Cadmium, a toxic heavy metal, is widely present in food. It has been reported that chronic cadmium exposure is associated with kidney disease, osteoporosis, cardiovascular disease and cancer. The aim ...of this study was to assess the dietary cadmium exposure and potential health risk in different age-sex groups of the Chinese population (children aged 4-11 years, young people aged 12-17 years and adults aged over 18 years), and in the southern and northern population using a semi-probabilistic method. Cadmium was detected in 228,687 food samples from 32 food categrories by graphite furnace atomic absorption spectrometry. The dietary cadmium exposures were estimated by combining the cadmium concentration data with food consumption data derived from the China National Nutrient and Health Survey 2002, and evaluated against the Provisional Tolerable Monthly Intake (PTMI) of 25 μg/kg BW/month established by the Joint FAO/WHO expert committee on food additives (JECFA). The mean dietary cadmium exposure of the general Chinese population (15.3 μg/kg BW/month) was below the PTMI. The high consumer exposures (95th percentile, P95) for the general population and different sub-groups were higher than the PTMI. The dietary cadmium exposure of the southern population was apparently higher than that of the northern population. Rice was the most important contributor to cadmium exposure for Chinese people, especially those living in the southern areas of China. These findings indicated that the health risk from dietary cadmium exposure of the general Chinese people was low, but the health risk of cadmium exposure of certain sub-groups should be of concern.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Overweight and obesity have increased rapidly in the past few decades in China, and less research has focused on the association between the consumption of ultra-processed foods (UPFs) and overweight ...or obesity in Chinese adults. The objective of this study was to determine the relationship of UPF consumption with the risk of overweight or obesity in Chinese adults. Residents aged 18 years and above who participated in the nationally representative survey Chinese Food Consumption Survey in 2017–2020 were included in this study. Dietary intake data were collected via non-consecutive three-day 24 h dietary recalls and weighing household foods and condiments. According to the NOVA food classification system, UPFs were classified depending on the purpose and extent of food processing. Multiple logistic regression and multivariate-adjusted restricted cubic spline (RCS) regressions were performed to estimate the association between UPF consumption (categorized into quartiles: quartile 1 (Q1), quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4)) and risk of overweight or obesity. A total of 38,658 adults aged 18 years and above participated in the present study. The prevalence of overweight and obesity in adults was 33.0% (95% CI: 32.91–33.10) and 9.6% (95% CI 9.55–9.67), respectively. After a multivariable adjustment, the risk of overweight or obesity was increased by 10% in Q3 (OR: 1.10, 95% CI: 1.04–1.17) compared to Q1 as a reference. Women (OR: 1.10, 95% CI: 1.01–1.20) and adults living in small and medium-sized cities (OR: 1.13, 95% CI: 1.01–1.26) with higher UPF consumption had higher odds of overweight or obesity. Nevertheless, the effect of higher UPF consumption on the risk of overweight or obesity was relatively weak for overall adults in China. The top three categories of subgroups consumption of UPFs were 1: sugar-sweetened beverages; 2: sauces, cheeses, spreads, and gravies; and 3: ultra-processed breads and breakfast cereals. These findings provide evidence that higher UPF consumption was positively associated with overweight or obesity, which was defined based on Chinese criteria among women and adults living in small and medium-sized cities in China. Further studies, such as intervention trials, are needed to identify the mechanism of correlation between the consumption of UPFs and health-related outcomes in Chinese adults. From a public health perspective, with the prevalence of overweight and obesity growing and the increase in UPF consumption in Chinese adults, it is necessary to promote healthy food intake and a balanced diet through active nutritional education actions for overweight and obesity prevention and control.
This study was aimed to evaluate the toxic effects of different concentrations (23, 90, 360 mg/kg BW) of atrazine (ATZ) on immune function in BALB/c mice. Some parameters of general immunotoxicity, ...humoral immunity, cellular immunity, and non-specific immunity were tested. The studies showed that the high-dose ATZ induced a significant reduction in the final body weight of mice, the absolute and relative weights of spleen, the counts of white blood cell (WBC), lymphocyte (LYM), monocyte (MON), and the number of splenocyte. An increase in the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and cholesterol (CHO) in the high-dose ATZ group was observed. Pathological examination showed that the medium- and high-doses of ATZ caused atrophy and destruction of thymus, spleen, and hepatorenal toxicity. The serum interleukin-5(IL-5) level of mice and the number of plaque-forming cell (PFC) in spleen cells in the high-dose ATZ group decreased significantly while there was a significant increase of the serum immunoglobulin G (IgG) in the high-dose ATZ group when compared to the negative control group. In the high-dose ATZ group, the proliferation ability of T and B lymphocytes as well as the delayed-type hypersensitivity (DTH) response were significantly decreased. The low-dose ATZ (23 mg/kg BW) caused a significant decrease in the number of WBC and neutrophil (NEUT), as well as the proportion of polychromatic and normoblast. In summary, we thought the low-dose ATZ has a slight effect on the immune system; it can be preliminarily concluded that the lowest observed adverse effect level (LOAEL) of atrazine is 23 mg/kg BW in mice. Atrazine can cause immunotoxicity mainly through cellular and humoral immunity pathways.
DNA double-strand breaks (DSBs) are essential intermediates in Ig gene rearrangements: V(D)J and class switch recombination (CSR). In contrast to V(D)J recombination, which is almost exclusively ...dependent on nonhomologous end joining (NHEJ), CSR can occur in NHEJ-deficient cells via a poorly understand backup pathway (or pathways) often termed alternative end joining (A-EJ). Recently, several components of the single-strand DNA break (SSB) repair machinery, including XRCC1, have been implicated in A-EJ. To determine its role in A-EJ and CSR, Xrcc1 was deleted by targeted mutation in the CSR proficient mouse B-cell line, CH12F3. Here we demonstrate that XRCC1 deficiency slightly increases the efficiency of CSR. More importantly, Lig4 and XRCC1 double-deficient cells switch as efficiently as Lig4-deficient cells, clearly indicating that XRCC1 is dispensable for A-EJ in CH12F3 cells during CSR.
Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to ...induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models.
In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL
) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs.
From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL
(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL
doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models.
Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.
To understand the distribution of the essential composition content of commercial follow-up formula for young children in China, to analyze the differences with the new requirements of national food ...safety standard, and to promote the implementation of the new national standard(GB 10767-2021).
The label information on the total of 483 follow-up formula for young children permitted from January 2017 to June 2022 were collected and recorded, the distribution of essential compositions were analyzed and compared with the new national food safety standard.
Compared with GB 10767-2010, 23 essential compositions were revised in the new national standard, 2 new essential compositions, α-linolenic acid and carbohydrates, were required, and 8 minimum requirements and 4 maximum requirements were revised, 16 new maximum requirements were developed. The whole change of the new standard was major. Comparing with GB 10767-2021, there were 8 essential compositions in commercial products with 100% compliance rate and 9 with m
DNA-dependent protein kinase catalytic subunit (DNA-PK) is a multifunctional serine‑threonine protein kinase that plays roles in non-homologous end joining of DNA repair in cells. NU7441 is a ...specific DNA-PKcs inhibitor. We investigated the effects of NU7441 on the transcriptome of BT549 triple negative breast cancer cells. Total RNA extracted from NU7441-treated or control BT549 cells was processed for preparation of sequencing libraries. Assessment of read quality was performed using fastqc tool. Trimming and filtering low-quality reads were performed using fastp. Reads were aligned by hisat2. SAM files were converted to BAM files using Samtools. The gene differential expression analysis, Gene Ontology (GO) analysis and KEGG pathway analysis were performed. After NU7441 treatment, total number of 2045 differential genes were selected according to |log2(FoldChange)| >= 1 & padj<= 0.05, among which 1365 genes were down-regulated and 680 genes were up-regulated. The differential expression genes in pattern recognition receptors (PRRs) immune responses signals, including NOD-like receptor signaling, Toll-like receptor signaling, RIG-I-like receptor signaling and cytosolic DNA-sensing pathways were noted in this paper.
ObjectiveTo preliminarily study the toxicity of combined exposure of low-dose of four polycyclic aromatic hydrocarbons.Methods8-week-old male SD rats were randomly divided into 5 groups with 10 rats ...each, and 0, 10, 50, 250 and 1 000 μg/kg·BW dose were continuously administered by gavage. Based on the actual exposure of four polycyclic aromatic hydrocarbons in human body, the proportion of gavage dose was set as benzo a pyrene∶benzo a anthracene∶chrysene∶benzo b fluoranthene=0.99∶2.92∶2.68∶1.68. The rats were sacrificed 30 days after exposure. Biological samples such as serum and organs were taken, organ coefficients were calculated, pathological sections of rat liver were made, pathological changes were observed, and liver function related indexes, oxidative stress related indexes and lipid metabolism related indexes were detected.ResultsCompared with the control group, the liver structure of the rats in the exposure group was significantly abnormal, the hepatic sinuses were enlarged, and the hepatocyt
ObjectiveTo investigate the hepatotoxicity induced by the combined exposure of eight types of PAHs （PAH8） in rats， the lower limit of the 95% confidence interval of benchmark dose （BMDL） of ...PAH8-induced hepatotoxicity was determined using the benchmark dose （BMD） method.MethodsMale SD rats were randomly divided into five groups （10 rats in each group） and were exposed to PAH8 at doses of 0， 10， 50， 250， and 1 000 μg/kg·BW， respectively. Rats were sacrificed after 30 d， and organ coefficients were calculated. Liver pathological examination and oil-red O staining were performed. Serum alanine aminotransferase， aspartate aminotransferase， malondialdehyde， glutathione peroxidase （GSH-Px）， triglyceride （TG）， total cholesterol （TC） levels， and liver TG and TC levels were measured. Hepatotoxicity data with statistical significance， toxicological significance， and dose-effect trend were selected. BMD analysis was performed using the BMDS 3.2 software. BMDL values of PAH8-induced hepatotoxicity in rats were obtained b
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•Triptolide induces double-strand breaks and promote the breaks caused by cisplatin.•Triptolide arrests cell cycle in S phase.•Triptolide down-regulates the levels of ...XRCC1/PARP1.•Triptolide sensitize triple-negative breast cancer cells to cisplatin.
Triptolide is a natural compound isolated from the Tripterygium wilfordii, which possesses anti-inflammatory and anti-tumor activities. Triptolide reportedly inhibits RNA polymerase II-mediated transcription and ATM activities to interfere with DNA repair. However, the roles of triptolide in DNA repair are still largely unknown. Triple negative breast cancer cells (TNBC) are insensitive to targeted anti-tumoral drugs, thus DNA damage chemotherapeutic drugs are the available treatments used in clinic, while the drug resistance of TNBC causes the challenge for successful cure. In this study, we investigated the efficiency of cisplatin in combination with triptolide in treatment of TNBC. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows triptolide suppresses the growth of two triple-negative breast cancer cells, BT549 and MDA-MB-231. Triptolide induces DNA breaks and arrests TNBC in the cell cycle S phase, and sensitizes TNBC to cisplatin. Western blot analysis shows triptolide down-regulated the levels of PARP1 and XRCC1, and slightly decreases the levels of RAD51. The results demonstrate triptolide interferes with single strand-break and base excision repair. The over-expressed PARP1/XRCC1 help the TNBC to resist triptolide. Based on these results, we conclude triptolide confers sensitization of TNBC to cisplatin via interference with XRCC1/PARP1-mediated base excision repair.
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