Oxidized Low-Density Lipoprotein Decreases the Survival of Bone Marrow Stem Cells via Inhibition of Bcl-2 Expression.

Therapy with mesenchymal stem cells (MSCs) is considered an attractive strategy for the repair or regeneration of damaged tissues. However, low survival of MSCs limits their applications clinically. Oxidized low-density lipoprotein (ox-LDL) is significantly increased in patients with hyperlipidemia and decreases the survival of MSCs. Bcl-2 is critically involved in important cell functions, including cell membrane integrity and cell survival. The present study was designed to test the hypothesis that ox-LDL attenuates the survival of MSCs through suppression of Bcl-2 expression. Bone marrow MSCs from C57BL/6 mice were cultured with ox-LDL at different concentrations (0-140 µg/mL) for 24 h with native LDL as control. Ox-LDL treatment substantially decreased the survival of MSCs dose-dependently and enhanced the release of intracellular lactate dehydrogenase (LDH) in association with a significant decrease in Bcl-2 protein level without change in BAX protein expression in MSCs. Bcl-2 overexpression effectively protected MSCs against ox-LDL-induced damages with preserved cell numbers without significant increase in LDH release. Treatment with N-acetylcysteine (NAC) (1 mM) effectively preserved Bcl-2 protein expression in MSCs and significantly attenuated ox-LDL-induced decrease of cell number and increase in the release of intracellular LDH. These data indicated that ox-LDL treatment resulted in a significant damage of cell membrane and dramatically decreased the survival of MSCs dose-dependently through inhibition of Bcl-2 expression. NAC treatment significantly protected MSCs against the damage of cell membrane by ox-LDL and promoted the survival of MSCs in association with preserved Bcl-2 expression.

Correction to "Inhibiting heme oxygenase-1 attenuates rat liver fibrosis by removing iron accumulation".

[This corrects the article on p. 2921 in vol. 19, PMID: 23704825.].

Targeting circRNA-MAP4K2 for the treatment of diabetes-induced retinal vascular dysfunction.

Diabetic retinopathy (DR) is an important ocular vascular disease in working-age adults. However, the molecular mechanism underlying retinal vascular dysfunction is still not fully understood in DR. Circular RNAs have been recognized as the crucial regulators in many biological processes and human diseases. Herein, we determined the role of circular RNA-MAP4K2 (cMAP4K2) in diabetes-induced retinal vascular dysfunction. The results showed that high glucose treatment led to increased levels of cMAP4K2 expression in vitro and in vivo. Silencing of cMAP4K2 could reduce endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviate retinal vascular dysfunction in vivo as shown by decreased vascular leakage and inflammation. By contrast, cMAP4K2 overexpression had an opposite effect on retinal vascular dysfunction. Mechanistically, cMAP4K2 acted as miR-377 sponge to affect the biological activity of miR-377, which led to increased expression of vascular endothelial growth factor A (VEGFA). Clinically, cMAP4K2 expression was significantly up-regulated in the clinical sample of DR patients. Collectively, cMAP4K2 is shown as a potential target for the diagnosis and treatment of diabetic retinopathy.

The Characteristics of Iodine Nutrition Status in China After 20 Years of Universal Salt Iodization: An Epidemiology Study Covering 31 Provinces.

Background: Despite the implementation of the universal salt iodization (USI) program for correction of iodine deficiency in China for ∼20 years, the actual iodine nutrition status of Chinese residents and the prevalence of iodine deficiency and iodine excess are issues that need to be addressed. This nationally representative cross-sectional study was conducted across all 31 provinces of mainland China to gather extensive data on iodine nutrition status and the influential factors. Methods: This study included 78,470 participants, aged 18 years or older, who were interviewed and asked to answer a questionnaire. Urine iodine concentration (UIC) was measured by the inductively coupled plasma mass spectrometry method, and goiter was examined by thyroid ultrasonography. In addition, sixty 9-11 years old school children in each province were randomly selected to evaluate the UIC and thyroid ultrasonography. The iodine nutrition status was determined according to the World Health Organization guidelines. Results: The iodized salt coverage was 95.37%. The median urine iodine (MUI) was 177.89 µg/L (interquartile range [IQR], 117.89-263.90 µg/L) and goiter prevalence was 1.17% (confidence interval [95% CI 0.95-1.43]) in the adult population. The MUI was 199.75 µg/L (IQR, 128.41-303.37 µg/L) in school-age children, and goiter prevalence was 3.50% [95% CI, 2.93-4.13]. The percentage of individuals with UIC <50 µg/L was 3.43%, <20%. Analysis indicated that sex, age, geographic factors, body mass index, and smoking habits influence the iodine nutrition level. Conclusion: The mandatory USI program has successfully eliminated iodine deficiency disorders, and the findings indicate that the iodine nutrition level in the general population is within the safe range.

Selenoprotein S attenuates high glucose and/or ox-LDL-induced endothelium injury by regulating Akt/mTOR signaling and autophagy.

Glucolipid metabolism disorder in diabetes mellitus (DM) causes human endothelial injury and autophagy dysfunction is an important cause of endothelial dysfunction (ED). Selenoprotein S (SelS) could protect endothelium from oxidative stress, inflammatory responses, and apoptosis. This study assessed the effect of SelS on autophagy in glucolipid metabolic disorders and protection of the resulted vascular endothelial injury. The results showed that high glucose (HG), high oxidized low-density lipoprotein (HL), and HG combined with HL (HGL) could reduce viability of human aortic endothelial cells (HAECs), induce HAECs injury and increase SelS expression in a time-dependent manner. HG, HL, and HGL also initially induced autophagy but later reduced it in HAECs, while activity of the Akt/mTOR signaling was inhibited, especially in HGL culture of HAECs. SelS overexpression reduced the endothelial injury and autophagy and activated the Akt/mTOR signaling in HG, HL and HGL-cultured HAECs, compared to the control. Conversely, knockdown of SelS expression had the opposite effects on HAECs. In conclusion, SelS demonstrated a protective effect on endothelial injury induced by high glucose and/or ox-LDL and the underlying molecular events might be related to its regulation of HAECs autophagy by activating the Akt/mTOR signaling. SelS could be a potential intervention target in prevention and treatment of diabetic vascular complications.

Exposure to the Chinese Great Famine in Early Life and Thyroid Function and Disorders in Adulthood: A Cross-Sectional Study.

Background: Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959-1961) in early life and thyroid function and disorders in adulthood. Methods: Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Results: Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood (ß = 0.024; p = 0.038), compared with the nonexposed participants. The association was significant among rural participants (ß = 0.039; p = 0.02) but not in urban participants (ß = 0.005; p = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules (p > 0.05). Conclusions: Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary-thyroid axis.

The antagonist of CXCR1 and CXCR2 protects db/db mice from metabolic diseases through modulating inflammation.

Interleukin-8 (IL-8, also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed that metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in db/db mice. The db/m and db/db mice were subcutaneously injected with G31P or equivalent normal saline once a day for 6 wk. The physical and metabolic parameters, glucose tolerance, insulin sensitivity, hepatic lipid accumulation, and inflammation markers were measured. G31P improved hepatic insulin sensitivity by modulating expression of genes related to gluconeogenesis and phosphorylated Akt levels. The expressions of several genes encoding proteins involved in de novo lipogenesis were decreased in G31P-treated db/db mice. Meanwhile, immune cell infiltration and cytokine release were attenuated in db/db mice with G31P treatment. G31P also improved the ratio of proinflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, G31P ameliorates metabolic disturbances via inhibition of CXCR1 and CXCR2 pathways in db/db mice. These data suggest that the selective inhibition of CXC chemokines may have therapeutic effects on symptoms associated with obesity and diabetes.

Selenoprotein S protects against high glucose-induced vascular endothelial apoptosis through the PKCßII/JNK/Bcl-2 pathway.

Vascular endothelial apoptosis is closely associated with the pathogenesis and progression of diabetic macrovascular diseases. Selenoprotein S (SelS) participates in the protection of vascular endothelial and smooth muscle cells from oxidative and endoplasmic reticulum stress-induced injury. However, whether SelS can protect vascular endothelium from high glucose (HG)-induced apoptosis and the underlying mechanism remains unclear. The present study preliminarily analyzed aortic endothelial apoptosis and SelS expression in diabetic rats in vivo and the effects of HG on human umbilical vein endothelial cell (HUVEC) apoptosis and SelS expression in vitro. Subsequently, SelS expression was up- or downregulated in HUVECs using the pcDNA3.1-SelS recombinant plasmid and SelS-specific small interfering RNAs, and the effects of high/low SelS expression on HG-induced HUVEC apoptosis and a possible molecular mechanism were analyzed. As expected, HG induced vascular endothelial apoptosis and upregulated endothelial SelS expression in vivo and in vitro. SelS overexpression in HUVECs suppressed HG-induced increase in apoptosis and cleaved caspase3 level, accompanied by reduced protein kinase CßII (PKCßII), c-JUN N-terminal kinase (JNK), and B-cell lymphoma/leukemia-2 (Bcl-2) phosphorylation. In contrast, inhibiting SelS expression in HUVECs further aggravated HG-induced increase in apoptosis and cleaved caspase3 level, which was accompanied by increased PKCßII, JNK, and Bcl-2 phosphorylation. Pretreatment with PKC activators blocked the protective effects of SelS and increased the apoptosis and cleaved caspase3 level in HUVECs. In summary, SelS protects vascular endothelium from HG-induced apoptosis, and this was achieved through the inhibition of PKCßII/JNK/Bcl-2 pathway to eventually inhibit caspase3 activation. SelS may be a promising target for the prevention and treatment of diabetic macrovascular complications.

Efficacy and safety of sitagliptin added to metformin and insulin compared with voglibose in patients with newly diagnosed type 2 diabetes

OBJECTIVE: To assess the efficacy and safety of sitagliptin compared with voglibose added to combined metformin and insulin in patients with newly diagnosed type 2 diabetes (T2DM). METHODS: In this 12-week prospective, randomized, parallel trial, 70 newly diagnosed T2DM patients with glycosylated hemoglobin (HbA1c) ≥9% and/or fasting plasma glucose (FPG) ≥11.1 mmol/L were randomized (1:1) to receive sitagliptin 100 mg per day + metformin + insulin glargine or voglibose 0.2 mg three times daily + metformin + insulin glargine. Change in HbA1c at week 12 was the primary endpoint. RESULTS: The mean baseline HbA1c was 11.0% in the patients. The changes in HbA1c from baseline were -6.00% in the sitagliptin group and -3.58% in the voglibose group, and the between-group difference was -2.42% (95% CI -1.91 to -2.93, p=0.02). The differences in FPG and homeostatic model assessment of β-cell function (HOMA-β) and the change in body weight between groups from baseline were -2.95 mmol/L (p=0.04), 43.91 (p=0.01) and -2.23 kg (p=0.01), respectively. One patient (2.9%) in the sitagliptin group and three patients (8.6%) in the voglibose group exhibited hypoglycemia. CONCLUSIONS: Sitagliptin added to combined metformin and insulin therapy showed greater efficacy and good safety regarding hypoglycemia in patients with newly diagnosed T2DM compared with voglibose.

Decreased Thyroid Peroxidase Antibody Titer in Response to Selenium Supplementation in Autoimmune Thyroiditis and the Influence of a Selenoprotein P Gene Polymorphism: A Prospective, Multicenter Study in China.

Background: Recent intervention studies have suggested that selenium (Se) is an effective treatment for autoimmune thyroiditis (AIT). However, the exact effect of Se on AIT is unclear as well as the mechanism of action. The aim of the present study was to explore the effect of Se on thyroid peroxidase antibody (TPOAb) titers in patients with AIT and to analyze the potential impact of the genetic background on the effect of Se supplementation. Methods: This was a randomized, placebo-controlled, double-blind trial. Three hundred and sixty-four patients with elevated TPOAb (>300 IU/mL) were recruited and randomized to receive Se yeast 200 µg/day supplementation or placebo. Urinary iodine concentration, serum thyrotropin, free thyroxine, TPOAb, Se, malondialdehyde, and serum glutathione peroxidase activity were measured at baseline and follow-up. Ninety-six patients were genotyped for single nucleotide polymorphism r25191G/A in the selenoprotein P (SEPP1/SELENOP) gene. Results: The median urinary iodine concentration was 182 µg/L. Serum Se increased significantly (p < 0.001) after Se treatment. TPOAb titer decreased by 10.0% at 3 months and by 10.7% at 6 months after Se supplementation, while there was a moderate increase in TPOAb titers over the follow-up period in patients receiving placebo. Glutathione peroxidase activity significantly increased (p < 0.001), and malondialdehyde significantly decreased (p < 0.001) after 6 months of Se supplementation. TPOAb titers decreased to variable extents in patients with different genotypes of single nucleotide polymorphism r25191G/A after Se supplementation. Serum TPOAb titers in patients with the AA genotype showed a more significant decrease (by 46.2%) than those with the GA and GG genotypes (by 14.5 and 9.8% respectively) at 3 months of Se supplementation (p = 0.070). Conclusions: Se supplementation significantly reduced TPOAb titers in patients with AIT, and there may be an important genetic component influencing interindividual differences in the decrease in TPOAb titers.

Diagnostic value of endoscopic ultrasound for insulinoma localization: A systematic review and meta-analysis.

BACKGROUND: Previous studies reported varies parameters of endoscopic ultrasound (EUS) for the localization of insulinomas, the purpose of this meta-analysis based on published studies to accuracy the diagnostic value of EUS. METHODS: PubMed, Embase, Web of science, Cochrane library and Wanfang digital database were searched to identify published studies up to April 2018, which diagnostic insulinoma by using EUS. Retrieved sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and receiver operating characteristic (ROC) curves data were summarized for meta-analysis. RESULTS: A total of 9 studies involved a total of 350 patients were included in final analysis. The summary sensitivity, specificity, PLR, and NLR were 0.81 (95%CI: 0.75-0.86), 0.90 (95%CI: 0.84-0.94), 7.90 (95%CI: 4.9-12.8), and 0.21 (95%CI: 0.16-0.29), respectively. Further, the pooled DOR was 37.00 (95%CI:19.55-70.04) and area under the ROC was 0.92 (95%CI: 0.90-0.84). CONCLUSION: The findings of this study demonstrate that EUS should be a routine diagnosis approach for the preoperative localization of insulinomas.

Iron Deficiency May Predict Greater Risk for Hypothyroxinemia: A Retrospective Cohort Study of Pregnant Women in China.

BACKGROUND: Pregnant women are highly vulnerable to iron deficiency (ID) due to the increased iron needs during pregnancy. ID decreases circulating thyroid hormone concentrations likely through impairment of iron-dependent thyroid peroxidase. The present study aimed to explore the association between ID and hypothyroxinemia in a retrospective cohort of pregnant women in China. METHODS: To investigate the relationship between ID and hypothyroxinemia, 723 pregnant women were retrospectively analyzed, including 675 and 309 women in the second and third trimesters, respectively. Trimester-specific hypothyroxinemia was defined as free thyroxine (fT4) levels below the 2.5th percentile of the reference range with normal serum thyrotropin (TSH) or TSH higher than the 97.5th percentile of the reference range in each trimester of pregnancy. Serum TSH, fT4, thyroid peroxidase antibodies, thyroglobulin antibodies, serum ferritin, soluble transferrin receptor, and urinary iodine concentrations were measured. Serum ferritin, soluble transferrin receptor, and total body iron were used to indicate the nutritional iron status. RESULTS: Cross-sectional multiple linear regression analysis showed that iron status was positively associated with serum fT4 levels in the first and second trimesters of pregnancy, but not in the third trimester. Logistic regression analysis showed that ID was an independent risk factor for hypothyroxinemia (odds ratio = 14.86 [confidence interval 2.31-95.81], p = 0.005 in the first trimester and odds ratio = 3.36 [confidence interval 1.01-11.21], p = 0.048 in the second trimester). The prospective analysis showed that pregnant women with ID during the first trimester of pregnancy had lower serum fT4 levels and a higher rate of hypothyroxinemia in the second or third trimester than those without ID. CONCLUSIONS: ID appears to be a risk factor to predict hypothyroxinemia in the first and second trimesters of pregnancy, but not in the third trimester. Pregnant women with ID in the first and second trimesters should be regarded as a high-risk group for maternal hypothyroxinemia.

A case series study of hypopituitarism in older patients with and without gastrointestinal symptoms.

OBJECTIVES: Some older individuals who present with gastrointestinal symptoms as their chief complaint were ultimately diagnosed with hypopituitarism instead of gastrointestinal diseases. The aim of this study was to find the characteristics of biochemical indicators in these patients so as to reduce early misdiagnosis. METHODS: We conducted a retrospective review of 45 patients with hypopituitarism who were at least 60 years of age. Two groups were included: group of hypopituitarism patients with gastrointestinal symptoms (Group G) included 23 patients with gastrointestinal symptoms and group of hypopituitarism patients without gastrointestinal symptoms (Group N) included 22 patients without these symptoms. In Group G, we investigated the prevalence of different gastrointestinal symptoms, the response of these symptoms to treatment, the occurrence of electrolyte disorders, and target gland dysfunction. Then, we compared the electrolyte and target gland function indices between the two groups. RESULTS: Nausea and vomiting were the most common complaints, accounting for 69.57% of the gastrointestinal symptoms in Group G. Hyponatremia was the most common electrolyte disorder, occurring in 72.86% (n = 18) of patients in Group G. Hypoadrenalism and hypothyroidism were reported by 69.57% and 60.78% of patients, respectively, in Group G. None of the gastrointestinal symptoms were relieved by 4 weeks of treatment with antacid and motility drugs. As mentioned, 18 patients also experienced refractory hyponatremia during early treatment including regular sodium supplements; however, their gastrointestinal symptoms and hyponatremia improved after only a week of treatment for hypopituitarism. Regarding the biochemical indicators, only serum sodium and cortisol in Group G were statistically lower compared with those in Group N (P < .05). CONCLUSION: Nausea and vomiting were the most common gastrointestinal symptoms in older patients with hypopituitarism, which were associated with lower serum sodium and cortisol. In addition, we hope to share the research to our gastroenterologists that serum sodium and cortisol should be tested when meeting elder patients with unexplained gastrointestinal symptoms.

Selenoprotein S Attenuates Tumor Necrosis Factor-α-Induced Dysfunction in Endothelial Cells.

Endothelial dysfunction, partly induced by inflammatory mediators, is known to initiate and promote several cardiovascular diseases. Selenoprotein S (SelS) has been identified in endothelial cells and is associated with inflammation; however, its function in inflammation-induced endothelial dysfunction has not been described. We first demonstrated that the upregulation of SelS enhances the levels of nitric oxide and endothelial nitric oxide synthase in tumor necrosis factor- (TNF-) α-treated human umbilical vein endothelial cells (HUVECs). The levels of TNF-α-induced endothelin-1 and reactive oxygen species are also reduced by the upregulation of SelS. Furthermore, SelS overexpression blocks the TNF-α-induced adhesion of THP-1 cells to HUVECs and inhibits the increase in intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Moreover, SelS overexpression regulates TNF-α-induced inflammatory factors including interleukin-1ß, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 and attenuates the TNF-α-induced activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Conversely, the knockdown of SelS with siRNA results in an enhancement of TNF-α-induced injury in HUVECs. These findings suggest that SelS protects endothelial cells against TNF-α-induced dysfunction by inhibiting the activation of p38 MAPK and NF-κB pathways and implicates it as a possible modulator of vascular inflammatory diseases.

CXCL8 Antagonist Improves Diabetic Nephropathy in Male Mice With Diabetes and Attenuates High Glucose-Induced Mesangial Injury.

Inflammation is recognized as a crucial contribution to diabetic nephropathy (DN). CXCL8 binds to its CXC chemokine receptors (CXCR1 and CXCR2) for recruiting neutrophil infiltration and initiates tissue inflammation. Therefore, we explored the effect of CXCR1 and CXCR2 inhibition on DN. This was achieved by CXCL8(3-72)K11R/G31P (G31P), an antagonist of CXCL8 that has exhibited therapeutic efficacy in inflammatory diseases and malignancies. In this study, we found that renal leukocyte accumulation and rapid increases of CXCL8 occurred in high-fat diet/streptozocin-induced diabetic mice. G31P effectively reduced urine volume, urine albumin/creatinine ratio, blood urea nitrogen, and creatinine clearance rate in mice with diabetes. In addition, renal histopathologic changes including mesangial expansion, glomerulosclerosis, and extracellular matrix deposition were partially moderated in G31P-treated diabetic mice. Furthermore, G31P attenuated renal inflammation and renal fibrosis of diabetic mice by inhibiting proinflammatory and profibrotic elements. G31P also inhibited high glucose-induced inflammatory and fibrotic factor upregulation in human renal mesangial cells. At the molecular level, G31P inhibited activation of CXCR1/2 downstream signaling JAK2/STAT3 and ERK1/2 pathways in in vitro and in vivo experiments. Our results suggest blockade of CXCR1/2 by G31P could confer renoprotective effects that offer potential therapeutic opportunities in DN.

[Pharmacological actions and mechanism of saponins from Dioscorea nipponica].

Dioscorea nipponica, a famous traditional Chinese medicine, belongs to the Dioscoreaceae family and has been widely distributed in the north, northeast and Qinghai regions of China. With its root and rhizome as an important herb material, it has been applied in China for several thousand years. Traditional Chinese medicine reported that this plant had been used for relieving cough and asthma, eliminating rheumatic aches, alleviating pain and improving blood circulation. Modern pharmacology studies have confirmed that saponins, the major active compounds in this herb, have shown various pharmacological actions including anti-tumor, anti-inflammatory,lipid-lowering, anti-fungal and anti-virus activities. Therefore, the studies on saponins from D. nipponica are valuable and promising. In this present research, the pharmacological actions, therapeutic effects and mechanism of saponins from D. nipponica were summarized in order to provide the theoretical basis for the further research.

The source of circulating selenoprotein S and its association with type 2 diabetes mellitus and atherosclerosis: a preliminary study.

BACKGROUND: Selenoprotein S (SelS) is a transmembrane protein that is expressed in the liver, skeletal muscle, adipose tissue, pancreatic islets, kidney, and blood vessels. In addition to its transmembrane localization, SelS is also secreted from hepatoma HepG2 cells (but not L6 skeletal muscle cells, 3T3-L1 adipocytes, Min6 pancreatic ß cells and human embryonic kidney 293 cells) and has been detected in the serum of some human subjects, with a detection rate of 31.1 %. These findings prove that serum SelS is secreted by hepatocytes. However, whether vascularly expressed SelS can be secreted has not been reported. Transmembrane SelS has been suggested to play different roles in the pathogenesis and progression of diabetes mellitus (DM) and atherosclerosis (AS), but the association of secreted SelS with DM and macroangiopathy remains unclear. RESEARCH DESIGN AND METHODS: Supernatants were collected from human umbilical vein endothelial cells (HUVECs), human aortic vascular smooth muscle cells (HA/VSMCs) and human hepatoma HepG2 cells that were untransfected or transfected with the indicated plasmid and concentrated for western blotting. Serum samples were collected from 158 human subjects with or without type 2 DM (T2DM) and/or AS. Serum SelS levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Secreted SelS was only detected in the supernatants of hepatoma HepG2 cells. The SelS detection rate among the 158 human serum samples was 100 %, and the average SelS level was 64.81 ng/dl. The serum SelS level in the isolated DM subjects was lower than the level in the healthy control subjects (52.66 ± 20.53 vs 70.40 ± 21.38 ng/dl). The serum SelS levels in the DM complicated with SAS subjects (67.73 ± 21.41 ng/dl) and AS subjects (71.69 ± 27.00 ng/dl) were significantly increased compared with the serum SelS level in the isolated DM subjects. There was a positive interaction effect between T2DM and AS on the serum SelS level (P = 0.002). Spearman correlation analysis showed that the serum SelS level was negatively correlated with fasting plasma glucose. CONCLUSIONS: Vascular endothelial and vascular smooth muscle cells could not secrete SelS. Serum SelS was primarily secreted by hepatocytes. SelS was universally detected in human serum samples, and the serum SelS level was associated with T2DM and its macrovascular complications. Thus, regulating liver and serum SelS levels might become a new strategy for the prevention and treatment of DM and its macrovascular complications.

Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study.

Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%-27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile.

Iron deficiency, an independent risk factor for isolated hypothyroxinemia in pregnant and nonpregnant women of childbearing age in China.

CONTEXT: Isolated hypothyroxinemia during early pregnancy may irreversibly damage the neurodevelopment of offspring. However, the causes are not well clarified. OBJECTIVE: To explore the association of iron deficiency (ID) with hypothyroid function of women in early pregnancy and nonpregnant women. DESIGN: A total of 7953 pregnant women of ≤ 12 weeks gestation and 2000 childbearing-aged women were recruited. A subpopulation including 3340 pregnant women and 1052 nonpregnant women with sufficient iodine intake and negative thyroid peroxidase antibody were studied. Mild and severe cases of hypothyroxinemia were defined as free T4 levels below the 10th percentile and the 5th percentile, respectively, with normal TSH. Total body iron, serum ferritin, and serum transferrin receptor were used as indicators for iron nutrition. RESULTS: Serum free T4 levels were significantly lower in both pregnant and nonpregnant women with ID compared with the corresponding groups without ID (both P < .05). The prevalence of mild and severe hypothyroxinemia was markedly higher in women with ID than those without, in both pregnant and nonpregnant women (all P < .01). Logistic regression indicated that ID was an independent risk factor for both mild and severe hypothyroxinemia in pregnancy (odds ratio [OR] = 2.440, 95% confidence interval [CI]: 1.324-4.496, P = .004; and OR = 3.278, 95% CI: 1.443-7.446, P = .005, respectively) and nonpregnancy (OR = 2.662, 95% CI: 1.330-5.329, P = .006; and OR = 3.254, 95% CI: 1.375-7.700, P = .007, respectively). CONCLUSIONS: An association between ID and isolated hypothyroxinemia was found in both pregnant and nonpregnant childbearing-aged women, independent of the effects of iodine and thyroid autoimmunity. We speculate that ID may be a pathogenic factor for hypothyroxinemia, even in pregnant women during the first trimester.

Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer.

CONTEXT: The aggressive role of TERT promoter mutations has been well established in differentiated thyroid cancer but has not been established in anaplastic thyroid cancer (ATC). RESEARCH DESIGN: We tested the mutation status by sequencing genomic tumor DNA and examined its relationship with clinicopathological characteristics of ATC. RESULTS: Among 106 American and Chinese ATC samples, TERT 1,295,228 C>T (termed TERT C228T) mutation was found in 37 (34.9%) cases, TERT promoter mutation 1,295,250 C>T was found in four cases (3.8%), and the two mutations were mutually exclusive and collectively found in 41 cases (38.7%). TERT C228T occurred in 28 of 90 (31.1%) wild-type BRAF cases vs nine of 16 (56.3%) BRAF V600E cases, with an odds ratio of 2.85 (95% confidence interval, 0.96-8.42; P = .05). Patient age was 67.6 ± 13.6 vs 61.6 ± 11.4 years in the TERT C228T vs wild-type TERT patients (P = .02), demonstrating an association between TERT C228T and older patient age. This association was also seen within the American cohort. In this cohort, which had more available clinicopathological data, TERT C228T was associated with distant metastasis of the tumor; specifically, distant metastasis occurred in 15 of 18 (83.3%) TERT C228T patients vs eight of 26 (30.8%) wild-type TERT patients, with an odds ratio of 11.25 (95% confidence interval, 2.53-50.08; P = .001). No association was found with patient sex, tumor size, lymph node metastasis, and extrathyroidal invasion of ATC. CONCLUSIONS: This is the largest study on the aggressive role of TERT promoter mutations in ATC, demonstrating an association of TERT C228T with BRAF V600E, older patient age, and tumor distant metastasis in ATC.