Antioxidant and antiglycation effects of scopolamine in rat liver cells

Tropane alkaloid, scopolamine is medicinally important compound produced by many plants of Solanaceous species. The present study was to investigate the antioxidant and antiglycation effects of this compound in culture of rat liver tissue. In this study, scopolamine at different concentrations were titred on rat liver cells. Then, the activity of glutathione peroxidase, superoxide dismutase and catalase as well as glyoxal and 2,2-diphenyl-1-picrylhydrazyl inhibition were measured by spectophotometry and changes in malondialdehyde (MDA) in liver cells were measured by high-performance liquid chromatography. The antioxidant and antiglycation activities of scopolamine increased as its concentrations increased in the liver cells, representing promotion of reactive oxygen species generation compared to control. Scopolamine exerts antioxidant and antiglycation activities in rat liver cells

MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway.

Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, and its mechanism has not been fully understood. The objectives of this study were to determine the role of miR-221/222 and its underlying mechanism in chemoresistance of ovarian cancer. We demonstrated that miR-221/222 expression levels were higher in A2780/CP cells compared with A2780 S cells. An in vitro cell viability assay showed that downregulation of miR-221/222 sensitized A2780/CP cells to cisplatin-induced cytotoxicity. Moreover, we found that knockdown of miR-221/222 by its specific inhibitors promoted the cisplatin-induced apoptosis in A2780/CP cells. Using bioinformatic analysis and luciferase reporter assay, miR-221/222 were found to directly target PTEN. Moreover, knockdown of miR-221/222 in A2780/CP cells significantly upregulated PTEN and downregulated PI3KCA and p-Akt expression. In conclusion, our results demonstrated that miR-221/222 induced cisplatin resistance by targeting PTEN mediated PI3K/Akt pathway in A2780/CP cells, suggesting that miR-221/222/PTEN/PI3K/Akt may be a promising prognostic and therapeutic target to overcome cisplatin resistance and treat ovarian cancer in the future

The study of hyoscyamine in oxidative stress of liver cells in male rat

Background and aims: Increased production of free radicals by endogenous systems and exogenous sources in cells leads to oxidative stress, which damages to the cells of various organs. Hyoscyamine is one of the important tropane alkaloid isolated from some Solanaceous species used to traditional medicine that they are used for their analgesic, anti-inflammatory, antipyretic, and anticonvulsant activities. The antioxidant and antiglycation properties of tropane alkaloids may represent a role in dealing with oxidative stress. The aim of this study was to investigate the antioxidant and antiglycation effects of hyoscyamine component on the liver cells in male rats. Methods: In this experimental- laboratory study, liver cells were isolated from male Sprague–Dawley rats. The cells cultured under standard conditions. Various concentrations of hyoscyamine (0-32 µM) were treated on rat liver cells. Then, the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) as well as glyoxal and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition were measured by spectrophotometry. High-performance liquid chromatography (HPLC) was performed for measuring malondialdehyde (MDA) in liver cells. Results: CAT, SOD and GPX enzyme activities increased as the concentration of hyoscyamine increased. DPPH showed a strong inhibition on reactive oxygen species generation compared to control group. The amount of SOD, CAT and GPX enzyme activities in 8 micromolar concentration of hyoscyamine compared with the control group significantly increased as 10.33 and 8.6 and 6.3 units (P<0.05). Also, hyoscyamine (4µM) reduced the amount of MDA, glyoxylate and DPPH compared to the control group as 1.94, 2.26, and 2.33 times (P<0.05). Conclusion: Our findings indicated that hyoscyamine had considerable antioxidant and antiglycation activities on rat liver cells. This compound protects liver cells against the damaging effects of free radicals. The effects of this compound for the treatment of diseases associated with oxidative stress would be useful in the future

Investigation of mutation in cystatin‌ B gene in patients affected by idiopathic generalized epilepsy in Chaharmahal and Bakhtiari province

Background and aims: Cystatin B gene encodes a protein that inhibits proteolytic activity of cathepsin enzymes. Mutation in this gene has been stated as one of the causes of idiopathic generalized epilepsy. This study aimed at screening the cstB gene mutations in 35 patients affected by idiopathic generalized epilepsy in the Chaharmahal and Bakhtiari province. Methods: In this descriptive-lab study, the researchers examined mutations in exons 1 to 3 and uncovered the cstB gene promoter region in 35 patients with Idiopathic Generalized Epilepsy.Using standard phenol-chloroform procedure. The researchers extracted DNA and then they utilized PCR-SSCP analysis for screening mutations in this gene. Finally suspected cases were sequenced. Results: In one of the samples, point mutation c.48C> T was found which was unknown. Investigating the bioinformatic examinations on this sample, it can be concluded that this shift has been occurred in the cstB gene intronic region. Conclusion: The results obtained from the samples of this study reveales that there is a slight relationship between idiopathic generalized epilepsy and the cstB gene mutations

Prediction and analysis of microRNAs involved in COVID-19 inflammatory processes associated with the NF-kB and JAK/STAT signaling pathways

COVID-19 is the cause of a pandemic associated with substantial morbidity and mortality. As yet, there is no available approved drug to eradicate the virus. In this review article, we present an alternative study area that may contribute to the development of therapeutic targets for COVID-19. Growing evidence is revealing further pathophysiological mechanisms of COVID-19 related to the disregulation of inflammation pathways that seem to play a critical role toward COVID-19 complications. The NF-kB and JAK/STAT signaling pathways are highly activated in acute inflammation, and the excessive activity of these pathways in COVID-19 patients likely exacerbates the inflammatory responses of the host. A group of non-coding RNAs (miRNAs) manage certain features of the inflammatory process. In this study, we discuss recent advances in our understanding of miRNAs and their connection to inflammatory responses. Additionally, we consider the link between perturbations in miRNA levels and the onset of COVID-19 disease. Furthermore, previous studies published in the online databases, namely web of science, MEDLINE (PubMed), and Scopus, were reviewed for the potential role of miRNAs in the inflammatory manifestations of COVID-19. Moreover, we disclosed the interactions of inflammatory genes using STRING DB and designed interactions between miRNAs and target genes using Cityscape software. Several miRNAs, particularly miR-9, miR-98, miR-223, and miR-214, play crucial roles in the regulation of NF-kB and JAK-STAT signaling pathways as inflammatory regulators. Therefore, this group of miRNAs that mitigate inflammatory pathways can be further regarded as potential targets for far-reaching-therapeutic strategies in COVID-19 diseases

Valproic Acid Promotes Apoptosis and Cisplatin Sensitivity Through Downregulation of H19 Noncoding RNA in Ovarian A2780 Cells

Abstract Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a lncRNA involving in cisplatin resistance in cancers. Valproic acid (VPA) is a commonly used drug for clinical treatment of seizure disorders. In addition, this drug may display its effects through regulation of noncoding RNAs controlling gene expression. The aim of the present study was the investigation of VPA treatment effect on H19 expression in ovarian cancer cells and also the relation of the H19 levels with apoptosis and cisplatin resistance. Briefly, treatment with VPA not only led to significant increase in apoptosis rate, but also increased the cisplatin sensitivity of A2780/CP cells. We found that following VPA treatment, the expression of H19 and EZH2 decreased, but the expression of p21 and PTEN increased significantly. To investigate the involvement of H19 in VPA-induced apoptosis and cisplatin sensitivity, H19 was inhibited by a specific siRNA. Our results demonstrate that H19 knockdown by siRNA induced apoptosis and sensitized the A2780/CP cells to cisplatin-induced cytotoxicity. These data indicated that VPA negatively regulates the expression of H19 in ovarian cancer cells, which subsequently leads to apoptosis induction, cell proliferation inhibition, and overwhelming to cisplatin resistance. The implication of H19→EZH2→p21/PTEN pathway by VPA treatment suggests

Investigation of RFLP Haplotypes β-Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran.

Introduction: Beta-thalassemia is one of the most prevalent inherited blood diseases among Iranians. The aim of this study was to elucidate the chromosomal background of beta-thalassemia mutations in Esfahan province, Iran. Materials and Methods: In this study, we investigated three frequent mutations (c.315+1G>A, c.93-21G>A and c.92+5G>C in β-globin gene, the frequency of RFLP haplotypes, and LD between markers at β-globin gene cluster) in 150 beta-thalassemia patients and 50 healthy individuals. The molecular and population genetic investigations were performed on RFLP markers HindIII in the c.315+1G>A of Gγ (HindIIIG) and Aγ (HindIIIA) genes, AvaII in the c.315+1G>A of β-globin gene and BamHI 3' to the β-globin gene. All statistical analyses were performed using Power Marker software and SISA server. Results: Fifty percent of beta-thalasemia patients were associated with these mutations. Haplotype I was the most prevalent haplotype among beta-thalassemia patients (39.33%) and normal individuals (46%). The commonest c.315+1G>A mutation in our population was tightly linked with haplotype III (43.75%) and haplotype I (31.25%). The second prevalent mutation, c.92+5G>C, was 90%, 6.66%, and 3.33% in linkage disequilibrium with haplotypes I, VII, and III, respectively. The c.93-21G>A mutation indicated a strong association with haplotype I (80%). Conclusion: Our study participants like beta-thalassemia patients from Kermanshah province was found to possess a similar haplotype background for common mutations. The emergence of most prevalent mutations on chromosomes with different haplotypes can be explained by gene conversion and recombination. High linkage of a mutation with specific haplotype is consistent with the hypothesis that chromosomes carrying beta-thalassemia mutations experienced positive selection pressure, probably because of the protection against malaria experienced by beta-thalassemia carriers. KEYWORDS: Beta-thalassemia; Haplotype; c.315+1G>A; c.92+5G>C; c.93-21G>

Effect of valproic acid on cisplatin-resistant ovarian cancer cell lines

Background and aims: Platinum resistance has been one of the most important problems in the management of ovarian cancer. The effects of various chemotherapeutic agents are limited in patients with platinum resistance. Therefore, developing new anticancer drugs that can improve the effect of currently used cytostatics is critical. The current study investigated the effects of valproic acid (VPA) alone and in combination with cisplatin on ovarian cancer cells. Methods: In this experimental study, the human ovarian cancer cell lines (A2780-S and A2780-CP) were grown in RPMI-1640 medium in appropriate culture conditions. The cells were treated with various concentrations of cisplatin (0.15-400 µg/mL) or VPA (10-2000 µg/mL) and were incubated for 24, 48, and 72 hours. Moreover, A2780 cells were co-treated with different concentrations of cisplatin and VPA for 48 hours. Afterward, cell viability was investigated using MTT assay. GraphPad Prism statistical software was used for the data analysis and ANOVA and Duncan’s test were conducted. Results: A dose- and time-dependent reduction was observed in cell viability following the treatment with cisplatin or VPA. Moreover, cotreatment of the A2780 cells with cisplatin and VPA resulted in a significantly greater inhibition of cell viability compared to the treatment with either agent alone. Conclusion: Overall, it can be argued that VPA does not only cause inhibition of proliferation and induction of apoptosis in ovarian cancer cells but also helps to enhance the antiproliferative effects of cisplatin and results in the increased susceptibility to cisplatin in resistant cells. VPA may therefore be used to treat cancer in the future. Keywords: Ovarian cancer, Cisplatin, Valproic acid, Platinum resistance, Antiproliferative effec

The impact of miR‐183/182/96 gene regulation on the maturation, survival, and function of photoreceptor cells in the retina

MicroRNAs (MiRNAs) play important roles in posttranscriptional processes to regulate gene expression. MiRNAs control various biological processes, such as growth, development, and differentiation. The continuous physiological function of photoreceptors and retinal pigment epithelium requires precise regulation to maintain their homeostasis and function; hence, these cells are highly susceptible to premature death in retinal degenerative disorders. MiRNAs are essential for the retinal cell maturation and function; the miR-183 cluster represents one of the most important regulatory factors for the photoreceptor cells. Various studies together with bioinformatics analyses have shown that many genes contributing to the differentiation pathway of photoreceptors are targets of the miR-183 cluster, and the miR-183 cluster dysregulation causes certain defects in the differentiation of the photoreceptors and other retinal neurons by influencing the expression of target genes. Misexpression of miR-183 cluster in the human retinal epithelial cells leads to the reprogramming and transformation of these cells to neuron- and photoreceptor-like cells, which are associated with the expression of neuron- and photoreceptor-specific markers in human retinal pigment epitheliums cells. The knockout of this cluster causes the destruction of the outer segment of the photoreceptors, which subsequently causes the cells to exhibit severe susceptibility to light and eventually degenerate. Hundreds of target genes in this family are likely to affect the development and maintenance of the retina. Identifying the genes that are regulated by the miRNA-183 cluster provides researchers with important insights into the complex development and regeneration mechanism of the retina and may offer a new way for maintaining and regenerating photoreceptor cells in neurodegenerative diseases

Apoptotic effects of valproic acid on miR-34a, miR-520h and HDAC1 gene in breast cancer

Identifying miRNAs involved in cancer and devising strategies to control their expression is a new therapeutic approach. Valproic acid (VPA) has attracted a lot of interest in cancer research. We evaluated the impact of VPA on the expression of miR-34a, miR-520h, and their target gene histone deacetylase 1 (HDAC1), as well as their relationship with apoptosis in breast cancer. First, through bioinformatics analyses, the possible target genes of miR-34a and miR-520h and their roles in apoptosis regulation were investigated. Then, miR-34a, miR-520h, and HDAC1 gene expression in tissues of breast cancer patients were determined using the qRT-PCR method. The anticancer impact of VPA on apoptosis and the expression levels of miR-34a, miR-520h, and HDAC1 gene were measured in MCF-7 and MDA-MB-231 cell lines. The bioinformatics analyses indicated that miR-34a and miR-520h might make a unique contribution in regulating the apoptosis pathway. The relative expression of miR-34a and miR-520h significantly decreased in cancer tissues, while the relative expression of HDAC1 increased. In the in vitro study, VPA led to apoptosis induction and increased lipid peroxidation products in breast cancer cells. Moreover, VPA increased the expression of miR- 34a and miR-520h and decreased HDAC1 expression in MCF-7 cells. In MDA-MB-231 cells, VPA decreased the expression of these miRNAs and increased the expression of HDAC1. It can be concluded that miR-34a and miR-520h are implicated in the apoptosis pathways, and thus, VPA can recruit as a possible option in breast cancer research due to its interference with epigenetic processes