The influence of Nrf2 gene promoter methylation on gene expression and oxidative stress parameters in preeclampsia.

BACKGROUND AND AIMS: Preeclampsia (PE) is a serious medical condition that usually causes high blood pressure and affects multiple organs. Considering the adverse effect of oxidative stress on the process of PE in pregnant women and regarding the role of the Nrf2 gene in placental oxidative pathways, this study was conducted to investigate the DNA methylation status of Nrf2 in PE and healthy pregnant women. MATERIALS AND METHODS: The present case-control study consisted of 70 PE and 70 healthy pregnant women. Blood and placenta samples were taken from all subjects, and the percentage of the Nrf2 gene methylation in the samples was assessed by the Methyl Light PCR method. Also, the Nrf2 gene expression was evaluated by real-time PCR. The total antioxidant capacity (TAC) and total oxidative status (TOS) were measured by the colorimetric method. RESULTS: In PE women, there was a significant increase in blood pressure, term of pregnancy, and BMI. In addition, there were enhanced Nrf2 DNA methylation percentage in placenta tissue and increased TOS levels in placenta tissue and blood compared to healthy pregnant women (P < 0.05). Also, in the PE group, there was a significant decrease in Nrf2 gene expression and TAC level in placenta tissue compared to the control group (P < 0.05). CONCLUSION: The Nrf2 gene undergoes epigenetic modifications of DNA hypermethylation in the PE placenta. Decreased expression of this gene and the changes in the level of oxidative parameters (TAC, TOS) confirm it.

Aberrant Methylation of the SOD1 GENE, its Expression and Enzyme Activity in the Placenta of Patients with Preeclampsia.

Background: Oxidative stress is involved in the pathogenesis of preeclampsia (PE). Dysregulation of SOD1 may be involved in the pathogenesis of PE. We examined and compared the methylation level of the promoter region (PMR) of the SOD1, gene expression, and enzyme activity of superoxide dismutase (SOD) in both placenta and maternal blood in PE women. Methods: A total of 140 blood samples and 40 placental tissue samples from PE and healthy pregnant controls were studied. The PMR of the SOD1 (Methylight PCR method), the expression (Real-time PCR), and its enzyme activity were investigated and compared in two groups. Results: The PMR of the SOD1 gene in the placental tissue of the patients was significantly increased compared to the control group (P= 0.008); this result was accompanied by a decrease in the expression of the gene and a decrease in the activity of the SOD enzyme. Meanwhile, the PMR of the SOD1 gene did not significantly change in the blood samples of the patients (P= 0.95), while a significant decrease in the expression of SOD1 (without a significant change in the SOD activity) was observed. Conclusion: The results showed significant changes in the PMR of the SOD1 gene and gene expression in placenta tissue. The results highlight the role of the placenta in complications during pregnancy and also revealed epigenetics as an important regulatory pathway in the pathogenesis of preeclampsia.

COVID-19 and renin angiotensin aldosterone system: Pathogenesis and therapy.

AIMS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the ACE2 component of the renin-angiotensin aldosterone system (RAAS) and infects the human cells. The aims of the present review were to look at the role and alteration of the RAAS components in SARS-CoV-2 infection, therapeutic approaches, and clinical trials in this field. METHODS: We surveyed the literature (PubMed, Web of Science, and Scopus) till August 18, 2021, and 59 published papers regarding the components of the RAAS and their role and alterations in SARS-CoV-2 infection along with various COVID-19 therapies based on the RASS components were included in the study. RESULTS: ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor inhibitors are agents that significantly enhance the ACE2 and Ang-(1-7) levels, which can be suggestive for their role as therapeutics against SARS-CoV-2 infection. Beta-adrenergic blockers, which negatively regulate renin release from juxtaglomerular cells, and vitamin D, as a regulator of the RAAS and renin expression, are proposed therapeutics in the treatment of COVID-19. Some antihyperglycemic agents could be potentially protective against COVID-19-induced lung injury. Also, the inhibition of the Janus kinase/signal transducer and activator of the transcription pathway as a potential treatment for COVID-19 has been suggested. Finally, resveratrol, an antioxidant that can suppress Ang II, has been suggested as an adjunct to other therapies. CONCLUSION: Regarding the suggested potential therapies for COVID-19, there are many clinical trials whose results might change the treatment strategies of SARS-CoV-2 infection. So, the results of well-organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID-19 will be useful in the management and therapy of the disease.

Comment on "Association between Interleukin-32 and Interleukin-17A Single Nucleotide Polymorphisms and Serum Levels with Polycystic Ovary Syndrome".

No Abstract.

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy.

BACKGROUND: [Corrected] Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. METHODS: In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. RESULTS: The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.