Knockdown of KAT5/KIF11 induces autophagy and promotes apoptosis in anaplastic thyroid cancer cells.

K (lysine) acetyltransferase (KAT) 5, which is a member of the KAT family of enzymes, has been found to act as a regulatory factor in various types of cancer. However, the role of KAT5 in anaplastic thyroid carcinoma (ATC) and its underlying mechanism is still elusive. The expression levels of KAT5 and kinesin family member 11 (KIF11) in ATC cells were assessed utilizing reverse transcription-quantitative PCR and western blot analyses. The cell proliferative ability was assessed via Cell Counting Kit-8 assay and using 5-ethynyl-2'-deoxyuridine staining. Flow cytometry and western blot analyses were applied for the assessment of cell apoptosis. Cell autophagy was investigated by employing western blot analysis and immunofluorescence staining. In addition, the enrichment of histone H3 lysine 27 acetylation (H3K27ac) and RNA polymerase II (RNA pol II) was analyzed by chromatin immunoprecipitation assay. It was shown that KAT5 expression was markedly increased in ATC cells. KAT5 depletion suppressed the cell proliferative capability but promoted the induction of apoptosis and autophagy. In addition, the autophagy inhibitor 3-methyladenine reversed the effects of KAT5 deficiency on the proliferative and apoptotic activities of 8505C cells. With regard to the mechanism, it was found that KAT5 inhibited the expression of KIF11 by repressing the enrichment of H3K27ac and RNA pol II. Upregulation of KIF11 expression reversed the effects of KAT5 silencing on the proliferative activity, apoptosis and autophagy of 8505C cells. In conclusion, the results indicated that KAT5 induced autophagy and promoted apoptosis of ATC cells by targeting KIF11, which may provide a promising target for the treatment of ATC.

Exposure to multiple metals and diabetes mellitus risk in dong ethnicity in China: from the China multi-ethnic cohort study.

Metals play an important role in the development of diabetes mellitus (DM). The association of metals with diabetes among the Dong ethnicity in China remains poorly understood. The current study aimed to evaluate the association of single metal exposure and multi-metal co-exposure with DM risk. Urinary concentrations of arsenic, cadmium, chromium, copper, iron, lead, manganese, mercury, molybdenum, nickel, strontium, vanadium, and zinc were measured using inductively coupled plasma-mass spectrometry (ICP-MS) among 4479 Dong ethnic participants aged 30-79 years from the China Multi-Ethnic Cohort (CMEC) study. Based on tertiles, the metal exposure can be divided into three groups: low, middle, and high exposure. Multivariate logistic regression models and principal component analysis were performed to determine exposure to single-metal and multi-metal co-exposure in relation to DM. A decrease in risk of DM was associated with iron (OR = 0.78, 95% CI: 0.61-1.00 and 0.68, 0.53-0.88 for the middle and high vs. low) and strontium (OR = 0.87, 95% CI: 0.69-1.12 and 0.67, 0.51-0.86 for the middle and high vs. low), respectively. A principal component 3 (PC3) characterized by iron and strontium showed an inverse association with DM. A principal component 4 (PC4) characterized by manganese and lead positively associated with DM. Exposure to high concentrations of urinary iron and strontium may reduce the risk of diabetes mellitus. This study revealed an increase in the risk of diabetes mellitus by co-exposure to high concentrations of urinary manganese and lead.

Family History of Hypertension and Cobalt Exposure Synergistically Promote the Prevalence of Hypertension.

It has been previously reported that family history of hypertension (FHH) and exposure to metals are each independent risk factor for hypertension, but the interaction between the two in relation to hypertension risk has been poorly studied. The object of this study is Dong ethnic group in Guizhou, China. The impacts of exposure to metals and FHH on hypertension incidence were examined by using the restrictive cubic spline (RCS) model as well as the multivariate logistic regression model. As a result, FHH, together with cobalt and lead exposure, was identified to show independent significant correlation with hypertension incidence (P < 0.05). The risk of hypertension increased with the increase in lead and cobalt exposure quartiles. Typically, the RCS model revealed such dose-response relation. To further confirm the association of cobalt, lead, and FHH with the risk of hypertension, multiplication and addition models were used to analyze the influence of the interactions between these variables on the risk of hypertension. The results showed that there was a multiplying interaction between the influence of the FHH and cobalt on the risk of hypertension. As for the additive interaction between cobalt and FHH, the relative excess risk due to interaction (RERI) was determined to be 0.596 (95% Cl: 0.001-1.191), the attributable proportion due to interaction (AP) was calculated as 0.256 (95% Cl: 0.075-0.437), whereas the synergy index (S) was identified to be 1.814 (95% Cl: 1.080-3.047). Our study provides some limited evidence that a FHH and cobalt exposure synergistically promote the prevalence of hypertension.

Analysis of Threshold Effect of Urinary Heavy Metal Elements on the High Prevalence of Nephrolithiasis in Men.

Exposure to heavy metals in the environment exerts serious effects on kidney health. However, the effects of joint exposure on the kidneys have been rarely studied, particularly in non-occupational exposure high-risk populations. This study provided a reference threshold range of heavy metals in urine and explored the effect of joint exposure on nephrolithiasis in men. The data were obtained from the China Multi-Ethnic Cohort database, and 1502 men were included in the study. A two-piece-wise regression model was used to assess the dose-response relationship between heavy metal exposure and nephrolithiasis. The least absolute shrinkage and selection operator regression model was used to calculate the score of joint exposure to heavy metals. The threshold effect analysis revealed a linear relationship between the concentration of arsenic (As) in the urine and the prevalence of nephrolithiasis, whereas a nonlinear relationship was observed with cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). In addition, As, Cd, Cr, Hg, and Pb may significantly affect the joint exposure effect. Moreover, the final risk of nephrolithiasis increased by 123% (P for trend < 0.001). This study found a threshold relationship between heavy metals (Cd, Cr, Hg, Pb) in male urine and the occurrence of nephrolithiasis. Joint exposure to heavy metals in urine caused a high-risk effect on nephrolithiasis. The study provided a reference threshold value of related studies and indicated that environmental pollution caused by heavy metals should be reduced.