Background: Psoriasis patients have obvious lipid metabolism disorders. The hyperlipidemia aggravates the development of psoriasis. In this study, we investigated that under the hyperlipidemia conditions, whether metformin could alleviate psoriasis via a Forkhead box O 3 (FOXO3)-driven pathway, as well as the mechanisms underlying. Methods: Wild type or FOXO3 knockdown HaCat cells were treated with free fatty acids (FFA) for 10 days and then co-treated with metformin for another 4 days. Triglyceride (TG) level, cell viability, proliferation, apoptosis, antioxidant enzymes, ROS levels, as well as the transcription activity of FOXO3 were analyzed. Results: Our data showed that FFA treatment promoted the proliferation and inhibited the apoptosis in HaCat cells. However, metformin could reversed all of these changes. Metformin treatment significantly increased the expressions and the activities of superoxide dismutase (SOD) and catalase (CAT), and reduced the reactive oxygen species (ROS) level, while FFA inhibited the antioxidant enzymes and increased the ROS level in HaCat cells. Metformin significantly promoted the autophagy and increase FOXO3 protein level in the nucleus under hyperlipidemia conditions, which was significantly inhibited by FFA treatment. However, all of the effects from metformin were partially blocked by FOXO3 knockdown. Conclusion: This study demonstrated that under the hyperlipidemia conditions, metformin has significant antiproliferation and proapoptosis effects by reducing ROS level as well as increasing autophagy. Both of these were responsible for the alleviation of psoriasis. All of these effects from metformin were through FOXO3-dependent pathway.

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Background: Piebaldism is a rare, autosomal dominant, and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SLUG genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Methods:In this paper, we report a case of piebaldism with café-au-lait macules resulting from a novel mutation of KIT gene c.1982C > T (p.Thr661Ile) in a three-generation Chinese family. The whole-exome sequencing, mitochondrial gene 3000X, and bioinformatics tools were used to identify the mutation in this new-found pedigree. In addition, we searched the databases of "Punmed, Chinese National Knowledge Infrastructure, CMJD, WANFANG MED ONLINE", reviewed 88 cases of piebaldism caused by KIT gene mutation, and summarized the relationship between clinical phenotype and genotype of piebaldism through logistic regression and other statistical methods. Results:The proband and her affected mother carried a heterozygous c.1982C > T missense mutation (p.Thr661Ile) on KIT gene. Bioinformatics analysis hinted that it had potential pathogenicity. The data showed that piebaldism patients with cafè-au-lait macules had KIT mutations almost located in the intracellular tyrosine kinase domain and were mostly related to the severe clinical phenotype of piebaldism. Conclusion: The new heterozygous c.1982C > T missense mutation on KIT caused piebaldism with café-au-lait macules in this Chinese family. This study provides a new reference index for clinicians to judge the severity of clinical phenotypes of piebaldism, broadens the understanding of the correlation between clinical phenotypes and genotypes of piebaldism, and provides reference of genetic counseling and prenatal diagnosis for affected families.

BackgroundClinical manifestations of gut problems except for inflammatory bowel disease (IBD) have not been well-established in patients with ankylosing spondylitis (AS). One study investigated that 30% patients with axial spondyloarthritis (axSpA) had irritable bowel syndrome (IBS) symptoms meeting Rome III criteria.[1]ObjectivesTo determine the frequency of symptoms meeting Rome IV functional bowel disorder (FBD) in patients with AS, investigate factors associated with FBD symptoms, and assess whether having FBD symptoms might influence AS disease activity.MethodsIn this cross-sectional study, we consecutively enrolled 153 AS patients without known colonic ulcer and 56 sex- and age-matched controls to evaluate FBD (or its subtypes) symptoms.[2] In AS group, logistic regression models were used to explore whether demographic data, disease activity, level of gut inflammation, drug use, and fibromyalgia [3] were associated with presence of gut symptoms. Finally, potential impacts of gut symptoms on AS disease status were assessed in linear regression models.ResultsSixty (39.2%) of 153 AS patients had FBD symptoms, which was more prevalent than controls (23.2%). Besides, symptoms compatible with IBS and chronic diarrhea were detected in 18 and 43 AS patients respectively. For AS group, multivariable logistic regression analyses showed that symptoms of FBD, IBS, and chronic diarrhea were negatively associated with using non-steroidal anti-inflammatory drug (NSAID), and positively associated with comorbid fibromyalgia, respectively. In exploration about effects of FBD (or its subtypes) symptoms on AS disease activity by multivariable linear regression analyses, FBD symptoms and chronic diarrhea had positive associations with assessments of AS respectively.ConclusionPatients with AS had frequent symptoms compatible with FBD, IBS, and chronic diarrhea, proportions of which were lower in those with NSAID-use. The improvement of FBD symptoms, especially chronic diarrhea, might be conducive to disease status of AS patients.References[1]Wallman JK, et al. Ann Rheum Dis. 2020;79:159-61.[2]Mearin F, et al. Gastroenterology. 2016;18:S0016-5085(16)00222-5.[3]Wolfe F, et al. J Rheumatol. 2011;38:1113-22.Figure 1.Frequencies with symptoms meeting FBD criteriaTable 1.Univariable and multivariable associations between gut symptoms and assessments of ASGut symptomsUnivariableMultivariableβpβpASDAS-CRPaFBD symptoms0.2340.1120.294< 0.001IBS symptoms0.0390.863Chronic diarrhea0.2170.1720.3010.002BASDAIbFBD symptoms0.747< 0.0010.764< 0.001IBS symptoms0.2020.560Chronic diarrhea0.7610.0020.845< 0.001BAS-GcFBD symptoms0.936< 0.0010.979< 0.001IBS symptoms0.0590.889Chronic diarrhea0.9030.0030.9490.001ASAS HIdFBD symptoms1.941< 0.0011.6730.003IBS symptoms2.2630.0081.7690.046Chronic diarrhea1.5000.0151.3430.030BASFIeFBD symptoms0.4330.0490.4280.048IBS symptoms0.2960.376Chronic diarrhea0.4480.0600.4250.069BASMIfFBD symptoms-0.3730.190-0.4930.075IBS symptoms-0.4420.304Chronic diarrhea-0.1790.564　　Besides gut symptoms, other clinical variables (Block-1) being chosen into hierarchical multivariable models were as follows: aHLA-B27, lnCRP, and lnESR; bHLA-B27 and lnESR; cHLA-B27 and lnCRP; dsex and TNFi; eHLA-B27, lnESR, and TNFi; fage and lnESR. Missing data ranging from 1-7%.Disclosure of InterestsNone declared