Moderate Endurance Training and MitoQ Improve Cardiovascular Function, Oxidative Stress, and Inflammation in Hypertensive Individuals: The Role of miR-21 and miR-222: A Randomized, Double-Blind, Clinical Trial.

OBJECTIVE: Hypertension (HTN) is among the leading causes of myocardial infarction, stroke, and kidney disease. The MitoQ supplement is a mitochondrial-targeted antioxidant that attenuates the generation of reactive oxygen species (ROS). miRNAs play an essential role in the pathophysiology of HTN. Regular aerobic exercise is recommended to decrease the risk of cardiovascular disease. We aimed to evaluate the effects of MitoQ supplementation and moderate endurance training (ET), alone and in combination, on cardiac function, blood pressure, the circulatory levels of miRNA-21 and miRNA-222, and oxidative status in individuals with HTN. MATERIALS AND METHODS: In a double-blind, randomized clinical trial (except for ET group), 52 male hypertensive subjects (40-55 years old) were randomly divided into four groups (n=13): Placebo, MitoQ (20 mg/day, oral), ET (Cycle ergometer, moderate intensity, 40-60% VO2 peak, three sessions/week for six weeks), and MitoQ+ET. Cardiac echocardiography indices, serum oxidative and inflammation status, and miRNAs 21 and 222 were assessed before and after interventions. RESULTS: Left ventricular mass [effect size (ES): -6.3, 95% confidence interval (CI): -11.2 to -1.4] and end-systolic/ diastolic diameters significantly improved in the intervention groups (ES: -0.05, 95% CI: -0.11 to 0.00 and -0.09, 95% CI: -0.16 to -0.02). Total serum antioxidant capacity (TAC) increased (ES: 36.0, 95% CI: 26.1 to 45.8), and malondialdehyde (MDA) (ES: -0.43, 95% CI: -0.53 to -0.32), IL-6 (ES: -1.6, 95% CI: -1.98 to -1.25), miR-21 (ES: -0.48, 95% CI: -0.61 to -0.35), and miR-222 (ES: -0.31, 95% CI: -0.44 to -0.18) significantly decreased in response to ET, MitoQ, and their combination. CONCLUSION: MitoQ and ET, individually and more pronouncedly in combination, can improve cardiovascular health in people with high blood pressure (BP) by reducing inflammation and increasing antioxidant defense, in association with reduction in circulatory miR-21 and miR-222 levels (registration number: IRCT20190228042870N1).

Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals.

OBJECTIVES: Hypertension (HTN) is one of the most important risk factors for cardiovascular diseases. Despite advances in treatment and control of HTN, the prevalence of HTN is still increasing. MitoQ is a supplement that acts on mitochondria and attenuates reactive oxygen species (ROS), which plays an important role in cardiovascular health. miRNAs play an important role in the pathophysiology of HTN. We evaluated the effects of MitoQ supplementation and endurance training (ET), alone and in combination, on functional indices of the heart and serum levels of miR-126, miR-27a, antioxidants, and NO, in patients with HTN. METHODS: In a double-blind randomized clinical trial, 52 male participants (age 40-55 years) were randomly divided into four groups (n = 13) of placebo, MitoQ (20 mg/day, oral), ET (cycle ergometer, moderate intensity, 40-60% VO2 peak, heart rate 120-140 b/min, 45 min a day, three days/week for six weeks), and MitoQ+ET. Cardiac function indices were assessed by echocardiography before and after interventions. RESULTS: Systolic blood pressure (SBP) significantly decreased in all intervention groups (P < 0.001) while DBP (P < 0.01) and LV hypertrophy (P < 0.05) were significantly decreased only in the MitoQ+ET group. Serum levels of SOD, GPx, and NO and the level of miR-126 significantly increased in all treatment groups, while miR-27a reduced in the ET (P < 0.05) and MitoQ+ET (P < 0.01) groups. CONCLUSIONS: Compared to MitoQ and ET alone, their combination has more prominent improving effects on cardiac health and amelioration of BP in the patients with HTN. These effects are through miR-126 and miR-27a modulation and ameliorating mitochondrial ROS production.

Infective endocarditis uncovered a very rare congenital heart disease.

In this article, we introduced a case of rare congenital anomalies that was asymptomatic until adulthood and was complicated by infective endocarditis and dissection of aortic valve leaflet.

Dietary Recommendations in Fracture Healing in Traditional Persian Medicine: A Historical Review of Literature.

BACKGROUND: Fracture repair is a complex process. An inappropriate diet is a contributing risk factor for fracture nonunion. The aim of this study was to extract dietary recommendations for fracture healing according to traditional Persian medicine (TPM) literature. METHOD: The contents relevant to diets in fracture healing were selected from main textbooks in TPM like Al Qanon fi Al-teb ( The Canon). Other reference textbooks in traditional medicine were also used for a comprehensive study in this respect. Finally content analysis was used for summarizing and describing the results. FINDINGS: Food stuffs are classified in TPM according to their nutritive value, their assimilability, and the quality of achieved chyme. Some light meals like chicken soup are recommended for the early days of fracture and high-nutrient and dense foods such as goat's or sheep's head and nuts are advised in following days for fracture healing acceleration and callus formation. Several recommendations are also provided for pacing the healing process. CONCLUSION: A comparison of Avicenna and other Persian sage's recommended regimens with the recent evidence revealed the potential positive effects of their regimen for bone healing acceleration. It can shed light on a part of history of orthopedics and add to current knowledge about bone fracture and its management.

Immunosuppressive effect of silymarin on mitogen-activated protein kinase signalling pathway: the impact on T cell proliferation and cytokine production.

Silymarin, a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have anti-inflammatory, hepatoprotective and anticarcinogenic effects. In this study, the in vitro immunomodulatory effect of silymarin was investigated using human CD4+ T cells. Peripheral blood mononuclear cells (PBMC) from healthy individuals were activated with anti-CD3 (5 µg/ml) plus anti-CD28 (2 µg/ml) and treated with 10, 50 and 100 µM silymarin. Cells were incubated 72 hr for proliferation assay using MTT and for viability analysis using PI staining and flow cytometry. Naive CD4+ T cell was also isolated from PBMC, activated with PHA/anti-CD28 and treated with 100 µM silymarin for 72 hr. MAPKs' activity of cell lysate from activated naive CD4+ T cells was assessed using an ELISA-based MAPKinase activity kit, and Th1/Th2/Th17-related cytokine expression was determined by Multi-analyte ELISA array kit. Results indicated a significant inhibition in proliferation of activated PBMC after 48-hr incubation with 100 µM silymarin without causing cell death. Moreover, MAPKs' activity (ERK1/2 and P38) and Th1-related cytokines (IL-2, TNF-α, IFN-γ) were significantly reduced in silymarin-treated cells compared with control after 72 hr. This study shows that silymarin has the ability to inhibit T cell proliferation and pro-inflammatory cytokine secretion in vitro. Furthermore, silymarin is able to inhibit ERK1/2 and P38 pathway activation in T cells stimulated through TCR engagement, a property that is likely associated with its ability to inhibit T cell proliferation and cytokine secretion. Therefore, silymarin, as an immune-response modifier, might be a valuable drug in therapeutic situations in which immunosuppression is required.