• Hermann Molloy posted an update 2 months ago

    BACKGROUND Tripartite motif-containing protein 21 (Trim21) is an E3 ubiquitin-protein ligase that plays pivotal roles in various diseases. However, its role in mediating keratinocyte inflammation, which is a hallmark of psoriasis, has not been thoroughly elucidated. OBJECTIVES To clarify whether Trim21 plays a pivotal role in regulating keratinocyte inflammation in psoriasis, while focusing on identifying key Trim21 substrates involved in mediating proinflammatory cytokine and chemokine production. METHODS Cytokine and chemokine secretion was examined by quantitative real-time PCR (qPCR) in Trim21-knockdown human keratinocytes. Downstream pathways and substrates of Trim21 were evaluated using immunoblotting, immunoprecipitation and immunofluorescence. The influence of Trim21 ubiquitination on its substrates was tested by in vitro ubiquitination assay, immunoprecipitation and immunofluorescence. iFSP1 manufacturer The effectiveness of targeting Trim21 for psoriasis treatment was assessed in vivo with haematoxylin and eosin (H&E) staining, immunofluorescence and qPCR. RESULTS Knocking down Trim21 expression alleviated keratinocyte inflammation. Trim21 colocalized with p65/Nuclear factor-κB (NF-κB) in the cytosol and physically bound and ubiquitinated p65 via a lysine 63 (K63) linkage. Instead of changing p65 protein stability, Trim21 enhanced the interaction of p65 with IκB kinase (IKK), which promoted p65 phosphorylation, nuclear transport and downstream gene activation. Finally, both in vitro and in vivo experiments verified that topical application of Trim21-specific small interfering RNA (siRNA) markedly ameliorated imiquimod (IMQ)-induced psoriasis-like lesions. CONCLUSIONS Our study confirms that upregulated Trim21 in psoriatic epidermis ubiquitylates p65 and activates the NF-κB pathway, which promotes keratinocyte inflammation. Hence, Trim21 represents a potential target for psoriasis treatment. This article is protected by copyright. All rights reserved.Neutrophilic leukemoid reaction (NLR) is defined as a leukocyte count with more than 50 g/L polymorphonuclear neutrophils (PMNs) in the absence of haematological malignancy. Inductive treatments and severe infections are among the main causes of NLR. Paraneoplastic neutrophilic leukemoid reaction (PNLR) is a rare cause of NLR, whose pathomechanism is unclear, with most cases described in patients with solid malignancies. We report the case of a PNLR that occurred during a metastatic melanoma and for which we retrospectively studied the relationship between PMNs count, tumour mass, serum LDH and G-CSF levels. This article is protected by copyright. All rights reserved.Extracorporeal membrane oxygenation (ECMO) is a form of life support used to treat neonates, children, and adults with cardiorespiratory failure refractory to conventional therapy. This therapy requires the use of anticoagulation to prevent clotting in the extracorporeal circuit, but anticoagulation also increases the risk of bleeding on ECMO. Both bleeding and thrombosis remain significant complications on ECMO and balancing these risks is challenging. Acquired platelet dysfunction is common during ECMO and quantitative and qualitative platelet dysfunction contributes to bleeding risk. Optimal platelet count, function, and transfusion thresholds are not well established during pediatric ECMO. In this review, we provide an overview of hemostatic alterations during ECMO, changes in platelet count and function, platelet monitoring techniques, bleeding risk, and future needs to best optimize patient management and care. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Bilateral tubal ectopic pregnancy is a very rare form of ectopic pregnancy. The incidence is higher in women undergoing assisted reproductive techniques or ovulation induction. We report the case of bilateral tubal ectopic pregnancy. The patient was 30 years old and had a 3-year history of infertility; she was referred to the in-vitro fertilization (IVF) program because of tubal factor infertility. A pregnancy resulted from the transfer of two embryos during an artificial cycle. Despite the increase in β-hCG values during the follow-up, 22 days after the embryo transfer, the β-hCG levels were 2,408 U/L and the serum progesterone (P4) level was 10.53 ng/ml. After application with methotrexate, β-hCG levels did not decrease effectively. Moreover, the sonographic screening revealed a suspicious bilateral tubal focus for ectopic pregnancy. A mini-laparotomy was performed and a bilateral tubal pregnancy was found. In the case of unilateral tubal pregnancy after the transfer of two embryos, the situation of the other tube should be systematically checked and β-hCG levels should be monitored. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.in English, Portuguese Os ácidos graxos poli-insaturados (AGPIs) ômega-3 (n-3) de cadeia longa, como os ácidos eicosapentaenoico e docosa-hexaenoico, têm sido associados à saúde humana em todas as etapas da vida, do desenvolvimento fetal ao envelhecimento. Esses AGPIs atuam como precursores de vários metabólitos envolvidos na prevenção de algumas doenças. Os efeitos reconhecíveis desses suplementos antes da gravidez (maturação dos oócitos), durante a gravidez (melhora do risco de parto prematuro, entre outros) e nos descendentes (em termos de função cognitiva e abordagem dos distúrbios do neurodesenvolvimento) são apresentados nesta revisão narrativa. Concluiu-se que a difusão desses suplementos pode melhorar o prognóstico desses pacientes de maneira simples, eficaz, e com altas taxas de segurança.in English, Portuguese OBJETIVO  Analisar a reprodutibilidade inter e intraobservador da visualização e continuidade da zona juncional (ZJ) por ecografia tridimensional (3D) em mulheres inférteis, e avaliar os fatores sociodemográficos, hormonais e estruturais que afetam essas avaliações. MéTODOS  Um estudo prospectivo conduzido no Centro de Procriação Medicamente Assistida do Hospital Senhora da Oliveira, em Guimarães, Portugal. Foi realizada ecografia transvaginal 3D e gerados 2 volumes por caso. Dois observadores, cegos às avaliações um do outro, analisaram os volumes obtidos e escolheram o melhor corte coronal. Após quatro meses, a mesma análise foi realizada por um dos observadores. A visualização da ZJ foi classificada como ótima, satisfatória e não satisfatória, e a continuidade, como contínua ou descontínua. Foram avaliadas as reprodutibilidades inter e intraobservador. A influência de fatores sociodemográficos, hormonais e estruturais na ZJ foi analisada. RESULTADOS  No total, 65 mulheres foram incluídas no presente estudo.

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