Environmental concentrations of cadmium and zinc and associating metabolomics profile alternations in urine of pregnant women in the first trimester: A prospective cohort study in Taiyuan, North China.

especially to pregnant women. In recent years, zinc (Zn) supplementation has attracted increasing attention among pregnant women. Thus, understanding the effects and interactions of Cd and Zn in pregnant women is critical. This study aimed to assess the urinary levels of Cd and Zn in pregnant women during early pregnancy, examine associated alterations in urine metabolomics, and identify potential metabolic biomarkers among distinct Cd and Zn groups. Urine samples from 185 pregnant women were collected, and inductively coupled plasma mass spectrometry (ICP-MS) was used to detect Cd and Zn contents. The women were then divided into four groups according to median contents of Cd and Zn. Alterations in the metabolite profile were assessed using a liquid chromatograph mass spectrometer (LC-MS). The results showed that the gravidity of pregnant women was closely related to urinary Cd levels and that the urinary Zn contents of pregnant women with morning sickness in the first trimester were lower than that of non-morning-sick pregnant women. A total of 51 metabolites exhibited significant differential expression in the high level of Cd and Zn (HCdHZn) compared with low level of Cd and Zn (LCdLZn), the diagnostic performance of these 51 metabolites were assessed using receiver operating characteristic curve analysis and revealed that octadecylamine was a promising diagnostic indicator for evaluating the combined effects of Zn and Cd. Metabolomics analysis showed that the arginine and proline pathways were upregulated in HCdHZn compared with that in LCdLZn, suggesting a potential risk of obesity. Although higer levels of bovinic acid in HCdHZn vs. HCdLZn (high level of Cd and low level of Zn) indicated that Zn has antioxidant and anti-inflammatory properties, excessive Zn may still cause harmful effect to the human health and should be supplemented with caution. The study findings may be valuable for potential risk ahissessment of the combined effects of Cd-Zn and their interactions in pregnant women.

Effects of chlorogenic acid on growth, metabolism, antioxidation, immunity, and intestinal flora of crucian carp (Carassius auratus).

In recent years, with the harm caused by the abuse of antibiotics and the increasing demand for green and healthy food, people gradually began to look for antibiotic alternatives for aquaculture. As a Chinese herbal medicine, leaf extract chlorogenic acid (CGA) of Eucommia ulmoides Oliver can improve animal immunity and antioxidant capacity and can improve animal production performance. In this study, crucian carp (Carassius auratus) was fed with complete feed containing 200 mg/kg CGA for 60 days to evaluate the antioxidant, immuno-enhancement, and regulation of intestinal microbial activities of CGA. In comparison to the control, the growth performance indexes of CGA-added fish were significantly increased, including final body weight, weight gain rate, and specific growth rate (P < 0.01), while the feed conversion rate was significantly decreased (P < 0.01). Intestinal digestive enzyme activity significantly increased (P < 0.01); the contents of triglyceride in the liver (P < 0.01) and muscle (P > 0.05) decreased; and the expression of lipid metabolism-related genes in the liver was promoted. Additionally, the non-specific immune enzyme activities of intestinal and liver tissues were increased, but the expression level of the adenylate-activated protein kinase gene involved in energy metabolism was not affected. The antioxidant capacity of intestinal, muscle, and liver tissues was improved. Otherwise, CGA enhanced the relative abundance of intestinal microbes, Fusobacteria and Firmicutes and degraded the relative abundance of Proteobacteria. In general, our data showed that supplementation with CGA in dietary had a positive effect on Carassius auratus growth, immunity, and balance of the bacteria in the intestine. Our findings suggest that it is of great significance to develop and use CGA as a natural non-toxic compound in green and eco-friendly feed additives.

Causal association of monounsaturated fatty acids with rheumatoid arthritis but not osteoarthritis: A two-sample Mendelian randomization study.

OBJECTIVES: Previous studies have indicated that dietary monounsaturated fatty acids (MUFAs) are associated with decreased risk of osteoarthritis (OA) and rheumatoid arthritis (RA). However, the causality of the observed associations is largely undetermined. We sought to ascertain the potential causal roles of two of the most common MUFAs, oleic acid and palmitoleic acid, in RA and OA risk using a two-sample Mendelian randomization approach. METHODS: For the outcomes, we used summary-level data for RA (14 361 people with RA and 43 923 controls) and OA (10 083 people with OA and 40 425 controls) from two genome-wide association studies in European ancestry. For the exposures, five single-nucleotide polymorphisms associated with palmitoleic acid and one associated with oleic acid with genome-wide significance (P < 5 × 10-8) were selected as instrumental variables. The causal effects were estimated using the inverse-variance weighted method with several sensitivity analyses. RESULTS: For genetically predicted levels, an increase of one SD in palmitoleic acid (odds ratio, 0.24; 95% confidence interval, 0.10-0.59; P = 0.002) and oleic acid (odds ratio, 0.78; 95% confidence interval, 0.67-0.90; P < 0.001) was significantly associated with lower risk of RA. However, genetic predisposition to either of the two individual MUFAs was not associated with OA risk. Sensitivity analyses yielded similar results. CONCLUSIONS: Our Mendelian randomization analyses suggest a causal relationship between higher genetically predicted MUFA levels and lower risks of RA. However, the causality between MUFAs and OA cannot be inferred from this study. Further research is required to unravel the role of MUFA supplementation in arthritis prevention.

Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study.

BACKGROUND AND AIMS: The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design. METHODS AND RESULTS: Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10-8) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated. CONCLUSION: This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.

Novel Tetrazole-Containing Analogues of Itraconazole as Potent Antiangiogenic Agents with Reduced Cytochrome P450 3A4 Inhibition.

Itraconazole has been found to possess potent antiangiogenic activity, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). In an effort to eliminate the CYP3A4 inhibition while retaining its antiangiogenic activity, we designed and synthesized a series of derivatives in which the 1,2,4-triazole ring is replaced with various azoles and nonazoles. Among these analogues, 15n with tetrazole in place of 1,2,4-triazole exhibited optimal inhibition of human umbilical vein endothelial cell proliferation with an IC50 of 73 nM without a significant effect on CYP3A4 (EC50 > 20 µM). Similar to itraconazole, 15n induced Niemann-Pick C phenotype (NPC phenotype) and blocked AMPK/mechanistic target of rapamycin signaling. These results suggest that 15n is a promising angiogenesis inhibitor that can be used in combination with most other known anticancer drugs.

Rheum rhabarbarum extract promotes healing of the incision through relieving inflammation and stimulating angiogenesis.

As one of the most important treatment strategies in clinic, surgery has improved to be more and more efficient and safe. However, the infection risk of incision caused by surgery is still the main concern of patients. In our research, we found extract of Rheum rhabarbarum (rhubarb) could be used to diminish this risk through promoting the healing of the incision. Using MTT assay, flow cytometry and clinical statics, we also tried to explore the mechanism of rhubarb's effect. The data showed that rhubarb extract decreased the number of leukocytesand neutrophils and inhibited the growth of bacteria. Moreover, the vascular endothelial cells cultured in medium containing rhubarb extract grow faster than control. The flow cytometry also demonstrates that the ratio of cells in S and G2/M phase increase after treated with rhubarb extract. There after, we hypothesize that rhubarb extract can promote incision healing through relieving inflammation and stimulating angiogenesis.

Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies.

BACKGROUND: The intake of fish and polyunsaturated fatty acids (PUFAs) may benefit cognitive function. However, optimal intake recommendations for protection are unknown. OBJECTIVE: We systematically investigated associations between fish and PUFA intake and mild-to-severe cognitive impairment risk. DESIGN: Studies that reported risk estimates for mild cognitive impairment (MCI), cognitive decline, dementia, Alzheimer disease (AD), or Parkinson disease (PD) from fish, total PUFAs, total n-3 (ω-3) PUFAs, or at least one n-3 PUFA were included. Study characteristics and outcomes were extracted. The pooled RR was estimated with the use of a random-effects model meta-analysis. A dose-response analysis was conducted with the use of the 2-stage generalized least-squares trend program. RESULTS: We included 21 studies (181,580 participants) with 4438 cases identified during follow-up periods (2.1-21 y). A 1-serving/wk increment of dietary fish was associated with lower risks of dementia (RR: 0.95; 95% CI: 0.90, 0.99; P = 0.042, I(2) = 63.4%) and AD (RR: 0.93; 95% CI: 0.90, 0.95; P = 0.003, I(2) = 74.8%). Pooled RRs of MCI and PD were 0.71 (95% CI: 0.59, 0.82; P = 0.733, I(2) = 0%) and 0.90 (95% CI: 0.80, 0.99; P = 0.221, I(2) = 33.7%), respectively, for an 8-g/d increment of PUFA intake. As an important source of marine n-3 PUFAs, a 0.1-g/d increment of dietary docosahexaenoic acid (DHA) intake was associated with lower risks of dementia (RR: 0.86; 95% CI: 0.76, 0.96; P < 0.001, I(2) = 92.7%) and AD (RR: 0.63; 95% CI: 0.51, 0.76; P < 0.001, I(2) = 94.5%). Significant curvilinear relations between fish consumption and risk of AD and between total PUFAs and risk of MCI (both P-nonlinearity < 0.001) were observed. CONCLUSIONS: Fishery products are recommended as dietary sources and are associated with lower risk of cognitive impairment. Marine-derived DHA was associated with lower risk of dementia and AD but without a linear dose-response relation.

The association of phosphatase and tensin homolog deleted on chromosome 10 polymorphisms and lifestyle habits with colorectal cancer risk in a Chinese population.

The PI3K signaling pathway plays an important role in the development of colorectal cancer (CRC) and other neoplasm. Somatic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) mutations and deletions or epigenetic silencing have been observed in multiple tumor types including CRC. To assess the association of PTEN polymorphisms and lifestyle habits with CRC risk in Chinese population, we carried out a case-control study which included 545 cases and 522 controls. In the present study, we genotyped eight single-nucleotide polymorphisms (SNPs) in PTEN and found that rs11202607 was associated with increased CRC risk (odds ratio (OR) = 1.40, 95 % confidence interval (CI) = 1.04-1.90). Stratification analysis by lifestyle habits showed a stronger association between rs11202607 and CRC risk among never tea drinkers than that among tea-drinkers (OR = 2.04, 95 % CI 1.29-3.22), and significant additive interaction between rs10490920 and tea drinking status was observed. Our study provided the evidence of an association between PTEN polymorphisms and the risk of CRC and significant additive interaction between PTEN polymorphism and tea drinking. Studies with larger sample size and further investigations into the mechanism are warranted to clarify the role of PTEN in colorectal carcinogenesis and the association between PTEN genetic variations, environment exposure, and CRC risk.