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Pathogenic and therapeutic role of exosomes in neurodegenerative disorders

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Neural Regeneration Research 2024年第1期19卷 75-79页

作者： christa C.Huber Hongmin Wang Division of Basic Biomedical Sciences Sanford School of MedicineUniversity of South DakotaVermillionSDUSA

Neurodegenerative disorders affect millions of people worldwide,and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming *** therapies exist to aid in symptomatic relief,effective treatments that can stop or reve rse the progress of each neurodegenerative disease are ***,research on the role of extracellular vesicles as disease markers and therapeutics has been intensively ***,30-150 nm in diameter,are one type of extracellular vesicles facilitating cell-to-cell *** are thought to play a role in disease propagation in a variety of neurodegenerative diseases,such as Alzheimer's disease,Parkinson s disease,and amyotrophic lateral ***,the exosomes derived from the patients are an invaluable source of disease *** the other hand,exosomes,especially those derived from stem cells,could serve as a therapeutic for these disorders,as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological *** review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative *** also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic ***,this review concludes with outstanding questions that remain to be addressed in exosomal research.

关键词： aging Alzheimer's disease biomarker drug exosome extracellular vesicle neurodegenerative disease Parkinson's disease therapy

Music alters heart rate and psychological responses but not muscle activation during light-intensity isometric exercise

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Sports Medicine and Health Science 2024年第4期6卷 394-401页

作者： Andrew R.Moore Jasmin C.Hutchinson christa Winter Paul C.Dalton Lori A.Bolgla Vincent J.Paolone Department of Kinesiology Augusta University112015th St.AugustaGA30912USA Department of Exercise Science&Athletic Training Springfield College263 Alden St.SpringfieldMA01109USA Department of Psychology Springfield College263 Alden St.SpringfieldMA01109USA Heart&Vascular Institute Penn State College of MedicinePenn State University500 HMC Crescent RoadNorth Lobby HersheyPA17033USA Department of Physical Therapy Augusta University112015th St.AugustaGA30912USA

Listening to music manipulates attention to be more externally focused,which has the potential to improve muscular *** study aimed to determine the effect of listening to music on muscle activation during an isometric exercise task,and compare this effect to those of other attentional focus *** healthy subjects(n=35;16 men/19 women)completed an isometric elbow flexion task for 1 min in three randomized and counterbalanced conditions:internal focus(INT),external focus with a simple distraction task(EXT),or listening to music(MUS).Muscle activation of the biceps and triceps brachii and heart rate(HR)were recorded throughout the exercise *** of perceived exertion(RPE),affective valence,and motivation were measured at the end of each *** was no difference in muscle activation measures among the three *** during MUS was lower than EXT at 15 s([89.4±11.8]beats/min vs.[93.1±12.9]beats/min;p=0.018)and 30 s([90.6±12.4]beats/min vs.[94.2±12.5]beats/min;p=0.026),and lower than INT at 60 s([93.3±13.3]beats/min vs.[96.7±12.0]beats/min;p=0.016).Overall RPE was higher for INT(13.4±2.2)than for MUS([12.6±2.0];p=0.020)and EXT([11.94±2.22];p<0.001).Affective valence was higher for MUS than for INT([2.7±1.4]vs.[2.1±1.5];p=0.011).Manipulating attentional focus did not alter muscle activation for a light-intensity isometric muscular endurance task,though MUS was reported as more positive and requiring less exertion to complete than *** music can therefore be recommended during light-intensity isometric exercise based on the psychological benefits observed.

关键词： Electromyography Attentional focus Rating of perceived exertion Elbow flexion

Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2349-2357页

作者： Rabea Voget Julian Breidenbach Tobias Claff Alexandra Hingst Katharina Sylvester Christian Steinebach Lan Phuong Vu Renato H.Weiße Ulrike Bartz Norbert Sträter christa E.Müller Michael Gütschow Pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnBonn 53121Germany Institute of Bioanalytical Chemistry Center for Biotechnology and BiomedicineLeipzig UniversityLeipzig 04103Germany Department of Natural Sciences University of Applied Sciences Bonn-Rhein-SiegRheinbach 53359Germany

A titrant for the SARS-CoV-2 main protease(M^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active M^(pro) by active-site *** covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant *** fluorogenic substrates of M^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay *** exploiting the new titrant,key kinetic parameters for the M^(pro)-catalyzed cleavage of these substrates were determined.

关键词： COVID-19 SARS-CoV-2 Main protease Peptide nitriles Fluorogenic substrates Active-site titration X-ray crystallography Inner filter effect

Adiponectin,a key adipokine in obesity related liver diseases

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World Journal of Gastroenterology 2011年第23期17卷 2801-2811页

作者： christa Buechler Josef Wanninger Markus Neumeier Department of Internal Medicine I University Hospital of RegensburgD-93042 RegensburgGermany

Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western *** liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin *** steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of *** liver biopsy no diagnostic tools to identify patients with NASH are available,and no effective treatment has been *** obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage,insulin resistance,and progressive liver *** of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver *** is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or *** antagonizes excess lipid storage in the liver and protects from inflammation and *** review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.

关键词： Hepatic steatosis Non-alcoholic steatohepatitis Adiponectin Obesity Adipose tissue

Activated microglia nibbling glycosaminoglycans from spinal cord perineural nets: a new mechanism for neuropathic pain

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3632-3634页

作者： christa E.Muller Tobias Claff PharmaCenter Bonn and Pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnAn der Immenburg 453121 BonnGermany

n a recent study published in Science,1 Tansley,Khoutorsky et *** a novel mechanism by which activated microglia can induce pain and pain *** involves the degradation of perineural nets(PNNs)around neurons in the spin... 详细信息

关键词： pain al. neural

Surgical management in pediatric neuroblastoma diagnosis and treatment:a 20-year,single-center experience

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World Journal of Pediatrics 2022年第2期18卷 120-125页

作者： Brianna Spencer Akshilkumar Patel Robert Cilley christa N.Grant Department of Surgery Penn State Health Milton SHershey Medical Center500 University DriveHersheyPA 17033USA Pennsylvania State University College of Medicine HersheyPAUSA Division of Pediatric Surgery Penn State Health Milton SHershey Medical CenterHersheyPAUSA

Background The currently utilized International Neuroblastoma Risk Group(INRG)staging system developed in 2009 uses image-defined risk factors as a measure of surgical risk,separating resectable neuroblastoma from those best preceded by *** previous International Neuroblastoma Staging System was based primarily on surgical *** hypothesized there would be a change to the role of the surgeon in neuroblastoma treatment in the more recent *** This is a single center 20-year retrospective analysis of 104 patients with International Classification of Diseases-9 and-10 codes for *** demographics,tumor site,cancer treatment modality,survival,biopsy technique,surgical intervention,and pathology staging were *** was analyzed by analysis of variance(ANOVA)and Student’s t *** There was a decrease in open surgeries for extra-adrenal neuroblastomas in the later decade(77%,31%,P=0.01).There was a narrowing of the time interval to surgery in the later cohort,likely as a result of uniformity in surgical timing on treatment protocols relying on INRG *** Our findings mirror changes in practice patterns *** found an increase in minimally invasive approaches but did not find a difference in the role of the surgeon under the INRG staging system.

关键词： International Neuroblastoma Risk Group International Neuroblastoma Staging System MYCN Neuroblastoma Resection

Glucocorticoid receptor gene haplotype structure and steroid therapy outcome in IBD patients

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World Journal of Gastroenterology 2010年第31期16卷 3888-3896页

作者： Jessica Mwinyi christa Wenger Jyrki J Eloranta Gerd A Kullak-Ublick Division of Clinical Pharmacology and Toxicol-ogy University Hospital Zurich

AIM: To study whether the glucocorticoid receptor (GR/ NR3C1) gene haplotypes influence the steroid therapy outcome in inflammatory bowel disease (IBD). METHODS: We sequenced all coding exons and flanking intronic sequences of the NR3C1 gene in 181 IBD patients, determined the single nucleotide polymorphisms, and predicted the NR3C1 haplotypes. Furthermore, we investigated whether certain NR3C1 haplotypes are significantly associated with steroid therapy outcomes. RESULTS: We detected 13 NR3C1 variants, which led to the formation of 17 different haplotypes with a certainty of > 95% in 173 individuals. The three most commonly occurring haplotypes were included in the association analysis of the influence of haplotype on steroid therapy outcome or IBD activity. None of the NR3C1 haplotypes showed statistically signifi cant association with glucocorticoid therapy success. CONCLUSION: NR3C1 haplotypes are not related to steroid therapy outcome.

关键词： Inflammatory bowel disease Steroid therapy Glucocorticoid receptor Pharmacogenetics Haplotype analysis

First report of colonoscopic closure of a gastrocolocutaneous PEG migration with over-the-scope-clip-system

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World Journal of Gastroenterology 2014年第32期20卷 11439-11442页

作者： Reto Bertolini christa Meyenberger Michael Christian Sulz Department of Gastroenterology and Hepatology 9000 St. Gallen Switzerland

Percutaneous endoscopic gastrostomy(PEG) is a common practice for long-term nutrition of patients who are unable to take oral food. We report of an 85-year old man with a history of recurrent larynx carcinoma and hemicolectomy many years ago due to unknown reason. Laryngectomy was indicated. Preoperatively a PEG was inserted endoscopically after an abdominal ultrasonography without abnormal findings. Few months after PEG insertion, the patient was evaluated for diarrhea and insufficient feeding without signs of infection or peritonism. An upper endoscopy and computed tomography scan confirmed a buried bumper syndrome with migration of the PEG tube into the colon as a rare complication. He underwent successful colonoscopic removal of the internal bumper and closure of the colonic orifice of the fistula with the over-the-scope-clip system(OTSC). OTSC is an endoscopic device for treatment of bleeding, perforation, leak and fistula in the gastrointestinal tract. To the best of our knowledge, this is the first report of the use of OTSC for colonoscopic closure of a gastrocolocutaneous fistula due to a buried bumper syndrome with transcolonic PEG tube migration.

关键词： Over-the-scope-clip Over-the-scope-clip system Enterocutaneous fistula Colon Buried bumper Percutaneous endoscopic gastrostomy Complication Migration

Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?

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World Journal of Gastroenterology 2007年第2期13卷 306-309页

作者： Kilian Weigand Carina Riediger Wolfgang Stremmel christa Flechtenmacher Jens Encke Department of Gastroenterology and Hepatology Medicine Ⅳ University of Heidelberg 69120 Heidelberg Germany Department of Pathology University of Heidelberg 69120 Heidelberg Germany

While cardiopulmonary symptoms are common in patients undergoing dassical or, due to physical exercise, exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio （INR）. No other causes for liver failure could be identified but physical exhaustion and hyperthermia.

关键词： Heat stroke Acute hepatic failure Heat shock Liver failure Hyperthermia