Genome-wide DNA methylation of lesional and peri-lesional skin in vitiligo: a comparative and integrated analysis of multi-omics in Chinese population.

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. Subsequently, we compared the methylation and transcriptome characteristics of all skin samples, and the related genes were further studied using scRNA-seq data. Finally, validation was performed using an external dataset. We observed more DNA hypomethylated sites in patients with vitiligo. Further integrated analysis identified 264 DMEGs that were mainly functionally enriched in cell division, pigmentation, circadian rhythm, fatty acid metabolism, peroxidase activity, synapse regulation, and extracellular matrix. In addition, in the peri-lesional skin, we found that methylation levels of 102 DMEGs differed prior to changes in their transcription levels and identified 16 key pre-DMEGs (ANLN, CDCA3, CENPA, DEPDC1, ECT2, DEPDC1B, HMMR, KIF18A, KIF18B, TTK, KIF23, DCT, EDNRB, MITF, OCA2, and TYRP1). Single-cell RNA analysis showed that these genes were associated with cycling keratinocytes and melanocytes. Further analysis of cellular communication indicated the involvement of the extracellular matrix. The expression of related genes was verified using an external dataset. To the best of our knowledge, this is the first study to report a comprehensive DNA methylation profile of clinical vitiligo and peri-lesional skin. These findings would contribute to future research on the pathogenesis of vitiligo and potential therapeutic strategies.

DNA methylation profiling and integrative multi-omics analysis of skin samples reveal important contribution of epigenetics and immune response in the pathogenesis of acne vulgaris.

The regulatory effect of DNA methylation on the pathogenesis of acne vulgaris is completely unknown. Herein we analyzed the DNA methylation profile in skin samples of acne vulgaris and further integrated it with gene expression profiles and single-cell RNA-sequencing data. Finally, 31,134 differentially methylated sites and 770 differentially methylated and expressed genes (DMEGs) were identified. The multi-omics analysis suggested the importance of DNA methylation in inflammation and immunity in acne. And DMEGs were verified in an external dataset and were closely related to early inflammatory acne. Additionally, we conducted experiments to verify the mRNA expression and DNA methylation level of DMEGs. This study supports the significant contribution of epigenetics to the pathogenesis of acne vulgaris and may provide new ideas for the molecular mechanisms of and potential therapeutic strategies for acne vulgaris.

Prevalence and risk factors of acne scars in patients with acne vulgaris.

BACKGROUND: Acne scar is a persistent complication of acne vulgaris. However, the prevalence and risk factors are still unclear. This study aimed to assess the global prevalence and risk factors of acne scars in patients with acne. MATERIALS AND METHODS: A systematic search of published studies in three databases was performed and the meta-analyses were conducted. RESULTS: Finally, we included 37 studies involving 24 649 acne patients. And, the pooled prevalence of acne scars in these patients was 47% (95% confidence interval [CI]: 38-56%). Besides, the differences in prevalence were observed based on the subgroup analysis for age, gender, acne severity, source of patients, and so on. Subsequently, we quantified the relationship of three risk factors with acne scars: male gender (odds ratio [OR]: 1.58, 95% CI: 1.19-2.09), positive family history of acne (OR: 2.73, 95% CI: 1.26-5.91), and acne severity (OR for moderate acne: 2.34, 95% CI: 1.54-3.57; OR for severe acne: 5.51, 95% CI: 2.45-12.41). CONCLUSION: Herein, we found that 47% of acne patients suffered from acne scars and identified three risk factors: male gender, positive family history of acne, and acne severity. In order to reduce acne scarring, attention and effective therapy early in the course of acne is important.

Acne and risk of mental disorders: A two-sample Mendelian randomization study based on large genome-wide association data.

Background: Despite a growing body of evidence that acne impacts mental disorders, the actual causality has not been established for the possible presence of recall bias and confounders in observational studies. Methods: We performed a two-sample Mendelian randomization (MR) analysis to evaluate the effect of acne on the risk of six common mental disorders, i.e., depression, anxiety, schizophrenia, obsessive-compulsive disorder (OCD), bipolar disorder, and post-traumatic stress disorder (PTSD). We acquired genetic instruments for assessing acne from the largest genome-wide association study (GWAS) of acne (N = 615,396) and collected summary statistics from the largest available GWAS for depression (N = 500,199), anxiety (N = 17,310), schizophrenia (N = 130,644), OCD (N = 9,725), bipolar disorder (N = 413,466), and PTSD (N = 174,659). Next, we performed the two-sample MR analysis using four methods: inverse-variance weighted method, MR-Egger, weighted median, and MR pleiotropy residual sum and outliers. Sensitivity analysis was also performed for heterogeneity and pleiotropy tests. Results: There was no evidence of a causal impact of acne on the risk of depression [odds ratio (OR): 1.002, p = 0.874], anxiety (OR: 0.961, p = 0.49), OCD (OR: 0.979, p = 0.741), bipolar disorder (OR: 0.972, p = 0.261), and PTSD (OR: 1.054, p = 0.069). Moreover, a mild protective effect of acne against schizophrenia was observed (OR: 0.944; p = 0.033). Conclusion: The increased prevalence of mental disorders observed in patients with acne in clinical practice was caused by modifiable factors, and was not a direct outcome of acne. Therefore, strategies targeting the elimination of potential factors and minimization of the occurrence of adverse mental events in acne should be implemented.

Association of Behçet's disease with the risk of metabolic syndrome and its components: a systematic review and meta-analysis.

The present meta-analysis aimed to elucidate the association of Behçet's disease (BD) with the risk of metabolic syndrome (MetS) and its components. Observational cohort studies were searched from the Embase, Web of Science, Medline, and Cochrane Library databases. The primary outcome was the association of BD with the risk of MetS and its relevant components. Effect estimates with odds ratios (ORs) were pooled using either the random-effects or fixed-effects models, according to heterogeneity. Leave-one-out sensitivity analyses were used to determine the stability of the results. Twenty-three studies, comprising 42,834 patients with BD, were included. Overall, a significant association between BD and the risk of MetS was found (pooled OR 2.26; 95% confidence interval [CI] 1.61-3.17; P < 0.0001). Among the components of MetS, significant associations were found between BD and diabetes mellitus (OR 1.21; 95% CI 1.10-1.33; P < 0.0001), BD and hypertension (OR 1.39; 95% CI 1.13-1.70; P = 0.002), and BD and dyslipidemia (OR 1.21; 95% CI 1.01-1.45; P = 0.04). Our study indicated an association between BD and the risk of MetS and some of its components (diabetes mellitus, hypertension, and dyslipidemia). Physician should consider these associations so that specific treatments are available for patients with comorbidities. Moreover, patients with BD should regularly monitor their blood pressure, fasting plasma glucose, and blood lipid levels.

Association of the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio with Gastrointestinal Involvement of Immunoglobulin a Vasculitis.

Objective: To illustrate the association of monocyte to high-density lipoprotein cholesterol ratio (MHR) and other serum indicators with the pathogenesis and prognosis of immunoglobulin A vasculitis (IgAV) patients in different subgroups. Methods: A total of 158 adult patients and 113 healthy controls were enrolled, and the clinical presentation and laboratory indexes were comprehensively assessed. Results: IgAV patients show significantly elevated levels of inflammatory parameters and lipid profiles compared to healthy controls (P < 0.05). Higher levels of the MHR and other normal inflammatory indicators were found in patients with Gastrointestinal (GI) involvement compared to other subgroups. And in group with GI involvement, significantly higher white blood cell (WBC), neutrophil, complement 4 (C4), NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) levels and lower levels of apolipoprotein-a (Apo-a) were observed. Their correlation analysis demonstrated positive results between MHR level and white blood cell (WBC) count (r = 0.416, P = 0.034), D-Dimer (r = 0.464, P = 0.026) and monocyte (r = 0.947, P < 0.001). And the time until first remission of skin purpura was shown positively correlated with their age (r = 0.456, P = 0.043), C-reactive protein (CRP) level (r = 0.641, P = 0.018), D-Dimer level (r = 0.502, P = 0.040) while negatively correlated with albumin (Alb) level (r=-0.626, P = 0.003) and low-density lipoprotein (LDL) level (r=-0.478, P = 0.033). Conclusion: Our study suggests that those biomarkers represented for inflammatory responses, lipid profile and immunological functions have significant differences in the subgroups of adult IgAV patients. In addition, we also found that MHR level may serve as a potential biomarker for the pathogenesis and prognosis of IgAV patients with GI involvement.

Transcriptome sequencing and gene expression analysis revealed early ovule abortion of Paeonia ludlowii.

BACKGROUND: Paeonia ludlowii (Stern & G. Taylor D.Y. Hong) belongs to the peony group of the genus Paeonia in the Paeoniaceae family and is now classified as a "critically endangered species" in China. Reproduction is important for this species, and its low fruiting rate has become a critical factor limiting both the expansion of its wild population and its domestic cultivation. RESULTS: In this study, we investigated possible causes of the low fruiting rate and ovule abortion in Paeonia ludlowii. We clarified the characteristics of ovule abortion and the specific time of abortion in Paeonia ludlowii, and used transcriptome sequencing to investigate the mechanism of abortion of ovules in Paeonia ludlowii. CONCLUSIONS: In this paper, the ovule abortion characteristics of Paeonia ludlowii were systematically studied for the first time and provide a theoretical basis for the optimal breeding and future cultivation of Paeonia ludlowii.

Hematological parameters in patients with acnes.

OBJECTIVE: To compare complete blood count (CBC) parameters and inflammatory factors in the patients with different grade of acne vulgaris and healthy controls. METHODS: A total of 20 patients were enrolled in this study. Patients were divided into mild group and moderate-to-severe group based on the acne severity, and compared to controls. Inflammatory factors (TNF-α, IL-6, IL-8, and IL1-α) detected by ELISA and complete blood count parameters (MPV, NLR, dNLR, PLR, LMR, and SII) obtained by routine blood tests were compared among the three group. RESULTS: All CBC parameters were not significantly elevated in patients with acne compared to healthy controls. However, the present studies have found that the inflammatory factors in acne patients were significantly elevated relative to healthy controls, and increase with the acne grade. CONCLUSIONS: Inflammatory factors are convenient parameters to show inflammatory response to acne vulgaris, and may be a new clinical method for judging the acne grades of objectively. Considering the use of antibiotic, we believe that this metric worth further study.

An Intelligent Diagnostic Model for Melasma Based on Deep Learning and Multimode Image Input.

INTRODUCTION: The diagnosis of melasma is often based on the naked-eye judgment of physicians. However, this is a challenge for inexperienced physicians and non-professionals, and incorrect treatment might have serious consequences. Therefore, it is important to develop an accurate method for melasma diagnosis. The objective of this study is to develop and validate an intelligent diagnostic system based on deep learning for melasma images. METHODS: A total of 8010 images in the VISIA system, comprising 4005 images of patients with melasma and 4005 images of patients without melasma, were collected for training and testing. Inspired by four high-performance structures (i.e., DenseNet, ResNet, Swin Transformer, and MobileNet), the performances of deep learning models in melasma and non-melasma binary classifiers were evaluated. Furthermore, considering that there were five modes of images for each shot in VISIA, we fused these modes via multichannel image input in different combinations to explore whether multimode images could improve network performance. RESULTS: The proposed network based on DenseNet121 achieved the best performance with an accuracy of 93.68% and an area under the curve (AUC) of 97.86% on the test set for the melasma classifier. The results of the Gradient-weighted Class Activation Mapping showed that it was interpretable. In further experiments, for the five modes of the VISIA system, we found the best performing mode to be "BROWN SPOTS." Additionally, the combination of "NORMAL," "BROWN SPOTS," and "UV SPOTS" modes significantly improved the network performance, achieving the highest accuracy of 97.4% and AUC of 99.28%. CONCLUSIONS: In summary, deep learning is feasible for diagnosing melasma. The proposed network not only has excellent performance with clinical images of melasma, but can also acquire high accuracy by using multiple modes of images in VISIA.

Effect of 30% Supramolecular Salicylic Acid Peel on Skin Microbiota and Inflammation in Patients with Moderate-to-Severe Acne Vulgaris.

INTRODUCTION: Thirty-percent supramolecular salicylic acid (SSA), a modified salicylic acid preparation, is a safe and effective treatment for moderate-to-severe acne vulgaris (AV). However, its mechanism of action remains unclear. We aimed to analyze the role of 30% SSA peels on skin microbiota and inflammation in patients with moderate-to-severe AV. METHODS: A total of 28 patients were enrolled and received 30% SSA peels biweekly for 2 months. The Global Acne Grading System (GAGS) score, skin water content, transepidermal water loss (TEWL), pH, and sebum levels were assessed. Skin microbial samples and perilesional skin biopsies were obtained at the onset and 2 weeks after treatment completion. Samples were characterized using a high-throughput sequencing approach targeting a portion of the bacterial 16S ribosomal RNA gene. RESULTS: After treatment, patients showed a significant improvement in their GAGS score and skin barrier indicators (P < 0.05). The GAGS score was positively associated with both the sebum concentration (R = 0.3, P = 0.027) and pH (R = 0.39, P = 0.003). Increased expression of caveolin-1 and decreased expression of interleukin (IL)-1a, IL-6, IL-17, transforming growth factor beta, and toll-like receptor 2 were observed in the skin tissue after treatment. The richness and evenness of the cutaneous microbiome decreased after treatment and the Staphylococcus proportion decreased significantly (P < 0.05), whereas the Propionibacterium proportion tended to decrease (P = 0.066). CONCLUSIONS: On the basis of analyses of the skin barrier and microbiota, we speculate that the 30% SSA peel may have a therapeutic effect in patients with moderate-to-severe AV by improving the skin microenvironment and modulating the skin microbiome, thus reducing local inflammation.

Efficacy of topical steroids in preventing radiation dermatitis: A systematic review and meta-analysis.

To evaluate the relative efficacy of topical steroids in preventing radiation dermatitis (RD). Multiple databases including Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), China Biological Medicine (SinoMed), and Wanfang Database were searched for randomized controlled trials (RCTs) of RD prevention in patients with cancer from inception to November 26, 2021, followed by an update on June 1, 2021. Six RCTs evaluating the efficacy of topical steroids in preventing RD in a total of 661 patients with cancer were included. RD incidence was lower with topical steroids compared with placebo at week 3 (relative risk [RR] = 0.68, 95% confidence interval [CI]: 0.31-1.50) and at radiation therapy (RT) completion (RR = 0.97, 95% CI: 0.93-1.00). Topical steroids demonstrated a less risk of developing dermatitis of Radiation Therapy Oncology Group (RTOG) grades 2 and 3 at the completion of RT (RR = 0.66, 95% CI: 0.55-0.80 and RR = 0.54, 95% CI: 0.38-0.77, respectively). However, topical steroids did not reduce RTOG grades 1 and 2 dermatitis at week 3(RR = 0.73, 95% CI: 0.45-1.14 and RR = 0.66, 95% CI: 0.27-1.60, respectively). Notably, the use of topical steroids did not decrease RD incidence when patients received combined chemotherapy (RR = 0.60, 95% CI: 0.42-0.86), and an obvious reduction in the incidence of RD at RT completion was found when patients used the topical steroids twice-daily (RR = 0.66, 95% CI: 0.47-0.93, P = 0.02). Topical steroids reduced RD incidence in patients receiving RT. Thus, twice-daily topical steroids may be recommended for patients at the beginning of RT.

Association between frontal fibrosing Alopecia and Rosacea: Results from clinical observational studies and gene expression profiles.

Background: In recent years, frontal fibrosing alopecia (FFA), a type of scarring alopecia, has attracted increasing attention. Several studies have reported the frequent occurrence of rosacea in FFA; however, the association between FFA and rosacea and the underlying pathogenesis have not been thoroughly clarified. Thus, this study aimed to quantify these relationships and investigate their shared molecular mechanisms. Methods: We evaluated the association between FFA and rosacea by analyzing clinical data from nine observational studies. We then analyzed the gene expression profiles of FFA and rosacea. First, differential expression analysis and weighted gene co-expression network analysis were used to identify the common differentially expressed genes (DEGs). Later, we conducted a functional enrichment analysis and protein-protein interaction network and used seven algorithms to identify hub genes. Then, we performed a correlation analysis between the hub genes and the gene set variation analysis scores of common pathways in the gene set enrichment analysis (GSEA). The results were validated using different datasets. Finally, transcription factors were predicted and verified, and CIBERSORT and single-sample GSEA were used to estimate the infiltrating immune cells. Results: Patients with FFA had significantly higher odds for rosacea (pooled odds ratio [OR], 2.46; 95% confidence interval [CI], 1.78-3.40), and the pooled prevalence of rosacea in patients with FFA was 23% (95% CI, 14-23%). Furthermore, we identified 115 co-DEGs and 13 hub genes (CCR5, CCL19, CD2, CD38, CD83, CXCL8, CXCL9, CXCL10, CXCL11, CXCR4, IRF1, IRF8, and PTPRC). Seven pathways showed a high correlation with these hub genes. In addition, one TF, STAT1, was highly expressed in both diseases, and the results of the immune infiltration analysis indicated the importance of M1 macrophages and effector memory CD8+ T cells. Conclusion: This study contributes to the understanding of the relationship between FFA and rosacea, and based on the hub genes, we reveal the potential pathologies shared by the two diseases. This finding provides new insights of underlying molecular mechanisms and it may inspire future research on this comorbidity.

Abortion occurs during double fertilization and ovule development in Paeonia ludlowii.

Paeonia ludlowii (Stern & Taylor) D.Y.Hong, an endangered species, is indigenous to Tibet, China and propagated only by seed under natural conditions. Its natural reproduction is constrained by low fecundity. Excess seed abortion is a key factor restricting its natural reproduction, cultivation, introduction, and protection. Understanding the specific origin and occurrence of aborted ovules is important for the protection of offspring. Using serial sectioning analysis, we studied the process of pollination and fertilization of P. ludlowii and examined the characteristics of aborted ovules, developmental differences after flowering of normal and aborted ovules, and their ratios at different positions in P. ludlowii ovaries. During pollination, fertilization, and seed development, ovule abortion was frequent, with a random abortion position. There were three types of abortion, namely, abnormal pistil, sterile ovules, and embryo and endosperm abortions. Of these, embryo and endosperm abortions could be divided into early abortion and middle abortion. The early aborted ovules stopped growing on day 12, the endoblast and endosperm in the embryo sac aborted gradually. Furthermore, the shape of the embryo sac cavity changed. The volume of aborted ovules was significantly different from that of fertile ovules. At ripening, the external morphology of different types of aborted seeds was significantly different. The possible reasons for the abortion of the ovules are also discussed.