A follow-up study on factors affecting the recovery of patients with hypothyroidism in different selenium environments.

BACKGROUND: Hypothyroidism is a major manifestation of autoimmune thyroid diseases (AITD). We previously reported that a low selenium (Se) status was linked to an elevated prevalence of thyroid diseases. We hypothesized that Se status may also influence the restoration of thyroid function. Thus, this study aimed to investigate the factors affecting the recovery of thyroid function in patients with (sub-)clinical hypothyroidism, with a specific focus on Se status. METHODS: We conducted a 6-year prospective cohort study comparing two counties with different Se concentrations. Demographic and disease data were collected from 1,190 individuals (549 Se-adequate and 641 Se-deficient) who completed a follow-up study in 2019. In addition, urinary iodine (I) levels, thyroid function, and serum and nail Se levels were measured. Logistic regression was used to investigate the relationship between Se deficiency and recovery of thyroid function. RESULTS: Sex and smoking status was similar between the two counties studied. Thyroid function recovery rate was significantly higher in Se-deficient counties (46.0% vs. 30.6%, P = 0.008). In the multivariate analysis, our results show that female sex (odds ratio [OR] (95% confidence interval [CI]) = 1.875 (1.080-3.257), P = 0.026] and increasing age [OR (95%CI) = 1.028(1.007-1.049), P = 0.009] were associated with the recovery rate. Additionally, our study revealed that while Se status was significant in the univariate analysis, this association appeared to disappear in the multivariate analysis. CONCLUSIONS: Female sex and increasing age have unfavorable effects on the recovery of thyroid function in patients over 30 years of age with (sub-) clinical hypothyroidism.

Translocated HMGB3 is involved in papillary thyroid cancer progression by activating cytoplasmic TLR3 and transmembrane TREM1.

The family of high mobility group box (HMGB) proteins participates in various biological processes including immunity, inflammation, as well as cancer formation and progression. However, its role in thyroid cancer remains to be clarified. We performed quantitative RT-PCR (qRT-PCR), western blot, enzyme-linked immunosorbent, immunohistochemistry, and immunofluorescence assays to evaluate the expression level and subcellular location of HMGB3. The effects of HMGB3 knockdown on malignant biological behaviors of thyroid cancer were determined by cell proliferation assays, cell cycle and apoptosis assays, and transwell chamber migration and invasion assays. Differential expression genes (DEGs) altered by HMGB3 were analyzed using the Ingenuity Pathway Analysis (IPA) and TRRUST v2 database. HMGB3 correlated pathways predicted by bioinformatic analysis were then confirmed using western blot, co-immunoprecipitation, dual-luciferase reporter assay, and flow cytometry. We found that HMGB3 is overexpressed and its downregulation inhibits cell viability, promotes cell apoptosis and cell cycle arrest, and suppresses cell migration and invasion in thyroid cancer. In PTC, both tissue and serum levels of HMGB3 are elevated and are correlated with lymph node metastasis and advanced tumor stage. Mechanistically, we observed the translocation of HMGB3 in PTC, induced at least partially by hypoxia. Cytoplasmic HMGB3 activates nucleic-acid-mediated TLR3/NF-κB signaling and extracellular HMGB3 interacts with the transmembrane TREM1 receptor in PTC. This study demonstrates the oncogenic role of HMGB3 cytoplasmic and extracellular translocation in papillary thyroid cancers; we recommend its future use as a potential circulating biomarker and therapeutic target for PTC.

Increased Incidence of Hashimoto Thyroiditis in Selenium Deficiency: A Prospective 6-Year Cohort Study.

CONTEXT: In 2015, we reported an increased prevalence of thyroid disease in a county of low habitual selenium (Se) intake in comparison to a neighboring county with higher intake in a cross-sectional survey in Shaanxi Province, China. OBJECTIVE: To explore longitudinal effects of low Se status, a prospective cohort study was conducted in the same area from 2013 to 2019, and thyroid peroxidase autoantibodies (TPO-Abs) and disease incidence were compared. METHODS: A total 1254 individuals from 1500 reinvited participants were successfully enrolled. Venous blood, fingernails, and urine samples were collected and analyzed to evaluate thyroid status, TPO-Abs, serum Se, and urinary iodine. Diagnosis of Hashimoto thyroiditis (HT) was based on elevated thyrotropin, presence of TPO-Abs, and ultrasound characteristics. Se deficiency was categorized using a serum concentration of 80 µg/L as a threshold, and tested by logistic regression for a relationship to TPO-Abs and HT. RESULTS: Se deficiency was observed in 46.2% of participants from the adequate-Se county (Ziyang) and in 89.7% from the low-Se county (Ningshan). Se concentrations in fingernails differed strongly by residency (Ziyang vs Ningshan; 678.7 vs 364.3 µg/kg; Z = -9.552; P < .001). Newly diagnosed HT in Ziyang was less frequent than in Ningshan (0.09% vs 0.31%; χ 2 = 4.350; P = .037). The conversion rate to seropositive TPO-Abs was 10.2% in Ningshan vs 5.6% in Ziyang. Excluding iodine as confounding factor, low-Se was confirmed as a risk factor for HT (relative risk [95% CI]; 3.65 [1.03-12.90]; P < .05). CONCLUSION: The data indicate an increased incidence of TPO-Ab seroconversion with low Se supply and support the hypothesis that Se deficiency contributes to HT as a modifiable risk factor.

Comprehensive Analysis of Expression and Prognostic Value of Selenoprotein Genes in Thyroid Cancer.

Background: Low selenium levels are associated with an increased incidence and advanced stage of thyroid cancers (THCAs). In response to changes in selenium levels, a hierarchy of selenoprotein biosynthesis allows tissue-specific fine-tuning of the 25 selenoproteins. To determine the role of individual selenoproteins on thyroid carcinogenesis, we carried out a multiomic data mining study. Methods: The expression levels of individual selenoproteins and their correlations with prognosis in THCAs were analyzed using Oncomine, GEPIA, and Kaplan-Meier plotter platforms. Co-expression analyses using the cBioportal database were carried out to identify genes that are correlated with selenoproteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments were performed for genes correlated with selenoproteins that were identified as clinically significant. Results and Discussion: DIO1, GPX3, SELENOO, SELENOP, SELENOS, and SELENOV were significantly downregulated in THCAs and were associated with poor prognoses. Biological processes including negative regulation of growth and angiogenesis were enriched in DIO1-positively and DIO1-negatively correlated genes, respectively. Many biological processes including negative regulation of growth and MAPK cascade were enriched in GPX3-positively and GPX3-negatively correlated genes, respectively. The antitumor effects of SELENOS might be attributed to their protection against endoplasmic reticulum (ER) stress. SELENOO was revealed to be correlated with ER stress, mitochondrial translation, and telomere maintenance. Biological processes of SELENOV-correlated genes were enriched in redox processes and ER calcium ion homeostasis. Moreover, cell adhesion and angiogenesis were also shown to be negatively regulated by SELENOV, providing an antimetastatic effect similar as DIO1. Conclusion: This study explored the distinct roles of the 25 selenoproteins in THCA pathogenesis, providing potential oncosuppressing effects of 6 selenoproteins.

TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer.

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among the triggering receptors expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease-free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not in macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

The Impact of Coexistent Hashimoto's Thyroiditis on Central Compartment Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Background: Hashimoto's thyroiditis (HT) is the most prevalent inflammatory disorder of the thyroid gland. Current studies have reported the coexistence rate between HT and papillary thyroid carcinoma (PTC) is quite high. The objective of this study was to evaluate the impact of HT on the predictive factors of central compartment lymph node metastasis (CLNM) in PTC. Methods: A retrospective investigation was performed on PTC patients. They were subclassified into HT and non-HT groups. The results of preoperative neck ultrasound (US) examinations were reviewed. The clinical characteristics and the predictive value for CLNM were explored and compared between the two groups. Results: A total of 756 patients were included in this study. There were more female patients (86.1%) in the PTC coexistent with the HT group than non-HT group. The patients with HT group had higher preoperative serum level of TSH. There was statistically significant difference between the HT patients and non-HT patients in nodular vascularization. Univariate and multivariate analyses showed that male, age ≤45 years old, tumor diameter >1 cm, and presence of suspicious central compartment lymph node on US, irregular nodular shape, multifocal carcinoma were independent predictive factors of CLNM in PTC patients. It was showed that male, age ≤45 years old, tumor diameter >1 cm, multifocality, and presence of suspicious central lymph node on US were risk factors for CLNM in non-HT patients. Only tumor diameter >1 cm and presence of suspicious central lymph node on US were independently correlated with CLNM in HT patients. The sensitivity of the multivariate model was 63.5%, and specificity was 88.9% for prediction CLNM in HT patients. For non-HT patients, the AUC was 80.6%, the sensitivity of the multivariate model was 64.5%, and specificity was 85.2. Conclusion: PTC combined with HT is more common in women, and TSH level in HT group is higher than that in patients with PTC alone. Regardless of that HT is not a related risk factor of CLNM in PTC, our result suggested that different predictive systems should be used for HT and non-HT patients respectively to have a more accurate evaluation of CLNM in clinic.

Combined treatment with a gastric inhibitory polypeptide receptor antagonist and a peptidyl peptidase-4 inhibitor improves metabolic abnormalities in diabetic mice.

OBJECTIVES: Dipeptidyl peptidase-4 inhibition and gastric inhibitory polypeptide (GIP) receptor antagonism have therapeutic effects in type 2 diabetes mellitus. We assessed the effects of sitagliptin and Pro3(GIP) in a mouse model of diabetes. METHODS: Diabetes was induced in C57BL/6J mice by a high-fat diet and intraperitoneal injection of streptozocin. Blood glucose was assessed weekly. Six weeks later, serum triglycerides, total cholesterol and glucose tolerance were assessed and pancreatic and adipose tissues were collected. RESULTS: Combination therapy with sitagliptin and Pro3(GIP) resulted in significantly greater reductions of blood glucose and triglycerides than either monotherapy. Combination therapy also improved insulin sensitivity and glucose tolerance. ß-cell mass and insulin-positive cell percentage in the pancreas was higher in mice receiving combination therapy compared with either monotherapy. Crown-like structures, inflammatory markers in adipose tissue, and serum leptin concentrations were decreased in mice receiving combination therapy compared with either monotherapy. CONCLUSIONS: Combination therapy with Pro3(GIP) and sitagliptin improved metabolic abnormalities in diabetic mice. Changes in serum leptins and reduced inflammatory cell infiltration in adipose tissue might account for the observed effects.

Selenium deficiency is linearly associated with hypoglycemia in healthy adults.

OBJECTIVE: The trace element selenium (Se) is needed for regular biosynthesis of selenoproteins, which contribute to antioxidative defense systems and affect redox-regulated signaling. Elevated Se intake and selenoprotein expression levels have been associated with impaired hydrogen peroxide-dependent signaling by insulin, leading to hyperglycemia and insulin resistance. The relation of low Se intake with glucose status and carbohydrate metabolism is poorly known. RESEARCH DESIGN AND METHODS: A cross sectional analysis among healthy subjects residing in two Chinese counties with different habitual Se intakes was conducted. Fasted glucose levels were related to Se concentrations of 5686 adults by linear regression analysis with Se, body mass index, age, thyroid status, insulin and sex as independent variables. RESULTS: Serum Se correlated strongly and positively with glucose in the Se-deficient population. There was no strong relationship of Se and glucose in the non-deficient population. Overt hypoglycemia (serum glucose < 2.8 mM) was observed in 19.2% of this random sample of subjects in the Se-deficient and in 1.4% of the moderately supplied population, respectively. CONCLUSIONS: An adequate Se supply constitutes an important factor for glucose homeostasis in human subjects. The interaction between Se status and glucose control is not limited to hyperglycemia, but apparently extends to hypoglycemia risk in Se deficiency. This newly identified relationship may be of relevance for the course of severe disease including major trauma, sepsis and COVID-19, where Se deficiency has been associated with mortality risk.

Effect of pulegone on the NLPR3 inflammasome during inflammatory activation of THP-1 cells.

Pulegone is a key active component of Schizonepeta essential oil and has been determined to have anti-inflammatory properties. However, the underlying molecular mechanisms with regard to the NLR family pyrin domain containing 3 (NLRP3) inflammasome, also known as the NALP3 inflammasome, have remained to be elucidated. NLRP3 represents a potential link between inflammation and immunity and may play possible key role in various pathologies. In the present study, the modulatory effects of pulegone on the NLRP3 inflammasome were investigated. THP-1 cells induced with phorbol myristate acetate were divided into various groups, including the Normal (control), lipopolysaccharide (LPS), LPS + ATP/nigericin, LPS + ATP/nigericin + 0.2% DMSO and pulegone (0.2, 0.1 and 0.05 mg/ml) groups. ELISA was used to detect the levels of interleukin (IL)-1ß and IL-18 in the cell supernatants and the influence of potassium ions was assessed. PCR was used to determine the expression levels of NLRP3, caspase-1, IL-1ß and IL-1α in the cell lysates. Furthermore, NLRP3 and apoptosis-associated speck-like protein (ASC) were detected via immunofluorescence assays and fluorescence microscopy was employed to determine the reactive oxygen species (ROS) levels in the THP-1 cells. The results indicated reduced levels of IL-18 and IL-1ß in the supernatant of the cells of the pulegone groups when compared with those in the LPS + ATP/nigericin group. In addition, reduced mRNA production of inflammasome-associated genes was detected in the cell lysates after pulegone treatment. The immunofluorescence analyses indicated significantly reduced protein expression levels of NLRP3 and ASC in the pulegone groups, as well as co-localization of the NLRP3 and ASC proteins. The pulegone groups also exhibited significantly reduced ROS levels. Furthermore, a high concentration of potassium ions significantly reduced the secretion of IL-1ß after induction/stimulation. In conclusion, the present study suggested that pulegone exerts its anti-inflammatory effects on LPS + ATP/nigericin-induced THP-1 cells via inhibition of NLRP3 expression, and its regulatory mechanism is associated with potassium channel and ROS pathways. It was hypothesized that pulegone first inhibits ROS signaling, to then inhibit NLRP3 expression as a downstream event. It appeared that NLRP3 may be situated further downstream and represented the link between inflammation and immunity.

Pulegone inhibits inflammation via suppression of NLRP3 inflammasome and reducing cytokine production in mice.

Context: Pulegone, a key compound in Schizonepeta essential oil, has been identified as an anti-inflammatory. However, its underlying molecular mechanisms on NLR family pyrin domain containing 3 (NLRP3) inflammasome have not been elucidated. Objective: Here, the modulatory effects of pulegone on NLRP3 inflammasome were investigated. Materials and methods: The C57BL/6J mice were randomly divided into five groups: Normal, Lipopolysaccharides (LPS), Dexamethasone (DEX, 5 mg/kg), Pulegone (0.095 and 0.190 g/kg) groups. All mice were challenged by LPS except for the Normal group. Results: A reduced expression of Interleukin-18 (IL-18), Interleukin-1ß (IL-1ß), Interleukin-5 (IL-5), Tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), Monocyte chemoattratctant protein-1 (MCP-1), Macrophage inflammatory protein-1ß (MIP-1ß), Monocyte colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) in serum were detected in the pulegone groups as compared to the LPS group. In addition, a reduced mRNA and protein expression production of ASC, NLRP3, and Caspase-1 were detected in lungs after pulegone administration. Histological analysis results indicated that the histological changes of lungs caused by LPS were ameliorated by pulegone. Immunohistochemical study showed a decreased positive cell numbers of P2X7R in Pulegone (0.095 and 0.190 g/kg) groups. Conclusion: Pulegone exerts anti-inflammatory effects on LPS-induced sepsis mice via inhibition of the NLRP3 expression.

Gender-Specific Risk of Central Compartment Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Our aim was to evaluate the impact of gender on the predictive factors of central compartment lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC). A retrospective study of 590 patients treated for PTC was performed. Univariate and multivariate analyses showed that gender (female; P = 0.001), age (≥45 y; P < 0.001), tumor size (>1 cm; P < 0.001), and multifocality (P = 0.004) were independent predictive factors of CLNM in PTC patients. Patients were divided into male group (n = 152) and female group (n = 438). Age (≥45 y; P = 0.001), T4 (P = 0.006) and multifocality (P = 0.024) were independent predictive risk factors of CLNM in male patients. As for female patients, age (≥45 y; P < 0.001), tumor size (>1 cm; P < 0.001), multifocality (P = 0.002), and microcalcification (P = 0.027) were independently correlated with CLNM. The sensitivity of the multivariate model for predicting CLNM in male patients was 64.9%, specificity was 82.9%, and area under the ROC curve (AUC) was 0.764. As for female patients, the sensitivity was 55.7%, specificity was 77.9%, and AUC was 0.73. This study showed that the predictive factors of CLNM indeed varied according to gender. To have a more accurate evaluation of CLNM, different predictive systems should be used for male and female patients.

Hydrogen peroxide positively regulates brassinosteroid signaling through oxidation of the BRASSINAZOLE-RESISTANT1 transcription factor.

Hydrogen peroxide (H2O2) is an important signaling molecule in plant developmental processes and stress responses. However, whether H2O2-mediated signaling crosstalks with plant hormone signaling is largely unclear. Here, we show that H2O2 induces the oxidation of the BRASSINAZOLE-RESISTANT1 (BZR1) transcription factor, which functions as a master regulator of brassinosteroid (BR) signaling. Oxidative modification enhances BZR1 transcriptional activity by promoting its interaction with key regulators in the auxin-signaling and light-signaling pathways, including AUXIN RESPONSE FACTOR6 (ARF6) and PHYTOCHROME INTERACTING FACTOR4 (PIF4). Genome-wide analysis shows that H2O2-dependent regulation of BZR1 activity plays a major role in modifying gene expression related to several BR-mediated biological processes. Furthermore, we show that the thioredoxin TRXh5 can interact with BZR1 and catalyzes its reduction. We conclude that reversible oxidation of BZR1 connects H2O2-mediated and thioredoxin-mediated redox signaling to BR signaling to regulate plant development.

Tongxinluo improves cognition by decreasing ß-amyloid in spontaneous hypertensive rats.

ß-Amyloid (Aß) accumulation in the brain is the major pathophysiology of Alzheimer disease (AD). Hypertension is a risk factor for AD by promoting Aß deposition. Traditional Chinese medicinal compound tongxinluo (TXL) can improve blood circulation and endothelium-dependent vasodilation. This study investigates the effects of TXL on cognition and Aß using spontaneously hypertensive rats (SHRs). TXL was intragastrically administered to SHRs at low-dose, mid-dose and high-dose for 15, 30 or 60days. Cognition was evaluated with a Morris Water Maze (MWM). Aß in the brain was detected by western blot, ELISA and Thioflavin-S staining. Western blot and RT-PCR were employed to exam the expression of receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein-1 (LRP-1) and amyloid precursor protein (APP). After TXL treatment for 60days, compared with the vehicle, the number of crossed platform and the time spent in the target quadrant increased in parallel with the increasing length of treatment in MWM. Moreover, the Aß in the hippocampus significantly decreased compared to the vehicle group, both in western blot and ELISA. Additionally, TXL reduced RAGE expression in a dose- and time-depended manner, but LRP-1 expression had no difference between TXL groups and vehicle groups. Furthermore, the ß-secretase expression was significantly decreased compared to the vehicle group, but APP expression had no difference. In conclusion, TXL improved cognition and decreased Aß in SHRs in a dose- and time-dependent manner, the underlying mechanism may involved in inhibiting RAGE and ß-secretase expression.

Proteomic comparison reveals the contribution of chloroplast to salt tolerance of a wheat introgression line.

We previously bred a salt tolerant wheat cv. SR3 with bread wheat cv. JN177 as the parent via asymmetric somatic hybridization, and found that the tolerance is partially attributed to the superior photosynthesis capacity. Here, we compared the proteomes of two cultivars to unravel the basis of superior photosynthesis capacity. In the maps of two dimensional difference gel electrophoresis (2D-DIGE), there were 26 differentially expressed proteins (DEPs), including 18 cultivar-based and 8 stress-responsive ones. 21 of 26 DEPs were identified and classified into four categories, including photosynthesis, photosynthesis system stability, linolenic acid metabolism, and protein synthesis in chloroplast. The chloroplast localization of some DEPs confirmed that the identified DEPs function in the chloroplast. The overexpression of a DEP enhanced salt tolerance in Arabidopsis thaliana. In line with these data, it is concluded that the contribution of chloroplast to high salinity tolerance of wheat cv. SR3 appears to include higher photosynthesis efficiency by promoting system protection and ROS clearance, stronger production of phytohormone JA by enhancing metabolism activity, and modulating the in chloroplast synthesis of proteins.

The Influence of Dihydrotestosterone on the Development of Graves' Disease in Female BALB/c Mice.

BACKGROUND: Graves' disease (GD) is a common organ-specific autoimmune disease characterized by hyperthyroidism that has significant sex differences in prevalence and clinical expressions. Abnormal cytokine production and T cell activation may result in various manifestations of GD. Studies have shown that androgen treatment can provide protection against autoimmune diseases, but the effects of androgen treatment on GD are still unknown. Therefore, this study investigated whether a potent bioactive androgen, 5α-dihydrotestosterone (DHT), could be of benefit in a BALB/c mouse model of GD. The aims of this study were to investigate (i) whether DHT pretreatment inhibits autoimmune responses, and (ii) the mechanism of immune protection of DHT in GD. METHODS: Female BALB/c mice were immunized three times with an adenovirus expressing the human thyrotropin receptor (TSHR) A-subunit (Ad-TSHR289). Three doses (1.5, 5, and 15 mg) of DHT or a matching placebo were implanted a week before the first immunization. Four weeks after the third immunization, mice were sacrificed, and blood, the spleen, and the thyroid were removed for further analysis. RESULTS: After DHT treatment, thyroid hormones were dramatically reduced compared with placebo. In addition, a remarkable reduction in interferon-γ and interleukin-2 production was observed in DHT-pretreated mice. CONCLUSIONS: DHT can alleviate the severity of GD by downregulating pro-autoimmune T helper 1 cells in female BALB/c mice. The protective influence was more noticeable with 5 mg and 15 mg doses of DHT.

THI1, a Thiamine Thiazole Synthase, Interacts with Ca2+-Dependent Protein Kinase CPK33 and Modulates the S-Type Anion Channels and Stomatal Closure in Arabidopsis.

Thiamine is required for both plant growth and development. Here, the involvement of a thiamine thiazole synthase, THI1, has been demonstrated in both guard cell abscisic acid (ABA) signaling and the drought response in Arabidopsis (Arabidopsis thaliana). THI1 overexpressors proved to be more sensitive to ABA than the wild type with respect to both the activation of guard cell slow type anion channels and stomatal closure; this effectively reduced the rate of water loss from the plant and thereby enhanced its level of drought tolerance. A yeast two-hybrid strategy was used to screen a cDNA library from epidermal strips of leaves for THI1 regulatory factors, and identified CPK33, a Ca(2+)-dependent protein kinase, as interactor with THI1 in a plasma membrane-delimited manner. Loss-of-function cpk33 mutants were hypersensitive to ABA activation of slow type anion channels and ABA-induced stomatal closure, while the CPK33 overexpression lines showed opposite phenotypes. CPK33 kinase activity was essential for ABA-induced stomatal closure. Consistent with their contrasting regulatory role over stomatal closure, THI1 suppressed CPK33 kinase activity in vitro. Together, our data reveal a novel regulatory role of thiamine thiazole synthase to kinase activity in guard cell signaling.

Low Population Selenium Status Is Associated With Increased Prevalence of Thyroid Disease.

CONTEXT: Epidemiological studies have supported the premise that an adequate selenium intake is essential for thyroid gland function. OBJECTIVE: The objective was to investigate whether the prevalence of thyroid disease differed in two areas that were similar, except for very different soil/crop selenium concentrations. DESIGN: Cross-sectional observational study. SETTING: The setting was two counties of Shaanxi Province, China, here defined as adequate- and low-selenium. PARTICIPANTS: A total of 6152 participants were selected by stratified cluster-sampling. MAIN OUTCOME MEASURES: Participants completed demographic and dietary questionnaires and underwent physical and thyroid ultrasound examinations. Serum samples were analyzed for thyroid function parameters and selenium concentration. Serum selenium was compared between different demographic, dietary, and lifestyle categories in the two counties. The relationship between selenium status, dietary factors, and pathological thyroid conditions was explored by logistic regression. RESULTS: Complete data sets were available from 3038 adequate-selenium participants and 3114 low-selenium participants in whom median (interquartile range) selenium concentrations differed almost 2-fold (103.6 [79.7, 135.9] vs 57.4 [39.4, 82.1] µg/L; P = .001). The prevalence of pathological thyroid conditions (hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and enlarged thyroid) was significantly lower in the adequate-selenium county than in the low-selenium county (18.0 vs 30.5%; P < .001). Higher serum selenium was associated with lower odds ratio (95% confidence interval) of autoimmune thyroiditis (0.47; 0.35, 0.65), subclinical hypothyroidism (0.68; 0.58, 0.93), hypothyroidism (0.75; 0.63, 0.90), and enlarged thyroid (0.75; 0.59, 0.97). CONCLUSIONS: Low selenium status is associated with increased risk of thyroid disease. Increased selenium intake may reduce the risk in areas of low selenium intake that exist not only in China but also in many other parts of the world.

Meta-Analysis Comparing Zero-Profile Spacer and Anterior Plate in Anterior Cervical Fusion.

BACKGROUND: Anterior plate fusion is an effective procedure for the treatment of cervical spinal diseases but is accompanied by a high incidence of postoperative dysphagia. A zero profile (Zero-P) spacer is increasingly being used to reduce postoperative dysphagia and other potential complications associated with surgical intervention. Studies comparing the Zero-P spacer and anterior plate have reported conflicting results. METHODOLOGY: A meta-analysis was conducted to compare the safety, efficacy, radiological outcomes and complications associated with the use of a Zero-P spacer versus an anterior plate in anterior cervical spine fusion for the treatment of cervical spinal disease. We comprehensively searched PubMed, Embase, the Cochrane Library and other databases and performed a meta-analysis of all randomized controlled trials (RCTs) and prospective or retrospective comparative studies assessing the two techniques. RESULTS: Ten studies enrolling 719 cervical spondylosis patients were included. The pooled data showed significant differences in the operation time [SMD = -0.58 (95% CI = -0.77 to 0.40, p < 0.01)] and blood loss [SMD = -0.40, 95% CI (-0.59 to -0.21), p < 0.01] between the two groups. Compared to the anterior plate group, the Zero-P group exhibited a significantly improved JOA score and reduced NDI and VAS. However, anterior plate fusion had greater postoperative segmental and cervical Cobb's angles than the Zero-P group at the last follow-up. The fusion rate in the two groups was similar. More importantly, the Zero-P group had a lower incidence of earlier and later postoperative dysphagia. CONCLUSIONS: Compared to anterior plate fusion, Zero-P is a safer and effective procedure, with a similar fusion rate and lower incidence of earlier and later postoperative dysphagia. However, the results of this meta-analysis should be accepted with caution due to the limitations of the study. Further evaluation and large-sample RCTs are required to confirm and update the results of this study.

Frequent amplification of AIB1, a critical oncogene modulating major signaling pathways, is associated with poor survival in gastric cancer.

Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors. It acts as a major oncogene in diverse cancers, whereas biological function of AIB1 in gastric cancer remains largely unclear. This study was designed to explore the role of AIB1 in gastric tumorigenesis and its potential as a useful prognostic marker and therapeutic target in this cancer. Our data demonstrated that AIB1 was significantly up-regulated in gastric cancer tissues as compared with control subjects. Moreover, AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not in control subjects. AIB1 amplification was positively associated with its protein expression, and was significantly correlated with poor patient survival. AIB1 knockdown in gastric cancer cells dramatically inhibited cell proliferation, invasiveness and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Mechanically, AIB1 promotes gastric cancer cell proliferation, survival and invasiveness through modulating major signaling pathways such as ErbB and Wnt/ß-catenin pathways. Collectively, these findings suggest that AIB1 plays an important role in the pathogenesis of gastric cancer and represents a potential prognostic marker and therapeutic target for this cancer.

Effects of different sera conditions on olfactory ensheathing cells in vitro.

Transplantation of olfactory ensheathing cells (OEC) is a promising therapy in spinal cord injury (SCI) treatment. However, the therapeutic efficacy of this method is unstable due to unknown reasons. Considering the alterations in the culture environment that occur during OEC preparation for transplantation, we hypothesize that these changes may cause variations in the curative effects of this method. In this study, we compared OEC cultured in medium containing different types and concentrations of serum. After purification and passage, the OEC were cultured for 7 days in different media containing 5%, 10%, 15% or 20% fetal bovine serum (FBS) or rat serum (RS), or the cells were cultured in FBS-containing medium first, followed by medium containing RS. In another group, the OEC were first cultured in 10% FBS for 3 days and then cultured with rat spinal cord explants with 10% RS for another 4 days. An MTT assay and P75 neurotrophin receptor immunofluorescence staining were used to examine cell viability and OEC numbers, respectively. The concentration of neurotrophin-3 (NT-3), which is secreted by OEC into the culture supernatant, was detected using the enzyme-linked immunosorbent assay (ELISA). RT-PCR was applied to investigate the NT-3 gene expression in OEC according to different groups. Compared with FBS, RS reduced OEC proliferation in relation to OEC counts (χ2 = 166.279, df = 1, p < 0.01), the optical density (OD) value in the MTT assay (χ2 = 34.730, df = 1, p < 0.01), and NT-3 concentration in the supernatant (χ2 = 242.997, df = 1, p < 0.01). OEC cultured with spinal cord explants secreted less NT-3 than OEC cultured alone (F = 9.611, df = 5.139, p < 0.01). Meanwhile, the order of application of different sera was not influential. There was statistically significant difference in NT-3 gene expression among different groups when the serum concentration was 15% (χ2 = 64.347, df = 1, p < 0.01). In conclusion, different serum conditions may be responsible for the variations in OEC proliferation and function.