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Hyperreactive B cells instruct their elimination by T cells to curb autoinflammation and lymphomagenesis.
Immunity
December 2024
Institute of Experimental Hematology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 81675 Munich, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Max-Planck Institute of Biochemistry, 82152 Planegg, Germany. Electronic address:
B cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not.
View Article and Find Full Text PDFBody mass index and waist-to-height ratio effect on mortality in non-alcoholic fatty liver: revisiting the obesity paradox.
Front Endocrinol (Lausanne)
December 2024
Department of Gastroenterology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Purpose: Emerging research indicates that individuals with non-alcoholic fatty liver disease (NAFLD) who carry excess weight have similar or even higher survival rates than their normal-weight counterparts. This puzzling "obesity paradox" may be attributed to underlying biases. To explore this phenomenon, we examined data extracted from the third National Health and Nutrition Examination Survey (NHANES) III, which spanned from 1988-1994.
View Article and Find Full Text PDFThe Paradox of Antimalarial Terpenoid Isonitrile Biosynthesis Explained. Proposal of Cyanoformate as an NC Delivery Vector.
J Nat Prod
December 2024
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States.
Marine sponge diterpenoid isonitriles are exceptional nitrogenous natural products that exhibit antiplasmodial activity. Their biosynthesis presents a biosynthetic puzzle: how do the elements of NC engage terpenyl carbocations in isoprenoid secondary metabolism, and what is the biosynthetic precursor of the NC group? Cyanoformic acid (NC-COOH, ) is proposed as a plausible delivery vehicle of NC that resolves a paradox in the commonly held proposition that an inorganic cyanide anion, CN, terminates terpenoid isonitrile (TI) biosynthesis. DFT calculations of NC-COOH and its conjugate base, cyanoformate, NC-COO (), support high nucleophilicity at N and explain bond-forming constitutionality: attack at N and formation of an isonitrile over its nitrile isomer.
View Article and Find Full Text PDFHydroxyurea blunts mitochondrial energy metabolism and osteoblast and osteoclast differentiation exacerbating trabecular bone loss in sickle cell mice.
Cell Death Dis
December 2024
Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Sickle cell disease (SCD) is a severe hematological disorder characterized by erythrocyte sickling that causes significant morbidity and mortality. Skeletal complications of SCD include a high incidence of bone loss, especially in vertebrae, leading to fragility fractures that contribute to disease burden. Whether hydroxyurea (HU), a front-line therapy for SCD ameliorates bone disease has not been established.
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