Psoriasis is characterized by scaly erythematous plaques resulted from keratinocytes hyperproliferation, immune cells infiltration and angiogenesis . The pathophysiological process is orchestrated by many cytokines including IL-1β, IL-6, TNF-α, IL-23, IL-17A, IL-22 and so on , , of which, IL-17A is the key player . During psoriasis development, IL-17 stimulates CCL20 expression by keratinocytes to attract CCR6+ IL-17A+cells including Th17, ILC3, Tc17, and γδ T cells into the skin to amplify the inflammation . The remarkable therapeutic efficacy of anti-IL-17A biologics further confirm the fundamental role of IL-17A in psoriasis pathogenesis , .
Although the biologics opens a new era of psoriasis therapy, maximumly less than 20–40% of patients achieved complete response (PASI100) to the initial anti-IL-17A biologics treatment, given that some of them experience mild to moderate relapse later on . The majority of patients only achieved partial response (PASI 50 or 75) with residual lesions left particularly on elbows and pretibial skin . Thus, the combination therapy with topical medicine is an optional strategy as considering the overall safety and efficacy . However, topical medicines are only limited to several categories such topical corticosteroids, calcineurin inhibitors, vitamin D derivatives and narrow-band UVB. It is very often that the residual lesions failed to response to all available topical medicine. Therefore, topical medications targeting new signaling pathway is even more in urgent need in the biologics era to meet the patients’ requirement of complete clearance of skin lesions.
Histone deacetylases (HDACs) are enzymes that remove acetyl from lysine residues on histones and non-histone proteins and result in chromatin condensation and transcription repression . HDAC1 belongs to the class I HDAC family. Previous research observed that HDAC1 was overexpressed in psoriatic skin and peripheral blood mononuclear cells (PBMCs), implying a possible role of HDAC1 in psoriasis pathogenesis , . Entinostat is a selective inhibitors of histone deacetylases (HDAC) 1 and 2. Systemic administration of Entinostat has been widely explored in clinic trials to treat various solid tumors and hematological malignancies, . Its anti-tumor activity attributes to the direct effects on tissue-specific tumor cells, innate and adaptive immune cells as well. Therefore, we investigated the topical therapeutic potentials of Entinostat on psoriasis in this study.
Bioinformatics analysis of RNA-sequencing data
Gene Expression Omnibus (GEO) is a public gene expression database containing a large amount of high-throughput sequencing submitted by research institutes worldwide . The dataset GSE121212 used in this work was downloaded from GEO, which contains skin transcriptomes of lesions from 28 psoriasis vulgaris (PV) and normal skin from 38 healthy control (NC). We defined the IL17A-correlated expression network as described by Shao, S. et al.. Briefly, The mapped counts of dataset GSE121212
The overexpression of HDAC1 in psoriatic lesions
We first investigate the potential link between psoriasis and HDAC1. The dataset GSE121212 was downloaded from GEO and converted into a log2-based expression intensity using the voom transformation. It contains lesional skin transcriptomes from 28 psoriasis patients and normal skin transcriptomes from 38 healthy individuals. Overall, the expression of 13315 gene was positively correlated with IL-17A (rs>0). The correlation coefficient varied among these 13315 genes. To determine an appropriate
In the present study, we demonstrate that topical Entinostat, a HDAC1 inhibitor is a potential topical therapeutic agent for psoriasis. It improves imiquimod-induced psoriasiform dermatitis with less IL-17A+ γδ T cells infiltration and great reduction of psoriasis-related cytokines in skin. In the context of psoriasis, Entinostat not only suppresses γδ+IL-17A T cells generation and IL-17-related cytokines production by T cells, but disrupts the cross talk between keratinocytes and T cells with
This study was supported by the National Natural Science Foundation of China (grants 81872524, 82073431) and China Postdoctoral Science Foundation [grant 2022M723613].
CRediT authorship contribution statement
Yanyun Jiang: Conceptualization, Methodology, Validation, Data curation, Writing – original draft, Project administration. Siyao Lu: Methodology, Investigation. Yuxian Lai: Methodology. Liangchun Wang: Conceptualization, Writing – review & editing, Supervision, Funding acquisition.
Conflict of interest
All authors have no conflicts of interest to declare.
Assessment of rhBMP-2-loaded bovine hydroxyapatite granules in the guided bone regeneration of critical bone defect in rat mandible bone
Journal of Dental Sciences, 2023
THE IMPACT OF COVID-19 INCIDENCE ON EMERGENCY MEDICAL SERVICES UTILIZATION
The Journal of Emergency Medicine, 2023
Comment je fais le diagnostic d’une malformation artérioveineuse cérébrale
Journal d'imagerie diagnostique et interventionnelle, 2023
Les malformations artérioveineuses (MAV) cérébrales sont des lésions rares, qui correspondent à la persistance d’une communication anormale (shunt) entre artère(s) et veine(s) avec inexistence du lit capillaire normal qui est remplacé par un réseau de vaisseaux anormaux sinueux et interconnectés appelé nidus. Elles sont découvertes à l’occasion du bilan d’un hématome cérébral, d’une crise d’épilepsie, d’un déficit neurologique focal ou de manière fortuite.
Le bilan TDM et IRM permet d’effectuer le diagnostic de manière non invasive. Les critères diagnostiques d’une MAV sont la présence d’un nidus et d’un drainage veineux précoce (shunt artérioveineux). Les artères nourricières sont dilatées et proviennent en général de branches de la carotide interne ou du système vertébrobasilaire (afférences piales) et plus rarement de branches de la carotide externe (afférences durales). Les séquences d’angio-IRM 4D sont très utiles pour détecter le shunt en mettant en évidence une (des) veine(s) au temps artériel. L’angiographie permet quant à elle de définir la stratégie thérapeutique à adopter. En cas d’hématome cérébral récent, la malformation peut être masquée et les examens doivent alors êtres répétés lorsque l’hématome est résorbé (2à 3mois après en général). Les critères de gravité radioanatomiques doivent être précisés dans le compte rendu car ils influencent la prise en charge.
Cet article a pour objectif d’exposer les techniques et les éléments clés permettant de faire le diagnostic d’une MAV cérébrale. Les critères de gravité ainsi que les moyens d’écarter les diagnostics différentiels sont également abordés.
Brain arteriovenous malformations (AVM) are rare lesions, which consist of the persistence of an abnormal communication (shunt) between artery(s) and vein(s) with nonexistence of the normal capillary bed which is replaced by a network of abnormal sinuous and interconnected vessels called nidus. They are discovered during the assessment of a cerebral hematoma, an epileptic seizure, a focal neurological deficit or incidentally.
CT and MRI scans allow for a non-invasive diagnosis. The diagnostic criteria for an AVM are the presence of a nidus and an early venous drainage (arteriovenous shunt). The feeding arteries are dilated and usually originate from branches of the internal carotid artery or vertebral-basilar system (pial feeders) and more rarely from branches of the external carotid artery (dural feeders). The 4D angio-MRI sequences are very useful to detect the shunt by highlighting one or more veins at the arterial time. Angiography is used to define the therapeutic strategy to be adopted. In the case of a recent cerebral hematoma, the malformation may be masked, and the examinations should be repeated when the hematoma has resolved (usually 2to 3months later). The radio-anatomical severity criteria must be specified in the report because they influence the management.
The purpose of this article is to present the techniques and key elements for the diagnosis of a cerebral AVM. Severity criteria as well as ways to rule out differential diagnoses are also discussed.
Comment on: Bariatric surgery before and after kidney transplantation: a propensity score–matched analysis
Surgery for Obesity and Related Diseases, Volume 19, Issue 5, 2023, pp. 509-510
Emergency Department use by Young Adults with Chronic Illness Before and During the COVID-19 Pandemic
Journal of Emergency Nursing, 2023
There was a significant decrease in emergency department encounters during the COVID-19 pandemic. Our large urban emergency department observed decreased encounters and admissions by youths with chronic health conditions. This study aimed to compare the frequency of emergency department encounters for certain young adults pre pandemic and during the COVID-19 pandemic.
A retrospective cohort study utilizing medical records of patients ages 20-26 from October 2018 to September 2019 and February 2020 to February 2021. Files set for inclusion were those with a primary diagnosis of human immunodeficiency virus, diabetes mellitus, epilepsy, cerebral palsy, sickle cell disease, asthma, and certain psychiatric disorders for potentially preventable health events.
We included 1,203 total encounters (853 pre pandemic and 350 during the pandemic), making the total number of subjects 568 (293 pre pandemic to 239 during the pandemic. During the pandemic, young adults with mental health conditions (53.1%) accounted for the majority of the encounters. Encounters requiring hospital admissions increased from 27.4% to 52.5% during the pandemic, primarily patients with diabetes (41.8% versus 61.1%) and mental health conditions (50% versus 73.3%).
The number of young adults with certain chronic health conditions decreased during COVID-19, with encounters for subjects with mental health conditions increasing significantly. The proportion of admissions increased during the pandemic with increases for subjects with mental health disorders and diabetes. The number of frequent users decreased during COVID-19. Future research is needed to understand better the causes for these disparities in young adults with chronic conditions who utilize the emergency department as a source of care.
© 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.