Metal Ions Bound to Prion Protein Affect its Interaction with Plasminogen Activation System

The Protein Journal - Prion diseases are a group of neurodegenerative diseases, which can progress rapidly. Previous data have demonstrated that prion protein (PrP) stimulates activation of...     

Heavy metal phytoremediation of aqueous solution by Typha domingensis

Aquatic Ecology - More has yet to be indicated on the ability of microphyte plants for the removal of heavy metals from contaminated environments. In the present research, the ability of the...     

Intraovarian injection of miR-224 as a marker of polycystic ovarian syndrome declines oocyte competency and embryo development

miR-224 is associated with polycystic ovary syndrome (PCOS) that is an epidemic in reproductive age women. Most studies of miR-224 have focused on in vitro analyses, whereas the in vivo effects are not widely understood. In this study, we have conducted in silico analysis and found two potential miR-224 target genes, Ptx3 and Smad4 that have roles in folliculogenesis. Because patients with PCOS have decreased numbers of follicular cells related to cell apoptosis, we also investigated two apoptotic genes, Bax and Bcl2. We used the intraovarian injection method to deliver miR-224 into a mouse model. Histological examination of the ovaries was done by fluorescent microscope. Fertilization, cleavage, and developmental competence rates were counted under a stereomicroscope and compared between the studied groups. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of miR-224 was conducted to determine the levels of the studied genes in the oocytes, cumulus cells, and blastocysts. The numbers of oocytes and fertilization rate indicated a higher apoptosis index ( p < 0.05) and increased numbers of degenerated embryos with irregular blastomeres and fragmented cytoplasm in the experimental group. RT-PCR results indicated a significant increase in miR-224 levels in the manipulated group. Of the four analyzed genes, Ptx3, Smad4, and Bcl2 had decreased levels in the transfected group, with increased Bax expression ( p < 0.05). This data showed that miR-224 negatively affected ovulation in the mouse model by decreasing Ptx3 and Smad4 expressions. The changes in Bcl2 and Bax expression levels, as apoptosis biomarkers, showed that apoptosis was a secondary outcome of the effect of miR-224.     

Ovarian cancer stem cell: A potential therapeutic target for overcoming multidrug resistance

The cancer stem cell (CSC) model encompasses an advantageous paradigm that in recent decades provides a better elucidation for many important biological aspects of cancer initiation, progression, metastasis, and, more important, development of multidrug resistance (MDR). Such several other hematological malignancies and solid tumors and the identification and isolation of ovarian cancer stem cells (OV-CSCs) show that ovarian cancer also follows this hierarchical model. Gaining a better insight into CSC-mediated resistance holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. Therefore, in this review, we will discuss some important mechanisms by which CSCs can escape chemotherapy, and then review the recent and growing body of evidence that supports the contribution of CSCs to MDR in ovarian cancer.     

CTNNBIP1 downregulation is associated with tumor grade and viral infections in gastric adenocarcinoma

Gastric cancer is a life-threatening disease; resulting from interaction among genetic, epigenetic, and environmental factors. Aberrant dysregulation and methylation changes in Wnt/β-catenin signaling downstream elements are a prevalent phenomenon encountered in gastric tumorigenesis. Also, viral infections play a role in gastric cancer development. CTNNBIP1 (β-catenin interacting protein 1) gene is an antagonist of Wnt signaling which binds to the β-catenin molecules. The CTNNBIP1 function as tumor suppressor gene or oncogene in different types of cancer is controversial. Moreover, its function and regulatory mechanisms in gastric cancer progression is unknown. In the present study, we examined CTNNBIP1 gene expression, the methylation status of the regulatory region of the gene, and their association with Epstein–Barr virus (EBV), and cytomegalovirus (CMV) and Helicobacter pylori infections in human gastric adenocarcinoma tissues in comparison with their adjacent nontumoral tissues. Our data revealed a significant downregulation of CTNNBIP1 in gastric tumors. Female patients showed lower level of CTNNBIP1 than males (p < 0.05). Also, decreased expression of CTNNBIP1 was markedly associated with well-differentiated tumor grades (p < 0.05). No methylation change was observed between tumoral and nontumoral tissues. Additionally, CTNNBIP1 down regulation was significantly associated with CMV infection (p < 0.05). In the absence of EBV infection, lower expression of CTNNBIP1 was observed. There was no association between H. pylori infection and CTNNBIP1 expression. Our findings revealed the tumor suppressor role for CTNNBIP1 in gastric adenocarcinoma. Interestingly, EBV and CMV infections modulate CTNNBIP1 expression.     

Adjuvant chemotherapy with melatonin for targeting human cancers: A review

Melatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re-establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer-specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.     

Antidiabetic potential of saffron and its active constituents

The prevalence of diabetes mellitus is growing rapidly worldwide. This metabolic disorder affects many physiological pathways and is a key underlying cause of a multitude of debilitating complications. There is, therefore, a critical need for effective diabetes management. Although many synthetic therapeutic glucose-lowering agents have been developed to control glucose homeostasis, they may have unfavorable side effects or limited efficacy. Herbal-based hypoglycemic agents present an adjunct treatment option to mitigate insulin resistance, improve glycemic control and reduce the required dose of standard antidiabetic medications. Saffron (Crocus sativus L.), whilst widely used as a food additive, is a natural product with insulin-sensitizing and hypoglycemic effects. Saffron contains several bioactive β carotenes, which exert their pharmacological effects in various tissues without any obvious side effects. In this study, we discuss how saffron and its major components exert their hypoglycemic effects by induction of insulin sensitivity, improving insulin signaling and preventing β-cell failure, all mechanisms combining to achieve better glycemic control.     

Mechanisms of statin-induced new-onset diabetes

Statins, with their lipid-lowering properties, are a first-line therapy for the prevention of cardiovascular diseases. Recent evidence, however, suggests that statins can increase the risk of new-onset diabetes (NOD). The molecular mechanisms of statin-induced NOD are not precisely known, although some pathophysiologic mechanisms have been suggested. Specific to the beta cell, these mechanisms include alterations in insulin secretion, changes in ion channels, modulation of signaling pathways, and inflammation/oxidative stress. Outwith the beta cell, other suggested mechanisms involve adipocytes, including alterations in adipocyte differentiation and modulation of leptin and adiponectin, and genetic and epigenetic mechanisms, including alterations in microRNA. The evidence supporting these and other mechanisms will be discussed. Greater understanding of the underlying mechanisms linking the onset of diabetes to statin therapy is essential and clinically relevant, as it may enable novel preventative or therapeutic approaches to be instituted and guide the production of a new generation of statins lacking this side effect.     

Positive correlation between vitamin D receptor gene TaqI variant and gastric cancer predisposition in a sample of Iranian population

Gastric cancer is the second cause of cancer-related mortality and the fourth most common cancers worldwide. Owing to the immune modulatory effect of vitamin D in the body, the role of vitamin D receptor gene in vitamin D regulation receives a great deal of research interest. The aim of the current study was to highlight the association between two variants of TaqI and FokI in the vitamin D receptor gene and gastric cancer predisposition in a sample of South Khorasan population. The present investigation consisted of 69 patients affected with gastric cancer and 100 healthy individuals. The genomic DNA was extracted by salting out the protocol from peripheral venous blood. Genotyping of TaqI and FokI variants were performed by PCR-RFLP method. Our findings manifested that TC genotype of TaqI polymorphism was statistically significant between the case and the control groups (p = 0.002). Moreover, the frequency of TC + CC genotypes was statistically significant between the two groups (p = 0.009). Furthermore, we could not find any meaningful association between FokI variant and the participant groups. The present results declared that, in our population, TC genotype of TaqI polymorphism has an association with gastric cancer susceptibility. In addition, more investigation with greater sample sizes is needed to confirm our results.