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Background and Aim: Mucopolysaccharidosis type III (MPS III) is a rare autosomal recessive lysosomal storage disease (LSD) caused by a deficiency of lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs), mainly in the central nervous system. Trehalose has been proposed as a potential therapeutic agent to attenuate neuropathology in MPS III. We conducted a single-arm, open-label study to evaluate the efficacy of trehalose treatment in patients with MPS IIIA and MPS IIIB. Methods: Five patients with MPS III were enrolled. Trehalose was administrated intravenously (15 g/week) for 12 weeks. Health-related quality of life and cognitive function, serum biomarkers, liver, spleen, and lung imaging were assessed to evaluate trehalose efficacy at baseline and trial end (week 12). Results: TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients, and the mean scores for quality of life were increased after the intervention. Serum GAG levels were reduced in all treated patients (however, the differences were not statistically significant). Alanine aminotransferase (ALT) levels were reduced in all patients post-treatment (p=0.0039). The mean levels of aspartate transaminase (AST) were also decreased after 12 weeks of treatment with Trehalose. Decreased serum pro-oxidant-antioxidant balance and increased GPX activity were observed at the end of the study. Decreases in mean splenic length were observed, whereas the liver volume did not change. Conclusion: Improvements in health-related quality of life and serum biomarkers (GAGs, liver aminotransferase levels, antioxidant status), as well as liver and spleen size, were found following 3 months of trehalose administration in patients with MPS IIIA and MPS IIIB.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of newly introduced antidiabetic drugs with potent hypoglycemic effects. Recent evidence suggests that these drugs have extraglycemic impacts and are therefore able to provide additional benefits beyond glucose lowering. Mitochondrial dysfunction is a central facet of many disorders that negatively impacts many tissues and organs, especially in the setting of diabetes. Therefore, it would be hugely beneficial if an antidiabetic drug could also provide mitochondrial benefits to improve cellular function and reduce the risk of diabetic complications. In this review, we have surveyed the literature for possible mitochondrial benefits of SGLT2is and we discuss the possible mechanisms involved., EXCLI Journal; 22:Doc53; ISSN 1611-2156

Diabetic patients are at higher risk of liver dysfunction compared with the normal population. Thus, using hypoglycemic agents to improve liver efficiency is important in these patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are newly developed antidiabetic drugs with potent glucose-lowering effects. However, recent limited evidence suggests that they have extra-glycemic benefits and may be able to exert protective effects on the liver. Hence, these drugs could serve as promising pharmacological agents with multiple benefits against different hepatic disorders. In this review, the current knowledge about the possible effects of SGLT2 inhibitors on different forms of liver complications and possible underlying mechanisms are discussed., EXCLI Journal; 22:Doc403; ISSN 1611-2156

Poor cognitive ability is a consequence of a wide variety of neurobehavioral disorders and is a growing health problem, especially among the elderly and patients with diabetes. The precise underlying cause of this complication is not well-defined. However, recent studies have highlighted the possible role of insulin hormone signaling in brain tissue. Insulin is a metabolic peptide integral to whole body energy homeostasis; it does, however, have extrametabolic impacts, such as upon neuronal circuits. Therefore, it has been suggested that insulin signaling may modify cognitive ability by yet unknown pathways. In the current review, we discuss the cognitive role of brain insulin signaling and consider the possible links between brain insulin signaling and cognitive ability., EXCLI Journal; 22:Doc237; ISSN 1611-2156

Background: Cyclodextrins (CDs) are commonly used host molecules of inclusion complex. However, due to the lack of a sensitive determination method, the absorption process of CDs remains unclear. Objective: In this study, an oleuropein (OL) inclusion complex employing hydroxylpropyl-betacyclodextrin (HP-beta-CD) as host molecules was prepared and the formation of inclusion complex was ascertained by FT-IR and DSC. Spectrophotometry was established for the determination of HP-beta-CD, based on the fact that the absorbance of phenolphthalein (PP) decreased in the presence of HP-beta-CD. Methods: The assay conditions were optimized to augment the method sensitivity. Molecular docking was employed to verify the strong interaction between PP and HP-beta-CD. The permeation process of free HP-beta-CD, HP-beta-CD of OL inclusion complex, free OL, and OL in the inclusion complex, was examined using an in vitro mouse small intestine model. Results: Though HP-beta-CD possessed a hydrophilic outside shell, it could permeate through the mouse small intestine quickly with a cumulative permeating amount of over 90% in 2 h. Free HPbeta- CD, the host molecule HP-beta-CD, and guest molecule OL of the inclusion complex exhibited consistent permeating profiles across the mouse small intestine. Conclusion: The approach for the determination of HP-beta-CD was accurate and precise (%RSD=2.98).

Introduction Statins are known to lower CRP, and this reduction has been suggested to contribute to the established efficacy of these drugs in reducing cardiovascular events and outcomes. However, the exact mechanism underlying the CRP-lowering effect of statins remains elusive. Methods In order to test the possibility of direct interaction, we performed an in silico study by testing the orientation of the respective ligands (statins) and phosphorylcholine (the standard ligand of CRP) in the CRP active site using Molecular Operating Environment (MOE) software. Results Docking experiments showed that all statins could directly interact with CRP. Among statins, rosuvastatin had the strongest interaction with CRP (pKi = 16.14), followed by fluvastatin (pKi = 15.58), pitavastatin (pKi = 15.26), atorvastatin (pKi = 14.68), pravastatin (pKi = 13.95), simvastatin (pKi = 7.98) and lovastatin (pKi = 7.10). According to the above-mentioned results, rosuvastatin, fluvastatin, pitavastatin and atorvastatin were found to have stronger binding to CRP compared with the standard ligand phosphocholine (pKi = 14.55). Conclusions This finding suggests a new mechanism of interaction between statins and CRP that could be independent of the putative cholesterol-lowering activity of statins.

Obesity remains a pervasive health concern worldwide with concomitant comorbidities such as cardiovascular diseases, diabetes, inflammation, and other metabolic disorders. A wealth of data validates dietary and lifestyle modifications such as restricting caloric intake and increasing physical activity to slow the obesity development. Recently, the advent of phytochemicals such as curcumin, the active ingredient in turmeric, has attracted considerable research interest in tracking down their possible effects in protection against obesity and obesity-related comorbidities. According to the existing literature, curcumin may regulate lipid metabolism and suppress chronic inflammation interacting with white adipose tissue, which plays a central role in the complications associated with obesity. Curcumin also inhibits the differentiation of adipocyte and improves antioxidant properties. In the present review, we sought to deliberate the possible effects of curcumin in downregulating obesity and curtailing the adverse health effects of obesity.

Background. Elevated serum low-density lipoproteins (LDL), the substrate for the formation of atherogenic oxidized LDLs (oxLDL), are a causal factor for atherosclerotic cardiovascular disease (ASCVD). Statins are well known to decrease LDL particle concentration and reduce ASCVD morbidity and mortality. Objective. To perform a meta-analysis of the effects of statins (i.e., type, dose, and duration of treatment) on serum levels of oxLDL and on immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels against oxLDL. Methods. PubMed, Scopus, Embase, and Web of Science were searched up to February 5th, 2021, for randomized controlled trials (RCT) evaluating the effect of statins on oxLDL and anti-oxLDL antibody levels. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. To evaluate the influence of each study on the overall effect size, a sensitivity analysis was performed using the leave-one-out method. Evaluation of the funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests was used to assess the presence of publication bias in the meta-analysis. Results. A total of 28 RCTs including 4019 subjects were finally included in the meta-analysis. The results indicated a significant decrease in circulating concentrations of oxLDL after treatment with statins (SMD: -2.150, 95% CI: -2.640, -1.697, p

Cancer is a leading cause of death and disability worldwide. Epigenetic deregulation is one of the most critical mechanisms in carcinogenesis and can be classified into effects on DNA methylation and histone modification. MicroRNAs are small noncoding RNAs involved in fine-tuning their target genes after transcription. Various microRNAs control the expression of histone modifiers and are involved in a variety of cancers. Therefore, overexpression or downregulation of microRNAs can alter cell fate and cause malignancies. In this review, we discuss the role of microRNAs in regulating the histone modification machinery in various cancers, with a focus on the histone-modifying enzymes such as acetylases, deacetylases, methyltransferases, demethylases, kinases, phosphatases, desumoylases, ubiquitinases, and deubiquitinases. Understanding of microRNA-related aberrations underlying histone modifiers in pathogenesis of different cancers can help identify novel therapeutic targets or early detection approaches that allow better management of patients or monitoring of treatment response.

Background. Obesity, especially severe obesity, is associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. Bariatric surgery is a durable and effective weight loss therapy for patients with severe obesity and weight-related comorbidities. Elevated plasma levels of lipoprotein (a) (Lp(a)) are causally associated with ASCVD. The aim of this meta-analysis was to analyze whether bariatric surgery is associated with Lp(a) concentrations. Methods. A literature search in PubMed, Scopus, Embase, and Web of Science was performed from inception to May 1st, 2021. A random-effects model and the generic inverse variance weighting method were used to compensate for the heterogeneity of studies in terms of study design, treatment duration, and the characteristics of the studied populations. A random-effects metaregression model was used to explore the association with an estimated effect size. Evaluation of funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests were used to assess the presence of publication bias in the meta-analysis. Results. Meta-analysis of 13 studies including 1551 patients showed a significant decrease of circulating Lp(a) after bariatric surgery (SMD: -0.438, 95% CI: -0.702, -0.174, p

Arterial stiffness describes the increased rigidity of the arterial wall that occurs as a consequence of biological aging and several diseases. Numerous studies have demonstrated that parameters to assess arterial stiffness, especially pulse-wave velocity, are predictive of those individuals that will suffer cardiovascular morbidity and mortality. Statin therapy may be a pharmacological strategy to improve arterial elasticity. It has been shown that the positive benefits of statin therapy on cardiovascular disease is attributable not only to their lipid-lowering capacity but also to various pleiotropic effects, such as their anti-inflammatory, antiproliferative, antioxidant, and antithrombotic properties. Additionally, statins reduce endothelial dysfunction, improve vascular and myocardial remodeling, and stabilize atherosclerotic plaque. The aim of the present review was to summarize the evidence from human studies showing the effects of statins on arterial stiffness.

Statins are a wide category of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor drugs extensively prescribed for hypercholesterolemia. In fact, many studies showed beneficial effects of these agents on a variety of related illnesses, which include increased atherosclerotic plaque stability, decreased proliferation of vascular smooth muscle, platelet aggregation, the dampening of vascular inflammation, and also anabolic effects on bone tissue. Therefore, these drugs are considered as pleiotropic agents having different clinical applications other than those for which they were initially developed. Controlled drug delivery is an efficient way of delivery in tissue engineering. Amongst different controlled release formulations, nanofibers are a novel, alternative, widely used agent because of their unique properties. These include their sustained release of drug, a high drug-loading capacity, flexible shapes with a high surface-to-volume ratio, and superior porosity. Electrospinning is an economic and a simple method employed to produce nanofibers. In this report, studies related to statin nanofiber applications have been reviewed and their results have been summarized. Four different applications of statin nanofibers have been reported, including bone generation, endothelial stenosis and thrombosis, peripheral nerve injury, and anti-inflammatory action. Studies carried out both in vitro and in vivo showed effectiveness of statins in bone healing, aneurysm, and the healing of sciatic nerve injury. In addition, statins showed apoptosis effects and anti-inflammatory effects, with dose-dependent reduction of IL-6 and dose-independent reduction of TNF-α. Despite these promising results, validation via clinical trials is yet to be performed. The scope of statins in their pleiotropic range of actions is still not completely explored, and studies are still needed to enlighten different useful aspects of such drugs.

The modern lifestyle has a negative impact on health. It is usually accompanied by increased stress levels and lower physical activity, which interferes with body homeostasis. Diabetes mellitus is a relatively common metabolic disorder with increasing prevalence globally, associated with various risk factors, including lower physical activity and a sedentary lifestyle. It has been shown that sedentary behavior increases the risk of insulin resistance, but the intermediate molecular mechanisms are not fully understood. In this mechanistic review, we explore the possible interactions between physical inactivity and insulin resistance to help better understand the pathophysiology of physical inactivity-dependent insulin resistance and finding novel interventions against these deleterious pathways.

Glucagon-like peptide-1 (GLP-1) receptor agonists are recently discovered antidiabetic drugs with potent hypoglycemic effects. Among different mechanisms of activity, these compounds were shown to reduce blood glucose by suppression of glucagon secretion and stimulation of glucose-dependent insulin secretion. These antidiabetic agents have a minor risk of hypoglycemia and have been suggested as a second-line therapy to be added to metformin treatment to further optimize glycemic control in diabetes. More recently, scientific evidence suggests that GLP-1 receptor agonists may particularly afford protection from diabetic nephropathy through modulation of the molecular pathways involved in renal impairment and so improve renal function. This additional benefit adds further weight for these compounds to become promising drugs not only for glycemic control but also to prevent diabetic complications. In this review, we have updated evidence on the beneficial effects of GLP-1 receptor agonists on diabetic nephropathy and detailed the underlying pathophysiological mechanisms.

Conflicting data suggest that statins could cause chronic liver disease in certain group of patients, while improving prognosis in those with chronic viral hepatitis (CVH). To quantify the potential protective role of statins on some main liver-related health outcomes in clinical studies on CVH patients. Data Sources: The search strategy was explored by a medical librarian using bibliographic databases, from January 2015 to April 2020. Data synthesis: The results showed no significant difference in the risk of mortality between statin users and non-users in the overall analysis. However, the risk of mortality significantly reduced by 39% in statin users who were followed for more than three years. Moreover, the risk of HCC, fibrosis, and cirrhosis in those on statins decreased by 53%, 45% and 41%, respectively. Although ALT and AST reduced slightly following statin therapy, this reduction was not statistically significant. A significant heterogeneity among studies was observed, resulting from differences in clinical characteristics between statin users and non-users, study designs, population samples, diseases stage, comorbidities, and confounding covariates. Not only long-term treatment with statins seems to be safe in patients affected by hepatitis, but also it significantly improves their prognosis.

Aims. This meta-analysis of randomized placebo-controlled clinical trials assessed the effect of glucose-like peptide-1-receptor agonists (GLP-1RA) on the lipid profile and liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods. Randomized placebo-controlled trials investigating GLP-1RA on the lipid profile and liver enzymes in patients with NAFLD were searched in PubMed-Medline, Scopus, Web of Science, and Google Scholar databases (from inception to January 2020). A random-effects model and a generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted. Weighted random-effects meta-regression was performed on potential confounders on lipid profile and liver enzyme concentrations. Results. 12 studies were identified (12 GLP-1RA arms; 677 subjects) that showed treatment with GLP-1RA reduced alanine transaminase (ALT) concentrations (WMD = −10.14, 95%CI = [−15.84, −0.44], P

Adipokines are a family of hormones and cytokines with both pro- and anti-inflammatory effects released into the circulation to exert their hormonal effects. Adipokines are closely involved in most metabolic pathways and play an important modulatory role in lipid and carbohydrate homeostasis as they are involved in the pathophysiology of most metabolic disorders. Incretin-based therapy is a newly introduced class of antidiabetic drugs that restores euglycemia through several cellular processes; however, its effect on adipokines expression/secretion is not fully understood. In this review, we propose that incretin-based therapy may function through adipokine modulation that may result in pharmacologic properties beyond their direct antidiabetic effects, resulting in better management of diabetes and diabetes-related complications.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are a class of newly introduced antidiabetic medications that potentially lower blood glucose by several molecular pathways. DPP-4 inhibitors are the other type of novel antidiabetic medications which act by preventing GLP-1 inactivation and thereby increasing the activity levels of GLP-1, leading to more glucose-induced insulin release from islet β-cells and suppression of glucagon release. Most patients with diabetes have concurrent hypertension and cardiovascular disorder. If antihyperglycemic agents can attenuate the risk of hypertension and cardiovascular disease, they will amplify their overall beneficial effects. There is conflicting evidence on the cardiovascular benefits of GLP-1R induction in laboratory studies and clinical trials. In this study, we have reviewed the main molecular mechanisms by which GLP-1R induction may modulate the cardiovascular function and the results of cardiovascular outcome clinical trials.

Pathophysiological pathways that are induced by chronic hyperglycemia negatively impact lipid metabolism. Thus, diabetes is commonly accompanied by varying degrees of dyslipidemia which is itself a major risk factor for further macro- and microvascular diabetes complications such as atherosclerosis and nephropathy. Therefore, normalizing lipid metabolism is an attractive goal for therapy in patients with diabetes. Incretin-based medications are a novel group of antidiabetic agents with potent hypoglycemic effects. While the impact of incretins on glucose metabolism is clear, recent evidence indicates their positive modulatory roles on various aspects of lipid metabolism. Therefore, incretins may offer additional beneficial effects beyond that of glucose normalization. In the current review, how these antidiabetic medications can regulate lipid homeostasis and the possible cellular pathways involved are discussed, incorporating related clinical evidence about incretin effects on lipid homeostasis.

Background. Although vaccine rollout for COVID-19 has been effective in some countries, there is still an urgent need to reduce disease transmission and severity. We recently carried out a meta-analysis and found that pre- and in-hospital use of statins may improve COVID-19 mortality outcomes. Here, we provide an updated meta-analysis in an attempt to validate these results and increase the statistical power of these potentially important findings. Methods. The meta-analysis investigated the effect of observational and randomized clinical studies on intensive care unit (ICU) admission, tracheal intubation, and death outcomes in COVID-19 cases involving statin treatment, by searching the scientific literature up to April 23, 2021. Statistical analysis and random effect modeling were performed to assess the combined effects of the updated and previous findings on the outcome measures. Findings. The updated literature search led to the identification of 23 additional studies on statin use in COVID-19 patients. Analysis of the combined studies (n=47; 3,238,508 subjects) showed no significant effect of statin treatment on ICU admission and all-cause mortality but a significant reduction in tracheal intubation (OR=0.73, 95% CI: 0.54-0.99, p=0.04, n=10 studies). The further analysis showed that death outcomes were significantly reduced in the patients who received statins during hospitalization (OR=0.54, 95% CI: 0.50-0.58, p

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that can lead to end-stage liver disease needing a liver transplant. Many pharmacological approaches are used to reduce the disease progression in NAFLD. However, current strategies remain ineffective to reverse the progression of NAFLD completely. Employing nanoparticles as a drug delivery system has demonstrated significant potential for improving the bioavailability of drugs in the treatment of NAFLD. Various types of nanoparticles are exploited in this regard for the management of NAFLD. In this review, we cover the current therapeutic approaches to manage NAFLD and provide a review of recent up-to-date advances in the uses of nanoparticles for the treatment of NAFLD.

Glucagon-like peptide 1 receptor agonists and dipeptidyl-peptidase 4 inhibitors are medications used for managing diabetes, mimicking the metabolic effects of incretin hormones. Recent evidence suggests that these medications have antioxidative potentials in the diabetic milieu. The pathophysiology of most diabetic complications involves oxidative stress. Therefore, if incretin-based antidiabetic medications can alleviate the free radicals involved in oxidative stress, they can potentially provide further therapeutic effects against diabetic complications. However, the molecular mechanisms by which these medications protect against oxidative stress are not fully understood. In the current review, we discuss the potential molecular mechanisms behind these pharmacologic agents’ antioxidative properties.

Statins, which are functionally known as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) inhibitors, are lipid-lowering compounds widely prescribed in patients with cardiovascular diseases (CVD). Several biological and therapeutic functions have been attributed to statins, including neuroprotection, antioxidation, anti-inflammation, and anticancer effects. Pharmacological characteristics of statins have been attributed to their involvement in the modulation of several cellular signaling pathways. Over the past few years, the therapeutic role of statins has partially been attributed to the induction of autophagy, which is critical in maintaining cellular homeostasis and accounts for the removal of unfavorable cells or specific organelles within cells. Dysregulated mechanisms of the autophagy pathway have been attributed to the etiopathogenesis of various disorders, including neurodegenerative disorders, malignancies, infections, and even aging. Autophagy functions as a double-edged sword during tumor metastasis. On the one hand, it plays a role in inhibiting metastasis through restricting necrosis of tumor cells, suppressing the infiltration of the inflammatory cell to the tumor niche, and generating the release of mediators that induce potent immune responses against tumor cells. On the other hand, autophagy has also been associated with promoting tumor metastasis. Several anticancer medications which are aimed at inducing autophagy in the tumor cells are related to statins. This review article discusses the implications of statins in the induction of autophagy and, hence, the treatment of various disorders.

The ongoing pandemic of COVID-19 is now the major issue in global health. Evidence implies that patients with diabetes are at a higher risk of severe disease or death due to COVID-19 than individuals without diabetes. However, the underlying mechanism for this differential effect in individuals with and without diabetes is not clearly understood. We have reviewed the pathophysiological pathways which may facilitate the entry of virus or an increase in its infectivity in host cells in the diabetic milieu. We suggest that the preexisting pathological pathways in patients with poorly controlled diabetes increase the risk of infectivity and are responsible for the higher levels of tissue injury and death in patients with diabetes.

Coronary artery diseases (CAD), as a leading cause of mortality around the world, has attracted the researchers’ attention for years to find out its underlying mechanisms and causes. Among the various key players in the pathogenesis of CAD cytokines, microRNAs (miRNAs) are crucial. In this study, besides providing a comprehensive overview of the involvement of cytokines, growth factors, and miRNAs in CAD, the interplay between miRNA with cytokine or growth factors during the development of CAD is discussed.

Acute inflammation has been described as a reactive dynamic process, promoted by the secretion of proinflammatory mediators, including lipid molecules like leukotrienes and prostaglandins, and counterbalanced by proresolving mediators including omega-3 polyunsaturated fatty-acid- (PUFA-) derived molecules. The switch from the initiation to the resolution phase of acute inflammatory response is crucial for tissue homeostasis, whereas the failure to resolve early inflammation by specialized proresolving mediators leads to chronic inflammation and tissue damage. Among PUFA-derived proresolving mediators, different eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives have been described, namely, resolvins (resolution phase interaction products), which exert their anti-inflammatory and immune-regulatory activities through specific G-protein-coupled receptors. In recent years, compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in different neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. This review summarizes current knowledge on the role of resolvins in resolution of inflammation and highlights available evidence showing the neuroprotective potential of EPA- and DHA-derived resolvins (E-series and D-series resolvins, respectively) in neurodegenerative diseases.

Background. The keratorefractive surgeries (KRS) are one of the most common ocular surgeries. One of the dangerous complications of these surgeries is infectious keratitis (IK), which is the second cause of blindness after cataract surgery. The purpose of this study was to estimate the prevalence of IK after KRS in different parts of the world. Methods. In order to obtain relevant studies, all national and international databases including IranMedex, SID, Magiran, IranDoc, Medlib, ScienceDirect, PubMed, Scopus, Cochrane, Embase, Web of Science, and Google Scholar were searched using standard keywords. Results. IK prevalence after KRS was 0.000496% (0.000145% for the left eye and 0.000149% for the right eye). IK prevalence after KRS in the United States, Europe, and Asia was 0.000667%, 0.000473%, and 0.000045%, respectively, in all of which the common microorganisms were Staphylococci. Meta-regression showed no significant association between IK after KRS and either sample size or publication year of the studies. IK prevalence after KRS in the right eye was more than that in the left one. Also, the probability of IK incidence after LASIK surgery was more than PRK and LASEK. In the evaluation of continents, IK after KRS in the United States was more frequent compared with Europe and Asia. Conclusions. This study provided data as to the overall prevalence of IK following KRS and its variations according to the types of eye, surgery, pathogenic microorganism, and geographical location.

Background: Statins are the most widely used drugs for decreasing elevated serum LDL-cholesterol (LDL-C) and thus for the prevention of atherosclerotic cardiovascular disease (ASCVD), but they have also some pleiotropic effects, including anti-inflammatory properties. Atherosclerosis is a low-grade inflammatory disease, and elevated ferritin is considered to be one of the markers of inflammation. Since the results of studies on the effects of statins on serum ferritin levels are conflicting, this meta-analysis was performed. Methods: A literature search was performed using major electronic databases (MEDLINE/PubMed, Scopus, Embase, and ISI Web of Science) from inception up to 5 March 2022 to find studies evaluating the effect of different statins on serum ferritin levels. The effect size was determined using weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs). Results: The meta-analysis of nine studies (1611 patients) analyzing the effects of statins on serum ferritin levels that were included showed a significant decrease in circulating ferritin levels caused by statins. The results did not suggest any significant association between the changes in concentrations of serum ferritin and the duration of treatment with statins. Conclusions: Statin therapy decreases the circulating concentrations of ferritin, which might be beneficial for the prevention and/or progression of ASCVD. This effect might be explained by the anti-inflammatory effects and maybe some other pleiotropic effects of statins and not by their lipid-lowering effects.

Background: Obesity, and in particular extreme obesity, as a global health problem is an important risk factor for many diseases, including atherosclerotic cardiovascular disease (ACVD). Bariatric surgery might stop or slow atherogenesis by decreasing excessive weight in the early stages of atherogenesis, by suppressing low-grade systemic inflammation as well as by inhibiting oxidative stress and endothelial dysfunction. The aim of this meta-analysis was to provide an answer to whether bariatric surgery has a significant effect on intima-media thickness (IMT) which is a surrogate marker of early atherosclerosis and has a good correlation with atherosclerotic coronary heart disease. Methods: A systematic literature search in PubMed, Scopus, Embase, and Web of Science as well as grey literature was performed from inception to 1 July 2022. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. Overall, the estimate of effect size was measured by a random effects meta-analysis. To account for the heterogeneity of studies regarding study design, characteristics of the populations, and treatment duration, a random-effects model (using the DerSimonian–Laird method) and the generic inverse variance weighting approach were used. To assess the existence of publication bias in the meta-analysis, the funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests were used. Results: The meta-analysis of 30 trials, including 1488 subjects, demonstrated a significant decrease in IMT after bariatric surgery. The reduction in IMT was also robust in the leave-one-out sensitivity analysis. It must be stressed that the results of the random-effects meta-regression did not suggest any relationship between the changes in IMT and delta body mass index (BMI) or duration of follow-up after the bariatric surgery. However, the subgroup analyses showed a better IMT reduction after laparoscopic sleeve gastrectomy (LSG) when compared to Roux-en-Y gastric bypass (RYGB). Within a year, the IMT follow-up values showed a further improvement. Conclusions: Bariatric surgery significantly reduced IMT. Significant associations were found between the surgery type and IMT changes, as well as a significant effect of follow-up duration on the changes of IMT after bariatric surgery.