Dysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance of tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired motility of iNKT cells and their exclusion from tumors both contribute to the diminished anti-tumor iNKT cell response.
View Article and Find Full Text PDFThe metabolite and peptide profiles of fresh cheese fermented by three novel probiotics, B6, B44 and KF7, were investigated using LC-MS/MS-based metabolomics and peptidomics. The multivariate analysis revealed significant differences in metabolite composition between the probiotic fresh cheese and the control sample. The differential metabolites were primarily lipids and lipid-like molecules and organic oxygen compounds, which were associated with fatty acid and carbohydrate-related pathways.
View Article and Find Full Text PDFDysfunction of intratumoral invariant natural killer T (iNKT) cells hinders their antitumor efficacy, but the underlying mechanisms and the relationship with endogenous antigen priming remain to be explored. Here, we report that antigen priming leads to metabolic reprogramming and epigenetic remodeling, which causes functional reprogramming in iNKT cells, characterized by limited cytokine responses upon restimulation but constitutive high cytotoxicity. Mechanistically, impaired oxidative phosphorylation (OXPHOS) in antigen-primed iNKT cells inhibited T-cell receptor signaling, as well as elevation of glycolysis, upon restimulation via reducing mTORC1 activation, and thus led to impaired cytokine production.
View Article and Find Full Text PDFJ Leukoc Biol
September 2023
CD8+ invariant natural killer T (iNKT) cells are functionally different from other iNKT cells and are enriched in human but not in mouse. To date, their developmental pathway and molecular basis for fate decision remain unclear. Here, we report enrichment of CD8+ iNKT cells in neonatal mice due to their more rapid maturation kinetics than CD8- iNKT cells.
View Article and Find Full Text PDFActivation of mTORC1 is essential for anti-tumor function of iNKT cells. The mechanisms underlying impaired mTORC1 activation in intratumoral iNKT cells remain unclear. Via generating mice and using flow cytometry, image approach, and RNA sequencing, we studied the role of Vam6 in controlling mTORC1 activation and intratumoral iNKT cell functions.
View Article and Find Full Text PDFWith the development of human genome sequencing and techniques such as intestinal microbial culture and fecal microbial transplantation, newly discovered microorganisms have been isolated, cultured, and researched. Consequently, many beneficial probiotics have emerged as next-generation probiotics (NGPs). Currently, "safety," "individualized treatment," and "internal interaction within the flora" are requirements of a potential NGPs.
View Article and Find Full Text PDFSeveral studies have claimed that the consumption of fermented dairy products can improve human gastrointestinal (GI) health. However, the numbers of systematic clinic trials are limited. In this study, a yogurt containing both probiotics and prebiotics was developed and a double-blind randomized controlled clinical trial was carried out to evaluate the effect of the product on human gastrointestinal health in three different aspects: (1) the effect on functional constipation (FC) and functional diarrhea (FD); (2) the effect on gastrointestinal (GI) tract immune system; and (3) the changes in GI tract microbiota.
View Article and Find Full Text PDFContext: Upper respiratory tract infection (URTI) is the most common illness in humans. Fermented milk containing probiotics can mitigate URTI symptoms.
Objective: This study tests the effect of fermented milk (Qingrun), a yogurt supplemented with subsp.
Holistic benefits of human milk to infants, particularly brain development and cognitive behavior, have stipulated that infant formula be tailored in composition like human milk. However, the composition of human milk, especially lipids, and their effects on brain development is complex and not fully elucidated. We evaluated brain lipidome profiles in weanling rats fed human milk or infant formula using non-targeted UHPLC-MS techniques.
View Article and Find Full Text PDFHedgehog (Hh) signaling plays vital roles in animal development and tissue homeostasis, and its misregulation causes congenital diseases and several types of cancer. Suppressor of Fused (Su(fu)) is a conserved inhibitory component of the Hh signaling pathway, but how it is regulated remains poorly understood. Here we demonstrate that in Drosophila Hh signaling promotes downregulation of Su(fu) through its target protein HIB (Hh-induced BTB protein).
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