Elevated levels of Zn, Cu and Co are associated with an increased risk of endometriosis: Results from a casecontrol study.

BACKGROUND: Endometriosis is a common gynecological disease that affects approximately 5 %∼10 % of reproductive-aged women. Zinc (Zn), selenium (Se), copper (Cu), cobalt (Co) and molybdenum (Mo) are essential trace elements and are very important for human health. However, studies on the relationship between mixtures of essential trace elements and the risk of endometriosis are limited and inconsistent. In particular, studies confirming the association via different sample types are limited. OBJECTIVE: This study aimed to investigate the associations between Zn, Se, Cu, Co and Mo concentrations in blood and follicular fluid (FF) and endometriosis risk in a Chinese population. METHODS: A total of 609 subjects undergoing in vitro fertilization (IVF) were recruited; 836 samples were analyzed, including 451 blood samples (234 controls and 217 cases) and 385 FF samples (203 controls and 182 cases). In addition, 227 subjects provided both blood and FF samples. Zn, Se, Cu, Co and Mo concentrations in blood and FF were quantified via inductively coupled plasma-mass spectrometry (ICP-MS). The associations between the levels of Zn, Se, Cu, Co and Mo and the risk of endometriosis were assessed using single-element models (logistic regression models), and the combined effect of the trace elements on endometriosis risk was assessed using multielement models (Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression). RESULTS: Based on the single-element models, significant associations of Zn concentrations in blood (high-level vs. low-level group: aOR = 14.17, 95 % CI: 7.31, 27.50) and FF (first tertile vs. second tertile group: aOR = 0.34, 95 % CI: 0.16, 0.71; third tertile vs. second tertile group: aOR = 2.32, 95 % CI: 1.38, 3.91, respectively) and Co concentrations in blood (first tertile vs. second tertile group, aOR = 0.24, 95 % CI: 0.12, 0.48) and FF (third tertile vs. second tertile group: aOR = 3.87, 95 % CI: 2.19, 6.84) with endometriosis risk were found after adjustment for all confounders. In FF, Cu and Mo levels were significantly greater among the cases than among the controls, with a positive association with endometriosis risk (Cu (first tertile vs. second tertile group: aOR = 0.39, 95 % CI: 0.19, 0.81; third tertile vs. second tertile group: aOR = 2.73, 95 % CI: 1.61, 4.66, respectively) and Mo (high-level vs. low-level group: aOR = 14.93, 95 % CI: 7.16, 31.12)). However, similar associations between blood Cu and Mo levels and endometriosis risk were not found. In addition, the levels of these five essential trace element mixtures in blood and in FF were significantly and positively associated with endometriosis risk according to the BKMR analyses; the levels of Zn and Cu in blood and the levels of Mo in FF were significantly related to the risk of endometriosis, and the posterior inclusion probabilities (PIPs) were 1.00, 0.99 and 1.00 for Zn and Cu levels in blood and Mo levels in FF, respectively. Furthermore, Zn and Mo were the highest weighted elements in blood and FF, respectively, according to WQS analyses. CONCLUSION: The risk of endometriosis was associated with elevated levels of several essential trace elements (Zn, Cu and Co). Elevated levels of these elements may be involved in the pathomechanism of endometriosis. However, further studies with larger sample sizes will be necessary to confirm these associations.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

Serum Cu, Zn and IL-1ß Levels May Predict Fetal Miscarriage Risk After IVF Cycles: A Nested Case-Control Study.

To explore the association between serum-related indicators (levels of inflammatory cytokines and essential trace elements) and miscarriage risk among infertile women undergoing assisted reproductive techniques (ART) on the 14th day after embryo transfer, and to develop and establish a multivariable algorithm model that might predict pregnancy outcome. According to a nested case-control study design, a total of 100 miscarriage cases and 100 live birth controls were included in this study, and women in both groups were infertile and have underwent in vitro fertilization (IVF). Pregnancy tests were performed and serum levels of five essential trace elements (vanadium (V), copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo)) and five inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α)) of the participants were measured on the 14th day after embryo transfer. The serum levels of five inflammatory cytokines were determined by multiple magnetic bead enzyme immunity analyzer; and the serum concentrations of five elements were determined simultaneously by inductively coupled plasma‒mass spectrometry (ICP ‒ MS). The logistic regression was used to evaluate the relationship between these serum indices and miscarriage risk among women undergoing ART, and a predictive model of pregnancy outcome based on these indices was established. The levels of IL-10, IL-1ß and TNF-α of infertile women in the live birth group were significantly higher than those in the miscarriage group (p = 0.009, p < 0.001, p = 0.006), and the levels of V, Cu, Zn and Se of infertile women in the live birth group were also significantly higher than those in the miscarriage group (all p < 0.001). Through logistic regression analyses, we found that serum levels of IL-1ß, TNF-α, V, Cu, Zn and Se were significantly and negatively associated with miscarriage risk. Different combination prediction models were generated according to the results of logistic regression analyses, and the combination of IL-1ß, Cu and Zn had the best prediction performance. The area under the curve (AUC) was 0.776, the sensitivity of the model was 60% and the specificity was 84%. In conclusion, the serum-related indicators of women undergoing ART on the 14th day after embryo transfer, including the inflammatory cytokines such as IL-1ß and TNF-α and the essential trace metal elements such as V, Cu, Zn and Se, were negatively correlated with miscarriage risk. A multivariate algorithm model to predict pregnancy outcome among women undergoing ART was established, which showed that IL-1ß, Cu and Zn might synergistically predict pregnancy outcome.

Serum Essential Trace Element Status in Women and the Risk of Endometrial Diseases: a Case-Control Study : Serum Essential Trace Element Status in Women and the Risk of Endometrial Diseases: a Case-Control Study.

Endometrial diseases, including uterine fibroids, polyps, intrauterine adhesion, endometritis, etc., are the major causes of infertility among women. However, the association between essential trace element status in women and the risk of endometrial disease is limited and unclear. This study aimed to investigate this association using a case-control study design; a total of 302 women patients with endometrial diseases and 302 healthy women were included. Compared to women in the control group, serum selenium (Se) (p = 0.024) and zinc (Zn) (p = 0.017) levels were significantly lower, while copper (Cu) (p = 0.004) and molybdenum (Mo) (p = 0.005) levels were significantly higher among women with endometrial diseases. In addition, compared to women in the first quartile of the copper/zinc (Cu/Zn) ratio value group, the adjusted ORs (95% CIs) of endometrial diseases were 1.50 (1.05, 2.14), 1.68 (1.18, 2.39), and 1.47 (1.02, 2.10), respectively, in the second, third, and fourth quartile of the Cu/Zn ratio value group (p trend = 0.047). In addition, the results from restricted cubic splines showed that the dose-response relationships of serum levels of these essential elements with the risk of endometrial diseases were nonlinear for Se, Cu, and Zn and relatively linear for Mo and Cu/Zn ratio. The present study showed serum levels of Zn and Se among women with endometrial diseases were significantly lower compared to that among healthy women, while serum levels of Cu and Mo were significantly higher, in addition, the serum Cu/Zn ratio value was also significantly and positively associated with the risk of endometrial diseases.

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques.

Background: Early embryonic arrest (EEA) leads to repeated cessation of fresh cycles among infertile women undergoing in vitro fertilization (IVF). Whether the levels of some essential trace elements [copper (Cu), zinc (Zn), selenium (Se) and cobalt (Co)] in the bodies of women are related to the risk of EEA warrants study. Objective: Our study aimed to investigate the associations of peripheral blood levels of Cu, Zn, Se, and Co and their mixtures with the risk of EEA. Methods: A total of 74 EEA cases (123 IVF cycles) and 157 controls (180 IVF cycles) from the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between June 2017 and March 2020 were included in our study. Demographic and clinical data were collected from electronic medical records. Cu, Zn, Se, and Co levels were measured in blood samples collected on the day of oocyte retrieval when infertile women entered clinical treatment for the first time using an inductively coupled plasma mass spectrometer (ICP-MS). Generalized estimating equation (GEE) models were used to evaluate the associations of four essential trace element concentrations individually with the risk of EEA, and Bayesian kernel machine regression (BKMR) was used to explore the associations between four essential trace element mixtures and the risk of EEA. Results: Se concentrations of infertile women were significantly lower in the case group compared with the control group. Co levels were significantly higher in the case group compared with the control group. The differences in Cu and Zn concentrations between the two groups were not significant. Based on single-metal models, Co was positively associated with the risk of EEA before and after adjustment for all confounders (odd ratio (OR) = 1.72, 95% confidence interval (CI): 1.18-2.52; OR = 2.27, 95% CI: 1.37-3.77, respectively), and Se was negatively associated with the risk of EEA before adjustment for all confounders (OR = 0.18, 95% CI: 0.07-0.51). BKMR analyses showed that Se was significantly and negatively associated with the risk of EEA when all the other three metals (Cu, Zn, and Co) were fixed at the 25th, 50th, or 75th percentiles, whereas Zn displayed a significant and positive association with the risk of EEA when all the other three metals (Cu, Se and Co) were fixed at the 25th, 50th, or 75th percentiles. Co did not show any effect on the risk of EEA when all the other metals (Cu, Zn, and Se) were fixed at the 25th, 50th, or 75th percentiles. In addition, an increasing trend of the joint effect of four essential trace elements on the risk of EEA was found, although it was not statistically significant. Conclusion: The levels of essential trace elements (Cu, Zn, Se, and Co) might correlate with the risk of EEA to some extent. The present study might provide a real-world perspective on the relationship between essential trace elements and the risk of EEA when considering them as a single element or as mixtures.

Effects of selenium levels on placental oxidative stress and inflammation during pregnancy: a prospective cohort study.

BACKGROUND: Studies on the impact of Se levels in different pregnancy periods on placental function are limited. AIM: This cohort study sought to investigate the levels of the trace element Se and to assess their effects on placental oxidative stress (OS) and mRNA expression of inflammatory genes during pregnancy. METHODS: The study population consisted of 2519 pregnant women from the Ma'anshan birth cohort. Se levels were measured in the first and second trimesters of pregnancy and in cord blood using inductively coupled plasma-mass spectrometry (ICP-MS). Placental stress and mRNA expression of inflammatory genes were assessed using RT-PCR. RESULTS: A statistically significant negative association was noted between Se levels in the second trimester of pregnancy and mRNA expression of placental HO-1(ß = -0.009, p < .01), HIF1α (ß = -0.005, p = .010), GRP78 (ß = -0.011, p < .001), CRP (ß = -.007, p = .033) and CD68 (ß = -0.006, p = .019). A negative association was noted between Se levels in cord blood and mRNA expression of placental HO-1 (ß = -0.007, p = .004), HIF1α (ß = -0.006, p = .005) and GRP78 (ß = -0.009, p = .004). We found that prenatal Se status was associated with placental stress and mRNA expression of inflammatory genes. CONCLUSION: Se deficiency during pregnancy, especially in the second trimester, leads to the production of OS and an increase in inflammatory mediators, affecting the growth and development of the fetus. Monitoring of pregnant women's nutritional status is necessary to prevent nutritional imbalances and deficiencies in important micronutrients in the fetal.

Iron-Related Factors in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus: the Ma'anshan Birth Cohort (MABC) Study.

Iron is an essential micronutrient while its excessive load has been related to the etiology of diabetes. We used data of 3289 pregnant women from the Ma'anshan birth cohort (MABC) study in China to examine the associations of three iron-related factors (i.e., serum iron (SI) concentration, hemoglobin level, and use of iron supplements) with risk of gestational diabetes mellitus (GDM). Emphatically explore the potential non-linear relationship between SI concentration and risk of GDM. SI concentration was measured in fasting blood using inductively coupled plasma mass spectrometry (ICP-MS). GDM diagnosis was determined by 75 g oral glucose tolerance test at 24~28 weeks. Restricted cubic splines with three knots were used to examine potential non-linear relationship between SI concentration and GDM risk. We observed a U-shape relation between SI concentration in the first trimester and risk of GDM. In the multivariate-adjusted model, compared with the middle level (ln(SI), 7.1-7.7 µg/L), both the lowest level (ln(SI) ≤ 7.1 µg/L) (odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.04-1.76) and the highest level (ln(SI) > 7.7 µg/L) (OR = 1.63, 95%CI = 1.16-2.28) increased risk of GDM. Associations of hemoglobin level in the first trimester and risk of GDM attenuated to non-significance after adjustment for pre-pregnancy body mass index (BMI) and blood pressure. Pre-pregnancy iron supplement use was associated with an increased risk of GDM (OR = 1.57, 95%CI = 1.06-2.32). In conclusion, the three iron-related factors are all related to GDM risk on some level.

The effect of formononetin on the proliferation and migration of human umbilical vein endothelial cells and its mechanism.

Formononetin is one of the main active components of traditional Chinese medicine red clover (Trifolium pratense L). Prior studies have demonstrated that formononetin is a typical phytoestrogen and exhibits an estrogen-like effect that protects the cardiovascular system with minimal side effects. In this study, we further investigated the role of formononetin in human umbilical vein endothelial cells (HUVECs) and its potential molecular mechanisms. We founded that formononetin promotes proliferation and migration of HUVECs as assessed by the MTT and wound healing assays. Meanwhile, insulin-like growth factor 1 (IGF-1) and intercellular adhesion molecule 1 (ICAM-1) protein levels were increased in a dose-dependent manner. Our findings illustrated that formononetin exhibits a protective effect on HUVECs, and the molecular mechanisms may correlate with IGF-1R and ICAM-1, as well as upregulation of vascular endothelial growth factor (VEGF) and activation of extracellular signal-regulated kinase (ERK).

Serum Concentrations of 15 Elements Among Helicobacter Pylori-Infected Residents from Lujiang County with High Gastric Cancer Risk in Eastern China.

Helicobacter pylori (H. pylori) infection can interfere with the absorption of most elements, and the variations of some element levels are related to the incidence of gastric cancer. However, there have been conflicting results concerning the influence of H. pylori infection on serum element levels. The present study aimed to compare the serum element concentrations of H. pylori-infected local residents with uninfected residents from Lujiang County with high gastric cancer risk in Eastern China. We used data and serum samples from the H. pylori screening-survey program which was a cross-sectional study. We took 155 samples randomly from the screening survey, identified 74 H. pylori-positive residents and 81 H. pylori-negative residents by a serological test. The serum concentrations of 15 elements (calcium, magnesium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, nickel, lead, cadmium, mercury, arsenic, and aluminum) were determined using inductively coupled plasma mass spectrometry. Serum cobalt was found at higher levels in the H. pylori-infected residents than the H. pylori-uninfected residents (0.246 vs 0.205 µg/L, P = 0.022), but no statistically significant differences in the serum levels of other elements were found. This is the first study to report the serum concentrations of 15 elements and their relationships with the infection status of H. pylori among local residents from Lujiang County with high gastric cancer risk. Although the International Agency for Research on Cancer has classified cobalt and other soluble cobalt salts as possibly carcinogenic to human beings, our results may provide a clue to the relationships between cobalt, H. pylori, and gastric cancer.

Toxic effect of cooking oil fumes in primary fetal pulmonary type II-like epithelial cells.

Epidemiological studies indicated that there is an increased risk of respiratory tract cancer among cooks and bakers. The cooking oil fumes are believed to conduct this risk, and many studies have focused on evaluating the mutagenicity and finding the mutagenic components in oil fumes. COFs contains two major classes of compounds. One class consists of polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene, benzo[b]fluoranthene, fluoranthene, and benzo[g,h,i]perylene. BaP is a known immunosuppressant. It can also alter cell cycle progression, induce inflammation, and impair DNA repair and apoptotic processes leading to aberrant cellular functioning. This study investigates the effect of toxicity of cooking oil fumes (COFs) in primary ICR mice' fetal lung type II-like epithelium cells (AEC II). The cells were cultured in different concentrations (0, 12.5, 25, 50, 100, and 200µg/ml) of COFs for different time periods. The results showed that cell viability decreased in a dose- and time- dependent manner, which is accompanied by increased malondialdehyde (MDA) level and decreased superoxide dismutase (SOD) and glutathione (GSH) activities. Moreover, comet assay suggested DNA damage, as well as increased production of DNA adducts induced by PAHs. The present study also shows that COFs may disturb cell cycles even at a very low dose. In summary, the present study indicates that COFs may lead to toxicity in AEC II cells.

[Study on experimental factors for extraction of alkaloids from Aconitum carmichaili].

OBJECTIVE: To determine the suitable conditions for extracting alkaloidals from Aconitum carmichaili. METHOD: Using methods in Chinese Pharmacopeia for determining yields of extraction, which include spectrometry and single-factor tests, we investigated vavious factors that would affect the extraction of alkaloids from Aconiti. RESULT: The suitable extractant was 85% ethanol, starting material was medium-size powder of aconiti, 10 times of the volume of the solvent was used in extraction for twice 1.75 h each time. The extraction yield was 1.21%, with a content of 0.33% alkaloids. CONCLUSION: Extraction conditions determined with single factor test was consistent and feasible.