There is a growing interest in therapeutically targeting the inflammatory response that underlies age-related chronic diseases including obesity and type 2 diabetes. Through integrative small RNA sequencing, we show the presence of conserved plant miR159a and miR156c in dried nuts having high complementarity with the mammalian TNF receptor superfamily member 1a (Tnfrsf1a) transcript. We detected both miR159a and miR156c in exosome-like nut nanovesicles (NVs) and demonstrated that such NVs reduce Tnfrsf1a protein and dampen TNF-α signaling pathway in adipocytes. Synthetic single-stranded microRNAs (ss-miRs) modified with 2′- O -methyl group function as miR mimics. In plants, this modification naturally occurs on nearly all small RNAs. 2′- O -methylated ss-miR mimics for miR156c and miR159a decreased Tnfrsf1a protein and inflammatory markers in hypertrophic as well as TNF-α-treated adipocytes and macrophages. miR156c and miR159a mimics effectively suppress inflammation in mice, highlighting a potential role of plant miR-based, single-stranded oligonucleotides in treating inflammatory-associated metabolic diseases.

The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H 2 S) were recently demonstrated in the context of different inflammatory diseases. In particular, H 2 S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H 2 S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H 2 S, more evidence is needed to understand the pathophysiology and the potential of H 2 S as a therapeutic agent. Within this review, we provide an overview on H 2 S biological effects, on its role in immune-mediated inflammatory diseases, on H 2 S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.

The authors wish to make the following correction to this paper [...]

Ever since its presence was reported in the brain, the nature and role of hydrogen sulfide (H2S) in the Central Nervous System (CNS) have changed. Consequently, H2S has been elected as the third gas transmitter, along with carbon monoxide and nitric oxide, and a number of studies have focused on its neuromodulatory and protectant functions in physiological conditions. The research on H2S has highlighted its many facets in the periphery and in the CNS, and its role as a double-faced compound, switching from protective to toxic depending on its concentration. In this review, we will focus on the bell-shaped nature of H2S as an angiogenic factor and as a molecule released by glial cells (mainly astrocytes) and non-neuronal cells acting on the surrounding environment (paracrine) or on the releasing cells themselves (autocrine). Finally, we will discuss its role in Amyotrophic Lateral Sclerosis, a paradigm of a neurodegenerative disease.