Diagnostic biomarker and therapeutic target applications of miR-326 in cancers: A systematic review

MicroRNAs (miRNAs) are endogenous mediators of RNA interference and have key roles in the modulation of gene expression under healthy, inflamed, stimulated, carcinogenic, or other cells, and tissues of a pathological state. Many studies have proved the association between miRNAs and cancer. The role of miR-326 as a tumor suppressor miRNA in much human cancer confirmed. We will explain the history and the role of miRNAs changes, especially miR-326 in cancers and other pathological conditions. Attuned with these facts, this review highlights recent preclinical and clinical research performed on miRNAs as novel promising diagnostic biomarkers of patients at early stages, prediction of prognosis, and monitoring of the patients in response to treatment. All related publications retrieved from the PubMed database, with keywords such as epigenetic, miRNA, microRNA, miR-326, cancer, diagnostic biomarker, and therapeutic target similar terms from 1899 to 2018 with limitations in the English language. Recently, researchers have focused on the impacts of miRNAs and their association in inflammatory, autoinflammatory, and cancerous conditions. Recent studies have suggested a major pathogenic role in cancers and autoinflammatory diseases. Investigations have explained the role of miRNAs in cancers, autoimmunity, and autoinflammatory diseases, and so on. The miRNA-326 expression has an important role in cancer conditions and other diseases.     

Morphine Inhibited the Rat Neural Stem Cell Proliferation Rate by Increasing Neuro Steroid Genesis

Up to present, a large number of reports unveiled exacerbating effects of both long- and short-term administration of morphine, as a potent analgesic agent, on opium-addicted individuals and a plethora of cell kinetics, although contradictory effect of morphine on different cells have been introduced until yet. To address the potent modulatory effect of morphine on neural multipotent precursors with emphasis on endogenous sex-related neurosteroids biosynthesis, we primed the rat neural stem cells isolated from embryonic rat telencephalon to various concentrations of morphine including 10, 20, 50 and 100 µM alone or in combination with naloxone (100 µM) over period of 72 h. Flow cytometric Ki-67 expression and Annexin-V/PI based necrosis and apoptosis of exposed cells were evaluated. The total content of dihydrotestosterone and estradiol in cell supernatant was measured by ELISA. According on obtained data, both concentration- and time-dependent decrement of cell viability were orchestrated thorough down-regulation of ki-67 and simultaneous up-regulation of Annexin-V. On the other hand, the addition of naloxone (100 µM), as Mu opiate receptor antagonist, could blunt the morphine-induced adverse effects. It also well established that time-course exposure of rat neural stem cells with morphine potently could accelerate the endogenous dihydrotestosterone and estradiol biosynthesis. Interestingly, naloxone could consequently attenuate the enhanced neurosteroidogenesis time-dependently. It seems that our results discover a biochemical linkage between an accelerated synthesis of sex-related steroids and rat neural stem cells viability.

     

A robust fuzzy stochastic programming model for the design of a reliable green closed-loop supply chain network

Recently, governmental legislations, limitation of natural resources and adverse effects of End-of-Life products on ecological system have spurred researchers to design closed-loop supply chains (CLSCs). Accordingly, designing green supply chains (SCs) that manage greenhouse gas emissions and prevent air pollution can be helpful for companies to heighten profitability and customer loyalty, besides, uncertainty of parameters and disruption strikes could adversely affect performance of SCs and lower quality of output decisions. Effective planning prevents great losses and increases reliability of manager's decisions against uncertainties. Therefore, this paper is proceeding to design a reliable bi-objective green CLSC that minimizes total costs of network aside with minimizing harmful gas emissions. The proposed model is capable of controlling adverse effects of disruptions via applying scenario-based stochastic programming approach. Also, an effective hybrid robust fuzzy stochastic programming method is extended to effectively control uncertainty of parameters and risk-aversion level of output decisions. Extended model analyzing is based on lead-acid battery SC case study that output results approve applicability and effectiveness of model.     

Murine mesenchymal stem cells isolated by low density primary culture system

Murine mesenchymal stem cells (mMSC) and the difficult task of isolation and purification of them have been the subject of rather extensive investigation. The present study sought to isolate these cells from two different mouse strains, one outbred and the other inbred, primarily through a relatively simple but novel approach, the most important feature of which was the low density primary culture of bone marrow cells. For this purpose, mononuclear cells from either NMRI or BALB/c bone marrow were plated at about 500 cells per well of 24-well plates and incubated for 7 days. At this point, the fibroblastic clones that had emerged were pooled together and expanded through several subcultures. To investigate the mesenchymal nature, we differentiated the cells into the osteoblastic, chondrocytic and adipocytic lineages in different subcultures up to passage 10. According to the results, 1 week after culture initiation, several clones each comprising several fibroblastic cells appeared in each plate. The cells from different passages were capable of differentiating into corresponding skeletal tissues. In the present investigation, the best culture condition for maximum proliferation and also the expression of certain surface marker on isolated cells were examined. In this term the two murine strains showed some differences.     

Expression of Thy 1.2 surface antigen increases significantly during the murine mesenchymal stem cells cultivation period

This study sought to investigate the absence or expression of some surface antigens on murine mesenchymal stem cells (mMSCs) during the cultivation period of primary culture to passage 3 (equivalent to about 15 or 16 population doubling number). For this purpose, bone marrow cells from 6-8-week-old mice (either NMRI or Balb/c) were cultivated in 75-cm(2) culture flask for three successive passages, in each of which the culture was examined for the expression of CD135, CD44, CD31, Thy1.2, CD11b, CD45, CD34, Vcam1, Sca-1, and c-Kit antigens, using flow cytometry. Passage-3 cells from each strain can easily be differentiated into bone and fat, which was indicative of their mesenchymal nature. Our results demonstrated that for each given antigen, the percentages of the cells expressing that antigen had been changed by subcultures. The statistical analysis showed that nearly all differences between the passages were statistically significant. In this term, the expressional changes of Thy 1.2 seemed to be very significant in such a way that the expression increased to about half of the whole population in passage 3. In conclusion, it seems that this antigen could be considered as an enriching antigen for mMSCs population from bone marrow adherent cell culture.     

Stable overexpression of DNA fragmentation factor in T-47D cells: sensitization of breast cancer cells to apoptosis in response to acetazolamide and sulfabenzamide

Alterations in expression of the DFF40 gene have been reported in some cancers. This study is an in vitro study of the therapeutic effects of gene transfer that lead to elevation in DFF40 expression within T-47D cells in the presence of sulfonamide drugs. In this study, we have constructed a eukaryotic expression vector for DFF40 and transfected it into T-47D cancer cells. We used real time RT-PCR to detect the expression of DFF40 and the MTT assay to determine effects of the sulfonamide drugs acetazolamide, sulfabenzamide, sulfathiazole and sulfacetamide on cell viability in the presence of increased and normal DFF40 levels. Cell cycle distribution was assessed by propidium iodide (PI) staining and the rates of apoptosis by annexin V/PI staining. The DNA laddering analysis was employed to evaluate apoptosis. We observed that overexpression of DFF40 was only effective in decreasing viability in cells incubated with acetazolamide and sulfabenzamide. There was enhanced apoptosis in these groups, particularly with acetazolamide. The cell cycle distribution analysis showed that in the presence of sulfonamide drugs there were no substantial changes in empty-vector or DFF40-transfected cells, except for those cells treated with sulfabenzamide or sulfathiazole. There was no DNA laddering in cells that expressed the empty vector when incubated with sulfonamide drugs. In contrast, we observed DNA laddering in cells that expressed DFF40 in the presence of acetazolamide. Our results have demonstrated that combinatorial use of some sulfonamides such as acetazolamide along with increased expression of DFF40 can potently kill tumor cells via apoptosis and may be beneficial for treatment of some chemoresistant cancers.     

The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats

Ghrelin expression and secretion seem to be influenced by the fat content of the diet. However, data on the probable adverse effect of high fat diet (HFD) with different dietary fats and saturation level of fatty acids is inconclusive. This study aimed at investigating the effects of HFDs on fasting total and acyl-ghrelin plasma levels, gastric fundus and duodenum ghrelin mRNA expressions. Weaned Wistar rats (n=50) were randomly divided to five groups of HFDs with fish oil (HF-F), olive oil (HF-O), soy oil (HF-S), butter (HF-B) and the controls. After 8weeks, blood samples were collected. While the animals were fasting for 24h, their blood and tissue samples were obtained. Plasma parameters of total and acyl ghrelin and ghrelin mRNA expression level in stomach and duodenum were measured. The HF-B fed group had lower fasting plasma acyl ghrelin level than the control, HF-F and HF-O groups (P<0.05); furthermore, the HF-F group had significantly higher acyl ghrelin level than the HF-S one (P<0.05). After feeding, all the groups, except for the HF-B one, had a significantly lower plasma acyl ghrelin levels (P<0.05), compared with the fasting state. Ghrelin mRNA expression levels in the gastric fundus and duodenum were significantly lower in the HF-B as compared to the control group. Furthermore, the HF-F group had significantly higher mRNA level in the duodenum, in comparison with the HF-B and HF-S groups. As HF-F and HF-O diets had the highest stimulatory effect on fasting ghrelin expression and plasma level, consumption of these dietary oils can play an important role in ghrelin regulation, which might affect feeding behavior and energy intake.     

Expression profile of MAGI2 gene as a novel biomarker in combination with major deregulated genes in prostate cancer

Complex molecular changes that occur during prostate cancer (PCa) progression have been described recently. Whole genome sequencing of primary PCa samples has identified recurrent gene deletions and rearrangements in PCa. Specifically, these molecular events disrupt the gene loci of phosphatase and tensin homolog (PTEN) and membrane-associated guanylate kinase inverted-2 (MAGI2). In the present study, we analyzed the expression profile of MAGI2 gene in a cohort of clinical PCa (n = 45) and benign prostatic hyperplasia (BPH) samples (n = 36) as well as three PCa cell lines. We also studied the expression of PCa-related genes, including PTEN, NKX3.1, SPINK1, DD3, AMACR, ERG, and TMPRSS2-ERG fusion in the same samples. The expression of MAGI2 mRNA was significantly down-regulated in PC3, LNCaP and DU-145 PCa cell lines (p = 0.000), and also in clinical tumor samples (Relative expression = 0.307, p = 0.002, [95 % CI 0.002–12.08]). The expression of PTEN, NKX3.1, SPINK1, DD3, and AMACR genes was significantly deregulated in prostate tumor samples (p range 0.000–0.044). A significant correlation was observed between MAGI2 and NKX3.1 expression in tumor samples (p = 0.006). Furthermore, the inclusion of MAGI2 in the gene panel improved the accuracy for discrimination between PCa and BPH samples with the sensitivity and specificity of 0.88 [CI 0.76–0.95] and 0.83 [CI 0.68–0.92], respectively. The data presented here suggest that MAGI2 gene can be considered as a novel component of gene signatures for the detection of PCa.     

Evaluation of dairy allergy among ulcerative colitis patients

The intestine is the largest mucosal organ of the body and also the first line immune homeostasis. Inflammatory bowel disease or IBD is divided into ulcerative colitis and Crohn''s disease. One of the problems that can occur with UC is dietary allergy to some foods. This study aimed to evaluated the dairy allergy among patients with ulcerative colitis. This study is a Case - control study, that studied 72 patients with Ulcerative Colitis, after recording history of the disease, colonoscopy and confirmed by biopsy and 72 person without history of colitis. In this study, in order to investigate of food allergy, used of the EUROMMUM kit with an international code number DP3420-1601-11E. We used chi-square and Monte Carlo method for analysis of data. Among UC patients, 30.6% mild, 52.8% moderate and 16.6% of cases were in sever stage. 9.7% of them reported a history of abdominal surgery due to disease. According to the chi-square and Monte Carlo methods, dairy allergy (including: cow milk, cow milk UHT and casein) in UC group was significant (P=0.00). This study indicated that there is significant relationship between UC and cow milk, cow milk UHT and casein. UC patients who are allergic to dairy products and the use of dairy products can increase the severity of UC.