Publications by authors named "Željko Reiner"

240 Publications

Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial.

Eur J Prev Cardiol 2021 Mar;28(1):33-43

Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), and INSERM, France.

Aims: Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment.

Methods And Results: The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL (P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80-0.96; 0.68, 0.49-0.94; and 0.65, 0.44-0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34-2.16; 3.16%, 0.38-5.94; 7.97%, 0.42-15.51; Pinteraction = 0.106).

Conclusions: PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.
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http://dx.doi.org/10.1177/2047487320941987DOI Listing
March 2021

Statin Therapy in Post-Operative Atrial Fibrillation: Focus on the Anti-Inflammatory Effects.

J Cardiovasc Dev Dis 2021 Feb 26;8(3). Epub 2021 Feb 26.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.

Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed.

Methods: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed.

Results: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF.

Conclusion: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits.
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http://dx.doi.org/10.3390/jcdd8030024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996747PMC
February 2021

Prediction of recurrent event in patients with coronary heart disease: the EUROASPIRE Risk Model.

Eur J Prev Cardiol 2020 Dec 29. Epub 2020 Dec 29.

Department of Public Health and Primary Care, Ghent University, C. Heymanslaan 10, 9000 Gent, Belgium.

Aims: Most patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years.

Methods And Results: Prospective data were available for 12 484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and the incidence of the primary endpoint was investigated. This model was then validated in the remaining 4484 patients. The final multivariate model revealed a higher risk for the primary endpoint with increasing age, a previous hospitalization for stroke, heart failure or PCI, a previous diagnosis of peripheral artery disease, self-reported diabetes and its glycaemic control, higher non-high-density lipoprotein cholesterol, reduced renal function, symptoms of depression and anxiety and living in a higher risk country. The model demonstrated excellent internal validity and proved very adequate in the validation cohort. Regarding external validity, the model demonstrated good discriminative ability in 20 148 MI patients participating in the SWEDEHEART register. Finally, we developed a risk calculator to estimate risks at 1 and 2 years for patients with stable CHD.

Conclusion: In patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.
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http://dx.doi.org/10.1093/eurjpc/zwaa128DOI Listing
December 2020

Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP).

Pharmacol Res 2021 Apr 17;166:105499. Epub 2021 Feb 17.

Department of Internal Medicine, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia. Electronic address:

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.
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http://dx.doi.org/10.1016/j.phrs.2021.105499DOI Listing
April 2021

Novel Experimental Agents for the Treatment of Hypercholesterolemia.

J Exp Pharmacol 2021 11;13:91-100. Epub 2021 Feb 11.

Zagreb School of Medicine, University of Zagreb, Zagreb, Croatia.

Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in most developed countries and even more in developing countries. Dyslipidemia is a well known main risk factor for ASCVD. Lipid-lowering treatment, particularly lowering LDL-cholesterol (LDL-C), can decrease the risk for ASCVD. New data and guidelines based upon them suggest that we should go with LDL-C levels as low as we can. Therefore, conventional lipid lowering agents (statins and statins+ezetimibe) are not enough mainly because of poor compliance and statin intolerance which is in the real world mostly pseudo-intolerance. PCSK9 inhibitors provided a new hope to further decrease LDL-C but are still expensive, they have to be injected subcutaneously twice a month and their long-lasting adverse effects are not known. Therefore, there is a constant need to develop novel, more potent, more safe, less expensive, more user friendly regimens of hypolipemic agents (bempedoic acid, selective PPAR alpha receptor modulators etc). One of the ways to overcome poor compliance and increase the potency of therapy with less adverse effects are fixed combinations of established drugs (statin+ezetimibe). The future of hypolipemic agents is based on antisense therapy, ie. the use of specific oligonucleotide sequences blocking the translation of the selected protein (targeting apolipoprotein CIII, lipoprotein (a), apolipoprotein B) or RNA silencing technique (PCSK9 mRNA) and are in various stages of clinical trials. Some of them are almost ready to use in everyday clinical practice. High risk and very high risk patients (eg. familial hypercholesterolemia, familial severe chylomicronemia syndrome) will benefit most. The aim of this review is to inform about novel hypolipemic agents - potent and safe drugs for dyslipidemia which should reduce the risk of ASCVD.
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http://dx.doi.org/10.2147/JEP.S267376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887150PMC
February 2021

Resveratrol and cardiac fibrosis prevention and treatment.

Curr Pharm Biotechnol 2021 Feb 12. Epub 2021 Feb 12.

Department of Cardiology, Ramsar Campus, Mazandaran University of Medical Sciences, Sari. Iran.

Cardiovascular diseases are some of the major causes of morbidity and mortality in developed or developing countries but in developed countries as well. Cardiac fibrosis is one of the most often pathological changes of heart tissues. It occurs as a result of extracellular matrix proteins accumulation at myocardia. Cardiac fibrosis results in impaired cardiac systolic and diastolic functions and is associated with other effects. Therapies with medicines have not been sufficiently successful in treating chronic diseases such as CVD. Therefore, the interest for therapeutic potential of natural compounds and medicinal plants has increased. Plants such as grapes, berries and peanuts contain a polyphenolic compound called "resveratrol" which has been reported to have various therapeutic properties for a variety of diseases. Studies on laboratory models that show that resveratrol has beneficial effects on cardiovascular diseases including myocardial infarction, high blood pressure cardiomyopathy, thrombosis, cardiac fibrosis, and atherosclerosis. In vitro animal models using resveratrol indicated protective effects on the heart by neutralizing reactive oxygen species, preventing inflammation, increasing neoangiogenesis, dilating blood vessels, suppressing apoptosis and delaying atherosclerosis. In this review, we are presenting experimental and clinical results of studies concerning resveratrol effects on cardiac fibrosis as a CVD outcome in humans.
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http://dx.doi.org/10.2174/1389201022666210212125003DOI Listing
February 2021

The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis.

Curr Med Chem 2021 Feb 8. Epub 2021 Feb 8.

School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, . Iran.

The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non-ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.
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http://dx.doi.org/10.2174/0929867328666210208182326DOI Listing
February 2021

The effects of L-carnitine supplementation on indicators of inflammation and oxidative stress: a systematic review and meta-analysis of randomized controlled trials.

J Diabetes Metab Disord 2020 Dec 15;19(2):1879-1894. Epub 2020 Sep 15.

Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maragheh University of Medical Sciences, Maragheh, Iran.

Objective: Several trials investigated the efficacy of L-carnitine administration on markers of inflammation and indicators of oxidative stress; however, their findings are controversial. The aim of this study was to conduct a comprehensive meta-analysis and a critical review, which would analyze all randomized controlled trials (RCTs) in order to determine the effects of L-carnitine supplementation on inflammatory markers and oxidative stress.

Methods: An electronic search was performed using Scopus, Cochrane Library, PubMed, Google scholar and Web of Science databases on publications from 1990 up to May 2020. Human RCTs conducted in healthy subjects or participants with certain disorders which investigating the efficacy of L-carnitine supplementation compared to control (placebo, usual treatment or no intervention) on inflammation and oxidative markers were included. Data were pooled applying a random-effects model and as the overall effect size, weighted mean difference (WMD) was presented. Between heterogeneity among studies was computed using Cochran's Q test and I-square (I). Quality of studies assessed using the Jadad scale. Dose-response analysis was measured using meta-regression. The funnel plot, as well as the Egger's regression test was applied to determine the publication bias.

Results: 44 trials (reported 49 effect sizes for different outcomes of interest) met the inclusion criteria for this meta-analysis. According to the findings, L-carnitine supplementation resulted in a significant reduction in C-reactive protein (CRP) (WMD: -0.10; 95% CI: -0.14, -0.06), interleukin 6 (IL-6) (WMD: -1.87; 95% CI: -2.80, -0.95), tumor necrosis factor-α (TNF-α) levels (WMD: -1.43; 95% CI: -2.03, -0.84), and malondialdehyde (MDA) (WMD: -0.47; 95% CI: -0.76, -0.18) levels, while there was a significant increase in superoxide dismutase (SOD) (WMD: 2.14; 95% CI: 1.02, 3.25). However, no significant effects of L-carnitine on glutathione peroxidase (GPx) (WMD: 0.02; 95% CI: -0.01, 0.05) and total antioxidant capacity (TAC) (WMD: 0.14; 95% CI: -0.05, 0.33) were found.

Conclusions: L-carnitine supplementation was associated with lowering of CRP, IL-6, TNF-α, and MDA, and increasing SOD levels, but did not affect other inflammatory and oxidative stress biomarkers.
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http://dx.doi.org/10.1007/s40200-020-00627-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843735PMC
December 2020

The effects of omega-3 fatty acids supplementation on metabolic status in pregnant women: a systematic review and meta-analysis of randomized controlled trials.

J Diabetes Metab Disord 2020 Dec 6;19(2):1685-1699. Epub 2020 Jun 6.

Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background And Objective: Data regarding the effects of omega-3 polyunsaturated fatty acids (PUFA) supplementation on metabolic status of pregnant women are limited. This systematic review and meta-analysis were done based on randomized controlled trials (RCTs) dealing with the effects of omega-3 PUFA supplementation on glycemic control, lipoproteins, inflammation and oxidative stress in pregnant women.

Methods: Following databases were searched for eligible studies published from inception to until 2019: MEDLINE, EMBASE, Web of Science, PubMed, Scopus, Cochrane Library, and Google scholar. Studies that evaluated the effect of omega-3 PUFA supplementation on parameters of glycemic control, lipoproteins, inflammation and oxidative stress in pregnant women were found by using the key MeSH. A study quality assessment was performed using the Cochrane Collaboration risk of bias tool and heterogeneity between studies was statistically computed using Cochrane's Q test and I-square (I). Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size.

Results: No significant effects of omega-3 PUFA supplementation on FPG, insulin, insulin resistance, total cholesterol, triglycerides, LDL-cholesterol, total cholesterol/HDL-cholesterol, interleukin 6 (IL-6), IL-8, and malondialdehyde were found. However, omega-3 PUFA significantly increased serum concentrations of HDL-cholesterol (WMD: 3.10; 95% CI: 0.18, 6.03) and reduced C-reactive protein (WMD: -1.85; 95% CI: -2.61, -1.09).

Conclusion: Based on the results of this meta-analysis omega-3 PUFA supplementation during pregnancy has a significant beneficial effect on HDL-cholesterol, and C-reactive protein.
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http://dx.doi.org/10.1007/s40200-020-00558-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843696PMC
December 2020

Metabolic and Anti-inflammatory Response to Melatonin Administration in Patients with Diabetic Nephropathy.

Iran J Kidney Dis 2021 Jan;1(1):22-30

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Introduction: Data on the effects of melatonin administration on metabolic parameters in patients with diabetic nephropathy (DN) is limited and controversial. This study was performed to analyze the effects of melatonin administration on metabolic status in patients with DN.

Methods: This randomized, double blind, placebo-controlled clinical trial was performed on 60 patients with DN. Patients were randomly assigned into two groups to take either 10 mg/d of melatonin (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at baseline and 12 weeks after intervention to quantify metabolic parameters.

Results: Melatonin administration significantly reduced plasma fasting glucose (β = -10.64 mg/dL; 95% CI: -20.37 to -0.90; P < .05), insulin (β = -2.37 μIU/mL, 95% CI: -3.33 to -1.41; P < .001), insulin resistance (β = -0.67, 95% CI: -0.98 to -0.35; P < .001), significantly increased insulin sensitivity (β = 0.01, 95% CI: 0.006 to 0.01; P < .05), and plasma HDL-cholesterol levels (β = 2.75 mg/dL, 95% CI: 0.75 to 4.75; P < .05) when compared with the placebo. Melatonin also caused a significant increase in total antioxidant capacity (TAC) (β = 140.45 mmol/L; 95% CI: 80.48 to 200.41; P < .001), and glutathione (GSH) levels (β = 50.36 μmol/L, 95% CI: 94.08 to 0.02; P < .05) when compared with placebo. Ultimately, melatonin could upregulate gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < .05) in comparison with placebo.

Conclusion: Results of this study indicated that melatonin administration for 12 weeks in DN patients had beneficial effects on glycemic control, HDL-cholesterol, TAC and GSH levels, and gene expression of PPAR-γ, but did not affect other metabolic parameters.
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January 2021

Dietary supplements, vitamins and minerals as potential interventions against viruses: Perspectives for COVID-19.

Int J Vitam Nutr Res 2021 Jan 13:1-18. Epub 2021 Jan 13.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The novel coronavirus (SARS-CoV-2) causing COVID-19 disease pandemic has infected millions of people and caused more than thousands of deaths in many countries across the world. The number of infected cases is increasing day by day. Unfortunately, we do not have a vaccine and specific treatment for it. Along with the protective measures, respiratory and/or circulatory supports and some antiviral and retroviral drugs have been used against SARS-CoV-2, but there are no more extensive studies proving their efficacy. In this study, the latest publications in the field have been reviewed, focusing on the modulatory effects on the immunity of some natural antiviral dietary supplements, vitamins and minerals. Findings suggest that several dietary supplements, including black seeds, garlic, ginger, cranberry, orange, omega-3 and -6 polyunsaturated fatty acids, vitamins (e.g., A, B vitamins, C, D, E), and minerals (e.g., Cu, Fe, Mg, Mn, Na, Se, Zn) have anti-viral effects. Many of them act against various species of respiratory viruses, including severe acute respiratory syndrome-related coronaviruses. Therefore, dietary supplements, including vitamins and minerals, probiotics as well as individual nutritional behaviour can be used as adjuvant therapy together with antiviral medicines in the management of COVID-19 disease.
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http://dx.doi.org/10.1024/0300-9831/a000694DOI Listing
January 2021

Effects of statins on preeclampsia: A systematic review.

Pregnancy Hypertens 2021 Mar 11;23:123-130. Epub 2020 Dec 11.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Polish Mother's Memorial Hospital Research Institute, Lodz, Poland; Halal Research Center of IRI, FDA, Tehran, Iran. Electronic address:

Background: Preeclampsia is a serious complication of pregnancy which increases the morbidity and mortality of both the fetus and pregnant woman. It is characterized by imbalances in angiogenesis, inflammation and endothelial dysfunction which cause the development of hypertension and proteinuria, sometimes progressing into a multisystem disorder. The aim of this systematic review was to analyze all the available data on statins and preeclampsia.

Method: MEDLINE/PubMed, OVID, EMBASE, Web of Sciences, and SCOPUS were searched from inception to May 5, 2020. Any study evaluating the effects of statins on women with preeclampsia or HELLP syndrome or who were at risk for it has been included as well as the studies on the placenta of preeclamptic women.

Results: 12 articles which included 136 pregnant women and 35 placental samples from hypertensive and normotensive women were analyzed. They showed contradictory effects of statins on blood pressure in preeclampsia, on soluble FMS-like tyrosine kinase-1 (sFlt-1) as well as soluble endoglin (sEng). However, statins caused a significant dose-dependent reduction of sFlt-1 secretion from isolated cytotrophoblasts and an increased secretion of sEng (at least in some studies) in primary HUVECs and placental explants obtained from patients with preeclampsia. Statins also increased eNOS in preeclamptic placentas. Statins were beneficial for patients with antiphospholipid syndrome (APS) preventing preeclampsia and it seems that they might prevent complications of HELLP.

Conclusion: It seems that statins might be beneficial for preventing or treating preeclampsia. Nevertheless, further studies are needed to provide definitive conclusions regarding these effects of statins.
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http://dx.doi.org/10.1016/j.preghy.2020.11.014DOI Listing
March 2021

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer.

Cancer Cell Int 2020 Nov 23;20(1):560. Epub 2020 Nov 23.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male population. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasiveness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different possible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabilities. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer.
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http://dx.doi.org/10.1186/s12935-020-01660-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685642PMC
November 2020

Statin therapy and sex hormones.

Eur J Pharmacol 2021 Jan 20;890:173745. Epub 2020 Nov 20.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Halal Research Center of IRI, FDA, Tehran, Iran; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland. Electronic address:

Current guidelines recommend statin therapy for all adult patients with coronary artery disease irrespective of sex. Over recent years, some concerns have been raised concerning the effects of statins on endogenous steroid hormones synthesis. The aim of this review was to summarize the effects of statins on endogenous sex hormones in order to clarify their role and safety in different clinical settings. Results suggest that HMG-CoA inhibitors may slightly impair adrenal and/or gonadal steroid hormone production. In men, statins do not cause any clinically-relevant harmful effects on erectile function and spermatogenesis and, in women, statins have beneficial effects in treatment of polycystic ovary syndrome (PCOS). Additional research is needed to provide specific clinical recommendations concerning this topic.
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http://dx.doi.org/10.1016/j.ejphar.2020.173745DOI Listing
January 2021

Effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Clin Nutr ESPEN 2020 Dec 16;40:27-33. Epub 2020 Oct 16.

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome (MetS) and related disorders.

Methods: Databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central library were searched until January 31, 2019.

Results: 14 effect sizes from 12 studies were identified eligible to be included in current meta-analysis. Flaxseed supplementation resulted in a significant reduction in interleukin 6 (IL-6) (WMD: -0.22; 95% CI: -0.43, -0.01) and malondialdehyde (MDA) (WMD: -0.17; 95% CI: -0.31, -0.03) and a significant increase in total antioxidant capacity (TAC) levels (WMD: 137.25; 95% CI: 68.04, 206.47). Flaxseed oil supplementation did not affect other biomarkers of inflammation and oxidative stress.

Conclusions: Overall, this meta-analysis demonstrated flaxseed oil supplementation decreased IL-6 and MDA levels, and increased TAC, but did not affect other biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.
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http://dx.doi.org/10.1016/j.clnesp.2020.09.017DOI Listing
December 2020

A systematic review and meta-analysis: The effects of probiotic supplementation on metabolic profile in patients with neurological disorders.

Complement Ther Med 2020 Sep 15;53:102507. Epub 2020 Jul 15.

Department of Addiction Studies, School of Medical, Kashan University of Medical Sciences, Kashan, Iran; Clinical Research Development Unit-Matini/Kargarnejad Hospital, Kashan University of Medical Sciences, Kashan, Iran. Electronic address:

Background And Objective: The objective of meta-analysis of randomized controlled trials (RCTs) was to evaluate the effects of probiotic supplementation on metabolic status in patients with neurological disorders.

Methods: The following databases were search up to April 2019: Pubmed, Scopus, Google scholar, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95 % Confidence Intervals (95 % CI).

Results: Nine studies were included in this meta-analysis. The findings suggested that probiotic supplementation resulted in a significant reduction in C-reactive protein (CRP) [Weighted Mean Difference (WMD): -1.06; 95 % CI: -1.80, -0.32] and malondialdehyde (MDA) levels (WMD: -0.32; 95 % CI: -0.46, -0.18). Supplementation with probiotics also significantly reduced insulin (WMD: -3.02; 95 % CI: -3.88, -2.15) and homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.71; 95 % CI: -0.89, -0.52). Probiotics significantly reduced triglycerides (WMD: -18.38; 95 % CI: -25.50, -11.26) and VLDL-cholesterol (WMD: -3.16; 95 % CI: -4.53, -1.79), while they increased HDL-cholesterol levels (WMD: 1.52; 95 % CI: 0.29, 2.75).

Conclusion: This meta-analysis demonstrated that taking probiotic by patients with neurological disorders had beneficial effects on CRP, MDA, insulin, HOMA-IR, triglycerides, VLDL-cholesterol and HDL-cholesterol levels, but did not affect other metabolic parameters.
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http://dx.doi.org/10.1016/j.ctim.2020.102507DOI Listing
September 2020

Medicinal plants and bioactive natural compounds as inhibitors of HMG-CoA reductase: A literature review.

Biofactors 2020 Nov 14;46(6):906-926. Epub 2020 Oct 14.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Cardiovascular diseases (CVDs) are one of the most important causes for mortality worldwide. Elevated levels of total cholesterol, and particularly LDL-cholesterol (LDL-C) are the main risk factor for acute myocardial infarction (AMI) and ischemic heart disease. The risk of CVDs could be reduced by decreasing the elevated cholesterol levels. β-hydroxy β-methylglutaryl-CoA reductase (HMGCoAR) is the primary and rate-limiting enzyme in the cholesterol biosynthesis pathway. Recently, the crucial role of nutraceuticals in maintaining normal physiological function was established. Nutraceuticals play an important role in preventing several non-communicable diseases such as obesity, CVDs, cancer, diabetes, and reducing hyperlipidemia. Although the effect of nutraceuticals and herbal medicine on CVDs and dyslipidemia was previously investigated thoroughly, the effect of these natural products on HMGCoAR as one of the important enzymes involved in CVDs etiopathogenesis has not yet been investigated. Therefore, the major aim of this paper was to review the effects of nutraceuticals and medicinal plants on HMGCoAR. Results indicate that different types of natural foods, isolated nutrients, herbal products, and dietary supplements as nutraceuticals decrease the expression and activity of HMGCoAR. This review shows that medicinal plants and nutraceuticals could be used to decrease HMGCoAR activity as accessible and convenient and economical natural compounds to prevent dyslipidemia and CVDs.
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http://dx.doi.org/10.1002/biof.1684DOI Listing
November 2020

Why might visit-to visit variability of lipoproteins have an effect on cardiovascular events?

Authors:
Željko Reiner

Atherosclerosis 2020 11 6;312:99-100. Epub 2020 Oct 6.

Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, Zagreb University, Croatia. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2020.09.028DOI Listing
November 2020

The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action.

Front Pharmacol 2020 26;11:1300. Epub 2020 Aug 26.

Department of Botany, University of Fort Hare, Alice, South Africa.

Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, and , and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects.
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http://dx.doi.org/10.3389/fphar.2020.01300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479177PMC
August 2020

Effects of whey protein on glycemic control and serum lipoproteins in patients with metabolic syndrome and related conditions: a systematic review and meta-analysis of randomized controlled clinical trials.

Lipids Health Dis 2020 Sep 21;19(1):209. Epub 2020 Sep 21.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Background: This systematic review and meta-analysis aimed to assess the effects of whey protein on serum lipoproteins and glycemic status in patients with metabolic syndrome (MetS) and related disorders.

Methods: Online databases, such as Web of Science, Cochrane Library, PubMed and Scopus were systematically searched by two independent authors from inception until 30th April 2020 for English randomized clinical trials investigating the efficacy of whey protein administration in subjects with Mets or related conditions on the parameters of glycemic and lipid control compared to certain control. In order to evaluate the included studies' methodological quality, Cochrane Collaboration risk of bias tool was applied. Using Cochrane's Q test and I-square (I) statistic, the included trials' heterogeneity was also examined. Using a random-effects model, data were pooled, and weighted mean difference (WMD) was considered as the overall effect size.

Results: Twenty-two studies were selected to be included in this meta-analysis. Consumption of whey protein resulted in significant reduction of HbA1c (WMD: -0.15; 95% CI: - 0.29, - 0.01) insulin (WMD: -0.94; 95% CI: - 1.68, - 0.21) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (WMD: -0.20; 95% CI: - 0.36, - 0.05). A significant reduction in triglycerides levels (WMD: -17.12; 95% CI: - 26.52, - 7.72), total cholesterol (WMD: -10.88; 95% CI -18.60, - 3.17), LDL-cholesterol levels (WMD: -8.47 95% CI: - 16.59, - 0.36) and total cholesterol/HDL-cholesterol ratio (WMD: -0.26; 95% CI: - 0.41, - 0.10) was found as well.

Conclusions: This meta-analysis suggests that supplementation with whey protein had beneficial effect on several indicators of glycemic control and lipid parameters in patients with MetS and related conditions.
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http://dx.doi.org/10.1186/s12944-020-01384-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504833PMC
September 2020

Peripheral arterial disease and intermittent claudication in coronary heart disease patients.

Int J Cardiol 2021 Jan 9;322:227-232. Epub 2020 Sep 9.

Department of Public Health and Primary Care, Ghent University, Belgium. Electronic address:

Background And Aim: Peripheral artery disease (PAD) is associated with an increased risk of fatal and non-fatal coronary heart disease (CHD). The aims of the this study were 1) to investigate the prevalence of PAD and suspected PAD in a large population of established CHD patients, and 2) to assess the prevalence and control of risk factors in these patients as well health-related quality of life.

Material And Methods: In the EUROASPIRE V survey, 8243 patients with documented CHD were recruited from 27 ESC member countries and were invited to attend a study visit. Patients were investigated using questionnaires, in-depth interviews and a clinical examination. Intermittent claudication (IC) was assessed using the Edinburgh Claudication Questionnaire. Patients without previously diagnosed PAD were suspected of having PAD if they were found to have IC.

Results: Overall, 6.4% of the patients had already a confirmed diagnosis of PAD and another 6.3% were suspected of having PAD. Independent of age and gender, patients with previously diagnosed PAD were significantly more frequently current smokers, had the lowest smoking cessation rates, were less physically active, reported more often previously diagnosed diabetes and had significantly higher blood pressure levels, compared to patients without PAD. They had also significantly higher levels of serum triglycerides, lower HDL-C levels, and had more often renal insufficiency. In comparison with patients without PAD, those with suspected PAD demonstrated significantly higher smoking cessation rates but their obesity rates were significantly higher. In CHD patients with a history of PAD, the use of calcium channel blockers and diuretics was significantly higher than in patients without PAD. Compared to the latter group, the use of diuretics, anti-arrhythmics and anti-depressants in patients with suspected PAD was significantly higher. Moreover, patients with previously diagnosed PAD had significantly higher levels of anxiety and depression and reported a significantly worse health-related quality of life (HRQoL), in comparison with those without PAD. HRQoL levels were significantly reduced in patients with suspected PAD as well.

Conclusion: In CHD patients without a previous diagnosis of PAD, IC is not infrequent. Diagnosed PAD was significantly associated with a worse CHD risk factor profile. Patients with known PAD as well as those with suspected PAD had a considerable loss of health-related quality of life. Therefore, physicians should consider to screen for IC in all their CHD patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.004DOI Listing
January 2021

Interaction Between Coronavirus S-Protein and Human ACE2: Hints for Exploring Efficient Therapeutic Targets to Treat COVID-19.

Angiology 2021 02 30;72(2):122-130. Epub 2020 Aug 30.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

With the global expansion of coronavirus disease 2019 (COVID-19) and the declaration of its outbreak as a Public Health Emergency of International Concern by the World Health Organization, there is an urgent need for vaccines and medicines to prevent and treat COVID-19. The responsible pathogen for the disease is the newly severe acute respiratory syndrome coronavirus (SARS-CoV) 2 belonging to the same family of viruses SARS-CoV and Middle East respiratory syndrome coronavirus that originally are zoonotic and have been associated with severe illness during the outbreaks in 2003 and 2012, respectively. The virulence of coronavirus strains is mainly associated with variations in surface proteins mediating cellular entry of the virus, which can help in finding effective therapeutic targets. In this review, we seek evidence showing the role of coronavirus spike protein (S-protein) and its potential cellular receptor, angiotensin-converting enzyme 2 (ACE2), during infection of coronaviruses, including the newly SARS-CoV-2 and its similar strain SARS-CoV. This review also discusses the therapeutic effect of inhibiting the renin-angiotensin system cascade, a target of ACE2, in patients having coronavirus with cardiovascular disease.
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http://dx.doi.org/10.1177/0003319720952284DOI Listing
February 2021

Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial.

Eur J Prev Cardiol 2020 Jul 27:2047487320941987. Epub 2020 Jul 27.

Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), and INSERM, France.

Aims: Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment.

Methods And Results: The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL ( < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively;  < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80-0.96; 0.68, 0.49-0.94; and 0.65, 0.44-0.97, respectively;  = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34-2.16; 3.16%, 0.38-5.94; 7.97%, 0.42-15.51;  = 0.106).

Conclusions: PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.
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http://dx.doi.org/10.1177/2047487320941987DOI Listing
July 2020

Inflammatory Biomarkers for Cardiovascular Risk Stratification in Familial Hypercholesterolemia.

Rev Physiol Biochem Pharmacol 2020 ;177:25-52

Halal Research Center of IRI, FDA, Tehran, Iran.

Familial hypercholesterolemia (FH) is a frequent autosomal genetic disease characterized by elevated concentrations of low-density lipoprotein cholesterol (LDL) from birth with increased risk of premature atherosclerotic complications. Accumulating evidence has shown enhanced inflammation in patients with FH. In vessels, the deposition of modified cholesterol lipoproteins triggers local inflammation. Then, inflammation facilitates fatty streak formation by activating the endothelium to produce chemokines and adhesion molecules. This process eventually results in the uptake of vascular oxidized LDL (OxLDL) by scavenger receptors in monocyte-derived macrophages and formation of foam cells. Further leukocyte recruitment into the sub-endothelial space leads to plaque progression and activation of smooth muscle cells proliferation. Several inflammatory biomarkers have been reported in this setting which can be directly synthetized by activated inflammatory/vascular cells or can be indirectly produced by organs other than vessels, e.g., liver. Of note, inflammation is boosted in FH patients. Inflammatory biomarkers might improve the risk stratification for coronary heart disease and predict atherosclerotic events in FH patients. This review aims at summarizing the current knowledge about the role of inflammation in FH and the potential application of inflammatory biomarkers for cardiovascular risk estimation in these patients.
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http://dx.doi.org/10.1007/112_2020_26DOI Listing
January 2021

The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials.

Clin Nutr ESPEN 2020 08 6;38:43-49. Epub 2020 May 6.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R Iran. Electronic address:

Introduction: So far, no study has summarized the findings on the effects of berberine intake on anthropometric parameters, C-reactive protein (CRP) and liver enzymes. This systematic review and meta-analysis were done based upon randomized controlled trials (RCTs) to analyze the effects of berberine on anthropometric parameters, CRP and liver enzymes.

Method: Following databases were searched for eligible studies published from inception to 30 July 2019: MEDLINE, EMBASE, Web of Science, Cochrane Library, PubMed and Google scholar. Necessary data were extracted. Data were pooled by the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI).

Result: 12 studies were included. Berberine treatment moderately but significantly decreased body weight (WMD = -2.07 kg, 95% CI -3.09, -1.05, P < 0.001), body mass index (BMI) (WMD = -0.47 kg/m, 95% CI -0.70, -0.23, P < 0.001), waist circumference (WC) (WMD = -1.08 cm, 95% CI -1.97, -0.19, P = 0.018) and C-reactive protein (CRP) concentrations (WMD = -0.42 mg/L, 95% CI -0.82, -0.03, P = 0.034). However, berberine intake did not affect liver enzymes, including alanine aminotransferase (ALT) (WMD = -1.66 I/U, 95% CI -3.98, 0.65, P = 0.160) and aspartate aminotransferase (AST) (WMD = -0.87 I/U, 95% CI -2.56, 0.82, P = 0.311).

Conclusion: This meta-analysis found a significant reduction of body weight, BMI, WC and CRP levels associated with berberine intake which may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders. Berberine administration had no significant effect on ALT and AST levels.
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http://dx.doi.org/10.1016/j.clnesp.2020.04.010DOI Listing
August 2020

The Effects of Nano-curcumin on Metabolic Status in Patients With Diabetes on Hemodialysis, a Randomized, Double Blind, Placebo-controlled Trial.

Iran J Kidney Dis 2020 07;14(4):290-299

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Introduction: This study evaluated the effects of nano-curcumin intake on metabolic status in patients with diabetes on hemodialysis (HD).

Methods: This randomized, double-blind, placebo-controlled clinical trial was performed on 60 patients with diabetes on HD. Participants were randomly divided into two groups to take either 80 mg/d nano-curcumin (n = 30) or placebo (n = 30) for 12 weeks.

Results: Nano-curcumin significantly decreased fasting plasma glucose (β = -19.68 mg/dL, 95% CI: -33.48 to -5.88; P < .05) and serum insulin levels (β = -1.70 μIU/mL, 95% CI: -2.96 to -0.44; P < .05) when compared with patients who received placebo. Nanocurcumin treatment was associated with a significant reduction in triglycerides (β = -16.13 mg/dL, 95% CI: -31.51 to -0.75; P < .05), VLDL-cholesterol (β = -3.22 mg/dL, 95% CI: -6.30 to -0.15; P < .05), total cholesterol (β = -17.83 mg/dL, 95% CI: -29.22 to -6.45; P < .05), LDL-cholesterol (β = -15.20 mg/dL, 95% CI: -25.53 to -4.87; P < .05), and total-cholesterol/HDL-cholesterol ratio (β = -1.15, 95% CI: -0.2.10 to -0.21; P < .05) when compared with the placebo. Nanocurcumin also resulted in a significant reduction of serum high sensitivity CRP (β = -0.78 mg/L, 95% CI: -1.41 to -0.15; P < .05), and plasma malondialdehyde (β = -0.25 μmol/L, 95% CI: -0.45 to -0.04; P < .05); but also with a significant increase in plasma total antioxidant capacity (β = 52.43 mmol/L; 95% CI: 4.52 to 100.35; P < .05) and total nitrite levels (β = 3.62 μmol/L, 95% CI: 2.17 to 5.08; P < .001) when compared with placebo.

Conclusion: Nano-curcumin intake for 12 weeks had beneficial effects on metabolic profile in patients with diabetes on HD.
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July 2020

Acute pancreatitis after ocrelizumab treatment for relapsing remitting multiple sclerosis.

Mult Scler Relat Disord 2020 Oct 7;45:102381. Epub 2020 Jul 7.

University Hospital Center Zagreb Department of Neurology, Referral Center for Autonomic Nervous System Disorders, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia. Electronic address:

Ocrelizumab is an anti-CD20 monoclonal antibody used in the treatment of relapsing remitting and primary progressive multiple sclerosis. The main side effects are infusion-related with long term administration raising the risk of infections. During randomized controlled trials five cases of pancreatitis have been reported. We present a case of a patient with no risk factors for pancreatitis who after administration developed acute pancreatitis albeit with a good recovery.
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http://dx.doi.org/10.1016/j.msard.2020.102381DOI Listing
October 2020

Molecular and Biological Functions of Quercetin as a Natural Solution for Cardiovascular Disease Prevention and Treatment.

Plant Foods Hum Nutr 2020 Sep;75(3):307-315

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IR, Iran.

Cardiovascular disease (CVD) is a worldwide health problem with growing up rates of mortality and morbidity. Many risk factors, including high blood pressure, cigarette smoking, diabetes, obesity, and dyslipidemia are responsible for CVD. CVD can be prevented by some simple and cost-effective steps such as smoking cessation, normalizing body weight, regular physical activity, and dietary changes, including decreasing saturated fats, increasing the intake of vegetables and fruits, and reducing sugar intake. In the last decades, growing up number of studies were performed to explain the possible function of non-nutrient substances from the diet which might prevent CVD. One of these natural compounds is quercetin which is widely present in vegetables, tea, fruits and wine. Many in vitro, in vivo and clinical studies have indicated the cardioprotective functions of quercetin. They can be explained by quercetin's reducing blood pressure, antioxidant potential and some other activities. This review evaluates the experimental and clinical studies that have studied the effect of quercetin in CVD and summarizes the molecular mechanisms of action as well as clinical effects of quercetin in CVD.
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http://dx.doi.org/10.1007/s11130-020-00832-0DOI Listing
September 2020

At a glance: economic impact of industry-sponsored clinical trials of pharmaceutical products.

J Med Econ 2020 Oct 17;23(10):1193-1195. Epub 2020 Jul 17.

Halal Research Center of IRI, FDA, Tehran, Iran.

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http://dx.doi.org/10.1080/13696998.2020.1787419DOI Listing
October 2020

The effect of nutraceuticals on multiple signaling pathways in cardiac fibrosis injury and repair.

Heart Fail Rev 2020 Jun 3. Epub 2020 Jun 3.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.

Cardiac fibrosis is one of the most common pathological conditions caused by different heart diseases, including myocardial infarction and diabetic cardiomyopathy. Cardiovascular disease is one of the major causes of mortality worldwide. Cardiac fibrosis is caused by different processes, including inflammatory reactions and oxidative stress. The process of fibrosis begins by changing the balance between production and destruction of extracellular matrix components and stimulating the proliferation and differentiation of cardiac fibroblasts. Many studies have focused on finding drugs with less adverse effects for the treatment of cardiovascular disease. Some studies show that nutraceuticals are effective in preventing and treating diseases, including cardiovascular disease, and that they can reduce the risk. However, big clinical studies to prove the therapeutic properties of all these substances and their adverse effects are lacking so far. Therefore, in this review, we tried to summarize the knowledge on pathways and mechanisms of several nutraceuticals which have shown their usefulness in the prevention of cardiac fibrosis.
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http://dx.doi.org/10.1007/s10741-020-09980-6DOI Listing
June 2020