Translational research : the journal of laboratory and clinical medicine
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Mounting evidence suggests that all organisms at the cellular level respond to stress by synthesizing heat shock proteins at the expense of other proteins, and the ability of human cells to respond to heat stress decreases with aging. We thus investigate the association of 3 variants (A1267G in HSPA1B, G190C in HSPA1A, and T2437C in HSPA1L) in the heat shock protein 70 (Hsp70) family with natural longevity in a Xinjiang Hetian Uygur population. A case-control study was conducted in 191 healthy individuals greater than 90 years of age, and 53 naturally died persons 65-70 years of age. ⋯ The haplotype results were strengthened by interaction analysis, which suggests an optimal model in which G190C and T2437C exert an interacting effect on longevity. No functional significance was observed between 190G and 190C alleles in both control and heat-inducible A549 cells (P>0.05). Taken together, our findings suggested that common genetic variants in Hsp70 family might contribute interactively to longevity the Xinjiang Hetian Uygur population.
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High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce alveolar coagulopathy and fibrin depositions within the airways. Hyperoxia has been shown to increase ventilator-induced lung injury (VILI), but the mechanisms that regulate interaction between high-tidal-volume mechanical ventilation and hyperoxia are unclear. We hypothesized that mechanical stretch with hyperoxia synergistically augmented neutrophil infiltration and production of plasminogen activator inhibitor-1 (PAI-1) via the nuclear factor-kappaB (NF-kappaB) pathway. ⋯ No statistically significant increase of neutrophil infiltration and inflammatory cytokine production was found in the mice ventilated at 6 mL/kg using hyperoxia. Hyperoxia-induced augmentation of VILI was attenuated in mice with pharmacologic inhibition of NF-kappaB activity by SN-50. We conclude that hyperoxia increased high-tidal-volume-induced cytokine production and neutrophil influx through activation of the NF-kappaB pathway.