ObjectivesCritically shortening of telomere length caused by various factors including environmental pollutants results in genome instability and age-associated diseases. Lead is one of the ...ubiquitous environmental and occupational pollutants, potentially affecting public health even at a low level. However, it is still unclear whether lead exposure affects telomere length. This study aims to investigate the association between lead exposure and peripheral white blood cell telomere length (PWBTL) in Chinese battery manufacturing plant workers.MethodsLead levels in blood (BLL) and urine (ULL) were evaluated using flame atomic absorption spectrometry and lead mobilisation test for body lead burden (BLB) assessment, respectively. Quantitative PCR was employed to determine relative PWBTL. Univariate and multivariate analyses were performed to examine the associations of telomere length and other variables.ResultsPWBTL averaged 1.76 (telomere/single-copy gene of albumin, T/S) in 144 battery plant workers. Significantly shorter PWBTL was observed in the workers with abnormal BLL and/or ULL than those with normal ones (1.66±0.63 vs 1.91±0.46, p=0.010). In all workers, PWBTL was in negative correlations with BLL, ULL, time working at the plant (working length) and body mass index. A strong inverse correlation was observed between PWBTL and BLB (r=−0.70, p<0.0001) in those with abnormal BLL and ULL. GLMSELECT model showed in the subgroup of inpatient workers, working length and BLB were significantly in inverse associations with PWBTL, while BLL was in weak positive association with PWBTL.ConclusionsThese findings suggest that PWBTL shortening is associated with long-term lead exposure and that PWBTL may be one of the targets damaged by lead toxicity.
To explore the association between the self-reported health status, depressive tendency, psychological capital, and self-acceptance of college students in China during the COVID-19 pandemic.
Using ...the online survey platform "questionnaire star", a two-phase cross-sectional study was conducted on a total number of 1438 undergraduates with informed consents. The questionnaires of Self-Rated Health Measurement Scale (SRHMS), the Center for Epidemiological Studies-Depression Scale (CES-D), Psychological Capital Questionnaire (PCQ-24), and self-acceptance questionnaire were administered to each participant.
Male college students had significantly higher depressive tendency scores than female (17.59 vs. 15.82) (
< 0.01). College students having no siblings had significantly higher psychological capital scores than those having siblings (108.63 vs. 105.60) (
< 0.05). Exercise had significantly positive associations with self-rated health, psychological capital, and self-acceptance scores, while online time per day had significantly negative associations. Multivariate analysis showed that the interaction between depressive tendency, psychological capital, and self-acceptance was statistically significant (
0.004,
0.013 for phase 1 and
0.002,
0.025 for phase 2) in health status with depressive tendency ranking the top (
-0.54 for phase 1 and -0.41 for phase 2,
< 0.001). Mediation analysis showed that psychological capital and self-acceptance modified the association of depressive tendency with health status.
Physical exercise is beneficial to both physical and psychological health. Depressive tendency is the main risk factor that associates with self-rated health. Regardless of depressive tendency level, high psychological capital and self-acceptance could improve college students' health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human beings are inevitably exposed to ubiquitous phthalate esters (PAEs). Processed, packaged foods are popular nowadays, in which emulsifiers are frequently added as food additives. It is unclear ...how emulsifiers affect the bioavailability of ingested PAEs contaminants and their toxicities. The purposes of our study were to explore whether food emulsifier Glycerin Monostearate (GMS) could increase the internal exposure levels of six priority controlled PAEs and affect their reproductive toxicities when male rats are exposed to PAEs mixture (MIXPs). The male rats were exposed to MIXPs by gavage for thirty days in combination with or without given GMS. Phthalate monoesters (MPAEs), primary metabolites of PAEs, in rat urine were used as biomarkers to predict the internal exposure levels of the six PAEs, and their concentrations were determined using UPLC-MS. The reproductive toxicity was evaluated using serum testosterone levels test and histopathology of testes. Results showed that compared to PAEs exposure alone, the internal exposure levels of PAEs increased by 30%-49% in the presence of GMS. PAEs exposure led to the reduction of testosterone level by 23.4%-42.1% in the presence and absence of GMS, respectively, compared to the baseline. Testosterone levels in MIXPs+GMS and DEHP+GMS group were decreased by 9.1% and 13.6%, respectively, compared with MIXPs and DEHP group. Histopathology showed that injuries of testis (deciduous spermatids) were observed, and GMS exacerbated the injuries. The results indicated food emulsifiers chronically taken up might increase safety risks of food PAEs contaminants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long‐term overweight and substantial weight gain over adulthood are known risk factors of endometrial cancer, but the timing of weight gain in relation to risk and the effect of weight change on age ...at diagnosis remain unclear. A population‐based case–control study was conducted to evaluate the long‐term effect of body weight on endometrial cancer risk. The study enrolled 668 incident cases and 674 population controls. Anthropometric features in each decade of adult life were ascertained through in‐person interview and analyzed for their associations with endometrial cancer using unconditional logistic regression. As expected, high body mass index (BMI) was significantly associated with increased risk. Women who were overweight or obese at the time of interview had adjusted odds ratios of 1.54 (95%CI 1.13–2.10) and 4.76 (95%CI 3.50–6.49), respectively, compared to women of normal weight. Similar associations were observed for BMI assessed at each decade of adult life. More importantly, women who were overweight (BMI ≥ 25) in their 20s or 30s and maintained the overweight throughout life had significantly higher risk than those who became overweight at ages 40s or 50s. Women with substantial weight gain (≥35%) in early adulthood (age 20s) developed the disease 10 years earlier than those without such weight change in early life. These observations further confirm the critical link between body weight and development of endometrial cancer.
Little is known about the causes of meningioma. Obesity and obesity-related traits have been reported in several epidemiological observational studies to be risk factors for meningioma. We performed ...an analysis of genetic variants associated with obesity-related traits to assess the relationship with meningioma risk using Mendelian randomization (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. We considered 11 obesity-related traits, identified genetic instruments for these factors, and assessed their association with meningioma risk using data from a genome-wide association study comprising 1,606 meningioma patients and 9,823 controls. To evaluate the causal relationship between the obesity-related traits and meningioma risk, we consider the estimated odds ratio (OR) of meningioma for each genetic instrument. We identified positive associations between body mass index (odds ratio OR
= 1.27, 95% confidence interval CI = 1.03-1.56, P = 0.028) and body fat percentage (OR
= 1.28, 95% CI = 1.01-1.63, P = 0.042) with meningioma risk, albeit non-significant after correction for multiple testing. Associations for basal metabolic rate, diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, total cholesterol, triglycerides and waist circumference with risk of meningioma were non-significant. Our analysis provides additional support for obesity being associated with an increased risk of meningioma.
Obesity among breast cancer survivors is associated with increased risk for recurrence and mortality. The hormone ghrelin plays a role in initiating appetite and thus regulating body weight. This ...study aims to determine the effect of a lifestyle intervention on ghrelin levels in breast cancer survivors with a body mass index (BMI) ≥ 25 kg/m
. The Lifestyle, Exercise, and Nutrition (LEAN) study was a 6-month randomized trial, examining the effectiveness of a weight loss intervention versus usual care in 151 breast cancer survivors with BMI ≥ 25 kg/m
. Ghrelin was measured in fasting baseline and 6-month blood samples. Baseline associations between ghrelin, body composition, and blood biomarkers were examined. Six-month change in ghrelin was compared between study arms. Ghrelin measurements were available for 149 women. At baseline, ghrelin was correlated with age (r = 0.28, p < 0.001) and inversely correlated with weight (r = -0.18, p = 0.03), lean body mass (r = -0.18, p = 0.02), and leptin (r = -0.18, p = 0.03). Over 6 months, ghrelin increased by 144 pg/mL (7.2%) in the intervention and decreased by 466 pg/mL (32.5%) in the usual care (p = 0.07). Among all women, greater weight loss was associated with an increase in ghrelin (p = 0.01). These findings indicate that weight loss, achieved through a lifestyle intervention, is associated with higher ghrelin levels in breast cancer survivors which may be informative for developing sustainable weight loss programming for this population. Future research should investigate the long term impacts of lifestyle interventions on ghrelin levels in the context of weight maintenance and weight regain.
The study was conducted to determine the effect of physical activity on DNA methylation and to predict the consequence of this effect concerning gene expression and breast cancer survival. Blood ...samples, collected from 12 breast cancer patients who participated in a randomized clinical trial of exercise, were examined for exercise-related changes in DNA methylation using a methylation microarray. Tumor samples of 348 breast cancer patients were analyzed with qRT-PCR and qMSP to determine gene expression and methylation identified in the microarray analysis. Cox regression models were developed to predict survival outcomes in association with gene expression and methylation. After 6 months of moderate-intensity aerobic exercise, changes in DNA methylation (
P
< 5 × 10
−5
) in peripheral blood leukocytes were detected in 43 genes from a panel of 14 495. Based on the list, we analyzed gene expression in association with overall survival in breast tumors and found three genes whose methylation was reduced after exercise were favorably in association with overall survival, i.e., higher expression associated with better survival. Of the three genes, L3MBTL1 was a putative tumor suppressor gene with known function to repress chromatin for transcription, which is activated mainly in germline stem cells. Further analyses of tumor features among patients indicated that high expression of L3MBTL1 was associated with low grade and hormone receptor–positive tumors, as well as low risk of disease recurrence and breast cancer death. In conclusion, the study suggests that increasing physical activity after a breast cancer diagnosis may affect epigenetic regulation of tumor suppressor genes, which have favorable impacts on survival outcomes of breast cancer patients.
The RNA binding protein Lin28 and its paralog Lin28B are associated with advanced human malignancies. Blocking the biogenesis of let-7 miRNA, a tumor suppressor, by Lin28/Lin28B has been thought to ...underlie their roles in cancer. Here we report that the mRNA for the human epidermal growth factor receptor 2 (HER2), a HER-family receptor tyrosine kinase known to play a critical role in cell proliferation and survival and also a major therapeutic target in breast cancer, is among several targets of Lin28 regulation. We show that Lin28 stimulates HER2 expression at the posttranscriptional level, and that enforced Lin28 expression promotes cancer cell growth via multiple mechanisms. Consistent with its pleiotropic role in regulating gene expression, Lin28 overexpression in primary breast tumors is a powerful predictor of poor prognosis, representing the first report on the impact of Lin28 expression on clinical outcome in human cancer. While revealing another layer of regulation of HER2 expression in addition to gene amplification, our studies also suggest novel mechanistic insights linking Lin28 expression to disease outcome and imply that targeting multiple pathways is a common mechanistic theme of Lin28-mediated regulation in cancer.
Bile acids are known to be genotoxic and contribute to colorectal cancer (CRC). However, the link between CRC tumor bile acids to tumor location, patient sex, microbiome, immune-regulatory cells, and ...prognosis is not clear.
We conducted bile acid analysis using targeted liquid chromatography-mass spectrometry (LC-MS) on tumor tissues from CRC patients (n = 228) with survival analysis. We performed quantitative immunofluorescence (QIF) on tumors to examine immune cells.
Twelve of the bile acids were significantly higher in right-sided colon tumors compared to left-sided colon tumors. Furthermore, in male patients, right-sided colon tumors had elevated secondary bile acids (deoxycholic acid, lithocholic acid, ursodeoxycholic acid) compared to left-sided colon tumors, but this difference between tumors by location was not observed in females. A high ratio of glycoursodeoxycholic to ursodeoxycholic was associated with 5-year overall survival (HR = 3.76, 95% CI = 1.17 to 12.1, P = 0.026), and a high ratio of glycochenodeoxycholic acid to chenodeoxycholic acid was associated with 5-year recurrence-free survival (HR = 3.61, 95% CI = 1.10 to 11.84, P = 0.034). We also show correlation between these bile acids and FoxP3 + T regulatory cells.
This study revealed that the distribution of bile acid abundances in colon cancer patients is tumor location-, age- and sex-specific, and are linked to patient prognosis. This study provides new implications for targeting bile acid metabolism, microbiome, and immune responses for colon cancer patients by taking into account primary tumor location and sex.
Highlights • There was a significant interaction between 5-HTTLPR genotype and job-related stress in the risk of insomnia. • Job-related stress played a predominant role in the risk of insomnia. • ...The effect of 5-HTTLPR for insomnia was relatively weaker than high job-related stress.
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