Jianhua Wu

Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignancies with limited reliable biomarkers for early detection and prognosis. This study integrated bulk and single‑cell transcriptomic data to identify post‑translational modification-related key genes and to characterise cellular and immune alterations in cSCC. Methods: Publicly available cSCC datasets and post-translational modification-related genes (PTMRGs) were analysed. Single-cell analysis identified key cell populations and differentially expressed genes (DEGs), which were intersected with bulk DEGs, weighted gene co‑expression network modules, and PTMRGs. Candidate genes were prioritised using five feature selection algorithms, validated by quantitative real-time polymerase chain reaction (qRT-PCR) and receiver operating characteristic (ROC) analysis [area under the curve (AUC) >0.7]. Functional exploration included predictive modelling, SHapley Additive Explanations (SHAP) interpretation, immune infiltration analysis, protein interaction mapping, drug prediction with molecular docking, intercellular communication inference, and pseudotime trajectory analysis. Results: Keratinocytes were identified as the key cell population, yielding 999 single-cell-differentially expressed genes (sc-DEGs). Bulk analysis detected 5,771 DEGs and 17 co‑expression modules; intersection yielded 19 candidate genes. Multi‑method feature selection nominated HIF1A, UBC, and GSTP1; validation retained HIF1A and GSTP1 as final diagnostic markers (upregulated in cSCC; AUCs >0.7). A least absolute shrinkage and selection operator (LASSO) classifier achieved the best performance. SHAP highlighted HIF1A and GSTP1 as dominant contributors. HIF1A was predicted to be nuclear, GSTP1 mitochondrial; both correlated positively with macrophages, natural killer (NK) cells, and neutrophils. Drug prediction and docking identified camptothecin, hydroquinone, and resveratrol with favorable binding (e.g., HIF1A-camptothecin −8.7 kcal/mol; GSTP1-camptothecin −8.6 kcal/mol). Cell-cell signaling was enhanced in cSCC [vascular endothelial growth factor (VEGF), endothelin (EDN) pathways; elevated MIF-(CD74+CXCR4) and MIF-(CD74+CD44)]. Keratinocyte pseudotime revealed progression from normal to metastatic states with concordant keratinocyte‑related gene programs. Conclusions: HIF1A and GSTP1 are promising diagnostic biomarkers for cSCC, linked to altered immune landscapes, enhanced intercellular signaling, and potential druggable interactions.

Background: It has been shown that the Basal cell carcinoma (BCC) is associated with chronic inflammation of skin conditions, the circulating inflammatory protein levels may be a more intuitive index in response to inflammation, however, the cause-and-effect relationship between circulating inflammatory proteins and BCC is currently unknown. Methods: This study performed a Mendelian randomization (MR) analysis using the plasma inflammatory protein levels from a large genome-wide protein quantitative trait loci study as the exposure data, and the outcome data from a GWAS for BCC. Inverse variance weighed, MR-Egger, maximum likelihood ratio, and weighted median for assessing causality between inflammatory proteins and BCC. MR-Egger regression and Cochran’s Q statistic were applied for sensitivity analysis and MRPRESSO was applied to exclude outliers. Inverse MR analysis was performed on inflammatory proteins found to be causally associated with BCC. Results: Six circulating inflammatory proteins with a causal relationship with BCC were obtained, including CCL4, was of a significant protective effect on BCC development. IL-18 and CCL28, were of suggestive protective effects on BCC development. CX3CL1, IL-17A, and CSF-1 were potential risk factors in the development of BCC. According to the results of reverse MR analysis, there is no significant causal relationship between BCC and the above-mentioned inflammatory proteins. Conclusion: This two-sample MR study revealed a strong association between circulating inflammatory proteins and the development of BCC. Specifically, CCL4, CCL28, IL-18, CX3CL1, IL-17A, and CSF-1 emerged as potential targets for prognostic evaluation and treatment of BCC. However, further experimental studies are needed to elucidate the specific mechanisms.

Background: Stomolophus meleagris envenomation causes severe cutaneous symptoms known as jellyfish dermatitis. The potential molecule mechanisms and treatment efficiency of dermatitis remain elusive because of the complicated venom components. The biological activity and molecular regulation mechanism of Troxerutin (TRX) was firstly examined as a potential treatment for jellyfish dermatitis. Methods: We examined the inhibit effects of the TRX on tentacle extract (TE) obtained from S. meleagris in vivo and in vitro using the mice paw swelling models and corresponding assays for Enzyme-Linked Immunosorbent Assay (ELISA) Analysis, cell counting kit-8 assay, flow cytometry, respectively. The mechanism of TRX on HaCaT cells probed the altered activity of relevant signaling pathways by RNA sequencing and verified by RT-qPCR, Western blot to further confirm protective effects of TRX against the inflammation and oxidative damage caused by TE. Results: TE significantly induced the mice paw skin toxicity and accumulation of inflammatory cytokines and reactive oxygen species in vivo and vitro. Moreover, a robust increase in the phosphorylation of mitogen-activated protein kinase (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways was observed. While, the acute cutaneous inflammation and oxidative stress induced by TE were significantly ameliorated by TRX treatment. Notablly, TRX suppressed the phosphorylation of MAPK and NF-κB by initiating the nuclear factor erythroid 2-related factor 2 signaling pathway, which result in decreasing inflammatory cytokine release. Conclusion: TRX inhibits the major signaling pathway responsible for inducing inflammatory and oxidative damage of jellyfish dermatitis, offering a novel therapy in clinical applications.

This study was to explore the activation of mast cells by microbubbles, with the focus on transient receptor potential (TRP) channels mediated degranulation and calcium influx. Bone marrow-derived mast cells (BMMCs) were primarily obtained from femurs in mice and induced differentiation for 4 weeks. After the purity identification, BMMCs were contacted by homogeneous microbubbles with the diameter of 1 mm for 1 h. & beta;-hexosaminidase and histamine levels in supernatants were assessed by enzyme-linked immunosorbent assay (ELISA) and the CD63 expression was tested by flow cytometry. The intracellular calcium binding with Fluo-4 AM dyes in BMMCs was observed under the fluorescence microscope and the mean fluorescence intensity was quantitatively measured by flow cytometry. & beta;-hexosaminidase release, histamine concentration, CD63 expression and calcium influx were significantly increased in BMMCs group upon microbubble stimulation compared to the control groups. After preconditioning with the available inhibitors and microbubble contact, only transient receptor potential vanilloid 1 (TRPV1) and TRPV4 inhibitors robustly suppressed the microbubble-induced degranulation. Likewise, the elevated fluorescence intensity of cytosolic calcium level was also significantly weaken. The results demonstrated microbubble stimulus effectively promoted BMMCs degranulation, which could be substantially restrained by inhibitors targeted for blocking TRPV1 or TRPV4 channel. The alternation of intracellular calcium level in BMMCs was consistent with the changes of degranulation capacity. It's suggested that the activation of BMMCs by microbubbles may involve specific TRP calcium dependent channels.

Background IgA vasculitis (IgAV) is an allergic disease of the vascular wall, the prognosis of the disease in adults is usually worse than that in children, but there is a lack of study to compare the clinical characteristics and complication predictors of IgAV between pediatric and adult patients. Methods This retrospective study included 158 cases of IgAV from the Departments of Dermatology, Pediatrics, Nephrology and Gastroenterology of Changhai Hospital. Details of the clinical characteristics, laboratory index and complication were collected. Results Multiple logistic regression analysis of the 158 IgAV patients (79 in children group and 79 in adult group) showed that the risk factors for gastrointestinal (GI) involvement were PLR > 184 in children group (OR = 6.963, P = 0.001) vs. NEU > 8.4 (OR = 4.332, P = 0.023) and NLR > 5.2 (OR = 4.077, P = 0.048) in adult group. Risk factors for renal involvement were age (OR = 0.818, P = 0.017), ENR > 2.6 (OR = 4.305, P = 0.034) and PLR > 04 (OR = 0.939, P = 0.024) in children group vs. RDW > 13.2 (OR = 5.453, P = 0.019) and ENR > 0.2 (OR = 4.667, P = 0.010) in adult group. Risk factors for arthralgia were the season of disease onset (OR = 0.609, P = 0.040) and NEU > 9.1 (OR = 7.761, P = 0.003) in children group vs. NEU > 7.0 (OR = 7.237, P = 0.07), LYM > 2.8 (OR = 9.129, P = 0.009), and PLT > 270 (OR = 6.466, P = 0.011) in adult group. Conclusions Different complication predictors of IgAV were observed between pediatric and adult patients, and different values of the same indicators in predicting the occurrence of complications were calculated, suggesting that the predictions should be differentiated in different patients with the same disease.

Background. Crisaborole has been considered a promising alternative for topical treatment of atopic dermatitis (AD), mainly supported by AD‐301 and AD‐302. However, critical insights into these two studies have previously been proposed. Objective. To make a comprehensive assessment of the application of crisaborole in mild to moderate AD. Methods. A systematic review and meta‐analysis were conducted, in which only randomized controlled trials comparing the application of crisaborole twice daily to vehicle or other active treatment in patients with mild to moderate AD were included. The selection of outcomes was based on the recommendation of the HOME initiative. Patient‐reported symptoms, clinician‐reported signs, health‐related quality of life, and the safety of crisaborole were all assessed using appropriate measurement instruments. Results. Eight RCTs with 2266 patients were included in the pooled analysis. Compared to those treated with vehicle, patients on crisaborole experienced a greater improvement in NRS (MD −0.70; 95% CI −0.94 to −0.47), POEM (MD −3.50; 95% CI −4.34 to −2.66), EASI (MD −14.49%; 95% CI −18.24% to −10.73%), ISGA (RR 1.45; 95% CI 1.28 to 1.63), DLQI (MD −1.54; 95% CI −2.17 to −0.92), and DFI (MD −1.16; 95% CI −1.72 to −0.59) during the 4‐week treatment. More patients achieved EASI 75 (RR 1.71; 95% CI 1.43 to 2.04) with crisaborole administration. There was no significant difference between two interventions in the incidence of AEs (RR 1.12; 95% CI 0.98 to 1.29), SAEs (RR 1.89; 95% CI 0.47 to 7.60), or AE‐related withdrawal (RR 0.87; 95% CI 0.47 to 1.60). One RCT also made comparison between crisaborole and pimecrolimus, suggesting that no significant difference was detected in the improvement of EASI or NRS at most time points. Conclusion. High‐quality evidence was provided to demonstrate that the short‐term application of crisaborole is safe and efficacious for the treatment of mild to moderate AD. The practical efficacy of crisaborole is similar to that of pimecrolimus.

Psoriasis is a chronic, inflammatory skin disease, frequently associated with dyslipidemia. Lipid disturbance in psoriasis affects both circulatory system and cutaneous tissue. Epidermal Langerhans cells (LCs) are tissue-resident DCs that maintain skin immune surveillance and mediate various cutaneous disorders, including psoriasis. However, the role of LCs in psoriasis development and their lipid metabolic alternation remains unclear. Here, we demonstrate that epidermal LCs of psoriasis patients enlarge with longer dendrites and possess elevated IL-23p19 mRNA and a higher level of neutral lipids when compared with normal LCs of healthy individuals. Accordantly, epidermal LCs from imiquimod-induced psoriasis-like dermatitis in mice display overmaturation, enhanced phagocytosis, and excessive secretion of IL-23. Remarkably, these altered immune properties in lesional LCs are tightly correlated with elevated neutral lipid levels. Moreover, the increased lipid content of psoriatic LCs might result from impaired autophagy of lipids. Bulk RNA-Seq analysis identifies dysregulated genes involved in lipid metabolism, autophagy, and immunofunctions in murine LCs. Overall, our data suggest that dysregulated lipid metabolism influences LC immunofunction, which contributes to the development of psoriasis, and therapeutic manipulation of this metabolic process might provide an effective measurement for psoriasis.

Candida albicans is the most common pathogen causing clinical Candida infections. Neutrophils are a key member of the host innate immunity that plays an essential role in clearing invading C. albicans. In addition to the well-known defensive approaches such as phagocytosis, degranulation, and reactive oxygen species production, the formation of neutrophil extracellular traps (NETs) has also become an important way for neutrophils to defend against various pathogens. C. albicans has been reported to be capable of activating neutrophils to release NETs that subsequently kill fungi. The induction of NETs is affected by both the morphology and virulence factors of C. albicans, which also develops specific strategies to respond to the attack by NETs. Our review specifically focuses on the mechanisms by which C. albicans triggers NET formation and their subsequent interactions, which might provide meaningful insight into the innate immunity against C. albicans infection.