Assessing the relationship between psoriasis and thyroid dysfunction through two sample MR analysis.

BACKGROUND: The association between psoriasis and hyperthyroidism/hypothyroidism remains inconclusive, with conflicting findings in prior studies. OBJECTIVES: This study employs Mendelian randomization methods to assess the potential relationship. METHODS: Given the inability to accurately observe the link between psoriasis and thyroid dysfunction, we prioritized utilizing known genetic variants to investigate the potential impacts of the disease.We analyzed data from genome-wide association studies (GWASs), FinnGen, and UK Biobank to extract information on psoriasis, hyperthyroidism, and hypothyroidism. Three MR approaches (MR Egger, weighted median, and inverse variance weighted) were used to scrutinize the causal link. RESULTS: Our analysis revealed no correlation between psoriasis and hyperthyroidism/hypothyroidism. However,  vulgar psoriasis and guttate psoriasis were associated with hypothyroidism/myxedema (IVW odds ratio (OR) = 1.00, 95% confidence interval (CI) = 1.00-1.00, P = 2.53E-03), and Graves' disease (IVW OR = 0.86, 95% CI = 0.72-1.01, P = 4.75E-02).In a subsequent analysis, we observed that hypothyroidism with mucinous edema showed no correlation with Graves' disease in the opposite(P = 9.33E-01). CONCLUSION: This MR analysis suggests no association between psoriasis and thyroid dysfunction, but highlights associations of vulgar/guttate psoriasis with hypothyroidism/myxedema and Graves' disease. In clinical practice, diagnosing guttate psoriasis requires vigilance for associated risks from hypothyroidism and Graves' disease. For patients with both vulgar psoriasis and hypothyroidism, careful monitoring for mucinous edema is crucial, as it may signal a hypothyroid crisis.

Short-Term Ambient Air Pollution and Urticaria in Guangzhou, China: Estimating the Association and Population Attributable Fraction.

Limited evidence is available regarding the association between acute exposure to ambient air pollutants and the risk of urticaria, even though the skin is an organ with direct contact with the external environment. This study utilized generalized additive models to investigate the association between particulate matter with an aerodynamic diameter smaller than 10 µm (PM10) and 2.5 µm (PM2.5), nitrogen dioxide (NO2) and sulfur dioxide (SO2), and daily outpatient visits for urticaria in Guangzhou, China from 2013 to 2017. We also estimated the attributable fraction of urticaria outpatient visits due to air pollution. A total of 216,648 outpatient visits due to urticaria occurred during the study period. All air pollutants were significantly associated with an increased excess risk of urticaria. Each 10 µg/m3 increase in PM2.5, PM10, NO2, and SO2 was associated with an increase of 1.23% (95% CI: 0.42%, 2.06%), 0.88% (95% CI: 0.28%, 1.49%), 3.09% (95% CI: 2.16%, 4.03%), and 2.82% (95% CI: 0.93%, 4.74%) in hospital visits for urticaria at lag05, respectively. It was estimated that 3.77% (95% CI: 1.26%, 6.38%), 1.91% (95% CI: 0.60%, 3.26%), 6.36% (95% CI: 4.38%, 8.41%), and 0.08% (95% CI: 0.03%, 0.14%) of urticaria outpatient visits were attributable to PM2.5, PM10, NO2, and SO2 using the World Health Organization's air quality guideline as the reference. Relatively stronger associations were observed during the cold season. This study indicates that short-term air pollution may play a significant role in outpatient visits for urticaria, and that such relationships could be modified by season.

LC-MS metabolomics reveal skin metabolic signature of psoriasis vulgaris.

Recent metabolic studies have indicated that several metabolites in blood and urine of psoriasis functionally involved in the pathogenesis of psoriasis, but the skin metabonomics research of psoriasis is limited. We aimed to investigate the metabolic profiling of lesional and nonlesional skin and screen out potential biomarkers for psoriasis. We performed liquid chromatography-mass spectrometry (LC-MS)-based nontargeted metabolomic analysis to compare metabolic profile between lesional and nonlesional skin from 12 patients with psoriasis vulgaris. A total of 3463 metabolites were detected, of which 769 (346 named and 423 unnamed) in positive ion mode and 179 (80 named and 99 unnamed) in negative ion mode were significantly different between lesional and nonlesional skin. These different metabolites were mainly derived from amino acid, lipid and nucleotide metabolism, and involved in cell proliferation and apoptosis regulation. Fourteen metabolites (10 upregulated and 4 downregulated) were identified as the most potentially significant biomarkers. Interestingly, seven of them were positively (l-gamma-glutamyl-l-leucine, 2-methylcitric acid, l-palmitoylcarnitine, inosine, eicosapentaenoic acid and 13-hydroxy-octadecaenoic acid) or negatively (l-serine) correlated with disease severity. Significant differences of metabolic characteristics were found between lesional and nonlesional skin, which may contribute to assess the severity of psoriasis and therapeutic responses.

Tofacitinib combined with melanocyte protector α-MSH to treat vitiligo through dextran based hydrogel microneedles.

Vitiligo can cause serious damage to the appearance of patients and affect physical and mental health, but there is currently no simple and effective treatment. According to the theory of autoimmune disorder, the separable hydrogel microneedles delivering alpha-melanocyte-stimulating hormone (α-MSH) and tofacitinib were designed to treat vitiligo. This hydrogel microneedles were formed by dextran methacrylate (DexMA) and cyclodextrin-adamantane based host-guest supramolecules (HGSM) through CC double bond polymerization and host-guest assembly. The microneedle tips formed by the double cross-linked hydrogel can pierce the stratum corneum and deliver melanocyte protector α-MSH and JAK inhibitor tofacitinib directly to the epidermis and dermis. Under the treatment of α-MSH/tofacitinib microneedles, massive deposition of melanin in epidermis and hair follicles significantly accelerated skin and hair pigmentation.

Review of secukinumab-induced adverse events of special interest and its potential pathogenesis.

Although secukinumab has demonstrated high efficacy and favorable safety in moderate-to-severe psoriasis and psoriatic arthritis, patients developing adverse events of special interest (AESI) were reported increasingly in real-world practice. A systematic literature search of the PubMed database was conducted to identify clinical studies or case reports on secukinumab-induced AESI. More than 1077 patients (aged 18-74 years) from 55 studies were reported to have 24 AESI 3 days to 96 weeks after secukinumab treatment. The four most common AESI was inflammatory bowel disease (n > 1000), eczematous drug eruption (n > 30), drug-associated vasculitis (n = 8), and drug-induced lupus erythematosus (n = 4). Most of these AESI were only mild to moderately severe and resolved after secukinumab discontinuation without or with symptomatic treatment. Secukinumab has the potential to develop a number of AESI by probably dysregulating the different expression of polar T-cell axes (Th1, Th2, Th17, Th22, and/or Treg) and driving various cytokines in some patients. Physicians should be aware of these AESI for timely diagnosis and proper treatment.

Injectable antimicrobial hydrogels with antimicrobial peptide and sanguinarine controlled release ability for preventing bacterial infections.

The emergence of antibiotic resistant bacteria represents a significant and common clinical problem worldwide as infections are becoming increasingly common. It is urgent to broaden the sources of biomaterials that can prevent both bacterial infection and antibiotic resistance. In this work, oxidized sodium alginate/aminated hyaluronic acid (OSA/AHA) hydrogel with various proportions was developed based on Schiff base reaction. Herein, polydopamine (PDA)-Bmkn2 nanoparticle and sanguinarine were incorporated into hydrogels to enhance antibacterial properties. The prepared PDA-Bmkn2 nanoparticles, with uniform particle size and good dispersion, could serve as a delivery system for Bmkn2. The prepared hydrogels showed appropriate swelling ratio, extremely good mechanical strengths and improved biodegradability. Meanwhile, the Bmkn2 and sanguinarine were released from the hydrogels in a sustainable manner. Furthermore, OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel (less than 10 µg/mL BmKn2 and 0.2 µg/mL sanguinarine) had excellent biocompatibility. Antibacterial experiments confirmed that OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel had effective antimicrobial activity on Escherichia coli and Staphylococcus aureus. Therefore, the prepared injectable hydrogels with good biocompatibility and excellent synergistic antibacterial activity promise great potential for preventing localized bacterial infections.

Secukinumab-induced multiple lentigines in areas of resolved psoriatic plaques: A case report and literature review.

Psoriasis is a systemic inflammatory disease commonly associated with postinflammatory hyper- and hypo-pigmentation. Psoriasis-related cytokines such as IL-17 and TNF can contribute to these pigmentation changes by regulating both the growth and pigment production of melanocytes. Here, we present the first reported the case of a patient with a 10-year history of severe psoriasis vulgaris, who developed multiple lentigines in areas of resolved psoriatic plaques during anti-IL-17A antibody secukinumab.

Circular RNA profiles and the potential involvement of down-expression of hsa_circ_0001360 in cutaneous squamous cell carcinogenesis.

Circular RNAs (circRNAs) act as sponges of noncoding RNAs and have been implicated in many pathophysiological processes, including tumor development and progression. However, their roles in cutaneous squamous cell carcinoma (cSCC) are not yet well understood. This study aimed to identify differentially expressed circRNAs and their potential functions in cutaneous squamous cell carcinogenesis. The expression profiles of circRNAs in three paired cSCC and adjacent nontumorous tissues were detected with RNA sequencing and bioinformatics analysis. The candidate circRNAs were validated by PCR, Sanger sequencing and quantitative RT-PCR in another five matched samples. The biological functions of circRNAs in SCL-1 cells were assessed using circRNA silencing and overexpression, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS), flow cytometry, transwell and colony formation assays. In addition, the circRNA-miRNA-mRNA interaction networks were predicted by bioinformatics. In summary, 1115 circRNAs, including 457 up-regulated and 658 down-regulated circRNAs (fold change ≥ 2 and P < 0.05), were differentially expressed in cSCC compared with adjacent nontumorous tissues. Of four selected circRNAs, two circRNAs (hsa_circ_0000932 and hsa_circ_0001360) were confirmed to be significantly decreased in cSCC using PCR, Sanger sequencing and quantitative RT-PCR. Furthermore, hsa_circ_0001360 silencing was found to result in a significant increase of the proliferation, migration and invasion but a significant decrease of apoptosis in SCL-1 cells in vitro, whereas hsa_circ_0001360 overexpression showed the opposite regulatory effects. hsa_circ_0001360 was predicted to interact with five miRNAs and their corresponding genes. In conclusion, circRNA dysregulation may play a critical role in carcinogenesis of cSCC, and hsa_circ_0001360 may have potential as a biomarker for cSCC.

Secukinumab monotherapy successfully treated severe refractory type V (atypical juvenile) pityriasis rubra pilaris: A case report and literature review.

Pityriasis rubra pilaris (PRP) is a rare heterogeneous group of papulosquamous inflammatory disorders with unknown etiology. PRP is often resistant to many conventional therapies which has made more challenging on treatment. More recently, several studies have shown encouraging clinical results of secukinumab in the treatment of PRP in adult, but no studies have explored its effects in children. We herein report a 7-year-old boy with severe type V PRP responded rapidly to secukinumab monotherapy (150 mg once weekly) when conventional therapies have failed. The patient showed rapid and dramatic improvement of erythema, palmoplantar hyperkeratosis, scaling, and itching within only 5 weeks, with no adverse effects. Secukinumab could be considered as a treatment option for refractory PRP in children, as recently reported in adult.

Successful clearance of extensive/recalcitrant cutaneous warts by acitretin monotherapy: A case series study.

Most available options for the treatment of warts are limited by the potential for scarring, pain, lack of response, or recurrences, and the patients are often unable to tolerate and accept those experiences. The aim of this study was to evaluate the clinical efficacy and safety of oral systemic acitretin monotherapy in patients with extensive/recalcitrant cutaneous warts. The patients were given a dose of acitretin of 0.8 mg kg-1 day-1 , and the clinical efficacy and safety of acitretin was assessed every 2 weeks for 2 months. A total of 14 patients (12 males and 2 females) were included, with an age of 14-60 years (mean 33 ± 14.7 years) and a course of 4-48 months (mean 21.6 ± 13.4 months). After 2 months of acitretin treatment, 42.9% (6/14) of patients (including warts of the feet, legs, and hands) exhibited complete response, 28.6% (4/14) excellent response, and 28.6% (4/14) good response. All patients demonstrated significant improvement, and the drug was well tolerated, with no patients discontinuing therapy due to side effects. Common mild side effects included dry skin and cheilitis. There were no recurrences during a follow-up period of 6 months. Acitretin monotherapy is an effective, safe, and well-tolerated treatment for patients with extensive/recalcitrant cutaneous warts who are unsuitable for or unwilling to accept traditional treatment methods.

Exome sequencing identifies a KRT9 pathogenic variant in a Chinese pedigree with epidermolytic palmoplantar keratoderma.

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is a rare skin disorder and its pathogenesis and inheritability are unknown. OBJECTIVE: To investigate the inheritance and pathogenesis of EPPK. METHODS: Two EPPK cases occurred in a three-generation Chinese family. Patient-parents trio EPPK was carried out and the identified candidate variants were confirmed by Sanger sequencing. RESULTS: A heterozygous missense pathogenic variant, c.488G > A (p.Arg163Gln), in the keratin (KRT) 9 gene was detected in the proband and his son via targeted exome sequencing, and then validated by Sanger sequencing. This pathogenic variant cosegregated with the EPPK in extended family members, and was predicted to be pathogenic by SIFT, PolyPhen2, PROVEAN, and Mutation Taster. This heterozygous variation was not evident in 100 healthy controls. CONCLUSION: This report describes a KRT9 c.488G > A (p.Arg163Gln) variant causing a diffuse phenotype of Chinese EPPK. The current results broaden the spectrum of KRT9 pathogenic variants responsible for EPPK and have important implications for molecular diagnosis, treatment, and genetic counseling for this family.

IL-22 Down-Regulates Cx43 Expression and Decreases Gap Junctional Intercellular Communication by Activating the JNK Pathway in Psoriasis.

The roles of IL-22 in the pathomechanisms of psoriasis have been well demonstrated. Gap junctional intercellular communication (GJIC) is widely known for its involvement in multiple biological and pathological processes such as growth-related events, cell differentiation, and inflammation. Here, we show that IL-22 significantly decreased GJIC and down-regulated Cx43 expression in HaCaT cells. Cx43 overexpression markedly inhibited the proliferation of and increased GJIC in HaCaT cells, but the silencing of Cx43 exerted the opposite effects. Additionally, Cx43 overexpression effectively rescued the IL-22-induced decrease in GJIC in HaCaT cells. The IL-22-induced down-regulation of Cx43 expression and decrease in GJIC can be significantly blocked by the JNK inhibitor SP600125 and by the overexpression of IL-22RA2 (which specifically binds to IL-22 and inhibits its activity), but not by the NF-κB inhibitor BAY11-7082, in HaCaT cells. Furthermore, the IL-22-induced down-regulation of Cx43 expression mediated by the JNK signaling pathway was confirmed in a mouse model of IL-22-induced psoriasis-like dermatitis. Similarly, Cx43 expression was significantly lower in the lesional skin than in the nonlesional skin of patients with psoriasis. These results suggest that IL-22 decreases GJIC by activating the JNK signaling pathway, which down-regulates Cx43 expression; this process is a possible pathomechanism of keratinocyte hyperproliferation in psoriasis.

Identification and functional characterization of a novel transglutaminase 1 gene mutation associated with autosomal recessive congenital ichthyosis.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a group of genetically heterogeneous diseases. Mutations in transglutaminase (TGase) 1 gene (TGM1, OMIM 190195) have been implicated in ARCI. However, little is known about TGM1 mutations in the Chinese population, and no functional studies have investigated the biological effect of mutant TGM1 on human epidermal keratinocytes (HaCaT) cells. OBJECTIVES: To identify the pathogenic mutations of TGM1 gene in two Chinese siblings with ARCI and gain insight into functional consequences of these mutations. METHODS: Fifteen exons and flanking splice sites of TGM1 gene were amplified by polymerase chain reaction and then underwent bidirectional Sanger sequencing. The HaCaT cells were transfected with lentiviral vectors, which overexpressed either wild-type or mutant TGM1 cDNAs with deleted homeodomain. Cell proliferation and cell cycle progression were detected. The expression of cyclin D1, cyclin B1, CDK4, TGM1, K10, involucrin, and filaggrin proteins were investigated by Western blot analysis. RESULTS: We found two compound heterozygous missense mutations (c.515C>T, R143C in exon 3 and c.759C>T, S212F in exon 4) in both siblings. HaCaT cells transfected with mutant TGM1 cDNAs displayed a lower growth rate and delayed S phase while overexpression of wild-type TGM1 cDNAs led to accelerated growth. HaCaT cells transfected with mutant TGM1 cDNAs displayed lower expression of differentiation markers such as involucrin and filaggrin. Our findings suggest that the compound heterozygous missense (c.515C>T, R143C) mutations in exon 3 and missense (c.759C>T, S212F) mutations in exon 4 result in the phenotype of ARCI. TGM1 mutations can suppress keratinocyte growth and cornified cell envelope formation.

MMP-9 gene polymorphisms (rs3918242, rs3918254 and rs4810482) and the risk of psoriasis vulgaris: No evidence for associations in a Chinese Han population.

Several previous studies including one of them co-authored by our group have revealed that serum and psoriatic plaque expression of matrix metalloproteinase-9 (MMP-9) was significantly upregulated in psoriasis. The aim of this study was to investigate the association of three single nucleotide polymorphisms (SNPs) and haplotypes of MMP-9 (rs3918242, rs3918254 and rs4810482) with psoriasis vulgaris in a Chinese Han population. The serum levels of MMP-9 in 245 psoriasis vulgaris cases and 256 healthy controls were assessed using ELSA kits, and the three SNPs were genotyped using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Four haplotypes based on the three SNPs were also analyzed. Our study showed that the serum MMP-9 levels in patients with psoriasis vulgaris were significantly higher than that in controls (P<0.05). However, the three SNPs were not significantly associated with psoriasis vulgaris susceptibility (all P>0.05). Similar results were found in further subgroup analysis based on gender, age of onset, family history, and serum MMP-9 levels, except that a protective effect of psoriasis vulgaris was detected among female subjects with the CT genotype of rs3918254 (OR=0.47, 95% CI=0.23-0.96, P=0.038), but this association did not survive after Bonferroni correction (P(adj)=0.076). The haplotype analysis also failed to show any association with psoriasis vulgaris. We found no evidence for the association between the MMP-9 polymorphisms and psoriasis vulgaris susceptibility in a Chinese Han population.

Lack of association between cytotoxic T-lymphocyte antigen-4+49A/G polymorphism and psoriasis and vitiligo: A meta-analysis of case-control studies.

BACKGROUND: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical negative regulator of T-cell activation and proliferation. Several studies have assessed the association between CTLA-4+49A/G polymorphism and psoriasis and vitiligo, but the results are inconsistent. AIMS: This study was conducted to examine the association between CTLA-4+49A/G polymorphism and psoriasis and vitiligo susceptibility. METHODS: The PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched according to predefined criteria for all relevant studies published prior to July 3, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs), and heterogeneity and publication bias tests were performed to estimate the strength of the association. RESULTS: Fourteen studies comprising six on psoriasis (700 cases, 781 controls) and eight on vitiligo (1514 cases, 2049 controls) were included. Overall, no significant association was detected between CTLA-4+49A/G polymorphism and psoriasis. There was still no significant relationship when the studies were limited to ethnicity (Asian and Caucasian), HWE or heterogeneity, except the limitation to heterogeneity in the dominant (OR=0.69, 95% CI=0.51-0.93, I(2)=0.0%) and additive (OR=0.69, 95% CI=0.48-0.98, I(2)=0.0%) models, and the limitation to both heterogeneity and HWE in the dominant model (OR=0.68, 95% CI=0.48-0.98, I(2)=0.0%). Both overall and subgroup analyses based on ethnicity, genotype frequencies, and heterogeneity also failed to demonstrate an association between CTLA-4+49A/G polymorphism and vitiligo. CONCLUSION: CTLA-4+49A/G polymorphism may not contribute to psoriasis and vitiligo susceptibility, but further well-designed studies with large sample size are warranted to confirm this conclusion.

[Mechanism and influence of silencing TGM1 gene by siRNA on cell cycle distribution of keratinocytes].

OBJECTIVE: To explore the effects of cell cycle distribution and expression of cell cycle related proteins before and after transglutaminase 1 (TGM1) gene silencing by small interfering RNA (siRNA) in immortalized human keratinocytes (HaCaT cells). METHODS: Before and after RNA interference (RNAi) silencing TGM1 gene expression in HaCaT cells, the changes of cell cycle status were detected by flow cytometry. And the expressions of cell cycle related proteins cyclin D1, cyclin B1 and CDK4 were detected by immunocytochemistry and Western blot. RESULTS: After TGM1 silencing, the HaCaT cells increased in G(0)/G(1) phase (78.27% ± 1.83% vs 56.84 % ± 2.72% and 57.19% ± 3.72%, both P < 0.05) while decreased in S phases (32.78% ± 5.48% vs 57.32% ± 2.91% and 55.71 % ± 2.84%, both P < 0.05) and G(2)/M phases (3.66% ± 0.30% vs 9.39% ± 0.68% and 9.77% ± 0.52%, both P < 0.05) . Moreover, arrest of cell cycle was induced in S phase. After TGM1 silencing, cell proliferation was significantly inhibited while wild-type TGM1 displayed an accelerated growth rate. Inmmnohistochemistry indicated that cyclin D1, cyclin B1 and CDK4 had a strongly negative expression after transfecting with TGM1 siRNA. Western blot indicated that a very low endogenous expression of cyclin D1, cyclin B1 and CDK4 proteins was observed after transfecting with TGM1 siRNA. CONCLUSIONS: TGM1 siRNA may block the cell cycle of HaCaT cells. It suggests that TGM1 expression in HaCaT cells are closely related with cell cycle.