Background:Lupus erythematosus tumidus (LET) is a rare photosensitive skin lupus subtype. Its erythematous swelling easily mimics erysipelas, cellulitis or herpes zoster, leading to frequent misdiagnosis. Atypical cases complicated by interface dermatitis and patient self-medication create prominent differential diagnostic difficulties. Case Presentation:A 58-year-old woman had scalp and facial erythema swelling for 1 year, worsened over 4 days. She was repeatedly misdiagnosed with bacterial infectious skin diseases and given ineffective antibiotics. Before admission, she took herbal decoctions and received bloodletting acupuncture by herself, aggravating facial edema. Examination showed infiltrative erythema and scalp alopecia. Full autoantibody, complement and routine lab tests were nearly normal. Cheek biopsy showed typical LET mucin deposition and periadnexal lymphocytic infiltration, while scalp biopsy unexpectedly revealed focal basal liquefaction degeneration. The final diagnosis of atypical LET was made after comprehensive clinicopathological evaluation. Combined hydroxychloroquine and methylprednisolone therapy induced obvious lesion remission within 6 months of follow-up. Conclusion:This atypical LET case illustrates key differential diagnostic traps caused by long-term misdiagnosis and conflicting pathological findings. Unsupervised herbal treatment and blood-letting acupuncture disturbs clinical manifestations and delays formal therapy. For patients presenting with facial edematous erythema accompanied by atypical epidermal pathological changes, comprehensive serological screening and thorough histopathological examination are warranted. Early clinicopathological combined diagnosis, antimalarial drugs and strict sun protection help avoid misdiagnosis and recurrence.
Hair follicles (HFs) are complex mini-organs characterized by a highly organized structure and cyclic regeneration. In recent years, hair follicle organoids (HFOs) have emerged as promising three-dimensional in vitro models that partially recapitulate the architecture and function of native hair follicles, providing new opportunities for studying hair biology and related disorders. This review first outlines the key biological features of HFs and highlights the essential role of epithelial–mesenchymal interactions in folliculogenesis, which serve as the foundation for organoid construction. We then summarize the fundamental principles of organoid technology and systematically compare current strategies for HFO generation, including primary cell-based co-culture systems and induced pluripotent stem cell (iPSC)-derived approaches, with an emphasis on their advantages and limitations. Furthermore, we discuss the applications of HFOs in disease modeling, drug screening, and regenerative medicine, while critically addressing current challenges such as difficulties in large-scale cultivation, limited maturity, and lack of standardization. Overall, HFOs represent a promising platform bridging basic research and clinical translation. Future efforts integrating biomaterials, microfluidic systems, and bioengineering technologies are expected to enhance their physiological relevance and accelerate their translational potential.
Background:Acrodermatitis continua of Hallopeau (ACH) is a chronic, relapsing variant of pustular psoriasis proven to be remarkably challenging to treat. There are cases in the literature describing successful treatment with biologic therapy for plaque psoriasis. However, there is less evidence on long-term management of the disease. Evidence from previous case reports suggests that for patients with plaque psoriasis who have failed monotherapy with biologics, the combination of biologics and small molecule drugs can be considered as a treatment option. For patients with ACH, there is currently a gap in research in this area. Further information is needed to help dermatologists formulate treatment plans for patients presenting with such diseases. Case Summary:We report the case of a 44-year-old man with an 8-year history of acrodermatitis continua of ACH. The patient started treatment with secukinumab (300 mg, once every 4 weeks) four years ago. This dramatically improved disease symptoms, with clearance of pustules and absence of pain. Unfortunately, the rash recurred after 2 years of treatment. The patient was transitioned to secukinumab (300 mg, once every 4 weeks) and apremilast (30 mg, twice daily), well-controlled ACH lesions. After 5 months, secukinumab was tapered to 300 mg every 8 weeks. During the 2 years of treatment, laboratory workup was within normal limits. Conclusion:This case underscores that the combination therapy of secukinumab and apremilast can offer a promising approach for the long-term management of ACH.
Background:Herpes Zoster (HZ) is a viral skin disease caused by reactivation of latent Varicella Zoster Virus (VZV) in human ganglia, presenting with unilateral neuropathic pain and vesicular rash. HZ imposes significant burden on patients and healthcare systems, often complicated by postherpetic neuralgia (PHN). The live attenuated zoster vaccine (ZVL, Zostavax) reduces HZ risk by 51% and PHN by 65% in adults ≥60 years. The recombinant zoster vaccine (RZV, Shingrix) shows approximately 90% efficacy in adults ≥50 years. Despite withdrawal of Zostavax from the U.S. market, RZV uptake remains suboptimal due to vaccine hesitancy and provider knowledge gaps. This study aims to analyze global research trends on HZ vaccines using bibliometric methods. Methods:Publications on "herpes zoster" and "zoster vaccine" were retrieved from the Web of Science Core Collection (WoSCC) database (1999-2024). Bibliometric and visualization tools including CiteSpace, VOSviewer, and R-bibliometrix were applied to analyze contributions by countries, institutions, journals, authors, references, and keywords. Results:A total of 719 articles from 261 journals across 56 countries were included. The United States led publications, with GlaxoSmithKline (GSK) as the most prolific institution. Vaccine was the most prolific journal; Levin et al. was the most productive author. The most cited article, "Efficacy of the Herpes Zoster Subunit Vaccine in Adults Aged 70 Years or Older," by Cunningham AL, appeared in the New England Journal of Medicine. Frequently used keywords included "herpes zoster," "vaccination," "postherpetic neuralgia," "efficacy," "subunit vaccine," and "safety". Conclusion:This bibliometric study comprehensively summarizes HZ vaccine research over 25 years, offering insights to guide future research and clinical practice.
Purpose:Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder. The IL-17A antagonist secukinumab has shown promising efficacy in international clinical trials; however, real-world evidence from China remains limited. This study evaluates the effectiveness and safety of secukinumab combined with surgical intervention for treating severe HS in a Chinese cohort. Patients and Methods:A retrospective analysis of 21patients with HS admitted to our hospital from May 2023 to August 2024 was conducted. The patients received combination therapy consisting of secukinumab and palliative surgery. The primary efficacy endpoint was the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at week 16. Secondary endpoints included HiSCR50 response rates at weeks 32 and 48, changes in the International Hidradenitis Suppurativa Severity Score System (IHS4), Visual Analog Scale (VAS) scores for pain, Dermatology Life Quality Index (DLQI) scores, and the incidence of adverse events at weeks 16, 32, and 48. Results:At week 16, the HiSCR50 response rate was 76.2% (16/21), accompanied by a significant 71.3% reduction in the IHS4 score from baseline (P < 0.001). Both the DLQI and VAS scores demonstrated notable decreases of 44.2% and 43.7% (P < 0.001 for both). By week 48, sustained improvements were observed in HiSCR50 response, IHS4 score, DLQI, and VAS scores, with reduction rates of 75.2%, 57.1%, and 65.3%. Only one patient reported mild eczema, and no serious adverse events were documented. Conclusion:Secukinumab in combination with surgical intervention rapidly and significantly improves clinical symptoms, quality of life, and pain levels in Chinese patients with moderate-to-severe HS, while demonstrating a favorable safety profile. This combined therapeutic approach may represent a novel treatment option for severe HS; however, further validation through large-scale, multicenter studies is warranted.
Vitiligo is an autoimmune skin disease with a complex pathogenesis closely linked to immune imbalance and oxidative stress. Currently, comprehensive curative treatments and effective relapse prevention strategies are lacking. Recently, the “gut-skin axis” hypothesis has offered new insights into the pathological mechanisms of vitiligo. Studies indicate that gut microbiota and their metabolic products significantly affect disease progression by regulating immune homeostasis and inflammatory responses in the host. This review systematically examines the effects of short-chain fatty acids, secondary bile acids, and tryptophan metabolites on the human immune system and the inflammatory milieu, and their direct impact on melanocytes. Furthermore, considering the reduced diversity of gut microbiota in individuals with vitiligo, this article also evaluates methods including probiotic intervention, the Mediterranean diet, and fecal microbiota transplantation, which may emerge as potential therapeutic strategies for vitiligo by restoring microbiota balance. Future multidimensional therapeutic strategies that target gut microbiota metabolites show promise for pioneering innovative approaches in vitiligo management.
INTRODUCTION:C3 is central for all complement activation pathways, thus making it an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or nonhuman primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly.METHODS:We first studied the compatibility of human C3 in the rat complement system, then developed a C3 humanized rat using the CRISPR/Cas9 technology. We thoroughly characterized the resultant human C3 humanized rats and tested the treatment efficacy of an established primate-specific C3 inhibitor in a model of complement-mediated hemolysis in the C3 humanized rats.RESULTS:We found that supplementing human C3 protein into the C3-deficient rat blood restored its complement activity, which was inhibited by rat factor H or compstatin, suggesting that human C3 is compatible to the rat complement system. The newly developed C3 humanized rats appeared healthy and expressed human but not rat C3 without detectable spontaneous C3 activation. More importantly, complement-mediated hemolysis in the C3 humanized rats was also inhibited by compstatin both in vitro and in vivo.CONCLUSION:The successfully developed C3 humanized rats provided a much-desired rodent model to evaluate novel C3 inhibitors in vivo as potential drugs.
Pemphigus foliaceus (PF) and bullous pemphigoid (BP) are distinct autoimmune bullous skin diseases mediated by autoantibodies targeting adhesion molecules in desmosomes and hemidesmosomes structural proteins in the epidermal-basement membrane zone, respectively. The coexistence of PF and BP is rare. We present the case of a 72-year-old male with clinical and histological features of both PF and BP. Treatment with immunoglobulin (10 g/day for 3 days), intravenous dexamethasone sodium phosphate (5 mg/day for 10 days), oral triamcinolone (30 mg/day for 10 days), and minocycline hydrochloride (20 mg/day for 10 days) resulted in significant improvement. This rare case highlights the importance of accurate diagnosis and effective treatment strategies for the coexistence of PF and BP.
The assembly of tissue-damaging membrane attack complexes (MACs; C5b-9) is a major mechanism by which excessive complement activation causes diseases. We previously developed a mouse anti-human C6 monoclonal antibody (mAb) 1C9 that selectively inhibits the assembly of MACs in human and non-human primates. In this project, we found that 1C9 also cross-reacted with rat and guinea pig C6, and determined its binding domains on C6 using different truncated C6 proteins. We then humanized the anti-C6 mAb by molecular modeling and complementarity-determining region grafting. After screening a library of 276 humanized variants with different combinations of humanized light and heavy chains in biophysical assays, we identified clone 3713 with the best developability profile, and an increased affinity against C6 when compared with the parental 1C9 mAb. This humanized 3713 mAb inhibited human, monkey, and rat complement-mediated hemolysis in vitro, and more importantly, it significantly reduced complement-mediated hemolysis in vivo in rats. These results demonstrated the successful humanization of the anti-C6 mAb and suggested that the humanized 3713 mAb could be further developed as a new therapeutic that selectively targets MAC for certain complement-mediated pathological conditions.
BACKGROUND:The skin, particularly the epidermis, is subjected to various external stresses, including ultraviolet (UV) irradiation. UV irradiation, mainly UVB at wavelength of 280-315 nm, can alter several epidermal functions, including cutaneous inflammation, epidermal hyperproliferation, DNA damage, disruption of epidermal permeability barrier and reduction in stratum corneum hydration levels. Because of the negative impacts of UVB irradiation on epidermal functions, great efforts have been made to develop regimens for the protection of alterations in epidermal function induced by UV irradiation. SUMMARY:While sunscreen can provide physical barrier to UV light, some natural ingredients can also effectively protect the skin from UVB irradiation-induced damages. Studies have demonstrated that either topical or oral administrations of some natural ingredients attenuate UVB irradiation-induced alterations in the epidermal function. The underlying mechanisms by which natural ingredients improve epidermal functions are attributable to antioxidation, stimulation of keratinocyte differentiation, increases in the content of epidermal natural moisturizers and inhibition of inflammation. KEY MESSAGE:Some natural ingredients exhibit protective and therapeutical benefits in photo-induced epidermal dysfunctions via divergent mechanisms.
Abstract Background: Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. Methods: A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Results: Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI = 1.263–2.818), and nonsystemic treatment (adjusted OR = 1.602, 95% CI = 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions: A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. Trial Registration: ClinicalTrials.gov (No. NCT05961605).
A 24-year-old woman presented with a 12-day history of erythema, papules, and itching on both hands and a 1-day history of a generalized rash with blisters. Notably, the patient was an investigator at a pharmaceutical company, and her work involved the manipulation of halogen bromoacetonitrile (BAN). The physical examination is shown in Figure 1. The patient was admitted to our hospital with contact dermatitis and received relevant symptomatic and supportive treatments, including initial intravenous prednisone (75 mg/day). The patient's condition continued to progress dramatically [Figure 2]. New lesions, including dark erythema and blisters that tended to fuse, the Nikolsky sign, and gradual massive erosions emerged to expose a large area of the dermis, accompanied by humid bleeding. The eyes, mouth, and genitals were also involved. The maximum dose of glucocorticoids was increased to 199 mg of prednisone daily, which was gradually reduced after disease control. Immunoglobulin (20 g/day) was administered for 7 days. Hemofiltration therapy was performed three times in the intensive care unit. Simultaneously, correction of hypoproteinaemia, regulation of electrolyte imbalance, fluid infusion, gastric mucosa protection, anti-infection, and hepatoprotective treatments were prescribed, with skin and mucous membrane care playing a crucial role in the patient's recovery. The skin lesions gradually improved [Figure 3]. Her discharge diagnosis was revised to contact toxic epidermal necrolysis (CTEN). Allergic contact dermatitis is a type IV hypersensitivity reaction with mild progress that occurs in previously sensitized individuals. In the present case, the patient progressed dramatically to CTEN, which is rare. In this condition, Fas ligands and related cytokines, mediated by cytotoxic CD8+ T cells, appear in the lesional epidermis and blisters. Fas/Fas ligand is coexpressed in many keratinocytes of lesional skin, resulting in massive epidermal destruction. This condition is dangerous and associated with a high mortality rate. CTEN caused by ultraviolet curing ink and S, S-dimethyl cyanoimidodithiocarbonate has been reported.[1-2] In the present case, the suspected sensitizer was BAN. BAN, a type of halogenated acetonitrile with the chemical formula C2H2BrN and a molecular weight of 119.948, is used for the chemical synthesis of new pharmaceutical products. Halogenated acetonitriles are emerging as a disinfection by-product that can be detected in various aquatic environments and are cytotoxic, genotoxic, mutagenic, and tumorigenic both in vitro and in vivo. BAN exposure induced liver and kidney injury and disrupted metabolic pathways of amino acids, energy, and lipids in mice.[3] At present, the treatment of TEN primarily includes timely withdrawal of the suspected sensitizer, glucocorticoids combined with immunoglobulins, and active skin care. A few nonpharmacological options for toxic epidermal necrolysis, including plasmapheresis and hemofiltration, have also been proposed. Continuous hemofiltration can efficiently control fluid balance and azotaemia and may be beneficial by rapidly removing noxious molecules and cytokines.[4] Continuous hemofiltration may be a safe and effective adjuvant therapy for patients with refractory or severe toxic epidermal necrolysis.[5] In the current case, three hemofiltration treatments were administered, which played a crucial role in disease control. Thus, hemofiltration may be an option for patients with an unsatisfactory response to conventional treatments.Figure 1: Patient's lesion on admission (a and b) Scattered bright red to dark red oedematous erythema and papules on both hands (c and d) the lateral aspect of the right thigh and the trunk with partial coalescence into large lesions. The erythema comprised scattered 1 to 10 mm blisters. No scales, erosions, or pustules were observedFigure 2: The patient's condition continued to progress dramatically with prednisone 75 mg/dayFigure 3: The skin lesions gradually improved after treatmentDeclaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Journal of the European Academy of Dermatology and VenereologyEarly View LETTER TO THE EDITOR Abrocitinib-A promising option for patients with refractory bullous pemphigoid Weiwei Jiang, Weiwei Jiang orcid.org/0000-0001-8919-3109 Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorXiuliang Ma, Xiuliang Ma Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorTao Guo, Tao Guo Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorMengmeng Song, Mengmeng Song Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorJunling Zhang, Corresponding Author Junling Zhang [email protected] Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China Correspondence Junling Zhang, Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No. 354, Beima Road, Hongqiao District, Tianjin 300120, China. Email: [email protected]Search for more papers by this author Weiwei Jiang, Weiwei Jiang orcid.org/0000-0001-8919-3109 Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorXiuliang Ma, Xiuliang Ma Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorTao Guo, Tao Guo Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorMengmeng Song, Mengmeng Song Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, ChinaSearch for more papers by this authorJunling Zhang, Corresponding Author Junling Zhang [email protected] Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China Correspondence Junling Zhang, Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No. 354, Beima Road, Hongqiao District, Tianjin 300120, China. Email: [email protected]Search for more papers by this author First published: 31 August 2023 https://doi.org/10.1111/jdv.19475Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Zeng FAP, Murrell DF. Bullous pemphigoid-what do we know about the most recent therapies? Front Med. 2022; 9:1057096. 2Sarny S, Hucke M, El-Shabrawi Y. Treatment of mucous membrane pemphigoid with Janus kinase inhibitor Baricitinib. JAMA Ophthalmol. 2018; 136(12): 1420–1422. 3Xiao Y, Xiang H, Li W. Concurrent bullous pemphigoid and plaque psoriasis successfully treated with Janus kinase inhibitor Baricitinib. Dermatol Ther. 2022; 35(10): e15754. 4James H, Paley GL, Brasington R, Custer PL, Margolis TP, Paley MA. Tofacitinib for refractory ocular mucous membrane pemphigoid. Am J Ophthalmol Case Rep. 2021; 22:101104. 5Youssef S, Gallitano S, Bordone LA, et al. Two cases of bullous pemphigoid effectively treated with oral tofacitinib. JAAD Case Rep. 2023; 32: 77–80. 6Nash D, Kirchhof MG. Bullous pemphigoid treated with Janus kinase inhibitor upadacitinib. JAAD Case Rep. 2023; 32: 81–83. 7Ciechanowicz P, Rakowska A, Sikora M, et al. JAK-inhibitors in dermatology: current evidence and future applications. J Dermatolog Treat. 2019; 30(7): 648–658. 8Juczynska K, Wozniacka A, Waszczykowska E, Danilewicz M, Wagrowska-Danilewicz M, Wieczfinska J, et al. Expression of the JAK/STAT signaling pathway in bullous pemphigoid and dermatitis herpetiformis. Mediators Inflamm. 2017; 2017:6716419. 9Simpson EL, Silverberg JI, Nosbaum A, Winthrop KL, Guttman-Yassky E, Hoffmeister KM, et al. Integrated safety analysis of Abrocitinib for the treatment of moderate-to-severe atopic dermatitis from the phase II and phase III clinical trial program. Am J Clin Dermatol. 2021; 22(5): 693–707. 10Deeks ED, Duggan S. Abrocitinib: first approval. Drugs. 2021; 81(18): 2149–2157. Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation
Ferroptosis is a form of regulated nonapoptotic cell death associated with iron-dependent lipid peroxidation, closely associated with Vitiligo. Although the impact of Curcumin (Cur), a polyphenolic compound derived from the plant Curcuma longa Linn, on vitiligo has been established, the specific role and potential mechanistic pathways through which Cur modulates ferroptosis in vitiligo remain elusive. In this study, the critical targets and potential mechanisms of Cur in treating vitiligo were predicted by network pharmacology and molecule docking. Then, the effects of Cur on Erastin-induced ferroptosis were investigated in melanocytes induced by Erastin in vitro. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of Cur acting on Vitiligo found that these intersection genes are associated with the vitiligo oxidative stress pathway, including nuclear factor erythroid 2-related factor 2(Nrf2)/Heme Oxygenase 1(HO-1) signaling pathway. Further molecular docking shows that Cur has a good binding effect with Nrf2(the binding energy of Cur and Nrf2 protein is -6 kcal/mol). Through the CCK8 assay, showed that 10 mu M Cur treatment 24 h after Erastin significantly improved cell viability In vitro. Then we found that Erastin induced cell death, ROS production, the mitochondrial membrane potential(MMP) decreased, Superoxide dismutase (SOD) and Glutathione (GSH) levels reduced, Malonaldehyde (MDA) and iron ion accumulation in melanocytes. In addition, the expression of glutathione peroxidase 4(GPX4) mRNA and protein was inhibited, while the expression of acyl-CoA synthetase long-chain family member 4(ACSL4), Transferrin Receptor Protein 1(TFR1) mRNA and protein was increased. However, the damage induced by Erastin was significantly relieved by Cur and Fer-1 treatment. Mechanistically, Cur treatment significantly promoted nuclear translocation of transcriptional factor Nrf2 and HO-1 expression. Interestingly, pretreatment with ML385, a selective Nrf2 inhibitor, counteracted antiferroptosis effects induced by Cur treatment. Taken together, these results demonstrate that Cur inhibits ferroptosis by regulating the Nrf2/HO-1 pathway to protect melanocytes.
Background Chloasma is a common skin hyperpigmentation condition, with treatment options ranging from topical agents to advanced interventions such as chemical peels and laser therapy. Salicylic acid, including its supramolecular form (SSA), has shown promise in managing chloasma. However, to date, no multicentre randomized controlled trial of SSA for chloasma is available. Objectives The purpose of this study was to assess the efficacy and safety of 30% SSA combined with 10% niacinamide in treating chloasma. Methods This multicentre (n = 15), randomized, double-blind, parallel placebo-controlled trial (Clinical trial registration number: ChiCTR2200065346) enrolled and randomized 300 participants (1 : 1) to either 30% SSA treatment or placebo, with 150 allocated to treatment and 150 to placebo in the full analysis set, and 144 to treatment and 147 to placebo in the per-protocol set. A Visia (R) Skin Analysis System was used at each visit to assess the degree of improvement in chloasma lesions. The primary endpoint was the effective rate after 16 weeks, assessed using the modified Melasma Area and Severity Index (mMASI) score [(pretreatment score - post-treatment score)/pretreatment score x 100%]. Results The total mMASI score, overall score on the Griffiths 10-point scale, and Griffiths 10 score for the left and the right sides of the face were significantly lower in the 30% SSA group than in the placebo group (all P < 0.001). One study of drug-related adverse events (AEs) and one study of drug-unrelated AEs were reported in the 30% SSA group. No AE was reported in the placebo group. Conclusions Among our patients, 30% SSA combined with 10% niacinamide was shown to be effective and safe for treating chloasma.
Psoriasis is a chronic inflammatory skin disease, the etiology of which has not been fully elucidated, in which CD8+ T cells play an important role in the pathogenesis of psoriasis. However, there is a lack of in-depth studies on the molecular characterization of different CD8+ T cell subtypes and their role in the pathogenesis of psoriasis. This study aims to further expound the pathogenesy of psoriasis at the single-cell level and to explore new ideas for clinical diagnosis and new therapeutic targets. Our study identified a unique subpopulation of CD8+ T cells highly infiltrated in psoriasis lesions. Subsequently, we analyzed the hub genes of the psoriasis-specific CD8+ T cell subpopulation using hdWGCNA and constructed a machine-learning prediction model, which demonstrated good efficacy. The model interpretation showed the influence of each independent variable in the model decision. Finally, we deployed the machine learning model to an online website to facilitate its clinical transformation.
Vitiligo is one of the common chronic autoimmune skin diseases in clinic, which is characterized by localized or generalized depigmentation and seriously affects the physical and mental health of patients. At present, the pathogenesis of vitiligo is not clear; mainly, heredity, autoimmunity, oxidative stress, melanocyte (MC) self-destruction, and the destruction, death, or dysfunction of MCs caused by various reasons are always the core of vitiligo. Regulatory cell death (RCD) is an active and orderly death mode of cells regulated by genes, which widely exists in various life activities, plays a pivotal role in maintaining the homeostasis of the organism, and is closely related to the occurrence and development of many diseases. With the deepening of the research and understanding of RCD, people gradually found that there are many different forms of RCD in the lesions and perilesional skin of vitiligo patients, such as apoptosis, autophagy, pyroptosis, ferroptosis, and so on. Different cell death modes have different mechanisms in vitiligo, and different RCDs can interact and regulate each other. In this article, the mechanism related to RCD in the pathogenesis of vitiligo is reviewed, which provides new ideas for exploring the pathogenesis and targeted treatment of vitiligo.
Because of the crucial role of epidermal permeability barrier in regulation of cutaneous and extracutaneous functions, great efforts have been made to identify and develop the regimens that can improve epidermal permeability barrier function. Studies have demonstrated that oral administration of natural ingredients can improve epidermal permeability barrier in various skin conditions, including inflammatory dermatoses and UV-irradiation. Moreover, topical applications of some natural ingredients can also accelerate the repair of epidermal permeability barrier after acute barrier disruption and lower transepidermal water loss in the intact skin. Natural ingredient-induced improvements in epidermal permeability barrier function can be attributable to upregulation of keratinocyte differentiation, lipid production, antioxidant, hyaluronic acid production, expression of aquaporin 3 and sodium-hydrogen exchanger 1. In this review, we summarize the benefits of topical natural ingredients in epidermal permeability barrier in normal skin with or without acute barrier disruption and the underlying mechanisms.
Xinghua Gao (高兴华)合作论文数Institute of Health Sciences, China Medical University;The First Hospital of China Medical University5