Chronic inflammatory skin diseases such as atopic dermatitis, psoriasis or rosacea are very common. Although their exact pathogenesis is not completely understood all three diseases are characterized ...by dysregulation of cutaneous innate immunity. Cathelicidin LL-37 is an important effector molecule of innate immunity in the skin and atopic dermatitis, psoriasis or rosacea show defects in cathelicidin expression, function or processing. In atopic dermatitis, cathelicidin induction might be disturbed resulting in defective antimicrobial barrier function. In contrast, psoriasis is characterized by overexpression of cathelicidin. However to date it is unclear whether pro- or anti-inflammatory functions of cathelicidin predominate in lesional skin in psoriasis. In rosacea, cathelicidin processing is disturbed resulting in peptide fragments causing inflammation, erythema and telangiectasias. In this review, the current evidence on the role of cathelicidin LL-37 in the pathogenesis of inflammatory skin diseases will be outlined. As cathelicidin LL-37 might also serve as a future treatment target potential novel treatment strategies for those diseases will be discussed.
Cannabinoids in hyperhidrosis Kaemmerer, Till; Clanner-Engelshofen, Benjamin Maximilian; Lesmeister, Tony ...
The Journal of dermatological treatment
34, Številka:
1
Journal Article
Recenzirano
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Hyperhidrosis can significantly curtail patient quality of life, from debilitating physical symptoms to social stigmatization and reduced life opportunities. Current treatments often prove ...unsatisfactory, especially in sufferers of generalized hyperhidrosis. In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids. We found a remarkable reduction in the volume of sweat and an improvement to the patient's quality of life using this novel low-cost and low-impact approach.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The disease burden of lichen planus and its impact on patients' quality of life have not been well studied. The aim of this mono-centre cross-sectional study was to investigate these factors. From ...June to September 2020, an anonymous survey was posted to 253 patients, who were diagnosed with lichen planus in our outpatient clinic from January 2018 to June 2020. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI), the EuroQol 5-dimension 3-level score, and further quality of life indicators. Beck Depression Inventory II was used to evaluate symptoms of depression. A total of 100 patients completed and returned the survey. Lichen planus affected quality of life in 78% of cases. DLQI was higher for multiple localizations (r = 0.454, p < 0.001). Patients with genital lichen planus had a significantly higher DLQI (mean ± standard deviation (SD) 8.68 ± 6.96) than patients who were not affected in the genital area (5.01 ± 5.49; p = 0.009). DLQI was also significantly higher for ungual lichen planus (9.83 ± 7.6; not affected: 5.65 ± 5.84; p-value 0.039), and for cutaneous LP (mean 8.1, SD 6.22; not affected: 5.63 ± 6.12; p-value 0.045). Twenty-nine percent of patients had mild to moderate symptoms of depression, and 6% had severe symptoms of depression. Depression and reduced quality of life are an undetected and relevant burden affecting patients with lichen planus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
As the relationship between exposome factors and inflammatory skin diseases is gaining increasing attention, the objective of this study was to investigate dietary patterns among acne and rosacea ...patients and to establish the disease risk attributable to nutrition. In this cross-sectional, controlled study, patients’ dietary habits were assessed via subjective ratings of beneficial and trigger foods, followed by standardized food frequency surveys (FFS). Scores for disease-specific risk stratification based on dietary habits were proposed. Clinical assessments, dermatologic examinations, and laboratory analyses were performed. A total of 296 patients (acne group (AG) n = 120, control group (ACG) n = 32; rosacea group (RG) n = 105, control group (RCG) n = 39) were included. The significant impact of diet on disease severity was self-reported by 80.8% of the AG and 70.5% of the RG. Leading dietary triggers were found in both groups, while beneficial food items were identified more clearly by the AG. FFS revealed significant dietary differences between the AG, RG, and control groups. Disease-specific scores showed greater precision for acne (odds ratio 14.5 AG, 5.5 RG). The AG had higher insulin-like growth factor (IGF)-1 levels correlating with dairy intake (p = 0.006). Overall, this study underlines the influence of diet on acne and rosacea, providing valuable disease-specific scores for dietary risk stratification. Consuming vegetables, legumes, oily fish, olive oil, and nuts, and limiting meat, cheese, and alcohol appear to be beneficial for both acne and rosacea. Future studies can build on these data to further improve preventive and therapeutic strategies.
Oxidatively modified low-density lipoprotein (oxLDL) plays a key role in the initiation of atherosclerosis by increasing monocyte adhesion. The mechanism that is responsible for the oxLDL-induced ...atherogenic monocyte recruitment in vivo, however, still remains unknown. Oxidation of LDL generates lysophosphatidylcholine, which is the main substrate for the lysophosphatidic acid (LPA) generating enzyme autotaxin. We show that oxLDL requires endothelial LPA receptors and autotaxin to elicit CXCL1-dependent arterial monocyte adhesion. Unsaturated LPA releases endothelial CXCL1, which is subsequently immobilized on the cell surface and mediates LPA-induced monocyte adhesion. Local and systemic application of LPA accelerates the progression of atherosclerosis in mice. Blocking the LPA receptors LPA
1 and LPA
3 reduced hyperlipidemia-induced arterial leukocyte arrest and atherosclerosis in the presence of functional CXCL1. Thus, atherogenic monocyte recruitment mediated by hyperlipidemia and modified LDL crucially depends on LPA, which triggers endothelial deposition of CXCL1, revealing LPA signaling as a target for cardiovascular disease treatments.
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► Modified LDL-induced monocyte adhesion via CXCL1 requires endothelial LPA receptors ► Unsaturated LPA promotes CXCL1-dependent monocyte adhesion and atherogenesis ► Hyperlipidemia enhances monocyte recruitment via the LPA
1 and LPA
3 receptors ► Blocking LPA
1 and LPA
3 impairs atherosclerosis and lesional macrophage accumulation
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 cancers.
Background and objectives
Ocular rosacea is a special manifestation of rosacea with unknown etiology. Eye involvement in rosacea patients is surprisingly common; however, it is often underdiagnosed, ...resulting in inappropriate treatment. We aimed to provide an updated epidemiologic perspective on ocular rosacea in Germany to improve patient care.
Patients and methods
Data of 777 rosacea patients were assessed using a detailed online questionnaire regarding ocular and skin symptoms, previous dermatological and ophthalmological consults, presence of type 1 hypersensitivities, and Demodex testing. All data were statistically analyzed.
Results
Most patients reported ocular symptoms (399/777, 51.4%), including red eyes (179/399, 44.9%), itching (187/399, 46.9%), sty or chalazion (309/399, 77.4%), and dryness (108/399, 27.1%). Ocular rosacea was confirmed in 149/309 cases who consulted an ophthalmologist (45.3%). A total of 159/399 (39.8%) had no pre‐existing allergies. Eye involvement was significantly associated with the presence of skin symptoms (P < 0.05), impacting patients' general well‐being and overall treatment satisfaction. About half of Demodex‐positive patients (21/45, 46.7%) showed ocular symptoms.
Conclusions
Eye involvement in rosacea patients was common, often presenting with unspecific symptoms.
Human papilloma virus (HPV)-related cancers are global health challenge. Insufficient comprehension of these cancers has impeded the development of novel therapeutic interventions. Bioinformatics ...empowered us to investigate these cancers from new entry points.
DNA methylation data of cervical squamous cell carcinoma (CESC) and anal squamous cell carcinoma (ASCC) were analyzed to identify the significantly altered pathways. Through analyses integrated with RNA sequencing data of genes in these pathways, genes with strongest correlation to the TNM staging of CESC was identified and their correlations with overall survival in patients were assessed. To find a potential promising drug, correlation analysis of gene expression levels and compound sensitivity was performed.
experiments were conducted to validate these findings. We further performed molecular docking experiments to explain our findings.
Significantly altered pathways included immune, HPV infection, oxidative stress, ferroptosis and necroptosis. 10 hub genes in these pathways (PSMD11, RB1, SAE1, TAF15, TFDP1, CORO1C, JOSD1, CDC42, KPNA2 and NUP62) were identified, in which only CDC42 high expression was statistically significantly correlated with overall survival (Hazard Ratio: 1.6,
= 0.045). Afatinib was then screened out to be tested.
experiments exhibited that the expression level of CDC42 was upregulated in HaCaT/A431 cells transfected with HPV E6 and E7, and the inhibitory effect of afatinib on proliferation was enhanced after transfection. CDC42-GTPase-effector interface-EGFR-afatinib was found to be a stable complex with a highest ZDOCK score of 1264.017.
We identified CDC42 as a pivotal gene in the pathophysiology of HPV-related cancers. The upregulation of CDC42 could be a signal for afatinib treatment and the mechanism in which may be an increased affinity of EGFR to afatinib, inferred from a high stability in the quaternary complex of CDC42-GTPase-effector interface-EGFR-afatinib.
Highlights • UVB triggers inflammasome mediated IL-1β release by keratinocytes. • LL-37 enhances UV-induced IL-1β secretion by acting on the P2X7 receptor. • P2X7 receptor activation results in an ...increase in intracellular calcium concentrations. • IL-1β and LL-37 work synergistically to promote angiogenesis. • LL-37 augments the proinflammatory and proangiogenic effects of UVB.
Anal squamous cell carcinoma (SCC) is a rare cancer with increasing incidence. Infection with high-risk human papillomavirus (HPV) subtypes is the major cause for its development. We retrospectively ...analyzed tumor samples from 54 anal SCC patients for infection with a panel of 32 HPV subtypes in a PCR-based approach, determined the PD-L1 expression status, and correlated the findings with the clinical data and the survival of the patients. Forty-two patients (77.8%) were HPV-positive and harbored at least one carcinogenic HPV subtype. HPV16 was the most frequently detected (n = 39, 72.2%). Four patients were infected with multiple HPV subtypes. HPV infection was significantly more often detected in female than in male patients (90.3% vs. 60.9%, p = 0.018). Patients with PD-L1 positive tumors showed a significantly better median overall survival (OS) compared with patients with PD-L1 negative tumors (69.3 vs. 28.3 months, p = 0.006). The median OS was significantly different among the distinct tumor stages (p = 0.029). Sex, grade of differentiation, and HPV infection status did not influence the median OS. Furthermore, HPV infection status and PD-L1 expression were not correlated. A multivariate Cox regression analysis revealed that PD-L1 expression status was an independent prognostic marker for survival (p = 0.012).
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