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Biomolecules Nov 2023The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and... (Review)
Review
The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and dermis. This can be primarily attributed to the diminishing population of epidermal stem cells and the reduction in collagen, which is the primary structural protein in the human body. The alterations occurring in the epidermis and dermis due to the aging process result in disruptions to the structure and functionality of the skin. This creates a microenvironment conducive to age-related skin conditions such as a compromised skin barrier, slowed wound healing, and the onset of skin cancer. This review emphasizes the recent molecular discoveries related to skin aging and evaluates preventive approaches, such as the use of topical retinoids. Topical retinoids have demonstrated promise in enhancing skin texture, diminishing fine lines, and augmenting the thickness of both the epidermal and dermal layers.
Topics: Humans; Vitamin A; Skin Aging; Skin; Retinoids; Aging
PubMed: 38002296
DOI: 10.3390/biom13111614 -
Nature Nov 2023Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation. Here we identify a...
Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation. Here we identify a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using skin injury models in mice, single-cell transcriptomics and genetic lineage tracing, ablation and gene deletion models, we demonstrate that CD201 progenitors control the pace of wound healing by generating multiple specialized cell types, from proinflammatory fibroblasts to myofibroblasts, in a spatiotemporally tuned sequence. We identified retinoic acid and hypoxia signalling as the entry checkpoints into proinflammatory and myofibroblast states. Modulating CD201 progenitor differentiation impaired the spatiotemporal appearances of fibroblasts and chronically delayed wound healing. The discovery of proinflammatory and myofibroblast progenitors and their differentiation pathways provide a new roadmap to understand and clinically treat impaired wound healing.
Topics: Animals; Mice; Cell Differentiation; Cell Hypoxia; Cell Lineage; Disease Models, Animal; Endothelial Protein C Receptor; Fascia; Fibroblasts; Gene Expression Profiling; Inflammation; Myofibroblasts; Signal Transduction; Single-Cell Gene Expression Analysis; Skin; Tretinoin; Wound Healing
PubMed: 37968392
DOI: 10.1038/s41586-023-06725-x -
Science (New York, N.Y.) Mar 2024Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are...
Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.
Topics: Animals; Mice; Adult Stem Cells; Cell Lineage; Cell Plasticity; Epidermis; Hair Follicle; Tretinoin; Wound Healing; Rejuvenation; Cell Culture Techniques; Neoplasms; Mice, Inbred C57BL
PubMed: 38452090
DOI: 10.1126/science.adi7342 -
Blood Advances Jul 2023Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute...
Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).
Topics: Humans; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Tretinoin; HLA-DR Antigens; Arsenic Trioxide
PubMed: 36799929
DOI: 10.1182/bloodadvances.2022008364 -
Reproductive Biology and Endocrinology... Aug 2023This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain.
METHODS
A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
RESULTS
A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation.
CONCLUSIONS
The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain.
TRIAL REGISTRATION
PROSPERO registration number: CRD42023415198.
Topics: Female; Humans; Antioxidants; Pelvic Pain; Vitamins; Endometriosis; Vitamin A; Ascorbic Acid; Vitamin K; Dietary Supplements
PubMed: 37644533
DOI: 10.1186/s12958-023-01126-1