity parameters,respectively,within obese ***:CI was prevalent in 32 out of 69 obese adolescents(46%)and 3 out of 29 lean adolescents(10%).C-reactive protein was significantly higher in obese adolescents with CI compared to obese adolescents without CI(p=0.012).Furthermore,peak oxygen uptake and peak cycling power output were significantly reduced(p<0.05)in obese adolescents with CI *** adolescents without *** chronotropic index was independently related to blood total cholesterol(standardized coefficientβ=-0.332;p=0.012)and C-reactive protein concentration(standardized coefficientβ=-0.269;p=0.039).Conclusion:CI is more common in the current cohort of obese adolescents,and is related to systemic inflammation and exercise intolerance.

关键词： Adolescents Cardiometabolic health Exercise tolerance Heart rate Obesity

A20 promotes colorectal cancer immune evasion by upregulating STC1 expression to block “eat-me” signal

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4403-4415页

作者： Min Luo Xueping Wang Shaocong Wu Chuan Yang Qiao Su Lamei Huang Kai Fu Sainan An Fachao Xie kenneth Kin Wah To Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China Laboratory Animal Centre The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080P.R.China School of Pharmacy The Chinese University of Hong KongHong KongChina

Immune checkpoint inhibitors(ICIs)have induced durable clinical responses in a subset of patients with colorectal cancer(CRC).However,the dis-satisfactory response rate and the lack of appropriate biomarkers for selecting suitable patients to be treated with ICIs pose a major challenge to current ***-related molecule A20 is closely related to cancer immune response,but the effect of A20 on“eat-me”signal and immunotherapy efficacy remains *** found that A20 downregulation prominently improved the antitumor immune response and the efficacy of PD-1 inhibitor in CRC in vitro and in *** A20 expression was associated with less infiltration of immune cells including CD3(+),CD8(+)T cells and macrophages in CRC tissues and also poorer ***-and loss-A20 functional studies proved that A20 could decrease the“eat-me”signal calreticulin(CRT)protein on cell membrane translocation via upregulating stanniocalcin 1(STC1),binding to CRT and detaining in ***,A20 inhibited GSK3βphosphorylating STC1 at Thr86 to slow down the degradation of STC1 *** findings reveal a new crosstalk between inflammatory molecule A20 and“eat-me”signal in CRC,which may represent a novel predictive biomarker for selecting CRC patients most likely to benefit from ICI therapy.

关键词： STC1 GSK3β A20

Tsc2 mutation induces renal tubular cell nonautonomous disease

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Genes & Diseases 2022年第1期9卷 187-200页

作者： Prashant Kumar Fahad Zadjali Ying Yao Daniel Johnson Brian Siroky Aristotelis Astrinidis Peter Vogel kenneth W.Gross John J.Bissler Department of Pediatrics University of Tennessee Health Science Center and Le Bonheur Children's HospitalMemphisTN 38103USA Children's Foundation Research Institute(CFRI) Le Bonheur Children's HospitalMemphisTN 38105USA Department of Clinical Biochemistry College of Medicine&Health SciencesSultan Qaboos UniversityMuscat 123Oman Molecular Bioinformatics Center University of Tennessee Health Science CenterMemphisTN 38163USA Department of Veterinary Pathology St.Jude Children's Research HospitalMemphisTN 38105USA Department of Molecular and Cellular Biology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Pediatric Medicine Department St.Jude Children's Research HospitalMemphisTN 38105USA

TSC renal cystic disease is poorly understood and has no approved *** a new principal cell-targeted murine model of Tsc cystic disease,the renal cystic epithelium is mostly composed of type A intercalated cells with an intact Tsc2 gene confirmed by sequencing,although these cells exhibit a Tsc-mutant disease *** used a newly derived targeted murine model in lineage tracing and extracellular vesicle(EV)characterization experiments and a cell culture model in EV characterization and cellular induction experiments to understand TSC *** lineage tracing experiments,we found principal cells undergo clonal expansion but contribute very few cells to the *** determined that cystic kidneys contain more interstitial EVs than noncystic kidneys,excrete fewer EVs in urine,and contain EVs in cyst ***,the loss of Tsc2 gene in EV-producing cells greatly changes the effect of EVs on renal tubular epithelium,such that the epithelium develops increased secretory and proliferative pathway *** demonstate that the mTORC1 pathway activity is independent form the EV production,and that the EV effects for a single cell line can vary *** cystogenesis involves significant contribution from genetically intact cells conscripted to the mutant phenotype by mutant cell derived EVs.

关键词： Cell nonautonomous trait Polycystic kidney disease Renalcystogenesis Tuberous sclerosis complex

The Gray Mouse Lemur: A Model for Studies of Primate Metabolic Rate Depression

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Genomics, Proteomics & Bioinformatics 2015年第2期13卷 77-80页

作者： kenneth B.Storey Institute of Biochemistry and Department of Biology Carleton University

The use of daily torpor and/or of multi-day torpor bouts during a hibernation season are energy-saving survival strategies that have been well-studied for many years,particularly for small mammals living in seasonally... 详细信息

关键词： Depression physiological suppression season environments Mouse perfusion intestine winter breeding

Diabetes mellitus as a risk factor for gastrointestinal cancer among American veterans

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World Journal of Gastroenterology 2009年第42期15卷 5274-5278页

作者： M Mazen Jamal Eugene J Yoon kenneth J Vega Mehrtash Hashemzadeh kenneth J Chang Division of Gastroenterology Veterans Affairs(VA) Medical CenterLong BeachCA 90822United States Division of Gastroenterology Department of Internal MedicineCollege of MedicineUniversity of CaliforniaIrvine Medical CenterOrangeCA 92868United States Division of Gastroenterology University of Florida/JacksonvilleJacksonvilleFL 32207United States

AIM:To assess the risk of biliary and pancreatic cancers in a large cohort of patients with type 2 diabetes mellitus(DM) .METHODS:Eligibility for this study included patients with type 2 DM(ICD-9 code 250.0) who were discharged from Department of Veteran Affairs hospitals between 1990 and ***-matched control patients without DM were selected from the same patient treatment files during the same *** information included age,sex and *** diagnoses included known risk factors based on their ICD-9 *** multivariate logistic regression,the occurrence of biliary and pancreatic cancer was compared between case subjects with DM and controls without ***:A total of 1172496 case and control subjects were *** mean age for study and control subjects was 65.8 ± 11.3 and 64.8 ± 12.6 years,*** frequency of pancreatic cancer in subjects with DM was increased(0.9%) in comparison to control subjects(0.3%) with an OR of 3.22(95% CI:3.03-3.42) .The incidence of gallbladder andextrahepatic biliary cancers was increased by twofold in diabetic patients when compared to *** OR and 95% CI were 2.20(1.56-3.00) and 2.10(1.61-2.53) ,***:Our study demonstrated that patients with DM have a threefold increased risk for developing pancreatic cancer and a twofold risk for developing biliary cancer.

关键词： 2型糖尿病退伍军人危险因素恶性肿瘤 logistic回归消化道风险因素美国

Bone morphogenetic protein 2 improves patellar tendon healing by promoting migration and proliferation of tenocytes

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Chinese Science Bulletin 2011年第13期56卷 1361-1369页

作者： TANG MeiKuen LEE kenneth K Key Laboratory for Regenerative Medicine of Ministry of Education Jinan University Joint Laboratory for Regenerative Medicine the Chinese University of Hong Kong-Jinan University School of Biomedical Sciences the Chinese University of Hong Kong International Base of Collaboration for Science and Technology (JNU) the Ministry of Science and Technology & Guangdong Province School of Biomedical Sciences the Chinese University of Hong Kong

The repair of injured tendons remains a great challenge because of the poor intrinsic healing capacity of tendons. In this study, we examined the spatiotemporal expression pattern of the bone morphogenetic protein 2 (bmp-2) gene in normal and experimentally injured rat patellar tendons. We also investigated the ability of exogenously applied BMP-2 to promote patellar tendon healing. In situ hybridization with bmp-2 and alk-6 (bmp-2 receptor) antisense riboprobes revealed that both genes were normally expressed at low levels in intact rat tendons. However, bmp-2 expression was significantly upregulated in tenocytes found in the wound site at 7 d and later following tendon injury. In addition, it was found that bmp-2 was expressed in cultured patellar tenocytes. Appli- cation of exogenous BMP-2 to the tendon wound site significantly enhanced tendon repair. Moreover, in vitro and in vivo studies further demonstrated that BMP-2 enhanced tenocyte proliferation and migration to the wound site. The detectable amount of BMP-2 in normal tendons suggests that a basal level of bmp-2 expression was likely present to maintain the normal functions of the patellar tendon. Injury to the tendon induced increased bmp-2 expression intrinsically, but the expression level was insufficient for proper tendon repair. Our findings indicate that it is possible to significantly improve tendon healing by applying exogenous BMP-2 to the wound site, inferring that this protein could be developed as a potential therapeutic reagent for the treatment of damaged tendons.

关键词：骨形态发生蛋白肌腱细胞愈合能力迁移扩散 BMP 表达模式原位杂交