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Clinical Nutrition ESPEN Apr 2022Diabetes mellitus is one of the most important life-threatening metabolic diseases of the 21st century. The use of complementary and alternative medicine in diabetic...
BACKGROUND AND AIMS
Diabetes mellitus is one of the most important life-threatening metabolic diseases of the 21st century. The use of complementary and alternative medicine in diabetic patients seems to be increasing. Saffron, a valuable herbal medicine, has several pharmacological properties such as anti-oxidant effect, which can play important role in ameliorating the complications of diabetes. The aim of this study was to systematically review the therapeutic effects of saffron and its bioactive components on oxidative stress in diabetes mellitus.
METHODS
In this systematic review, databases such as PubMed, SCOPUS, Embase, ProQuest, and Web of Sciences were searched from the beginning to December 2021. All eligible in vitro, animal, and human studies that examined the effect of saffron on oxidative stress indices in diabetes were prepared in the form of a full article in English.
RESULTS
In the end, only 31of the 389 articles met the criteria for analysis. Of the 31 articles, 4 were in-vitro studies, 25 were animal studies, and 2 were clinical trials studies. Saffron supplementation may activate insulin receptor substrate 1 (IRS1) and peroxisome proliferator-activated receptor gamma (PPAR-γ), which can improve hyperglycemia and insulin transduction signal in adipose tissue, and regulate glucose metabolism, leading to an increased nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1 expression, amelioration of mitochondrial function, and an increased levels of antioxidant enzymes.
CONCLUSION
Most studies have shown that saffron supplementation significantly enhanced the production and activity of antioxidant enzymes and decreased oxidative stress indices in diabetes mellitus. However, human pharmacokinetic and more accurate clinical trial studies are needed to determine dose ranges and the exact mechanisms of action of saffron and its active components in diabetes.
Topics: Animals; Antioxidants; Crocus; Diabetes Mellitus; Humans; Oxidative Stress; Plant Extracts
PubMed: 35331485
DOI: 10.1016/j.clnesp.2022.01.022 -
Frontiers in Physiology 2022Blood flow restriction (BFR) exercise may be a potential exercise program to promote angiogenesis. This review aims to compare the effects of exercise with and without...
BACKGROUND
Blood flow restriction (BFR) exercise may be a potential exercise program to promote angiogenesis. This review aims to compare the effects of exercise with and without BFR on angiogenesis-related factors in skeletal muscle among healthy adults.
METHODOLOGY
Searches were made in Web of Science, Scopus, PubMed, and EBSCO databases from January 2001 to June 2021. Studies were screened, quality was evaluated, and data were extracted. The review protocol was registered at PROSPERO (PROSPERO registration number: CRD42021261367). Standardized mean differences (SMD) of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptorγcoactivator-1α (PGC-1α) and endothelial nitric oxide synthase (eNOS) were analyzed using Revman 5.4 software with a 95% confidence interval (95% CI).
RESULTS
Ten studies fulfilled the inclusion criteria with a total of 75 participants for BFR group and 77 for CON group. BFR exercise elicits greater expression of VEGF (heterogeneity test, = 0.09, I = 44%; SMD, 0.93 [0.38, 1.48], < 0.05), VEGFR-2 (heterogeneity test, = 0.81, I = 0%; SMD, 0.64 [0.08, 1.21], < 0.05), HIF-1α (heterogeneity test, = 0.67, I = 0%; SMD, 0.43 [0.03, 0.82], < 0.05), PGC-1α (heterogeneity test, = 0.02, I = 54%; SMD, 0.74 [0.21, 1.28], < 0.05) and eNOS (heterogeneity test, = 0.88, I = 0%; SMD, 0.60 [0.04, 1.17], < 0.05) mRNA than non-BFR exercise. In the sub-group analysis, resistance exercise with BFR elicits greater expression of VEGF (heterogeneity test, = 0.36, I = 6%; SMD, 1.66 [0.97, 2.35], < 0.05) and HIF-1α (heterogeneity test, = 0.56, I = 0%; SMD, 0.51 [0.01, 1.02], < 0.05) mRNA than aerobic exercise with BFR.
CONCLUSION
Exercise with BFR elicited more angiogenesis-related factors mRNA expression than exercise without BFR, but not VEGF and PGC-1α protein expression. Therefore, BFR training may be a potential training program to improve vascular function.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021261367].
PubMed: 35250618
DOI: 10.3389/fphys.2022.814965 -
Inflammation Research : Official... Mar 2022Ischemia-reperfusion injury (IRI) is the inexplicable aggravation of cellular dysfunction that results in blood flow restoration to previously ischemic tissues. COX... (Review)
Review
INTRODUCTION
Ischemia-reperfusion injury (IRI) is the inexplicable aggravation of cellular dysfunction that results in blood flow restoration to previously ischemic tissues. COX mediates the oxidative conversion of AA to various prostaglandins and thromboxanes, which are involved in various physiological and pathological processes. In the pathophysiology of I/R injuries, COX has been found to play an important role. I/R injuries affect most vital organs and are characterized by inflammation, oxidative stress, cell death, and apoptosis, leading to morbidity and mortality.
MATERIALS AND METHODS
A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the Cyclooxygenase modulations in ischemic injury. Here, we have discussed the COX Physiology and downstream signalling pathways modulated by COX, e.g., Camp Pathway, Peroxisome Proliferator-Activated Receptor Activity, NF-kB Signalling, PI3K/Akt Signalling in ischemic injury.
CONCLUSION
This review will discuss the various COX types, specifically COX-1 and COX-2, which are involved in developing I/R injury in organs such as the brain, spinal cord, heart, kidney, liver, and intestine.
Topics: Cyclooxygenase 2; Cyclooxygenase Inhibitors; Humans; Phosphatidylinositol 3-Kinases; Prostaglandins; Reperfusion Injury
PubMed: 35175358
DOI: 10.1007/s00011-022-01546-6 -
Brain Sciences Jan 2022Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents,... (Review)
Review
Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA's role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy.
PubMed: 35053844
DOI: 10.3390/brainsci12010101 -
The Lancet. Gastroenterology &... Apr 2022There are no licensed treatments for non-alcoholic fatty liver disease (NAFLD), but three different classes of antihyperglycaemic drugs-peroxisome proliferator-activated... (Review)
Review
Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review.
There are no licensed treatments for non-alcoholic fatty liver disease (NAFLD), but three different classes of antihyperglycaemic drugs-peroxisome proliferator-activated receptor (PPAR) agonists, glucagon-like peptide-1 receptor (GLP-1R) agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors-show promise in the treatment of the disease. We did a systematic review of randomised controlled trials examining the efficacy of PPAR agonists, GLP-1R agonists, or SGLT2 inhibitors for specifically treating NAFLD in adults with or without type 2 diabetes. A total of 25 active-controlled or placebo-controlled trials met our inclusion criteria: eight for PPAR agonists, ten for GLP-1R agonists, and seven for SGLT2 inhibitors. 2597 individuals (1376 [53%] men vs 1221 [47%] women; mean age 52 years (SD 6); mean BMI 32 kg/m (SD 3); 1610 [62%] with type 2 diabetes) were included. Pioglitazone, lanifibranor, and GLP1-R agonists (mostly liraglutide and semaglutide) improved individual histological features of NASH (ie, steatosis, ballooning, lobular inflammation) or achieved resolution of NASH without worsening of fibrosis. SGLT2 inhibitors (mostly empagliflozin and dapagliflozin) reduced liver fat content, as assessed by magnetic resonance-based techniques.
Topics: Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35030323
DOI: 10.1016/S2468-1253(21)00261-2 -
Critical Reviews in Toxicology Aug 2021Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in...
Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in alteration of homeostasis, reproductive, and developmental, and immune system impairments. The immunotoxicity of EDCs involves many mechanisms altering gene expression that depend on the activation of nuclear receptors such as the aryl hydrocarbon receptor (AHR), the estrogen receptor (ER), and the peroxisome proliferator-activated receptor (PPAR), which also results in skin and intestinal disorders, microbiota alterations and inflammatory diseases. This systematic review aims to review different mechanisms of immunotoxicity and immunomodulation of T cells, focusing on T regulatory (Treg) and Th17 subsets, B cells, and dendritic cells (DCs) caused by specific EDCs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), bisphenols (BPs) and polyfluoroalkyl substances (PFASs). To achieve this objective, a systematic study was conducted searching various databases including PubMed and Scopus to find , , and biomonitoring studies that examine EDC-dependent mechanisms of immunotoxicity. While doing the systematic review, we found species- and cell-specific outcomes and a translational gap between and experiments. Finally, an adverse outcome pathway (AOP) framework is proposed, which explains mechanistically toxicity endpoints emerging from different EDCs having similar key events and can help to improve our understanding of EDCs mechanisms of immunotoxicity. In conclusion, this review provides insights into the mechanisms of immunotoxicity mediated by EDCs and will help to improve human health risk assessment.
Topics: Endocrine Disruptors; Humans; Immune System; Polychlorinated Dibenzodioxins; Receptors, Estrogen
PubMed: 35015608
DOI: 10.1080/10408444.2021.2009438 -
Journal of Gastrointestinal Surgery :... Feb 2022The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may...
BACKGROUND
The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may regulate its expression and whether obese patients have changes in adipose tissue expression of PPAR-γor potential regulators such as miR-27. Thus, our aims were to analyze PPAR-γ and miR-27 expression in adipose tissue of obese patients, and to correlate their levels with clinical variables.
SUBJECTS AND METHODS
We included 43 morbidly obese subjects who underwent sleeve gastrectomy (31 of them completed 1-year follow-up) and 19 non-obese subjects. mRNA expression of PPAR-γ1 and PPAR-γ2, miR-27a, and miR-27b was measured by qPCR in visceral and subcutaneous adipose tissue. Clinical variables and serum adipokine and hormone levels were correlated with PPAR-γ and miR-27 expression. In addition, a systematic review of the literature regarding PPAR-γ expression in adipose tissue of obese patients was performed.
RESULTS
We found no differences in the expression of PPAR-γ and miR-27 in adipose tissue of obese patients vs. controls. The literature review revealed discrepant results regarding PPAR-γ expression in adipose tissue of obese patients. Of note, we described a significant negative correlation between pre-operative PPAR-γ1 expression in adipose tissue of obese patients and post-operative weight loss, potentially linked with insulin resistance markers.
CONCLUSION
PPAR-γ1 expression in adipose tissue is associated with weight loss after sleeve gastrectomy and may be used as a biomarker for response to surgery.
Topics: Adipose Tissue; Gastrectomy; Gene Expression; Humans; MicroRNAs; Obesity, Morbid; PPAR gamma; Peroxisome Proliferator-Activated Receptors; Weight Loss
PubMed: 34882294
DOI: 10.1007/s11605-021-05216-6 -
Oxidative Medicine and Cellular... 2021() and its ingredients (IFP) have a variety of biological activities and are widely used to treat osteoporosis (OP). Herein, we conducted a systematic review to... (Meta-Analysis)
Meta-Analysis
Antiosteoporosis Effect and Possible Mechanisms of the Ingredients of Fructus Psoraleae in Animal Models of Osteoporosis: A Preclinical Systematic Review and Meta-Analysis.
OBJECTIVE
() and its ingredients (IFP) have a variety of biological activities and are widely used to treat osteoporosis (OP). Herein, we conducted a systematic review to evaluate the efficacy of IFP for an animal model of OP from the current literatures. Potential mechanisms of IFP in the treatment of OP were also summarized.
MATERIALS AND METHODS
We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang, Web of Science, Chinese Biomedical Literature Database, and Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to June 2021. The inclusion criteria were animal studies that assessed the efficacy and safety of IFP for OP, regardless of publication status or language. The exclusion criteria included (1) other types of studies (in vitro studies, case reports, clinical trials, reviews, abstracts, comments, and editorials), (2) combination with other compounds, (3) compared with other traditional Chinese medicine, (4) not osteoporosis or bone loss model, (5) studies with insufficient data, (6) lack of a control group, and (7) duplicate publications. The modified Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-item quality checklist was used to evaluate the risk of bias of included studies. We computed the relative risk (RR) and the standard mean difference (SMD) for dichotomous outcomes and continuous outcomes, respectively. When heterogeneity was detected or there was significant statistical heterogeneity ( < 0.05 or > 50%), a random-effects model was employed, followed by further subgroup analysis and metaregression estimations to ascertain the origins of heterogeneity. Otherwise, we used a fixed-effects model ( ≥ 0.05 or ≤ 50%). The primary outcome measures were bone mineral density (BMD), serum osteocalcin(S-OCN), bone volume over total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone maximum load, and elasticity modulus. The secondary outcome measure was the antiosteoporosis mechanisms of IFP. The STATA 12.0 software was used to analyze the data.
RESULTS
Overall, 16 studies focusing on 379 animals were enrolled into the study. The risk of bias score of included studies ranged from 4 to 7 with an average score of 5.25. The present study provided the preliminary preclinical evidence that administration of IFP could significantly increase the S-OCN, BMD, BV/TV, and Tb.N while Tb.Th and Tb.Sp were remarkably decreased by IFP in OP model animals ( < 0.05). Moreover, IFP could significantly improve the bone biomechanical indicator bone maximum load and elasticity modulus ( < 0.05). In terms of the possible mechanisms of treatment of OP, IFP exerts anti-OP effects in animal models probably through osteoprotegerin/receptor activator of the nuclear factor-B ligand/receptor activator of nuclear factor-B (OPG/RANKL/RANK), peroxisome proliferator activated receptor (PPAR-)/Axin2/Wnt, antioxidative stress via forkhead box O3a (FoxO3a)/Axin2/Wnt, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), estrogen-like effect, and gamma-aminobutyric acid/gamma-aminobutyric acid receptor (GABA/GABARI) signaling pathway.
CONCLUSION
Taken together, the findings suggest the possibility of developing IFP as a drug or an ingredient in diet for the clinical treatment of OP. We recommend that rigorous, as well as high-quality, trials involving large sample sizes should be conducted to confirm our findings.
Topics: Animals; Fruit; Medicine, Chinese Traditional; Osteoporosis
PubMed: 34868453
DOI: 10.1155/2021/2098820 -
Frontiers in Endocrinology 2021Per- or polyfluoroalkyl substances (PFAS), a family of synthetic polyfluorinated compounds, are widely used in consumer products. Ubiquitous exposures to PFAS, in...
Per- or polyfluoroalkyl substances (PFAS), a family of synthetic polyfluorinated compounds, are widely used in consumer products. Ubiquitous exposures to PFAS, in consideration of their persistence, bioaccumulation potential, and toxicities have led to concerns regarding possible harmful effects during critical periods of development in early-life and long-term consequences on health. The potential effects of PFAS depend on various factors including the type of PFAS and the timing and level of exposure. We performed a systematic review of the epidemiologic literature to assess the effects of early-life PFAS exposure on prenatal and postnatal growth, adiposity, and puberty in children and adolescents. For birth size, most studies indicated that prenatal PFAS exposure, in particular long-chain PFAS, may impair fetal growth, albeit some reports of null associations with maternal PFAS. For growth within 2 years of age, prenatal PFAS exposure showed no associations with height and either null or negative associations with weight. However, postnatal PFAS exposures were inversely related to height and weight at 2 years in a cross-sectional study. For postnatal adiposity, prenatal PFAS may mostly have negative associations with body mass index in the first 2 years of life, but positive relationships with adiposity in childhood and adolescence, although some studies showed null associations. For puberty, the evidence for associations between early-life PFAS exposure and pubertal development or sex hormone levels were limited and inconclusive. From experimental studies, plausible mechanisms through which PFAS may affect early-life growth and puberty include PFAS-induced activation of peroxisome proliferator-activated receptor, alterations of thyroid or steroid hormone synthesis and metabolism, and their weak estrogenic or anti-androgenic properties. Although the published literature suggests possible effects of PFAS exposures on early-life growth, adiposity, and puberty, current human evidence is limited in establishing PFAS-induced effects on early-life physical development. Further investigation is warranted to clarify PFAS-induced effects on growth and physical development in consideration of the critical time-window of exposure, concomitant exposure to chemical mixtures including various PFAS types, and possible non-monotonic dose-response relationship for growth and adiposity trajectories.
Topics: Adiposity; Alkanesulfonic Acids; Carboxylic Acids; Child; Child Development; Environmental Exposure; Environmental Pollutants; Fetal Development; Fluorocarbons; Gonadal Steroid Hormones; Humans; Puberty
PubMed: 34566884
DOI: 10.3389/fendo.2021.683297 -
Clinical Journal of Gastroenterology Dec 2021Dyslipidemia is a very common medical disorder affecting nearly 33.5% of US adults over 20 years of age. It represents the major risk factor for non-alcoholic fatty... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dyslipidemia is a very common medical disorder affecting nearly 33.5% of US adults over 20 years of age. It represents the major risk factor for non-alcoholic fatty liver (NAFLD) and cardiovascular diseases, which is the most common cause of death worldwide. Elafibranor is a peroxisome proliferator-activated receptor (PPAR) alpha and delta dual agonist. A novel dual peroxisome proliferator-activated receptor alpha/delta (PPAR-α/δ), elafibranor, the agonist is an emerging therapy with promising hepatoprotective results.
OBJECTIVES
To estimate the efficacy of elafibranor in patients with liver abnormalities especially non-alcoholic steatohepatitis (NASH).
METHODS
We searched the following databases: PubMed, SCOPUS, Web of Science, and Cochrane Library for relevant clinical trials assessing the use of silymarin in patients with NAFLD. Risk of bias assessment was performed using Cochrane's risk of bias tool. We included the following outcomes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), HOMA-IR, total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C).
RESULTS
We included four clinical trials. We found that elafibranor significantly reduced the levels of ALT {MD = - 4.60 [- 8.17, - 1.04], (P = 0.01)}, GGT {MD = - 16.57 [- 26.59, - 6.56], (P < 0.01)}, TC {MD = - 0.37 [- 0.66, - 0.08], (P = 0.01)}, TG {MD = - 0.37 [- 0.51, - 0.24], (P < 0.01)}, ALP {(MD = - 14.45 [- 18.99, - 9.91], (P < 0.01)}, and LDL {MD = - 0.20 [- 0.33, - 0.07], (P = 0.003)}. There was no significant difference regarding HOMA-IR {MD = - 0.32 [- 0.88, 0.24], (P = 0.26) and AST (P = 0.53).
CONCLUSION
PPAR-alpha/delta dual agonist, elafibranor, is a promising drug that improves most metabolic parameters in dyslipidemic patients.
Topics: Adult; Chalcones; Humans; Non-alcoholic Fatty Liver Disease; Propionates
PubMed: 34370218
DOI: 10.1007/s12328-021-01491-7