Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage

[Abstract] Aging is a process of cellular and tissue dysfunction characterized by different hallmarks, including cellular senescence. However, there is proof that certain features of aging and senescence can be ameliorated. Here, we provide evidence that small extracellular vesicles (sEVs) isolated from primary fibroblasts of young human donors ameliorate certain biomarkers of senescence in cells derived from old and Hutchinson-Gilford progeria syndrome donors. Importantly, sEVs from young cells ameliorate senescence in a variety of tissues in old mice. Mechanistically, we identified sEVs to have intrinsic glutathione-S-transferase activity partially due to the high levels of expression of the glutathione-related protein (GSTM2). Transfection of recombinant GSTM2 into sEVs derived from old fibroblasts restores their antioxidant capacity. sEVs increase the levels of reduced glutathione and decrease oxidative stress and lipid peroxidation both in vivo and in vitro. Altogether, our data provide an indication of the potential of sEVs as regenerative therapy in aging

Extracellular Vesicles as Potential Tools for Regenerative Therapy

[Abstract] Small extracellular vesicles released by fibroblasts from young human donors diminish lipid peroxidation in senescent cells and in different old mice organs due to their enrichment in Glutathione-S-transferase Mu lipid antioxidant activity.The London School of Medicine and Dentistry; MGU0497Biotechnology and Biological Sciences Research Council; BB/P000223/1Instituto de Salud Carlos III; CP19-0010Ministerio de Economía, Industria y Competitividad; SAF2016-78666RXunta de Galicia; ED481B 2017/11

Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-beta Pathway

QMUL, MRC (MR/K501372/1) and BBSRC (BB/P000223/1)

The non-coding transcriptome as a dynamic regulator of cancer metastasis.

Since the discovery of microRNAs, non-coding RNAs (NC-RNAs) have increasingly attracted the attention of cancer investigators. Two classes of NC-RNAs are emerging as putative metastasis-related genes: long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs). LncRNAs orchestrate metastatic progression through several mechanisms, including the interaction with epigenetic effectors, splicing control and generation of microRNA-like molecules. In contrast, snoRNAs have been long considered "housekeeping" genes with no relevant function in cancer. However, recent evidence challenges this assumption, indicating that some snoRNAs are deregulated in cancer cells and may play a specific role in metastasis. Interestingly, snoRNAs and lncRNAs share several mechanisms of action, and might synergize with protein-coding genes to generate a specific cellular phenotype. This evidence suggests that the current paradigm of metastatic progression is incomplete. We propose that NC-RNAs are organized in complex interactive networks which orchestrate cellular phenotypic plasticity. Since plasticity is critical for cancer cell metastasis, we suggest that a molecular interactome composed by both NC-RNAs and proteins orchestrates cancer metastasis. Interestingly, expression of lncRNAs and snoRNAs can be detected in biological fluids, making them potentially useful biomarkers. NC-RNA expression profiles in human neoplasms have been associated with patients' prognosis. SnoRNA and lncRNA silencing in pre-clinical models leads to cancer cell death and/or metastasis prevention, suggesting they can be investigated as novel therapeutic targets. Based on the literature to date, we critically discuss how the NC-RNA interactome can be explored and manipulated to generate more effective diagnostic, prognostic, and therapeutic strategies for metastatic neoplasms

Weight-Normative versus Weight-Inclusive Narratives in Weight-Related Public Health Campaigns: Effects on Anti-Fat Attitudes, Stigma, Motivation, and Self-Efficacy

Research has shown that weight-related public health campaigns can inadvertently stigmatise individuals with obesity. We compared the effects of weight-normative (personal responsibility and public health crisis) versus weight-inclusive (Health at Every Size [HAES] and fat acceptance) campaign narratives on anti-fat attitudes and reactions to campaigns in two studies. In study 1, participants (n = 283) from a range of Body Mass Index (BMI) categories viewed one of four mock campaigns before rating their anti-fat-attitudes (dislike, fear of fat, willpower, social distance), and reactions to the campaign (motivation, stigma). In study 2, participants (n = 175) in overweight or obese BMI categories viewed one of four mock campaigns before rating their reactions to the campaign (motivation, stigma, self-efficacy). Study 1 results showed that weight-normative campaigns were perceived as significantly more stigmatising than weight-inclusive ones. However, weight-inclusive campaigns did not decrease anti-fat attitudes or increase motivation for health behaviour change in this sample. Similarly, study 2 results showed that the personal responsibility campaign was rated as significantly more stigmatising than other campaigns among women with overweight or obesity. Fat acceptance was rated as the least stigmatising campaign in this sample, but weight-inclusive narratives did not increase motivation or self-efficacy for health behaviour change. Future research should focus on developing campaign narratives that are non-stigmatising, motivating, and efficacious by addressing health behavior benefits irrespective of sex or weight

Surface-enhanced raman scattering (Sers) spectroscopy for sensing and characterization of exosomes in cancer diagnosis

28 pags., 14 figs. -- This article belongs to the Special Issue Exosomes in Cancers TherapyExosomes are emerging as one of the most intriguing cancer biomarkers in modern oncology for early cancer diagnosis, prognosis and treatment monitoring. Concurrently, several nano-plasmonic methods have been applied and developed to tackle the challenging task of enabling the rapid, sensitive, affordable analysis of exosomes. In this review, we specifically focus our attention on the application of plasmonic devices exploiting surface-enhanced Raman spectroscopy (SERS) as the optosensing technique for the structural interrogation and characterization of the heteroge-neous nature of exosomes. We summarized the current state-of-art of this field while illustrating the main strategic approaches and discuss their advantages and limitations.This research was supported by the Spanish Ministerio de Economia y Competitividad (CTQ2017-88648R and RYC-2016-20331), the Generalitat de Cataluña (2017SGR883), and the Universitat Rovira I Virgili (FR 2019-B2)