Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study.

BACKGROUND: To assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer. METHODS: Data of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence. RESULTS: After a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15-1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15-1.20), 1.20 (1.18-1.22), 1.69 (1.47-1.93), 1.06 (1.06-1.07), 1.08 (1.07-1.09), 1.81 (1.37-2.39), or 0.29 (0.18-0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43-5.48), 4.03 (2.69-6.03), 1.97 (1.40-2.77), 4.69 (2.98-7.37), 2.51 (1.75-3.59), 2.09 (1.51-2.89), or 2.22 (1.55-3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19-1.41). CONCLUSIONS: Unhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Exposure to acrylamide and increased risk of depression mediated by inflammation, oxidative stress, and alkaline phosphatase: Evidence from a nationally representative population-based study.

BACKGROUND: The health risk associated with acrylamide exposure has emerged as a significant issue of public health, attracting global attention. However, epidemiologic evidence on whether and how daily acrylamide exposure increases depression risk of the general population is unclear. METHODS: The study included 3991 adults from the National Health and Nutrition Examination Survey. The urinary metabolites of acrylamide (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) identified as reliable indicators of acrylamide exposure were examined to determine their relationships with depressive symptoms that were evaluated using the 9-item Patient Health Questionnaire. Besides, the measurements of alkaline phosphatase (ALP) and biomarkers of inflammation (white blood cell [WBC] count) and anti-oxidative stress (albumin [ALB]) were conducted to investigate their mediation roles in above relationships. RESULT: AAMA, GAMA, and ΣUAAM (AAMA+GAMA) were linearly associated with increased risk of depressive symptoms. Each 2.7-fold increase in AAMA, GAMA, or ΣUAAM was associated with a 30 % (odds ratio: 1.30; 95 % confidence interval: 1.09, 1.55), 47 % (1.47; 1.16, 1.87), or 36 % (1.36; 1.13, 1.63) increment in risk of depressive symptoms, respectively. Increased WBC count (mediated proportion: 4.48-8.00 %), decreased ALB (4.88-7.78 %), and increased ALP (4.93-5.23 %) significantly mediated the associations between acrylamide metabolites and depressive symptoms. CONCLUSIONS: Acrylamide exposure of the general adult population was related to increased risk of depressive symptoms, which was mediated in part by inflammation, oxidative stress, and increased ALP. Our findings provided pivotal epidemiologic evidence for depression risk increment from exposure to acrylamide.

Exposure to ambient air pollutants during circadian syndrome and subsequent cardiovascular disease and its subtypes and death: A trajectory analysis.

BACKGROUND: The association between exposure to air pollutants and cardiovascular disease (CVD) trajectory in individuals with circadian syndrome remains inconclusive. METHODS: The individual exposure levels of air pollutants, including particulate matter (PM) with aerodynamic diameter ≤ 2.5 µm (PM2.5), PM with aerodynamic diameter ≤ 10 µm (PM10), PM2.5 absorbance, PM with aerodynamic diameter between 2.5 µm and 10 µm, nitrogen dioxide (NO2), nitrogen oxides (NOx), and air pollution score (overall air pollutants exposure), were estimated for 48,850 participants with circadian syndrome from the UK Biobank. Multistate regression models were employed to estimate associations between exposure to air pollutants and trajectories from circadian syndrome to CVD/CVD subtypes (including coronary heart disease [CHD], atrial fibrillation [AF], heart failure [HF], and stroke) and death. Mediation roles of CVD/CVD subtypes in the associations between air pollutants and death were evaluated. RESULTS: After a mean follow-up time over 12 years, 12,570 cases of CVD occurred, including 8192 CHD, 1693 AF, 1085 HF, and 1600 stroke cases. In multistate model, per-interquartile range increment in PM2.5 (hazard ratio: 1.08; 95 % confidence interval: 1.06, 1.10), PM10 (1.04; 1.01, 1.06), PM2.5 absorbance (1.04; 1.02, 1.06), NO2 (1.07; 1.03, 1.11), NOx (1.08; 1.04, 1.12), or air pollution score (1.06; 1.03, 1.08) was associated with trajectory from circadian syndrome to CVD. Significant associations between the above-mentioned air pollutants and trajectories from circadian syndrome and CVD to death were observed. CVD, particularly CHD, significantly mediated the associations of PM2.5, NO2, NOx, and air pollution score with death. CONCLUSIONS: Long-term exposure to air pollutants during circadian syndrome was associated with subsequent CVD and death. CHD emerged as the most prominent CVD subtype in CVD progression driven by exposure to air pollutants during circadian syndrome. Our study highlights the importance of controlling air pollutants exposure and preventing CHD in people with circadian syndrome.

Cross-sectional and longitudinal associations of PAHs exposure with serum uric acid and hyperuricemia among Chinese urban residents: The potential role of oxidative damage.

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-µmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 µmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms.

Prenatal pregnancy-related anxiety predicts boys' ADHD symptoms via placental C-reactive protein.

Many modes of stress (i.e. life events, catastrophic events) during pregnancy have been found to increase the risk of externalizing behaviors, and probably in a sex-specific way. Maternal immune activation may be the sex-difference mechanism, but direct evidence that assess three factors in conjunction -- maternal stress, maternal immune activation, and offspring neurodevelopment --from human beings is lacking. This prospective study followed 2926 pregnant women from early pregnancy to 36 months after delivery. Pregnancy-related anxiety symptoms assessment was completed three times using the Pregnancy-Related Anxiety Questionnaire; child attention deficit hyperactivity disorder (ADHD) symptoms were assessed by the parent version of the Conners' Hyperactivity Index. More importantly, nine inflammatory cytokines were detected in placental tissues for the sex-difference mechanism investigation. Our results showed that after controlling for confounding factors, pregnancy-related anxiety during at least two trimesters of pregnancy increased the risk of ADHD for boys (adjusted odds ratio (aOR) = 3.37, 95 % confidence interval (95 % CI) = 1.78-6.38), but not for girls (aOR = 1.02, 95 %CI = 0.44-2.38), which confirmed previous findings. Besides, the structural equation models revealed that placental C-reactive protein (CRP) mRNA expression significantly mediated the association between pregnancy-related anxiety and ADHD for boys (indirect effect: ß = 0.025, P = 0.022), but not for girls (indirect effect: ß = 0.005, P = 0.589). This prospective study suggested that frequent pregnancy-related anxiety during pregnancy and its induced-placental inflammation partially contributed to the sex-bias of ADHD symptoms.

Medical applications of macrocyclic polyamines.

Macrocyclic polyamines comprise a special group of heterocycles that bind different guests. Over the past decade, medical interest has focused on macrocyclic polyamines owning to their chemical and biological properties. The discovery and development of the bicyclam AMD3100 highlighted the clinical potential of such compounds in AIDS, cancer and stem-cell mobilization. Many macrocyclic polyamines and their transition metal complexes had the cytotoxic activities to tumors through binding DNA, cleaving DNA, crosslinking DNA, or depleting the endogenous ATP levels of the tumor cells. Furthermore, macrocyclic polyamines also could be labeled with metal ionic radii and have applications in cancer radioimmunotherapy and in vivo magnetic resonance imaging (MRI). The current rational design, and medical applications of macrocyclic polyamines will be reviewed in this manuscript.

HeLa cells apoptosis induced by 1,7-dimethyl-1,4,7,10-tetraazacyclododecane.

Preliminary pharmacological tests showed that 1,7-dimethyl-1,4,7,10-tetraazacyclododecane (DMC) had antitumor activity against HeLa and A549 cell lines in vitro. The HeLa cells apoptosis induced by DMC was examined by flow cytometric meter, and further confirmed by observing the morphological changes and DNA fragmentation. No observation of A549 cells induced apoptosis was observed by DMC.

DNA hydrolysis promoted by 1,7-dimethyl-1,4,7,10-tetraazacyclododecane.

Several acyclic and macrocyclic polyamines were evaluated for their ability to cleave DNA. 1,7-Dimethyl-1,4,7,10-tetraazacyclododecane (DMC) could hydrolyze double-strand DNA at a concentration of 25microM. pH 7.2 was the optimal condition to cleave DNA in the presence of DMC. Supercoiled DNA hydrolytic cleavage by DMC was supported by the evidence from free radical quenching and T4 ligase ligation.

Specific inhibition effects of N-pentafluorobenzyl-1-deoxynojirimycin on human CD4+ T cells.

We first synthesized N-pentafluorobenzyl-1-deoxynojirimycin (5F-DNM), one new derivative of 1-deoxynojirimycin (DNM). Effects on human peripheral blood mononuclear cells (PMBC) and secretion of cytokines from human PBMC by 5F-DNM were investigated. It was first found that 5F-DNM remarkably inhibited the secretion of interleukin-4 (IL-4) and had a specific inhibition on the expression of CD4 molecules. 5F-DNM, much less toxic than cyclosporin A, might be used as a new candidate of immunosuppressant for specifically treating Th2-mediated immune diseases.