Dermatological diseases pose a significant challenge due to their chronic nature, complex pathophysiology, and the need for effective, patient-friendly treatments. Recent advancements in liposomal and gel-based formulations have played a crucial role in improving drug delivery, therapeutic efficacy, and patient compliance. Liposomal formulations have garnered considerable attention in dermatology due to their ability to encapsulate both hydrophilic and lipophilic compounds, enabling controlled drug release and enhanced skin penetration. However, challenges such as formulation complexity, stability issues, and regulatory constraints remain. Similarly, gel-based formulations are widely used due to their ease of application, biocompatibility, and ability to retain active ingredients. However, they also face limitations, including restricted penetration depth, susceptibility to microbial contamination, and challenges in achieving sustained drug release. The integration of liposomal and gel-based technologies offers a promising strategy to overcome current challenges and optimize dermatological drug delivery. This review explores both well-established therapies and recent innovations, offering a comprehensive overview of their applications in the treatment of prevalent dermatological conditions. Ultimately, continued research is essential to refine these formulations, expanding their clinical utility and enhancing therapeutic effectiveness in dermatology.

Human Leukocyte Antigen-G (HLA-G) is a key immunomodulatory molecule with multiple isoforms, including recently identified variants lacking the α1 domain (HLA-G Δα1). The absence of the α1 domain may reduce immune inhibition, particularly of Natural Killer (NK) cells, which are often suppressed during viral infections such as SARS-CoV-2. This suggests a novel immune regulatory mechanism that could mitigate COVID-19-related complications, including coagulopathies. This study investigates the influence of full-length and Δα1 HLA-G isoforms in NK-cell activity in vitro during SARS-CoV-2 infection and whether their expression associates with viral persistence and coagulopathy in COVID-19 patients, using vascular specimens retrieved from surgical procedures. RCC7 cell lines engineered to express either the full-length or Δα1 form of HLA-G were infected with Omicron SARS-CoV-2 to assess NK cell-mediated cytotoxicity in a co-culture system. Contrary to full-length, Δα1 HLA-G only partially inhibited NK activation, allowing greater cytotoxicity and higher IFN-I/II expression. To evaluate clinical relevance, vascular tissues from coagulopathic COVID-19 patients were analyzed for in situ SARS-CoV-2 persistence and HLA-G isoform expression. SARS-CoV-2 negative tissues more frequently expressed Δα1 and displayed higher systemic interferon (IFNs) levels. Among infection-positive cases, Δα1 expression was also associated with stronger IFN-β and IFN-γ responses. These in vivo trends mirror in vitro findings, supporting a model in which full-length HLA-G dampens NK-mediated clearance of infected vascular cells, favoring viral persistence and potentially contributing to immunothrombosis, while Δα1 permits enhanced antiviral immunity. Overall, these findings identify distinct immunomodulatory roles for HLA-G isoforms in SARS-CoV-2 infection. The Δα1 variant exhibits reduced inhibitory potency, partially preserving NK-cell antiviral functions and modulating interferon responses, whereas full-length HLA-G may facilitate vascular viral persistence and coagulopathy. HLA-G isoform profiling may thus represent a novel biomarker and therapeutic target in COVID-19 associated vascular pathology.

Polyomaviruses are a family of small DNA viruses capable of establishing persistent infections, and they can pose significant pathogenic risks in immunocompromised hosts. While traditionally studied in the context of viral reactivation and immune suppression, recent evidence has highlighted the gut microbiota as a critical regulator of host immunity and viral pathogenesis. This review examines the complex interactions between polyomaviruses, the immune system, and intestinal microbiota, emphasizing the role of short-chain fatty acids (SCFAs) in modulating antiviral responses. We explore how dysbiosis may facilitate viral replication, reactivation, and immune escape and also consider how polyomavirus infection can, in turn, alter microbial composition. Particular attention is given to the Firmicutes/Bacteroidetes ratio as a potential biomarker of infection risk and immune status. Therapeutic strategies targeting the microbiota, including prebiotics, probiotics, and fecal microbiota transplantation (FMT), are discussed as innovative adjuncts to immune-based therapies. Understanding these tri-directional interactions may offer new avenues for mitigating disease severity and improving patient outcomes during viral reactivation.