Inflammation influences the development of cancer. The nitric oxide synthase (NOS2) is induced by inflammatory cytokines, e.g., tumor necrosis factor ␣ and interleukin 1, and produces nitric oxide (NO ⅐ ), a critical mediator of the inflammatory response. Because p53 governs NO ⅐ production by transcriptionally transrepressing NOS2, we used a genetic strategy to determine whether NO ⅐ and p53 cooperatively regulate tumorigenesis. Lymphomas developed more rapidly in p53؊/؊NOS2؊/؊ or p53؊/؊NOS2؉/؊ mice than in p53؊/؊NOS2؉/؉ mice that were crossbred into a >95% C57BL6 background and maintained in a pathogenfree condition. Likewise, sarcomas and lymphomas developed faster in p53؉/؊NOS2؊/؊ or p53؉/؊NOS2؉/؊ than in p53؉/؊NOS2؉/؉ mice. When compared with the double knockout mice, p53؊/؊NOS2؉/؉ mice showed a higher apoptotic index and a decreased proliferation index with an increased expression of death receptor ligands, CD95-L and tumor necrosis factor-related apoptosis-inducing ligand, and the cell cycle checkpoint protein, p21 waf1 , in the spleen and thymus before tumor development. Furthermore, mice deficient in both p53 and NOS2 produced a high level of anti-inflammatory interleukin 10 when compared with p53-deficient mice. These studies provide genetic and mechanistic evidence that NO ⅐ can suppress tumorigenesis.
ObjectivesTo evaluate the effect of oral nutritional supplementation (ONS) plus dietary counselling (DC) (intervention) versus DC alone (control) on growth and upper respiratory tract infection (URTI) in nutritionally at-risk, picky eating children in India.MethodsWe performed a 90-day, prospective, randomized, controlled trial. A total of 255 children aged 24–72 months with a weight-for-age z-score ≥−2 and <−1, picky eating behaviour, and acute URTI were randomized to the control (n = 128) or intervention group (n = 127). The outcomes included the change in weight-for-age z-score from days 1 to 90 and the URTI incidence.ResultsThe mean age was 44.0 ± 14.3 months. The intervention group showed a significantly greater increase in mean weight-for-age and body mass index-for-age z-scores compared with the control group from day 10 onwards. Higher energy intake in the intervention group was observed at all follow-up visits, except for day 10. The incidence of URTI in the control group was 2.01 times higher than that in the intervention group, controlling for confounding factors.ConclusionsONS plus DC is effective for improving weight and reducing the incidence of URTI in nutritionally at-risk, picky eating children with an acute URTI episode.
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