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Neurology India 2018Sepsis is a leading cause of death in medical and surgical intensive care units (ICUs). Disturbance of consciousness of varying severity is an early warning sign of... (Review)
Review
Sepsis is a leading cause of death in medical and surgical intensive care units (ICUs). Disturbance of consciousness of varying severity is an early warning sign of developing sepsis in the majority of cases. Sepsis-associated encephalopathy (SAE) is the most frequent type of encephalopathy in the ICU and is defined as a state of diffuse cerebral dysfunction caused by the inflammatory response of the body to various infections, where the inflammatory process does not affect the central nervous system (CNS) directly and the primary symptom is a disturbed level of consciousness. The aim of this comprehensive review was to collect the latest scientific knowledge regarding the epidemiology, clinical aspects, pathogenesis, diagnosis, and possible prevention strategies related to SAE.
Topics: Blood-Brain Barrier; Critical Care; Cytokines; Humans; Incidence; Mitochondrial Diseases; Oxidative Stress; Sepsis-Associated Encephalopathy
PubMed: 29547154
DOI: 10.4103/0028-3886.227299 -
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 -
Acta Histochemica Jan 2023Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral... (Review)
Review
OBJECTIVES
Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family. Although EMP2 expression has been investigated in several diseases, much remains unknown regarding its mechanism of action and the extent of its role in pathogenesis. Our aim was to perform a systematic review on the involvement of EMP2 in disease processes and the current usage of anti-EMP2 therapies.
METHODS
A Boolean search of the English-language medical literature was performed. PubMed, Scopus, Cochrane, and Web of Science were used to identify relevant citations. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
52 studies met the inclusion criteria for qualitative analysis. Of those, 28 (53.8%) were human-only studies, 11 (21.2%) were animal-only studies, and 13 (25%) studies included both human and animal models. Furthermore, 34 (65.4%) studies focused on EMP2's role in neoplasms, while the remaining 18 (34.6%) articles evaluated its role in other pathologies.
CONCLUSION
Overall, the evidence suggests the mechanisms of action of EMP2 are context dependent. Promising results have been produced by utilizing EMP2 as a biomarker and therapeutic target. More studies are warranted to better understand the mechanism and comprehend the role of EMP2 in the pathogenesis of diseases.
Topics: Animals; Humans; Membrane Glycoproteins; Membrane Proteins
PubMed: 36455339
DOI: 10.1016/j.acthis.2022.151976 -
Nutrition Journal Oct 2023The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines,... (Meta-Analysis)
Meta-Analysis Review
The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis.
BACKGROUND
The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease.
METHODS
Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods.
RESULTS
A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group.
CONCLUSION
Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance.
PROSPERO REGISTERATION COD
CRD42023426374.
Topics: Humans; Dietary Supplements; Leptin; Cytokines; Linoleic Acids, Conjugated; Interleukin-6; Adipokines; Cardiovascular Diseases; Glycemic Control; Malondialdehyde; Liver; Blood Glucose
PubMed: 37794481
DOI: 10.1186/s12937-023-00876-3 -
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 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 -
Nutrients May 2020Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans...
Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans and different animal species through a systematic review following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In humans, dietary histidine may be associated with factors that improve metabolic syndrome and has an effect on ion absorption. In rats, histidine supplementation increases food intake. It also provides neuroprotection at an early stage and could protect against epileptic seizures. In chickens, histidine is particularly important as a limiting factor for carnosine synthesis, which has strong anti-oxidant effects. In fish, dietary histidine may be one of the most important factors in preventing cataracts. In ruminants, histidine is a limiting factor for milk protein synthesis and could be the first limiting AA for growth. In excess, histidine supplementation can be responsible for eating and memory disorders in humans and can induce growth retardation and metabolic dysfunction in most species. To conclude, the requirements for histidine, like for other EAA, have been derived from growth and AA composition in tissues and also have specific metabolic roles depending on species and dietary levels.
Topics: Animals; Chickens; Dietary Supplements; Eating; Fishes; Gastrointestinal Absorption; Histidine; Humans; Rats; Ruminants
PubMed: 32423010
DOI: 10.3390/nu12051414 -
Journal of Nippon Medical School =... 2018Epigenetic inactivation of tumor suppressor genes is an important molecular mechanism in the formation and development of human tumors. The purpose of our study was to... (Review)
Review
BACKGROUND/AIM
Epigenetic inactivation of tumor suppressor genes is an important molecular mechanism in the formation and development of human tumors. The purpose of our study was to evaluate the correlation between the methylation level of the secreted frizzled-related protein 1 (SFRP1) gene and the risk of renal cell carcinoma (RCC).
METHODS
The relevant literature was searched in detail in several electronic databases. The methodological heterogeneity was analyzed by meta-regression and subgroup analyses. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to summarize the dichotomous outcomes of our meta-analysis.
RESULTS
The ten included articles contained 535 RCC samples and 475 normal controls. The results demonstrated that the methylation level of the SFRP1 promoter region was significantly correlated with an increased incidence of RCC (OR=13.72; 95% CI: 6.01-31.28; P=0.000). Furthermore, the eligible studies that had sufficient clinical data about the RCC cases were included in the analysis, and the results indicated that the frequency of SFRP1 promoter methylation was associated with a higher histological grade (P=0.000), tumor stage (P=0.033), tumor size (≥5 cm; P=0.029), and distant metastasis (P=0.047).
CONCLUSION
Our results indicate that the methylation level of the SFRP1 promoter region is increased in patients with RCC compared to normal controls and might be involved in the occurrence and development of RCC. Additional well-designed studies are needed to further verify our conclusions.
Topics: Carcinoma, Renal Cell; Confidence Intervals; Humans; Incidence; Intercellular Signaling Peptides and Proteins; Kidney Neoplasms; Membrane Proteins; Meta-Analysis as Topic; Methylation; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Promoter Regions, Genetic; Risk
PubMed: 29731501
DOI: 10.1272/jnms.2018_85-13 -
The American Journal of Clinical... Aug 2023Serving whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly... (Meta-Analysis)
Meta-Analysis
Whey Protein Premeal Lowers Postprandial Glucose Concentrations in Adults Compared with Water-The Effect of Timing, Dose, and Metabolic Status: a Systematic Review and Meta-analysis.
BACKGROUND
Serving whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly understood but may involve stimulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin secretion together with a slower gastric emptying rate.
OBJECTIVES
The objective of this systematic review and meta-analysis was to review all randomized clinical trials investigating premeals with whey protein in comparison with a nonactive comparator (control) that evaluated plasma glucose, GLP-1, GIP, insulin, and/or gastric emptying rate. Secondary aims included subgroup analyses on the timing and dose of the premeal together with the metabolic state of the participants [lean, obese, and type 2 diabetes mellitus (T2DM)].
METHODS
We searched EMBASE, CENTRAL, PUBMED, and clinicaltrials.gov and found 16 randomized crossover trials with a total of 244 individuals. The last search was performed on 9 August, 2022.
RESULTS
Whey protein premeals lowered peak glucose concentration by -1.4 mmol/L [-1.9 mmol/L; -0.9 mmol/L], and the area under the curve for glucose was -0.9 standard deviation (SD) [-1.2 SD; -0.6 SD] compared with controls (high certainty). In association with these findings, whey protein premeals elevated GLP-1 (low certainty) and peak insulin (high certainty) concentrations and slowed gastric emptying rate (high certainty) compared with controls. Subgroup analyses showed a more pronounced and prolonged glucose-lowering effect in individuals with T2DM compared with participants without T2DM. The available evidence did not elucidate the role of GIP. The protein dose used varied between 4 and 55 g, and meta-regression analysis showed that the protein dose correlated with the glucose-lowering effects.
CONCLUSIONS
In conclusion, whey protein premeals lower postprandial blood glucose, reduce gastric emptying rate, and increase peak insulin. In addition, whey protein premeals may elevate plasma concentrations of GLP-1. Whey protein premeals may possess clinical potential, but the long-term effects await future clinical trials.
Topics: Humans; Adult; Whey Proteins; Glucagon; Blood Glucose; Diabetes Mellitus, Type 2; Water; Insulin; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide; Glucose; Gastric Emptying; Postprandial Period
PubMed: 37536867
DOI: 10.1016/j.ajcnut.2023.05.012