Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes in the immune system, a deteriorating circadian system, and reductions in sirtuin-1 (SIRT1) activity. In non-tumor cells, several effects of melatonin are abolished by inhibiting SIRT1, indicating mediation by SIRT1. Melatonin is, in addition to its circadian and antioxidant roles, an immune stimulatory agent. However, it can act as either a pro- or anti-inflammatory regulator in a context-dependent way. Melatonin can stimulate the release of proinflammatory cytokines and other mediators, but also, under different conditions, it can suppress inflammation-promoting processes such as NO release, activation of cyclooxygenase-2, inflammasome NLRP3, gasdermin D, toll-like receptor-4 and mTOR signaling, and cytokine release by SASP (senescence-associated secretory phenotype), and amyloid-β toxicity. It also activates processes in an anti-inflammatory network, in which SIRT1 activation, upregulation of Nrf2 and downregulation of NF-κB, and release of the anti-inflammatory cytokines IL-4 and IL-10 are involved. A perhaps crucial action may be the promotion of macrophage or microglia polarization in favor of the anti-inflammatory phenotype M2. In addition, many factors of the pro- and anti-inflammatory networks are subject to regulation by microRNAs that either target mRNAs of the respective factors or upregulate them by targeting mRNAs of their inhibitor proteins.

https://www.mdpi.com/1422-0067/20/5/1223/pdf

Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks.

As a self-degradative mechanism, macroautophagy/autophagy has a role in the maintenance of energy homeostasis during critical periods in the development of cells. It also controls cellular damage through the eradication of damaged proteins and organelles. This process is accomplished by tens of ATG (autophagy-related) proteins. Recent studies have shown the involvement of non-coding RNAs in the regulation of autophagy. These transcripts mostly modulate the expression of ATG genes. Both long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to modulate the autophagy mechanism. Levels of several lncRNAs and miRNAs are altered in this process. In the present review, we discuss the role of lncRNAs and miRNAs in the regulation of autophagy in diverse contexts such as cancer, deep vein thrombosis, spinal cord injury, diabetes and its complications, acute myocardial infarction, osteoarthritis, pre-eclampsia and epilepsy.Abbreviations: AMI: acute myocardial infarction; ATG: autophagy-related; lncRNA: long non-coding RNA; miRNA: microRNA.

Exploring the role of non-coding RNAs in autophagy.

Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.14215

Serum microRNA profile enables preoperative diagnosis of uterine leiomyosarcoma

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage regression. The etiology of OA is diverse, the exact pathogenesis of which remains unclear. Autophagy is a conserved maintenance mechanism in eukaryotic cells. Dysfunction of chondrocyte autophagy is regarded as a crucial pathogenesis of cartilage degradation in OA. MircoRNAs (miRNAs) are a category of small noncoding RNAs, acting as posttranscriptional modulators that regulate biological processes and cell signaling pathways via target genes. A series of miRNAs are involved in the progression of chondrocyte autophagy and are connected with numerous factors and pathways. This article focuses on the mechanisms of chondrocyte autophagy in OA and reviews the role of miRNA in their modulation. Potentially relevant miRNAs are also discussed in order to provide new directions for future research and improve our understanding of the autophagic network of miRNAs.

/pdf/modulated-autophagy-by-micrornas-in-osteoarthritis-203bimfu31.pdf

Modulated Autophagy by MicroRNAs in Osteoarthritis Chondrocytes

The participation of sirtuins in the regulation of oxidative stress and inflammation lies at the basis of their possible modes of action and is related to their expression in various cell structures; their location in the mitochondria and blood plasma has been indicated as of primary importance. Despite many existing studies, research on sirtuins continues to present an opportunity to discover new functions and dependencies, especially when it comes to women's gynecological health. Sirtuins have a significant role in both the formation and the course of many gynecological diseases. Their role is particularly important and well documented in the course of the development of cancer within the female reproductive organs; however, disturbances observed in the ovary and oocyte as well as in follicular fluid are also widely investigated. Additionally, sirtuins take part in some gynecological disturbances as regulative factors in pathways associated with insulin resistance, glucose and lipids metabolism disorders. In this review, we would like to summarize the existing knowledge about sirtuins in the manner outlined above.

https://www.mdpi.com/2076-3921/10/1/84/pdf

Sirtuins-The New Important Players in Women's Gynecological Health.

Background: MiRNAs may be associated with the risk of uterine sarcoma and related molecular mechanism remains unclear.Methods: A total of 101 patients with uterine sarcoma (cases) and 54 he...

Elevated levels of serum MiR-152 and miR-24 in uterine sarcoma: potential for inducing autophagy via SIRT1 and deacetylated LC3

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Elevated levels of serum MiR-152 and miR-24 in uterine sarcoma: potential for inducing autophagy via SIRT1 and deacetylated LC3