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Journal of Molecular Medicine (Berlin,... Sep 2021As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing... (Meta-Analysis)
Meta-Analysis
As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing of ECM remodeling pathways, we conducted a systematic review in which we describe protein and mRNA markers for ECM remodeling that are differentially expressed in the hearts of animals with anthracycline-induced cardiomyopathy. We included 68 studies in mice, rats, rabbits, and pigs with follow-up of 0.1-8.2 human equivalent years after anthracycline administration. Using meta-analysis, we found 29 proteins and 11 mRNAs that were differentially expressed in anthracycline-induced cardiomyopathy compared to controls. Collagens, matrix metalloproteinases (MMPs), inflammation markers, transforming growth factor ß signaling markers, and markers for cardiac hypertrophy were upregulated, whereas the protein kinase B (AKT) pro-survival pathway was downregulated. Their expression patterns over time from single time point studies were studied with meta-regression using human equivalent years as the time scale. Connective tissue growth factor showed an early peak in expression but remained upregulated at all studied time points. Brain natriuretic peptide (BNP) and MMP9 protein levels increased in studies with longer follow-up. Significant associations were found for higher atrial natriuretic peptide with interstitial fibrosis and for higher BNP and MMP2 protein levels with left ventricular systolic function.
Topics: Animals; Anthracyclines; Apoptosis; Cardiomyopathies; Disease Models, Animal; Extracellular Matrix; Extracellular Matrix Proteins; Fibrosis; Gene Expression Regulation; Myocardium; RNA, Messenger; Signal Transduction; Time Factors; Ventricular Function, Left; Ventricular Remodeling
PubMed: 34052857
DOI: 10.1007/s00109-021-02098-8 -
Nutrients Feb 2021Asprosin is a recently discovered protein released during fasting conditions mainly by adipocytes from white adipose tissue. As a glucogenic peptide, it stimulates the...
Asprosin-A Fasting-Induced, Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity, Diabetes, or Infertility? A Review of the Literature.
Asprosin is a recently discovered protein released during fasting conditions mainly by adipocytes from white adipose tissue. As a glucogenic peptide, it stimulates the release of glucose from hepatic cells by binding to the OLFR734 receptor and leading to the activation of the G protein-cAMP-PKA pathway. As it crosses the blood-brain barrier, it also acts as an orexigenic peptide that stimulates food intake through activation of AgRP neurons in the hypothalamus; thus, asprosin participates in maintaining the body's energy homeostasis. Moreover, studies have shown that asprosin levels are pathologically elevated in obesity and related diseases. However, the administration of anti-asprosin antibodies can both normalize its concentration and reduce food intake in obese mice, which makes it an interesting factor to combat obesity and related diseases. Current research also draws attention to the relationship between asprosin and fertility, especially in men. Asprosin improves age- and obesity-related decrease in fertility potential by improving sperm motility. It should also be mentioned that plasma asprosin levels can be differentially modulated by physical activity; intense anaerobic exercise increases asprosin level, while aerobic exercise decreases it. However, further research is necessary to confirm the exact mechanisms of asprosin activity and its potential as a therapeutic target.
Topics: Adipokines; Adipose Tissue, White; Animals; Blood-Brain Barrier; Diabetes Mellitus; Eating; Energy Metabolism; Fasting; Female; Fibrillin-1; Glucose; Homeostasis; Humans; Infertility; Male; Mice; Mice, Obese; Obesity; Signal Transduction; Sperm Motility
PubMed: 33673009
DOI: 10.3390/nu13020620 -
Peptides Nov 2020The 28-amino acid peptide hormone ghrelin plays a unique role in the gut-brain axis: It is mainly produced peripherally in gastric X/A-like cells but stimulates food...
The 28-amino acid peptide hormone ghrelin plays a unique role in the gut-brain axis: It is mainly produced peripherally in gastric X/A-like cells but stimulates food intake centrally via hypothalamic nuclei; thus, providing orexigenic communication between the gut and central food intake-regulatory centers. Another component of the gut-brain axis that gained increasing interest in recent years due to its ability to influence central signaling via metabolites is the gut microbiome. Interestingly, there is increasing evidence that changes in the microbiome are related to alterations in ghrelin expression, secretion, activation and signaling. Since ghrelin is supposedly implicated in the pathogenesis of obesity, changes in the microbiome were hypothesized to improve obesity via modulation of ghrelin abundance and receptor interaction. To shed more light on the association between the microbiome and ghrelin a systematic search of Medline, EMBASE and Web of science using the search term combination "microbiome AND ghrelin" was performed. As a result of the search, 42 publications were included into this systematic review, of which 30 publications reported preclinical and 12 manuscripts presented clinical data. In addition to a critical analysis of the present data, gaps in knowledge were highlighted in order to foster further research.
Topics: Animals; Female; Gastrointestinal Microbiome; Ghrelin; Humans; Male; Mice; Probiotics; Rats; Signal Transduction
PubMed: 32846187
DOI: 10.1016/j.peptides.2020.170388 -
Biomeditsinskaia Khimiia May 2020The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the...
The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the C-peptide, indicating its positive effect on many organs and tissues, including the kidneys, nervous system, heart, vascular endothelium and blood microcirculation. Studies on experimental models of diabetes mellitus in animals, as well as clinical trials in patients with diabetes, have shown that the C-peptide has an important regulatory effect on the early stages of functional and structural disorders caused by this disease. The C-peptide exhibits its effects through binding to a specific receptor on the cell membrane and activation of downstream signaling pathways. Intracellular signaling involves G-proteins and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+/K+-ATPase and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. This review gives an idea of the C-peptide as a bioactive endogenous peptide that has its own biological activity and therapeutic potential.
Topics: Animals; Anti-Inflammatory Agents; C-Peptide; Diabetes Mellitus, Type 1; Humans; Insulin; Signal Transduction
PubMed: 32588825
DOI: 10.18097/PBMC20206603196 -
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 -
Pharmacological Research Jun 2020Since the discovery of Nesfatin-1 in 2006, intensive research was finalized to further and deeper investigate the precise physiological functions of the peptide at both...
Since the discovery of Nesfatin-1 in 2006, intensive research was finalized to further and deeper investigate the precise physiological functions of the peptide at both central and peripheral levels, rapidly enriching the knowledge regarding this intriguing molecule. Nesfatin-1 is a hypothalamic peptide generated via the post-translational processing of its precursor Nucleobindin 2, a protein supposed to play a role in many biological processes thanks to its ability to bind calcium and to interact with different intracellular proteins. Nesfatin-1 is mainly known for its anorexic properties, but it also controls water intake and glucose homeostasis. Recent experimental evidences describe the peptide as a possible direct/indirect orchestrator of central and peripheral cardiovascular control. A specific Nesfatin-1 receptor still remains to be identified although numerous studies suggest that the peptide activates extra- and intracellular regulatory pathways by involving several putative binding sites. The present paper was designed to systematically review the latest findings about Nesfatin-1, focusing on its cardiovascular regulatory properties under normal and physiopathological conditions. The hope is to provide the conceptual basis to consider Nesfatin-1 not only as a pleiotropic neuroendocrine molecule, but also as a homeostatic modulator of the cardiovascular function and with a crucial role in cardiovascular diseases.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Cardiovascular System; Hemodynamics; Humans; Nucleobindins; Prognosis; Signal Transduction; Translational Research, Biomedical
PubMed: 32201244
DOI: 10.1016/j.phrs.2020.104766 -
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