Integration of scRNA-Seq and TCGA RNA-Seq to Analyze the Heterogeneity of HPV+ and HPV- Cervical Cancer Immune Cells and Establish Molecular Risk Models

Background: Numerous studies support that Human papillomavirus (HPV) can cause cervical cancer. However, few studies have surveyed the heterogeneity of HPV infected or uninfected (HPV+ and HPV-) cervical cancer (CESC) patients. Integration of scRNA-seq and TCGA data to analyze the heterogeneity of HPV+ and HPV- cervical cancer patients on a single-cell level could improve understanding of the cellular mechanisms during HPV-induced cervical cancer. Methods: CESC scRNA-seq data obtained from the Gene Expression Omnibus (GEO) database and the Seurat, Monocle3 package were used for scRNA-seq data analysis. The ESTIMATE package was used for single-sample gene immune score, CIBERSORT package was used to identify immune scores of cells, and the “WGCNA” package for the weighted correlation network analysis. Univariate Cox and LASSO regression were performed to establish survival and relapse signatures. KEGG and GO analyses were performed for the signature gene. Gene Expression Profiling Interactive Analysis was used for Pan-cancer analysis. Results: In the HPV+ CESC group, CD8+ T cells and B cells were down-regulated, whereas T reg cells, CD4+ T cells, and epithelial cells were up-regulated according to scRNA-seq data. Survival analysis of TCGA-CESC revealed that increased expression of naive B cells or CD8+ T cells favors the survival probability of CESC patients. WGCNA, univariate Cox, and LASSO Cox regression established a 9-genes survival signature and a 7-gene relapse model. Pan-cancer analysis identified IKZF3, FOXP3, and JAK3 had a similar distribution and effects in HPV-associated HNSC. Conclusion: Analysis of scRNA-seq and bulk RNA-seq of HPV+ and HPV- CESC samples revealed heterogeneity from transcriptional state to immune infiltration. Survival and relapse models were adjusted according to the heterogeneity of HPV+ and HPV- CESC immune cells to assess the prognostic risk accurately. Hub genes represent similar protection in HPV- associated HNSC while showing irrelevant to other potential HPV-related cancer

Efficacy and safety results of micellar water, cream and serum for rosacea in comparison to a control group

Background: Rosacea is a common inflammatory skin disorder with centrofacial erythema, flushing, telangiectasia, papules/pustules, and possible ocular or phymatous manifestation. Patients' skin is particularly sensitive to chemical and physical stimuli leading to burning, stinging, dryness, and skin tightness. Objective: Dermatological evaluation of the efficacy and safety of skin care products designed for centrofacial erythema in rosacea patients, in comparison with a control group using objective measurements. Rosacea symptoms (itching, tension, warmth, burning, dryness) and quality of life were examined. Methods Sixty Caucasians with centrofacial erythema were enrolled in an 8-week prospective study, fifty of them exclusively using the study products (micellar water, cream, and serum) with ten participants randomly assigned to a control group. Patients were evaluated at baseline (V0), at 4 weeks (V1), and at 8 weeks (V2). Three-dimensional objective measurements (VECTRA(R)) as well as standardized questionnaires were used. Results: Results were compared with the control group. A significant reduction of 16% in skin redness as indicated by VECTRA(R)analysis was seen in the intervention group comparing V0-V2. Furthermore, rosacea-associated symptoms diminished by 57.1%, while life quality of affected patients within the intervention group improved by 54.5% comparing V0-V2, respectively. Conclusions: A skin care regime suitable for sensitive and redness-prone skin led to an enhanced clinical appearance, to a decrease of associated symptoms in rosacea patients, and to an improved life quality

Rosacea and perioral dermatitis: a single‐center retrospective analysis of the clinical presentation of 1032 patients

Background Rosacea is a common chronic inflammatory cutaneous disorder affecting nearly 5.5 % of the adult population. Our aim was to evaluate the prevalence and epidemiology of rosacea and perioral dermatitis (POD) in an ambulatory care setting. Methods We retrospectively analyzed medical data of patients with a confirmed diagnosis of rosacea or perioral dermatitis (POD) presenting at our university hospital outpatient clinic during a 3‐year period. Results Out of 1032 patients, 81.5 % were diagnosed with rosacea and 18.5 % with POD. Overall prevalence was 1.4 % for rosacea and 0.3 % for POD. 69.3 % of the analyzed patients were female. Overall mean age was 49.3 ± 7.7 (1–92) years; the women’s average age was less than the men’s. Patients with POD were younger and predominantly female, whereas patients with phymatous rosacea were older and predominantly male. The most common phenotypes were papulopustular rosacea (68.4 %), erythematotelangiectatic rosacea (22.5 %), and phymatous rosacea (8.0 %). Special forms of rosacea were diagnosed in 15.8 % of the patients; the most frequent were ocular rosacea (6.9 %) and steroid‐induced rosacea (5.4 %). Conclusions The large patient cohort analyzed in our study provides a good estimate of the frequency of the rosacea subtypes, special forms and of perioral dermatitis in a hospital‐based outpatient care setting

Comparative analysis of the phototoxicity induced by BRAF inhibitors and alleviation through antioxidants

Background Small molecules tackling mutated BRAF (BRAFi) are an important mainstay of targeted therapy in a variety of cancers including melanoma. Albeit commonly reported as side effect, the phototoxic potential of many BRAFi is poorly characterized. In this study, we evaluated the phototoxicity of 17 distinct agents and investigated whether BRAFi‐induced phototoxicity can be alleviated by antioxidants. Methods The ultraviolet (UV) light absorbance of 17 BRAFi was determined. Their phototoxic potential was investigated independently with a reactive oxygen species (ROS) and the 3T3 neutral red uptake (NRU) assay in vitro. To test for a possible phototoxicity alleviation by antioxidants, vitamin C, vitamin E phosphate, trolox, and glutathione (GSH) were added to the 3T3 assay of selected inhibitors. Results The highest cumulative absorbance for both UVA and UVB was detected for vemurafenib. The formation of ROS was more pronounced for all compounds after irradiation with UVA than with UVB. In the 3T3 NRU assay, 8 agents were classified as phototoxic, including vemurafenib, dabrafenib, and encorafenib. There was a significant correlation between the formation of singlet oxygen (P = .026) and superoxide anion (P < .001) and the phototoxicity observed in the 3T3 NRU assay. The phototoxicity of vemurafenib was fully rescued in the 3T3 NRU assay after GSH was added at different concentrations. Conclusion Our study confirms that most of the BRAF inhibitors exhibited a considerable phototoxic potential, predominantly after exposure to UVA. GSH may help treat and prevent the phototoxicity induced by vemurafenib

Dermal fillers do not induce upregulation of NLRP3 inflammasomes or expression of inflammatory cytokines in granulomas

Background: Filling materials have increasingly been used in aesthetics over the last decades. Understanding the pathophysiology of granuloma formation as a very relevant unwanted side effect of filler application may be essential to help avoid these adverse events. Aims: Our aim was to investigate the role of the inflammasome in the formation of filler granuloma, as a central column of the innate immune response. Methods RPMI 1640 medium was used for growth of THP-1 cells and the induction of THP-1 macrophages. Sonication was applied in order to crush the acrylic particles of the filler. ELISA was the method of analysis for the specific cytokines. Biopsy specimens of filler granuloma were analyzed by various immunohistochemical methods. GraphPad Prism 5 software was used for the statistical data analysis. Results: Neither was the sensor NALP3 overexpressed, nor could an elevated expression of cleaved IL-1 beta, IL-18, or IFN-gamma be detected. Furthermore, no increased expression of IL-8 or IL-1 beta was detectable in vitro. Conclusion No increased inflammasome activation could be observed;however, filler granulomas were infiltrated with granulocytes and macrophages. Therefore, we speculate that an unspecific immune response might be the key player in the formation of filler granuloma