The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway regulates cell proliferation, differentiation, and migration, along with angiogenesis and metabolism. Additionally, it could mediate skin development and homeostasis. There is much evidence to suggest that dysregulation of PI3K/Akt pathway is frequently associated with several human cutaneous malignancies like malignant melanoma (MM), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (SCC), as well as their poor outcomes. Nevertheless, emerging roles of PI3K/Akt pathway cascade in a group of common non-malignant skin disorders including acne and psoriasis, among others, have been recognized. The enhanced understanding of dysfunction of PI3K/Akt pathway in patients with these non-malignant disorders has offered a solid foundation for the progress of updated therapeutic targets. This article reviews the latest advances in the roles of PI3K/Akt pathway and their targets in the skin homeostasis and progression of a wide range of non-malignant skin disorders and describes the current progress in preclinical and clinical researches on the involvement of PI3K/Akt pathway targeted therapies.

Solar ultraviolet radiation (UVR) is the primary pathogenetic factor in skin photoaging. It can disrupt cellular homeostasis by damaging DNA, inducing an inflammatory cascade, immunosuppression, and extracellular matrix (ECM) remodeling, resulting in a variety of dermatologic conditions. The skin microbiome plays an important role in the homeostasis and maintenance of healthy skin. Emerging evidence has indicated that highly diverse gut microbiome may also have an impact on the skin health, referred to as the gut-skin axis (GSA). Oral and topical probiotics through modulating the skin microbiome and gut-skin microbial interactions could serve as potential management to prevent and treat the skin photoaging by multiple pathways including reducing oxidative stress, inhibiting ECM remodeling, inhibiting the inflammatory cascade reaction, and maintaining immune homeostasis. In this review, the effects of oral and topical probiotics in skin photoaging and related mechanisms are both described systematically and comprehensively.

Skin infections are common diseases for which patients seek inpatient and outpatient medical care. Globally, an increasing number of people are affected by skin infections that could lead to physical and psychological damage. Skin infections always have a broad spectrum of clinical presentations that require physicians to make an aggressive and accurate diagnosis for prescribing the proper symptomatic antimicrobials. In most instances, the treatment for skin infections mainly includes oral or topical anti-infective drugs. However, some of the classical anti-infective drugs have limitations, such as poor water solubility, low bioavailability, and poor targeting efficiency, which can lead to poor efficacy, adverse effects, and drug resistance. Therefore, research priorities should focus on the development of more effective drug delivery systems with new materials. Hydrogels are a highly multifunctional class of medical materials with potential applications in dermatology. Several hydrogel dressings with anti-infective functions have been formulated and demonstrated to improve the efficacy and tolerance of oral or topical classical anti-infective drugs to a certain degree. In this study, the medical applications of hydrogels for the treatment of various skin infections are systematically reviewed to provide an important theoretical reference for future research studies on the treatment options for skin infections.

Sarcoidosis, a multisystemic granulomatous disease with unknown etiology, is characterized by formation of noncaseating granulomas, which can affect all organs. Recent studies have made outstanding achievement in understanding the pathology, etiology, genetics, and immune dysregulation involved in granuloma formation of sarcoidosis. Antigen stimulation in genetically predisposed individuals enhances the phagocytic activity of antigen-presenting cells, including macrophages and dendritic cells. CD4 + T cells initiate dysregulated immune responses and secrete significant quantities of inflammatory cytokines, including interleukin (IL)-2 and interferon-gamma (IFN-γ), which play a crucial role in modulating the aggregation and fusion of macrophages to form granulomas. The current therapeutic strategies focus on blocking the formation and spread of granulomas to protect organ function and alleviate symptoms. The efficacy of traditional treatments, such as glucocorticoids and immunosuppressants, has been confirmed in the management of sarcoidosis. Promising therapeutic agents encompass inhibitors of cytokines, like those targeting tumor necrosis factor (TNF)-α, as well as inhibitors of signaling pathways, such as Janus kinase (JAK) inhibitors, which exhibit favorable prospects for application. Although there has been progress in the identification of biomarkers for the diagnosis, prognosis, activity and severity of sarcoidosis, specific and sensitive biomarkers have yet to be identified. This review outlines recent advancements in the molecular mechanisms and therapeutic strategies for the sarcoidosis.

Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate. Epidermal barrier dysfunction, inflammatory response, and chronic pruritus interact with each other, contributing to the pathogenesis and pathophysiology of AD in the elderly. Although fundamental medications are essential for managing AD in the elderly, older adults often struggle with regular usage of moisturizing emollients, topical medications, and avoidance of environmental triggers, leading to recurrent or even exacerbated disease progression. Therefore, a systematic medication approach is necessary to control pruritus and skin lesions. Traditional systemic treatments may not adequately meet the treatment needs of moderate and severe AD in the elderly and may even pose certain safety risks. Biologics and Janus kinase (JAK) inhibitors, exhibiting excellent clinical efficacy, have made significant breakthroughs in AD treatment. Existing evidence suggests that dupilumab, a human monoclonal IgG4 antibody, has been confirmed as an effective and safe first-line systematic treatment for moderate to severe AD in the elderly, with no notable differences between adults and the elderly. However, the limited inclusion of elderly patients in related clinical studies hinders the generalizability of these findings. As older patients face a higher risk of adverse events with JAK inhibitors, JAK inhibitors are recommended when no other suitable treatment options are available. Obtaining population-specific data is crucial for making evidence-based treatment choices when managing AD in older adults with JAK inhibitors.

Granulomatous rosacea (GR) is a rare inflammatory skin disease characterized by persistent, hard, yellow, brown, red, or flesh-colored papules, plaques, or nodules on the face. Limited data are available on patients treated for GR, with only case reports and case series published. Herein, we describe the case of a 53-year-old woman who presented to the hospital with persistent red to brown and pink patches on both cheeks accompanied by a burning sensation for one month. Histopathological examination of a cutaneous biopsy revealed granulomatous inflammation in focal areas. Both acid-fast and Periodic acid-Schiff staining were negative. The patient was diagnosed with GR based on her clinical presentation and laboratory test results. She was treated with abrocitinib, a JAK-1 inhibitor, for 20 weeks. This resulted in substantial improvement in her rash and the associated burning sensation. Subsequent follow-up visits indicated no adverse effects or relapses. Additionally, a literature review was conducted to compare with the current case, which concluded that abrocitinib is a viable treatment option for GR, exhibiting a relatively high safety profile with minimal side effects.