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Translational Neurodegeneration May 2020Alzheimer's disease is a neurodegenerative disorder. Therapeutically, a transplantation of bone marrow mesenchymal stem cells (BMMSCs) can play a beneficial role in... (Meta-Analysis)
Meta-Analysis
Transplantation of bone marrow mesenchymal stem cells improves cognitive deficits and alleviates neuropathology in animal models of Alzheimer's disease: a meta-analytic review on potential mechanisms.
BACKGROUND
Alzheimer's disease is a neurodegenerative disorder. Therapeutically, a transplantation of bone marrow mesenchymal stem cells (BMMSCs) can play a beneficial role in animal models of Alzheimer's disease. However, the relevant mechanism remains to be fully elucidated.
MAIN BODY
Subsequent to the transplantation of BMMSCs, memory loss and cognitive impairment were significantly improved in animal models with Alzheimer's disease (AD). Potential mechanisms involved neurogenesis, apoptosis, angiogenesis, inflammation, immunomodulation, etc. The above mechanisms might play different roles at certain stages. It was revealed that the transplantation of BMMSCs could alter some gene levels. Moreover, the differential expression of representative genes was responsible for neuropathological phenotypes in Alzheimer's disease, which could be used to construct gene-specific patterns.
CONCLUSIONS
Multiple signal pathways involve therapeutic mechanisms by which the transplantation of BMMSCs improves cognitive and behavioral deficits in AD models. Gene expression profile can be utilized to establish statistical regression model for the evaluation of therapeutic effect. The transplantation of autologous BMMSCs maybe a prospective therapy for patients with Alzheimer's disease.
Topics: Alzheimer Disease; Animals; Bone Marrow Transplantation; Cognitive Dysfunction; Disease Models, Animal; Humans; Mesenchymal Stem Cell Transplantation
PubMed: 32460886
DOI: 10.1186/s40035-020-00199-x -
Biomedicine & Pharmacotherapy =... Jul 2020The vascular endothelium plays a vital role in regulating normal vascular function. Endothelial lining maintains the balance of thrombolytic and fibrinolytic...
The vascular endothelium plays a vital role in regulating normal vascular function. Endothelial lining maintains the balance of thrombolytic and fibrinolytic microenvironment in the vasculature. Alterations of vascular endothelium referred to as endothelial dysfunction, caused the pathological changes in vessel wall such activation of proinflammatory and procoagulatory that initiate atherosclerosis. The concept that endothelial dysfunction plays a critical role in the initiation of atherosclerosis due to vascular inflammation gained tremendous attention. Diabetes mellitus is a metabolic-related disease that caused high mortality and morbidity, leading to its cardiovascular complication over the past decade. Atherosclerosis is the leading cardiovascular complication in diabetes mellitus. Despite metabolic and glycemic control, atherosclerotic plaque progression remains an enormous problem in diabetes mellitus complications. Thus, new inroads therapeutic approach in preventing complications that induced inflammation in endothelial cells could help prevent the disease progression. Signal peptide-CUB-EGF like domain-containing protein 2 (SCUBE2) expressed in vascular endothelium and reported to involve in inflammation. A recent study reported an increased SCUBE2 expression in diabetes mellitus and correlated with high expression of endothelin-1 (ET-1), a proinflammatory endothelial cell-derived peptide. Moreover, this gene showed to increase during atherosclerosis development. The present systematic review will summarize the involvement of SCUBE2 in vascular endothelium function changes and vascular complication, particularly in diabetes mellitus and atherosclerosis.
Topics: Adaptor Proteins, Signal Transducing; Atherosclerosis; Blood-Brain Barrier; Calcium-Binding Proteins; Diabetic Angiopathies; Endothelium, Vascular; Hedgehog Proteins; Humans
PubMed: 32278240
DOI: 10.1016/j.biopha.2020.110129 -
Toxins Apr 2020Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of...
Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of low-molecular-weight peptide toxins that have evolved to target voltage-gated ion channels to interfere with the central system of prey and produce pain or paralysis for efficient hunting. Peptide toxins usually contain several intramolecular disulfide bonds, which confer chemical, thermal and biological stability. In addition, centipede peptides generally have novel structures and high potency and specificity and therefore hold great promise both as diagnostic tools and in the treatment of human disease. Here, we review the centipede peptide toxins with reported effects on ion channels, including Nav, Kv, Cav and the nonselective cation channel polymodal transient receptor potential vanilloid 1 (TRPV1).
Topics: Animals; Arthropod Proteins; Arthropod Venoms; Bites and Stings; Chilopoda; Drug Discovery; Humans; Ion Channels; Membrane Transport Modulators; Protein Conformation; Signal Transduction; Structure-Activity Relationship
PubMed: 32260499
DOI: 10.3390/toxins12040230 -
Frontiers in Endocrinology 2020Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with obesity. Although multiple pharmacotherapeutics are in development, currently there...
Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with obesity. Although multiple pharmacotherapeutics are in development, currently there are limited strategies specifically targeting NAFLD. This systematic review summarizes the existing literature on hepatic effects of medications used for weight loss. Glucagon-like peptide 1 (GLP-1) agonists are the best-studied in this regard, and evidence consistently demonstrates reduction in liver fat content, sometimes accompanied by improvements in histological features of steatohepatitis and reductions in serum markers of hepatic injury such as alanine aminotransferase (ALT). It remains unclear whether these benefits are independent of the weight loss caused by these agents. Literature is limited regarding effects of orlistat, but a small number of reports suggest that orlistat reduces liver fat content and improves histologic features of NASH, benefits which may also be driven primarily by weight loss. A sizeable body of literature on hepatic effects of metformin yields mixed results, with a probability of modest benefit, but no consistent signal for strong benefit. There are insufficient data on hepatic effects of topiramate, phentermine, naltrexone, bupropion, and lorcaserin. Finally, a few studies to date suggest that sodium-glucose co-transporter-2 (SGLT2) inhibitors may reduce liver fat content and cause modest reductions in ALT, but further study is needed to better characterize these effects. Based on available data, GLP-1 agonists have the strongest evidence base demonstrating beneficial effects on NAFLD, but it is not clear if any weight loss medication has effects on NAFLD superior to those of nutritional modification and exercise alone.
Topics: Anti-Obesity Agents; Fatty Liver; Humans; Non-alcoholic Fatty Liver Disease; Prognosis; Weight Loss
PubMed: 32153507
DOI: 10.3389/fendo.2020.00070 -
BMC Cardiovascular Disorders Dec 2019The most significant manifestation of heart failure is exercise intolerance. This systematic review and meta-analysis was performed to investigate whether dipeptidyl... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The most significant manifestation of heart failure is exercise intolerance. This systematic review and meta-analysis was performed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1 RAs), widely used anti-diabetic drugs, could improve exercise tolerance in heart failure patients with or without type 2 diabetes mellitus.
METHODS
An electronic search of PubMed, EMBASE and the Cochrane Library was carried out through March 8th, 2019, for eligible trials. Only randomized controlled studies were included. The primary outcome was exercise tolerance [6-min walk test (6MWT) and peak O consumption], and the secondary outcomes included quality of life (QoL), adverse events (AEs) and all-cause death.
RESULT
After the literature was screened by two reviewers independently, four trials (659 patients) conducted with heart failure patients with or without type 2 diabetes met the eligibility criteria. The results suggested that targeting the DPP-4-GLP-1 pathway can improve exercise tolerance in heart failure patients [MD 24.88 (95% CI 5.45, 44.31), P = 0.01] without decreasing QoL [SMD -0.51 (95% CI -1.13, 0.10), P = 0.10]; additionally, targeting the DPP-4-GLP-1 pathway did not show signs of increasing the incidence of serious AEs or mortality.
CONCLUSION
Our results suggest that DPP-4 inhibitors or GLP-1 RAs improve exercise tolerance in heart failure patients. Although the use of these drugs for heart failure has not been approved by any organization, they may be a better choice for type 2 diabetes mellitus patients with heart failure. Furthermore, as this pathway contributes to the improvement of exercise tolerance, it may be worth further investigation in exercise-intolerant patients with other diseases.
Topics: Aged; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Exercise Tolerance; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart Failure; Humans; Incretins; Male; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Recovery of Function; Signal Transduction; Treatment Outcome
PubMed: 31870322
DOI: 10.1186/s12872-019-01275-5 -
Tidsskrift For Den Norske Laegeforening... Aug 2009Myositis-specific antibodies (MSA) are autoantibodies that are almost exclusively detected in idiopathic inflammatory myopathies (IIM). This article provides an overview... (Review)
Review
BACKGROUND
Myositis-specific antibodies (MSA) are autoantibodies that are almost exclusively detected in idiopathic inflammatory myopathies (IIM). This article provides an overview of these autoantibodies and how they can be used clinically to identify subgroups of IIM.
MATERIAL AND METHODS
The article is based on a non-systematic literature review and our own experience.
RESULTS
MSA can be detected in up to 50 % of patients with IIM. Patients with anti-synthetase antibodies have a constellation of clinical findings termed "the anti-synthetase syndrome", in which interstitial lung disease dominates the clinical picture. Anti-Mi2 antibodies is another myositis-specific antibody. Patients with anti-Mi2 antibodies often have classical dermatomyositis, while the anti-SRP antibody identifies patients with severe myopathy, poor response to treatment with corticosteroids and histological findings of muscle cell necrosis - often lacking inflammatory infiltrates. The newly detected anti-CADMp140 appears to be associated with amyopathic or hypomyopathic dermatomyositis, previously called dermatomyositis sine myositis. Anti-p155 antibodies are most often found in patients who also have cancer.
INTERPRETATION
Myositis-specific antibodies may be useful for identification of clinical subgroups of IIM and can thereby affect the choice of medical treatment.
Topics: Amino Acyl-tRNA Synthetases; Anti-Inflammatory Agents; Autoantibodies; Dermatomyositis; Disease Progression; Humans; Immunosuppressive Agents; Intercellular Signaling Peptides and Proteins; Myositis; Nuclear Proteins; Peptides; Signal Recognition Particle
PubMed: 19721478
DOI: 10.4045/tidsskr.09.35501