-
Microvascular Research Nov 2021Cardiovascular health is strongly influenced by diet. The levels of inflammatory factors like ICAM-1 and VCAM-1 are high in patients with atherosclerosis or predisposing...
The association between zinc and endothelial adhesion molecules ICAMs and VCAM-1 and nuclear receptors PPAR-ɑ and PPAR-γ: A systematic review on cell culture, animal and human studies.
BACKGROUND
Cardiovascular health is strongly influenced by diet. The levels of inflammatory factors like ICAM-1 and VCAM-1 are high in patients with atherosclerosis or predisposing factor for heart disease. Antioxidant and anti-inflammatory functions are attributed to zinc. We systematically reviewed cell culture, human or animal studies for determining the relationship between zinc status and ICAMs or VCAM-1 levels.
METHODS
PubMed, Google Scholar, Scopus, and Cochrane databases from database inception till 30th August 2020 were systematically searched to obtain any possible article for inclusion.
RESULTS
After screening and removing unrelated or duplicate articles by the title and abstract by two independent reviewers, 15 articles were included. Results indicating an inverse relationship between zinc status with ICAM-1 or VCAM-1 levels and the development of endothelial inflammation, plaque formation, or atherosclerosis. A direct relationship between zinc status and PPAR-α or γ levels was also observed. Zinc oxide (ZnO), zinc nanoparticles, or ions can cause endothelial activation and increased levels of ICAM-1 and VCAM-1.
CONCLUSION
Normal function of the endothelium is linked with zinc level. Zinc deficiency causes atherosclerosis, most probably via increased production of ICAM-1 and VCAM-1; and decreased expression of PPAR-ɑ and PPAR-γ receptors. Contrarily, endothelial activation and increased ICAM-1 and VCAM-1 levels can be caused by ZnO, zinc nanoparticles, or zinc ions.
Topics: Animals; Atherosclerosis; Cells, Cultured; Disease Models, Animal; Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Metal Nanoparticles; PPAR alpha; PPAR gamma; Signal Transduction; Vascular Cell Adhesion Molecule-1; Zinc; Zinc Oxide
PubMed: 34197877
DOI: 10.1016/j.mvr.2021.104217 -
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 -
Molecules (Basel, Switzerland) Feb 2021For centuries, natural medicines have represented the only option for treating human diseases and, nowadays, plant phytochemicals are considered as promising compounds...
For centuries, natural medicines have represented the only option for treating human diseases and, nowadays, plant phytochemicals are considered as promising compounds to treat or prevent chronic conditions. Among them, hop flowers ( L.), typically used in brewing industries to give the typical aroma and flavor to beer, have attracted particular attention for their health promoting properties. Several studies and human interventional trials have demonstrated the beneficial effects of these molecules on weight gain, lipid metabolism, glucose homeostasis, insulin sensitivities, and inflammation by acting on different targets. All these activities suggest a possible role of bitter hop acid in preventing metabolic syndrome and its related diseases. A systematic quest on PubMed and Scopus databases was performed to identify pre-clinical and clinical studies focusing on this topic. This systematic review summarizes the results obtained by different cell lines, animal models, and human interventional trials to propose -α-acids as medical nutrition therapy to treat or prevent metabolic syndrome and its related disorders as diabetes, dislipidemia inflammation, etc.
Topics: Acids; Beer; Diabetes Mellitus; Flowers; Humans; Humulus; Inflammation; Lipid Metabolism; Metabolic Syndrome; Phytochemicals
PubMed: 33670177
DOI: 10.3390/molecules26040954 -
Obesity Reviews : An Official Journal... Jul 2019Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Recently, some novel compounds have been investigated for the prevention and...
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Recently, some novel compounds have been investigated for the prevention and treatment of NAFLD. Oleoylethanolamide (OEA), an endogenous PPAR-α agonist, has exhibited a plethora of pharmacological properties for the treatment of obesity and other obesity-associated metabolic complications. This systematic review was performed with a focus on the effects of OEA on the risk factors for NAFLD. PubMed, Scopus, Embase, ProQuest, and Google Scholar databases were searched up to December 2018 using relevant keywords. All articles written in English evaluating the effects of OEA on the risk factors for NAFLD were eligible for the review. The evidence reviewed in this article illustrates that OEA regulates multiple biological processes associated with NAFLD, including lipid metabolism, inflammation, oxidative stress, and energy homeostasis through different mechanisms. In summary, many beneficial effects of OEA have led to the understanding that OEA may be an effective therapeutic strategy for the management of NAFLD. Although a wide range of studies have demonstrated the most useful effects of OEA on NAFLD and the associated risk factors, further clinical trials, from both in vivo studies and in vitro experiments, are warranted to verify these outcomes.
Topics: Animals; Dose-Response Relationship, Drug; Endocannabinoids; Humans; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oleic Acids; Peroxisome Proliferator-Activated Receptors; Risk Factors
PubMed: 31111657
DOI: 10.1111/obr.12853 -
Adolescent Psychiatry (Hilversum,... 2023Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This...
BACKGROUND
Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This systematic review evaluated preclinical and clinical research on the effects of CBD on depressive and anxiety disorders in adolescence and young adulthood. To provide context, we discuss CBD's mechanism of action and neurodevelopmental effects.
METHODS
PubMed was searched for articles published through June 2022. Preclinical or clinical CBD administration studies with > 1 that examined depressive and/or anxiety disorders were eligible.
RESULTS
Initially, 224 publications were identified. After excluding duplicates and applying eligibility criteria, 6 preclinical (depression: ≈133; anxiety: ≈161) and 4 clinical (anxiety: =113) articles remained. Due to the low number of studies, results were synthesized qualitatively. The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence were used to rate each study's evidence. The preclinical effects of CBD on depression-like behavior appear to differ by sex, early life stress, and duration of use. Despite no evidence that CBD exerts anxiolytic effects in preclinical adolescent models, CBD may reduce anxiety symptoms in human adolescents and young adults with anxiety disorders.
CONCLUSIONS
The existing evidence suggests that CBD may reduce symptoms of anxiety in adolescents and young adults. However, the evidence is sparse and limited by variations in samples and CBD dosing duration. Further research is needed to understand the potential benefits and/or harms of CBD for depression and anxiety disorders in this population. Implications for clinical practice and research are discussed.
PubMed: 38919887
DOI: 10.2174/0122106766233339230919143924 -
Nutrients Apr 2024Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease... (Meta-Analysis)
Meta-Analysis
Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1β, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.
Topics: Animals; Humans; Antioxidants; Cytochrome P-450 CYP2E1; Cytokines; Disease Models, Animal; Fatty Liver, Alcoholic; Lipid Peroxidation; Liver; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species
PubMed: 38674865
DOI: 10.3390/nu16081174 -
BMC Medicine Feb 2017Raised plasma lipoprotein(a) (Lp(a)) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease. Several types of pharmacological... (Meta-Analysis)
Meta-Analysis Review
Comparison of the effects of fibrates versus statins on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of head-to-head randomized controlled trials.
BACKGROUND
Raised plasma lipoprotein(a) (Lp(a)) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease. Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a) levels. There is suggestive evidence that statins and fibrates, two frequently employed lipid-lowering drugs, can lower plasma Lp(a). The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a) using a meta-analysis of randomized head-to-head trials.
METHODS
Medline and Scopus databases were searched to identify randomized head-to-head comparative trials investigating the efficacy of fibrates versus statins in reducing plasma Lp(a) levels. Meta-analysis was performed using a random-effects model, with inverse variance weighted mean differences (WMDs) and 95% confidence intervals (CIs) as summary statistics. The impact of putative confounders on the estimated effect size was explored using random effects meta-regression.
RESULTS
Sixteen head-to-head comparative trials with a total of 1388 subjects met the eligibility criteria and were selected for this meta-analysis. Meta-analysis revealed a significantly greater effect of fibrates versus statins in reducing plasma Lp(a) concentrations (WMD, -2.70 mg/dL; 95% CI, -4.56 to -0.84; P = 0.004). Combination therapy with fibrates and statins had a significantly greater effect compared with statin monotherapy (WMD, -1.60 mg/dL; 95% CI, -2.93 to -0.26; P = 0.019) but not fibrate monotherapy (WMD, -1.76 mg/dL; 95% CI, -5.44 to +1.92; P = 0.349) in reducing plasma Lp(a) concentrations. The impact of fibrates versus statins in reducing plasma Lp(a) concentrations was not found to be significantly associated with treatment duration (P = 0.788).
CONCLUSIONS
Fibrates have a significantly greater effect in reducing plasma Lp(a) concentrations than statins. Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins.
Topics: Atherosclerosis; Female; Fibric Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoprotein(a); Randomized Controlled Trials as Topic; Risk Factors
PubMed: 28153024
DOI: 10.1186/s12916-017-0787-7 -
Metabolism: Clinical and Experimental Nov 2019Cholesterol efflux is the initial step in the reverse cholesterol transport pathway by which excess cholesterol in peripheral cells is exported and subsequently packaged...
Cholesterol efflux is the initial step in the reverse cholesterol transport pathway by which excess cholesterol in peripheral cells is exported and subsequently packaged into high-density lipoprotein (HDL) particles. Adiponectin is the most abundantly secreted adipokine that possesses anti-inflammatory and vasculoprotective properties via interaction with transmembrane receptors, AdipoR1 and AdipoR2. Evidence suggests that low levels of adiponectin may be a useful marker for atherosclerotic disease. A proposed anti-atherogenic mechanism of adiponectin involves its ability to promote cholesterol efflux. We performed a systematic review of the role of adiponectin in cholesterol efflux and HDL biogenesis, and of the proteins and receptors believed to be implicated in this process. Nineteen eligible studies (7 clinical, 11 fundamental, 1 clinical + fundamental) were identified through Ovid Medline, Ovid Embase, and Pubmed, that support the notion that adiponectin plays a key role in promoting ABCA1-dependent cholesterol efflux and in modulating HDL biogenesis via activation of the PPAR-γ/LXR-α signalling pathways in macrophages. AdipoR1 and AdipoR2 are suggested to also be implicated in this process, however the data are conflicting/insufficient to establish any firm conclusions. Once the exact mechanisms are unravelled, adiponectin may be critical in defining future treatment strategies directed towards increasing HDL functionality and ultimately reducing atherosclerotic disease.
Topics: ATP Binding Cassette Transporter 1; Adiponectin; Animals; Biological Transport; Cholesterol; Humans; Lipoproteins, HDL; Liver; Macrophages; Receptors, Adiponectin
PubMed: 31377319
DOI: 10.1016/j.metabol.2019.153953 -
Cardiovascular Diabetology Mar 2019Using a meta-analysis of randomized controlled trials (RCTs), this study aimed to investigate the efficacy and safety of pemafibrate, a novel selective peroxisome... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Using a meta-analysis of randomized controlled trials (RCTs), this study aimed to investigate the efficacy and safety of pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia.
METHODS
A search was performed using the MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov databases. We decided to employ RCTs to evaluate the effects of pemafibrate on lipid and glucose metabolism-related parameters in patients with dyslipidemia. For statistical analysis, standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were calculated using the random effect model.
RESULTS
Our search yielded seven RCTs (with a total of 1623 patients) that satisfied the eligibility criteria of this study; hence, those studies were incorporated into this meta-analysis. The triglyceride concentration significantly decreased in the pemafibrate group (SMD, - 1.38; 95% CI, - 1.63 to - 1.12; P < 0.001) than in the placebo group, with a reduction effect similar to that exhibited by fenofibrate. Compared with the placebo group, the pemafibrate group also showed improvements in high-density and non-high-density lipoprotein cholesterol levels as well as in homeostasis model assessment for insulin resistance. Furthermore, the pemafibrate group showed a significant decrease in hepatobiliary enzyme activity compared with the placebo and fenofibrate groups; and, total adverse events (AEs) were significantly lower in the pemafibrate group than in the fenofibrate group (OR, 0.60; 95% CI, 0.49-0.73; P < 0.001). In contrast, the low-density lipoprotein cholesterol level was significantly higher in the pemafibrate group than in the placebo (P = 0.006) and fenofibrate (P < 0.001) groups.
CONCLUSIONS
The lipid profile significantly improved in the pemafibrate group than in the placebo group. In addition to the pemafibrate group having an improved lipid profile, which was comparable with that of the fenofibrate group, the AEs were significantly lower than in the fenofibrate group and an improvement in hepatobiliary enzyme activity was also recognized. However, we believe that actual clinical data as well as long-term efficacy and safety need to be investigated in the future.
Topics: Benzoxazoles; Biliary Tract; Biomarkers; Butyrates; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Lipids; Liver; Male; Middle Aged; PPAR alpha; Treatment Outcome
PubMed: 30898163
DOI: 10.1186/s12933-019-0845-x -
Molecular Genetics and Genomics : MGG Feb 2016Peroxisome proliferator-activated receptors (PPARγ), adiponectin (ADIPOQ) and fat mass and obesity-associated gene (FTO) have been reported as a key candidate genes for... (Meta-Analysis)
Meta-Analysis
Peroxisome proliferator-activated receptors (PPARγ), adiponectin (ADIPOQ) and fat mass and obesity-associated gene (FTO) have been reported as a key candidate genes for obesity, type 2 diabetes (T2D) susceptibility and insulin resistance, and we hypothesize that in the background of obesity, the effect of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) variant could potentially influence T2D susceptibility. To decipher a more accurate estimation toward its population-specific impact of these variants toward susceptibility to T2D, a case-control study, systematic review and a meta-analysis was performed in a South Asian population. A case-control analysis of 518 T2D cases and 518 controls of Karnataka origin were performed to analyze the association of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) on the risk of T2D. In addition, a systematic review and meta-analysis for PPARγ2 (rs1801282) and FTO (rs9939609) was elucidated from Asian population. Our investigation showed that PPARγ2 (rs1801282) and FTO (rs9939609) are associated with T2D susceptibility. When T2D cohort was further stratified according to the obesity status, PPARγ2 (rs1801282) and FTO (rs9939609) showed association with T2D only in the obese diabetic group and ADIPOQ (rs16861194) showed no difference in risk of susceptibility to the disease. The meta-analysis of PPARγ2 (rs1801282) showed population-specific association for T2D susceptibility as opposed to FTO (rs9939609) which showed no difference in population effect toward T2D susceptibility. In conclusion, our study showed that PPARγ2 (rs1801282) and FTO (rs9939609) variants are associated with T2D susceptibility when associated with adiposity in Indian population.
Topics: Adiponectin; Adiposity; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Asian People; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Humans; India; Male; Middle Aged; Obesity; PPAR gamma; Polymorphism, Single Nucleotide; Proteins
PubMed: 26243686
DOI: 10.1007/s00438-015-1097-4