Association between environmental exposure to perchlorate, nitrate, and thiocyanate and serum α-Klotho levels among adults from the National Health and nutrition examination survey (2007-2014).

BACKGROUND & AIMS: Aging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels. METHODS: This secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007-2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels. RESULTS: Urinary thiocyanate levels were negatively associated with α-Klotho levels (ß = - 0.006; 95% confidence interval, - 0.010 to - 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (ß = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels. CONCLUSIONS: Urinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases.

[Sodium Ferulate Attenuates Oxidative Stressvia Suppressing NALP3 Inflammasome and ERK Signal Pathway].

OBJECTIVES: Study the gene and protein expression of NACHT-PYD-containing protein 3 (NALP3) inflammasome and extracellular regulated protein kinase (ERK), the intervention effects of sodium ferulate (SF) in human lung epithelial cells A549 under oxidative stress, and to investigate the possible mechanism. METHODS: Human lung epithelial cells A549 cultured in vitro were divided into 6 groups, including control group,H2O2(200 umol/L) group, SF group (400 ug/mL), caspase-1 blockers (Z-VAD) group (Z-VAD 20 umol/L+H2O2200 umol/L), ERK blockers (PD98059) group (PD98059 50 umol/L+H2O2 200 umol/L), and SF+H2O2 group (SF 400 ug/mL+H2O2 200 umol/L). Fluorescent quantitative real-time PCR (qRT-PCR) was performed to detect the mRNA levels of caspase-1 and NALP3, the expression of caspase-1, NALP3, phosphorylated ERK p-ERK, ERK protein were evaluated by Western blot. The level of interleukin-1 ß (IL-1ß) were detected by ELISA. RESULTS: Compared with the control group,H2O2 not only increased the mRNA and protein expression levels of caspase-1 and NALP3 and the protein expression levels of p-ERK/ERK, but also enhanced the secretion of IL-1ß in human lung epithelial cells A549 (P<0.05),while SF group showed no statistic significance of those indicators above (P>0.05). The Z-VAD group, the PD98059 group and the SF+H2O2 group resisted the effects of H2O2 on A549 cells by decreasing the mRNA and protein expressions of caspase-1 and NALP3,and the protein expression of p-ERK/ERK, as well as reducing the secretion of IL-1ß(P<0.05),when compared with the H2O2 group. CONCLUSIONS: SF may reduce the expression of caspase-1, NALP3 and IL-1ß by inhibiting ERK, so as to reduce the inflammation caused by oxidative stress.

[Sodium Ferulate Attenuates Oxidative Stress Induced Inflammation via Suppressing NALP3 and NF-κB Signal Pathway].

OBJECTIVE: To study the effects of sodium ferulate on inflammation in human lung epithelial cells (A549) under oxidative stress and itsinfluence onthe expression of inflammasome NACHT-PYD-containing protein 3 (NALP3) and nuclear factor kappa B (NF-κB). METHODS: Human lung epithelial cells A549 cultured in vitro were divided into 4 groups, including control group, H2O2 (100µmol/L) stress group, NF-κB blockers group (PDTC 100 µmol/L+ H2O2 100 µmol/L), sodium ferulate (SF) intervention group (SF 400µg/mL+ H2O2 10µmol/L). The expression of NALP3,IκBα protein were evaluated by Western blot, while mRNA levels of NALP3, NF-κB (P65) were measured by qRT-PCR. The level of interleukin-1beta (ILß1) were detected by ELISA. RESULTS: H2O2 not only increased the mRNA and protein expression levels of NALP3, but also enhanced the secretion of ILß1p in human lung epithelial cells A549 (P<0. 05) when compared with control group. NF-κB blockers PDTC and sodium ferulateresisted the effects of H2O2 on A549 cells, that decreased the mRNA and protein expression of NALP3 and the mRNA expression of NF-κB (P65), reduced the degeneration of IκBα and the secretion of IL-1ß (P<0. 05) when compared to H2O2 stress group. CONCLUSION: SF may reduce the expression of NALP3 and IL-1ß by inhibiting NF-κB, so as to reduce the inflammation caused by oxidative stress.

[Hypoxemia induced the changing structure of the lung tissue in SD rat though changing blood clotting and the effects of breviscapine's intervention].

OBJECTIVE: To investigate the expressions of plasminogen activator inhibitor-1 (PAI-1), activated protein C (APC) and the histology structures of the rat lung tissues in the different hypoxia time; and to investigate the effects of breviscapine to the above changes. METHODS: Eighty SD rats were randomly divided into A (control), B (hypoxia), C (hypoxia + low-dose breviscapine) and D (hypoxia + high-dose breviscopine) groups with 20 rats in each group. Each hypoxia group placed daily pressure (101 kpa, 10% O2) environment for 8 h, low-dose and high-dose breviscapine groups were given of 10 mg/kg, 40 mg/kg breviscapine by intraperitoneal injection. On the 3rd, 7th, 14th and 21st d, 5 rats were randomly taken from each group and were killed for examination. The hematoxylin and eosin stain (HE stain) was performed for observation on pathological changes in the rat lung tissues. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for detection of the mRNA levels of transforming growth factor (TGF-beta1) and Plasminogen activator inhibitor-1 (PAI-1). Western blot analysis was applied for detection of the expression of PAI-1. Besides, APC in the bronchoalveolar lavage fluid (BALF) was determined by ELISA. RESULTS: (1) The HE stain demonstrated that compared with A group, the degree of thickening of alveolar septal the mRNA expressions of TGF-beta1 and PA-1, and the protein expressions of PAI-1 in B group were increased (P < 0.05), and the expression of APC in the BALF was decreased (P < 0.05). And with prolonged hypoxia, the more significant of these changes were observed. Positive correlation was found between the mRNA levels of PAI-1 and TGF-beta1 (r = 0.936, P < 0.05). (2) Compared with B group, the increased thicknesses of alveolar septal in C and D groups were lightened, the mRNA expressions of TGF-beta1 and PAI-1, and the protein expression of PAI-1 were decreased (P < 0.05), and the expressions of APC in the BALF was increased (P < 0.05). With increasing dose, the expression levels of each factor gradually reduced or increased. CONCLUSION: Hypoxia may cause coagulant function abnormality to increase clotting activity and reduce fibrinolytic activity and the anticoagulant activity, inducing alveolar septal thickening, and the mechanism of above changes may related to the TGF-beta1 signaling pathways. Breviscapine could improve hypoxia-induced hypercoagulable state that alleviate alveolar septal thickening.