Tanshinone Alleviates UVA-induced Melanogenesis in Melanocytes via the Nrf2-regulated Antioxidant Defense Signaling Pathway.

BACKGROUND: As a complex of natural plant compounds, tanshinone is renowned for its remarkable antioxidant properties. However, the potential impact of tanshinone on melanocyte pigmentation regulation has yet to be elucidated. This study aimed to explore the protective effects of tanshinone I (T-I) and dihydrotanshinone (DHT) on melanogenesis by modulating nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in human epidermal melanocyte (HEM) cells. METHODS: HEM cells and Nrf2 knockdown HEM cells were subjected to ultraviolet A (UVA) and treated with T-I and/or DHT. Then, the anti-melanogenic properties of T-I and DHT were examined by assessing tyrosinase activity, melanogenesis-related proteins, and melanin content in UVA-irradiated HEM cells. Furthermore, the antioxidant activities of T-I and DHT were evaluated by assessing oxidant formation and modulation of Nrf2-related antioxidant defenses, including reactive oxygen species (ROS), glutathione (GSH) content, and the activity and expression of antioxidant enzymes, such as catalase (CAT), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD). RESULTS: Our findings revealed that T-I and DHT diminished melanogenesis in UVAirradiated HEM cells, activated Nrf2-antioxidant response element signaling, and enhanced antioxidant defenses in the irradiated cells. Furthermore, Nrf2 knockdown by shRNA abolished the anti-melanogenesis effects of T-I and DHT on HEM cells against oxidative damage. CONCLUSION: These results suggest that T-I and DHT inhibit UVA-induced melanogenesis in HEM cells, possibly through redox mechanisms involving Nrf2 signaling activation and increased antioxidant defenses. This indicates that T-I and DHT have potential as whitening agents in cosmetics and medical treatments for hyperpigmentation disorders.

The Effectiveness and Safety of Dupilumab for the Treatment of Recalcitrant Chronic Actinic Dermatitis: A Case Series.

Background: Although dupilumab is an effective treatment approach for chronic actinic dermatitis (CAD) in some cases, its effectiveness and safety in CAD have not been sufficiently assessed. Purpose: Evaluation of the effectiveness and safety of dupilumab in patients with recalcitrant CAD was performed. Methods: We retrospectively reviewed the medical records of CAD patients treated with dupilumab. Data regarding demographics were collected, and disease severity scores were assessed using the following: Clinical Severity Score of CAD (CSS-CAD), Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS)-itch scores. Results: After 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 CAD patients. Only one patient achieved a good response and most of the patients (62.5%, 10/16) had no significant symptom improvement after 4 weeks of treatment. However, after 12 weeks of treatment, 43.75% (7/16) of the patients reached excellent response (>75% improvement of CSS-CAD), 31.25% (5/16) good response (50%-75% improvement of CSS-CAD), 6.25% (1/16) partial response (25%-50% improvement of CSS-CAD), and only 18.75% (3/16) no response (<25% improvement of CSS-CAD). One patient complained of injection site reaction at the first injection. Conclusion: This study supports dupilumab as an effective and safe treatment option for patients with recalcitrant CAD. Patients may require at least 4 weeks of treatment before the partial response is noted.

Integrated analysis reveals SMARCD1 is a potential biomarker and therapeutic target in skin cutaneous melanoma.

OBJECTIVE: SMARCD1 is a part of the SWI/SNF chromatin remodeling complex family, which consists of transcription factors that are implicated in various types of cancer. Examining SMARCD1 expression in human cancers can provide valuable insights into the development and progression of skin cutaneous melanoma (SKCM). METHODS: Our study comprehensively examined the association between SMARCD1 expression and numerous factors, including prognosis, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) in SKCM. Then we utilized immunohistochemical staining to measure the SMARCD1 expression in both SKCM tissues and normal skin tissues. Furthermore, we conducted in vitro experimentation to evaluate the effects of SMARCD1 knockdown on SKCM cells. RESULTS: We found that aberrant expression of SMARCD1 across 16 cancers was strongly correlated with overall survival (OS) and progression-free survival (PFS). In addition, our research revealed that SMARCD1 expression is associated with multiple factors in different types of cancer, including immune infiltration, TME, immune-related genes, MSI, TMB, and sensitivity to anti-cancer drugs. SMARCD1 is likely involved in various SKCM signaling pathways and biological processes. Additionally, our research revealed that an SMARCD1-based risk factor model accurately predicted OS in SKCM patients. Furthermore, the downregulation of SMARCD1 expression demonstrated a significant inhibition of SKCM cell proliferation and migration, as well as an increase in apoptosis and cell cycle arrest. CONCLUSION: We conclude that SMARCD1 is a promising diagnostic, prognostic, and therapeutic biomarker for SKCM, and its expression has significant clinical implications for the development of novel treatment strategies.

Successful Treatment of Severe Subcorneal Pustular Dermatosis with Adalimumab.

Subcorneal pustular dermatosis (SPD) is a rare, chronic pustular dermatosis. The pathogenesis of SPD has not been fully elucidated, but some studies have found that tumor necrosis factor (TNF)-α may be associated with its pathogenesis. Some patients with multidrug-resistant SPD have improved significantly after treatment with the anti-TNF-α agent (adalimumab). We present a case of a 28-year-old female with severe SPD who responded rapidly to adalimumab (80mg/week) in combination with acitretin and methylprednisolone within a week. With adalimumab (40 mg next week and followed by 40mg every two weeks) and gradually ceasing other systemic medication, the patient's condition continued to improve without relapse or side effects. The outcome of this case suggests that adalimumab might be an effective treatment option against multidrug-resistant SPD.

T-Cell Lymphoblastic Lymphoma with Cutaneous Involvement in a Child: A Rare Case Report.

T-cell lymphoblastic lymphoma (T-LBL) is a heterogeneous malignancy derived from T-cells that more commonly affects teens and males. Most commonly, T-LBL exhibits signs of lymph nodes, bone marrow, and mediastinal mass invasion, but in rare cases, the disease manifests cutaneously. We present a case of both cutaneous and systemic presentation of T-LBL in 9-year-old man in which the skin immunophenotype analysis showed TdT expression with positivity of CD3, CD4 and CD99. Review of all currently described cases of cutaneous T-LBL revealed that the most frequently positive tumor markers were TdT (100%), CD3 (100%), CD4 (59.1%) and CD99 (40.9%). Cutaneous involvement may be a prognostic factor in treating T-LBL with chemotherapy.

Meta-analysis of the efficacy of adding platelet-rich plasma to 308-nm excimer laser for patients with vitiligo.

OBJECTIVE: Platelet-rich plasma (PRP) is a novel treatment option for vitiligo. PRP has been reported to be effective in combination with 308-nm excimer laser therapy, but there is no consensus on their combination use. Therefore, this meta-analysis assessed the efficacy and safety of the combination regimen in patients with vitiligo compared with laser therapy alone. METHODS: The meta-analysis was performed by searching PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang to identify relevant publications published through 1 February 2022. RESULTS: Six studies involving 302 patients were included. Compared with phototherapy alone, combination treatment with PRP and 308-nm excimer laser therapy significantly improved the total response rate and reduced the no response rate. Additionally, the proportions of patients with repigmentation rates of ≥75%, ≥50%, and ≥25% were significantly higher in the combination group than in the monotherapy group. In addition, the rates of adverse events for combination therapy were comparable to those for laser therapy alone, and the recurrence rates were low. CONCLUSIONS: This meta-analysis provided evidence supporting the combined use of PRP and 308-nm excimer laser therapy as a valuable treatment modality for patients with vitiligo based on its superiority to monotherapy.

Effects of tea polyphenols on UVA-induced melanogenesis via inhibition of α-MSH-MC1R signalling pathway.

Introduction: Ultraviolet (UV) irradiation is a major environmental factor affecting photoaging, which is characterized by skin wrinkle formation and hyperpigmentation. Although many factors are involved in the melanogenesis progress, UV is thought to play a major role in tanning. The pathway of α-melanocyte-stimulating hormone (α-MSH)-melanocortin receptor 1 (MC1R) is associated with UV-induced melanogenesis. Thus, α-MSH antagonists may have applications in the prevention of melanogenesis. Aim: To investigate the effects of tea polyphenols (TPS) on pigmentation, and further explore the underlying mechanism. Material and methods: Human keratinocyte cell line (HaCaT) cells and Human epidermal melanocytes (HEM) were exposed to UVA and treated with different concentrations of TPS or Nonapeptide-1 acetate salt (N-1A). Then, cell viability, melanin content, and tyrosinase activity of both kinds of cells were detected. Quantification of α-MSH in HaCaT cells and HEM cells determined by ELISA assays. Immunohistochemistry of HEM cells was employed to further investigate the expression of melanogenesis-related proteins. Results: The different concentrations of TPS were found to decrease the melanin content, tyrosinase activity and melanogenesis-related proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein (TRP)1, and TRP2. Besides, TPS inhibited α-MSH-MC1R signalling through directly suppressed α-MSH expression rather than the down-regulated expression level of MC1R. Conclusions: Our findings indicate that TPS may be a potential whitening agent for use in cosmetics and the medical treatment of hyperpigmentation disorders.

Green Tea Polyphenols Cause Apoptosis and Autophagy in HPV-16 Subgene-Immortalized Human Cervical Epithelial Cells via the Activation of the Nrf2 Pathway.

Infection with human papillomavirus (HPV) is relatively common and certain high-risk HPV strains can induce epithelial dysplasia, increasing the risk of cervical cancer. Green tea polyphenol (GTP) preparations exhibit diverse anti-inflammatory, antioxidative, and antitumor properties In Vitro and In Vivo. Topical GTP application has been recommended as a treatment for genital warts, but the effect of GTP treatment on HPV infection and HPV-associated cancer remains to be established. The present study aimed to explore the mechanism by which GTP affected HPV type 16 (HPV-16)-positive immortalized human cervical epithelial cells. Survival, apoptosis, and autophagocytosis of these cells following GTP treatment was assessed using CCK-8 assay, flow cytometry, and monodansylcadaverine (MDC) staining. These cells were further transfected with an shRNA specific for Nrf2 to generate stable Nrf2-knockdown cells. The levels of Caspase-3, Bcl-2, Bax, P53, Rb, HPV-16 E6, HPV-16 E7, P62, Beclin1 and LC3B were determined via Western blotting. These analyses revealed that GTP treatment induced autophagy and apoptosis in HPV-16-positive cells, while Nrf2 gene knockdown reversed GTP-induced autophagic and apoptotic effects. Together, these results suggested that GTP could alleviate HPV infection and HPV-associated precancerous lesions In Vitro by regulating the Nrf2 pathway, highlighting the therapeutic potential of GTP in treating HPV infection.

Efficacy of low-fluence 1064 nm Q-switched Nd: YAG laser for the treatment of melasma: A meta-analysis and systematic review.

BACKGROUND: Melasma is considered as a type of acquired facial pigmentary disorder that is challenging to treat. Low-fluence 1064 nm Q-switched Nd: YAG laser (LQSNY) has clinical benefits against melasma; however, there are some disputes. OBJECTIVE: To explore these contentious views, we conducted a meta-analysis and systematic review to evaluate the efficacy and safety of LQSNY monotherapy and combined therapy for the treatment of melasma. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant articles from inception to July 2021. The resulting data were analyzed using the Review Manager 5.3 software. RESULTS: Twelve eligible studies comprising 358 patients were included. No significant differences in melasma area and severity index (MASI) were observed between the LQSNY and drug groups (mean difference (MD):-0.26, 95% confidence interval (CI):-1.16-0.64, p = 0.57). We found that combination therapy with LQSNY and drugs had a greater MASI improvement compared with LQSNY therapy alone (MD: 1.78, 95% CI 0.93-2.63, p < 0.0001); nevertheless, no statistically significant results were found in melanin index (MI) and self-assessment. The melasma improvement was similar when using LQSNY alone and LQSNY combined with other lasers in terms of RMASI (MD 0.05, 95% CI:-0.61, 0.70, p = 0.56). Compared with intense pulsed light (IPL) alone, LQSNY with IPL provided an added benefit for melasma severity (MD:3.23, 95% CI:0.65-5.81, p = 0.01). CONCLUSION: Low-fluence 1064 nm Q-switched Nd: YAG laser can be applied as an alternative treatment for drug intolerance. Combination therapy with LQSNY and drugs or other lasers may have pleasantly surprising efficacy, but numerous studies are still needed to verify this.

Efficacy of NB-UVB as Add-on Therapy to Antihistamine in the Treatment of Chronic Urticaria: A Systematic Review and Meta-analysis.

INTRODUCTION: Narrow-band ultraviolet B (NB-UVB) phototherapy has been used for the treatment of chronic urticaria (CU), but the clinical efficacy of this treatment modality requires further evidence. A systematic review and meta-analysis of randomized clinical trials were conducted to evaluate the efficacy and safety of NB-UVB as add-on therapy in the treatment of CU. METHODS: A literature search was conducted in the Cochrane, Embase, PubMed, Web of Science, CNKI, CBM, VIP and WanFang databases up to October 2020. A total of nine studies involving 713 participants met the inclusion criteria. RESULTS: Two trials showed a significant difference in the Urticaria Activity Score between therapy with NB-UVB + antihistamines and that with antihistamines alone (mean difference 8.23, 95% confidence interval [CI] 5.78-10.68, p < 0.00001). Six trials (563 participants) showed a significant benefit of NB-UVB as add-on therapy to antihistamines in the total effective rate (risk ratio [RR] 1.56, 95% CI 1.39-1.75, p < 0.00001). In terms of adverse events, no statistically significant differences were found for NB-UVB + antihistamines versus antihistamines alone (RR 1.10, 95% CI 0.67-1.79, p = 0.71). Combination therapy of NB-UVB + antihistamines yielded a significantly lower risk of recurrence (RR 0.25, 95% CI 0.14-0.44, p < 0.00001). CONCLUSION: Our meta-analysis suggests that combination therapy of NB-UVB + antihistamines is significantly more effective in treating CU than antihistamines alone.

Successful Treatment of Chronic Actinic Dermatitis with Dupilumab: A Case Report and Review of the Literature.

Chronic actinic dermatitis (CAD) is a rather rare photosensitive disease characterized by a persistent eczematous eruption in sun-exposed sites. The pathogenesis of CAD has not been completely elucidated. The clinical treatment of CAD is still challenging and not standardized. Some patients with severe CAD have achieved satisfactory clinical results with dupilumab when conventional therapies have failed. We herein report the case of a 45-year-old male with severe CAD who responded rapidly to combined treatment with dupilumab (600 mg for 1 week, and then 300 mg every 2 weeks) in 2 months. The patient experienced continuous improvement and no side effects from dupilumab (300 mg every month), having ceased other systemic medications. Dupilumab could be considered as an alternative or adjunctive treatment for CAD.