Altered Purinergic Signaling and CD8+ T Cell Dysregulation in STAT3 GOF Syndrome.

Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants in STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8+ T cells have been implicated as pathogenic drivers of autoimmunity.

Circadian Disruption Impacts Fetal Development in Mice Using High-Frequency Ultrasound.

The developmental origins of health and disease theory suggests that environmental exposures during early life, particularly during prenatal life, can greatly influence health status later in life. Irregular light-dark cycles, such as those experienced during shift work, result in the repeated disruption of circadian rhythms, which negatively impacts physiological and behavioral cycles. The purpose of our study was to assess parameters in the developing mouse embryo and fetus using high frequency ultrasound when exposed to circadian disruption.

Inflammatory Mesenchymal Stromal Cells and IFN-responsive T cells are key mediators of human bone marrow niche remodeling in CHIP and MDS.

Somatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP), potentially progressing to myelodysplastic syndromes (MDS). Here, we investigated how CHIP and MDS remodel the human bone marrow (BM) niche relative to healthy elderly donors, using single cell and anatomical analyses in a large BM cohort. We found distinct inflammatory remodeling of the BM in CHIP and MDS.

Pummelo fruit extract () reduces oxidative damage in peripheral blood of obese patients.

Objectives: To verify the level of oxidation of biomolecules in the peripheral blood of obese patients before and after incubation with the pummelo pulp extract at 25 mg/mL.

Methods: This investigation included 241 individuals, distributed across the following groups: control (n = 69; 30 men and 39 women); pre-obesity (n = 78; 29 men and 49 women); level I obesity (n = 62; 20 men and 42 women); and level II or III obesity (n = 32; 11 men and 21 women).

Results: TBARS and MN levels were significantly altered by incubation with pummelo extract in both genders and in all the groups according to their obesity level.

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.