Syndecans and diabetic complications: A narrative review.

Syndecan (SDC) is a member of the heparan sulfate proteoglycan (HSPG) family. It appears to play a role in the aetiology of diabetic complications, with decreased levels of SDCs being reported in the kidney, retina, and cardiac muscle in models of diabetes mellitus (DM). The reduced levels of SDCs may play an important role in the development of albuminuria in DM. Some studies have provided the evidence supporting the mechanisms underlying the role of SDCs in DM. However, SDCs and the molecular mechanisms involved are complex and need to be further elucidated. This review focuses on the underlying molecular mechanisms of SDCs that are involved in the development and progression of the complications of DM, which may help in developing new strategies to prevent and treat these complications.

Factors associated with prolonged QTc interval in Iranian population: MASHAD cohort study.

AIM: QTc interval prolongation is a growing global issue which can cause torsades de pointes, a potentially fatal arrhythmia. We aimed to identify risk factors for prolonged QT interval in men and women. METHODS: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study collected electrocardiogram interval data. QT was corrected for heart rate using the Bazett's formula. Ordinal logistic regression with crude (univariable) and adjusted (multivariate) association analyses in the form of odds ratio and corresponding 95% confidence interval (CI) were used to identify the factors associated with QTc prolongation. RESULTS: A total of 8878 individuals including 5318 females and 3560 males, aged 35 to 65 years, were included in this cross-sectional study. Participants with QTc prolongation were more likely to be older and have hypercholesterolemia, hypertension (HTN), and Type 2 diabetes mellitus (T2DM), but to have lower levels of physical activity (P < 0.05). Age (OR = 1.68, 95%CI = 1.18-2.39), hypercholesterolemia (OR = 1.77, 95%CI = 1.24-2.51), HTN (OR = 1.36, 95%CI = 1.06-1.73), T2DM (OR = 1.59, 95%CI = 1.19-2.13), severe anxiety (OR = 1.80, 95%CI = 1.05-3.11) and mild depression (OR = 1.38, 95%CI = 1.01-1.88) were independent risk factors for prolonged QTc interval in men. For women, only HTN (OR = 1.29, 95%CI = 1.02-1.63) and T2DM (OR = 1.50, 95%CI = 1.14-1.97) were independent risk factors. CONCLUSIONS: Older age, Hypercholesterolemia, HTN, T2DM, severe anxiety and mild depression in men, and HTN and T2DM in women were associated with high risk of prolonged QTc interval. Healthcare practitioners should be aware of the risk factors of QTc interval prolongation and should exercise caution in the management of certain patients.

Utilizing the sublingual form of squalene in COVID-19 patients: a randomized clinical trial.

In this study, the efficacy of sublingual squalene in decreasing the mortality rate among patients with COVID-19 was investigated. Squalene was extracted from pumpkin seed oil with a novel method. Then, the microemulsion form of squalene was prepared for sublingual usage. In the clinical study, among 850 admitted patients, 602 eligible COVID-19 patients were divided in two groups of control (N = 301) and cases (N = 301) between Nov 2021 and Jan 2022. Groups were statistically the same in terms of age, sex, BMI, lymphocyte count on 1st admission day, hypertension, chronic kidney disease, chronic respiratory disease, immunosuppressive disease, and required standard treatments. The treatment group received five drops of sublingual squalene every 4 h for 5 days plus standard treatment, while the control group received only standard treatment. Patients were followed up for 30 days after discharge from the hospital. The sublingual form of squalene in the microemulsion form was associated with a significant decrease in the mortality rate (p < 0.001), in which 285 (94.7%) cases were alive after one month while 245 (81.4%) controls were alive after 1 month of discharge from the hospital. In addition, squalene appears to be effective in preventing re-hospitalization due to COVID-19 (p < 0.001), with 141 of controls (46.8%) versus 58 cases (19.3%). This study suggests sublingual squalene in the microemulsion as an effective drug for reducing mortality and re-hospitalization rates in COVID-19 patients.Trial Registration Number: IRCT20200927048848N3.

The effects of statins on the function and differentiation of blood cells.

Statins are inhibitors of ß-hydroxy ß-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR). They are used in patients with cardiovascular risk and/or suffering with cardiovascular disease. In addition to their efficient lipid-lowering effects, statins exhibit independent so called pleiotropic effects potentially affecting several immune response properties including immune cell activation, migration, cytokine generation, immune metabolism, and survival. Statins also regulate innate and acquired immunity. The focus of this review is to highlight the role of statins in modulating the function and differentiation of various blood cells. Given the proposed wider application of these medicines and their potentially important advantages in treatment of inflammatory and autoimmune disorders, more studies are needed with special focus on the molecular targets of statins included in regulating the immune response.

Association between dietary copper and cardiovascular disease: A narrative review.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity. Several studies have investigated the relationship between trace element status, including copper status, and CVDs in population studies; however, there are controversies about the role of dietary copper and CVD. We aimed to review the association between dietary copper intake with CVD and this association's related factors by reviewing both animal models and human studies. Some animal model studies have reported a strong relationship between dietary copper intake and atherogenesis based on the possible molecular pathways, whilst other studies have not confirmed this relationship. Human studies have not revealed a relationship between CVDs and dietary copper intake, but there is uncertainty about the optimal amount of dietary copper intake in relation reducing the risk of CVDs. These associations may be influenced by ethnicity, gender, underlying co-morbidities and the methods used for its measurement.

Association of dietary and blood inflammatory indicators with depression, anxiety, and stress in adults with vitamin D deficiency.

BACKGROUND: There is growing evidence that vitamin D may be related to mental health. The aim of the current study was to investigate the association of dietary and blood inflammatory factors with mental health disorders in subjects with vitamin D deficiency, shedding further light on the complex interplay of these conditions. METHOD: In this cross-sectional study, 306 subjects completed the validated Depression, Anxiety, and Stress Scale questionnaire to evaluate their depression, anxiety, and stress scores. Dietary inflammatory index (DII) and healthy eating index (HEI) were calculated using a validated 65-item food frequency questionnaire. Blood samples were taken and vitamin D, cytokine, and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) were calculated using standard laboratory methods. RESULTS: The subjects were divided into two groups based on their vitamin D levels: a vitamin D < 20 µg/dl group (N = 257) and a vitamin D ≥ 20  µg/dl group (N = 49). Between group analysis revealed that only DII (p = 0.015), platelet (p = 0.04), and hs-CRP (p = 0.015) were significantly different. In adults with vitamin D levels below 20 µg/dl, NLR and DII were significantly higher in subjects with anxiety (p < 0.05), and this relationship remained significant only for NLR after adjusting for age and sex. Additionally, PLR and HEI were significantly different in depressed compared to non-depressed subjects, and this association remained significant only for HEI after adjusting for age and sex. CONCLUSION: In subjects with vitamin D deficiency, increased levels of PLR, NLR, and DII were associated with depression and anxiety, while HEI was negatively associated with depression. These associations were not found in subjects with vitamin D levels ≥20 µg/dl.

Compositional and functional properties of high-density lipoproteins in relation to coronary in-stent restenosis.

Introduction: In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Use of drugs such as statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed to evaluate the compositional and functional alterations of HDL in individuals with ISR. Material and methods: This case-control study included 21 ISR, 26 non-ISR (NISR), 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/ml) and HDL3 (d: 1.125-1.210 g/ml) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to take up free cholesterol (FC) from triglyceride-rich lipoproteins (TGRLs) during lipolysis was assessed. Results: No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. The NISR group showed lower triglyceride content in HDL2 and higher phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy (r = 0.50), angiography-negative (r = 0.55) and ISR (r = 0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to take up free cholesterol was not different among the groups. Conclusions: Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to take up free cholesterol from TGRLs during lipolysis was not associated with ISR in this study.

Prediction of type 2 diabetes mellitus using hematological factors based on machine learning approaches: a cohort study analysis.

Type 2 Diabetes Mellitus (T2DM) is a significant public health problem globally. The diagnosis and management of diabetes are critical to reduce the diabetes complications including cardiovascular disease and cancer. This study was designed to assess the potential association between T2DM and routinely measured hematological parameters. This study was a subsample of 9000 adults aged 35-65 years recruited as part of Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study. Machine learning techniques including logistic regression (LR), decision tree (DT) and bootstrap forest (BF) algorithms were applied to analyze data. All data analyses were performed using SPSS version 22 and SAS JMP Pro version 13 at a significant level of 0.05. Based on the performance indices, the BF model gave high accuracy, precision, specificity, and AUC. Previous studies suggested the positive relationship of triglyceride-glucose (TyG) index with T2DM, so we considered the association of TyG index with hematological factors. We found this association was aligned with their results regarding T2DM, except MCHC. The most effective factors in the BF model were age and WBC (white blood cell). The BF model represented a better performance to predict T2DM. Our model provides valuable information to predict T2DM like age and WBC.

Investigating the inflammatory status in the patients candidate for second angiography after coronary stent implantation.

BACKGROUND: Inflammation has been shown to be an important feature of atherosclerosis. We aimed to assess a profile of inflammatory cytokines and growth factors in patients with established coronary artery disease (CAD), 12 months after stent implantation. METHODS: A total of 193 patients with CAD, who were candidates for angiography, 12 months after stent implantation (cases), were compared with 107 patients with CAD, who were candidates for their first angiography (controls). Fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) were measured using routine methods. The serum concentrations of IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, EGF and VEGF were determined using competitive chemiluminescence immunoassays. RESULTS: Serum levels of FBG (p = .002), TG (p = .029) and hs-CRP (p = .005) were significantly lower in cases than controls. The cytokines and growth factor profiles in cases were significantly different from controls. After multivariate analysis, serum levels of IL-2 (p < .001), IL-4 (p = .028) were significantly lower in cases compared with the controls while serum levels of IL-8, TNF-α, MCP-1, EGF and VEGF were significantly higher in the cases (p < .001). CONCLUSIONS: In patients with CAD and higher consumption of drug used (statins, aspirin and glucose lowering agents) to mitigate the risk of a secondary event, the level of hs-CRP one year after stent implantation decreased despite of significant higher serum levels of pro- and anti-inflammatory cytokines and growth factors.

Adherence to dietary approaches to stop hypertension (DASH) diet in relation to psychological function in recovered COVID-19 patients: a case-control study.

BACKGROUND: Follow-up of patients after recovery from coronavirus disease 2019 (COVID-19) and identifying the adverse effects of the disease in other organs is necessary. Psychiatric symptoms can persist after patients recover from the infection. AIM: We aimed to examine the adherence to the dietary approach to stop hypertension (DASH) diet in relation to psychological function in individuals who have recovered from COVID-19. METHOD: This case-control study was conducted on 246 eligible adults (123 cases and 123 controls). A valid and reliable food frequency questionnaire (FFQ) was used to determine dietary intake. Depression, anxiety and stress, insomnia, sleep quality, and quality of life of participants were evaluated using DASS, Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaires, respectively. RESULTS: There was a significant inverse correlation between total depression score with vegetables, depression, anxiety, and stress score and dietary intake of nuts, legumes, and whole grains (p < 0.05). There was a significant positive correlation between stress scores and the intake of red and processed meat (P < 0.05). In multivariate-adjusted regression model, a significant association was found between adherence to DASH diet and depression and stress only in case group (OR = 0.7863, 95% CI 0.746-0.997, p = 0.046 and OR = 0.876, 95% CI 0.771-0.995, p = 0.042, respectively). CONCLUSION: Adherence to a DASH diet might be associated with depression and stress reduction in recovered COVID-19 patients.

Associação do Genótipo e Fenótipo da Paraoxonase-1 com Angiografia Positiva para Doença Arterial Coronariana / Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease

Resumo Fundamento Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas. Objetivos Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC). Métodos Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante. Resultados A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019). Conclusões A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.

Abstract Background It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. Objective To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). Methods A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. Results Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). Conclusions The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.

Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease. / Associação do Genótipo e Fenótipo da Paraoxonase-1 com Angiografia Positiva para Doença Arterial Coronariana.

BACKGROUND: It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. OBJECTIVE: To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). METHODS: A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. RESULTS: Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). CONCLUSIONS: The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.

FUNDAMENTO: Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas. OBJETIVOS: Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC). MÉTODOS: Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante. RESULTADOS: A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019). CONCLUSÕES: A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.

Evaluating the efficacy of extracted squalene from seed oil in the form of microemulsion for the treatment of COVID-19: A clinical study.

This study investigates the effect of the nanostructure of squalene in the form of microemulsion on COVID-19 patients. In this blinded clinical trial, a comparison was made between the efficacy of squalene treatment and controls. A total of 30 COVID-19 patients admitted to the emergency department, and the infection ward was equally allocated to case (n = 15) and control (n = 15) groups according to their age and underlying diseases. The baseline characteristics of subjects, including age, gender, time of treatment onset, underlying condition, white blood cells count, and lymphocyte count were similar (p < 0.05). Baseline laboratory tests and computed tomography (CT) scans were performed for the study groups. The treatment group received 5 mg of intravenous squalene twice a day and standard treatment for 6 days, while controls received only standard treatment. After 6 days of treatment, clinical and CT scan changes were evaluated and compared in intervention and control groups. The need for oxygen therapy (p = 0.020), 2 days of no fever (p = 0.025), cough alleviation (p = 0.010), and lung high-resolution computed tomography improvement (p = 0.033) were significantly different between cases and controls within 7 days of admission. No adverse effects were observed in the treatment group. Our data suggest that squalene could be considered as a potential treatment for COVID-19, and further studies are required to confirm the results.

Dietary protein is the strong predictor of coronary artery disease; a data mining approach.

BACKGROUNDS: Coronary artery disease (CAD) is the major cause of mortality and morbidity globally. Diet is known to contribute to CAD risk, and the dietary intake of specific macro- or micro-nutrients might be potential predictors of CAD risk. Machine learning methods may be helpful in the analysis of the contribution of several parameters in dietary including macro- and micro-nutrients to CAD risk. Here we aimed to determine the most important dietary factors for predicting CAD. METHODS: A total of 273 cases with more than 50% obstruction in at least one coronary artery and 443 healthy controls who completed a food frequency questionnaire (FFQ) were entered into the study. All dietary intakes were adjusted for energy intake. The QUEST method was applied to determine the diagnosis pattern of CAD. RESULTS: A total of 34 dietary variables obtained from the FFQ were entered into the initial study analysis, of these variables 23 were significantly associated with CAD according to t-tests. Of these 23 dietary input variables, adjusted protein, manganese, biotin, zinc and cholesterol remained in the model. According to our tree, only protein intake could identify the patients with coronary artery stenosis according to angiography from healthy participant up to 80%. The dietary intake of manganese was the second most important variable. The accuracy of the tree was 84.36% for the training dataset and 82.94% for the testing dataset. CONCLUSION: Among several dietary macro- and micro-nutrients, a combination of protein, manganese, biotin, zinc and cholesterol could predict the presence of CAD in individuals undergoing angiography.

Effect of Curcumin on Severity of Functional Dyspepsia: a Triple Blinded Clinical Trial.

BackgroundFunctional dyspepsia is the main cause of upper abdominal discomfort affecting 5-10% of the world population. Despite various therapeutic approaches, up to 50% of patients with functional dyspepsia seek alternative treatments. In the present study we evaluated the effect of curcumin supplementation along with famotidine therapy on severity of functional dyspepsia. A total of 75 patients with functional dyspepsia according to Rome III criteria were allocated into intervention (N = 39) or control (N = 36) groups. The intervention group was treated with a combination of 500 mg curcumin and 40 mg famotidine daily for 1 month. The control group received placebo and 40 mg famotidine. Severity of dyspepsia symptoms was determined using the Hong Kong questionnaire at baseline, after the 1 month treatment and after a 1 month follow-up. The presence of H. pylori antigens in the stool samples was also investigated in all subjects. No significant difference was observed between intervention and control groups in biochemical indices, severity of dyspepsia and rate of H. pylori infection. A significant decrease was observed in severity of dyspepsia (p < 0.001) and rate of H. pylori infection (p = 0.004) immediately after the treatment and follow-up in the curcumin intervention group. This study indicated that curcumin therapy could be a favorable supplementation in the symptom management of functional dyspepsia. Moreover, curcumin could help efficient eradication of H. pylori in these patients.

The association between genetic polymorphisms of the interleukin-10, tumor necrosis factor-alpha, and annexin A5 gene loci and restenosis after percutaneous coronary angioplasty and stenting.

BACKGROUND: Advances in the technology for percutaneous coronary angioplasty, such as coated stents, have reduced its complications, but restenosis remains an important clinical problem. The factors associated with an increased risk of restenosis include diabetes mellitus and multiple coronary artery disease. It is also possible that genetic factors play a role in restenosis although there are little data on this. We have investigated the association of three genetic markers of genes involved in inflammation leading to restenosis. MATERIALS AND METHODS: In this case-control study, 306 unrelated Iranian patients who were thought to have restenosis on clinical grounds were investigated. Based on the results of angiography, 104 patients were found to have >50% stenosis within an implanted stent, and these were allocated to the in-stent restenosis (ISR) group; 202 patients with no in-stent stenosis or stenosis ≤50% were allocated to the non-ISR (NISR) group. Demographic data were collected from medical records. Biochemical parameters were measured using routine methods. Genotypes of the interleukin-10 (IL-10), annexin A5 (AnxA5), and tumor necrosis factor-alpha (TNFα) loci were determined using real-time polymerase chain reaction and a high-resolution melting assay. RESULTS: Fasting blood glucose, serum triglycerides, and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were higher in the ISR group than in the NISR group (P < 0.05), and a history of diabetes mellitus was significantly related to the presence of restenosis (P < 0.001). There were no significant differences in the frequency of the genetic polymorphisms of IL-10, AnxA5, and TNFα genes and the presence of ISR. CONCLUSION: After adjustment for clinical variables, the genetic polymorphisms at the IL-10, TNFα, and ANXA5 gene loci do not appear to be risk factors for >50% ISR in our population. However, our data suggested a significant association between diabetes mellitus, serum hs-CRP, stent type, and restenosis.

Efficacy of phospholipidated curcumin in nonalcoholic fatty liver disease: a clinical study.

Curcumin is a safe and dietary phytochemical that can improve different pathophysiologic features of non-alcoholic fatty liver disease (NAFLD). Here, we investigated the efficacy of phospholipidated curcumin supplementation in NAFLD patients. In this single-arm study, 36 patients were recruited. Each patient received three capsules a day (each containing 500 mg of phospholipidated curcumin [overall content of curcuminoids per capsule: 100 mg]) for a period of 8 weeks. The results indicated that phospholipidated curcumin supplementation reduced NAFLD severity and ameliorated ultrasonographic and biochemical measures (including liver transaminases and lipid profile) associated with disease progression.

Curcumin: A Natural Pan-HDAC Inhibitor in Cancer.

BACKGROUND: Histone deacetylases (HDACs) are a group of histone modification enzymes with pivotal role in disease pathogenesis especially in cancer development. Increased activity of certain types of HDACs and positive effects of HDAC inhibition has been shown in several types of cancers. Furthermore, few HDAC inhibitors have been approved by the FDA for cancer treatment, and this has generated interest in finding new HDAC inhibitors as potential anti-cancer agents. Curcumin, a natural polyphenol extracted from turmeric, is a safe and bioactive phytochemical with a wide range of molecular targets and pharmacological activities including promising anti-cancer properties. METHODS: A systematic literature search using appropriate keywords was made to identify articles reporting the modulatory effect of curcumin on HDACs in different types of cancer in vitro and in vivo. RESULTS: HDACs have emerged as novel targets of curcumin that their modulation may contribute to the putative anti-cancer effects of curcumin. Curcumin inhibits HDAC activity, and down-regulates the expression of HDAC types 1, 2, 3, 4, 5, 6, 8 and 11 in different cancer cell lines and mice, while the activity and expression of HDAC2 have been reported to be up-regulated by curcumin in COPD and heart failure models. CONCLUSION: Available in vitro and in vivo data are encouraging and in favor of the HDAC inhibitory activity of curcumin but clinical evidence on the efficacy of curcumin as an adjunct treatment in cancer patients is lacking.

Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial.

OBJECTIVE: Previous experimental studies have suggested curcumin as a safe phytochemical that can improve insulin resistance through effects on adiponectin and leptin. This study aimed to investigate the effect of curcumin on circulating adiponectin and leptin concentrations in patients with metabolic syndrome. METHODS: In this pilot, randomized, double-blind, placebo-controlled trial, subjects who met the criteria of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria were randomly assigned to curcumin (n = 59; 1000 mg/d) or a placebo (n = 58) for 8 wk. Serum adiponectin and leptin concentrations were determined before and after intervention. The pooled effect size for the impact of curcumin supplementation on serum adiponectin and leptin levels was also estimated using random-effects metaanalysis. RESULTS: Eight-week supplementation with curcumin was associated with a significant increase in serum adiponectin levels (P < 0.001) and a reduction in serum leptin concentrations (P < 0.001). Serum leptin:adiponectin ratio was also improved by curcumin (P < 0.001). These beneficial effects of curcumin remained significant after adjustment for changes in serum lipids and glucose concentrations and baseline differences in body mass index and serum levels of glucose and glycated hemoglobin as potential confounders of treatment response. Metaanalysis suggested that curcumin supplementation can increase adiponectin levels by 76.78% (95% CI: 6.14-147.42; P = 0.0330), and reduce leptin by 26.49% (95% CI: -70.44 to 17.46), however this latter effect size did not reach statistical significance (P = 0.238). CONCLUSIONS: Curcumin can improve serum levels of adiponectin and leptin in patients with metabolic syndrome. This trial was registered at the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/) under Trial No. UMIN000018339.

Investigation of the efficacy of generic and brand-name tiotropium bromide in the management of chronic obstructive pulmonary disease: A randomized comparative trial.

INTRODUCTION: The beneficial effects of tiotropium bromide, a long acting anticholinergic bronchodilator, in the management of chronic obstructive pulmonary disease have been shown in previous studies. The present study aimed to compare the efficacy and safety of generic (Tiova®) and brand-name (Spiriva®) tiotropium preparations in patients with COPD. METHODS AND MATERIALS: In this randomized double-blind parallel-group trial, 79 patients with documented COPD were assigned to Tiova® or Spiriva® for a period of 4 weeks. Assessment of pulmonary function (using spirometry), quality-of-life (using St. George respiratory Questionnaire [SGRQ]) and severity of respiratory symptoms (using breathlessness, cough and sputum scale [BCSS]) was performed at baseline and at the end of treatment period. RESULTS: There were significant increases in FEV1 and reductions in FVC by the end of study in both Tiova® and Spiriva® groups. FEV1/FVC ratio did not change significantly neither in the Tiova® nor in Spiriva® group. Overall SGRQ score as well as subscale scores of symptoms, activity and impacts were improved by both drugs. In the BCSS scale, the frequency and severity of three main symptoms (dyspnea, cough and sputum) was decreased by both drugs. Baseline as well as post-treatment values of spirometric parameters, SGRQ and BCSS scores was comparable between the groups, apart from a lower post-treatment frequency of cough and sputum in the Spiriva® versus Tiova® group. There was no report of adverse events in either of the study groups. CONCLUSION: The findings of this comparative trial showed equivalent efficacy and safety of Spiriva® and Tiova® in lessening the symptoms as well as improving the quality of life in patients with COPD. This finding has an important translational value given the significantly lower costs of generic versus brand-name products.