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Peptides Nov 2021Ghrelin is a gut hormone with numerous physiological effects, including the regulation of energy balance, insulin sensitivity, vascular health, and body composition.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ghrelin is a gut hormone with numerous physiological effects, including the regulation of energy balance, insulin sensitivity, vascular health, and body composition. Acylated (AG) and des-acylated (DAG) ghrelin constitute approximately 22 % and 78 % of total plasma ghrelin (TG), respectively. Alterations in the TG concentration and the AG/DAG ratio may be implicated in conditions involving energy imbalances and insulin resistant states (e.g., metabolic syndrome or Type 2 diabetes mellitus). Exercise is a therapeutic option that can potentially optimize ghrelin levels. Understanding the precise intensity and dose of exercise to optimize ghrelin levels may lead to targeted interventions to restore metabolic regulation in obesity and other clinical conditions.
OBJECTIVE
To perform a systematic review and meta-analysis on the effects of acute exercise on pre-prandial levels of TG, AG, and DAG in healthy adults and to determine if sample demographics or exercise doses moderate such effects.
METHODS
Electronic databases (PubMed, Medline, SPORTDiscus, Web of Science, and Google Scholar) were searched with articles published through August 2020. The following criteria was determined a priori for article inclusion: (i) the study was a randomized controlled trial (RCT),(ii) exercise was an acute bout, (iii) the exercise bout for the intervention group(s)/condition was structured, (iv) the control group/condition received no exercise, (v) participants were adults age 18 or older, (vi) ghrelin was sampled through blood, (vii) there was at least one baseline measure and one post-exercise measure of ghrelin, (viii) there were at least 3 timepoints where ghrelin was measured while participants were fasted to allow for pre-prandial total area-under-the-curve (AUC) calculation, (ix) participants were healthy with no overt disease, (x) interventions were carried out without any environmental manipulations. Standardized mean difference (SMD) with 95 % confidence intervals were calculated using the restricted maximum likelihood estimation Moderator analyses to determine whether the overall pooled effect was influenced by: sex, ghrelin form, method of ghrelin analysis, age, body mass index, body fat percentage, fitness, intensity of exercise bout, duration of exercise bout, energy expenditure, and length of AUC data.
RESULTS
The analysis included 24 studies that consisted of 52 trials, n = 504 (age 27.0 (8.8) years, BMI 24.7 (2.7) kg/m) and measured AG (n = 38 trials), DAG (n = 7), and TG (n = 7). The overall model indicated that exercise lowered ghrelin levels compared to control (no exercise); (SMD=-0.44, p < 0.001), and exercise intensity exhibited an inverse relationship with ghrelin levels (regression coefficient (ß)=-0.016, p = 0.04). There was no significant difference by ghrelin form (p = 0.18).
DISCUSSION
Acute exercise significantly lowers plasma ghrelin levels, with higher intensity exercise associated with greater ghrelin suppression. The majority of studies applied a moderate intensity exercise bout and measured AG, with limited data on DAG. This exercise dose may be clinically significant in individuals with metabolic dysregulation and energy imbalance as a therapy to optimize AG levels. More work is needed to compare moderate and high intensity exercise and the ghrelin response in clinical populations.
Topics: Acylation; Body Mass Index; Energy Metabolism; Exercise; Fasting; Female; Ghrelin; Humans; Male
PubMed: 34391825
DOI: 10.1016/j.peptides.2021.170625 -
Molecular Neurobiology Aug 2021Sirtuins are the class III of histone deacetylases that depend on nicotinamide adenine dinucleotide for their activity. Sirtuins can influence the progression of...
Sirtuins are the class III of histone deacetylases that depend on nicotinamide adenine dinucleotide for their activity. Sirtuins can influence the progression of neurodegenerative disorders by switching between deacetylation and acetylation processes. Histone acetylation occurs when acetyl groups are added to lysine residues on the N-terminal part of histone proteins. Deacetylation, on the other hand, results in the removal of acetyl groups. Pharmacological modulation of sirtuin activity has been shown to influence various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. In this review, mechanistic perspective of sirtuins has been discussed in anti-inflammatory, antiapoptotic, and neuroprotective effects in various disorders. We have discussed the structure, neurobiology, and physiology of sirtuins in neurodegenerative disease. Recent preclinical and clinical studies and their outcome have also been elucidated. The aim of this review is to fill in the gaps in our understanding of sirtuins' role in histone acetylation and deacetylation in all neurodegenerative diseases. Here, we emphasized on reviewing all the studies carried out in various labs depicting the role of sirtuin modulators in neuroprotection and highlighted the ideas that can be considered for future perspectives. Taken together, sirtuins may serve as a promising therapeutic target for the treatment of neurodegenerative disorders.
Topics: Acetylation; Animals; Anti-Inflammatory Agents; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Sirtuins
PubMed: 33877561
DOI: 10.1007/s12035-021-02387-w -
Nutrients Mar 2021Elevated inflammation in pregnancy has been associated with multiple adverse pregnancy outcomes and potentially an increased susceptibility to future chronic disease....
Elevated inflammation in pregnancy has been associated with multiple adverse pregnancy outcomes and potentially an increased susceptibility to future chronic disease. How maternal dietary patterns influence systemic inflammation during pregnancy requires further investigation. The purpose of this review was to comprehensively evaluate studies that assessed dietary patterns and inflammatory markers during pregnancy. This review was guided by the Preferred Reporting Items for Systematic Review and Meta-Analyses. Included studies were sourced from EMBASE, PubMed, Web of Science, and Scopus and evaluated using The Quality Assessment Tool for Quantitative Studies. Inclusion criteria consisted of human studies published in English between January 2007 and May 2020 that addressed associations between dietary patterns and inflammatory markers during pregnancy. Studies focused on a single nutrient, supplementation, or combined interventions were excluded. A total of 17 studies were included. Despite some inconsistent findings, maternal diets characterized by a higher intake of animal protein and cholesterol and/or a lower intake of fiber were shown to be associated with certain pro-inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), IL-8, serum amyloid A (SAA), and glycoprotein acetylation (GlycA)). Future studies that explore a broader range of inflammatory markers in the pregnant population, reduce measurement errors, and ensure adequate statistical adjustment are warranted.
Topics: Acetylation; Biomarkers; C-Reactive Protein; Diet; Female; Glycoproteins; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Maternal Nutritional Physiological Phenomena; Pregnancy; Pregnancy Trimesters; Prenatal Care; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha
PubMed: 33806342
DOI: 10.3390/nu13030834 -
Cells Jan 2021The wound healing that follows myocardial infarction is a complex process involving multiple mechanisms, such as inflammation, angiogenesis and fibrosis. In the last two...
The wound healing that follows myocardial infarction is a complex process involving multiple mechanisms, such as inflammation, angiogenesis and fibrosis. In the last two decades, the involvement of WNT signaling has been extensively studied and effects on virtually all aspects of this wound healing have been reported. However, as often is the case in a newly emerging field, inconsistent and sometimes even contradictory findings have been reported. The aim of this systematic review is to provide a comprehensive overview of studies in which the effect of interventions in WNT signaling were investigated in in vivo models of cardiac injury. To this end, we used different search engines to perform a systematic search of the literature using the key words "WNT and myocardial and infarction". We categorized the interventions according to their place in the WNT signaling pathway (ligand, receptor, destruction complex or nuclear level). The most consistent improvements of the wound healing response were observed in studies in which the acylation of WNT proteins was inhibited by administering porcupine inhibitors, by inhibiting of the downstream glycogen synthase kinase-3β (GSK3β) and by intervening in the β-catenin-mediated gene transcription. Interestingly, in several of these studies, evidence was presented for activation of cardiomyocyte proliferation around the infarct area. These findings indicate that inhibition of WNT signaling can play a valuable role in the repair of cardiac injury, thereby improving cardiac function and preventing the development of heart failure.
Topics: Animals; Apoptosis; Humans; Inflammation; Myocardium; Myocytes, Cardiac; Neovascularization, Physiologic; Wnt Signaling Pathway; Wound Healing
PubMed: 33494313
DOI: 10.3390/cells10020207 -
Frontiers in Bioengineering and... 2020Synthetic biology holds promise to revolutionize the life sciences and biomedicine via expansion of macromolecular diversity outside the natural chemical space. Use of...
Synthetic biology holds promise to revolutionize the life sciences and biomedicine via expansion of macromolecular diversity outside the natural chemical space. Use of non-canonical amino acids (ncAAs) via codon reassignment has found diverse applications in protein structure and interaction analysis, introduction of post-translational modifications, production of constrained peptides, antibody-drug conjugates, and novel enzymes. However, simultaneously encoding multiple ncAAs requires complex engineering and is sometimes restricted by the cell's poor uptake of ncAAs. In contrast the open nature of cell-free protein synthesis systems offers much greater freedom for manipulation and repurposing of the biosynthetic machinery by controlling the level and identity of translational components and reagents, and allows simultaneous incorporation of multiple ncAAs with non-canonical side chains and even backbones (N-methyl, D-, β-amino acids, α-hydroxy acids etc.). This review focuses on the two most used -based cell-free protein synthesis systems; cell extract- and PURE-based systems. The former is a biological mixture with >500 proteins, while the latter consists of 38 individually purified biomolecules. We delineate compositions of these two systems and discuss their respective advantages and applications. Also, we dissect the translational components required for ncAA incorporation and compile lists of ncAAs that can be incorporated into polypeptides via different acylation approaches. We highlight the recent progress in using unnatural nucleobase pairs to increase the repertoire of orthogonal codons, as well as using tRNA-specific ribozymes for acylation. We summarize advances in engineering of translational machinery such as tRNAs, aminoacyl-tRNA synthetases, elongation factors, and ribosomes to achieve efficient incorporation of structurally challenging ncAAs. We note that, many engineered components of biosynthetic machinery are developed for the use but are equally applicable to the systems. These are included in the review to provide a comprehensive overview for ncAA incorporation and offer new insights for the future development in cell-free systems. Finally, we highlight the exciting progress in the genomic engineering, resulting in strains free of amber and some redundant sense codons. These strains can be used for preparation of cell extracts offering multiple reassignment options.
PubMed: 33117774
DOI: 10.3389/fbioe.2020.01031 -
Drug Discovery Today Aug 2020Dysregulated transcription factors (TFs) fuel aberrant gene expression networks, resulting in cell overproliferation, migration, and immunosuppression. Given that TFs...
Dysregulated transcription factors (TFs) fuel aberrant gene expression networks, resulting in cell overproliferation, migration, and immunosuppression. Given that TFs are regarded to have vital roles in tumors, various approaches are exploited to modulate their activities. Nevertheless, except for some ligand-binding nuclear receptors, most TFs are still considered 'undruggable' targets. Responding to extra- or intracellular stimuli, TFs are decorated with an array of post-translational modifications (PTMs) to regulate their subcellular localizations, protein-protein/DNA interactions, and stability. These PTMs orchestrate the multiple functions of TFs, thus offering numerous potential targets. In this review, we systematically review emerging concepts and effective agents in PTMs-associated TF-targeting, which could provide paradigms for cancer treatment.
Topics: Acetylation; Animals; Humans; Methylation; Neoplasms; Phosphorylation; Protein Processing, Post-Translational; Transcription Factors
PubMed: 32540433
DOI: 10.1016/j.drudis.2020.06.005 -
Arteriosclerosis, Thrombosis, and... Mar 2020Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current...
OBJECTIVE
Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but fibrinolysis was found to be decreased, as a consequence of increased density and decreased permeability of clots. Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis. Other modifications were studied less or contrasting results were found. Therefore, substantial gaps in the knowledge about the effect of post-translational modifications remain.
CONCLUSIONS
Overall, post-translational modifications do affect clot formation and characteristics. More studies need to be performed to reveal the effects of all post-translational modifications and the effects on thrombotic diseases. Expanding the knowledge about modifications of fibrinogen can ultimately contribute to optimizing treatments for thrombotic diseases.
Topics: Acetylation; Animals; Fibrinogen; Fibrinolysis; Glycosylation; Humans; Oxidation-Reduction; Polymerization; Protein Processing, Post-Translational; Thrombosis
PubMed: 31914791
DOI: 10.1161/ATVBAHA.119.313626