Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism.

BACKGROUND: The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinformatics and clinical data analysis to determine its role in CKD. RESULTS: We analyzed the transcriptomic and clinical data from the Nephroseq v5 database and found that the Klotho gene was mainly expressed in the tubulointerstitium, and its expression was significantly positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with blood urea nitrogen (BUN) in CKD. We further found that Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium by analyzing two large sample-size CKD tubulointerstitial transcriptome datasets. By analyzing 10-year clinical data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we also found that Klotho negatively correlated with inflammatory biomarkers and triglyceride and positively correlated with eGFR in the CKD population. Mediation analysis showed that Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism, while in the CKD population, it primarily manifested by mediating the inflammatory response. Restricted cubic spline (RCS) analysis showed that the optimal concentration range for Klotho to exert its biological function was around 1000 pg/ml. Kaplan-Meier curves showed that lower cumulative hazards of all-cause mortality in participants with higher levels of Klotho. We also demonstrated that Klotho could reduce cellular inflammatory response and improve cellular lipid metabolism by establishing an in vitro model similar to CKD. CONCLUSIONS: Our results suggest that Klotho exerts protection in CKD, which may be mainly related to the regulation of inflammatory response and lipid metabolism, and it can serve as a potential biomarker for CKD.

Association between ethylene oxide levels and depressive symptoms: A cross-sectional study based on NHANES 2013-2018 database.

BACKGROUND AND AIM: Ethylene oxide (EO) is a commonly used compound with known health risks. However, the specific association between EO exposure and the development of depressive symptoms has not been well established. Therefore, this study aimed to examine the potential association between EO exposure, as indicated by hemoglobin adduct of ethylene oxide (HbEO) levels, and the occurrence of depressive symptoms. METHODS: We employed logistic regression, restricted cubic spline, and subgroup analysis to investigate the association between EO exposure and the occurrence of depressive symptoms. Additionally, we conducted a mediating effect analysis to explore the potential factors influencing the association between EO exposure and depressive symptoms. RESULTS: Elevated HbEO levels were associated with the development of depressive symptoms. After adjusting for potential confounders, the highest quartile of HbEO levels showed an odds ratio (OR) of 3.37 [95 % confidence interval (CI): 1.87-6.10, P = 0.002] compared with the lowest quartile. Additionally, a linear association was observed between HbEO levels and the risk of depressive symptoms. We also revealed that the levels of several inflammatory factors and triglycerides mediated the association between EO exposure and the occurrence of depressive symptoms. CONCLUSIONS: Higher levels of EO exposure were related to an increased risk of developing depressive symptoms. The analysis also suggested that the inflammatory response might play a mediating role in the pathway from EO exposure to depressive symptoms.

Coffee consumption and all-cause and cardiovascular mortality in older adults: should we consider cognitive function?

Background: The association between coffee and mortality risk has been found in most previous studies, and recent studies have found an association between coffee consumption and cognition. However, there is still a lack of research exploring whether the association between coffee and mortality is influenced by cognitive function. Objective: The purpose of this study was to explore the association of coffee, caffeine intake in coffee and decaffeinated coffee with all-cause mortality and cardiovascular disease (CVD) mortality in older adults with different cognitive performances. Methods: The study was based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Coffee and caffeine consumption data were obtained from two 24-h dietary recalls. Individual cognitive functions were assessed by CERAD-word learning test (CERAD-WLT), animal fluency test (AFT), and digit symbol substitution test (DSST). In addition, principal component analysis (PCA) was performed with the above test scores to create global cognitive score. The lowest quartile of scores was used to classify cognitive performance. Cox regression and restricted cubic spline (RCS) were applied to assess the relationship between coffee and caffeine consumption and mortality. Results: In the joint effects analysis, we found that those with cognitive impairment and who reported without drinking coffee had the highest risk of all-cause and cardiovascular mortality compared with others. In the analysis of population with cognitive impairment, for all-cause mortality, those who showed cognitive impairment in the AFT displayed a significant negative association between their total coffee consumption and mortality {T3 (HR [95% CI]), 0.495 [0.291-0.840], p = 0.021 (trend analysis)}. For DSST and global cognition, similar results were observed. Whereas for CERAD-WLT, restricted cubic spline (RCS) showed a "U-shaped" association between coffee consumption and mortality. For CVD mortality, a significant negative trend in coffee consumption and death was observed only in people with cognitive impairment in AFT or DSST. In addition, we observed that decaffeinated coffee was associated with reduced mortality in people with cognitive impairment. Conclusion: Our study suggested that the association between coffee consumption and mortality is influenced by cognition and varies with cognitive impairment in different cognitive domains.

Association between exposure to multiple polyaromatic hydrocarbons and periodontitis: findings from a cross-sectional study.

The impact of environmental pollutant exposure on periodontitis has raised significant concerns. But the association between exposure to multiple polyaromatic hydrocarbons (PAHs) and periodontitis still remained unclear. Our study investigated the association of exposure to multiple PAHs with periodontitis. A total of 1880 participants from the National Health and Nutrition Examination Survey (NHANES) were included in this study. Urinary samples of the participants exposed to six PAHs, namely, 1-hydroxynaphthalene (1-OHN), 2-hydroxynaphthalene (2-OHN), 3-hydroxyfluorene (3-OHF), 2-hydroxyfluorene (2-OHF), 1-hydroxyphenanthrene (1-OHPhe), and 1-hydroxypyrene (1-OHPyr), were investigated. Multiple logistic regression, restricted cubic spline, and Bayesian kernel machine regression (BKMR) models were employed to identify the association between PAH exposures and periodontitis. The dose-response analysis exhibited a gradual increase in the periodontitis risk with an increase in multiple PAHs. After adjustment for several potential confounders, the odds ratio of the highest quartile (Quartile 4) was 1.648 (95% confidence interval (CI) 1.108-2.456, P = 0.014, P-t = 0.017) for 2-OHN, 2.046 (95%CI 1.352-3.104, P < 0.001, P-t = 0.005) for 3-OHF, 1.996 (95% CI 1.310-3.046, P = 0.001, P-t = 0.003) for 2-OHF, 1.789 (95% CI 1.230-2.604, P = 0.002, P-t = 0.003) for 1-OHPhe, and 1.494 (95% CI 1.025-2.181, P = 0.037, P-t = 0.021) for 1-OHPyr compared with that of the lowest quartile (Quartile 1). BKMR illustrated that the overall effect of the PAH mixture was positively related to periodontitis. Mediation analysis identified blood neutrophils as a partial mediator of 3-OHF and 2-OHF. Exposure to multiple PAHs was positively associated with periodontitis in US adults, and blood neutrophils mediate the effects of 3-OHF and 2-OHF therein.

Association between exposure to phenols and parabens and cognitive function in older adults in the United States: A cross-sectional study.

BACKGROUND: People are commonly exposed to mixtures of parabens and phenols. Most studies investigating such exposure and cognitive performance tend to assess only single chemicals, and the tools used to assess cognitive function are not uniform. OBJECTIVE: This study aimed to examine the association between multiple parabens and phenols and cognitive function in older Americans. METHODS: The study included data of older Americans from two cycles of the NHANES survey. Participants were divided into normal cognitive performance and low cognitive performance groups based on the scores of four cognitive tests: the Immediate Recall test (IRT), the Delayed Recall test (DRT), the Animal Fluency test (AFT) and the Digit Symbol Substitution test (DSST). Generalized linear regression models (GLMs), restricted cubic spline (RCS), weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were used to assess relationships between chemical exposure and cognitive performance. RESULTS: In this cross-sectional study, a total of 961 participants, 470 males and 491 females, were included. GLMs revealed positive association between high levels of bisphenol A (BPA) and low cognitive performance on DRT, especially in male (OR (95%CI): 2.25 (1.10-4.61)), and this association was consistent with WQS and BKMR. In female participants, the third quartile of BPA exposure showed a positive association with low cognition on IRT and global cognition. GLMs also showed that high levels of propylparaben were positively associated with cognitive performance on the IRT in male participants (OR (95%CI): 0.37 (0.18-0.76)). In BKMR, an overall positive correlation between the mixture and low cognition as measured with DRT was observed in male subjects when the mixture was at the 65th percentile or higher. CONCLUSION: Exposure to a mixture of parabens and phenols was positively associated with low cognitive performance on DRT in older male subjects, while BPA was the main driver of this outcome.

Penetration Enhancing of an Erythrocyte-Mimicking Nanoplatform via Papaverine for Radiosensitization.

PURPOSE: Radiotherapy (RT) is recommended as an extensive therapeutic regimen for cancer patients; however, cancer radio-resistance results from reduced oxygen levels (hypoxia) in the tumor microenvironment. Herein, we report a therapeutic strategy that greatly enhances the treatment effects of RT. METHODS: Specifically, papaverine (ppv), an FDA-approved smooth muscle relaxant, was applied in the strategy. Ppv improved blood flow via vasodilation to deliver sufficient oxygen to the hypoxic solid tumor and further resulted in increased tumor penetration of the radiosensitizer, significantly enhancing the radiosensitization compared with no ppv treatment. Additionally, tantalum oxide nanospheres were cloaked in red blood cell membranes (TaOx@M) to achieve greater biocompatibility, non-immunogenicity, and a longer circulation time. RESULTS: As a high-Z element, tantalum provides localized dose enhancement and thereby boosts the efficacy of RT. Vasodilation, the oxygenation of cancer cells, and the improved accumulation and retention of TaOx@M in the tumor region were verified in vivo. Furthermore, compared with RT alone, the combined vasodilation and nanosphere camouflaging strategy more efficiently suppressed the growth of K7M2 tumors in mice. CONCLUSION: The results of this study suggest that the integration of TaOx@M and ppv has excellent potential for improving RT efficacy.

Shape Deformation and Drag Variation of a Coupled Rigid-Flexible System in a Flowing Soap Film.

We experimentally study the soap film flow past a rigid plate with a trailing closed filament of a small bending modulus acting as a flexible afterbody. The complex fluid-structure interactions due to the deformable afterbody shape and corresponding dynamics are studied. We find that the shape of the afterbody is determined by filament length, filament bending modulus, and flow speed. A significant drag reduction of approximately 10.0% is achieved under specific conditions. We analyze the drag mechanism by characterizing the deformable afterbody shape. Our experiment and modeling suggest that such a flow control strategy and sizable drag reduction are expected to occur over a specific flow speed regime when a suitable flexible coating is added.