Three possible diagnostic biomarkers for gastric cancer: miR-362-3p, miR-362-5p and miR-363-5p.

Aim: MicroRNAs can be regarded as biomarkers for gastric cancer (GC) diagnosis in the early stages. This study assesses the expression levels of miR-362-3p, miR-362-5p and miR-363-5p as potential biomarkers for GC. Materials & methods: The expression levels of the miRNAs in 90 pairs of GC and adjacent normal tissue samples were analyzed by quantitative real-time reverse transcription PCR (qRT-PCR) and some bioinformatics tools were utilized for analyzing the target genes and possible molecular pathways in which these miRNAs participate. Results & conclusion: There was a significant overexpression of the miRNAs in GC cells and an outstanding correlation between their overexpression with some clinicopathological features of the patients.

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MiR-138-5p improves the chemosensitivity of MDA-MB-231 breast cancer cell line to paclitaxel.

BACKGROUND: Chemotherapy is a predominant strategy for breast cancer (BC) treatment and paclitaxel (PTX) has been known as a conventional chemotherapeutic drug. However, insensitivity of BC cells to PTX limits the anti-tumor effects of this agent. MicroRNAs are closely related to BC which are suggested as therapeutic factors in the combination therapy of BC. We examined the possible efficacy of miR-138-5p restoration in combination with PTX to impove BC treatment. METHODS: The human breast cancer cell line MDA-MB-231 was transfected with miR-138-5p mimics and treated with PTX, in a combined or separate manner. The MTT assay was accomplished to determine inhibitory doses of PTX. Annexin V/PI assay and DAPI staining were applied to evaluate apoptosis. Flow cytometry was applied to determine cells arrested in different phases of the cell-cycle. Expression levels of molecular factors involved in cell migration, proliferation, apoptosis, and cell cycle were determined via western blotting and qRT-PCR. RESULTS: MiR-138-5p combined with PTX suppressed cell migration via modulating MMP2, E-cadherin, and vimentin and sustained colony formation and proliferation by downregulation of the PI3K/AKT pathway. qRT-PCR showed that miR-138-5p increases BC chemosensitivity to PTX by regulating the apoptosis factors, including Bcl-2, Bax, Caspase 3, and Caspase 9. Moreover, miR-138-5p restoration and paclitaxel therapy combined arrest the cells in the sub-G1 and G1 phases of cell cycle by regulating p21, CCND1, and CDK4. CONCLUSIONS: Restored miR-138-5p intensified the chemosensitivity of MDA-MB-231 cell line to PTX, and the combination of miR-138-5p with PTX might represent a novel approach in BC treatment.

An updated review of the role of lncRNAs and their contribution in various molecular subtypes of breast cancer.

Introduction: Breast cancer (BC) is the most significant threat to women's life. To demonstrate its molecular mechanisms, which results in BC progression, it is crucial to develop approaches to enhance prognosis and survival in BC cases.Areas covered: In the current study, we aimed to highlight the updated data on the oncogenic and tumor suppressive roles of lncRNAs in the progression of various subtypes of BC by specifically putting importance on the functional characteristics, modulatory agents, therapeutic potential, future perspectives and challenges of lncRNAs in BC. We reviewed recent studies published between 2019 and 2020.Expert opinion: The latest investigations have demonstrated that the long non-coding RNAs (lncRNAs) participate in different BC molecular subtypes via different molecular mechanisms; however, the exact functional information of the lncRNAs has yet to be elucidated. The studied lncRNAs could be more applicable as therapeutic targets in BC treatment after pre-clinical and clinical studies.

An Updated Review of the Cross-talk Between MicroRNAs and Epigenetic Factors in Cancers.

BACKGROUND: Growing evidence indicates that miRs have critical activities in adjusting cellular processes, e.g., cell death, proliferation, and cell-cycle. INTRODUCTION: This study aimed to provide a concise review of the recent findings regarding tumoral miRs and the cross-talk between miRs and epigenetic factors. RESULTS: Like the protein-coding genes, the expression levels of miRs are mediated by various transcriptional networks. Indeed, the expression of miRs could be epigenetically modulated by DNA methylation factors and histone modifiers. Furthermore, miRs can suppress critical factors, which mediate epigenetic modifications. Besides, miRs have been implicated in cancer development, metastasis, and chemo-resistance. The aberrant expression of miRs and dysregulated modulatory circuits between miRs and epigenetic factors participate in tumor progression. CONCLUSION: Identifying tumoral miRs can provide ample opportunity to overcome chemo- resistance and bring a forefront treatment for affected patients.

MiRNA-138-5p: A strong tumor suppressor targeting PD-L-1 inhibits proliferation and motility of breast cancer cells and induces apoptosis.

MicroRNAs are important regulators in multiple cellular processes and are closely related to a variety of cancers including breast cancer (BC). Immunotherapy using different methods such as modulating immune check points has been known as an advanced and successful procedure in cancer treatment. Here we investigated the effects of miRNA-138-5p restoring on Programmed Death Ligand 1 (PD-L-1) expression, BC biological behaviors and T-cell exhaustion. Breast cancer specimens and cell lines were provided and qRT-PCR and western blotting were used to measure the expression of miRNA-138-5p, PD-L-1 and other underlying genes. MTT and colony formation assays and scratch test were employed to specify proliferation, cloning and migration in miRNA-138-5p-transfected MDA-MB-231 cells respectively. DAPI staining assay and flow-cytometry were used to investigate apoptosis rate and cell cycle development. Finally, isolated T-cells were co-cultured with transfected BC cells to explore the effect of miRNA-138-5p on T-cell exhaustion. qRT-PCR revealed down-regulation ofmiRNA-138-5p conversely, up-regulation of PD-L-1 in BC tissues and cell lines. Transfection of miRNA-138-5p into MDA-MB-231 cells inhibited PD-L-1 expression. Western blotting, MTT and colony formation assays affirmed the anti-proliferative effect ofmiRNA-138-5p through down-regulating PI3K/AKT pathway. Also, miRNA-138-5p induced apoptosis in BC cells via up-regulating Caspase-9 and Caspase-3 and arresting cell cycle at sub-G1 phase. Moreover, scratch test and western blotting indicated that miRNA-138-5p inhibits cell motility via targeting MMP2, MMP9 and vimentin but up-regulating E-cadherin. Finally, miRNA-138-5p restrains T-cell exhaustion via suppressing PD-L-1 expression in BC cells leading to disrupt PD-L-1/PD-1 interaction and modulate effector cytokines in T-cells.

miR-424: A novel potential therapeutic target and prognostic factor in malignancies.

microRNAs are endogenous, noncoding RNAs. Showing both tumor-suppressive and oncogenic characteristics, miRNAs can regulate important processes in malignancies. This review aimed at highlighting the recent studies on the contribution of miR-424 to the modulation of carcinogenesis and exploring its probable clinical effectiveness in the diagnosis and therapy of malignancies. The data were extracted from all papers published from 2013 until 2020. Mature miR-424 leads to the degradation of its target transcripts or the suppression of translation via binding to the molecular targets. miR-424 is involved in modulating p53, PI3K/Akt, Wnt, and other molecular pathways, thereby regulating cellular growth, apoptosis, differentiation, chemoresistance, and cancer immunity. miR-424 was introduced as a tumor-suppressive miR in numerous types of cancers while as an oncogene in several cancers. Regarding the cancer dependent role of miR-424, it may be a prognostic and diagnostic biomarker and a potential candidate for the treatment of cancers.

MicroRNA -383-5p restrains the proliferation and migration of breast cancer cells and promotes apoptosis via inhibition of PD-L1.

AIMS: MicroRNAs (miRs) play pivotal roles in breast cancer development. The dysregulation of miRs has been associated with PD-L1-mediated immune suppression. This study aimed to examine the effect of transfected miR-383-5p on breast cancer cells and T-cells and its association with clinicopathological features in affected patients. MAIN METHODS: Initially, miR-383-5p and PD-L1 expression levels were investigated in breast cancer tissues. Then, MDA-MB-231 cells were transfected with miR-383-5p mimics to perform analyses. Cell viability was investigated using the MTT assay, and the annexin V/PI staining assay was performed to examine apoptosis induction. Furthermore, the effect of miR-383-5p on cell migration and cell cycle progression was analyzed using the wound-healing assay and flow cytometry, respectively. Gene and protein expressions were studied using qRT-PCR and western blotting. Finally, the effect of miR-383-5p on T-cells, which were co-cultured with cancer cells, was investigated. KEY FINDINGS: Compared to non-malignant tissues, PD-L1 was up-regulated, and miR-383-5p expression was downregulated in breast cancer tissues. Moreover, miR-383-5p reduced breast cancer cell viability via inducing apoptosis and modulating the expression of apoptosis-related genes. Besides, miR-383-5p could inhibit the migration of breast cancer cells via down-regulating metastasis-related genes. Besides, transfected miR-383-5p induced the secretion of pro-inflammatory cytokines from T-cells. Furthermore, the results showed that miR-383-5p might exert its tumor-suppressive effect via inhibiting the PI3K/AKT/mTOR pathway. The inhibitory effect of transfected miR-383-5p on the PI3K/AKT/mTOR pathway might be the underlying mechanism for inhibiting tumoral PD-L1 expression. SIGNIFICANCE: Overall, miR-383-5p can be a promising therapeutic agent for treating breast cancer.

The correlation between microRNAs and Helicobacter pylori in gastric cancer.

Helicobacter pylori infection and H. pylori-related gastric inflammation can be considered as the most significant promoter of gastric cancer (GC). Recent investigations have evaluated the regulatory function of microRNAs (miRNAs) in H. pylori pathogenesis and H. pylori-related diseases, especially GC. The present study reviewed the correlation between miRNAs and H. pylori in gastrointestinal diseases. Furthermore, the current review highlighted the role of H. pylori pathogen and some H. pylori-related virulence factors in the deregulation of various miRNAs, especially oncogenic miRNAs (miRs) and their associated molecular pathways. Among the related studies, some have focused on the effects of H. pylori infection on regulatory networks of miRs, while others have highlighted the effects of alterations in the expression level of miRs in H. pylori-related diseases. The connectivity between miRNAs and H. pylori is regulated by various molecular pathways and different molecular targets of miRNAs.

Effect of troxerutin on apelin-13, apelin receptors (APJ), and ovarian histological changes in the offspring of high-fat diet fed rats.

OBJECTIVES: Maternal high-fat diet (HFD) consumption has been linked to metabolic disorders and reproductive dysfunctions in offspring. Troxerutin (TRO) has anti-hyperlipidemic, anti-oxidant, and anti-inflammatory effects. This study examined the effects of TRO on apelin-13, its receptors mRNA and ovarian histological changes in the offspring of HFD fed rats. MATERIALS AND METHODS: Female Wistar rats were randomly divided into control diet (CD) or HFD groups and received these diets for eight weeks. After mating, dams were assigned into four subgroups: CD, CD + TRO, HFD, and HFD + TRO, and received their respective diets until the end of lactation. Troxerutin (150 mg/kg/day) was gavaged in the CD + TRO and HFD + TRO groups during pregnancy. On the postnatal day (PND) 21 all female offspring were separated and fed CD until PND 90. On PND 90 animals were sacrificed and ovarian tissue samples were collected for further evaluation. RESULTS: Results showed that HFD significantly decreased serum apelin-13 in the female offspring of the HFD dams, which was significantly reversed by TRO. Moreover, real-time polymerase chain reaction (PCR) analysis revealed that TRO treatment significantly decreased the ovarian mRNA expression of the apelin-13 receptor in the troxerutin-received offspring. Furthermore, histological examination revealed that TRO increased the number of atretic follicles in the ovaries of HFD+TRO offspring. CONCLUSION: Maternal high fat feeding compromises ovarian health including follicular growth and development in the adult offspring and troxerutin treatment improved negative effects of maternal HFD on the apelin-13 level and ovarian development of offspring.

An Interleukin-6 Single Nucleotide Polymorphism and Susceptibility to Prostate Adenocarcinoma and Bone Metastasis in an Iranian Population

Objective: Interleukin-6 (IL-6) is an inflammatory cytokine shown to be a strong factor for growth, proliferation and metastasis with many malignancies. The promoter single nucleotide polymorphism (SNPs) -174G>C (rs1800795) can alter the transcriptional pattern of this gene. The present study was aimed at assessing effects of the IL-6 (rs1800795) SNP on risk of benign prostate hyperplasia (BPH) and prostatic adenocarcinoma (PCa). Methods: The project was performed on 112 men with PCa, 118 with BPH and 250 healthy controls. After DNA extraction, genotyping of IL-6 (rs1800795) was performed using PCR TaqMan Allelic Discrimination (ABI MGB). Results: The G allele frequency for rs1800795 of the IL-6 gene was 74.1%, 68.6% and 67% in PCa patients, BPH patients and healthy men, respectively. PCa and control groups showed significant differences (P =0.030, OR = 1.73, 95% CI: 1.05-2.21). The GG genotype was more frequent in the PCa group, whereas the GC genotype was more common in the BPH in comparison to other groups. Conclusion: The current study identified IL-6 -174G>C (rs1800795) as a significant predictor of susceptibility for prostate cancer and bone metastasis in a northwest Iranian population.

Comparison of the Effects of Clofibrate and Silafibrate on Sperm Parameters Quality and Sex Hormones in Male Rats.

PURPOSE: Fibrates are drugs widely used for the treatment of hyperlipidemic disorders. Previous studies on a novel analogue of clofibrate, called silafibrate, have shown good lipid lowering effects. This study was designed to assess the role of silafibrate as a peroxisome proliferator-activated receptors (PPARs) agonist on sperm health and spermatogenesis in adult male rats. MATERIAL AND METHODS: Seventy male Wistar rats were randomly allocated into 7 groups: Cl-10, Cl-20, and Cl-40 mg/kg/day (clofibrate); Si-10, Si-20, and Si-40 mg/kg/day (silafibrate); and C, control. After a 28-day treatment, all rats were euthanized. Blood samples were taken for determination of testosterone, total antioxidant capacity, levels of malondialdehyde, and oxidized low-density lipoprotein. Reproductive organs were dissected and spermatozoa collected from the epididymis for analysis. RESULT: Sperm parameters (count, motility, viability, and morphology) and total serum testosterone decreased significantly in clofibrate-treated (20 and 40 mg/kg) rats (P < 0.05) as compared with normal rats. CONCLUSION: We conclude that PPARs agonists have significant adverse effect on sperm viability, motility, and total serum testosterone, and could be harmful for sperm parameters and male reproductive function in rats.

Poisonous Spiders: Bites, Symptoms, and Treatment; an Educational Review.

More than 40,000 species of spiders have been identified in the world. Spider bites is a common problem among people, however few of them are harmful but delay in treatment can cause death. Since the spider bites are risk full to human, they should be taken seriously, especially in endemic areas. Our objective in this review was to study about poisonous spiders and find out treatments of them. Therefore, we collected related articles from PubMed database and Google Scholar. Three important syndromes caused by spider bites are loxoscelism, latrodectism and funnel web spider syndrome. Many treatments are used but much more studies should have done to decrease the mortality. In this review, we describes different venomous spiders according to their appearance, symptoms after their bites and available treatments.