Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications.

The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full-thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.

A review on ferroptosis and photodynamic therapy synergism: Enhancing anticancer treatment.

Ferroptosis is an iron-dependent programmed cell death modality, which has showed great potential in anticancer treatment. Photodynamic therapy (PDT) is widely used in clinic as an anticancer therapy. PDT combined with ferroptosis-promoting therapy has been found to be a promising strategy to improve anti-cancer therapy efficacy. Fenton reaction in ferroptosis can provide oxygen for PDT, and PDT can produce reactive oxygen species for Fenton reaction to enhance ferroptosis. In this review, we briefly present the importance of ferroptosis in anticancer treatment, mechanism of ferroptosis, researches on PDT induced ferroptosis, and the mechanism of the synergistic effect of PDT and ferroptosis on cancer killing.

IPL-PDT as an effective treatment for mild-to-moderate acne vulgaris: A prospective, single-center, self-controlled study.

BACKGROUND: High recurrence rate of mild-to-moderate acne vulgaris following traditional therapy poses a significant challenge. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) with intense pulsed light (IPL) has emerged as a promising intervention. OBJECTIVES: This study aimed to evaluate the efficacy and safety of IPL-PDT for the treatment of mild-to-moderate acne vulgaris. METHODS: In this prospective, self-controlled study, eligible patients aged from 18 to 45 years old with Pillsbury grade Ⅰ-III facial acne were included. Patients were treated with three sessions of IPL-PDT at three-week interval, with follow-ups at 3 weeks and 2 months after the final treatment. RESULTS: A total of 31 patients were enrolled. At 3 weeks post-treatment, the mean count of acne lesions decreased significantly (P < 0.001), with 87.1 % of patients achieving treatment success (defined as ≥ 75 % clearance rate of acne lesions). Recurrence rate at 2-month follow-up was 9.68 %. No severe adverse reactions were observed. LIMITATIONS: This study is a single-center, self-controlled study. Multi-center study designed as randomize controlled trials involving a larger patient cohort is necessary. CONCLUSIONS: IPL-PDT is a promising therapy for mild-to-moderate acne vulgaris, exhibiting high efficacy, minimal adverse effects, and a low recurrence rate.

Successful treatment by a chlorin e6 derivative mediated photodynamic therapy combined holmium laser for cervical and vaginal giant condyloma acuminata and low-grade intraepithelial neoplasia:A case report.

Photodynamic therapy (PDT) is proved effective for treating low-grade squamous intraepithelial lesions (LSIL) and condylomata acuminata (CA). 5-Aminolevulinicacid (5-ALA) is the most common applied photosensitizer, but high rate of unbearable pain and relative long incubation time were reported. Here, we report a 27-year-old woman suffering from cervical and vaginal giant CA with LSIL involving the whole right vaginal fornix, cervical surface, and vaginal wall. Holmium yttrium aluminum garnet (Ho: YAG) laser was first applied to remove the giant CA lesions. STBF, a derivative of chlorin e6 (Ce6) was then applied on suspicious lesions as a new photosensitizer for 1 h. Lesions were exposed to LED illumination with a wavelength of 630 nm and light dose of 200-284 J/cm2 for cervical canal and the vaginal surfaces, 100-150 J/cm2 for cervix surface. Vaginal giant CA and LSIL lesions got complete remission at 6-month follow-up. Mild tolerable adverse reactions were observed after STBF-PDT and relieved in 24 h. Thus, the combination of Ho: YAG laser and STBF-PDT may be a novel option for cervical and vaginal giant CA and LSIL, especially for special vaginal fornix areas.

Radiotherapy may exacerbated anti-programmed cell death 1 treatment induced vitiligo: A case report.

Immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors combined with chemoradiotherapy shows great potential for cancer treatment and is getting extensively researched. However, a plethora of immune-related adverse events (irAEs) has been observed during anti-PD-1 treatment, including cutaneous adverse events, such as vitiligo and pruritus. These adverse events may lead to treatment discontinuation. When anti-PD-1 treatment is combined with radiotherapy (RT), irAEs may be exacerbated. Here we present a case report of an elderly patient with stage IIIb rectal cancer, who developed PD-1 inhibitor-associated vitiligo. After a session of RT, vitiligo lesions enlarged shortly thereafter. After discontinuation of anti-PD-1 treatment, vitiligo lesions and pruritus quickly improved with appropriate treatment. The rectal cancer achieved clinical complete response with no sign of recurrence or metastasis during follow-up. Considering the similar mechanism of anti-PD-1 treatment in targeting cancer and in inducing irAEs, cutaneous adverse events may be associated with favourable clinical response. Additionally, cutaneous irAEs aggravated by RT in this patient may suggested significant immune activation, which may occasionally contribute to tumour regression and favourable clinical outcome.

Single cell transcriptome profiling reveals cutaneous immune microenvironment remodeling by photodynamic therapy in photoaged skin.

Background: The immune microenvironment plays a critical role in maintaining skin homeostasis, which is closely related to the dysfunction in photoaged skin such as autoimmunity and tumorigenesis. Several recent studies have demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in alleviating photoaging and skin cancer. However, the underlying immune mechanisms and the immune microenvironment change by ALA-PDT remain largely unknown. Methods: To illustrate the effects of ALA-PDT on immune microenvironment in photoaged skin, single cell RNA sequencing (scRNA-seq) analysis of photoaged skin on the extensor side of the human forearm before and after ALA-PDT was performed. R-packages of Seurat, clusterProfiler, Monocle, CellChat were used for cell clustering, differentially expressed genes analysis, functional annotation, pseudotime analysis and cell-cell communication analysis. The gene sets related to specific functions were extracted from the MSigDB database, which were used to score the functions of immune cells in different states. We also compared our result with published scRNA-seq data of photoaged skin of the eyelids. Results: The increase score of cellular senescence, hypoxia and reactive oxygen species pathway in immune cells and the decrease of immune receptor activity function and proportion of naive T cells were found in skin photoaging. Moreover, the function of T cell ribosomal synthesis was also impaired or down regulated and function of G2M checkpoint was up regulated. However, ALA-PDT showed promising results in reversing these effects, as it improved the above functions of T cells. The ratio of M1/M2 and percentage of Langerhans cells also decreased with photoaging and increased after ALA-PDT. Additionally, ALA-PDT restored the antigen presentation and migration function of dendritic cells and enhanced cell-cell communication among immune cells. These effects were observed to last for 6 months. Conclusion: ALA-PDT has potential to rejuvenate immune cells, partially reversed immunosenescence and improved the immunosuppressive state, ultimately remodelling the immune microenvironment in photoaged skin. These results provide an important immunological basis for further exploring strategies to reverse skin photoaging, chronological aging and potentially systemic aging.

A novel chlorin e6 derivative-mediated photodynamic therapy STBF-PDT reverses photoaging via the TGF-ß pathway.

OBJECTIVE: Photoaging is characterized by wrinkles in the skin and the deterioration of the skin barrier function, mainly caused by long-term exposure to ultraviolet (UV) radiation. Photodynamic therapy (PDT) has been shown to treat photoaging. The novel photosensitizer ShengTaiBuFen(STBF) is a derived substance of Chlorin e6(Ce6) that can exert photodynamic effects directly. In this study, we investigated the availability and the mechanism of STBF-PDT in the treatment of photoaging. METHODS: Fluorophotometer was used to determine therapeutic parameters for in vivo experiments. Camera photographs, dermoscopy, HE and Masson staining, skin pH, trans epidermal water loss (TEWL), epidermal water content, and sebum testing were used together to evaluate the results of the treatment. Dark toxicity and therapeutic parameters for in vitro experiments were determined by CCK8 analysis. Scratch assay was used to identify the cell migration of STBF-PDT on HaCaT cells. qPCR and Western blot were used to evaluate the TGF-ß/Smad signaling pathway in human dermal fibroblast (HDF) cells. RESULTS: We investigated the optimal STBF concentration and time of incubation in vivo and in vitro experiments. STBF-PDT improved the skin phenotype of photoaged mice. The skin of photoaged mice treated with 80 J/cm2 STBF-PDT became smooth, while skin flakes were reduced. The epidermis of STBF-PDT-treated mice was thinner, and the cells were neatly arranged, with increased dermal collagen. In vitro, STBF-PDT promoted the migration of HaCaT cells below a light dose of 0.1 J/cm2. HDF cells co-cultured with HaCaT cells treated with low-dose STBF-PDT showed activation of the TGF-ß pathway. CONCLUSION: As a novel photosensitizer, STBF-mediated low-dose PDT could reverse photoaging via the TGF-ß pathway.

Photoinactivation of Moraxella catarrhalis Using 405-nm Blue Light: Implications for the Treatment of Otitis Media.

Moraxella catarrhalis is one of the major otopathogens of otitis media (OM) in childhood. M. catarrhalis tends to form biofilm, which contributes to the chronicity and recurrence of infections, as well as resistance to antibiotic treatment. In this study, we aimed to investigate the effectiveness of antimicrobial blue light (aBL; 405 nm), an innovative nonpharmacological approach, for the inactivation of M. catarrhalis OM. M. catarrhalis either in planktonic suspensions or 24-h old biofilms were exposed to aBL at the irradiance of 60 mW cm-2 . Under an aBL exposure of 216 J cm-2 , a >4-log10 colony-forming units (CFU) reduction in planktonic suspensions and a >3-log10 CFU reduction in biofilms were observed. Both transmission electron microscopy and scanning electron microscopy revealed aBL-induced morphological damage in M. catarrhalis. Ultraperformance liquid chromatography results indicated that protoporphyrin IX and coproporphyrin were the two most abundant species of endogenous photosensitizing porphyrins. No statistically significant reduction in the viability of HaCaT cells was observed after an aBL exposure of up to 216 J cm-2 . Collectively, our results suggest that aBL is potentially an effective and safe alternative therapy for OM caused by M. catarrhalis. Further in vivo studies are warranted before this optical approach can be moved to the clinics.