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Regulation of neuronal bioenergetics as a therapeutic strategy in neurodegenerative diseases 认领
1
作者 Isaac G.Onyango James P.Bennett Gorazd B.Stokin 《中国神经再生研究:英文版》 SCIE CAS 2021年第8期1467-1482,共16页
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a heterogeneous group of debilitating disorders with multifactorial ... Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a heterogeneous group of debilitating disorders with multifactorial etiologies and pathogeneses that manifest distinct molecular mechanisms and clinical manifestations with abnormal protein dynamics and impaired bioenergetics. Mitochondrial dysfunction is emerging as an important feature in the etiopathogenesis of these age-related neurodegenerative diseases. The prevalence and incidence of these diseases is on the rise with the increasing global population and average lifespan. Although many therapeutic approaches have been tested, there are currently no effective treatment routes for the prevention or cure of these diseases. We present the current status of our knowledge and understanding of the involvement of mitochondrial dysfunction in these diseases and highlight recent advances in novel therapeutic strategies targeting neuronal bioenergetics as potential approach for treating these diseases. 展开更多
关键词 AGING Alzheimer's disease amyotrophic lateral sclerosis Huntington's disease mitochondrial biogenesis mitochondrial dysfunction mtDNA mutations NEURODEGENERATION oxidative stress Parkinson's disease
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Real-world disease activity and sociodemographic,clinical and treatment characteristics of moderate-to-severe inflammatory bowel disease in Brazil 认领
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作者 Cyrla Zaltman Rogério Serafim Parra +26 位作者 Ligia Yukie Sassaki Genoile Oliveira Santana Maria de Lourdes AbreuFerrari Sender J Miszputen Heda M B S Amarante Roberto Luiz Kaiser Junior Cristina Flores Wilson R Catapani JoséMiguel Luz Parente Mauro Bafutto Odery Ramos Carolina D Gonçalves Isabella MirandaGuimaraes Jose J R da Rocha Marley R Feitosa Omar Feres Rogerio Saad-Hossne Francisco Guilherme Cancela Penna Pedro Ferrari Sales Cunha Tarcia NF Gomes Rodrigo Bremer Nones Mikaell AlexandreGouvea Faria Mírian Perpétua Palha Dias Parente António S Scotton Rosana Fusaro Caratin Juliana Senra Júlio Maria Chebli 《世界胃肠病学杂志:英文版》 SCIE CAS 2021年第2期208-223,共16页
BACKGROUND Understanding the treatment landscape of inflammatory bowel diseases(IBD)is essential for improving disease management and patient outcomes.Brazil is the largest Latin American country,and it presents socio... BACKGROUND Understanding the treatment landscape of inflammatory bowel diseases(IBD)is essential for improving disease management and patient outcomes.Brazil is the largest Latin American country,and it presents socioeconomic and health care differences across its geographical regions.This country has the highest increase in IBD incidence and prevalence in Latin America,but information about the clinical and treatment characteristics of IBD is scarce.AIM To describe the sociodemographic,clinical,and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast,South and Northeast/Midwest regions.METHODS Multicenter,cross-sectional study with a 3-year retrospective chart review component.Patients with moderate-to-severe Crohn’s disease(CD)or ulcerative colitis(UC)were consecutively enrolled between October 2016 and February 2017.Active CD at enrollment was defined as a Harvey Bradshaw Index≥8 or a CD Activity Index≥220 or a calprotectin level>200μg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year;active UC was defined as a partial Mayo score≥5.Descriptive statistics were used to analyze all variables.RESULTS In a total of 407 included patients,CD was more frequent than UC,both overall(264 CD/143 UC patients)and by region(CD:UC ratios of 2.1 in the Southeast,1.6 in the South and 1.2 in the Northeast/Midwest).The majority of patients were female(54.2%of CD;56.6%of UC),and the mean ages were 45.9±13.8 years(CD)and 42.9±13.0 years(UC).The median disease duration was 10.0(range:0.5-45)years for both IBD types.At enrollment,44.7%[95%confidence interval(CI):38.7-50.7]of CD patients and 25.2%(95%CI:18.1-32.3)of UC patients presented with active disease.More than 95%of IBD patients were receiving treatment at enrollment;CD patients were commonly treated with biologics(71.6%)and immunosuppressors(67.4%),and UC patients were commonly treated with mesalazine[5-Aminosalicylic acid(5-ASA)]derivates(69.9%)and immunosuppressors(44.1%).More than 5 展开更多
关键词 Inflammatory bowel disease Crohn's disease Ulcerative colitis Disease activity EPIDEMIOLOGY Treatment
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文章速递Proteolysis targeting chimera technology:a novel strategy for treating diseases of the central nervous system 认领
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作者 Ke Ma Xiao-Xiao Han +1 位作者 Xiao-Ming Yang Song-Lin Zhou 《中国神经再生研究:英文版》 SCIE CAS CSCD 2021年第10期1944-1949,共6页
Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting ... Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting chimera(PROTAC)technology is a novel strategy to solve this problem.PROTAC technology uses the ubiquitin-protease system to eliminate mutated,denatured,and harmful proteins in cells.It can be reused,and utilizes the protein destruction mechanism of the cells,thus making up for the deficiencies of traditional protein degradation methods.It can effectively target and degrade proteins,including proteins that are difficult to identify and bind.Therefore,it has extremely important implications for drug development and the treatment of neurological diseases.At present,the targeted degradation of mutant BTK,mHTT,Tau,EGFR,and other proteins using PROTAC technology is gaining attention.It is expected that corresponding treatment of nervous system diseases can be achieved.This review first focuses on the recent developments in PROTAC technology in terms of protein degradation,drug production,and treatment of central nervous system diseases,and then discusses its limitations.This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases. 展开更多
关键词 Alzheimer’s disease disease treatment drug development Huntington’s disease proteolysis targeting chimera stroke targeted degradation
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文章速递Perianal fistulodesis–A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae 认领
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作者 Roxanne Villiger Daniela Cabalzar-Wondberg +8 位作者 Daniela Zeller Pascal Frei Luc Biedermann Christian Schneider Michael Scharl Gerhard Rogler Matthias Turina Andreas Rickenbacher Benjamin Misselwitz 《世界胃肠外科杂志:英文版(电子版)》 SCIE CAS 2021年第2期187-197,共11页
BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.AIM To challenge and novel minimally invasive treatment options are needed.METHODS Patients with Crohn’s disease(CD)in remission an... BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.AIM To challenge and novel minimally invasive treatment options are needed.METHODS Patients with Crohn’s disease(CD)in remission and patients without inflammatory bowel disease(non-IBD patients)were treated with fistulodesis,a method including curettage of fistula tract,flushing with acetylcysteine and doxycycline,Z-suture of the inner fistula opening,fibrin glue instillation,and Zsuture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks.Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included.The primary end point was fistula healing,defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.RESULTS Fistulodesis was performed in 17 non-IBD and 3 CD patients,with a total of 22 fistulae.After 24 wk,all fistulae were healed in 4 non-IBD and 2 CD patients(overall 30%)and fistula remained closed until the end of follow-up at 10-25 mo.In a secondary per-fistula analysis,7 out of 22 fistulae(32%)were closed.Perianal disease activity index(PDAI)improved in patients with fistula healing.Low PDAI was associated with favorable outcome(P=0.0013).No serious adverse events were observed.CONCLUSION Fistulodesis is feasible and safe for perianal fistula closure.Overall success rates is at 30%comparable to other similar techniques.A trend for better outcomes in patients with low PDAI needs to be confirmed. 展开更多
关键词 Fistula Fibrin glue Crohn's disease Perianal disease activity index Inflammatory bowel disease Fistula closure
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The neuroimaging of neurodegenerative and vascular disease in the secondary prevention of cognitive decline 认领
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作者 Morgan J.Schaeffer Leona Chan Philip A.Barber 《中国神经再生研究:英文版》 SCIE CAS 2021年第8期1490-1499,共10页
Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent ... Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent years. Thus, future trials must begin during the preclinical phases of the disease before symptom onset. Age related cognitive decline is often the result of two coexisting brain pathologies: Alzheimer's disease(amyloid, tau, and neurodegeneration) and vascular disease. This review article highlights some of the common neuroimaging techniques used to visualize the accumulation of neurodegenerative and vascular pathologies during the preclinical stages of dementia such as structural magnetic resonance imaging, positron emission tomography, and white matter hyperintensities. We also describe some emerging neuroimaging techniques such as arterial spin labeling, diffusion tensor imaging, and quantitative susceptibility mapping. Recent literature suggests that structural imaging may be the most sensitive and cost-effective marker to detect cognitive decline, while molecular positron emission tomography is primarily useful for detecting disease specific pathology later in the disease process. Currently, the presence of vascular disease on magnetic resonance imaging provides a potential target for optimizing vascular risk reduction strategies, and the presence of vascular disease may be useful when combined with molecular and metabolic markers of neurodegeneration for identifying the risk of cognitive impairment. 展开更多
关键词 AMYLOID arterial spin labeling cognitive decline DEMENTIA imaging magnetic resonance imaging positron emission tomography quantitative susceptibility mapping TAU vascular disease white matter hyperintensities
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Role of diet and nutrition in inflammatory bowel disease 认领
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作者 Marina Moreira de Castro Lívia Bitencourt Pascoal +5 位作者 Karine Mariane Steigleder Beatriz Piatezzi Siqueira Ligiana Pires Corona Maria de Lourdes Setsuko Ayrizono Marciane Milanski Raquel Franco Leal 《世界实验医学杂志》 2021年第1期1-16,共16页
Inflammatory bowel diseases(IBDs)are closely linked to nutrition.The latest research indicates that diet and nutrition are significantly involved in the etiopathogenesis of the disease,although their specific role thr... Inflammatory bowel diseases(IBDs)are closely linked to nutrition.The latest research indicates that diet and nutrition are significantly involved in the etiopathogenesis of the disease,although their specific role throughout its clinical course still remains unclear.This study reviewed how diet and nutrition are associated with IBD development and management.Even though specific diets have been shown to bring about positive outcomes,there is currently no scientific consensus regarding an appropriate diet that would benefit all IBD patients.We suggest that individualized dietary recommendations are of the greatest importance and that diets should be planned to provide individual IBD patients with specific nutrient requirements while keeping all the clinical aspects of the patients in mind.Further research is clearly necessary to investigate nutritional factors involved in IBD development and,especially,to evaluate the applications of the diets during the course of the disease. 展开更多
关键词 Crohn’s disease Ulcerative colitis Inflammatory bowel disease DIET NUTRITION
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Dyslipidemia and cardiovascular disease risk factors in patients with type 1 diabetes:A single-center experience 认领
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作者 Sari Krepel Volsky Shlomit Shalitin +7 位作者 Elena Fridman Michal Yackobovitch-Gavan Liora Lazar Rachel Bello Tal Oron Ariel Tenenbaum Liat de Vries Yael Lebenthal 《世界糖尿病杂志:英文版(电子版)》 SCIE CAS 2021年第1期56-68,共13页
BACKGROUND Type 1 diabetes(T1D)contributes to altered lipid profiles and increases the risk of cardiovascular disease(CVD).Youth with T1D may have additional CVD risk factors within the first decade of diagnosis.AIM T... BACKGROUND Type 1 diabetes(T1D)contributes to altered lipid profiles and increases the risk of cardiovascular disease(CVD).Youth with T1D may have additional CVD risk factors within the first decade of diagnosis.AIM To examine risk factors for dyslipidemia in young subjects with T1D.METHODS Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D(86 males;baseline mean age 12.2±5.6 years and hemoglobin A1c 8.4%±1.4%)were followed in a single tertiary diabetes center for a median duration of 15 years.Predictors for outcomes of lipid profiles at last visit(total cholesterol[TC],triglycerides[TGs],low-density lipoprotein-cholesterol[LDL-c],and highdensity lipoprotein-cholesterol[HDL-c])were analyzed by stepwise linear regression models.RESULTS At baseline,79.5%of the patients had at least one additional CVD risk factor(borderline dyslipidemia/dyslipidemia[37.5%],pre-hypertension/hypertension[27.6%],and overweight/obesity[16.5%])and 41.6%had multiple(≥2)CVD risk factors.A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1%of the cohort.Predictors of elevated TC:family history of CVD(β[SE]=23.1[8.3],P=0.006);of elevated LDL-c:baseline diastolic blood pressure(DBP)(β[SE]=11.4[4.7],P=0.003)and family history of CVD(β[SE]=20.7[6.8],P=0.017);of elevated TGs:baseline DBP(β[SE]=23.8[9.1],P=0.010)and family history of CVD(β[SE]=31.0[13.1],P=0.020);and of low HDL-c levels:baseline DBP(β[SE]=4.8[2.1],P=0.022]).CONCLUSION Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD.It is of utmost importance to prevent and control modifiable risk factors such as these,as early as childhood,given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia. 展开更多
关键词 Type 1 diabetes Children and adolescents Cardiovascular disease risk factors DYSLIPIDEMIA HYPERTENSION Family history of cardiovascular disease risk factors
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Amyloid beta peptides, tau protein acetylation and therapeutic strategies for treating Alzheimer’s disease: a review 认领
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作者 Sanjib Guha Rajalakshmi Subramaniyam 《TMR生命研究》 2021年第1期49-58,共10页
Alzheimer’s disease(AD)is the most common progressive neurodegenerative disorder.It is often lethal and currently lacks a satisfactory therapy.The disease has a specific neuro-pathological profile:accumulation of pro... Alzheimer’s disease(AD)is the most common progressive neurodegenerative disorder.It is often lethal and currently lacks a satisfactory therapy.The disease has a specific neuro-pathological profile:accumulation of proteinaceous deposits in the brain–amyloid plaques(containingβ-amyloid peptides)and neurofibrillary tangles which are accumulation of a profusion of long stringy tangles of proteins called tau.Between the two highly recognized AD hypotheses,amyloid beta(Aβ)peptide aggregation and accumulation play a significant role and are considered as an important mechanism of AD pathology.Aβis a proteolytic product of amyloid precursor protein and genetic studies supported the relevance of Aβin AD pathogenesis.A large number of small molecules were studied for their ability to inhibit Aβ-aggregation in oligomer form or after fibrillization.However,the protein-misfolding process has certain setbacks which are inevitable due to the different morphology of protein.In recent years,it has been demonstrated that tau also plays a central role in pathogenesis of this disease.Moreover,abnormal post-translational modifications of tau,in particular,increases in acetylation at specific sites likely contribute to the toxicity of tau.Although it is evident that tau with these aberrant post-translational modifications likely facilitates neurodegeneration,the precise cellular mechanisms by which tau compromises neuronal function remain unknown.In addition,much remains to be learned about new interventions that might be developed to prevent or reduce the negative impact of tau posttranslational modifications-related damage.This review article addresses the key roles of amyloid beta and tau protein in AD as well as the possible therapeutic agents that can reduce the toxic levels of both the proteins,and thus providing beneficial effect for the AD patients. 展开更多
关键词 Alzheimer’s disease Amyloid beta peptide Tau acetylation Therapeutic strategies Disease models
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Effects of Palivizumab Guideline Changes on RSV Admissions in Patients with Congenital Heart Disease and Prematurity 认领
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作者 John Pham Stephen Nageotte +1 位作者 Jon Detterich Grace Kung 《心血管病(英文)》 2021年第1期34-44,共11页
<strong>Background:</strong><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Respiratory syncytial virus (RSV) causes significant morbidit... <strong>Background:</strong><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Respiratory syncytial virus (RSV) causes significant morbidity and mortality in patients with a history of prematurity and congenital heart disease (CHD). In 2014, the guidelines for Palivizumab became more restrictive for this population. We hypothesized the percentage of RSV+ admissions would increase overall and in this target group (TG) specifically.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">We conducted a retrospective review of patients under age 2 years admitted with bronchiolitis two seasons prior to the change (Pre) and two seasons after (Post). Our TG included patients who were eligible prior to the 2014 changes but currently no longer eligible. We used chi-square analysis to answer the two main hypotheses: 1</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;"> Percent RSV+/total bronchiolitis Pre vs Post and 2</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;"> Percent of TG/RSV+ Pre vs Post.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> 1283 patients (546 pre, 737 post) were admitted with the diagnosis of RSV between 2012-2016, 866 actually tested positive for RSV (367 Pre, 499 Post). There was no significant difference in the number of total patients admitted with RSV (Pre = 67.2%, Post = 67.7%) or in our TG (Pre 7.1% vs Post 8.2%). TG overall had a more complicated course: longer length of stay, median 5 days, IQR 2</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">12 vs 3 days, IQR 1</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span 展开更多
关键词 2014 American Academy of Pediatrics Children Congenital Heart Disease Guidelines Infants PALIVIZUMAB PREMATURITY Respiratory Syncytial Virus
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A Case Report about Persistent Left Superior Vena Cava: Is it Always Asymptomatic? 认领
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作者 Özge Çetinarslan Arda Payas Ibrahim Taskin Rakici 《心血管病(英文)》 2021年第1期52-57,共6页
<div style="text-align:justify;"> A persistent left superior vena cava (PLSVC) is a rare malformation which affects approximately 0.3<span>% </span><span>-</span><span> &l... <div style="text-align:justify;"> A persistent left superior vena cava (PLSVC) is a rare malformation which affects approximately 0.3<span>% </span><span>-</span><span> </span><span>0.5% of the population and it is presented along with a right-sided superior vena cava in 82.2% of the cases reported</span><span minion="" pro="" capt","serif";color:#943634;"="" style=""> </span><span minion="" pro="" capt","serif";color:#943634;background:yellow;"=""></span><span>[<a href="#ref1">1</a>]</span><span color:#943634;background:yellow;"=""></span><span minion="" pro="" capt","serif";color:#943634;background:yellow;"=""></span><span>.</span><span "=""><span> Clinicians diagnose it incidentally by difficulties with pacemaker implantation, central venous catheterization or screening for another etiologies when it is not accompanied by other anomalies it is typically asymptomatic. W. Schummer </span><i><span>et al.</span></i><span> described the embryogenesis and the anatomic variations of persistent LSVC according to the positioning of a central venous catheter on the chest radiograph: type I, normal;type II, only PLSVC;type IIIa, right and left superior vena cava with connection;type IIIb, right and left superior vena cava without connection</span></span><span> </span><span>[<a href="#ref2">2</a>]</span><span>. </span><span "=""><span>In 92% of individuals with PLSVC, the PLSVC drains into a dilated coronary sinus (CS) and rest 8% drain directly into the left atrium. PLSVC is caused by a failure in the closure of the left anterior cardinal vein during embryogenic development</span></span><span minion="" pro="" capt","serif";color:#943634;"=""><span> </span><span style="background:yellow;"></span></span><span color:#943634;"=""><span>[<a href="#ref3">3</a>]</span><span style="background:yellow;"></span></span><span minion="" pro="" capt","serif";color:#943634;background:yellow;"=""></span><span>. </span><span>The coronary sinus (CS) is a vein that transmits venous blood to the right atrium though atrioventricular groove 展开更多
关键词 Case Report Persistent Left Superior Vena Cava (PLSVC) Congenital Heart Disease COVID-19 Cardiac Imaging
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Experimental models of metabolic and alcoholic fatty liver disease 认领
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作者 Delfin Gerard Buyco Jasmin Martin +3 位作者 Sookyoung Jeon Royce Hooks Chelsea Lin Rotonya Carr 《世界胃肠病学杂志:英文版》 SCIE CAS 2021年第1期1-18,共18页
Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significa... Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease(ALD).Indeed,MetS also significantly contributes to liver injury in ALD patients.This“syndrome of metabolic and alcoholic steatohepatitis”(SMASH)is thus expected to be a more prevalent presentation in liver patients,as the obesity epidemic continues.Several pre-clinical experimental models that couple alcohol consumption with NAFLDinducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH.These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation,oxidative stress,and the induction of innate immune response.There are significant limitations in the applicability of these models to human disease,such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption.Thus,there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients. 展开更多
关键词 Non-alcoholic fatty liver disease Alcoholic liver disease Non-alcoholic steatohepatitis Animal models Insulin resistance Oxidative stress
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Chronic peripheral inflammation: a possible contributor to neurodegenerative diseases 认领
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作者 Patrick Süβ Addison J.Lana Johannes C.M.Schlachetzki 《中国神经再生研究:英文版》 SCIE CAS 2021年第9期1711-1714,共4页
The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the... The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases. In addition, progressive systemic inflammation is increasingly recognized during aging. Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules. There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances. In this perspective, we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia, the resident immune cells of the brain parenchyma. 展开更多
关键词 AGING Alzheimer's disease INFLAMMATION innate immune system MICROGLIA NEURODEGENERATION Parkinson's disease
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Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide dual receptor agonist DA-CH5 is superior to exendin-4 in protecting neurons in the 6-hydroxydopamine rat Parkinson model 认领
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作者 Ling-Yu Zhang Qian-Qian Jin +1 位作者 Christian Hölscher Lin Li 《中国神经再生研究:英文版》 SCIE CAS 2021年第8期1660-1670,共11页
Patients with Parkinson's disease(PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), can re-sensiti... Patients with Parkinson's disease(PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular coagonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine(6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1(IRS-1)/alpha serine/threonine-protein kinase(Akt)/c AMP response element-binding protein(CREB) pathway. We also found that DA-CH5(10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines(tumor necrosis factor-α, interleukin-1β). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was upregulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDAunilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China. 展开更多
关键词 neurodegenerative disease Parkinson's disease insulin resistance inflammation GLP-1/GIP receptor unimolecular co-agonist
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Nephrotic syndrome in syngeneic hematopoietic stem cell transplantation recipients: A case report 认领
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作者 Ming-Chuan Bai Jing-Jing Wu +2 位作者 Kou-Rong Miao Jing-Feng Zhu Hui-Juan Mao 《世界临床病例杂志》 SCIE 2021年第3期614-622,共9页
BACKGROUND Hematopoietic stem cell transplantation(HSCT)is widely used in the treatment of hematological diseases.However,complications after transplantation,such as acute and chronic graft-vs-host disease(GVHD),still... BACKGROUND Hematopoietic stem cell transplantation(HSCT)is widely used in the treatment of hematological diseases.However,complications after transplantation,such as acute and chronic graft-vs-host disease(GVHD),still seriously affect the quality of life and even threaten the lives of patients.There is evidence that glomerular diseases can manifest as GVHD.However,GVHD should not occur as a result of syngeneic HSCT.CASE SUMMARY A 20-year-old male diagnosed with T lymphoblastic lymphoma(stage IIIA,aaIPI 1)in September 2013 was treated with six cycles of hyper-CVAD and achieved complete remission.He underwent syngeneic HSCT in June 2014,and had no kidney disease history before the transplant.However,nephrotic syndrome occurred 24 mo later in the patient after syngeneic HSCT.Renal biopsy was performed,which led to a diagnosis of atypical membranous nephropathy.After treatment with glucocorticoids combined with cyclophosphamide and cyclosporine,the nephrotic syndrome was completely relieved.CONCLUSION We report a case of delayed nephrotic syndrome after syngeneic HSCT.Antibodymediated autoimmune glomerular disease may be the underlying mechanism.After treatment with immunosuppressive agents,the nephrotic syndrome was completely relieved but further long-term follow-up is still needed. 展开更多
关键词 Syngeneic hematopoietic stem cell transplantation Nephrotic syndrome Graft vs host disease CYCLOSPORINE Autoimmune glomerular disease Case report
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The Yin-Yang of osteopontin in nervous system diseases: damage versus repair 认领
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作者 Giuseppe Cappellano Domizia Vecchio +7 位作者 Luca Magistrelli Nausicaa Clemente Davide Raineri Camilla Barbero Mazzucca Eleonora Virgilio Umberto Dianzani Annalisa Chiocchetti Cristoforo Comi 《中国神经再生研究:英文版》 SCIE CAS 2021年第6期1131-1137,共7页
Osteopontin is a broadly expressed pleiotropic protein,and is attracting increased attention because of its role in the pathophysiology of several inflammatory,degenerative,autoimmune,and oncologic diseases.In fact,in... Osteopontin is a broadly expressed pleiotropic protein,and is attracting increased attention because of its role in the pathophysiology of several inflammatory,degenerative,autoimmune,and oncologic diseases.In fact,in the last decade,several studies have shown that osteopontin contributes to tissue damage not only by recruiting harmful inflammatory cells to the site of lesion,but also increasing their survival.The detrimental role of osteopontin has been indeed well documented in the context of different neurological conditions(i.e.,multiple sclerosis,Parkinson’s,and Alzheimer’s diseases).Intriguingly,recent findings show that osteopontin is involved not only in promoting tissue damage(the Yin),but also in repair/regenerative mechanisms(the Yang),mostly triggered by the inflammatory response.These two apparently discordant roles are partly related to the presence of different functional domains in the osteopontin molecule,which are exposed after thrombin or metalloproteases cleavages.Such functional domains may in turn activate intracellular signaling pathways and mediate cell-cell and cell-matrix interactions.This review describes the current knowledge on the Yin and Yang features of osteopontin in nervous system diseases.Understanding the mechanisms behind the Yin/Yang would be relevant to develop highly specific tools targeting this multifunctional protein. 展开更多
关键词 Alzheimer’s disease cytokine immunity MICROGLIA multiple sclerosis NEUROINFLAMMATION neuroprotection NEUROTOXICITY Parkinson’s disease Spp1 stroke
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Current application and future directions of photobiomodulation in central nervous diseases 认领
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作者 Muyue Yang Zhen Yang +1 位作者 Pu Wang Zhihui Sun 《中国神经再生研究:英文版》 SCIE CAS 2021年第6期1177-1185,共9页
Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions.Photobiomodulation can promote neurogenesis and elici... Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions.Photobiomodulation can promote neurogenesis and elicit anti-apoptotic,antiinflammatory and antioxidative responses.Its therapeutic effects have been demonstrated in studies on neurological diseases,peripheral nerve injuries,pain relief and wound healing.We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019.The NCBI PubMed database,EMBASE database,Cochrane Library and ScienceDirect database were searched.We reviewed 95 papers and analyzed.Photobiomodulation has wide applicability in the treatment of stroke,traumatic brain injury,Parkinson’s disease,Alzheimer’s disease,major depressive disorder,and other diseases.Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases.However,additional studies with adequate sample size are needed to optimize treatment parameters. 展开更多
关键词 Alzheimer’s disease central nervous system diseases major depressive disorder Parkinson’s disease PHOTOBIOMODULATION STROKE traumatic brain injury
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Colonic Crohn’s disease-decision is more important than incision:A surgical dilemma 认领
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作者 Maria Michela Chiarello Maria Cariati Giuseppe Brisinda 《世界胃肠外科杂志:英文版(电子版)》 SCIE CAS 2021年第1期1-6,共6页
The most common localization for intestinal Crohn’s disease(CD)is the terminal ileum and ileocecal area.It is estimated that patients with CD have one in four chance of undergoing surgery during their life.As surgery... The most common localization for intestinal Crohn’s disease(CD)is the terminal ileum and ileocecal area.It is estimated that patients with CD have one in four chance of undergoing surgery during their life.As surgery in ulcerative colitis ultimately cures the disease,in CD,regardless of the extent of bowel removed,the risk of disease recurrence is as high as 40%.In elective surgery,management of isolated Crohn’s colitis continues to evolve.Depending on the type of surgery performed,colonic CD patients often require further medical or surgical therapy to prevent or treat recurrence.The elective surgical treatment of colonic CD is strictly dependent on the localization of disease,and the choice of the procedure is dependent of the extent of colonic involvement and previous resection.The most common surgical options in colonic CD are total proctocolectomy(TPC)with permanent ileostomy,segmental bowel resection,subtotal colectomy.TPC completely removes all colonic and rectal disease and avoids the use of a potentially diseased anus.We will review current options for the elective surgical treatment of colonic CD,based on the current literature and our own personal experience. 展开更多
关键词 Crohn’s disease Colonic Crohn’s disease Surgery Surgical treatment Colonic resection Segmental colectomy Total colectomy
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Clinical outcomes in patients with native valve infective endocarditis and diabetes mellitus 认领
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作者 Temidayo Abe Harry Onoriode Eyituoyo +4 位作者 Gabrielle De Allie Titilope Olanipekun Valery Sammah Effoe Kikelomo Olaosebikan Paul Mather 《世界心脏病学杂志:英文版(电子版)》 CAS 2021年第1期11-20,共10页
BACKGROUND There is a lack of data on the clinical outcomes in patients with native valve infective endocarditis(NVIE)and diabetes mellitus(DM).AIM To investigate(1)trends in the prevalence of DM among patients with N... BACKGROUND There is a lack of data on the clinical outcomes in patients with native valve infective endocarditis(NVIE)and diabetes mellitus(DM).AIM To investigate(1)trends in the prevalence of DM among patients with NVIE;and(2)the impact of DM on NVIE outcomes.METHODS We identified 76385 with NVIE from the 2004 to 2014 National Inpatient Sample,of which 22284(28%)had DM.We assessed trends in DM from 2004 to 2014 using the Cochrane Armitage test.We compared baseline comorbidities,microorganisms,and in-patients procedures between those with vs without DM.Propensity match analysis and multivariate logistic regression were used to investigate study outcomes in in-hospital mortality,stroke,acute heart failure,cardiogenic shock,septic shock,and atrioventricular block.RESULTS Crude rates of DM increased from in 22%in 2004 to 30%in 2014.There were significant differences in demographics,comorbidities and NVIE risk factors between the two groups.Staphylococcus aureus was the most common organism identified with higher rates in patients with DM(33.1%vs 35.6%;P<0.0001).After propensity matching,in-hospital mortality(11.1%vs 11.9%;P<0.0001),stroke(2.3%vs 3.0%;P<0.0001),acute heart failure(4.6%vs 6.5%;P=0.001),cardiogenic shock(1.5%vs 1.9%;P<0.0001),septic shock(7.2%vs 9.6%;P<0.0001),and atrioventricular block(1.5%vs 2.4%;P<0.0001),were significantly higher in patients with DM.Independent predictors of mortality in NVIE patients with DM include hemodialysis,congestive heart failure,atrial fibrillation,staphylococcus aureus,and older age.CONCLUSION There is an increasing prevalence of DM in NVIE and it is associated with poorer outcomes.Further studies are crucial to identify the clinical,and sociodemographic contributors to this trend and develop strategies to mitigate its attendant risk. 展开更多
关键词 Infective endocarditis Native valve infective endocarditis Diabetes mellitus Valvular heart disease Cardiovascular disease National Inpatient Sample
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Prone Transpsoas Approach for Adjacent Segment Disease and Flatback Deformity: Technical Note and Case Report 认领
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作者 Timothy E. O’Connor Mary Margaret O’Hehir +2 位作者 Jennifer Z. Mao Jeffrey P. Mullin John Pollina 《现代神经外科学进展(英文)》 2021年第1期20-28,共9页
The prone transpsoas approach is a relatively new technique to correct segmental kyphosis and global sagittal imbalance in a minimally invasive fashion. Here, we provide a detailed case report using the prone transpso... The prone transpsoas approach is a relatively new technique to correct segmental kyphosis and global sagittal imbalance in a minimally invasive fashion. Here, we provide a detailed case report using the prone transpsoas approach to address adjacent segment disease and flatback deformity. This technique allows considerable restoration of segmental lordosis with lateral interbody placement and posterior decompression and fusion using a single position approach. Our experience with the surgical technique and the advantages and challenges unique to this approach are discussed. 展开更多
关键词 Prone Transpsoas Adjacent Segment Disease Flatback Deformity
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Small Molecular Weight Compounds Antagonistic to Amyloid Peptide<sub>25-35</sub> 认领
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作者 W. Robert Williams 《生物科学与医学(英文)》 2021年第1期41-51,共11页
High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator ... High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator of this condition. A<em>β</em> initiates cell receptor and synapse dysfunction, and causes mitochondrial damage within neurons. Neurotransmitters and various small molecular weight compounds ameliorate the effects of A<em>β</em> on cell membranes. This study uses a molecular modeling technique to compare the structures of A<em>β</em>25-35 and compounds known to antagonize properties of the polypeptide. Compounds provide good fits to the peptide amino acid residues, revealing planarity in their linear structures and fitting points. Compounds and polypeptide share relative molecular similarity, affinity for receptors and apoptosis modulating properties indicative of their potential for competition at neuron membrane sites. The therapeutic targeting of A<em>β</em> by small molecular weight compounds may benefit from a multi-drug approach. 展开更多
关键词 Alzheimer’s Disease Beta-Amyloid Peptide Beta-Amyloid Antagonists Molecular Modeling
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