Circ-LTBP1 is involved in doxorubicin-induced intracellular toxicity in cardiomyocytes via miR-107/ADCY1 signal.

Although doxorubicin (DOX) is a broad-spectrum and anthracycline chemotherapeutic agent, cardiotoxicity limits its clinical application. Therefore, it is meant to prevent the clinical side effects of DOX. Human cardiomyocyte-like AC16 cells were treated with DOX to induce intracellular toxicity. AC16 cell viability was determined by Cell Counting Kit 8 and 5-ethynyl-2'-deoxyuridine assays. The tumor necrosis factor-α and interleukin-6 abundances were quantified by matched kits. The apoptosis rate was measured by flow cytometry. Western blot analysis was conducted to measure the protein expression levels in AC16 cells. Oxidative stress was analyzed by measuring superoxide dismutase and malondialdehyde production. The quantitative real-time polymerase chain reaction was conducted to assess the expression levels of circ-latent transforming growth factor-beta binding protein-1 (circ-LTBP1), microRNA-107 (miR-107), and Adenylate cyclase 1 (ADCY1) expression in AC16 cells. The interaction relationship among circ-LTBP1, miR-107, and ADCY1 was verified by dual-luciferase reporter and RNA immunoprecipitation assays. As a result, treatment with DOX induced the proliferation inhibition, inflammation, apoptosis, and oxidative stress in AC16 cells, which were rescued by circ-LTBP1 inhibition or miR-107 upregulation. MiR-107 was confirmed as a target of circ-LTBP1, and inhibition of circ-LTBP1-mediated effects on DOX-stimulated cells were abolished by downregulation of miR-107. Circ-LTBP1 mediated ADCY1 expression by sponging miR-107 in AC16 cells. The upregulation of miR-107 increased cell proliferation and inhibited inflammation, apoptosis, and oxidative stress in DOX-stimulated cells through downregulation of ADCY1. Circ-LTBP1 was found to enhance DOX-induced effects on proliferation inhibition, inflammation, apoptosis, and oxidative stress in AC16 cells through competitively sponging miR-107 and elevating ADCY1.

LncRNA NORAD promotes the progression of myocardial infarction by targeting the miR-22-3p/PTEN axis.

NORAD is a newly identified long non-coding RNA (lncRNA) that plays an important role in cancers. NORAD has been found to be highly expressed in the mouse model of acute myocardial infarction (AMI). However, the role of NORAD in the regulation of AMI remains unknown. In the present study, we aimed to investigate the function of NORAD in AMI and explore the potential regulatory mechanisms. A mouse model of AMI was established and NORAD was knocked-down. The infarcted size of heart tissues and the cardiac function were evaluated. In addition, two cardiomyocyte cell lines were treated with hypoxia/re-oxygenation (H/R) to mimic AMI . Luciferase reporter assay, RNA pull-down assay, fluorescence hybridization, qRT-PCR, and western blot analysis were performed. Apoptotic cells and the levels of L-lactate dehydrogenase (LDH) and malondialdehyde (MDA) were detected. Our results show that downregulation of NORAD efficiently attenuates heart damage in the AMI mouse model. NORAD interacts with miR-22-3p. Knock-down of NORAD inhibits H/R-induced cell apoptosis and reduces LDH and MDA levels, while its effects are abolished by miR-22-3p inhibitor. MiR-22-3p interacts with PTEN and inhibits its expression. Overexpression of miR-22-3p inhibits H/R-induced cell apoptosis and reduces LDH and MDA levels, while its effects are abolished by overexpression of PTEN. Finally, overexpression of NORAD inhibits the AKT/mTOR signaling pathway, and its effects are attenuated by overexpression of miR-22-3p. Taken together, our study reveals that NORAD promotes the progression of AMI by regulating the miR-22-3p/PTEN axis, and the AKT/mTOR signaling may also be involved in the regulatory processes.

Association between inflammatory biomarkers and hypertension among sedentary adults in US: NHANES 2009-2018.

Our study focuses on the relationship between inflammatory biomarkers and hypertension among sedentary adults in the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We categorized 24,614 participants into two groups based on their daily sedentary time: 9607 individuals in the sedentary group (≥7 h) and 15,007 in the non-sedentary group (<7 h). We found that the sedentary group had a significantly higher prevalence of hypertension than the non-sedentary group. Using weighted multiple logistic regression and smoothing curves, we assessed the correlation between inflammatory biomarkers and hypertension among the sedentary adults. The odds ratios for hypertension were 1.92 for the monocyte to high-density lipoprotein ratio (MHR), 1.15 for the systemic inflammation response index (SIRI), and 1.19 for the natural logarithm of the systemic immune-inflammation index (lnSII), all showing nonlinear associations. Furthermore, a significant positive correlation was found between sedentary time and inflammatory biomarkers (MHR, SIRI, and lnSII). Our findings suggest that prolonged sedentary behavior in the US significantly increases hypertension risk, likely due to marked increases in inflammation markers.

Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma.

Background: Hypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood. Methods: A total of 113 patients with MM osteolytic lesions were studied retrospectively. Flow cytometry and atomic absorption spectroscopy were used to detect calcium content. Immunofluorescence and Western blotting were used to investigate protein expression. GEO and miRNA databases were used to screen miRNAs. Exosomal miR-4261 migration was investigated by Transwell assay. Dual-luciferase assays confirmed the targeting relationship between miR-4261 and ATP2B4. An RBC oxidative stress model was constructed, and Omega-Agatoxin IVA was used to study the role of plasma membrane Ca2+-ATPase 4 (PMCA4) in RBCs. Results: The results showed that MM RBCs had calcium overload, and serum calcium levels increased as the number of RBCs decreased. The expression of PMCA4 in MM RBCs was significantly lower than in normal RBCs. The exosomal miR-4261 produced by MM cells could be transferred to RBCs to downregulate the expression of ATP2B4. Conclusions: Studies have confirmed that RBCs experience calcium overload in MM with osteolytic lesions, which is related to the downregulation of ATP2B4 by MM exosomal miR-4261.

Effect of folic acid combined with pravastatin on arteriosclerosis in elderly hypertensive patients with lacunar infarction.

ABSTRACT: This study aimed to assess the effect of folic acid combined with pravastatin on atherosclerosis-related indexes in elderly patients with hypertension complicated with lacunar cerebral infarction.A total of 134 elderly hypertensive patients with lacunar cerebral infarction were randomly divided into 3 groups using the random number table method. Group A, the folic acid group, had 45 cases and received low-dose folic acid (0.8 mg/d) treatment on the basis of antihypertensive treatment. Group B, the pravastatin group, had 45 cases and received pravastatin (20 mg/d) treatment on the basis of antihypertensive treatment. Group C, the folic acid combined with the pravastatin group, had 44 cases. Members of this group received pravastatin (20 mg/d) and low-dose folic acid (0.8 mg/d) based on antihypertensive treatment. Levels of folic acid, homocysteine (Hcy), tumor necrosis factor alpha (TNF-a), matrix metallopeptidase 9 (MMP-9), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were measured by ELISA before treatment in all 3 groups. Carotid intima-media thickness (IMT) was measured using ultrasound, and systolic and diastolic blood pressure were measured with a mercury column. After 8 weeks of treatment, the levels of folic acid, Hcy, TNF-a, MMP-9, TC, LDL-C, and systolic and diastolic blood pressure were compared among the 3 groups. IMT levels were measured at 12 weeks of treatment.After 8 weeks of treatment, compared with group B, patients in groups A and C had folic acid levels significantly higher than baseline levels, with significantly lower Hcy levels (both P < .05). Patients in group C presented significantly decreased TNF-a, MMP-9, TC, and LDL-C levels and systolic and diastolic blood pressure after 8 weeks of treatment, compared with those in groups A and B (both P < .05). These patients also showed significantly decreased IMT levels compared with those in the other groups (P < .05).Low-dose folic acid combined with pravastatin in elderly patients with lacunar cerebral infarction can reduce the level of homocysteine, improve the degree of carotid atherosclerosis, protect vascular endothelium, and reduce blood lipids and blood pressure, presenting better benefits than pravastatin alone.