Salivary iodine concentration in pregnant women and its association with iodine status and thyroid function.

PURPOSE: There have been no reports on the application of salivary iodine concentration (SIC) in evaluating iodine nutrition in pregnant women. This study aimed to clarify the relationship between SIC and indicators of iodine nutritional status and thyroid function during pregnancy, to investigate whether salivary iodine can be applied to the evaluation of iodine nutritional status in pregnant women, and to provide a reference basis for establishing a normal range of salivary iodine values during pregnancy. METHODS: Pregnant women were enrolled in the Department of Obstetrics, the people's hospital of Yuncheng Country, Shandong Province, from July 2021 to December 2022, using random cluster sampling. Saliva, urine, and blood samples were collected from pregnant women to assess iodine nutritional status, and venous blood was collected to determine thyroid function. RESULTS: A total of 609 pregnant women were included in this study. The median spot urinary iodine concentration (SUIC) was 261 µg/L. The median SIC was 297 µg/L. SIC was positively correlated with SUIC (r = 0.46, P < 0.0001), 24-h UIC (r = 0.30, P < 0.0001), 24-h urinary iodine excretion (24-h UIE) (r = 0.41, P < 0.0001), and estimated iodine intake (EII) (r = 0.52, P < 0.0001). After adjusting for confounders, there was a weak correlation between SIC and serum total iodine and serum non-protein-bound iodine (P = 0.02, P = 0.04, respectively). Pregnant women with a SIC < 176 µg/L had a higher risk of insufficient iodine status (OR = 2.07, 95% CI 1.35-3.19) and thyroid dysfunction (OR = 2.71, 95% CI 1.18-6.21) compared to those with higher SIC. Those having SIC > 529 µg/L were more likely to have excessive iodine status (OR = 2.82, 95% CI 1.81-4.38) and thyroid dysfunction (OR = 3.04, 95% CI 1.36-6.78) than those with lower SIC values. CONCLUSION: SIC is associated with urinary iodine concentration and thyroid function in pregnant women. SIC < 176 µg/L was associated with an increased risk for iodine deficiency and hypothyroxinemia, while SIC > 529 µg/L was related to excess and thyrotoxicosis. SIC can be used as a reference indicator for evaluating the iodine nutrition status of pregnant women, but it needs further investigation and verification. TRIAL REGISTRATION: NCT04492657(Aug 9, 2022).

A catchment-wide microplastic pollution investigation of the Yangtze River: The pollution and ecological risk of tributaries are non-negligible.

The Yangtze River is an important global channel for plastics and microplastics (MPs) to enter the sea. However, the existing research on MPs in the Yangtze River has primarily focused on the mainstream region, without regarding the occurrence, spatial distribution, and ecological risks associated with tributaries, as well as their relationship with the mainstream. To address this knowledge gap, we conducted a large-scale catchment-wide investigation of the surface water in the Yangtze River, encompassing MPs (48 µm-5 mm) of the mainstream and 15 important tributaries. Tributaries and upstream regions exhibited relatively higher levels of MPs compared with the mainstream and different sections of the river. The distribution of MPs is primarily influenced by the emission of arable land and the pH of water. Notably, the upstream tributary areas demonstrated the highest ecological risks associated with MPs. Further analysis highlighted that the tributaries accounted for a contribution ranging from 16% to 67% in quantity and from 14% to 90% in mass of the microplastics observed in the mainstream. Our results suggest that the pollution of tributaries and their associated ecological risk migration must be effectively regulated.

Effect of different iodide intake during pregnancy and lactation on thyroid and cardiovascular function in maternal and offspring rats.

OBJECTIVE: We aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats. METHODS: Pregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 µg/d), normal pregnant iodide intake (NPI, 12.5 µg/d), 5 times (5 HI, 62.5 µg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 µg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRß was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system. RESULTS: High iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = -0.909, p = 0.012; r = -0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = -0.917, p = 0.01; r = -0.859, p = 0.028; r = -0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = -0.990, p = 0.0002) and Txnrd2 expression (r = -0.979, p = 0.001; r = -0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased. CONCLUSION: In addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function.

Prostaglandin E1 Improves Cerebral Microcirculation Through Activation of Endothelial NOS and GRPCH1.

Endothelial dysfunction greatly contributes to microcirculation disorder. The role of prostaglandin E1 (PGE1) in cerebral microcirculation was explored in vitro. LPS (0.5 or 1 µg/ml) was added to induce injury in human brain microvascular endothelial cells (HCMEC/D3). CCK-8 was applied to check viabilities of HCMEC/D3 before and after LPS treatment. Western blot witnessed the changes in protein expressions of inflammatory cytokines, IL-6 and TNF-α. Caspase-3/7 activity was analyzed and so were the protein expressions of pro-apoptotic gene BAX and anti-apoptotic gene Bcl-2. mRNA expressions of eNOS and GTPCH1 were evaluated by RT-qPCR. After overexpressing eNOS or GTPCH1 in LPS-induced HCMEC/D3 cells, viabilities, inflammatory cytokines, caspase-3/7 activity, and apoptosis-related genes were detected. The modulation of PGE1 in eNOS and GTPCH1 production, viability, inflammation, and apoptosis was investigated. The inhibitor of eNOS or GTPCH1 was introduced to examine impacts of eNOS or GTPCH1 could have on the PGE1 function. LPS decreased cell viabilities, eNOS and GTPCH1 expression, and promoted inflammation and apoptosis in HCMEC/D3 cells. Overexpressed eNOS or GTPCH1 promoted cell viabilities and suppressed inflammation and apoptosis. PGE1 enhanced viability and decreased inflammation and apoptosis in cells treated by LPS. PGE1 activated eNOS and GTPCH1 and inhibition of eNOS or GTPCH1 led to the attenuation of the protective functions of PGE1 in LPS-induced cells. PGE1 protected HCMEC/D3 cells from injuries induced by LPS by activation of eNOS and GTPCH1, suggesting that PGE1 might be used to help maintain cerebral microcirculation in future.

L-Arginine Ameliorates High-Fat Diet-Induced Atherosclerosis by Downregulating miR-221.

OBJECTIVES: Atherosclerosis (AS) is a severe disease in which the inside of an artery narrows because of plaque formation, leading to endothelial injury in the patients. Although it has been found that endothelial nitric oxide synthase (eNOS), which produces a low concentration of NO, is necessary for endothelial function and integrity, the regulatory mechanisms of eNOS expression against the pathogenesis and development of AS are unclear. Evidence has indicated that diet supplementation with L-arginine could reduce the size of the endothelial injury lesions in AS patients. In addition, nonencoding microRNAs (miRNAs) were found to be a promising tool that regulates the expression of eNOS in human endothelial cells. DESIGN: The aim of this research was to explore the role of L-arginine in the development of AS and the mechanisms by which miR-221 influences the possible signaling pathways in endothelial cells during AS. RESULTS: The results suggested that L-arginine could prevent oxidized low-density lipoprotein-induced apoptosis in endothelial cells, which is associated with the downregulation of miR-221. Similar results were also observed in rat AS models. CONCLUSION: This research could provide potential therapies for the treatment of AS.

Bayesian analysis of isothermal titration calorimetry for binding thermodynamics.

Isothermal titration calorimetry (ITC) is the only technique able to determine both the enthalpy and entropy of noncovalent association in a single experiment. The standard data analysis method based on nonlinear regression, however, provides unrealistically small uncertainty estimates due to its neglect of dominant sources of error. Here, we present a Bayesian framework for sampling from the posterior distribution of all thermodynamic parameters and other quantities of interest from one or more ITC experiments, allowing uncertainties and correlations to be quantitatively assessed. For a series of ITC measurements on metal:chelator and protein:ligand systems, the Bayesian approach yields uncertainties which represent the variability from experiment to experiment more accurately than the standard data analysis. In some datasets, the median enthalpy of binding is shifted by as much as 1.5 kcal/mol. A Python implementation suitable for analysis of data generated by MicroCal instruments (and adaptable to other calorimeters) is freely available online.

MiR-208a-3p aggravates autophagy through the PDCD4-ATG5 pathway in Ang II-induced H9c2 cardiomyoblasts.

Pathological cardiac hypertrophy is the main determinant of the development of heart failure, for which there is often no effective therapy. The dysregulation of autophagy is implicated in hypertrophy, but the mechanism linking these processes is unclear. In this study, we characterized the regulatory role of miR-208a-3p in autophagy in H9c2 cardiomyoblasts induced by Angiotensin II (Ang II). We found that miR-208a-3p was up-regulated in Ang II-induced H9c2 cardiomyoblasts and in starvation-induced autophagy. The overexpression of miR-208a-3p increased Ang II-induced autophagy, and this was accompanied by the inhibition of programmed cell death protein (PDCD4) and upregulation of autophagy protein 5 (ATG5). A dual-luciferase report assay confirmed the direct binding between miR-208a-3p and PDCD4. PDCD4 knockdown up-regulated autophagy, and its overexpression down-regulated this process. Moreover, the PDCD4-mediated regulation of autophagy was modulated by ATG5. Taken together, these findings indicate that miR-208a-3p promotes autophagy during Ang II-induced hypertrophy and provide a basis for the development of therapies for hypertrophic-induced cardiac dysfunction.

Comparison of lifestyle and living environment among high risk immigrant and low risk host residents: implications for esophageal cancer etiology.

BACKGROUND: It has been hypothesized that the high prevalence of esophageal squamous cell carcinoma (ESCC) in China is associated with specific environments and lifestyles. A previous study found that immigrant residents (IR) from Henan, residing long term in the town of Caihu, had significantly greater risk of dying from ESCC than host residents (HR). OBJECTIVES: This study was conducted to compare lifestyle and living environments between high risk IR and low risk HR to determine risk factors for ESCC. METHODS: The subjects included randomly selected IR and HR living in Caihu. Information on lifestyle and the living environment of participants was collected by interview using a structured questionnaire. RESULTS: The IR were found to have a higher consumption of hot food (P<0.05), pickled vegetables (P<0.05) and a lower consumption of fresh fruits and vegetables, and alcohol (P<0.05), compared with the HR. There were no significant differences in income and cigarette smoking between the two populations. Fewer IR families had a separate kitchen (P<0.05) than host families. CONCLUSIONS: Our study provided some epidemiological evidence indicating that dietary factors, such as hot food, pickled vegetables, salt, and low fruit and vegetable intake, as well as a poor living environment, are possibly related to the higher prevalence of ESCC in IR. However, cigarette smoking, alcohol drinking and income were not shown to be risk factors for immigrant susceptibility to ESCC in our study.

The high incidence of esophageal cancer in parts of China may result primarily from genetic rather than environmental factors.

About 40,000 inhabitants migrated from a high-risk area of esophageal squamous cell carcinoma (ESCC) to a low-risk area of esophageal cancer 40 years ago. Little is known about the change in the mortality in esophageal cancer among these immigrants. This study examined the impact of changing environments on esophageal cancer by comparing age-standardized mortality rates of immigrant group to the rates of native population (natives who live in high cancer location and have never moved) and host populations (hosts who live in low cancer location and have never moved people). All ESCC deaths taking place during 1999-2004 among the migrant, native, and host populations were identified by retrospective population-based screening. Direct age-adjusted mortality rates were calculated by using the China population of year 2000 as standard population. From 1999-2004, the average annual age-adjusted mortality of ESCC for the migrant, native, and host population was 61.6/100,000, 59.7/100,000, and 6.7/100,000, respectively. No decreasing tendency was found in mortality rate of ESCC in the population of young immigrants. The mortality rate of ESCC of migrants remained high even they had been living in the low endemic region for 40 years. This study strongly suggested that genetic susceptibility, rather than environment exposure, is responsible for the high risk of ESCC in the migrants.

[Detection of apoptosis genes differentially expressed in patients with different degrees of benzene poisoning by cDNA microarray].

OBJECTIVE: To investigate the differential expression of apoptosis genes in patients with different degrees of benzene poisoning by cDNA microarray. METHODS: Peripheral mononuclear cells were isolated from seven patients with benzene poisoning of different degrees (suspected 1 case, moderate 2, severe 2), and seven age and sex matched normal control subjects. Total RNA was extracted and purified, followed by reverse transcription to cDNAs with concomitant incorporation of fluorescent dCTP (Cy3 or Cy5). Then 177 genes associated with cell apoptosis were hybridized against the cDNAs probes in microarray. Fluorescent signals were scanned to detect apoptosis genes differentially expressed in patients and normal subjects. RESULTS: Forty one genes were found to be differentially expressed between benzene-poisoned patients and normal controls; among the 41 genes, three were up-regulated among patients with mild to moderate degrees of benzene poisoning and one up-regulated among all patients. The total amount of differentially expressed genes of apoptosis decreased with the aggravation of benzene poisoning. CONCLUSIONS: Differential expression of apoptosis genes was found in patients with benzene poisoning, suggesting a role of altered apoptosis in benzene-induced hematotoxicity.

[Analysis on tumor related gene expression profiles in benzene poisoning using cDNA microarray].

OBJECTIVE: To detect target genes for further study by way of analyzing the gene expression profiles of benzene poisoning by using cDNA microarray. METHODS: Peripheral mononuclear cells were isolated from seven patients with benzene poisoning of different degrees, and sevene age-and sex-matched normal subjects. Total RNA was extracted and purified, followed by revese transcription to cDNAs with concomitant incorporation of fluorescent dCTP (Cy3 or Cy5). The cDNAs were used as probes in microarray of 2780 cloned cDNA. Fluorescent signals were scanned to detect genes differentially expressed in patients and normal subjects. RESULTS: Among 7 pieces of cDNA microarray of 2780 tumour related genes, the expression of 16 genes, such as GRO1, TGFBR3, LYN ctc was upregulated, whereas the expression of 28 genes, such as FOSB, DJ-1, MCT-1 etc was down-regulated. CONCLUSION: Abnormal expression of tumour related genes of patients exposed to benzene suggests that they may be the key genes, which play important role in benzene-induced leucocythemia. cDNA microarray technique is useful to indicate the expression mode of benzene poisoning tumour related genes, and to find rapidly and effectively new research object and the way of gene therapy.

[Association of p53, PCNA expression and trace element content in esophageal mucosa].

BACKGROUND & OBJECTIVE: There were abnormal changes of trace element in esophageal cancer patient's hair and serum in the high risk area. But it was still unknown that the relationship between p53 and proliferating cell nuclear antigen(PCNA) expression and the trace element content in varied esophageal mucosa. This study was designed to probe the relationship of trace element content and p53 mutation, PCNA expression in esophgeal mucosa. METHODS: Esophageal biopsy specimen of 151 cases were divided into four groups (normal, esophagitis, dysplasia, and early carcinoma). The quantitative determination of trace element was performed was performed by using X-ray energy spectrometry and the detection of PCNA expression and p53 mutation was performed by using S-P immunohistochemistry method. RESULTS: The contents of Zn, Se, Mo, were 1.74 +/- 0.32, 1.53 +/- 0.64, 0.58 +/- 0.21, 0.20 +/- 0.08; 0.15 +/- 0.06, 0.10 +/- 0.03, 0.04 +/- 0.02, 0; 4.73 +/- 1.31, 3.45 +/- 1.19, 3.51 +/- 1.32, 2.51 +/- 1.04; respectively in four groups. There was a significant difference in varied histological typies(P < 0.05). The contents of Cu/Zn, Ni were 0.57 +/- 0.17, 0.89 +/- 0.18, 2.45 +/- 0.48, 2.92 +/- 1.08; 0.45 +/- 0.05, 1.27 +/- 0.11, 2.46 +/- 0.24, 2.58 +/- 0.33; respectively, which increased gradually in pace with upgrade of esophageal lesions, with significant difference (P < 0.05). The postive rates of p53 and PCNA were 0, 46.15%, 100%; 31.19%, 84.62%, 100% respectively in normal esophageal epithelium, dysplasia, and early carcinoma, with significant difference (P < 0.01), and had significant correlation to trace element. CONCLUSION: The content variation of Zn, Se, Mo, Cu, Ni could be possessed of certain effect on p53 mutation and PCNA overexpression of esophageal epithelium in the high risk area.

Effect of manganese on heat stress protein synthesis of new-born rats.

AIM: To study the effect of manganese (Mn) on heat stress protein 70 (HSP70) synthesis in the brain and liver of new-born rats whose mother-rats were exposed to Mn. METHODS: 32 female rats were randomly divided into four groups. One group was administrated with physiological saline only as control group, the other three groups were administrated with 7.5, 15 and 30 mg x kg(-1) manganese chloride (MnCl2) by intraperitioneal injection every two days for two weeks. After delivery, the mother-rats received MnCl2 unceasingly for a week with the same method. Then the contents of Mn Zn Cu and Fe in the livers of the new-born rats were determined by atomic absorption spectroscopy; The level of HSP70 in the brains and the livers of the new-born rats as detected by Western-dot-blotting, and the SOD activities were measured simultaneously. RESULTS: The contents of Mn in the livers of new-born rats of the experimental groups(respective 1.38+/-0.18, 2.73+/-0.65,3.44+/-0.89 microg x g(-1)) were significantly increased compared with the control group(0.88+/-0.18 microg x g(-1); P<0.01); The contents of Fe in the livers of new-born rats of 15 and 30 mg x kg(-1) experimental groups (426+/-125, 572+/-175 microg x g(-1), respectively) were significantly increased compared with the control group(286+/-42 microg x g(-1); P<0.05); the levels of Zn in the livers of the new-born rats of three experimental groups(254+/-49, 263+/-47, 213+/-28 microg x g(-1), respectively) were lower than those of the control group(335+/-50 microg x g(-1); respective P<0.05, P<0.01); and the levels of Cu showed no significant difference among the four groups(three experimental groups: 75+/-21, 68+/-241 and 78+/-18 microg x g(-1); control group: 83+/-9 microg x g(-1); P<0.05). There was a significant increase in the levels of HSP70 in the brains of new-born rats of the 30 mg x kg(-1) group (19.5 x 10(3)+/- 1.3 x 10(3)A;control group:14.3 x 10(3)+/-1.4 x 10(3)A; P<0.01) and the levels of HSP70 in the livers of new-born rats of three experimental groups(respective 19.6 x 10(3)+/- 3.9 x 10(3)A,18.5 x 10(3)+/-3.8 x 10(3)A, 22.4 x 10(3)+/-1.9 x 10(3)A) also increased than control group(13.3 x 10(3)+/-1.0 x 10(3)A;P<0.01), but the SOD activities showed no significant difference among brains of the four groups (experimental groups: 5.04+/-0.43, 4.83+/-0.48, 4.60+/-0.84 ku x g(-1); control group: 4.91+/-0.37 ku x g(-1); P<0.05). The SOD activities in the livers of 15 mg x kgP< group(5.41+/-0.44 ku x gP<) was lower than the control group(5.95+/-0.36 ku x gP<; P<0.05). CONCLUSION: While mother-rats were exposed to manganese, the metabolisms of Mn Zn and Fe of new-born rats in the livers were influenced and were situated in a stress status, thus HSP70 syntheses is induced in the brains and livers of new-born rats, but the mechanism of this effect in the developmental toxicity of Mn remains to be further studied.