P19

Major histocompatibility complex class II (MHC-II) deficiency or bare lymphocyte syndrome (BLS) is a rare, early-onset, autosomal recessive, and life-threatening inborn error of immunity. We aimed to assess the demographic, clinical, laboratory, follow-up, and treatment characteristics of patients with MHC-II deficiency, together with their survival. We retrospectively investigated 21 patients with MHC-II deficiency. Female/male ratio was 1.63. The median age at diagnosis was 16.3 months (5 months-9...

NIPP1 is a ubiquitously expressed regulatory subunit of protein phosphatase-1. Its embryonic deletion in keratinocytes causes chronic sterile skin inflammation, epidermal hyperproliferation and resistance to mutagens in adult mice. To explore the primary effects of NIPP1 deletion, we first examined hair-cycle progression of NIPP1 skin knockouts (SKOs). The entry of the 1st hair cycle in the SKOs was delayed due to prolonged quiescence of hair-follicle stem cells (HFSCs). In contrast, the entry of the 2nd hair cycle in the SKOs was advanced as a result of precocious activation of HFSCs...

Patients with hypertension or obesity can develop glomerular dysfunction characterized by injury and depletion of podocytes. To better understand the molecular processes involved, young mice were treated with either deoxycorticosterone acetate (DOCA) or fed a high-fat diet (HFD) to induce hypertension or obesity, respectively. The transcriptional changes associated with these phenotypes were measured by unbiased bulk mRNA-sequencing of isolated podocytes from experimental models and their respective controls...

Anti-cancer peptides (ACPs) are short peptides known for their ability to inhibit tumor cell proliferation, migration, and the formation of tumor blood vessels. In this study, we designed ACPs to target receptors often overexpressed in cancer using a systematic in silico approach. Three target receptors (CXCR1, DcR3, and OPG) were selected for their significant roles in cancer pathogenesis and tumor cell proliferation. Our peptide design strategy involved identifying interacting residues (IR) of these receptors, with their natural ligands serving as a reference for designing peptides specific to each receptor...

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In recent years, the problems associated with continuous cropping (CC) that cause soil degradation have become increasingly serious. As a key soil quality property, dissolved organic matter (DOM) affects the circulation of carbon and nutrients and the composition of bacterial communities in soil. However, research on the changes in the molecular composition of DOM after CC is limited. In this study, the soil chemical properties, DOM chemical diversity, bacterial community structure, and their interactions are explored in the soil samples from different CC years (CC1Y, CC3Y, CC5Y, and CC7Y) of tobacco...

INTRODUCTION: Citrus chlorotic dwarf-associated virus (CCDaV) is an economically important citrus virus associated with leaf curling, deformation, and chlorosis found in China. Plants have evolved RNA silencing to defend against viral infections; however, the mechanism by which CCDaV suppresses RNA silencing in citrus remains unknown. METHODS: Six proteins encoded by CCDaV were ectopically expressed in Nicotiana benthamiana 16c using the pCHF3 vector to identify RNA-silencing suppression activities...

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA...

Psoriatic arthritis and plaque psoriasis are autoimmune conditions affecting multiple organs, including the skin. The pathophysiology and etiology of these conditions are not fully understood; however, numerous factors are believed to play a critical role, including genetics and environmental risk factors. Furthermore, research suggests the IL-23/IL-17 pathway partially mediates these diseases. Once the IL-23 receptor is bound and activated, two subunits, p19, and p40, act through different signaling pathways...

BACKGROUND: Efficacy and safety of mirikizumab, a p19-targeted anti-interleukin-23 monoclonal antibody, for moderately to severely active ulcerative colitis was demonstrated previously. We evaluated clinical response, baseline characteristics, and clinical status in patients not responding by 12 weeks (W) of induction who then received extended induction treatment. METHOD: Patients unresponsive to 300 mg of intravenous (IV) mirikizumab every 4 weeks by W12 received 3 additional 300 mg IV doses every 4 weeks...

Risankizumab is a high-affinity neutralizing anti-interleukin (IL)-23 monoclonal antibody marketed in over 40 countries across the globe to treat several inflammatory diseases, such as plaque psoriasis (PsO), psoriatic arthritis (PsA), and Crohn's disease (CD). This paper reviews the regulatory approval, mechanism of action, pharmacokinetics (PKs)/pharmacodynamics, immunogenicity, and clinical efficacy and safety data for risankizumab, focusing on the three main approved indications. Risankizumab binds to the p19 subunit of IL-23 and inhibits IL-23 from interacting with the IL-23 receptor and subsequent signaling...

A tomato bushy stunt virus (TBSV)-derived vector system was applied for the delivery of CRISPR/Cas9 gene editing materials, to facilitate rapid, transient assays of host-virus interactions involved in the RNA silencing pathway. Toward this, single guide RNAs designed to target key components of the virus-induced host RNA silencing pathway ( AGO2 , DCL2 , HEN1 ) were inserted into TBSV-based GFP-expressing viral vectors TBSV-GFP (TG) and its P19 defective mutant TGΔP19. This produced rapid, efficient, and specific gene editing in planta...

BACKGROUND: Risankizumab and guselkumab, inhibitors of the interleukin (IL)-23 p19 subunit, are approved for treatment of adult patients with moderate-to-severe plaque psoriasis, and both have shown superiority over placebo in randomised clinical trials. Both agents have also shown superiority to the IL-17 inhibitor secukinumab at different timepoints. We investigated the efficacy and safety of the IL-23 p19 inhibitor mirikizumab versus placebo and secukinumab for patients with moderate-to-severe plaque psoriasis...

Thrace is a part of the Marmara Region northwest of Türkiye. This region hosts several lentic ecosystems used for irrigation and drinking water supply. The present study was conducted to analyze the temporal distributions of water quality parameters (WQPs) of lentic ecosystems (lacustrine habitats), including lakes (L1-L2), reservoirs (R1-R12), and ponds (P1-P19) of the Thrace Region. Thirty-three lacustrine habitats were identified in the region. Freshwaters were collected in the wet (end of winter) and dry (end of summer) seasons of 2021-2022 and tested for 12 WQPs...

Tomato torrado virus (ToTV) is a type member of the Torradovirus genus in the Secoviridae family known to cause severe necrosis in susceptible tomato varieties. ToTV also infects other Solanaceae plants, including Nicotiana benthamiana, where it induces distinctive disease symptoms: plant growth drop with the emergence of spoon-like malformed systemic leaves. Virus-induced post-transcriptional gene silencing (PTGS) is significant among plant defense mechanisms activated upon virus invasion. The PTGS, however, can be counteracted by suppressors of RNA silencing commonly found in viruses, which efficiently disrupt the antiviral defense of their host...

BACKGROUND: The major antigens encoded by Mycobacterium tuberculosis-specific genomic regions of differences (RDs) could be useful in the development of new vaccines and/or diagnostic reagents using T-cell and/or antibody assays. In particular, RD1 proteins PE35, PPE68, ESXA, ESXB, and RD9 protein ESXV and their peptides have been identified as major T-cell antigens. However, little is known about their antibody reactivities in different mammalian species. This study aims to determine the antigen-specific antibody reactivities to the above antigens and their peptides in three different mammalian species, i...

Florfenicol (FLO) has been shown to elicit diverse toxic effects in plants, insects, and mammals. Previously, our investigations revealed that FLO induced abnormal cardiac development and early embryonic mortality in chicken embryos. However, the effect of FLO on mitochondrial responses in stem cells remains unclear. In this study, we show that FLO significantly diminishes proliferation viability and obstructs the directed differentiation of P19 stem cells (P19SCs) into cardiomyocytes. Proteomic analysis revealed 148 differentially expressed proteins in response to FLO...

BACKGROUND: Short-term efficacy and safety of brazikumab (MEDI2070), a human monoclonal antibody and anti-p19 subunit inhibitor of interleukin-23, was demonstrated in a phase 2a trial in patients with moderate-to-severe active Crohn's disease (CD). We report brazikumab long-term safety and tolerability from the open-label period of this phase 2a study. METHODS: Patients who completed the 12-week, double-blind induction period were eligible for inclusion in an open-label period where all patients received subcutaneous brazikumab (210 mg) every 4 weeks for 100 weeks...

Psoriasis is a chronic inflammatory cutaneous disease, affecting up to 3% of the worldwide population. Several clinical phenotypes can be distinguished. Among these, erythrodermic psoriasis (EP) is a rare and severe variant (less than 3% of cases), characterized by severe generalized erythema and scaling affecting at least 90% of the body surface area. EP is often a life-threatening condition, since several systemic symptoms (tachycardia, fever, fatigue, lymphadenopathy, dehydration, serum electrolyte disturbances) can be associated...

BACKGROUND AND AIMS: Crohn's disease (CD) symptoms are a main driver for impaired quality of life and fast relief is important for patient care. Stool frequency (SF) and abdominal pain score (APS) are patient reported outcomes (PROs) measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab (RZB), a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints...