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Objective: Telmisartan is an angiotensin receptor blocker (ARB) that specifically blocks angiotensin II type-1 receptors (AT1R). Telmisartan has been proven to have antidiabetic effects via a variety of mechanisms, and it can be utilized in some diabetic patients due to its dual benefit for hypertensive patients with type 2 DM (T2DM) and when the other oral antidiabetic medications are intolerable or contraindicated. However, its precise underlying hypoglycemic mechanism is still obscure. Aim of work: We sought to establish a link between telmisartan administration and myostatin expression in skeletal muscles of T2DM rat model as a potential hypoglycemic mechanism of telmisartan. Materials and Methods: 32 male albino rats were included in the study; 8 rats served as controls (group I). T2DM was inducted in the other 24 rats, which were then randomly subdivided into 3 groups (8 in each): (group II) the Diabetic group and (groups III and IV) which were treated with either telmisartan (8 mg/kg/day) or metformin (250 mg/kg/day) respectively via oral gavage for a 4-week period. Results: Telmisartan administration resulted in a significant improvement in OGTT, HOMA-IR, glucose uptake, and muscle mass/body ratios in Telmisartan group as compared to Diabetic group (p < 0.05). Additionally, telmisartan induced a significant boost in adiponectin and IL-10 serum levels with a substantial drop in TNF-α and IL-6 levels in Telmisartan group compared to diabetic rats (p < 0.05). Moreover, telmisartan significantly boosted SOD and GSH, and decreased MDA levels in the skeletal muscles of telmisartan group. Furthermore, a significant downregulation of myostatin and upregulation of insulin receptor, IRS-1, and IRS-3 genes in the skeletal muscles of Telmisartan group were also detected. Histologically, telmisartan attenuated the morphological damage in the skeletal muscle fibers compared to diabetic rats, as evidenced by a considerable decrease in the collagen deposition area percentage and a reduction in NF-kB expression in the muscle tissues of group III. Conclusion: Telmisartan administration dramatically reduced myostatin and NF-kB expressions in skeletal muscles, which improved insulin resistance and glucose uptake in these muscles, highlighting a novel antidiabetic mechanism of telmisartan in treating T2DM.
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BACKGROUND: Obstructive sleep apnoea (OSA) is a major cause of cardiovascular morbidity and mortality worldwide. Previous studies showed high prevalence of OSA in heart failure. We aimed to evaluate the association of OSA with cardiac dysfunction and the importance of myocardial performance index (Tei) in identifying cardiac dysfunction. METHODS: Participants with OSA and sinus rhythm were included, while participants with arrhythmia, debilitating disease, or significant valvular heart disease were excluded. Thirty participants were enrolled, consecutively allocated in a single group, and underwent nocturnal polysomnography, electrocardiogram, and transthoracic echocardiography. RESULTS: The prevalence of hypertension, diabetes, and smoking in the study population was 50%, 30%, and 23.3%, respectively. The mean body mass index and apnoea-hypopnoea index (AHI) of the study population was 40.11 ± 7.5 kg/m2 and22.12 ± 13.54 events/h, respectively. There were statistically significant differences between mild, moderate, and severe OSA regarding the left ventricular end diastolic diameter, left ventricular end systolic diameter, ejection fraction, and fractional shortening (p = 0.006, p = 0.002, p = 0.014 and p = 0.011),respectively. There were statistically significant regular positive correlations between the AHI and the right and left Tei (r = 0.447, p = 0.001 and r = 0.391, p = 0.003),respectively. CONCLUSIONS: The prevalence of OSA was more in patients with comorbidities especially hypertension and diabetes. OSA was significantly associated with ventricular remodelling and cardiac dysfunction. A significant regular positive correlation was observed between the severity of OSA and worsening cardiac function as measured by Tei. Echocardiographic evaluation of the right and left ventricles and the right and left Tei could be considered as potentially valid, reproducible, and clinically applicable non-invasive methods for estimation of ventricular global function in patients with OSA.
Asunto(s)
Hipertensión , Apnea Obstructiva del Sueño , Disfunción Ventricular Izquierda , Humanos , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/etiología , Estudios Transversales , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Remodelación Ventricular , Hipertensión/complicacionesRESUMEN
Background: Cerebrovascular stroke (CVS) is a potentially fatal disease. The most common risk factor for CVS is hypertension. Aim: While most studies in the field have focused on the functional roles of long noncoding RNAs (lncRNAs) NEAT1, GAS5, and HOTAIR in CVS, less attention has been paid to their clinical relevance to stroke incidence and prognosis. Also, a link has not yet been made between these lncRNAs and hypertension, our study aim was to investigate whether the expression of these lncRNAs differed between CVS with and without hypertension, as well as to compare each group to controls. Method: In total, 181 CVS patients were enrolled, including 91 chronic hypertensive patients with stroke, 90 stroke patients without hypertension, and 51 control subjects. blood samples were collected on the day of recruitment from patients with CVS and controls. Real-time qRT-PCR was used to detect the expression of target lncRNAs in serum. Results: When compared to controls, there was a statistically higher level of lncNEAT1 in each case group (median (IQR)â¯=â¯3.68 (1.35-7.35) and 3.05 (0.95-6.45) for the hypertensive and non-hypertensive groups, respectively, with a significantly higher level in the hypertensive group (Pâ¯=â¯0.04). When compared to controls, lncHOTAIR was significantly downregulated in all case groups (medians in hypertensive and non-hypertensive patients were 0.13, and 0.34, respectively), with a significantly lower level in the hypertensive group (Pâ¯=â¯0.05). LncGAS5 levels in patients were significantly lower (median (IQR)â¯=â¯0.16 (0.02-0.55) and 0.25 (0.03-0.99) for the hypertensive and non-hypertensive groups, respectively) compared to controls, with a significantly lower level in the hypertensive group (Pâ¯=â¯0.02). There was a significant positive correlation between NEAT1 and GAS5, but a significant negative correlation between each with HOTAIR in both patients' groups. We also detected a significant negative correlation between each NEAT1 or GAS5 and NIHSS score while a significant positive correlation between HOTAIR and NIHSS. ROC curve analysis for GAS5 was able to differentiate patients with CVS hypertensive from patients with CVS non-hypertensive. Conclusion: Patients in each case group had statistically higher levels of NEAT1 and lower levels of HOTAIR and GAS5 compared to control levels, with higher significant NEAT1 but lower significant HOTAIR and GAS5 in the hypertensive group. Therefore, lncRNAs NEAT1, HOTAIR, and GAS5 could be used as diagnostic and prognostic biomarkers of CVS that correlate with NIHSS score and could produce a novel target for CVS therapy.
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BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease which affects various tissues and organs mainly joints. Serum microRNAs are considered a new class of non-coding RNA which plays a vital role in pathogenesis of RA. METHODS: The current study was conducted on 80 RA patients and 80 healthy participants. Serum expression levels of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 were evaluated via real-time quantitative polymerase chain reaction (PCR). RESULTS: Significant upregulation of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 was reported in the present study with respect to the control group (P = .031, P = .017, P = .026, P = .036 and P = .05, respectively). Furthermore, significant positive correlation between the abovementioned microRNAs with DAS28 score (P < .001, each) was demonstrated. CONCLUSION: Early detection of RA could be achieved through evaluation of serum expression of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 which also may be used as targets for treatment of patients with RA.