Epigenetic regulation in myocardial infarction: Non-coding RNAs and exosomal non-coding RNAs.

Myocardial infarction (MI) is one of the leading causes of deaths globally. The early diagnosis of MI lowers the rate of subsequent complications and maximizes the benefits of cardiovascular interventions. Many efforts have been made to explore new therapeutic targets for MI, and the therapeutic potential of non-coding RNAs (ncRNAs) is one good example. NcRNAs are a group of RNAs with many different subgroups, but they are not translated into proteins. MicroRNAs (miRNAs) are the most studied type of ncRNAs, and have been found to regulate several pathological processes in MI, including cardiomyocyte inflammation, apoptosis, angiogenesis, and fibrosis. These processes can also be modulated by circular RNAs and long ncRNAs via different mechanisms. However, the regulatory role of ncRNAs and their underlying mechanisms in MI are underexplored. Exosomes play a crucial role in communication between cells, and can affect both homeostasis and disease conditions. Exosomal ncRNAs have been shown to affect many biological functions. Tissue-specific changes in exosomal ncRNAs contribute to aging, tissue dysfunction, and human diseases. Here we provide a comprehensive review of recent findings on epigenetic changes in cardiovascular diseases as well as the role of ncRNAs and exosomal ncRNAs in MI, focusing on their function, diagnostic and prognostic significance.

Association between serum Vitamin D levels and prognostic factors in nonmetastatic breast cancer patients.

Background: Breast cancer is among the most common malignancies in women around the world. There is evidence of high prevalence of serum/blood Vitamin D deficiency in Iranian women. Considering the multitude of factors that may be involved in the prognosis and lifespan of breast cancer patients, this study investigated the level of Vitamin D in Iranian patients with nonmetastatic breast cancer. Materials and Methods: This cross-sectional study was carried out on 214 women diagnosed with breast cancer, who were referred to the radio-oncology department. Serum Vitamin D level of the patients was measured. Prognostic factors were determined based on demographic and pathological characteristics. The results were analyzed using descriptive statistics tests, Chi-square, one-way analysis of variance, Kaplan-Meier, and Cox regression model in SPSS v22. For all cases, the significance level was considered to be P < 0.05. Results: The total mean of 25-hydroxyvitamin D serum level was 25.15 ± 17.68 ng/ml. There was no significant relationship between levels of Vitamin D with disease stage, tumor size, tumor grade, estrogen receptor, progesterone receptor, and Human epidermal growth factor receptor 2 (P > 0.05). The mean survival time was 5 years and 45 days. Conclusion: No relationship was found between serum Vitamin D levels and the factors affecting the prognosis of nonmetastatic breast cancer. The Cox analysis showed that the survival time was not influenced by Vitamin D as a prognosis factor.

Evidence for the Benefits of Melatonin in Cardiovascular Disease.

The pineal gland is a neuroendocrine gland which produces melatonin, a neuroendocrine hormone with critical physiological roles in the circadian rhythm and sleep-wake cycle. Melatonin has been shown to possess anti-oxidant activity and neuroprotective properties. Numerous studies have shown that melatonin has significant functions in cardiovascular disease, and may have anti-aging properties. The ability of melatonin to decrease primary hypertension needs to be more extensively evaluated. Melatonin has shown significant benefits in reducing cardiac pathology, and preventing the death of cardiac muscle in response to ischemia-reperfusion in rodent species. Moreover, melatonin may also prevent the hypertrophy of the heart muscle under some circumstances, which in turn would lessen the development of heart failure. Several currently used conventional drugs show cardiotoxicity as an adverse effect. Recent rodent studies have shown that melatonin acts as an anti-oxidant and is effective in suppressing heart damage mediated by pharmacologic drugs. Therefore, melatonin has been shown to have cardioprotective activity in multiple animal and human studies. Herein, we summarize the most established benefits of melatonin in the cardiovascular system with a focus on the molecular mechanisms of action.

Vitamin D and Non-coding RNAs: New Insights into the Regulation of Breast Cancer.

Breast cancer, a life-threatening serious disease with a high incident rate among women, is responsible for thousands of cancer-associated death worldwide. Numerous investigations have evaluated the possible mechanisms related to this malignancy. Among them, non-coding RNAs (ncRNAs), i.e., microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs have recently attracted attention of researchers. In addition to recent studies for evaluating the role of ncRNAs in breast cancer etiology, some investigations have revealed that vitamin D has regulatory and therapeutic roles in breast cancer. Moreover, an important link between vitamin D and ncRNAs in cancer therapy has been highlighted. Herein, the aim of this study was to discuss the available data on the mentioned link in breast cancer.

Non-coding RNAs and Exosomes: Their Role in the Pathogenesis of Sepsis.

Sepsis is characterized as an uncontrolled host response to infection, and it represents a serious health challenge, causing excess mortality and morbidity worldwide. The discovery of sepsis-related epigenetic and molecular mechanisms could result in improved diagnostic and therapeutic approaches, leading to a reduced overall risk for affected patients. Accumulating data show that microRNAs, non-coding RNAs, and exosomes could all be considered as novel diagnostic markers for sepsis patients. These biomarkers have been demonstrated to be involved in regulation of sepsis pathophysiology. However, epigenetic modifications have not yet been widely reported in actual clinical settings, and further investigation is required to determine their importance in intensive care patients. Further studies should be carried out to explore tissue-specific or organ-specific epigenetic RNA-based biomarkers and their therapeutic potential in sepsis patients.

MicroRNA and exosome: Key players in rheumatoid arthritis.

Rheumatoid arthritis (RA) is known as one of important autoimmune disorders which can lead to joint pain and damage throughout body. Given that internal (ie, genetic and epigenetic alterations) and external factors (ie, lifestyle changes, age, hormones, smoking, stress, and obesity) involved in RA pathogenesis. Increasing evidence indicated that cellular and molecular alterations play critical roles in the initiation and progression of RA. Among various targets and molecular signaling pathways, microRNAs (miRNAs) and their regulatory networks have key roles in the RA pathogenesis. It has been showed that deregulation of many miRNAs involved in different stages of RA. Hence, identification of miRNAs and their signaling pathways in RA, could contribute to new knowledge which help to better treatment of patients with RA. Besides miRNAs, exosomes have been emerged as key messengers in RA pathogenesis. Exsosomes are nanocarriers which could be released from various cells and lead to changing of behaviors recipient cells via targeting their cargos (eg, proteins, messenger RNAs, miRNAs, long noncoding RNAs, DNAs). Here, we summarized several miRNAs involved in RA pathogenesis. Moreover, we highlighted the roles of exosomes in RA pathogenesis.

Epi-Drugs and Epi-miRs: Moving Beyond Current Cancer Therapies.

Epigenetic modifications determine phenotypic characteristics in a reversible, stable and genotype-independent manner. Epigenetic modifications mainly encompass CpG island methylation and histone modifications, both being important in the pathogenesis of malignancies. The reversibility of epigenetic phenomenon provides a suitable therapeutic option that is reactivation of epigenetically silenced tumor-suppressor genes. Inhibition of DNA methyltransferase, histone deacetylase and Aurora B kinase, individually or collectively, could feasibly prevent or reverse the impact of epigenetic silencing. MicroRNAs [miRNAs] are an important layer of epigenetic controlling of gene expression, and serve as diagnostic and prognostic biomarkers as well as treatment targets for several types of cancer. miRNAs are involved inepigenetically silencing or activation of genes, tumor suppressor genes and oncogenes, and their modulation opens new horizons for designing novel cancer therapeutic agents.

Effects of camel thorn distillate on recurrent oral aphthous lesions.

BACKGROUND: Near 20 % of people suffer from recurrent oral aphthous ulcers. These painful ulcers are found on the oral mucosa. We conducted this study to evaluate the effect of the camel thorn distillate on this condition. PATIENTS AND METHODS: 93 patients with recurrent aphthous ulcers were selected and divided into two groups. One group was given a placebo (n = 44) and the other was given camel thorn distillate (n = 49). The diameter of the lesions and the severity of the pain were measured 3, 5, 7, 10 and 14 days after initiation of therapy. The lesion diameters and pain scores of the two groups were compared using the t-test. RESULTS: Complete resolution time ranged from 3 to 7 days (mean = 4.02) in the group treated with camel thorn distillate, whereas in the control group, complete resolution time ranged from 7 to 14 days (mean = 8.9, p < 0.001). CONCLUSIONS: The efficacy of camel thorn distillate is comparable to that of other drugs used to treat oral aphthous ulcers. Its therapeutic effect may be due to the flavanones (alhagitin and alhagidin) that are present in this plant.