Falls, fracture and frailty risk in multiple sclerosis: a Mendelian Randomization study to identify shared genetics.

INTRODUCTION: Patients with multiple sclerosis (MS) commonly present musculoskeletal disorders characterized by lower bone mineral density (BMD) and muscle weakness. However, the underlying etiology remains unclear. Our objective is to identify shared pleiotropic genetic effects and estimate the causal relationship between MS and musculoskeletal disorders. MATERIALS AND METHODS: We conducted linkage disequilibrium score regression (LDSR), colocalization, and Mendelian randomization (MR) analyses using summary statistics from recent large-scale genome-wide association studies (GWAS), encompassing MS, falls, fractures, and frailty. Additional MR analyses explored the causal relationship with musculoskeletal risk factors, such as BMD, lean mass, grip strength, and vitamin D. RESULTS: We observed a moderate genetic correlation between MS and falls (RG = 0.10, P-value = 0.01) but not between MS with fracture or frailty in the LDSR analyses. MR revealed MS had no causal association with fracture and frailty but a moderate association with falls (OR: 1.004, FDR q-value = 0.018). We further performed colocalization analyses using nine SNPs that exhibited significant associations with both MS and falls in MR. Two SNPs (rs7731626 on ANKRD55 and rs701006 on OS9 gene) showed higher posterior probability of colocalization (PP.H4 = 0.927), suggesting potential pleiotropic effects between MS and falls. The nine genes are associated with central nervous system development and inflammation signaling pathways. CONCLUSION: We found potential pleiotropic genetic effects between MS and falls. However, our analysis did not reveal a causal relationship between MS and increased risks of falls, fractures, or frailty. This suggests that the musculoskeletal disorders frequently reported in MS patients in clinical studies are more likely attributed to secondary factors associated with disease progression and treatment, rather than being directly caused by MS itself.

Clinical and Pathological Features of Pilomatrixoma in Children: A Retrospective Study.

INTRODUCTION: Pilomatrixoma is a benign skin neoplasm that is common in children and is often misdiagnosed. This study aimed to summarize the clinical and pathological features of pilomatrixoma in children. METHODS: Data on demographic information, clinical and pathological features, diagnosis, and treatment of 171 patients with pilomatrixoma from Shenzhen Baoan Women's and Children's Hospital were collected and analyzed retrospectively. RESULTS: The mean age of the patients was 5.7 (standard deviation [SD] = 3.9) years old, and there were 2 age peaks (≤1 year old, 5-11 years old) and 2 age valleys (2-4 years old, ≥12 years old). The mean disease course was 9.3 (SD = 14.1) months, 69.0%, 86.5%, and 95.3% of the patients' disease course in 6 months, 12 months, and 24 months, respectively. The mean tumor volume was 0.6 (SD = 1.0) cm3, and 81.3% of the patients' tumor volume ≤1.0 cm3. Tumors were distributed sequentially in the head and neck (77.2%), upper limbs (12.9%), trunk (7.6%), and lower limbs (2.3%). The correct rates of clinical and ultrasonic diagnosis were 50.9% and 38.6%, respectively. The two most common pathological features of pilomatrixoma were shadow cells (99.4%) and basaloid cells (94.7%). There were no significant differences in age, disease course, or tumor volume between the male and female patients (p > 0.05). The age and tumor volume of the patients in different body parts were significantly different (P1 = 3.10E-05 and P2 = 5.60E-05, respectively). The correlation between the disease course and tumor volume was positively significant (p ≤ 0.05). There was a significant correlation between the disease course and tumor volume in patients with tumors at upper limbs (p = 0.03). CONCLUSION: The age of children with pilomatrixoma presented 2 peaks and 2 valleys. Most patients had disease courses in 24 months and with tumor volumes ≤1.0 cm3. The correct rates of clinical and ultrasonic diagnosis were relatively low. The head and neck were the most common distribution sites of pilomatrixoma, and shadow cells and basaloid cells were the most common pathological features. The tumor volume was positively correlated with disease course in patients with pilomatrixoma.

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

OBJECTIVE: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. METHODS: We built gene expression predictive models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. RESULTS: TWAS identified 171 genes for SLE (p<1.0×10-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. CONCLUSIONS: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. METHODS: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. RESULTS: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10-8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=-0.242) and non-albumin protein (rg=0.238). CONCLUSION: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Cold atmospheric plasma promotes different types of superficial skin erosion wounds healing.

Superficial skin erosion wounds are very common in the clinic, and conventional treatments are not always effective; thus, effective and novel therapy is needed. Cold atmospheric plasma (CAP) has been recognised as a promising approach to wound healing. The purpose of this study is to show the potential clinical application of CAP for the healing of different kinds of superficial skin wounds. Seven patients with different kinds of superficial skin wounds (two patients with pyoderma gangrenosum, two patients with trauma would, one patient with giant genital wart, one patient with diabetic foot, and one patient with chronic eczema) were recruited to this study. All patients accepted and received CAP treatment every other day till the wound healed. The expected results were complete wound healing after CAP treatment. All patients achieved complete wound healing after several rounds (range from two to eight) of CAP treatment, and there was no side effect observed. CAP may provide a new and effective choice to solve the problem of the healing of superficial wounds that are not only caused by trauma but also because of eczema. CAP has certain value in the treatment of superficial skin diseases in the future.

Integration of expression quantitative trait loci and pleiotropy identifies a novel psoriasis susceptibility gene, PTPN1.

BACKGROUND: Psoriasis is a common inflammatory skin disease, whereas schizophrenia is a psychiatric disorder with substantial comorbidity. Although these two disorders manifest with apparently unrelated phenotypes, there is some evidence suggesting that they share common genetic factors. METHODS: We implemented a genetic analysis incorporating pleiotropy and annotation to genome-wide association summary statistics data for approximately 120 000 psoriasis and schizophrenia samples, as well as whole blood expression quantitative trait loci in 5311 samples. RESULTS: We observed a significant pleiotropic effect between psoriasis and schizophrenia (p = 5.92 × 10-43 ). We characterized an enrichment of whole blood expression quantitative trait loci in genome-wide association data for psoriasis and schizophrenia (q1 /q0  > 1.5, p < 10-77 ) and we revealed that common variants for both diseases were more likely to confer expression quantitative trait loci effects (q1 /q0  = 4.197, SE = 0.183). Through joint analysis of the associations in the combined psoriasis and schizophrenia data set, we identified a potential susceptibility PTPN1 gene for psoriasis, which may affect the risk of psoriasis through modulation of the function of TYK2 kinase. CONCLUSIONS: The results of the present study highlight the expression quantitative trait loci enrichment and pleiotropy in psoriasis and schizophrenia, and also suggest a possible key role of the PTPN1 gene in the etiology of psoriasis.

Identification of cell types, tissues and pathways affected by risk loci in psoriasis.

Many common variants have been found associated with the risk of psoriasis, but the underlying mechanism is still largely unknown, mostly owing to the difficulty in dissecting the mechanism of each variant using representative cell type and tissue in biological experiments. We applied an integrative method SNPsea which has been developed by investigators in Broad, to identify the most relevant cell types, tissues, and pathways to psoriasis by assessing the condition specificity affected by psoriasis genome-wide association studies-implicated genes. We employed this software on 89 single-nucleotide polymorphisms with genome-wide significance in Han Chinese and Caucasian populations. We found significant evidence for peripheral blood CD56 + NK cells (P = 1.30 × 10(-7)), Langerhans cells (P = 4.96 × 10(-6)) and CD14+ monocytes (P < 4.80 × 10(-5)) in psoriasis. We suggested that the DNase I hypersensitivity sites in CD14+ cells were active in psoriasis (P = 2.20 × 10(-16)). In addition, we discovered that biotic stimulus response, cytokine production and NF-κB pathways were significantly activated in psoriasis (P < 1.00 × 10(-5)). In conclusion, we found several innate immune cells and immune pathways in psoriasis that will help guide biological experiments for psoriasis risk variants in future.

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population.

BACKGROUND: Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. METHODS: We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. RESULTS: We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10-8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10-16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. LIMITATIONS: Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. CONCLUSION: We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.

Four genetic variants interact to confer susceptibility to atopic dermatitis in Chinese Han population.

Atopic dermatitis is a chronic inflammatory skin disease and is affected by environmental and genetic factors. Gene-gene/environment interactions are strongly believed to contribute to the genetic risk of common diseases. A number of gene-environment interactions of atopic dermatitis were performed. However, there are few comprehensive investigations on the gene-gene (or genetic variants) interactions for atopic dermatitis. We explored the association model of 6 single nucleotide polymorphisms (SNPs) which were most significant (P < 10E-05) in our previous genome wide association study (GWAS) for atopic dermatitis, and search for the possible genetic variant interactions based on the previous GWAS data using Generalized Multifactor Dimensionality Reduction and Plink 1.07 in the combined sample of 4,636 cases and 13,559 controls. The most significant associated evidence was observed under dominant model for SNPs rs3126085, rs12085366, and rs7701890, recessive model for SNP rs17173197, and additive model for SNPs rs2393903 and rs6010620. Three significant pair-way interactions were observed, including PRKAG2 and FLG SNPs (rs17173197 × rs3126085, P combined = 1.11E-15), PRKAG2 and TMEM232-SLC25A46 SNPs (rs17173197 × rs7701890, P combined = 2.22E-15), PRKAG2 and TNFRSF6B-ZGPAT SNPs (rs17173197 × rs6010620, P combined = 6.66E-16). Besides, a three-way significant interaction among PRKAG2, TMEM232-SLC25A46 and TNFRSF6B-ZGPAT SNPs (rs17173197 × rs7701890 × rs6010620, P combined = 5.99E-15) was observed in this study. These four genetic variant interactions confer susceptibility to atopic dermatitis, and highlight the genetic variant interactions in the etiology of atopic dermatitis in Chinese Han population.

Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase (MVK) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. METHODS: The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. RESULTS: An average of 1.35×10(5) variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. CONCLUSIONS: The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.

Role of T cells in liver metastasis.

The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.

Pleiotropic Genetic Effects between Multiple Sclerosis and Musculoskeletal Traits.

Background: Musculoskeletal disorders were commonly reported in patients with multiple sclerosis. However, the underlying etiology linking Multiple Sclerosis (MS) and musculoskeletal disorders is not well studied. With large-scale Genome-Wide Association Studies (GWAS) publicly available, we conducted genetic correlation analysis to identify shared pleiotropic genetic effects between MS and musculoskeletal traits. We also conducted Mendelian Randomization (MR) to estimate the causal relation between MS and increased risks of musculoskeletal disorders. Methods: Linkage Disequilibrium Score Regression (LDSR) analysis was performed to estimate heritability and genetic correlation. Univariable, multivariable, and bidirectional MR analyses were conducted to estimate the causal relation. These analyses were done by utilizing the recent GWAS summary statistics of MS, fracture, frailty, falls, and several musculoskeletal risk factors, including bone mineral density, lean mass, grip strengths, and vitamin D. Results: LDSR analysis showed a moderate genetic correlation of MS with falls (RG=0.10, p=0.01) but not with fracture and frailty. Genetic variants (rs13191659) in LINC00240 gene which is associated with iron status biomarkers was found to be associated with both MS and falls. In MR analyses after excluding outlier SNPs with potential pleiotropic effects and correcting for multiple testing, MS presented no causal association with fracture and frailty but a minimal association with falls. Falls showed causally increased risks of fracture and frailty. Conclusion: Our study suggests a potential genetic correlation with shared pleiotropic genetic effects between MS and falls. However, we didn't find evidence to support the causal relation between MS and increased risks of falls, fracture, and frailty.

The crucial roles of m6A RNA modifications in cutaneous cancers: Implications in pathogenesis, metastasis, drug resistance, and targeted therapies.

N6-methyladenosine (m6A) is the most abundant internal modification on RNA. It is a dynamical and reversible process, which is regulated by m6A methyltransferase and m6A demethylase. The m6A modified RNA can be specifically recognized by the m6A reader, leading to RNA splicing, maturation, degradation or translation. The abnormality of m6A RNA modification is closely related to a variety of biological processes, especially the occurrence and development of tumors. Recent studies have shown that m6A RNA modification is involved in the pathogenesis of skin cancers. However, the precise molecular mechanisms of m6A-mediated cutaneous tumorigenesis have not been fully elucidated. Therefore, this review will summarize the biological characteristics of m6A modification, its regulatory role and mechanism in skin cancers, and the recent research progress of m6A-related molecular drugs, aiming to provide new ideas for clinical diagnosis and targeted therapy of cutaneous cancers.

Clinical and histopathological characteristics, diagnosis and treatment, and comorbidities of Bowen's disease: a retrospective study.

Background: Bowen's disease (BD) is a slow-growing precancerous skin condition, often concurrent with other diseases, with a high misdiagnosis rate. Previous studies show that patients with BD in different populations have differentiated characteristics. Materials and methods: A retrospective study was conducted in a tertiary hospital in Shenzhen, China. Data about demographic information, diagnosis and treatment, clinical and pathological characteristics, and comorbidities of 50 patients with BD were collected and analyzed. Results: Clinical data of onset age and disease course of 43 patients with BD were available, the average onset age of male and female patients are 55.1 (standard deviation (SD) = 15.29) and 58.2 (SD = 15.59) years old, respectively; the average disease course of male and female patients are 25.3 (SD = 28.63) and 33.9 (SD = 49.65) months, respectively. The onset age (p = 0.52) and disease course (p = 0.49) between male and female patients are not significantly different. Interestingly, there is a negative correlation between onset age and disease course (r = -0.245, p = 0.11). The correct rate of clinical diagnosis is relatively low (54.00%); Some patients with BD are misdiagnosed as Bowenoid papulosis (10.00%), actinic keratosis (8.00%), basal cell carcinoma (8.00%), seborrheic keratosis (6.00%), and pigmented naevus (4.00%). Trunk and limbs are the most common distribution sites of BD lesions, and 94.00% patients with BD are treated with surgical resection; 66.00% patients with BD had comorbidities, including skin diseases (48.48%), cardiovascular diseases (39.39%), gastrointestinal diseases (30.30%), respiratory diseases (27.27%), and tumors (18.18%). The most commonly observed histopathological characteristics of BD are squamous-cell hyperplasia (86.00%), disordered maturation with atypical keratinocytes (74.00%), atypical mitoses (60.00%), hyperkeratosis with hypokeratosis (48.00%), dermal inflammatory cell infiltration (36.00%), and koilocytosis (22.00%). Conclusion: BD often occurs in middle-aged and elderly people and is easily misdiagnosed. The onset age and disease course of patients with BD are not significantly different between males and females, whereas there is a negative correlation between the onset age and disease course. BD is more likely to occur in trunk and limbs in the Chinese population, and most patients with BD are concurrent with comorbidities.

Roles of AIM2 Gene and AIM2 Inflammasome in the Pathogenesis and Treatment of Psoriasis.

Psoriasis is an immune-mediated chronic inflammatory skin disease caused by a combination of environmental incentives, polygenic genetic control, and immune regulation. The inflammation-related gene absent in melanoma 2 (AIM2) was identified as a susceptibility gene for psoriasis. AIM2 inflammasome formed from the combination of AIM2, PYD-linked apoptosis-associated speck-like protein (ASC) and Caspase-1 promotes the maturation and release of inflammatory cytokines such as IL-1ß and IL-18, and triggers an inflammatory response. Studies showed the genetic and epigenetic associations between AIM2 gene and psoriasis. AIM2 gene has an essential role in the occurrence and development of psoriasis, and the inhibitors of AIM2 inflammasome will be new therapeutic targets for psoriasis. In this review, we summarized the roles of the AIM2 gene and AIM2 inflammasome in pathogenesis and treatment of psoriasis, hopefully providing a better understanding and new insight into the roles of AIM2 gene and AIM2 inflammasome in psoriasis.

Cognitive Process of Psoriasis and Its Comorbidities: From Epidemiology to Genetics.

Psoriasis (PsO) is a chronic inflammatory skin disease that affects approximately 2% of the population all over the world. Comorbidities of PsO have increasingly garnered more interest in the past decades. Compared with the normal population, the incidences of comorbidities are higher among patients with PsO. In the last 20 years, researchers have focused on studying the genetic components of PsO, and genetic associations between PsO and its comorbidities were elucidated. This review provides an in-depth understanding and summarization of the connection between PsO and its comorbidities from the perspectives of epidemiology and genetics. Further understanding of PsO and its comorbidities will promote research on the pathogenesis, drug development, novel therapy methods, and personalized and precision treatment of PsO and its comorbidities.

MiR-193b-3p-ERBB4 axis regulates psoriasis pathogenesis via modulating cellular proliferation and inflammatory-mediator production of keratinocytes.

Psoriasis is an auto-inflammatory skin disease characterized by abnormal activation of epidermal keratinocytes, aberrant neovascularization, and dysregulation of immune cells. MicroRNAs are small non-coding RNAs that mainly function in the post-transcriptional regulation of gene expression. Recently, accumulating evidence has demonstrated that expression of microRNAs is dysregulated in psoriasis patients and microRNAs play key roles in psoriasis pathogenesis. Downregulation of miR-193b-3p has been identified to be associated with psoriasis development. However, the precise functions and action mechanisms of miR-193b-3p in psoriasis pathogenesis remain unclear. In this study, we confirmed the downregulation of miR-193b-3p in psoriasis patients, psoriasis-like inflammatory cellular models, and an imiquimod (IMQ) -induced mouse model. A negative correlation was found between miR-193b-3p level and patient Psoriasis Area and Severity Index (PASI) score. Furthermore, miR-193b-3p suppressed proliferation, inflammatory-factor secretion, and the STAT3 and NF-κB signaling pathways in keratinocytes. Importantly, intradermal injection of agomiR-193b-3p blocked, whereas antagomiR-193b-3p augmented, the psoriasis-like inflammation in the IMQ-induced mouse model. Bioinformatics analysis and the dual-luciferase reporter assay showed that miR-193b-3p targets ERBB4 3' untranslated region (UTR). In addition, ERBB4 induced proliferation, inflammatory-factor production, and the STAT3 and NF-κB pathways in keratinocytes. Most importantly, forced expression of ERBB4 could attenuate the effects of miR-193b-3p in keratinocytes, indicating that miR-193b-3p inhibits keratinocyte activation by directly targeting ERBB4. In conclusion, our findings demonstrated that the miR-193b-3p-ERBB4 axis underlies the hyperproliferation and aberrant inflammatory-factor secretion of psoriatic keratinocytes, providing a novel, microRNA-related causal mechanism and a potential therapeutic target in psoriasis.

Dermoscopic Features Summarization and Comparison of Four Types of Cutaneous Vascular Anomalies.

Objective: Dermoscopic features of cutaneous vascular anomalies have been reported, but the described features currently known are limited and not well-understood. The aim of this study is to comprehensively summarize and compare the dermoscopic features of the four different types of cutaneous vascular anomalies [infantile hemangiomas (IH), cherry angioma (CA), angiokeratomas (AK), and pyogenic granuloma (PG)] in the Chinese Han population. Materials and Methods: Dermoscopic features of 31 IH, 172 CA, 31 AK, and 45 PG were collected based on the contact non-polarized mode of dermoscopy at 20-fold magnification. Dermoscopic features including background, lacunae, vessel morphology and distribution were collected and summarized. Additionally, we compared these features by age stage, gender, and anatomical locations in CA. Results: The dermoscopic features of IH included the red lacunae, red/red-blue/red-white backgrounds, and vessel morphology such as linear curved vessels, serpiginous vessels, coiled vessels. For CA, the lacunae appeared reddish brown to reddish blue or only red. In terms of vascular morphology, serpentine vessels, coiled vessels, looped vessels, and curved vessels could be seen in the lesions. A few lesions were black or presented with a superficial white veil. There were statistical differences in red background (P = 0.021), unspecific vessel distribution (P = 0.030), black area (P = 0.029), and white surface (P = 0.042) among different age groups. Red-brown lacunae (P = 0.039), red-blue (P = 0.013), red-white background (P = 0.015), black area (P = 0.016), and white surface (P = 0.046) were of statistical difference in terms of the locations of lesions. Lacunae were also observed in AK, which presented with red, dark purple, dark blue, black. Global dermoscopic patterns that were characterized by a homogeneous area were obvious in all PG lesions, among which 30 (66.7%) were red-white and 15 (33.3%) were red. As for local features, "white rail" lines were detected in 19 (42.2%) lesions and white collarette was seen in 34 (75.6%) lesions. Conclusions: Dermoscopy is an applicable diagnostic tool for the diagnosis of cutaneous vascular anomalies. It is necessary to take into account the age stage and lesion location when we diagnose CA using dermoscopy.

Assay for Transposase-Accessible Chromatin Using Sequencing Analysis Reveals a Widespread Increase in Chromatin Accessibility in Psoriasis.

Psoriasis is a complex, chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and a disordered immune response; however, its exact etiology remains unknown. To better understand the regulatory network underlying psoriasis, we explored the landscape of chromatin accessibility by using an assay for transposase-accessible chromatin using sequencing analysis of 15 psoriatic, 9 nonpsoriatic, and 19 normal skin tissue samples, and the chromatin accessibility data were integrated with genomic, epigenomic, and transcriptomic datasets. We identified 4,915 genomic regions that displayed differential accessibility in psoriatic samples compared with both nonpsoriatic and normal samples, nearly all of which exhibited an increased accessibility in psoriatic skin tissue. These differentially accessible regions tended to be more hypomethylated and correlated with the expression of their linked genes, which comprised several psoriasis susceptibility loci. Analyses of the differentially accessible region sequences showed that they were most highly enriched with FRA1 and/or activator protein-1 transcription factor DNA-binding motifs. We also found that AIM2, which encodes an important inflammasome component that triggers skin inflammation, is a direct target of FRA1 and/or activator protein-1. Our study provided clear insights and resources for an improved understanding of the pathogenesis of psoriasis. These disease-associated accessible regions might serve as therapeutic targets for psoriasis treatment in the future.