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Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Bone Research 2024年第1期12卷 180-198页

作者： Morten S.Hansen Kaja Madsen Maria Price Kent Søe Yasunori Omata Mario M.Zaiss Caroline M.Gorvin Morten Frost Alexander Rauch Molecular Endocrinology Laboratory(KMEB) Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of Clinical Research Faculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark Clinical Cell Biology Pathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of Metabolism and Systems Research(IMSR)and Centre for diabetes Endocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK Centre for Membrane Proteins and Receptors(COMPARE) Universities of Birmingham and NottinghamBirmingham B152TTUK Department of Molecular Medicine University of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic Surgery Faculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal Medicine 3 Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany steno diabetes center Odense Odense University HospitalDK-5000 Odense CDenmark

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from CD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density *** analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature *** conclus

关键词： osteoclast programming identif

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Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

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World Journal of Clinical Pediatrics 2024年第1期13卷 150-154页

作者： Annemarie Cecilie Grauslund Emilie Bundgaard Lindkvist Steffen Ullitz Thorsen Søren Ballegaard Jens Faber Jannet Svensson Anna Korsgaard Berg Department of Pediatrics Herlev and Gentofte HospitalHerlev 2730Denmark Copenhagen University Hospital Steno Diabetes Center CopenhagenHerlev 2730Denmark Department of Clinical Immunology RigshospitaletUniversity of CopenhagenCopenhagen 2100Denmark Department of Endocrinology Herlev and Gentofte HospitalHerlev 2730Denmark Department of Clinical Medicine Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2200Denmark

Type 1 diabetes(T1D)is associated with general-and diabetes-specific stress which has multiple adverse *** measuring stress is of great *** algometer measuring pressure pain sensitivity(PPS)has been shown to correlate to certain stress measures in ***,it has never been investigated in children and *** aim of our study was to examine associations between PPS and glycated hemoglobin(HbA1c),salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with ***-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study *** cortisol,PPS and questionnaires were collected,measured,and answered on ***1c was collected from medical *** found correlations between PPS and HbA1c(rho=0.35,P=0.046),cortisol(rho=-0.25,P=0.02)and Perceived Stress Scale(rho=-0.44,P=0.02)in different subgroups based on *** scored higher in PPS than females(P<0.001).We found PPS to be correlated to HbA1c but otherwise inconsistent in *** PPS values indicated either measurement difficulties or hypersensibility towards pain.

关键词： Stress Children and adolescents Type 1 diabetes Autonomic dysfunction

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Quantities of comorbidities affects physical, but not mental health related quality of life in type 1 diabetes with confirmed polyneuropathy

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World Journal of diabetes 2019年第2期10卷 87-95页

作者： Anne-Marie L Wegeberg Theresa Meldgaard Sofie Hyldahl Poul Erik Jakobsen Asbjφrn M Drewes Birgitte Brock Christina Brock Mech-Sense Department of Gastroenterology and HepatologyAalborg University Hospital and Clinical InstituteAalborg UniversityAalborg 9000Denmark steno diabetes center north Judland Region NordjyllandAalborg 9000Denmark steno diabetes center Copenhagen Region HovedstadenGentofte 2820Denmark

BACKGROUND A large number of adults with long-term type 1 diabetes are affected by symmetrical peripheral *** complications increase socioeconomic expenses and diminish the individual quality of *** 36-Item Short Form Health Survey(SF-36)is a generic patient reported questionnaire,measuring mental and physical health related quality of *** hypothesized that diabetic neuropathy would decrease physical and mental quality of life measured with SF-36,and that clinical appearance may be associated with the *** To investigate if diabetic neuropathy would decrease physical and mental quality of life measured with SF-36,and if clinical appearance may be associated with the *** Forty-eight adults[age 50±9 years,10 females,disease duration 32(14-51)years]with verified diabetic symmetrical peripheral neuropathy and 21 healthy participants(age 51±6 years,6 females)underwent standardised nerve conduction testing and completed the SF-36 ***,disease duration,number of comorbidities,both diabetes related and nondiabetes related,vibration perception threshold,number of hypoglycaemic events,HbA1c and administration way of insulin was *** In comparison to healthy subjects,patients’mental composite score was not significantly diminished(51.9±8.9 vs 53.1±5.5,P=0.558),while the physical composite score was(46.3±11.7 vs 54.6±3.3,P=0.002).As expected,the overall physical health related symptoms in patients were associated to total number of comorbidities(Pdiabetes(P=0.0002)and HbA1c(P=0.005)as well as comorbidities not related to diabetes(P=0.0006).CONCLUSION The finding of this study emphasises the importance of focusing on quality of life in adults with diabetes and especially in those with multiple comorbidities as well as the possibility of HbA1c as a biomarker for severe complication.

关键词： Quality of life 36-Item Short Form Health Survey(SF-36) diabetes mellitus,Type 1 Diabetic neuropathies Comorbidity

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The vascular endothelial growth factor system-a new player in the pathogenesis and development of metabolic dysfunction-associated steatotic liver disease

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Hepatobiliary Surgery and Nutrition 2023年第6期12卷 963-965页

作者： Henning Grønbæk Anders Mellemkjær Søren Nielsen Faidon Magkos Department of Hepatology&Gastroenterology Aarhus University HospitalAarhusDenmark Clinical Institute Aarhus UniversityAarhusDenmark steno diabetes center Aarhus Aarhus University HospitalAarhusDenmark Department of Nutrition Exercise and SportsUniversity of CopenhagenFrederiksbergDenmark

The pathogenesis of liver disease from simple steatosis-metabolic dysfunction-associated steatotic liver disease(MASLD)-and the transition to inflammation and fibrosis-metabolic dysfunction-associated steatohepatitis(... 详细信息

关键词： Vascular endothelial growth factor B(VEGF-B) metabolic dysfunction-associated steatotic liver disease(MASLD) non-alcoholic fatty liver disease(NAFLD)

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The effect of sustained, long-term changes in alcohol intake on cardiovascular risk

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Open Journal of Preventive Medicine 2012年第4期2卷 444-451页

作者： Ulla Toft Charlotta Pisinger Mette Aadahl Allan Linneberg Cathrine Lau Torben Jorgensen Research Centre for Prevention and Health GlostrupDenmark steno diabetes center GentofteDenmark

Objective: To investigate whether sustained long-term changes in alcohol intake are predictive of cardiovascular risk. Methods: The study population was a subpopulation of the five-year intervention study, Inter99 study, (1999-2006), Copenhagen, denmark (n = 2117;30 - 60 years). Alcohol intake was assessed by questionnaires at baseline, one-, three- and five-year follow-up. The associations between sustained long-term changes in alcohol intake and cardiovascular risk factors (HDL and non-HDL cholesterol, systolic and diastolic blood pressure (BP);the absolute risk of ischemic heart disease (CRS)) at five-year follow-up were explored by linear regression models. The alcohol variables were tested for linear association with the response variable. Results: Sustained increased alcohol intake was significantly associated with increased CRS (β = 0.0028;P = 0.006) and a decreased HDL cholesterol (β = -0.0028;P = 0.005). Among participants with a moderate overall alcohol in-take at baseline increased alcohol intake was significantly associated with an increased plasma triglyceride (β = 0.0069;P = 0.04). No association with triglyceride was found for participants with a high alcohol intake. Change in wine intake was significantly negatively associated with changes in diastolic BP (β = 0.0015;P = 0.02). Conclusions: Sustained increase in the long-term intake of alcohol was a significant risk factor for an increased CRS, increased triglyceride level and decreased HDL cholesterol. Increased wine intake was associated with decreased diastolic BP.

关键词： Alcohol Consumption Cardiovascular Disease Intervention Studies

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糖尿病患者足溃疡减压指南(2023年更新版)——《国际糖尿病足工作组:糖尿病相关的足病预防与管理指南(2023)》的一部分

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感染、炎症、修复 2024年第1期25卷 1-22页

作者： Sicco A.Bus David G.Armstrong Ryan T.Crews Catherine Gooday Gustav Jarl Klaus Kirketerp-Moller Vijay Viswanathan Peter A.Lazzarini on behalf of the International Working Group on the Diabetic Foot 陈燕刘斌张晓诗邓武权(译) 王爱萍许樟荣(审校) Amsterdam UMC University of AmsterdamDepartment of Rehabilitation MedicineAmsterdamthe Netherlands Amsterdam Movement Sciences program Rehabilitation&DevelopmentAmsterdamthe Netherlands Southwestern Academic Limb Salvage Alliance(SALSA) Department of SurgeryKeck School of Medicine of University of Southern California(USC)Los AngelesCaliforniaUSA Dr.William M.Scholl College of Podiatric Medicine's center for Lower Extremity Ambulatory Research(CLEAR)at Rosalind Franklin University North ChicagoIllinoisUSA Elsie Bertram diabetes Centre Norfolk and Norwich University HospitalsNorwichUK Department of Prosthetics and Orthotics Faculty of Medicine and HealthÖrebro UniversityÖrebroSweden University Health Care Research center Faculty of Medicine and HealthÖrebro UniversityÖrebroSweden Copenhagen Wound Healing center Bispebjerg University HospitalCopenhagenDenmark steno diabetes center CopenhagenDenmark MV Hospital for diabetes ChennaiIndia School of Public Health and Social Work Queensland University of TechnologyBrisbaneAustralia Allied Health Research Collaborative The Prince Charles HospitalBrisbaneAustralia 不详重庆大学附属中心医院重庆400014 东部战区空军医院糖尿病足中心江苏南京210002 战略支援部队特色医学中心北京100101

减轻组织的机械性压力在治愈糖尿病相关的足溃疡所需的多种干预措施中最为重要。本文是2023年国际糖尿病足工作组(IWGDF)发布的减压治疗促进糖尿病相关的足溃疡愈合的循证指南,也是对2019年IWGDF指南的更新。我们遵循推荐、评估、发展... 详细信息

减轻组织的机械性压力在治愈糖尿病相关的足溃疡所需的多种干预措施中最为重要。本文是2023年国际糖尿病足工作组(IWGDF)发布的减压治疗促进糖尿病相关的足溃疡愈合的循证指南,也是对2019年IWGDF指南的更新。我们遵循推荐、评估、发展和评价分级(GRADE)方法学,以患者-干预-比较-结局(patient-intervention-control-outcome,PICO)模式设计临床问题和重要结果,进行系统评价和Meta分析,制定评判表汇总,为每个问题编写推荐和理由。每项推荐都是基于系统综述中发现的证据,在无证据情况下则采用专家意见,以及对判断项目的GRADE等级总结进行仔细权衡,包括可预期和不可预期的影响、证据的确定性、患者价值、所需资源、成本效益、公平性、可行性和可接受性。为了治愈糖尿病患者神经性前足底或中足底溃疡,要使用不可拆卸的齐膝高减压装置作为首选减压干预措施。如果患者存在对不可拆卸减压装置的禁忌证或不能耐受,考虑使用可拆卸齐膝(或踝)高减压装置作为减压干预措施的第二选择。如果无可用的减压装置,考虑使用合适的鞋具结合毡制泡沫作为减压干预措施的第三选择。如果这种非手术减压治疗不能治愈前足底溃疡,可以考虑跟腱延长术、跖骨头切除术、关节置换术或跖骨截骨术。为了治疗继发于屈趾畸形的神经性足底或小趾远端溃疡,可行趾屈肌腱切开术。为了促进后足、非足底或并发感染或缺血的溃疡的愈合,提出了进一步的推荐。所有推荐都已在减压临床路径中进行了总结,以帮助促进本指南在临床实践中的实施。这些减压推荐将帮助医务人员为糖尿病相关的足溃疡患者提供最佳的治疗和预后,降低患者感染、住院和截肢的风险。

关键词：糖尿病足溃疡减压减压装置指南国际糖尿病足工作组

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Bone Loss in Women with Type 1 diabetes

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Journal of diabetes Mellitus 2015年第4期5卷 252-257页

作者： Maj-Britt Tanderup Jorgensen Jesper Olund Christensen Ole Lander Svendsen Department of Endocrinology I Bispebjerg University HospitalCopenhagenDenmark steno diabetes center GentofteDenmark center for Clinical and Basic Research BallerupDenmark

Background: Although osteoporosis has been investigated and debated in the diabetic population over the past decades, very little is known about the spontaneous changes in bone mineral density (BMD) and biochemical markers of bone turnover in pre- and postmenopausal type 1 diabetic (T1DM) women over time. Aim: To measure spontaneous changes in BMD and biochemical markers of bone turnover in pre- and postmenopausal T1DM women. Subjects: 53 T1DM women (31 premenopausal and 22 postmenopausal) from the outpatient clinic were enrolled in the study in 1993 and 35 (22 premenopausal, 13 postmenopausal) were reexamined in 1997. Method: BMD was measured at femoral neck (f.n.), spine (L2 - L4), total body and forearm with DXA or SXA in 53 T1DM women. 4 years later a re-scan was carried out on 35 T1DM. Results: In premenopausal subjects a yearly decrease less than 1% at f.n., spine, forearm and total body was observed, though only statistically significant (s.s.) at f.n., p ≤ 0.05. In postmenopausal subjects a s.s. decrease less than 2% was observed at f.n., forearm and total body, p ≤ 0.05. In general, osteopenic or osteoporotic values were observed at the measured skeletal sites. Only at f.n. a lower s.s. BMD compared to age-matched reference women was seen. Conclusion: Small or non-significant changes in BMD and biochemical markers of bone turnover were observed in pre- and postmenopausal T1DM subjects after a 4-year period.

关键词： Bone Turnover Bone Mineral Density Biochemical Markers of Bone Turnover Premenopausal Postmenopausal

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Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer's disease

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Translational Neurodegeneration 2020年第3期9卷 458-472页

作者： Jin Xu Giulia Bankov Min Kim Asger Wretlind Jodie Lord Rebecca Green Angela Hodges Abdul Hye Dag Aarsland Latha Velayudhan Richard J.B.Dobson Petroula Proitsi Cristina Legido-Quigley on behalf of the AddNeuroMed Consortium Institute of Pharmaceutical Science King's College LondonLondonUK. Institute of Psychiatry Psychology&NeuroscienceKing's College LondonLondonUK. steno diabetes center Copenhagen GentofteDenmark center for Age Related Medicine Stavanger University HospitalStavangerNorway 不详

Background:There is an urgent need to understand the pathways and processes underlying Alzheimer's disease(AD)for early diagnosis and development of effective *** study was aimed to investigate Alzheimer's dementia using an unsupervised lipid,protein and gene multi-omics integrative ***:A lipidomics dataset comprising 185 AD patients,40 mild cognitive impairment(MCI)individuals and 185 controls,and two proteomics datasets(295 AD,159 MCI and 197 controls)were used for weighted gene CO-expression network analyses(WGCNA).Correlations of modules created within each modality with clinical AD diagnosis,brain atrophy measures and disease progression,as well as their correlations with each other,were *** ontology enrichment analysis was employed to examine the biological processes and molecular and cellular functions of protein modules associated with AD *** species were annotated in the lipid modules associated with AD *** associations between established AD risk loci and the lipid/protein modules that showed high correlation with AD phenotypes were also ***:Five of the 20 identified lipid modules and five of the 17 identified protein modules were correlated with clinical AD diagnosis,brain atrophy measures and disease *** lipid modules comprising phospholipids,triglycerides,sphingolipids and cholesterol esters were correlated with AD risk loci involved in immune response and lipid *** five protein modules involved in positive regulation of cytokine production,neutrophil-mediated immunity,and humoral immune responses were correlated with AD risk loci involved in immune and complement systems and in lipid metabolism(the APOE ε4 genotype).Conclusions:Modules of tightly regulated lipids and proteins,drivers in lipid homeostasis and innate immunity,are strongly associated with AD phenotypes.

关键词： Alzheimer's disease Dementia Brain atrophy sMRI Rate of cognitive decline Lipidomics Proteomics AD risk loci WGCNA

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Caffeine Increases VerticalJumping Height in Young Trained Males Before But Not After a Maximal Effort Strength Training Session

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Journal of Science in Sport and Exercise 2020年第2期2卷 145-153页

作者： Daniel S.Tangen Stian R.Nielsen Kristoffer J.Kolnes Jφrgen Jensen Department of Physical Performance Norwegian School of Sport SciencesSognsveien 220UllevaI StadionPO Box 40140806 OsloNorway steno diabetes center Odense Odense University Hospital5000 Odense CDenmark

The aim of the present study was to investigate the effect of caffeine on vertical jumping height in rested condition and after a heavy strength training *** well-trained young males with experience in jump and strength training were included in this double-blinded,randomised study with cross-over ***(3 mg/kg body weight)or placebo were ingested 45 min prior to the jump *** was performed on a force platform and vertical jumping height was *** a standardized warm up,participants performed jumping series consisting of three maximal jumps with 30 s rest between jumps followed by five maximal jumps with 7 s rest between *** participants performed a heavy strength training of the leg muscles(leg press:3×15 reps)and the jumping series was repeated immediately after(30 s),and after 5 min and 15 min *** increased the maximal vertical counter movement jump height(P≤0.05)and mean value of the 5-jump sequence prior to the strength *** increased jump height by 2.2 cm±0.5 cm at the first *** lactate after the strength training increased to 6.97±1.20 and 7.77±0.54 mmol/L in PLA and CAF,respectively(P=0.19).The jump height was reduced by 8 cm after the strength *** were no differences in jump height after ingestion of caffeine or placebo immediately after the strength training session or in the recovery period,but blood lactate in the recovery period was higher in CAF compared to PLA(ANOVA;P<0.05).Conclusion:Caffeine increased the vertical jump height in the resting ***,after a maximal effort strength training session the positive effect of caffeine was no longer significant.

关键词： Lactate Fatigue Recovery Force-velocity Athletes

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Hyperbaric Oxygen Treatment for Diabetic Retinopathy and Neuropathy in a Streptozotocin Induced Diabetic Rat Model

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Journal of Biomedical Science and Engineering 2021年第12期14卷 391-401页

作者： Jesper G. Madsen Martin N. Skov Kasper Hansen Christoffer Laustsen Niels Ejskjær Henning Andersen Michael Pedersen Department of Clinical Medicine Comparative Medicine Lab Aarhus University Aarhus Denmark Zoophysiology Department of Biology Aarhus University Aarhus C Denmark Department of Forensic Medicine Aarhus University Aarhus N Denmark Department of Clinical Medicine The MR Research Centre Aarhus University Aarhus Denmark Department of Clinical Medicine Aalborg University Aalborg Denmark steno diabetes center north denmark Aalborg University Hospital Aalborg Denmark Department of Neurology Aarhus University Hospital Aarhus Denmark

Aim: diabetes Mellitus is a global public health challenge with major and potentially devastating complications, and concomitant complications include retinopathy and neuropathy due to hypoxia and microvascular dysfunction. In this study, we investigated the effect of hyperbaric oxygen therapy as a method to transiently improve tissue oxygenation on diabetic retinopathy and neuropathy in a streptozotocin induced type-1 diabetic rat model (Wistar). Methods: Streptozotocin induced type-1 diabetic rats received 10 sessions of 2-h hyperbaric oxygen exposures (pO2 = 309 kPa) over 2 weeks. Animals were exposed to light stimuli to produce light evoked potentials to estimate the effect of oxygen treatment on diabetic retinopathy. Sciatic nerves were exposed and stimulated to produce muscle evoked potential, which were recorded in the muscles of the foot and subsequently used to evaluate the effect of oxygen treatment on diabetic neuropathy. Results: We found significantly shorter light evoked potential latency and increased amplitude in hyperbaric oxygen treated animals. No change was found in nerve conduction. Conclusions: This study showed that hyperbaric oxygen therapy is a potentially effective treatment for diabetic retinopathy, improving both latency and amplitude of light evoked potentials.

关键词： Diabetic Neuropathy Diabetic Retinopathy Hyperbaric Oxygen Therapy

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