miR-1246-overexpressing exosomes improve UVB-induced photoaging by activating autophagy via suppressing GSK3ß.

Stem cell paracrine has shown potential application in skin wound repair and photoaging treatment. Our previous study demonstrated that miR-1246-overexpressing Exosomes (OE-EXs) isolated from adipose-derived stem cells (ADSCs) showed superior photo-protecting effects on UVB-induced photoaging than that of the vector, however, the underlying mechanism was unclear. The simultaneous bioinformatics analysis indicated that miR-1246 showed potential binding sites with GSK3ß which acted as a negative regulator for autophagy. This study was aimed to explore whether OE-EXs ameliorate skin photoaging by activating autophagy via targeting GSK3ß. The results demonstrated that OE-EXs significantly decreased GSK3ß expression, enhanced autophagy flux and autophagy-related proteins like LC3II, while suppressed p62 expression. Meanwhile, OE-EXs markedly reversed the levels of intracellular ROS, MMP-1, procollagen type I and DNA damage in human skin fibroblasts caused by UVB irradiation, but the ameliorating effects were significantly inhibited when 3-Methyladenine (3-MA) was introduced to block the autophagy pathway. Further, OE-EXs could reverse UVB-induced wrinkles, epidermal hyperplasia, and collagen fibers reduction in Kunming mice, nevertheless, the therapeutical effects of OE-EXs were attenuated when it was combinative treated with 3-MA. In conclusion, OE-EXs could cure UVB induced skin photoaging by activating autophagy via targeting GSK3ß.

Health of unpaid carers in Wales, UK: a population data linkage study.

BACKGROUND: The population of unpaid carers in Wales increased to record. There is no systematic approach to record unpaid caring status, resulting in limited quantitative evidence on unpaid carers' health. The aim of this study is to: (i) create an e-cohort of unpaid carers by linking routinely collected health and administrative datasets in Wales, UK. (ii) investigate whether long-term health conditions and multimorbidity are more prevalent amongst unpaid carers than non-carers. METHODS: Unpaid carers were identified by linking primary care dataset, National Survey for Wales data with demographic characteristics in the Secure Anonymise Information Linkage Databank. The clinical codes identified in Cambridge Multimorbidity Score were used to explore the prevalence of long-term health conditions. RESULTS: A total of 91 220 unpaid carers in Wales were identified between 1 January 2010 and 1 March 2022. Unpaid carers were found at higher risk of managing 35 of 37 long-term health conditions and multimorbidity than non-carers, exacerbated amongst younger age groups and deprived communities. CONCLUSIONS: The creation of the first e-cohort of unpaid carers in Wales provides opportunities to perform rapid analysis to systematically understand health needs and evaluate initiatives in future. To better support unpaid carers, flexible approaches focusing on early identification and prevention is crucial.

Long Non-coding RNA H19-Overexpressing Exosomes Ameliorate UVB-Induced Photoaging by Upregulating SIRT1 Via Sponging miR-138.

UVB-induced photoaging is characterized by wrinkle formation, slackness and senile plaques, affecting the health and beauty of human being. Our previous study revealed that exosomes derived from adipose-derived stem cells (ADSCs) could efficiently alleviate UVB-induced photodamage. However, the functional ingredients in exosomes were undefined. LncRNA H19, one of the well-researched lncRNAs in exosomes, exhibits multiple physiological effects. This study aims to demonstrate the photo-protective role of lncRNA H19 on skin photoaging in UVB-irradiated human skin fibroblasts cells (HSFs) and Kunming mice. LncRNA H19-overexpressing exosomes (H19-Exo) were isolated from the supernatant of ADSCs infected with lncRNA H19-loaded lentivirus. The results showed that H19-Exo significantly inhibited MMPs production, DNA damage and ROS generation while enhancing procollagen type I synthesis in UVB-irradiated HSFs. Meanwhile, H19-Exo markedly reversed epidermal thickening and collagen degradation in UVB-irradiated mice. Furthermore, luciferase reporter assays indicated that lncRNA H19 acted as a sponge for miR-138 expression, and SIRT1 was targeted by miR-138. Evidence from both in vitro and in vivo studies also revealed that H19-Exo could enhance SIRT1 expression by knocking down miR-138. In conclusion, lncRNA H19 served as a therapeutic candidate in treating UVB-induced skin photoaging by upregulation of SIRT1 via miR-138.

miR-1246-overexpressing exosomes suppress UVB-induced photoaging via regulation of TGF-ß/Smad and attenuation of MAPK/AP-1 pathway.

Stem cell therapy is widely employed for the treatment of skin diseases, especially in skin rejuvenation. Exosomes derived from stem cells have been demonstrated to possess anti-photoaging effects; however, the precise components within exosomes that are responsible for this effect remain unknown. Previously, miR-1246 was found to be one of the most abundant nucleic acids in adipose-derived stem cells (ADSCs)-derived exosomes. This study examined whether miR-1246 was the major therapeutic agent employed by ADSCs to protect against UVB-induced photoaging. Lentivirus infection was used to obtain miR-1246-overexpressing ADSCs and exosomes. We then determined the anti-photoaging effects of miR-1246-overexpressing exosomes (OE-EX) on both UVB-irradiated human skin fibroblasts (HSFs) and Kunming mice. The results showed that OE-EX could significantly decrease MMP-1 by inhibiting the MAPK/AP-1 signaling pathway. Meanwhile, OE-EX markedly increased procollagen type I secretion by activating the TGF-ß/Smad pathway. OE-EX also exhibited an anti-inflammatory effect by preventing the UVB-induced degradation of IκB-α and NF-κB overexpression. Animal experiments demonstrated that OE-EX could reduce UVB-induced wrinkle formation, epidermis thickening, and the loss of collagen fibers reduction in Kunming mice. The combined results suggested that miR-1246 is the key component within ADSCs-derived exosomes that protects against UVB-induced skin photoaging.

Feature Genes Selection Using Supervised Locally Linear Embedding and Correlation Coefficient for Microarray Classification.

The selection of feature genes with high recognition ability from the gene expression profiles has gained great significance in biology. However, most of the existing methods have a high time complexity and poor classification performance. Motivated by this, an effective feature selection method, called supervised locally linear embedding and Spearman's rank correlation coefficient (SLLE-SC2), is proposed which is based on the concept of locally linear embedding and correlation coefficient algorithms. Supervised locally linear embedding takes into account class label information and improves the classification performance. Furthermore, Spearman's rank correlation coefficient is used to remove the coexpression genes. The experiment results obtained on four public tumor microarray datasets illustrate that our method is valid and feasible.