Recent studies highlight that gut dysbiosis, an imbalanced state of intestinal microbiota, exacerbates skin inflammation. Here, we showed the presence of gut microbiota alterations in two patients with recalcitrant acne and investigated the impact of its therapeutic modulation together with gold nanoshell‐mediated photothermal therapy (gold PTT).

Cutaneous fibrosis is characterized by aberrant wound healing with excessive extracellular matrix deposition, sustained inflammation, and oxidative stress, while currently available therapies show limited efficacy and safety. A Dual Hyaluronic Acid Compound (DHC), consisting of high-molecular-weight, low-molecular-weight, and minimally cross-linked hyaluronic acid, has demonstrated regenerative and antioxidant properties, but its anti-fibrotic effects have not been fully explored. This study investigated the anti-fibrotic potential of DHC using a bleomycin-induced murine dermal fibrosis model and a UVB-irradiated ex vivo human skin model. In C57BL/6 mice, dermal fibrosis was induced by daily bleomycin injections for three weeks, followed by intradermal DHC administration. Histological and biomechanical analyses showed that DHC significantly reduced dermal thickness, collagen deposition, and skin hardness compared with untreated fibrotic controls. DHC decreased α-SMA expression and increased MMP1 levels, indicating attenuation of myofibroblast activation and enhanced matrix remodeling. It also reduced macrophage markers (CD68, CD163) and pro-inflammatory cytokines (IL-1β, TNF-α). Furthermore, DHC restored superoxide dismutase (SOD) and catalase (CAT) activity and upregulated NRF2, HO-1, and NQO1 expression in the in vivo model. Similarly, DHC upregulated SOD and CAT activity and reduced pro-inflammatory cytokines (IL-6, TNF-α) in the ex vivo human skin model. These findings suggest that DHC exerts multimodal anti-fibrotic effects through coordinated regulation of fibroblast activation, inflammation, and oxidative stress, supporting its potential as a therapeutic approach for cutaneous fibrosis.

Skin aging arises from extracellular matrix degradation, inflammation, and pigmentation dysregulation, yet most existing rejuvenation strategies target only a subset of these processes. This study investigated the multimodal rejuvenation potential of a dual hyaluronic acid compound (DHC), composed of low- and high-molecular-weight HA integrated within a minimally cross-linked hybrid complex. In vitro assays using dermal fibroblasts, melanoma cells, and macrophages demonstrated that DHC enhanced fibroblast viability, collagen I/III and elastin production, antioxidant enzyme activity, and wound-healing capacity while reducing senescence markers. DHC markedly suppressed melanogenesis by downregulating the gene expression of MITF, TYR, and TRP1, and exerted strong anti-inflammatory activity by decreasing nitric oxide (NO) production and key cytokines, including TNF-α, IL-1β, IL-6, and CCL1. In a UVB-induced photoaging rat model, DHC reduced wrinkle depth, epidermal thickening, and melanin accumulation while improving elasticity, collagen density, hydration, and barrier integrity. Across these outcomes, DHC demonstrated biological effects that were comparable to, and in selected endpoints greater than, those of commonly used biostimulators and HA fillers in preclinical models. Collectively, these laboratory findings suggest that DHC exhibits broad preclinical bioactivity through combined biostimulatory, antioxidant, anti-inflammatory, and pigmentation-modulating effects. Further mechanistic and clinical studies are required to determine its translational relevance.

Roh H, et al. Ann Dermatol. 2025 Oct;37:e39. https://doi.org/10.5021/ad.25.166

Monopolar radiofrequency (MRF) is a well-established modality for non-invasive facial rejuvenation; however, its clinical utility is frequently constrained by patient discomfort and inconsistent thermal delivery. This study evaluated the efficacy, safety, and mechanistic profile of a novel MRF system incorporating continuous water cooling (RF-CWC) designed to optimize thermal distribution and enhance patient tolerance. In a prospective, single-arm clinical trial involving 22 female participants, a single RF-CWC treatment utilizing region-specific static and sliding delivery modes yielded statistically significant improvements in jawline lifting, alongside a volumetric increase in the midface and a concomitant volumetric reduction in the lower face (p < 0.001) over an 8-week follow-up period, with no adverse events reported. To elucidate the underlying cellular mechanisms, the system was further evaluated using an ultraviolet B (UVB)-induced ex vivo human skin model and an in vivo porcine model. Histological, immunohistochemical, and ELISA analyses revealed that RF-CWC effectively mitigated UVB-induced dermal degradation ex vivo by significantly up-regulating elastin, insulin-like growth factor, and hyaluronic acid, while down-regulating matrix metalloproteinase-1, interleukin-1α, and heat shock protein 72 (p < 0.05). Furthermore, the in vivo model demonstrated time-dependent increases in collagen types I and III and elastin without thermal tissue damage, with the sliding mode and higher shot counts correlating with enhanced extracellular matrix (ECM) remodeling. Comparative analyses demonstrated that RF-CWC achieved superior ECM restoration and reduced inflammatory cell infiltration relative to traditional cryogen spray-cooled RF systems. Taken together, these findings suggest that the RF-CWC system may promote robust ECM remodeling and significant facial neocollagenesis while minimizing inflammatory responses, potentially presenting an optimized, highly effective, and patient-friendly advancement in MRF technology.

Skin barrier dysfunction and pruritus, central to inflammatory dermatoses, are closely associated with impaired epidermal structural proteins and persistent inflammatory signaling. To address these pathological features, this study aimed to explore the potential anti-inflammatory, barrier-restorative, and anti-pruritic effects of DualPep-ATO, a human-derived cell-penetrating peptide (CPP), using integrated in vitro, ex vivo, and exploratory clinical approaches. Allergic and inflammatory responses were evaluated in rat basophilic leukemia cells and lipopolysaccharide-stimulated macrophages, while barrier-repair properties were partially assessed in ultraviolet B (UVB)-irradiated human epidermal keratinocytes and ex vivo human skin tissue. Mechanistically, DualPep-ATO exhibited no cytotoxicity and successfully suppressed β-hexosaminidase release, nitric oxide production, and pro-inflammatory cytokine expression. Furthermore, it contributed to mitigating skin barrier damage by restoring key epidermal structural proteins, specifically filaggrin, loricrin, and involucrin. Translating these findings clinically, a four-week topical application of a DualPep-ATO cream in adults with compromised skin significantly decreased transepidermal water loss and itch severity. With high participant satisfaction and no reported adverse events, this peptide may serve as a promising peptide-based topical strategy for inflammatory skin conditions associated with barrier dysfunction and pruritus.