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The interplay between the microbes and the skin barrier holds pivotal significance in skin health and aging. The skin and gut, both of which are critical immune and neuroendocrine system, harbor microbes that are kept in balance. Microbial shifts are seen with aging and may accelerate age-related skin changes. This comprehensive review investigates the intricate connection between microbe dynamics, skin barrier, and the aging process. The gut microbe plays essential roles in the human body, safeguarding the host, modulating metabolism, and shaping immunity. Aging can perturb the gut microbiome which in turn accentuates inflammaging by further promoting senescent cell accumulation and compromising the host's immune response. Skin microbiota diligently upholds the epidermal barrier, adeptly fending off pathogens. The aging skin encompasses alterations in the stratum corneum structure and lipid content, which negatively impact the skin's barrier function with decreased moisture retention and increased vulnerability to infection. Efficacious restoration of the skin barrier and dysbiosis with strategic integration of acidic cleansers, emollients with optimal lipid composition, antioxidants, and judicious photoprotection may be a proactive approach to aging. Furthermore, modulation of the gut-skin axis through probiotics, prebiotics, and postbiotics emerges as a promising avenue to enhance skin health as studies have substantiated their efficacy in enhancing hydration, reducing wrinkles, and fortifying barrier integrity. In summary, the intricate interplay between microbes and skin barrier function is intrinsically woven into the tapestry of aging. Sound understanding of these interactions, coupled with strategic interventions aimed at recalibrating the microbiota and barrier equilibrium, holds the potential to ameliorate skin aging. Further in-depth studies are necessary to better understand skin-aging and develop targeted strategies for successful aging. [ABSTRACT FROM AUTHOR]

Metformin is a widely used drug for treatment of diabetes mellitus, due to its safety and efficacy. In addition to its role as an antidiabetic drug, numerous beneficial effects of metformin have enabled its use in various diseases. Considering the anti-androgenic, anti-angiogenic, anti-fibrotic and antioxidant properties of metformin, it may have the potential to improve chronic inflammatory skin diseases. However, further evidence is needed to confirm the efficacy of metformin in dermatological conditions, This review focuses on exploring the therapeutic targets of metformin in acne vulgaris, hidradenitis suppurativa and rosacea, by studying their pathogeneses. [ABSTRACT FROM AUTHOR]

Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for pruritus in atopic dermatitis, psoriasis, and other diseases, such as prurigo nodularis and lichen planus, with rapid itch relief compared with conventional treatments. The most common adverse effects reported include nasopharyngitis, acne, and elevated blood creatine phosphokinase levels. Janus kinase inhibitors are currently prescribed with warnings about a potential increase in malignancies and cardiovascular diseases and usage in people of older ages. This review aims to provide knowledge about itch and the Janus kinase and signal transducer and activator of transcription pathway and to analyse the current evidence for itch relief by Janus kinase inhibitors. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with bimodal incidence peaks in early childhood and middle-aged and older adults. Few studies have focused on the risk of dementia in AD. The aims of this study were to analyse the incidence, and risk factors for dementia in patients with AD. This nationwide population-based retrospective cohort study enrolled 38,391 adults ≥40 years of age with AD and 2,643,602 controls without AD from the Korean National Health Insurance System (NHIS) database from 2009 to 2016. The cumulative incidence probability of all-cause dementia, Alzheimer’s disease, or vascular dementia at 8 years was 50, 39, and 7 per 1,000 person-years in patients with AD, respectively. The adjusted risks of all-cause dementia (hazard ratio (HR), 1.072; 95% confidence interval (95% CI) 1.026– 1.120), and Alzheimer’s disease (HR 1.051; 95% CI 1.000–1.104) were increased in patients with AD. The effect of AD on the development of all-cause dementia and Alzheimer’s dementia varied according to age and diabetes mellitus (all p for interaction, <0.05). The risks of all-cause dementia and Alzheimer’s disease were increased in patients with AD. Management of modifiable risk factors is important for preventing dementia in patients with AD. [ABSTRACT FROM AUTHOR]

Psoriasis is a complex chronic inflammatory cutaneous disorder. To date, robust molecular mechanisms of psoriasis have been reported. Among diverse aberrant immunopathogenetic mechanisms, the current model emphasizes the role of Th1 and the IL-23/Th17 axis, skin-resident immune cells and major signal transduction pathways involved in psoriasis. The multiple genetic risk loci for psoriasis have been rapidly revealed with the advent of a novel technology. Moreover, identifying epigenetic modifications could bridge the gap between genetic and environmental risk factors in psoriasis. This review will provide a better understanding of the pathogenesis of psoriasis by unraveling the complicated interplay among immunological abnormalities, genetic risk foci, epigenetic modification and environmental factors of psoriasis. With advances in molecular biology, diverse new targets are under investigation to manage psoriasis. The recent advances in treatment modalities for psoriasis based on targeted molecules are also discussed. [ABSTRACT FROM AUTHOR]

Erythroid differentiation regulator 1 (Erdr1) is known to be involved in the inflammatory process via regulating the immune system in many cutaneous disorders, such as psoriasis and rosacea. However, the role of Erdr1 in various hair loss disorders remains unclear. The aim of this study was to investigate the putative role of Erdr1 in alopecias. Skin samples from 21 patients with hair loss disorders and five control subjects were retrieved, in order to assess their expression levels of Erdr1. Results revealed that expression of Erdr1 was significantly downregulated in the epidermis and hair follicles of patients with hair loss disorders, when compared to that in the control group. In particular, the expression of Erdr1 was significantly decreased in patients with alopecia areata. We propose that Erdr1 downregulation might be involved in the pathogenesis of hair loss, and could be considered as a novel biomarker for hair loss disorders. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that can be debilitating, impacting all body areas, including the genital region. Genital AD results in impairments in daily activity levels, sexual function and sleep, contributing to impaired quality of life in patients with moderate-to-severe AD. Upadacitinib (UPA) is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs. JAK2, JAK3 and tyrosine kinase 2, indicated for the treatment of moderate to severe AD. The SCORing Atopic Dermatitis (SCORAD) measure assesses the extent and severity to which a body area is affected, as well as itch and sleeplessness due to AD. In this post-hoc analysis of the Measure Up 1 and Measure Up 2 studies, we evaluated the proportion of patients whose genital AD resolved with UPA 15 mg or UPA 30 mg compared with placebo. Measure Up 1 and 2 are phase 3 multicenter, randomized, double-blind studies comparing the safety and efficacy of UPA 15 mg and UPA 30 mg to placebo in adolescent and adult patients with moderate-to-severe AD. Patients were randomized to oral once daily UPA 15 mg, UPA 30 mg or placebo. The current study assessed the proportion of patients with genital involvement at baseline who achieved genital AD resolution at week 2 and week 16 based on data collected from the SCORAD. Non-responder imputation was used. Of the 1679 participants, 239 (14.2%) had genital AD at baseline and were randomized to UPA 15 mg (n=77), UPA 30 mg (n=86) or placebo (n=76). More participants with genital involvement vs. those without were male (61.1% vs. 54.1%), ≥18 years old (92.1% vs. 85.5%), and severe according to the Validated Investigator Global Assessment Scale for Atopic Dermatitis (66.9% vs. 47.2%) at baseline. On average, participants with genital involvement at baseline also reported greater disease duration (25.0 vs. 22.8 years) and higher Dermatology Life Quality Index (DLQI) scores (19.2 vs. 16.3). At week 2, the proportion of patients whose genital AD was resolved was 70.1% of the UPA 15 mg group, and 82.6% of the UPA 30 mg group, both of which were greater than the placebo group (31.6%; P<0.001). At week 16, the proportion of patients whose genital AD was resolved increased in the UPA 15 mg (80.5%) and UPA 30 mg (83.7%) groups, but not in the placebo group (28.9%) which remained lower than both groups (P<0.001). More patients with moderate-to-severe AD achieved resolution of their genital AD with UPA 15 mg or 30 mg monotherapy daily compared to placebo, with >70% rapidly achieving genital AD resolution after 2 weeks and >80% after 16 weeks of UPA treatment. In addition to overall improvements in moderate-to-severe AD with UPA, resolution of genital AD may correspond to improvements in sexual functioning, reductions in sleeplessness and greater quality of life. These findings underscore the importance of considering genital involvement when assessing the burden of AD to comprehensively inform integrated shared decision-making treatment discussions between patients and physicians. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic cutaneous inflammatory disease that affects the facial skin. Clinically, rosacea can be categorized into papulopustular, erythematotelangiectatic, ocular, and phymatous rosacea. However, the phenotypic presentations of rosacea are more heterogeneous. Although the pathophysiology of rosacea remains to be elucidated, immunologic alterations and neurovascular dysregulation are thought to have important roles in initiating and strengthening the clinical manifestations of rosacea. In this article, we present the possible molecular mechanisms of rosacea based on recent laboratory and clinical studies. We describe the genetic predisposition for rosacea along with its associated diseases, triggering factors, and suggested management options in detail based on the underlying molecular biology. Understanding the molecular pathomechanisms of rosacea will likely aid toward better comprehending its complex pathogenesis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a case study of an 18-year-old female with recurrent purpuric/ecchymotic patches on upper and lower extremities who was diagnosed with Gardner-Diamond syndrome after the autoerythrocytes sensitization test.