A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4 T helper cell signaling, differentiation and epigenetic remodeling.

While inputs regulating CD4 T helper cell (Th) differentiation are well-defined, the integration of downstream signaling with transcriptional and epigenetic programs that define Th-lineage identity remain unresolved. PI3K signaling is a critical regulator of T cell function; activating mutations affecting PI3Kδ result in an immunodeficiency with multiple T cell defects. Using mice expressing activated-PI3Kδ, we found aberrant expression of proinflammatory Th1-signature genes under Th2-inducing conditions, both and .

Preclinical evaluation of the efficacy and safety of AAV8-TNAP-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.

We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP), with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4x108 up to 4x1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4x106 up to 4x109 (vg/b) was administered to 8-week-old AlplPrx1/Prx1 mice (a late-onset HPP model).

Anaphylaxis in pediatric patients: single-center study in a private hospital.

This study aimed to characterize the profile of probable anaphylaxis cases treated at a private pediatric hospital emergency department in São Paulo. It investigated triggering factors, the presence of cofactors, treatments administered, and follow-up for these cases through interviews with the patients' families. A single-center cross-sectional study analyzed medical records of children and adolescents treated between 2016 and 2020.

Endoplasmic reticulum stress in the salivary glands of patients with primary Sjögren's syndrome, associated Sjögren's syndrome, and non-Sjögren's sicca syndrome: a comparative analysis and the influence of chloroquine.

Background: Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are adaptive mechanisms for conditions of high protein demand, marked by an accumulation of misfolded proteins in the endoplasmic reticulum (ER). Rheumatic autoimmune diseases (RAD) are known to be associated with chronic inflammation and an ERS state. However, the activation of UPR signaling pathways is not completely understood in Sjögren's disease (SD).

Evaluating the Immunoprotective and Diagnostic Potential of Schistosoma mansoni Epitopes from Sm050890 and Sm141290 Proteins Identified Through Reverse Vaccinology.

Purpose: Schistosomiasis remains a parasitic disease affecting millions of people worldwide, requiring interventions like vaccination. In previous work, our group used reverse vaccinology to identify two epitopes from the Schistosoma mansoni proteins, Sm050890 (44-58) and Sm141290 (225-239). This study evaluated the immune response profile and protection induced by peptides, as a mixture of immunogens, in murine vaccination trials.