PI3K involvement has been implicated in the TLR signal pathway. However, the precise roles of the different classes of PI3K in the pathway remain elusive. In this study, we have explored the functions of class I and class III PI3K in the TLR signal pathway using specific kinase mutants and PI3K lipid products. Our results reveal that class III PI3K specifically regulates CpG oligodeoxynucleotide (ODN)-induced cytokine and NO production as well as NF-κB activation, whereas class I PI3K regulates both CpG ODN- and LPS-induced IL-12 production and NF-κB activation. Additional studies of CpG ODN uptake with flow cytometric analysis show that class III PI3K, but not class I, regulates cellular CpG ODN uptake. Furthermore, experiments with MyD88-overexpressing fibroblast cells transfected with dominant-negative mutants of PI3K demonstrate that class III PI3K regulates CpG ODN-mediated signaling upstream of MyD88, while class I PI3K regulation is downstream of MyD88. These results suggest that class I and class III PI3K play distinct roles in not only the uptake of CpG ODN, but also responses elicited by CpG ODN and LPS.
The human six-transmembrane epithelial antigen of the prostate (STEAP) proteins, which include STEAP1–4 and atypical STEAP1B, contain six transmembrane domains and are located in the cell membrane. STEAPs are considered archaeal metal oxidoreductases, based on their heme groups and F420H2:NADP+ oxidoreductase (FNO)-like structures, and play an important role in cell metal metabolism. Interestingly, STEAPs not only participate in biological processes, such as molecular transport, cell cycling, immune response, and intracellular and extracellular activities, but also are closely related to the occurrence and development of several diseases, especially malignant tumors. Up to now, the expression patterns of STEAPs have been found to be diverse in different types of tumors, with controversial participation in different aspects of malignancy, such as cell proliferation, migration, invasion, apoptosis, and therapeutic resistance. It is clinically important to explore the potential roles of STEAPs as new immunotherapeutic targets for the treatment of different malignant tumors. Therefore, this review focuses on the molecular mechanism and function of STEAPs in the occurrence and development of different cancers in order to understand the role of STEAPs in cancer and provide a new theoretical basis for the treatment of diverse cancers.
The global nutrition transition has contributed to child obesity and dental caries in developing countries, including Vietnam. Few studies have described the nutrition and oral health of mothers and children. This a descriptive study of the nutrition and oral health characteristics of a convenience sample of 571 children aged 2 to 5 years and their mothers from 5 urban preschools in Central and South Vietnam. The mothers completed a written survey, and the children received dental exams and weight/height measurements. High rates of bottle-feeding and the consumption of sweets were reported. One in 4 children were overweight/obese. Dental caries increased in prevalence and severity by age—at 5 years, 86.7% of children had tooth decay in an average of 8.5 teeth, and 70.9% experienced mouth pain. Most mothers and children suffered from untreated dental disease. Public health programs should focus on nutrition and oral health promotion, as well as dental treatment from pregnancy and birth onward.
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