Kuniko Kadoya,1 Patrick Nido,1 Robin Chung,1 Raymond E Boissy,2 Edward T Kisak,3 Khadija Nader,1 John M Newsam,3 Tsing Cheng,1 Rahul C Mehta,1 Prithwiraj Maitra11Research and Development, Skincare, Allergan Aesthetics, an AbbVie company, Irvine, CA, USA; 2Department of Dermatology, College of Medicine, University of Cincinnati, Cincinnati, OH, USA; 3Executive Leadership, Tioga Research, Inc., San Diego, CA, USACorrespondence: Prithwiraj Maitra, Research and Development, Skincare, Allergan Aesthetics, an AbbVie company, 2525 Dupont Drive, Irvine, CA, 92612-1531, USA, Tel +1 714 246-4500, Email prithwiraj.maitra@abbvie.comBackground: Hyperpigmentation is a difficult-to-manage chronic condition typically treated using topical agents and cosmetic procedures. Topical treatments frequently include hydroquinone (HQ) 4%, which is limited by tolerability concerns for long-term use. Therefore, HQ-free cosmeceutical topical treatments for long-term control of hyperpigmentation are needed.Purpose: This exploratory study sought to characterize the potential mechanism of action of a novel, cosmetic, topical, HQ-free, pigment-correcting serum formulated with lotus sprout extract, tranexamic acid (TXA), and niacinamide (LTN) designed to target 6 key cellular pathways of the melanin life cycle aimed at improving the appearance of skin hyperpigmentation.Patients and Methods: In vitro studies were conducted using the MelanoDerm human skin model. Gene expression, melanin concentrations, and histology were assessed after treatment with LTN serum or commercially available comparator formulations; samples were also examined with individual typology angle (ITA) and electron microscopy. Delivery and skin penetration of TXA and phenylethyl resorcinol (PER) were assessed using Franz-type diffusion cells.Results: LTN serum significantly (P≤ 0.05) decreased expression of genes associated with melanogenesis. Median ITAs indicated paler skin color when treated with LTN serum compared with control (51.3° vs 28.9°). Electron micrographs demonstrated that LTN serum affected melanosome development and promoted melanosome degradation in melanocytes and keratinocytes. The LTN serum formulation is optimally designed to facilitate delivery of TXA and PER into epidermis and dermis. LTN serum led to greater inhibition of melanin production versus comparator formulations.Conclusion: LTN serum is the first topical to target 6 key pathways in the melanin life cycle, including melanosome degradation, aimed at improving the appearance of hyperpigmentation. Overall, our in vitro results reinforce observed clinical efficacy while providing further mechanistic insights into LTN serum treatment effects. The LTN serum may be a potential long-term, HQ-free treatment option for patients with hyperpigmentation.Keywords: hyperpigmentation, melanogenesis, melanin, delivery/vectorization/penetration, formulation/stability, cosmeceuticals
Jian Chen,1,2 Bingxue Bai11Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Dermatology, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, 523059, People’s Republic of ChinaCorrespondence: Bingxue Bai, Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China, Tel +86 15114517408, Email baibingxue@hrbmu.edu.cnBackground and Objective: Atopic dermatitis (AD) is a complex immune-mediated disorder in which aberrant activation of CD4⁺ T cells plays a critical pathogenic role. We integrated dynamic CD4⁺ T cell expression quantitative trait loci (eQTL) data with Mendelian randomization (MR) to dissect the causal effect of transcriptional changes on AD risk.Methods: This study integrated dynamic CD4⁺ T-cell eQTL analysis, two-sample MR, colocalization analysis, single-cell transcriptomic, pseudotime, cell–cell communication and protein–protein interaction (PPI) analyses, with virtual single-cell knockout further used to evaluate gene regulatory effects in AD. We systematically analyzed gene expression and genetic variation in CD4⁺ T cells from 119 individuals of European ancestry across multiple activation time points (0 h, 16 h, 40 h, and 5 days).Results: We performed two-sample Mendelian randomization (MR) integrating dynamic CD4⁺ T-cell eQTL, OneK1K, eQTLGen, and FinnGen R12 AD cohort data. The analysis identified 298 genes significantly associated with AD (FDR < 0.05), including key regulators such as FADS1, IRF5, and IL1RN, showing distinct causal effects between resting and activated states. Colocalization confirmed 11 core genes (eg, KDELR2, FADS1) underlying AD risk loci. Single-cell transcriptomic and pseudotime analyses revealed dynamic CD4⁺ T-cell regulatory trajectories, while cell–cell communication and protein interaction networks linked several candidates (IRF5, CTSS, PTGER4) to therapeutic pathways of existing AD drugs. Virtual single-cell knockouts of AHI1, CTSS, PTGER4, and PPP5C showed gene-specific regulatory patterns in skin barrier and immune-related pathways.Conclusion: We demonstrate that understanding the dynamic characteristics of CD4⁺ T cells is crucial for AD, and prioritize genes for future research into its pathogenesis.Keywords: atopic dermatitis, dynamic eQTL, single-cell analysis, Mendelian randomization analysis, virtual knockout
Chi Zhang,1 Tingxuan Zhang,1 Kaihao Du,1 Weiwei Xue,1 Zhanjin Wang,1 Yuying Du,1 Zhan Wang21Clinical Medical College, Qinghai University, Xining, Qinghai, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qinghai University, Xining, Qinghai, People’s Republic of ChinaCorrespondence: Zhan Wang, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qinghai University, Xining, Qinghai, People’s Republic of China, Email ufofu01@163.comObjective: To integrate expression quantitative trait locus-based Mendelian randomization (eQTL-MR), spatial transcriptomics, summary-data-based Mendelian randomization (SMR), mediation MR, and exploratory virtual knockout to prioritize candidate genes and potential metabolic mediation pathways in atopic dermatitis (AD).Methods: Whole-blood eQTL and AD genome-wide association study data were analyzed by two-sample MR, followed by intersection with differentially expressed genes from lesional versus non-lesional AD skin spatial transcriptomics, SMR, and the heterogeneity in dependent instruments (HEIDI) test. MR of 1,400 plasma metabolomic traits was integrated with gene–metabolite and gene–AD estimates. Spatial expression and scTenifoldKnk applied to spot-level expression matrices were used for exploratory functional interpretation.Results: MR identified 1,671 candidate genes; 66 overlapped with spatial transcriptomic differentially expressed genes, and 13 were prioritized by SMR/HEIDI. Eighty-six metabolites and 198 of 1,118 gene–metabolite tests were nominally associated (IVW P < 0.05); post hoc BH correction retained 36 gene–metabolite tests at FDR < 0.05. Twenty-four exploratory mediation paths involving 12 of the prioritized genes and 17 metabolites were identified. Among 6,603 spatial spots, ENO1, S100A10, MPZL2, and GPX3 showed distinct expression patterns across reference-based spot labels. Detailed estimates are provided in Supplementary Tables 1– 4, supplied as separate files.Conclusion: These computational findings suggest candidate gene–metabolite relationships in AD. The mediation paths did not survive correction for multiple testing. Interpretation of the spatial expression and virtual-knockout results requires additional methodological validation and independent experimental confirmation.Keywords: atopic dermatitis, Mendelian randomization, summary-data-based Mendelian randomization, mediation Mendelian randomization, spatial transcriptomics, virtual knockout
Shreya K Gowda,1 Biswanath Behera,1 Noemi Plozner,2 Giuseppe Stinco,2 Enzo Errichetti21Department of Dermatology and Venereology, AIIMS, Bhubaneswar, Odisha, India; 2Institute of Dermatology, Department of Medicine, University of Udine, Udine, ItalyCorrespondence: Noemi Plozner, Institute of Dermatology, Department of Medicine, University of Udine, Friuli Venezia Giulia, Piazzale Santa Maria della Misericordia, 15, Udine, 33100, Italy, Tel +39 0432559822, Email noemiplozner@hotmail.itAbstract: Alopecias are broadly classified as scarring and non-scarring disorders. However, distinguishing between these groups can be difficult in the early stages because scarring changes may not yet be apparent, and several conditions share overlapping clinical features. Delayed or incorrect diagnosis may result in irreversible hair loss. Trichoscopy has emerged as a valuable non-invasive tool that improves diagnostic accuracy. In this review, we systematically assessed trichoscopic findings of the main alopecias (both scarring and not) and proposed a two-step assessment algorithm. A systematic review of 235 eligible studies was conducted, beginning with identifying the clinical pattern of hair loss, followed by trichoscopy application to differentiate among the considered conditions. Although this review provides a comprehensive data of characteristic trichoscopic findings, interpretation of the evidence should consider the substantial methodological heterogeneity among the included studies, inconsistent and variable terminology of reported findings.Keywords: alopecias, dermoscopy, diagnosis, differential diagnosis, hair disorders
Xiaofeng Chen,1,2,* Dehai Xian,3,* Yan Huang,4,* Jianqiao Zhong,1 Jingdong Lai41Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Dermatology, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, 620500, People’s Republic of China; 3Department of Anatomy, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Dermatology, Suining First People’s Hospital, Suining, 629000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingdong Lai, Email 2639120837@qq.com Jianqiao Zhong, Email zjq7632@hotmail.comBackground: Psoriasis is a chronic immune-mediated inflammatory skin disease closely linked to immune dysregulation and oxidative stress (OS), in which M1-skewed macrophage polarization plays a critical pathogenic role. Loganin (Log), a natural plant extract, exerts anti-inflammatory and antioxidant bioactivities; however, its effect on psoriasis remains unexplored.Objective: To investigate the preventive effect and potential mechanism of Log against imiquimod (IMQ)-induced psoriasis-like dermatitis in mice under prophylactic administration.Methods: Thirty BALB/c mice were randomly assigned to five groups: vaseline, normal saline (NS), low-dose Log (50 mg/kg), medium-dose Log (100 mg/kg), and high-dose Log (200 mg/kg). Except for the vaseline group, all mice were topically treated with IMQ cream and simultaneously received daily intragastric administration of the corresponding agents for six consecutive days. Skin lesions were assessed using PASI scoring. Back skin tissues were collected for H&E staining and immunofluorescence analysis of M1/M2 macrophage phenotypes. Inflammatory-related molecules were detected by RT-PCR and ELISA, and OS-related biomarkers were measured by ELISA.Results: IMQ successfully induced typical psoriasis-like skin lesions and inflammatory responses in mice. Log intervention alleviated skin lesions and pathological changes, lowered PASI scores, reduced M1 macrophage phenotype, and elevated M2-type phenotype. Log also decreased the levels of pro-inflammatory and OS-related mediators while increasing anti-inflammatory and antioxidant indicators. These changes were accompanied by altered expression of TLR4/NF-κB signaling-related molecules.Conclusion: Prophylactic administration of Log ameliorates IMQ-induced psoriasis-like lesions in mice. This protective effect is associated with modulation of macrophage M1/M2 polarization, regulation of TLR4/NF-κB signaling, attenuation of inflammation, and enhancement of antioxidant capacity.Keywords: loganin, psoriasis, macrophage polarization, TLR4/NF-kB signaling, IMQ model, oxidative markers
