Simvastatin-Loaded Nanoniosome Protects H9c2 Cells from Oxygen-Glucose Deprivation/ Reperfusion Injury by Downregulating Inflammation.

Background: Simvastatin (SIM) has anti-inflammatory and antioxidant properties against cardiac ischemia/reperfusion injury (I/RI). However, it suffers from low bioavailability and a short half-life. Nanoniosomes are novel drug delivery systems that may increase SIM effectiveness. The present research evaluates the impact of SIM-loaded nanoniosomes on the oxygen-glucose deprivation/reperfusion (OGD/R) injury model of H9c2 cells. Methods: Cells were seeded based on five groups: (1) control; (2) OGD/R; (3) OGD/R receiving SIM; (4) OGD/R receiving nanoniosomes; and (5) OGD/R receiving SIM loaded nanoniosomes. OGD/R injury of the H9c2 cells was treated with SIM or SIM loaded nanoniosomes. Cell viability, two inflammatory factors, necroptosis factors, along with HMGB1 and Nrf2 gene expressions were assessed. Results: The cells treated with SIM loaded nanoniosomes showed a significant elevation in the cell viability and a reduction in HMGB1, Nrf2, TNF-α, IL-1ß, RIPK1, and ROCK1 expression levels compared to the OGD/R and SIM groups. Conclusion: Based on our findings, nanoniosomes could safely serve as a drug delivery system to counterbalance the disadvantages of SIM, resulting in improved aqueous solubility and stability.

Abnormal expression of long non-coding RNAs RMRP, CTC-487M23.5, and DGCR5 in the peripheral blood of patients with Bipolar disorder.

Long non-coding RNAs (lncRNAs) have been recently considered as one of the regulatory mechanisms of the nervous system. Hence, lncRNAs may be considered diagnostic biomarkers for bipolar disorder (BD). We aimed to investigate the expression of RMRP, CTC-487M23.5, and DGCR5 lncRNAs in bipolar patients. The levels of these three lncRNAs were measured in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy subjects by real-time PCR. Moreover, we performed a ROC curve analysis between the gene expression and some clinical features of BD patients. Significant upregulation of RMRP and CTC-487M23.5 and no significant change in levels of DGCR5 was observed in BD individuals compared with controls. Also, we found upregulation of RMRP and downregulation of CTC-487M23.5 and DGCR5 in females with BD. The areas under the ROC curve (AUC) for RMRP and CTC-487M23.5 lncRNAs were 0.80 and 0.61, respectively. There was no significant correlation between the expression of these three lncRNAs and clinical features in PBMCs of BD patients. These results suggest a role for RMRP and CTC-487M23.5 in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these two lncRNAs might be beneficial as potential biomarkers for BD.

Reduction of GAS5 and FOXD3-AS1 long non-coding RNAs in patients with bipolar disorder.

Bipolar disorder (BD) patients suffer from severe disability and premature death because of failure in prognosis, diagnosis, and treatment. Although neural mechanisms of bipolar have not been fully discovered, studies have shown long noncoding RNAs (lncRNAs) can play an important role in signaling pathways such as PI3K/AKT pathway. There has been little study on deregulated lncRNAs and the lncRNAs' mode of action in the BD. Hence, we aimed to investigate the expression of PI3K/AKT pathway-related lncRNAs named TUG1, GAS5, and FOXD3-AS1 lncRNAs in the PMBC in 50 bipolar patients and 50 healthy controls. Our results showed that FOXD3-AS1 and GAS5 under-expressed significantly in bipolar patients compared to healthy controls (P = 0.0028 and P < 0.0001 respectively). Moreover, after adjustment, all P values remained significant (q value < 0.0001). According to the ROC curve, AUC (area under the curve), specificity, and sensitivity of these lncRNAs, GAS5 and FOXD3-AS1 might work as BD candidate diagnostic biomarkers. Taken together, the current results highlight that the dysregulation of FOXD3-AS1 and GAS5 may be associated with an increased risk of BD.

Immunogenicity Evaluation of Recombinant Edible Vaccine Candidate Containing HER2-MUC1 against Breast Cancer.

Human epithelial growth factor receptor2 (Her2) and polymorphic epithelial mucin (MUC1) are tumor-associated antigens that have been extensively investigated in adenocarcinomas. Generally, each of these molecules was used separately for diagnosis of adenocarcinomas and as an injective vaccines in cancer therapy researches, but not in the chimeric form as an edible immunogen. In this study, Her2, MUC1, and a novel fusion structure were expressed in the seeds and hairy roots of transgenic plants appropriately. The mice groups were immunized either by feeding of transgenic seeds or hairy roots. All immunized groups showed a considerable rise in anti-glycoprotein serum IgG and IgA, and IFNÉ£ cytokine. However, the animals received chimeric protein showed significant higher immune responses in comparison to ones received one of these immunogen. The results indicated that the oral immunization of an animal model with transgenic plants could effectively elicit immune responses against two major tumor-associated antigens.

Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with type 2 diabetes and its chronic complications.

UNLABELLED: SUBJECT AND AIMS: Endothelial derived nitric oxide (eNOS) is involved in several functions playing important role in development of type 2 diabetes and insulin resistance. The aim of this study was to examine the association between eNOS intron 4 VNTR polymorphism and type 2 diabetes in an Iranian population. METHODS: A total of 220 patients with type 2 diabetes and 96 healthy control subjects were recruited from the same area. Genotyping was performed using PCR. RESULTS: A significant difference was found in genotype frequencies of eNOS polymorphism between patients and controls (aa+ab vs. bb p=0.02, OR 2.0 95% CI; 1.05-3.96). Also allele a frequency was significantly increased in patients with diabetes compared with controls (p=0.007, OR 2.1 95% CI; 1.19-4.08). We found that in patients with diabetic neuropathy the frequency of 'a' allele was significantly increased compared to the controls p=0.03, OR=1.8 95% CI (1.00-3.7). Both genotype and allele frequencies were significantly different between patients who were complication free compared to the controls [aa+ab vs. bb p=0.007, OR=2.6 95% CI (1.2-5.8) and p=0.001, OR=2.8 95% CI (1.4-5.9)] respectively with the a allele conferring the risk. CONCLUSION: The association between eNOS VNTR polymorphism and T2DM seems to be stronger in patients without diabetic complications indicating diverse effect of eNOS polymorphism on diabetes and diabetic microvascular complications.