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INTRODUCTION: Acute pulmonary thromboembolism (PTE) is a life-threatening disease. Considering the availability and accessibility of assessing the serum lipids, this study aims to define the predictive value of lipid profile, as well as the history of lipid disorders, for the mortality of PTE patients. CONTENT: Clinical studies, in which the relation of lipid profile, including triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol, as well as history of imbalance of lipids, with mortality of PTE patients was reported, were included. Non-English articles, reviews, letters, editorials, and non-English papers were excluded. A systematic search was conducted in PubMed, Embase, Scopus, and Web of Science databases. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal tools and CMA 4 was utilized for the quantitative synthesis. Out of 3,724 records, six studies were included in this systematic review. Lipid profile is suggested as a prognostic marker for survival in patients with PTE so higher initial serum HDL, LDL, and total cholesterol levels were associated with lower mortality rates in PTE patients. In addition, dyslipidemia was found to be associated with mortality of PTE patients. Based on the quantitative synthesis, there was a greater serum level of HDL in the survival group (standardized mean difference: -0.98; 95â¯% CI: -1.22 to -0.75; p-value<0.01). SUMMARY AND OUTLOOK: Mortality is lower in PTE patients with greater serum lipid levels; therefore, the early prognosis of PTE may be ascertained by measuring serum lipids within the first 24â¯h of admission.
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Drug hypersensitivities are common reactions due to immunologic responses. They are of utmost importance because they may generate severe and fatal outcomes. Some drugs may cause Adverse Drug Reactions (ADRs), such as drug hypersensitivity reactions (DHRs), which can occur due to the interaction of intact drugs or their metabolites with Human Leukocyte Antigens (HLAs) and T cell receptors (TCRs). This type develops over a period of 24-72 h after exposure and is classified as type IV of DHRs. Acute generalized exanthematic pustulosis (AGEP), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are types of Severe Cutaneous Adverse Reactions (SCARs). In this review, we aim to discuss the types of ADRs, the mechanisms involved in their development, and the role of immunogenetic factors, such as HLAs in type IV DHRs, single-nucleotide polymorphisms (SNPs), and some epigenetic modifications, e.g., DNA/histone methylation in a variety of genes and their promoters which may predispose subjects to DHRs. In conclusion, development of promising novel in vitro or in vivo diagnostic and prognostic markers is essential for identifying susceptible subjects or providing treatment protocols to work up patients with drug allergies as personalized medicine.
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OBJECTIVES: Metastasis in breast cancer is the first cause of death in patients. The epidermal growth factor (EGF) increases cancer cells' invasion, and migration. Melatonin's inhibitory effects on various types of cancer were confirmed. This study aimed to investigate whether melatonin could apply its impact through the EGF-related pathways or not. METHODS: First, MDA-MB-231 and MCF7 cells were cultured, and then melatonin effects on cell viability were determined by MTT assay. Transwell invasion assay was applied to identify the invasiveness of these breast cancer cell lines under treatment of EGF and melatonin. Real-time RT-PCR then investigated the expression of MMP9 and MMP2 in determined groups. Cell proliferation was also assayed under EGF and melatonin treatment using Ki67 assessment by flow cytometry. RESULTS: The rate of invasion and migration of EGF-treated cells increased in both groups, in which melatonin caused increased invasion by EGF just in MCF7 cells. MMP9 and MMP2 expression increased significantly in both cell lines under EGF treatment, and melatonin increased these genes' expression in both cell lines (p<0.05). EGF increased the MMP9 and MMP2 gene expression, and melatonin increased EGF-induced expression (p<0.05). The EGF reduced the expression of the Ki67 protein in the MCF7 cell line, which was negatively affected by melatonin and EGF. In contrast, along with melatonin, EGF did not affect the proliferation of the MDA-MB-231 cell line. CONCLUSIONS: The results of this study show that melatonin in the presence of EGF does not show the anti-cancer properties previously described for this substance.
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INTRODUCTION: Coronary artery disease (CAD) in young adults can have devastating consequences. The cardiac developmental gene MEIS1 plays important roles in vascular networks and heart development. This gene effects on the regeneration capacity of the heart. Considering role of MEIS1 in cardiac tissue development and the progression of myocardial infarction this study investigated the expression levels of the MEIS1, HIRA, and Myocardin genes in premature CAD patients compared to healthy subjects and evaluated the relationships between these genes and possible inflammatory factors. METHODS AND RESULTS: The study conducted a case-control design involving 35 CAD patients and 35 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were collected, and gene expression analysis was performed using real-time PCR. Compared with control group, the number of PBMCs in the CAD group exhibited greater MEIS1 and HIRA gene expression, with fold changes of 2.45 and 3.6. The expression of MEIS1 exhibited a negative correlation with IL-10 (r= -0.312) expression and positive correlation with Interleukin (IL)-6 (r = 0.415) and tumor necrosis factor (TNF)-α (r = 0.534) gene expression. Moreover, there was an inverse correlation between the gene expression of HIRA and that of IL-10 (r= -0.326), and a positive correlation was revealed between the expression of this gene and that of the IL-6 (r = 0.453) and TNF-α (r = 0.572) genes. CONCLUSION: This research demonstrated a disparity in expression levels of MEIS1, HIRA, and Myocardin, between CAD and healthy subjects. The results showed that, MEIS1 and HIRA play significant roles in regulating the synthesis of proinflammatory cytokines, namely, TNF-α and IL-6.
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Enfermedad de la Arteria Coronaria , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide , Proteínas Nucleares , Transactivadores , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Enfermedad de la Arteria Coronaria/genética , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Interleucina-10/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Leucocitos Mononucleares/metabolismo , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide/genética , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Transactivadores/genética , Transactivadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Background: Triple-negative breast cancer (TNBC) with a poor prognosis and survival is the most invasive subtype of breast cancer. Usually, TNBC requires a chemotherapy regimen at all stages, but chemotherapy drugs have shown many side effects. We assumed that combination therapy of vinblastine and silibinin might reduce the vinblastine toxicity and dose of vinblastine. Materials and Methods: The MDA-MB-231 were cells subjected to MTT assay for IC50 determination and combination effects, which were measured based on Chou-Talalay's method. The type of cell death was determined by using a Flow-cytometric assay. Cell death pathway markers, including Bcl-2, Bax, and caspase-3 were analyzed by western blot and Real-Time PCR. Results: The treatment of MDA-MB-231 cells exhibited IC50 and synergism at the combination of 30 µM of silibinin and 4 µm of vinblastine in cell viability assay (CI=0.69). YO-PRO-1/PI double staining results showed a significant induction of apoptosis when MDA-MB-231 cells were treated with a silibinin and vinblastine combination (p<0.01). Protein levels of Bax and cleaved caspase-3 were significantly upregulated, and Bcl-2 downregulated significantly. Significant upregulation of Bax (2.96-fold) and caspase-3 (3.46-fold) while Bcl-2 was downregulated by 2-fold. Conclusion: Findings established a preclinical rationale for the combination of silibinin and vinblastine. This combination produces synergistic effects in MDA-MB-231 cells by altering pro- and anti-apoptotic genes, which may reduce the toxicity and side effects of vinblastine.
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[This corrects the article DOI: 10.1007/s40200-023-01198-1.].
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This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.
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This study aimed at modelling the underlying predictor of ASCVD through the Bayesian network (BN). Data for the AZAR Cohort Study, which evaluated 500 healthcare providers in Iran, was collected through examinations, and blood samples. Two BNs were used to explore a suitable causal model for analysing the underlying predictor of ASCVD; Bayesian search through an algorithmic approach and knowledge-based BNs. Results showed significant differences in ASCVD risk factors across background variables' levels. The diagnostic indices showed better performance for the knowledge-based BN (Area under ROC curve (AUC) = 0.78, Accuracy = 76.6, Sensitivity = 62.5, Negative predictive value (NPV) = 96.0, Negative Likelihood Ratio (LR-) = 0.48) compared to Bayesian search (AUC = 0.76, Accuracy = 72.4, Sensitivity = 17.5, NPV = 93.2, LR- = 0.83). In addition, we decided on knowledge-based BN because of the interpretability of the relationships. Based on this BN, being male (conditional probability = 63.7), age over 45 (36.3), overweight (51.5), Mets (23.8), diabetes (8.3), smoking (10.6), hypertension (12.1), high T-C (28.5), high LDL-C (23.9), FBS (12.1), and TG (25.9) levels were associated with higher ASCVD risk. Low and normal HDL-C levels also had higher ASCVD risk (35.3 and 37.4), while high HDL-C levels had lower risk (27.3). In conclusion, BN demonstrated that ASCVD was significantly associated with certain risk factors including being older and overweight male, having a history of Mets, diabetes, hypertension, having high levels of T-C, LDL-C, FBS, and TG, but Low and normal HDL-C and being a smoker. The study may provide valuable insights for developing effective prevention strategies for ASCVD in Iran.
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Aterosclerosis , Enfermedades Cardiovasculares , Diabetes Mellitus , Hipertensión , Humanos , Masculino , Femenino , Estudios de Cohortes , Enfermedades Cardiovasculares/complicaciones , LDL-Colesterol , Teorema de Bayes , Sobrepeso/complicaciones , Factores de Riesgo , Hipertensión/complicacionesRESUMEN
BACKGROUND: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-ß genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). METHODS: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1α (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-ß between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. CONCLUSION: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Metabolismo de los Lípidos/genética , Sirtuina 1/genética , Sirtuina 1/metabolismo , Sirtuina 1/uso terapéutico , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Irán , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Activados del Proliferador del Peroxisoma/uso terapéutico , Neurregulinas/metabolismo , Neurregulinas/uso terapéutico , ARN Mensajero/metabolismo , ARN Mensajero/uso terapéutico , Suplementos DietéticosRESUMEN
Background: Aortic valve replacement (AVR) may complicate conduction abnormalities and require permanent pacemaker (PPM) implantation. New techniques that lessen this challenge may lead to the development of new approaches. Our objective was to evaluate the contemporary incidence of early postoperative PPM implantation in patients undergoing isolated AVR and root disease with the standard AVR surgical technique compared with the novel suture AVR technique. Methods: The clinical data of 354 patients (250 male, 104 female) who underwent surgery for isolated AVR and root disease in different referral cardiology departments in Tabriz, Iran, over 4 years were analyzed. Patients with preoperative significant conduction abnormalities were excluded from the study. The patients were evaluated for in-hospital mortality, postoperative PPM implantation, and their stay in the ICU after surgery. Results: The mean age of the patients was 52.46±16.13 years. Totally, 183 patients (51.7%) were operated on with the new suture AVR technique. In-hospital mortality was lower in this group than in the group that underwent the "classic" surgical technique (2.5% vs 3.7%). PPM implantation was required in 3 patients (0.8%) after the novel suture AVR technique, whereas it was needed in 12 patients (3.4%) in the other group (P=0.024). The mortality rate was 9 patients (2.5%) in group 1 and 13 patients (3.7%) in group 2, which was not statistically significant (P=0.296). According to the logistic regression, the survival rate in the group operated on with the classical surgical method was 0.27 times higher than that in the patients operated on with the new method. Conclusion: Permanent complete AV block is a critical complication after AVR surgery. A lower PPM requirement and higher survival in patients operated on with the new method was the main finding of this study. New techniques with lower PPM requirements may be suitable for cardiac surgery.
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Introduction: Previous meta-analyses investigating the therapeutic effects of L-carnitine on lipid profiles have demonstrated inconsistent results. The present umbrella meta-analysis aimed to investigate the impact of efficacy of L-carnitine on lipid profiles in adults. Methods: Databases including PubMed, Scopus, and Embase, Web of Science, and Google Scholar were searched up to June 2023. Meta-analysis was performed using a random-effects model. Results: Our results from thirteen meta-analyses indicated that L-carnitine supplementation significantly total cholesterol (TC) (ES = -1.05 mg/dL, 95% CI: -1.71, -0.39; p = 0.002), triglycerides (TG) (ES = -2.51 mg/dL; 95% CI: -3.62, -1.39, p < 0.001), and low-density lipoprotein-cholesterol (LDL-C) (ES = -4.81 mg/dL; 95% CI: -6.04, -3.59; p < 0.001). It also increased high-density lipoprotein-cholesterol (HDL-C) (ES: 0.66 mg/dL, 95% CI: 0.20, 1.12, p = 0.005) levels. Conclusion: The present umbrella meta-analysis suggests supplementation with L-carnitine in a dosage of more than 2 g/day can improve lipid profile. Thus, L-carnitine supplementation can be recommended as an adjuvant anti-hyperlipidemic agent.
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Three-dimensional (3D) myocardial tissues for studying human heart biology, physiology and pharmacology have recently received lots of attention. Organoids as 3D mini-organs are created from multiple cell types (i.e. induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs)) with other supporting co-cultured cells such as endothelial cells or fibroblasts. Cardiac organoid culture technologies are bringing about significant advances in organ research and allows for the establishment of tissue regeneration and disease modeling. The present review provides an overview of the recent advances in human cardiac organoid platforms in disease biology and for cardiovascular regenerative medicine.
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BACKGROUND: Obesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet. METHODS: This triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit. DISCUSSION: New evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20190303042905N2 . Registered on 31 January 2021.
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Dieta Reductora , PPAR alfa , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR alfa/uso terapéutico , Ácido Butírico/uso terapéutico , Péptido 1 Similar al Glucagón/uso terapéutico , Proteína Desacopladora 1/genética , Factores de Transcripción , Obesidad/diagnóstico , Obesidad/tratamiento farmacológico , Obesidad/genética , Suplementos Dietéticos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: The slow coronary flow (SCF) phenomenon is considered a coronary artery disorder. Because of the critical function of peroxisome proliferator-activated receptors (PPARs) in regulating the oxidative stress and inflammatory reactions in cardiovascular disease, The aim of the current study was to investigate the expression of the genes for uncoupling proteins 1 and 2 (UCP1 and UCP2), peroxisome proliferator-activated receptors and (PPAR- PPAR-), and PPAR- in SCF patients. METHODS: In this case-control study, coronary angiography examination was used to analyze 35 individuals with SCF and 35 subjects with normal coronary flow (NCF). SCF was diagnosed using the TIMI (thrombolysis in myocardial infarction frame count) method. The SCF phenomenon is thought to be the TIMI > 27. In the peripheral blood mononuclear cells (PBMCs), the messenger ribonucleic acid (mRNA) expression levels of the PPAR-, PPAR-, UCP1, and UCP2 genes were evaluated. RESULTS: UCP1 and UCP2 expression levels were significantly higher in the SCF group compared to the NCF group (P = 0.034 and P0.001, respectively). The PPAR- and PPAR- levels were found to be significantly lower in the SCF group compared to the NCF group (P = 0.015, P0.001, respectively). According to the results of the logistic regression analysis, high UCP1 and UCP2 levels and low PPAR- and PPAR- levels are each independent predictors of the SCF phenomenon. CONCLUSION: This research provided evidence about the potential role of PPAR-α, PPAR-γ, UCP1, and UCP2 as biomarkers in SCF. More investigations are suggested to assess the functions of these factors in SCF patients mechanistically.
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Enfermedad de la Arteria Coronaria , Circulación Coronaria , Humanos , Estudios de Casos y Controles , Circulación Coronaria/fisiología , PPAR gamma/genética , Leucocitos Mononucleares , Angiografía Coronaria , Vasos Coronarios , Proteína Desacopladora 1/genéticaRESUMEN
Objective: type 2 diabetes, metabolic disorder, is one of the main risk factors for cardiovascular disease, leading to angiogenesis injury. The present study wanted to discover the effect of sodium butyrate (NaB) and voluntary exercise, alone or together, on miR-126 and related proteins in rats with type 2 diabetes. Methods: thirty-five male Wistar rats (200-250 g) were randomly divided into five groups: control, diabetes, diabetes-NaB, diabetes-exercise, and diabetes-NaB-exercise. Type 2 diabetes was induced by intraperitoneal injection of streptozotocin (35 mg/kg) and high-fat diet. The rats were then administrated NaB (200 mg/kg. ip) or were subjected to voluntary exercise, or combined NaB and voluntary exercise for 8 weeks. MiR-126 expression in the cardiac tissue was determined by real-time PCR, and the SPRED-1 and RAF proteins expression levels were measured by western blot. Results: NaB and voluntary exercise up-regulated cardiac miR-126 and RAF expression levels and down-regulated SPRED-1 in cardiac tissue of type 2 diabetic rats. Moreover, the combination of NaB and voluntary exercise amplified their effects on those parameters. Both NaB and voluntary exercise or together markedly modulated serum glucose and HbA1c. Conclusion: The present findings demonstrated that NaB combined with exercise could improve cardiac angiogenesis by increasing miR-126 and affecting related proteins. Thus, NaB together with voluntary exercise might be a promising intervention for the treatment and prevention of type 2 diabetes.
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Introduction: Atherosclerotic cardiovascular disease (ASCVD) is the first leading cause of mortality globally. To identify the individual risk factors of ASCVD utilizing the machine learning (ML) approaches. Materials & methods: This cohort-based cross-sectional study was conducted on data of 500 participants with ASCVD among Tabriz University Medical Sciences employees, during 2020. The data with ML methods were developed and validated to predict ASCVD risk with naive Bayes (NB), spurt vesture machines (SVM), regression tree (RT), k-nearest neighbors (KNN), artificial neural networks (ANN), generalized additive models (GAM), and logistic regression (LR). Results: Accuracy of the models ranged from 95.7 to 98.1%, with a sensitivity of 50.0 to 97.3%, specificity of 74.3 to 99.1%, positive predictive value (PPV) of 0.0 to 98.0%, negative predictive value (NPV) of 68.4 to 100.0%, positive likelihood ratio (LR +) of 13.8 to 96.4%, negative likelihood ratio (LR-) of 3.6 to 51.9%, and area under ROC curve (AUC) of 62.5 to 99.4%. The ANN fit the data best with an accuracy of 98.1% (95% CI: 96.5-99.1), a specificity of 99.1% (95% CI: 97.7-99.9), a LR + of 96.4% (95% CI: 36.2-258.8), and AUC of 99.4% (95% CI: 85.2-97.0). Based on the optimal model, sex (females), age, smoking, and metabolic syndrome were shown to be the most important risk factors of ASCVD. Conclusion: Sex (females), age, smoking, and metabolic syndrome were predictors obtained by ANN. Considering the ANN as the optimal model identified, more accurate prevention planning may be designed.
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Background: Non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of metabolic syndrome is closely associated with type 2 diabetes mellitus. Myo-inositol (MI)-a 6-C sugar alcohol-with insulin-mimetic, anti-diabetic, lipid-lowering, and anti-inflammatory properties has exerted favorable effects on insulin resistance-related disorders and metabolic disease, while recent animal studies revealed its positive effects on liver function. This study aimed to investigate the effects of MI supplementation on cardiometabolic factors, anthropometric measures, and liver function in obese patients with NAFLD. Methods: This double-blinded placebo-controlled randomized clinical trial was carried out on 48 obese patients with NAFLD who were randomly assigned to either MI (4g/day) or placebo (maltodextrin 4g/day) along with dietary recommendations for 8 weeks. Glycemic indices, lipid profile, liver enzymes anthropometric measures, and blood pressure were evaluated pre- and post-intervention. Dietary intakes were assessed using a 3-day 24 h recall and analyzed by Nutritionist IV software. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and beta-cell function (HOMA-B) was also estimated. Results: Anthropometric measures decreased significantly in both groups, while the reduction in weight (p = 0.049) and systolic blood pressure (p = 0.006) in the MI group was significantly greater than in the placebo group after adjusting for baseline values and energy intake. Although energy and macronutrient intakes decreased significantly in both groups, between-group differences were not significant after adjusting for the potential confounders. MI supplementation led to a significant reduction in serum fasting insulin (p = 0.008) and HOMA-IR (p = 0.046). There were significant improvements in lipid profile, liver enzymes, and aspartate aminotransferase/alanine aminotransferase ratio as well as serum ferritin level in the MI group, compared to the placebo group at the endpoint. By MI supplementation for eight weeks, 1 in 3 patients reduced one- grade in the severity of NAFLD. Conclusion: MI supplementation could significantly improve IR, lipid profile, and liver function in patients with NAFLD. Further clinical trials with larger sample sizes, longer duration, different MI doses, and other inositol derivatives are recommended.
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BACKGROUND: Inadequate angiogenesis in patients with type 2 diabetic heart could result in deprived collateral formation. Herein, we aimed to investigate the effects of sodium butyrate (NaB) along with voluntary exercise simultaneously on the mechanisms acting on cardiac angiogenesis. MATERIALS AND METHODS: Animals were divided into the following five groups: control (Con), diabetic rats (Dia), diabetic rats treated with NaB (200 mg/kg, i.p.) (Dia-NaB), diabetic rats receiving voluntary exercise (Dia-Exe), and diabetic rats treated with NaB and exercise simultaneously (Dia-NaB-Exe). After an eight-week duration, NO metabolites levels were measured using Griess method, the VEGF-A and VEGFR2 expressions was examined by PCR, the expressions of VEGF-A and VEGFR2 proteins was investigated by western blot, and ELISA method was used for Akt, ERK1/2 expression. RESULTS: Cardiac VEGF-A and VEGFR2 expressions were higher in the Dia-Exe and Dia-NaB-Exe groups compared to the Dia group. However, a combination of exercise and NaB enhanced the VEGF-A expression in cardiac tissue compared to the Dia-NaB and Dai-Exe groups. Heart NOx concentration was higher in the treated groups compared to the Dia group. The expression of cardiac Akt levels increased in both the Dia-Exe and Dia-NaB-Exe groups compared to the Dia groups. In addition, cardiac ERK1/2 expression was found to be higher in the Dia-NaB-Exe group compared to the Dia group. CONCLUSION: The findings of this study showed the therapeutic potential of a novel combination therapy of sodium butyrate and voluntary exercise in improving cardiac angiogenesis with the enhanced involvement mechanism in high fat/STZ-induced type 2 diabetic rats.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Condicionamiento Físico Animal , Ratas , Animales , Diabetes Mellitus Tipo 2/metabolismo , Ácido Butírico/farmacología , Ácido Butírico/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Wistar , Transducción de SeñalRESUMEN
In the current study, we aimed to investigate the effect of saffron supplementation on glycemic status, lipid profile, atherogenic indices, and oxidative status in patients with type-2 diabetes (T2DM). In a randomized, double-blind controlled trial, 70 patients were randomly allocated into two groups (n = 35, each) and received 100 mg/day of saffron or placebo for eight weeks. Dietary intake, weight, body mass index (BMI), waist and hip circumferences (WC and HC), waist to hip ratio (WHR), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, and Homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile, atherogenic indices, oxidative status, and liver enzymes were determined before and after the intervention. At the end of the eighth week, saffron intervention could significantly reduce FBS (7.57%), lipid profile (except high-density lipoprotein cholesterol [HDL-C]), atherogenic indices, and liver enzymes (p < .05). Moreover, saffron could improve oxidative status (nitric oxide [NO] and malondialdehyde [MDA] reduced by 26.29% and 16.35%, respectively). Catalase (CAT) concentration remained unchanged. Saffron supplementation may alleviate T2DM by improving glycemic status, lipid profile, liver enzymes, and oxidative status. Further investigation is necessary to assess possible side effects and confirm the positive effect of saffron as a complementary therapy in clinical recommendations for T2DM.