Dual role of microRNA-1297 in the suppression and progression of human malignancies

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded and tiny RNAs that modulate several biological functions, more importantly, the pathophysiology of numerous human cancers. They are bound with target mRNAs and thereby regulate gene expression at post-transcriptional levels. MiRNAs can either trigger cancer progression as an oncogene or alleviate it as a tumor suppressor. Abnormal expression of microRNA-1297 (miR-1297) has been noticed in several human cancers suggesting a distinct role for the miRNA in tumorigenesis. More specifically, it is both up-regulated and down-regulated in various cancers suggesting that it can act as both tumor suppressor and oncogene. This review systematically highlights the different roles of miR-1297 in the pathophysiology of human cancers, explains the mechanisms underlying miR-1297-mediated tumorigenesis, and discusses its potential prognostic, diagnostic, and therapeutic importance. © 202

Evaluation of local and circulating osteopontin in malignant and benign primary bone tumors

Purpose: The development of novel and efficient biomarkers for primary bone cancers is of grave importance. Methods: The expression pattern of osteopontin (OPN) was investigated in the 153 patients with benign (n = 72) and malignant (n = 81) primary bone cancers. Both local and circulating OPN mRNA expression levels and their protein concentration in serum and tumor site were assessed using real-time qRT-PCR, ELISA, and immunohistochemistry techniques, respectively. As a control, 29 healthy individuals were considered. The number of 153 tumor tissue specimens and the 153 paired margins were taken on surgical resection from the patients. 153 blood samples were also drained from all participants, then peripheral blood mononuclear cells (PBMC) and sera were separated. Results: The mean mRNA expression was significantly higher in all of the cancerous tissues than the paired margins and the PBMC of the patients than the controls. Consistently, the protein concentrations of OPN in serum and tumor tissues were significantly higher in the patients. Furthermore, the malignant cases had significantly elevated the mRNA levels and the protein compared to the benign cases. OPN could potentially differentiate the patients from the controls with 100 sensitivity and specificity in serum. Moreover, OPN could predict some of the malignant cases' clinicopathological features, including metastasis, recurrence, grade, and response to chemotherapy. Conclusions: In conclusion, OPN might be involved in the pathogenesis of primary bone tumors and can be considered as a potential biomarker to bone cancer diagnosis. © 202

Small dense low-density lipoprotein-lowering agents

Metabolic disorders, including obesity, diabetes, and hyperlipidemia, as well as cardiovascular diseases (CVD), particularly atherosclerosis, are still leading causes of death worldwide. Plasma levels of low-density lipoprotein (LDL) are currently being considered as a critical risk factor for the diseases mentioned above, especially atherosclerosis. Because of the heterogeneous nature of LDL, many studies have already been conducted on its subclasses, especially small dense LDL (sdLDL). According to available evidence, sdLDL levels can be considered as an ideal alternative to LDL levels for monitoring CVD and early diagnosis of atherosclerosis. Recently, several researchers have focused on factors that are able to decrease sdLDL levels and improve health quality. Therefore, the purpose of this study is to describe the production process of sdLDL particles and review the effects of pharmaceutical and dietary agents as well as lifestyle on sdLDL plasma levels. In brief, their mechanisms of action are discussed. Apparently, cholesterol and LDL-lowering compounds are also effective in the reduction of sdLDL levels. In addition, improving lipid profile, especially the reduction of triglyceride levels, appropriate regimen, and lifestyle can decrease sdLDL levels. Therefore, all the aforementioned parameters should be taken into consideration simultaneously in sdLDL levels reducing strategies. © 2020 De Gruyter. All rights reserved

Dysregulation of microRNAs regulating survivin in CD4+ T cells in multiple sclerosis

Background: Impaired elimination mechanisms of the autoreactive lymphocytes, like T lymphocytes, via apoptosis may be the cause of continues inflammatory state in multiple sclerosis (MS). BIRC5 gene codify for the survivin, which participates in the modulation of apoptosis and cell survival. The objective of this study was investigation of the role of important confirmed miRNAs, including miR-335, miR-485, miR-542, and miR-708, in the regulation of survivin mRNA in the CD4+ T cells of MS cases. Methods: In this study, 50 RRMS patients as well as 50 healthy matched controls were recruited. The peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples and CD4+ T cells were prepared. After that, RNA was extracted, cDNA was synthesized, and the expression levels of miR-335, miR-485, miR-542, and miR-708 were measured using Real-time PCR. Moreover, the mRNA expression of survivin was detected. Serum level of survivin was detected using ELISA. Results: The mRNA of survivin was 2-folds upregulated in the CD4+ T cells from MS patients in comparison to the healthy controls (P = 0.0053). Serum level of survivin was higher in patients than controls. There was statistically significant downregulation of miR-485 (P = 0.001) and miR-708 (P = 0.011) in CD4+ T cells of patients compared with controls. The miR-485 downregulation had statistically significant correlation with the mRNA expression and serum level of survivin. Conclusion: miRNAs play a role in the regulation of survivin, and therefore apoptosis of CD4+ T cells, and hence are probably participating in a persistent inflammatory condition in MS patients. © 2020 Elsevier B.V

Effects of Securigera Securidaca seed extract in combination with glibenclamide on antioxidant capacity, fibroblast growth factor 21 and insulin resistance in hyperglycemic rats

Ethnopharmacological relevance: Undesired effects of synthetic antidiabetic agents have made researchers to seek for safer and healthier resources. With this aspect, herbal materials have attracted substantial research interest and are being extensively investigated. Considering that herb-drug interactions can be a double-edged sword presenting both risks and benefits, investigation of such interactions is greatly in demand. Aim of the study: to investigate possible beneficial effects of hydroalcoholic extract of Securigera Securidaca seed (HESS) on antioxidant capacity, fibroblast growth factor 21 (FGF21) and insulin resistance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. Materials and methods: Forty male Wistar rats were randomly divided in to eight equal groups including healthy and diabetic controls and six treated groups with a various doses of HESS alone and in combination with glibenclamide, for 35 consecutive days. Serum samples were taken and analyzed for biochemical profile, HOMA indexes, FGF21, oxidative/nitrosative stress and inflammatory biomarkers as compared with the controls. Moreover, total phenolic and flavonoid contents of herbal extract were assessed. Results: The herbal extract was found to be rich in flavonoid and phenolic components. Both of glibenclamide and the HESS decreased glucose and insulin resistance, as well as increased body weight and insulin sensitivity. Moreover, the extract could mitigate oxidative/nitrosative stress and inflammation dose-dependently, however, the standard drug was less effective than HESS. Induction of diabetes increased FGF21 levels and both of the treatments could reduce its contents, however, glibenclamide was more effective than HESS. Conclusions: The results clearly show that there is no contradiction between HESS and glibenclamide. Moreover, the herbal extract could augment antioxidant and anti-inflammatory properties of the standard drug. © 2019 Elsevier B.V

MiR-613 Promotes Cell Death in Breast Cancer Cells by Downregulation of Nicotinamide Phosphoribosyltransferase and Reduction of NAD

NAD is mainly biosynthesized by the enzymatic action of nicotinamide phosphoribosyltransferase (NAMPT) through the salvage pathway. NAD is indispensable for the proper function and metabolism of all living cells, including cancer cells. Our previous researches revealed that inhibition of NAMPT by miRNA (miR) could suppress NAD levels and thereby hinder the growth and promotion of breast cancer (BC). Therefore, the current study was undertaken to investigate the inhibitory effects of miR-613 on NAMPT and BC cells' survival. Bioinformatics analysis and luciferase reporter assay confirmed that NAMPT 3�-untranslated region is a direct target for miR-613. The expression of miR-613 was noticed to be significantly decreased in both clinical tissue samples and BC cells by real-time PCR. Following transfection with miR-613 mimic, the expression of miR-613 was elevated in the BC cells leading to inhibition of NAMPT expression at both mRNA and protein level as measured by real-time PCR and western blotting, respectively. Inhibition of NAMPT led to a remarkable reduction in the concentration of NAD in the BC cells. The transfection also declined cell viability roughly 40 in MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Consistently, the apoptosis rate was remarkably increased, around 65 in these cells as assayed by labeling the cells with Annexin V-fluorescein isothiocyanate (FITC) and Propidium Iodide. Targeting the NAMPT-mediated NAD salvage pathway by miR-613 is a novel approach for managing BC, which is worth further investigation. © 2021, Mary Ann Liebert, Inc., publishers 2021