Extracellular vesicles (EVs) comprise apoptotic bodies, microvesicles and exosomes, and they perform as key regulators in cell-to-cell communication in normal as well as diseased states. EVs contain natural cargo molecules, such as miRNA, mRNA and proteins, and transfer these functional cargos to neighboring cells or more distant cells through circulation. These functionally active molecules then affect distinct signaling cascades. The message conveyed to the recipient cells is dependent upon the composition of the EV, which is determined by the parent cell and the EV biogenesis. Because of their properties such as increased stability in circulation, biocompatibility, low immunogenicity and toxicity, EVs have drawn attention as attractive delivery systems for therapeutics. This review focuses on the functional use of exosomes in therapy and the potential advantages and challenges in using exosomes for therapeutic purposes.

Macrophages are a heterogeneous population of phagocytic cells present in all tissues. Recently, several drugs that target the epigenetic machinery have emerged as attractive molecules for treating infection and inflammation by modulating macrophages. Treatment of lipopolysaccharide (LPS)-challenged macrophages with epigenetic modifiers leads to phenotype switching. This could provide stimulatory/destructive (M1) or suppressive/protective (M2) therapeutic strategies, which are crucial in the cytokine milieu in which the macrophages reside. In this review, we provide an overview of macrophage functional diversity during various diseases, including infection, as well as the current status in the development and clinical utility of epigenetic modifiers.

Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema, and respiratory failure. Here, we examined the efficacy of DNA methyl transferase (DNMT) inhibitor Aza (5-Aza 2-deoxycytidine), histone deacetylase (HDAC) inhibitor TSA (Trichostatin A), and combination therapy (Aza+TSA) in protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed a substantial attenuation of adverse lung histopathological changes, and inflammations. Importantly, these protective effects were due to significant macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK-HuR-TNF and activation of STAT3-Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI. This finding gives further evidence that the epigenetic treatment has a therapeutic potential for patients with sepsis.

Myocardial infarction, atherosclerosis and hypertension are the most common heart-related diseases that affect both the heart and the blood vessels. Multiple independent risk factors have been shown to be responsible for cardiovascular diseases. The combination of a healthy diet, exercise and smoking cessation keeps these risk factors in check and helps maintain homeostasis. The dynamic monolayer endothelial cell integrity and cell-cell communication are the fundamental mechanisms in maintaining homeostasis. Recently, it has been revealed that small non-coding RNAs (ncRNAs) play a critical role in regulation of genes involved in either posttranscriptional or pretranslational modifications. They also control diverse biological functions like development, differentiation, growth, and metabolism. Among ncRNAs, the short interfering RNAs (siRNAs) and microRNAs (miRNAs) have been extensively studied, but their specific functions remain largely unknown. In recent years, miRNAs are efficiently studied as one of the important candidates for involvement in most biological processes and have been implicated in many human diseases. Thus, the identification and the respective targets of miRNAs may provide novel molecular insight and new therapeutic strategies to treat diseases. This review summarizes the recent developments and insight on the role of miRNAs in cardiovascular disease prognosis, diagnostic and clinical applications.

Small nucleolar RNAs (snoRNAs) are a group of noncoding RNAs that perform various biological functions, including biochemical modifications of other RNAs, precursors of miRNA, splicing, and telomerase activity. The small Cajal body-associated RNAs (scaRNAs) are a subset of the snoRNA family and collect in the Cajal body where they perform their canonical function to biochemically modify spliceosomal RNAs prior to maturation. Failure of sno/scaRNAs have been implicated in pathology such as congenital heart anomalies, neuromuscular disorders, and various malignancies. Thus, understanding of sno/scaRNAs demonstrates the clinical value.