Aijun Chen

Melanoma is a highly heterogeneous and aggressive malignancy. Hypoxia within the tumor microenvironment is closely associated with tumor progression. However, the role of hypoxia-inducible factor 2α (HIF2α), a key transcription factor, in melanoma remains poorly understood. In this study, transcriptome analysis compared HIF2α expression between melanoma patient and control samples. Single-cell RNA sequencing categorized cells into high- and low-HIF2α expression groups. Ligand–receptor interactions (CellChat), enrichment analysis (GSEA/GSVA), immune regulatory network, and metabolic pathway analyses were performed. The correlation between HIF2α and genes involved in hypoxia, autophagy, and epithelial–mesenchymal transition (EMT) was explored, alongside its relationship with clinical stage. Experimentally, A375 cells were cultured under normoxic and hypoxic conditions, transfected with ShRNA-NC or ShRNA-HIF2α, and mRNA levels of HIF2α, E-cadherin, N-cadherin, and Vimentin were quantified using real-time PCR. Differential expression analysis showed significant upregulation of HIF2α in melanoma samples. Ligand–receptor interaction analysis emphasized its role in modulating the tumor microenvironment. Enrichment analyses (GSEA/GSVA) revealed HIF2α involvement in key oncogenic pathways. Correlation analysis linked HIF2α to genes related to hypoxia, autophagy, and EMT, and its expression was associated with advanced clinical stages. In vitro, hypoxia increased HIF-2α, N-cadherin, and Vimentin mRNA levels, while decreasing E-cadherin. HIF-2α knockdown reversed these effects, promoting E-cadherin and suppressing N-cadherin and Vimentin under hypoxia. This study underscores the critical role of HIF2α in melanoma progression, suggesting its involvement in regulating the tumor microenvironment and associated metabolic pathways. As a potential biomarker and therapeutic target, HIF2α offers new insights into the clinical management and treatment of melanoma.

The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.

Psoriasis is a chronic inflammatory skin disease with a prevalence of 0.14% to 1.99%. The underlying pathology is mainly driven by the abnormal immune responses including activation of Th1, Th17, Th22 cells and secretion of cytokines. Patients with psoriasis are more likely to develop cardiovascular disease (CVD) which has been well recognized as a comorbidity of psoriasis. As mediators of hemostasis and thromboinflammation, platelets play an important part in CVD. However, less is known about their pathophysiological contribution to psoriasis and psoriasis-associated CVD. A comprehensive understanding of the role of platelet activation in psoriasis might pave the path for more accurate prediction of cardiovascular (CV) risk and provide new strategies for psoriasis management, which alleviates the increased CV burden associated with psoriasis. Here we review the available evidence about the biomarkers and mechanisms of platelet activation in psoriasis and the role of platelet activation in intriguing the common comorbidity, CVD. We further discussed the implications and efficacy of antiplatelet therapies in the treatment of psoriasis and prevention of psoriasis-associated CVD.

Differential expression of heat shock proteins in cutaneous squamous cell carcinoma

Background: Nail involvement has a tremendous impact on psoriasis patients. Early detection and prompt intervention of psoriatic nail damage are necessary. Methods: A total of 4290 patients confirmed to have psoriasis between June 2020 and September 2021 were recruited from the Follow-up Study of Psoriasis database. Among them, 3920 patients were selected and divided into the nail involvement group (n = 929) and the non-nail involvement group (n = 2991) by inclusion and exclusion criteria. Univariate and multivariable logistic regression analyses were performed to identify the predictors of nail involvement for the nomogram. Calibration plots, the receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the discriminative and calibrating ability and clinical utility of the nomogram. Results: Sex, age at onset, duration, smoking, drug allergy history, comorbidity, sub-type of psoriasis, scalp involvement, palmoplantar involvement, genital involvement, and PASI score were selected to establish the nomogram for nail involvement. AUROC (0.745; 95% CI: 0.725–0.765) indicated the satisfactory discriminative ability of the nomogram. The calibration curve showed favorable consistency, and the DCA showed the good clinical utility of the nomogram. Conclusion: A predictive nomogram with good clinical utility was developed to assist clinicians in evaluating the risk of nail involvement in psoriasis patients.

Warts are benign lesions caused by infection of the keratinocytes by the human papillomavirus (HPV). There is still no consensus on the standard treatment for plantar warts, and the various treatments (both destructive and non-destructive) have variable efficacy with a long list of shortcomings, such as higher recurrence, pain, and scarring. Local hyperthermia was considered a safe, effective, and promising therapy in the treatment of plantar warts. After getting approval from the hospital’s ethics committee, the present study was designed to assess the clinical efficacy of local hyperthermia in the treatment of plantar warts. A total of 38 patients were enrolled in the study, and all patients received a standard regimen in a 5-week schedule, with local 45°C treatment for 30 mins on days 1, 2, 3, 14, 15, 22, 29, and 36. Of the 38 patients, complete resolution of the warts was observed in 13 (34.2%), 8 (21.1%) achieved partial remission, and 17 (44.7%) revealed poor response to the treatment. Patients were followed up for at least 3 months, and there was no recurrence of lesions in the 13 clinically cured patients at the last follow-up. The findings in the current study demonstrate that local hyperthermia is a safe, effective, and promising therapy for the treatment of plantar warts.

Objectives: Ultraviolet B (UVB) is one of the most dangerous insults for skin, which can cause skin sunburn, pigment disease, photoaging, and photocarcinogenesis. This study aimed to identify pathogenic genes related to ferroptosis in the skin of humans after UVB radiation. Methods: The gene expression profiles (GSE41078, GSE54413) were downloaded from the Gene Expression Omnibus (GEO) database, and the ferroptosis-related genes (FRGs) were downloaded from the Genecards database. To identify the differentially expressed genes (DEGs) and obtain differentially expressed FRGs by intersecting DEGs with FRGs. To identify the functional annotation and potential pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Differentially expressed FRGs-associated protein-protein interaction network (PPI) was performed by STRING database and Cytoscape software. Results: A total of 628 co-expressed DEGs of the two profiles (GSE41078 and GSE54413) were identified, including 371 upregulated and 257 downregulated DEGs. A total of 32 differentially expressed FRGs were identified. The results of GO analyses showed that, in the biological processes, UVB had a great influence on the response to oxidative stress; in the molecular functions, UVB had a great influence on antioxidant activity; in the cellular components, UVB had a great influence on endocytic vesicle lumen. The key pathways of differentially expressed FRGs were identified by KEGG analyses. The most significant 12 central node genes were identified by PPI network. Conclusion: We identified differentially expressed FRGs candidate genes and pathways in UVB-induced skin photodamage, which could contribute to the development of new therapeutic targets for skin photodamage.

Ultraviolet (UV) irradiation has been well documented to be linked with almost all skin problems we know, and both dermis and epidermis may be affected to varying degrees by UV irradiation. Every time when exposed to sunlight without protection, our skin will step closer to photoaging, leading to irreversible consequences ultimately. Heat shock protein 27 (HSP27) is a vital protein involved in cell growth, autophagy, apoptosis, drug resistance, tumor genesis and metastasis. Evidence suggests that the organism is subjected to various internal and external environmental stresses (heat, oxidative stress, organic toxicants, etc.), and HSP27 with high expression has protective function. However, the expression of HSP27 in coping with UV irradiation have not been examined thoroughly. In this study, photodamage models were developed through different doses of UVB irradiation in human epidermal keratinocytes (HEKs) (30 mJ/cm²), human dermal fibroblasts (HDFs) (150 mJ/cm²) and mouse skin (2,700 mJ/cm²). HSP27 knockdown decreased cell viability and increased the incidence of UVB-induced reactive oxygen species (ROS) production. We got consistent results in vivo and vitro. Compared with that in the UVB group, the expression of LC3B was significantly lower, while the expression of p62 was significantly higher in the UVB + si-HSP27 group. It was also revealed that HSP27 knockdown reduced the expressions of some antioxidants, such as superoxide dismutase (SOD) and catalase (CAT), which accelerated UVB-induced ROS release. Moreover, histological results showed that epidermis was thickened and collagen fibers were disorganized in the UVB + si-HSP27 group. These findings have demonstrated that HSP27 might play a photoprotective role in the UVB-induced skin damage process by maintaining the normal autophagy and antioxidant level. It is implied that HSP27 could be a potential therapeutic target of photodamage. However, determination of the definitive mechanism requires further exploration.