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Diabetes/metabolism Research and Reviews Nov 2017Presence of fat in the pancreas increases the risk of metabolic co-morbidities. Detection and quantification of pancreatic fat is not a routine clinical practice, at... (Meta-Analysis)
Meta-Analysis Review
Presence of fat in the pancreas increases the risk of metabolic co-morbidities. Detection and quantification of pancreatic fat is not a routine clinical practice, at least in part because of need to use expensive imaging techniques. We aimed to systematically review common markers of pancreatic fat in blood and to investigate differences in these markers associated with fatty pancreas. The search was conducted in 3 databases (EMBASE, Scopus, and MEDLINE). Studies in humans were eligible for inclusion if they reported on biological markers and percentage of pancreatic fat or fatty pancreas prevalence. Data were pooled for correlation and effect size meta-analysis. A total of 17 studies including 11 967 individuals were eligible for meta-analysis. Markers of lipid metabolism, including circulating triglycerides (r = 0.38 [95% confidence interval (CI) 0.31, 0.46]) and high-density lipoprotein cholesterol (r = -0.33 [95% CI -0.35, -0.31]), and markers of glucose metabolism, including glycated haemoglobin (r = 0.39 [95% CI 0.30, 0.48], insulin (r = 0.38 [95% CI 0.33, 0.43]), and homeostasis model assessment-insulin resistance (r = 0.37 [95% CI 0.30, 0.44], yielded the best correlations with percentage of pancreatic fat. Further, effect size analysis showed large and medium effects for the above markers of lipid and glucose metabolism. Circulating levels of triglycerides and glycated haemoglobin appear to be the best currently available markers of pancreatic fat. The approach of non-invasive and accurate detection of pancreatic fat by blood analysis should be further explored in the future, by investigating other potential biological markers of pancreatic fat.
Topics: Adipose Tissue; Biomarkers; Cholesterol, HDL; Humans; Insulin Resistance; Lipid Metabolism; Lipids; Pancreas; Triglycerides
PubMed: 28730683
DOI: 10.1002/dmrr.2918 -
Drug Discovery Today Mar 2020International efforts are underway to develop chemical probes for specific protein families, and a 'Target 2035' call to expand these efforts towards a comprehensive...
International efforts are underway to develop chemical probes for specific protein families, and a 'Target 2035' call to expand these efforts towards a comprehensive chemical coverage of the druggable human genome was recently announced. But what is the druggable genome? Here, we systematically review structures of proteins bound to drug-like ligands available from the Protein Data Bank (PDB) and use ligand desolvation upon binding as a druggability metric to draw a landscape of the human druggable genome. The vast majority of druggable protein families, including some highly populated and disease-associated families, are almost orphan of small-molecule ligands. We propose a list of 46 druggable domains representing 3440 human proteins that could be the focus of large chemical probe discovery efforts.
Topics: Databases, Protein; Drug Design; Drug Discovery; Genome, Human; Humans; Ligands; Protein Binding; Proteins
PubMed: 32084498
DOI: 10.1016/j.drudis.2020.02.006 -
Phytotherapy Research : PTR Mar 2022The cardioprotective role of naringin has been scientifically well demonstrated in various experimental models such as diabetic cardiomyopathy, ischemic heart diseases,... (Meta-Analysis)
Meta-Analysis Review
The cardioprotective role of naringin has been scientifically well demonstrated in various experimental models such as diabetic cardiomyopathy, ischemic heart diseases, diet-induced cardiac injury, antihypertensive and anti-platelet activities through various mechanisms. However, there is no meta-analysis performed on the cardioprotective activity of naringin. This systematic review and meta-analysis were focused to summarize and conclude the therapeutic benefits of naringin in various cardiovascular disorders using pre-clinical evidence. The online search was performed using electronic databases such as PubMed/Medline, Scopus, ScienceDirect, and Google scholar. The search was mainly focused on the role of naringin in various cardiovascular disorders in experimental animals. Based on the inclusion and exclusion criteria 34 studies were selected. The meta-analysis revealed that naringin could significantly alleviate various physical and chemical stimuli induced cardiovascular disorders such as diabetic cardiomyopathy, ischemic heart diseases, oxidative stress-induced cardiac injury, diet-induced cardiovascular dysfunctions in experimental models involving multiple mechanisms such as antioxidant (ROS/RNS pathways), anti-inflammatory (COX-2, IL-6, TNF-α, NF-κB pathways), enhancing angiogenic factors (VEGF, VCAM, HIF-1α, iNO), suppressing the apoptotic factors (BCL-2, BAX, caspases) and modulation of PCSK-9, PKCα/β, PPAR-α, JAK/STAT, MAPKs (p38α, ERK1/2, JNK), and PI3K/AKT/mTOR/p70S6K associated pathways. Further, these changes at the cellular and molecular levels were manifested as improvement in the structural, functional, and physiology of the heart upon the naringin treatment. In conclusion, this systematic review and meta-analysis support the available scientific evidence on the therapeutic benefits of naringin in the management of various cardiovascular conditions.
Topics: Animals; Flavanones; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases
PubMed: 35084066
DOI: 10.1002/ptr.7368 -
Obesity Reviews : An Official Journal... Jun 2017This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we... (Review)
Review
This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we used the literature search including clinical and animal studies using the Medline and Google Scholar (up to December 2015). Out of 63 screened studies, 17 presented eligibility criteria, such as the use of ursolic acid on adiposity, energy expenditure and skeletal muscle mass in mice and humans. In the literature, we found that several physiological and molecular mechanisms are implicated in the effects of ursolic acid on obesity, energy expenditure, hepatic steatosis, skeletal muscle mass loss and physical fitness, such as (1) increase of thermogenesis by modulation adipocyte transcription factors, activation of 5' adenosine monophosphate-activated protein kinase and overexpression of the uncoupling protein 1 thermogenic marker; (2) enhancement of skeletal muscle mass by activation in bloodstream growth hormone and insulin-like growth factor-1 concentrations secretion, as well as in the activation of mammalian target of rapamycin and inhibition of ring-finger protein-1; and (3) improvement of physical fitness by skeletal muscle proliferator-activated receptor gamma co-activator alpha and sirtuin 1 expression. Therefore, supplementation with ursolic acid may be an adjunctive therapy for prevention and treatment of obesity-mediated and muscle mass-mediated metabolic consequences.
Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Disease Models, Animal; Energy Metabolism; Humans; Muscle, Skeletal; Obesity; Thermogenesis; Transcription Factors; Triterpenes; Uncoupling Protein 1; Ursolic Acid
PubMed: 28335087
DOI: 10.1111/obr.12523 -
American Journal of Physiology.... Apr 2016Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na(+)-K(+)-ATPase (NKA), Na(+)/H(+) exchangers (NHEs), epithelial Na(+) channels (ENaC), and K(+) channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.
Topics: Animals; Epithelial Cells; Epithelial Sodium Channels; Gastrointestinal Absorption; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Ion Transport; Membrane Transport Modulators; Potassium Channels; Signal Transduction; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase
PubMed: 26744474
DOI: 10.1152/ajpgi.00369.2015 -
BMC Immunology Oct 2023This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.
OBJECTIVE
This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.
METHODS
Three databases (PubMed/MEDLINE, Scopus, and Web of Science (WoS)) and reference list of included documents were searched for related observational studies published until 2nd October 2023. To determine the quality of the selected observational studies, the Newcastle-Ottawa Scale (NOS) was used.
RESULTS
After a primary search of three databases, 19492records were appeared. When duplicates and irrelevant documents were removed, 14 articles were found to have eligible criteria. The design of the identified studies was cross-sectional, case-control and cohort. Evidence showed an adverse association between 25(OH)D and the biomarkers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP), Interleukin-1beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor- alfa (TNF-α) during pregnancy. On the contrary, some studies represented that 25(OH)D positively correlated with hs-CRP in the cord blood. One study suggested a direct association between serum concentrations of 25(OH)D and Interleukin-8 (IL-8), macrophage inflammatory protein (MIP), and TNF-α levels in mothers with gestational diabetes mellitus (GDM). A case-control study showed that lower serum concentration of 25(OH)D positively correlated with total antioxidant capacity (TAC) levels in participants.
CONCLUSIONS
Evidence confirmed the supposition of the direct relationship between vitamin D levels and biomarkers with anti-inflammatory and anti-oxidative properties. However, the Existence of inconsistent evidence confirms the need for further studies in mothers with GDM and hypertensive disorders.
PROSPERO REGISTRATION CODE
CRD42020202600.
Topics: Pregnancy; Female; Humans; Vitamin D; Pregnant Women; C-Reactive Protein; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Case-Control Studies; Vitamins; Biomarkers; Inflammation; Interleukin-6; Oxidative Stress
PubMed: 37891486
DOI: 10.1186/s12865-023-00577-w -
Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis.Viruses Mar 2023Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive... (Meta-Analysis)
Meta-Analysis Review
Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.
Topics: Humans; Spike Glycoprotein, Coronavirus; COVID-19; SARS-CoV-2; Mutation; Protein Binding
PubMed: 37112836
DOI: 10.3390/v15040856 -
Journal of Agricultural and Food... Nov 2023Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive dysfunction and behavioral impairment. Salidroside (Sal) is a phenylpropanoid mainly isolated from species with various pharmacological effects. However, the exact anti-AD mechanism of Sal has not been clearly elucidated. This meta-analysis aims to investigate the possible mechanisms by which Sal exerts its anti-AD effects by evaluating behavioral indicators and biochemical characteristics. A total of 20 studies were included, and the results showed that the Sal treatment significantly improved behavior abnormalities in AD animal models. With regard to neurobiochemical indicators, Sal treatment could effectively increase the antioxidant enzyme superoxide dismutase, decrease the oxidative stress indicator malondialdehyde, and decrease the inflammatory indicators interleukin 1β, interleukin 6, and tumor necrosis factor α. Sal treatment was effective in reducing neuropathological indicators, such as amyloid-β levels and the number of apoptotic cells. When the relevant literature on the treatment of rodent AD models is combined with Sal, the therapeutic potential of Sal through multiple mechanisms was confirmed. However, further confirmation by higher quality studies, larger sample sizes, and more comprehensive outcome evaluations in clinical trials is needed in the future.
Topics: Animals; Alzheimer Disease; Neurodegenerative Diseases; Oxidative Stress; Amyloid beta-Peptides; Neuroprotective Agents
PubMed: 37934032
DOI: 10.1021/acs.jafc.3c06672 -
Journal of Cellular Physiology Jul 2022Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the... (Review)
Review
Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the signaling mechanisms that associate with skin/mucosal blistering are being elucidated, specific treatment strategies targeting PV-specific pathomechanisms, particularly kinase signaling, have yet to be established. Hence, the aim of this review was to systematically evaluate molecules in the class of kinases that are essential for acantholysis and blister formation and are therefore candidates for targeted therapy. English articles from PubMed and Scopus databases were searched, and included in vitro, in vivo, and human studies that investigated the role of kinases in PV. We selected studies, extracted data and assessed risk of bias in duplicates and the results were reported according to the methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The risk of bias assessment was performed on in vivo studies utilizing SYRCLE's risk of bias tool. Thirty-five studies were included that satisfied the pathogenicity criterion of kinases in PV, the vast majority being experimental models that used PV sera (n = 13) and PV-IgG (n = 22). Inhibition of kinase activity (p38MAPK, PKC, TK, c-Src, EGFR, ERK, mTOR, BTK, and CDK2) was achieved mostly by pharmacological means. Overall, we found substantial evidence that kinase inhibition reduced PV-associated phosphorylation events and keratinocyte disassociation, prevented acantholysis, and blocked blister formation. However, the scarce adherence to standardized reporting systems and the experimental protocols/models used did limit the internal and external validity of these studies. In summary, this systematic review highlighted the pathogenic intracellular events mediated by kinases in PV acantholysis and presented kinase signaling as a promising avenue for translational research. In particular, the molecules identified and discussed in this study represent potential candidates for the development of mechanism-based interventions in PV.
Topics: Acantholysis; Autoantibodies; Blister; Humans; Immunoglobulin G; Keratinocytes; Pemphigus; Phosphorylation
PubMed: 35616233
DOI: 10.1002/jcp.30784 -
Metabolism: Clinical and Experimental Mar 2017In this systematic review we analyzed studies that assessed serum concentrations of lipopolysaccharide (LPS) and/or lipopolysacharide-binding protein (LBP) in diabetic... (Meta-Analysis)
Meta-Analysis Review
In this systematic review we analyzed studies that assessed serum concentrations of lipopolysaccharide (LPS) and/or lipopolysacharide-binding protein (LBP) in diabetic patients compared with healthy people. Articles were selected using PubMed and Scopus. Search terms used were endotoxemia, endotoxins, LPS, LBP, diabetes mellitus (DM), type 1 (T1DM), type 2 (T2DM), insulin resistance, humans, epidemiologic studies, population-based, survey, representative, cross-sectional, case-control studies, observational, and clinical trials. Two authors independently extracted articles using predefined data fields, including study quality indicators. There was a great variability in the estimates of metabolic endotoxemia among the studies. Most of the studies observed higher LPS or LBP concentrations in diabetic subjects than in healthy controls. T1DM and T2DM subjects presented higher mean fasting LPS of 235.7% and 66.4% compared with non-diabetic subjects, respectively. Advanced complications (e.g. macroalbuminuria) and disease onset exacerbate endotoxemia. Antidiabetic medications decrease fasting LPS concentrations. Among these medications, rosiglitazone and insulin present higher and lower effects, respectively, compared with other treatments. T1DM and T2DM seem to increase metabolic endotoxemia. However, some confounders such as diet, age, medication, smoking and obesity influence both diabetes and endotoxemia manifestation. A better understanding of the interaction of these factors is still needed.
Topics: Acute-Phase Proteins; Carrier Proteins; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Endotoxemia; Humans; Insulin Resistance; Lipopolysaccharides; Membrane Glycoproteins
PubMed: 28183445
DOI: 10.1016/j.metabol.2016.12.009