International Journal of Endocrinology The latest articles from Hindawi © 2019 , Hindawi Limited . All rights reserved. Use of PEGylated Recombinant Human Growth Hormone in Chinese Children with Growth Hormone Deficiency: A 24-Month Follow-Up Study Thu, 19 Sep 2019 16:05:03 +0000 Objective. Once-weekly PEGylated recombinant human growth hormone (rhGH) is the sole long-acting GH formulation available currently for pediatric patients with GH deficiency (GHD). The aim of this study was to evaluate the efficacy and safety of PEGylated rhGH therapy compared to daily rhGH therapy in GHD children treated for two years. Methods. A total of 98 children (49 children for the PEGylated rhGH group and 49 children for the daily rhGH group) with GHD were enrolled in this single-center, prospective, nonrandomized cohort study. PEGylated rhGH or daily rhGH was administered for 2 years. Height, height SDS, height velocity (HV), IGF-1, bone age (BA), and adverse events were determined throughout the treatment. Results. HV significantly increased over the baseline and was similar in both groups. In the PEGylated rhGH cohort, the mean ± SD HV was improved from 3.78 ± 0.78 cm/y at the baseline to 12.44 ± 3.80 cm/y at month 3, to 11.50 ± 3.01 cm/y at month 6, to 11.00 ± 2.32 cm/y at month 12, and finally 10.08 ± 2.12 cm/y at month 24 in the PEGylated rhGH group. In the daily rhGH group, HV was 3.36 ± 1.00 cm/y at baseline, increasing to 12.56 ± 3.71 cm/y at month 3, to 11.82 ± 2.63 cm/y at month 6, to 10.46 ± 1.78 cm/y at month 12, and to 9.28 ± 1.22 cm/y at month 24. No serious adverse event related to PEGylated rhGH or daily rhGH occurred during the 24-month study. Conclusion. PEGylated rhGH replacement therapy is effective and safe in pediatric patients with GHD. The adherence to once-weekly PEGylated rhGH therapy is superior to daily rhGH in children with GHD. Yu Qiao, Zengmin Wang, Jinyan Han, and Guimei Li Copyright © 2019 Yu Qiao et al. All rights reserved. The Prevalence of Celiac Disease-Specific Auto-Antibodies in Type 1 Diabetes in a Moroccan Population Thu, 19 Sep 2019 15:05:12 +0000 Objective. We aimed to determine the prevalence of specific auto-antibodies to celiac disease (CD) in Moroccan type 1 diabetic (T1D) patients and compare the clinical and biological characteristics of seropositive and seronegative cases. Patients and Methods. A cross-sectional study was carried out on 276 T1D patients including 109 adults and 167 pediatric cases. The screening for CD was performed by an Elisa IgA anti-tissue transglutaminase antibody (tTGA) testing, combined with IgA quantification by nephelometry. Positive-IgA-tTGA cases were secondly tested for anti-endomysial antibodies (EMA) using an immunofluorescence technique, and the IgA deficiency cases were screened for IgG-tTGA. Patients with low positive tTGA titers underwent HLA-DQ2/DQ8 typing. Sociodemographic and clinical data of the patients were collected using a hetero-administered questionnaire. The comparison of clinical and biological data between seropositive and seronegative diabetics was done using independent T, Mann–Whitney U, chi-squared, and Fisher tests, which were considered significant if value <0.05. Results. The prevalence of CD-specific auto-antibodies was estimated to be 9.1% (IC = 95%), with 25 positive cases in tTGA and EMA testing. Eight cases displayed low titers of IgA-tTGA, among which 4 were positive for HLA-DQ2, 1 for HLA-DQ8, and 1 for both DQ2 and DQ8. The other 2 cases had a biopsy-proven CD. Compared to seronegative patients, seropositive cases had a higher percentage of associated autoimmune disorders (16% vs. 2.4%, ), with a significant lower height Z-scores (median: −0.90 (−3.93 to 0.95) vs. −0.51 (−4.54 to 2.18), ) and a higher HbA1c level (median: 11.30% (7.31 to 16.00) vs. 9.30% (4.40 to17.31), ).Conclusion. The current study gave evidence of a high prevalence of CD specific auto-antibodies in T1D population. The co-existence of these two conditions was associated with a poor glycemic control, a lower height, and other autoimmune diseases. These findings may suggest the necessity of a systematic screening of CD in T1D patients. Ider Oujamaa, Majda Sebbani, Lahcen Elmoumou, Aïcha Bourrahouate, Rabiy El Qadiry, Soufian El Moussaoui, Imane Ait Sab, Mohamed Sbihi, Laila Ennazk, Ghizlane El Mghari-Tabib, Nawal El Ansari, Hicham Baizri, Mohamed Amine, and Brahim Admou Copyright © 2019 Ider Oujamaa et al. All rights reserved. RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease Wed, 18 Sep 2019 16:05:18 +0000 Objective. Fatty liver is a rising global health concern, significantly increasing the burden of health care cost. Nonalcoholic fatty liver disease (NAFLD) has a correlation with metabolic syndrome and its complications. Method. We reviewed the literature regarding the mechanisms of developing NAFLD through AGE-RAGE signaling. Results. NAFLD, metabolic syndrome, and production of advanced glycation end-products (AGEs) share many common risk factors and appear to be connected. AGE induces production of the receptor for AGE (RAGE). AGE-RAGE interaction contributes to fat accumulation in the liver leading to inflammation, fibrosis, insulin resistance, and other complications of the fatty liver disease. The immune system, especially macrophages, has an important defense mechanism against RAGE pathway activities. Conclusion. Soluble form of RAGE (sRAGE) has the capability to reduce inflammation by blocking the interaction of AGE with RAGE. However, sRAGE has some limitations, and the best method of usage is probably autotransplantation of transfected stem cells or monocytes, as a precursor of macrophages and Kupffer cells, with a virus that carries sRAGE to alleviate the harmful effects of AGE-RAGE signaling in the settings of fatty liver disease. Kamyar Asadipooya, Kamran B. Lankarani, Rishi Raj, and Mohammadreza Kalantarhormozi Copyright © 2019 Kamyar Asadipooya et al. All rights reserved. Serum Fibroblast Growth Factor 21 Levels Are Positively Associated with Metabolic Syndrome in Patients with Type 2 Diabetes Tue, 10 Sep 2019 16:05:10 +0000 Background. Fibroblast growth factor 21 (FGF21) acts as a potent metabolic regulator. Serum FGF21 levels were significantly higher in obesity and type 2 diabetes mellitus (T2DM) populations. The aim of this study was to evaluate the relationship between serum FGF21 levels and metabolic syndrome (MetS) in T2DM patients. Methods. Fasting blood samples were obtained from 126 T2DM patients. MetS and its components were defined according to the diagnostic criteria from the International Diabetes Federation. Serum FGF21 concentrations were measured using a commercially available enzyme-linked immunosorbent assay. Results. Among these patients, 84 (66.7%) had MetS. Female gender, hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), body weight (BW), body mass index (BMI), body fat mass, fasting glucose, glycated hemoglobin level (HbA1c), triglyceride level (TG), urine albumin-to-creatinine ratio (UACR), insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and FGF21 levels were higher, whereas high-density lipoprotein cholesterol level (HDL-C) and estimated glomerular filtration rate (eGFR) were lower in DM patients with MetS. Univariate linear analysis revealed that hypertension, BMI, WC, body fat mass, SBP, DBP, logarithmically transformed TG (log-TG), low-density lipoprotein cholesterol (LDL-C) level, log-glucose, log-creatinine, log-UACR, log-insulin, and log-HOMA-IR positively correlated, whereas HDL-C and eGFR negatively correlated with serum FGF21 levels in T2DM patients. Multivariate forward stepwise linear regression analysis revealed that body fat mass (adjusted R2 change = 0.218; ) and log-TG (adjusted R2 change = 0.036; ) positively correlated, whereas eGFR (adjusted R2 change = 0.033; ) negatively correlated with serum FGF21 levels in T2DM patients. Conclusions. This study showed that higher serum FGF21 levels were positively associated with MetS in T2DM patients and significantly positively related to body fat mass and TG but negatively related to eGFR in these subjects. Ruo-Yao Gao, Bang-Gee Hsu, Du-An Wu, Jia-Sian Hou, and Ming-Chun Chen Copyright © 2019 Ruo-Yao Gao et al. All rights reserved. Decreased Serum microRNA-21, microRNA-25, microRNA-146a, and microRNA-181a in Autoimmune Diabetes: Potential Biomarkers for Diagnosis and Possible Involvement in Pathogenesis Mon, 09 Sep 2019 09:05:11 +0000 Objective. Previous studies have revealed dysregulated circulating microRNAs (miRNAs) in patients with type 1 diabetes (T1D). Here, we explored the serum levels of miR-21, miR-25, miR-146a, and miR-181a in patients with autoimmune diabetes (T1D and latent autoimmune diabetes of adults (LADA)) compared with type 2 diabetes (T2D) and nondiabetic individuals. Design, patients, and measurements. The serum levels of miR-21, miR-25, miR-146a, and miR-181a in patients with T1D (n = 29), LADA (n = 16), and T2D (n = 31) and in nondiabetic individuals (n = 19) were determined by quantitative real-time polymerase chain reaction, and receiver-operating characteristic (ROC) curves were evaluated to determine the discriminatory performances of these four miRNAs. Furthermore, target genes and pathways potentially modulated by these four miRNAs were predicted by bioinformatics analysis to investigate the possible functions of these miRNAs in autoimmune diabetes. Subsequently, multiple logistic regression analysis was performed to identify independent predictors for autoimmune diabetes, and a nomogram was established. Results. miR-21, miR-25, miR-146a, and miR-181a were significantly downregulated in the serum of patients with autoimmune diabetes compared with those in T2D patients and nondiabetic individuals (). The areas under the ROC curves of these four miRNAs were greater than 0.80 (). Bioinformatics analysis suggested that miR-21, miR-25, miR-146a, and miR-181a regulated multiple genes in pathways associated with immunity, inflammatory responses, hyperglycemia, and metabolism, which are involved in the pathogenesis of autoimmune diabetes. Multiple logistic regression analysis identified miR-25 (odds ratio (OR): 0.001, ),miR-146a (OR: 0.136, ), and fasting C-peptide levels (OR: 0.064, ) as independent predictors of autoimmune diabetes. Conclusions. miR-25 and miR-146a may serve as potential circulating biomarkers and provide insights into the pathogenesis of autoimmune diabetes. Yiwen Liu, Minglei Ma, Jie Yu, Fan Ping, Huabing Zhang, Wei Li, Lingling Xu, and Yuxiu Li Copyright © 2019 Yiwen Liu et al. All rights reserved. A Chinese Family with Familial Dysalbuminemic Hyperthyroxinemia (FDH) due to R242H Mutation on Human Albumin Gene: Reevaluating the Role of FDH in Patients with Asymptomatic Hyperthyroxinemia Mon, 09 Sep 2019 07:05:02 +0000 Objective. Familial dysalbuminemic hyperthyroxinemia (FDH) has now become an established cause for spurious asymptomatic hyperthyroxinemia. Several different codon mutations on albumin gene had been identified. We here provided an established but rarely reported heterozygous mutation based on gene sequencing results from a Chinese family. Methods. The proband is a 14-year-old girl with light goiter and asymptomatic clinical presentations, whose thyroid function test by a one-step immunoassay showed increased free thyroxine (FT4) and free triiodothyronine (FT3) but nonsuppressed thyrotropin (TSH). All thyroid auto-antibodies were in the normal range. Blood samples were collected from her and most of her immediate family members for target gene sequencing and verification. Results. Hyperthyroxinemia was also confirmed in the proband’s mother and one of her uncles and his son. In the proband and these three pedigrees, the high-throughput gene screening sequencing and the following Sanger sequencing disclosed a heterozygous mutation in the albumin gene, which located in its exon 7 (c.725G > A), and correspondingly leads to an arginine replacement with a histidine (R242H) in its protein. This is an established mutation named as R218H if present without signal peptide sequence. Conclusions. For patients with asymptomatic hyperthyroxinemia, FDH should be clinically excluded before embarking on further investigations for other specific causes. Hongbing Liu, Jianmin Ran, Chuping Chen, Guangshu Chen, Ping Zhu, Rongshao Tan, and Yan Liu Copyright © 2019 Hongbing Liu et al. All rights reserved. Retracted: Vesicle-Associated Membrane Protein-Associated Protein A Is Involved in Androgen Receptor Trafficking in Mouse Sertoli Cells Sun, 08 Sep 2019 10:05:01 +0000 International Journal of Endocrinology Copyright © 2019 International Journal of Endocrinology. All rights reserved. Nomogram-Based New Recurrence Predicting System in Early-Stage Papillary Thyroid Cancer Thu, 05 Sep 2019 13:05:38 +0000 Background and Objectives. The clinicopathological risk factors to predict recurrence of papillary thyroid cancer (PTC) patients remain controversial. Methods. PTC patients treated with thyroidectomy between January 1997 and December 2011 at the First Affiliated Hospital of Zhejiang University (Zhejiang cohort) were included. Multivariate Cox regression analysis was conducted to identify independent recurrence predictors. Then, the nomogram model for predicting probability of recurrence was built. Results. According to Zhejiang cohort (N = 1,697), we found that the 10-year event-free survival (EFS) rates of PTC patients with early-stage (TNM stages I, II, and III) were not well discriminated (91.6%, 89.0%, and 90.7%; ). The multivariate Cox model identified age, bilaterality, tumor size, and nodal status as independent risk factors for tumor recurrence in PTC patients with TNM stages I–III. We then developed a nomogram with the C-index 0.70 (95% CI, 0.64 to 0.76), which was significantly higher () than the AJCC staging system (0.52). In the validation group, the C-index remained at a similar level. Conclusions. In this study, we build up a new recurrence predicting system and establish a nomogram for early-stage PTC patients. This prognostic model may better predict individualized outcomes and conduct personalized treatments. Yongfeng Ding, Zhuochao Mao, Jiaying Ruan, Xingyun Su, Linrong Li, Thomas J. Fahey III, Weibin Wang, and Lisong Teng Copyright © 2019 Yongfeng Ding et al. All rights reserved. First Report on Association of Hyperuricemia with Type 2 Diabetes in a Vietnamese Population Mon, 02 Sep 2019 00:07:11 +0000 Background. Uric acid is a powerful free-radical scavenger in humans, but hyperuricemia may induce insulin resistance and beta-cell dysfunction. The study aimed to evaluate the association between hyperuricemia and hyperglycemia, considering the confounding factors in a Vietnamese population. Methods. A population-based cross-sectional study recruited 1542 adults aged 50 to 70 years to collect data on socioeconomic status, lifestyle factors, and clinical patterns. Associations between hyperuricemia and hyperglycemia (isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG-IGT, and type 2 diabetes (T2D)) were evaluated by multinomial logistic regression analysis in several models, adjusting for the confounding factors including socioeconomic status, lifestyle factors, and clinical measures. Results. Uric acid values were much higher in IFG, IFG-IGT, and T2D groups compared to those in the normal glucose tolerance (NGT) group. The significant association of hyperuricemia with IFG, IFG-IGT, and T2D was found in the model unadjusted and remained consistently in several models adjusted for socioeconomic status, lifestyle factors, and clinical patterns. In the final model, the consistent hyperglycemia risk was found in total sample (OR = 2.23 for IFG, OR = 2.29 for IFG-IGT, and 1.75 for T2D, ) and in women (OR = 2.90 for IFG, OR = 3.96 for IFG-IGT, and OR = 2.49 for T2D, ) but not in men. Conclusions. It is the first report in Vietnamese population suggesting the significant association of hyperuricemia with IFG, IFG-IGT, and T2D; and the predominant association was found in women than in men, taken into account the confounding factors. Tran Quang Binh, Pham Tran Phuong, Nguyen Thanh Chung, Bui Thi Nhung, Do Dinh Tung, Tran Quang Thuyen, Duong Tuan Linh, Bui Thi Thuy Nga, Nguyen Anh Ngoc, and Le Danh Tuyen Copyright © 2019 Tran Quang Binh et al. All rights reserved. miR-29a Negatively Affects Glucose-Stimulated Insulin Secretion and MIN6 Cell Proliferation via Cdc42/β-Catenin Signaling Wed, 28 Aug 2019 05:05:09 +0000 Background. Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet β cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of β cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in β-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods. Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3′-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. Results. miR-29a overexpression inhibited proliferation () and GSIS under high-glucose stimulation (). Cdc42 overexpression promoted proliferation () and GSIS under high-glucose stimulation (). miR-29a overexpression decreased Cdc42 expression (), whereas miR-29a downregulation increased Cdc42 expression (). The results showed that the Cdc42 mRNA 3′-UTR is a direct target of miR-29a in vitro. Additionally, Cdc42 reversed miR-29a-mediated inhibition of proliferation and GSIS (). Furthermore, miR-29a inhibited β-catenin expression (), whereas Cdc42 promoted β-catenin expression ().Conclusion. By negatively regulating Cdc42 and the downstream molecule β-catenin, miR-29a inhibits MIN6 proliferation and insulin secretion. Jing Duan, Xian-Ling Qian, Jun Li, Xing-Hua Xiao, Xiang-Tong Lu, Lin-Chen Lv, Qing-Yun Huang, Wen Ding, Hong-Yan Zhang, and Li-Xia Xiong Copyright © 2019 Jing Duan et al. All rights reserved. Effects of Osteocalcin on Synthesis of Testosterone and INSL3 during Adult Leydig Cell Differentiation Wed, 28 Aug 2019 05:05:06 +0000 Proliferation and differentiation of adult Leydig cells are mainly completed in puberty. In many studies, apart from normal postnatal development process, it is widely indicated that, through administrating EDS, Leydig cell population is eliminated and regenerated. It is believed that osteocalcin released from osteoblasts, which is responsible for modulating bone metabolism, induces testosterone production in Leydig cells, independent of the HPG axis. In addition, INSL3 produced by Leydig cells, such as testosterone, plays a critical role in bone metabolism and is known to reflect the development process and functional capacities of Leydig cells. This study is aimed at investigating OC-mediated testosterone regulation and INSL3 synthesis during differentiation of adult Leydig cells that are independent of LH. For this purpose, male rats were divided into 2 groups: prepubertal normal rats and adult EDS-injected rats. Each group was divided into 4 subgroups in which GnRH antagonist or OC was applied. After adult Leydig cells completed their development, testicular tissue samples obtained from the sacrificed rats were examined by light-electron microscopic, immunohistochemical, and biochemical methods. Slight upregulation in 3βHSD, INSL3, and GPRC6A expressions along with the increase in serum testosterone levels was observed in groups treated with osteocalcin against GnRH antagonist. In addition, biochemical and microscopic findings in osteocalcin treated groups were similar to those in control groups. While there was no significant difference in the number of Leydig cells reported, the presence of a significant upregulation in INSL3 and GPRC6A expressions and the increase in serum testosterone and ucOC levels were observed. After evaluation of findings altogether, it is put forward that, for the first time in this study, although osteocalcin treatment made no significant difference in the number of Leydig cells, it increased the level of testosterone through improving the function of existing adult Leydig cells during normal postnatal development process and post-EDS regeneration. This positive correlation between osteocalcin-testosterone and osteocalcin-INSL3 is concluded to be independent of LH at in vivo conditions. Gulfidan Coskun, Leman Sencar, Abdullah Tuli, Dilek Saker, Mustafa Muhlis Alparslan, and Sait Polat Copyright © 2019 Gulfidan Coskun et al. All rights reserved. “Gut Microbiota-Circadian Clock Axis” in Deciphering the Mechanism Linking Early-Life Nutritional Environment and Abnormal Glucose Metabolism Tue, 27 Aug 2019 00:05:14 +0000 The prevalence of diabetes mellitus (DM) has been increasing dramatically worldwide, but the pathogenesis is still unknown. A growing amount of evidence suggests that an abnormal developmental environment in early life increases the risk of developing metabolic diseases in adult life, which is referred to as the “metabolic memory” and the Developmental Origins of Health and Disease (DOHaD) hypothesis. The mechanism of “metabolic memory” has become a hot topic in the field of DM worldwide and could be a key to understanding the pathogenesis of DM. In recent years, several large cohort studies have shown that shift workers have a higher risk of developing type 2 diabetes mellitus (T2DM) and worse control of blood glucose levels. Furthermore, a maternal high-fat diet could lead to metabolic disorders and abnormal expression of clock genes and clock-controlled genes in offspring. Thus, disorders of circadian rhythm might play a pivotal role in glucose metabolic disturbances, especially in terms of early adverse nutritional environments and the development of metabolic diseases in later life. In addition, as a peripheral clock, the gut microbiota has its own circadian rhythm that fluctuates with periodic feeding and has been widely recognized for its significant role in metabolism. In light of the important roles of the gut microbiota and circadian clock in metabolic health and their interconnected regulatory relationship, we propose that the “gut microbiota-circadian clock axis” might be a novel and crucial mechanism to decipher “metabolic memory.” The “gut microbiota-circadian clock axis” is expected to facilitate the future development of a novel target for the prevention and intervention of diabetes during the early stage of life. Liyuan Zhou, Lin Kang, Xinhua Xiao, Lijing Jia, Qian Zhang, and Mingqun Deng Copyright © 2019 Liyuan Zhou et al. All rights reserved. Comparative Proteome Analysis of Epicardial and Subcutaneous Adipose Tissues from Patients with or without Coronary Artery Disease Sun, 25 Aug 2019 09:05:13 +0000 Background and Aims. Owing to its unique anatomical structure and metabolism, epicardial adipose tissue (EAT) has attracted amount of attention in coronary artery disease (CAD) research. Here, we analyzed differences in proteome composition in epicardial (EAT) and subcutaneous adipose tissues (SAT) from patients with or without CAD. Methods. EAT and SAT samples were collected from 6 CAD patients and 6 non-CAD patients. Isobaric Tagging for Relative and Absolute Quantitation (iTRAQ) analysis combined with liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed to identify the differentially expressed proteins. Results. In total, 2348 proteins expressed in EAT and 2347 proteins expressed in SAT were separately identified. 385 differentially expressed proteins were found in EAT and 210 proteins were found in SAT in CAD patients compared to non-CAD patients. Many proteins differentially expressed in EAT of CAD patients were involved in biological functions associated with CAD development such as cell-to-cell signaling and interaction, inflammatory response, and lipid metabolism. Differential expressions of proteins (MMP9, S100A9, and clusterin) in EAT or SAT were involved in several signaling pathways such as mitochondrial dysfunction, acute phase inflammation, and LXR/RXR activation, which was confirmed by western blotting, and similar results were obtained. Conclusions. The largest profiles of differentially expressed proteins in EAT and SAT between CAD patients and non-CAD patients were identified. The significant signal pathways, mitochondrial dysfunction, and LXR/RXR activation, which differential proteins were involved in, were firstly found to play roles in EAT of CAD patients, and clusterin was firstly found to be upregulated in EAT of CAD patients. Yu xing Zhao, Hui juan Zhu, Hui Pan, Xue mei Liu, Lin jie Wang, Hong bo Yang, Nai shi Li, Feng ying Gong, Wei Sun, and Yong Zeng Copyright © 2019 Yu xing Zhao et al. All rights reserved. Relationship between Echocardiographic and Magnetic Resonance-Derived Measurements of the Thoracic Aorta in Turner Syndrome Patients Tue, 20 Aug 2019 10:05:13 +0000 Introduction. Turner syndrome (TS) is assigned to the rare diseases group. Morbidity and mortality of TS patients are high, particularly due to the cardiovascular disorders, so monitoring for cardiovascular complications must be ensured. The data demonstrate a strong correlation between 2-dimensional echocardiographic (2Decho) evaluation and magnetic resonance imaging (MRI); still, according to recent guidelines, MRI remains a gold standard. In this study, we aimed to compare aortic dimensions on MRI and 2Decho in TS patients. Methods. 50 TS patients (≥18 years) were enrolled into the cross-sectional study. 2Decho and MRI were performed. The measurements of the aorta were assessed in five standard positions on 2Decho and in 9 standard positions on MRI; ASI (aortic size index) of the ascending aorta was calculated since reduced adult height is observed in TS patients. Results. ASI on echocardiography strongly correlated with ASI on MRI in all positions of the ascending aorta, but significantly larger medians of ASI were found on 2Decho in all positions of the ascending aorta and arch when compared with MRI measurements. Still, the prevalence of aortic sinus dilation was significantly and more frequently (52% vs. 38%, ) observed on MRI when compared with 2Decho. Conclusion. The relation of aortic size was significant in all positions when comparing the MRI and 2Decho methods; still, the dilatation of the sinus of aorta was more frequently found on MRI compared with echocardiography. Rūta Krikščiūnienė, Inesa Navickaitė, Eglė Ereminienė, Saulius Lukoševičius, Birutė Žilaitienė, and Rasa Verkauskienė Copyright © 2019 Rūta Krikščiūnienė et al. All rights reserved. Glibenclamide-Induced Autophagy Inhibits Its Insulin Secretion-Improving Function in β Cells Thu, 15 Aug 2019 18:05:04 +0000 Diabetes is a metabolic disease, partly due to hypoinsulinism, which affects ∼8% of the world’s adult population. Glibenclamide is known to promote insulin secretion by targeting β cells. Autophagy as a self-protective mechanism of cells has been widely studied and has particular physiological effects in different tissues or cells. However, the interaction between autophagy and glibenclamide is unclear. In this study, we investigated the role of autophagy in glibenclamide-induced insulin secretion in pancreatic β cells. Herein, we showed that glibenclamide promoted insulin release and further activated autophagy through the adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) pathway in MIN-6 cells. Inhibition of autophagy with autophagy inhibitor 3-methyladenine (3-MA) potentiated the secretory function of glibenclamide further. These results suggest that glibenclamide-induced autophagy plays an inhibitory role in promoting insulin secretion by activating the AMPK pathway instead of altering the mammalian target of rapamycin (mTOR). Jiali Zhou, Xincong Kang, Yushuang Luo, Yuju Yuan, Yanyang Wu, Meijun Wang, and Dongbo Liu Copyright © 2019 Jiali Zhou et al. All rights reserved. Compound C Protects Mice from HFD-Induced Obesity and Nonalcoholic Fatty Liver Disease Wed, 14 Aug 2019 17:05:04 +0000 Objectives. The aim of this study was to investigate the effects of compound C on an in vivo mouse model of high-fat diet- (HFD-) induced obesity and hepatosteatosis. Methods. C57BL/6 mice were fed with a standard diet (n = 5) for 16 weeks and then injected saline once a day for 4 weeks as the normal chow group. Mice (n = 10) were fed with HFD for 16 weeks to induce obesity and hepatosteatosis and then divided into two groups: HFD + vehicle group injected with the vehicle solution (saline) and HFD + compound C group injected with compound C in saline (5 mg/kg i.p., once a day) for 4 weeks. Liver histology was observed. The expression levels of genes related to lipid metabolism and proinflammation in liver tissue were examined. NLRP3 inflammasome expression in liver tissue was detected by the western blot assay. HepG2 cells were pretreated with compound C and/or AICAR for 1 h and then treated with palmitic acid (PA) for 3 h. The cells were collected, and mRNA levels were determined. Results. There was a significant reduction in body-weight gain and daily food intake in the HFD + compound C group compared with the HFD + vehicle group (). The glucose tolerance test (GTT) and insulin tolerance test (ITT) showed that compound C alleviated insulin resistance. Histology analysis showed a significant reduction of hepatic steatosis by compound C. Compound C also significantly decreased fatty acid synthesis genes, while increased fatty acid oxidation genes. Furthermore, compound C significantly reduced the expression of proinflammatory markers and NLRP3 inflammasome (). Compound C enhanced mRNA levels of SOD1, SOD2, catalase, GPx1, and GPx4 and reduced the p-AMPK/AMPK ratio, which were stimulated by palmitic acid (PA). The effect was enhanced by AICAR. Conclusion. Our data suggest that compound C is a potent NAFLD suppressor and an attractive therapeutic target for hepatic steatosis and related metabolic disorders. Fang Wang, Yuxing Liu, Jingjing Yuan, Wenjun Yang, and Zhaohui Mo Copyright © 2019 Fang Wang et al. All rights reserved. Thyroid Dysfunction and Cytological Patterns among Patients Requested for Thyroid Function Test in an Endemic Goiter Area of Gondar, North West Ethiopia Wed, 14 Aug 2019 13:30:03 +0000 Background. Thyroid dysfunction is the most common endocrine disorder in clinical practice, and about half of the population with thyroid dysfunction remains undiagnosed. There is a fairly wide spectrum of thyroid dysfunction, which can be identified by patterns of thyroid function test results. The prevalence of thyroid dysfunction among the population varies in different studies. Methods. A cross-sectional study was conducted from February 8th to April 8th, 2017, among patients who requested for the thyroid function test in an endemic goiter area at the Gondar Hospital, University of Gondar. A pretested structured questionnaire was used to collect the data. Three milliliters of blood samples was collected in a plain test tube and centrifuged for serum separation. The thyroid function test was done by using the MINI-VIDAS automation following the manufacturer manual (Setema PLC, Italy). Data were entered and analyzed using SPSS version 20. Descriptive statistics were used for data presentation, and value < 0.05 was considered significant. Result. Of the total 384 study participants, 346 (90.1%) were females and the study participants’ mean age was 38 ± 13.9 years. The overall thyroid dysfunction prevalence was 26.3% (101): 1.6% was identified as subclinical hypothyroidism, 0.5% hypothyroidism, 9.6% subclinical hyperthyroidism, and 14.6% hyperthyroidism, and 23.4% had goiter. Furthermore, for cytological pattern analysis, 144 study participants who fulfilled indications for fine-needle aspiration cytology (FNAC) in thyroid nodules were included. Of the total, 3 (2.1%) had thyroid carcinoma, 46 (32%) had cystic degenerated follicular cells, and 82 (57%) had nodular thyroid goiter. In addition, a clinical presentation of a total of 144 study participants, showed lymphadenites in 7 participants (4.8%), hypertension in 9 (6.2%), and cardiac failure in 12 (8.3%). Conclusion. The prevalence of thyroid dysfunction was high. The majority of thyroid dysfunction cases were newly diagnosed and more common in females. In addition, the most common disorders were subclinical hyperthyroidism and hyperthyroidism. Follicular cell with cyst degeneration and thyroid nodular goiter were the predominant FNAC findings. For early diagnosis and appropriate intervention in goiter endemic areas, the thyroid function test should be closely monitored. Daniel Asmelash, Kumlgn Tesfa, and Belete Biadgo Copyright © 2019 Daniel Asmelash et al. All rights reserved. Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism Thu, 01 Aug 2019 15:05:01 +0000 Background. The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs. Methods. From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results. Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (), were larger (), and presented more vascular () and lymphatic () invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion. In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal. A. P. Santos, J. Vinagre, P. Soares, I. Claro, A. C. Sanches, L. Gomes, I. Fernandes, A. L. Catarino, J. Preto, B. D. Pereira, A. P. Marques, F. Rodrigues, C. Amaral, G. Rocha, J. C. Mellidez, H. Simões, J. M. Lopes, M. J. Bugalho, and On behalf of the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism Copyright © 2019 A. P. Santos et al. All rights reserved. GNPDA2 Gene Affects Adipogenesis and Alters the Transcriptome Profile of Human Adipose-Derived Mesenchymal Stem Cells Thu, 01 Aug 2019 01:05:42 +0000 Background. Genome-wide association studies have found an obesity-related single-nucleotide polymorphism rs10938397 near the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) encoding, an enzyme that catalyzes the deamination of the glucosamine-6-phosphate involved in the hexosamine signaling pathway, but the molecular mechanisms underlying the missing link between GNPDA2 and obesity remain elusive. Methods. As obesity is accompanied by an increase in the size and the number of adipocytes, the present study investigates the possible mechanism of the GNPDA2 in adipogenesis using GeneChip® Human Transcriptome Array 2.0 in human adipose-derived mesenchymal stem cells. Results. We found that overexpression of GNPDA2 enhanced accumulation of lipid droplets, and knocking down the gene decreased accumulation of lipid droplets. GO term enrichment analysis indicated that most differentially expressed genes (DEGs) affected by deficiency of GNPDA2 have functions to lipid and glucose metabolism. Further KEGG enrichment analysis showed that the greatest proportion of DEGs are involved in thermogenesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, carbon metabolism, and fatty acid metabolism including fatty acid degradation, elongation, and biosynthesis. Conclusion. These findings suggest that GNPDA2 may be a critical gene for lipid and glucose metabolism, and the expression level of GNPDA2 alters the transcriptome profile of human adipose-derived mesenchymal stem cells. Lijun Wu, Feifei Ma, Xiaoyuan Zhao, Mei-Xian Zhang, Jianxin Wu, and Jie Mi Copyright © 2019 Lijun Wu et al. All rights reserved. The Value of Adrenal Androgens for Correcting Cortisol Lateralization in Adrenal Venous Sampling in Patients with Normal Cortisol Secretion Wed, 31 Jul 2019 07:05:16 +0000 The management of patients with adrenocorticotropic hormone-independent Cushing’s syndrome and bilateral adrenal masses is challenging. Adrenal venous sampling (AVS) has been used to identify functional lesions in previous studies, but it is not always reliable. The present study aims to address the variability of cortisol in the adrenal veins of patients without excessive cortisol secretion and investigate the use of adrenal androgens to correct the cortisol lateralization ratio in AVS. Thirty-seven patients with primary aldosteronism underwent successful AVS. Patients with normal cortisol secretion exhibited a wide range of cortisol concentrations in the right (601-89, 400 nmol/l) and left (331-35, 300 nmol/l) adrenal veins. The median cortisol gradients between adrenal venous and peripheral venous samples were 15.25 and 10.14 in the right and left sides, respectively, and the cortisol lateralization ratio (high side to low side) was as high as 9.49 (median 1.54). The mean plasma levels of cortisol in the adrenal venous and peripheral venous samples decreased from t-15 to t0. Significant positive correlations were observed between the cortisol concentrations and both androstenedione and dehydroepiandrosterone concentrations in the right and left adrenal veins. After correcting for androstenedione or dehydroepiandrosterone levels, the cortisol lateralization ratio was less than 2 in most adrenal venous samples. The present study demonstrated the wide variation in cortisol concentrations in the adrenal veins of patients with normal cortisol secretion. The adrenal androgens might be ideal analytes used as normalizers when assessing the cortisol lateralization of AVS in normal or hypercortisolism cases. Wenjing Zhang, Keying Zhu, Hongyun Li, Yan Zhang, Dalong Zhu, Xuebin Zhang, and Ping Li Copyright © 2019 Wenjing Zhang et al. All rights reserved. The Association between a 24-Hour Blood Pressure Pattern and Circadian Change in Plasma Aldosterone Concentration for Patients with Aldosterone-Producing Adenoma Mon, 29 Jul 2019 10:05:28 +0000 The absence of nocturnal blood pressure (BP) decline is associated with hypertensive complications. Data regarding circadian BP patterns in patients with aldosterone-producing adenoma (APA) are limited and equivocal. We evaluated the circadian BP profile in patients with APA and its relationship with the circadian aldosterone rhythm. BP in patients with APA and in those with essential hypertension (EH) were assessed through in-hospital 24-h ambulatory blood pressure monitoring. Over a 24-h in-hospital period, plasma aldosterone levels taken at midnight, 0400, 0800, 1200, 1600, and 2000 h were measured. To evaluate a correlation between BP and hormone rhythm, we included 27 patients with APA (APA group) and 27 patients with EH (EH group). Both groups had similar age, sex ratio, body mass index, duration of hypertension, family history of hypertension, and lipid profiles. The day-night BP differences in both patient groups were similar, whether expressed as absolute values or percentages. The proportions of patients with dipping BP profiles were also comparable (APA group, 5 of 27; EH group, 7 of 27; χ2 = 0.429; P = 0.513). At each time point, APA group plasma aldosterone concentrations (PACs) were higher than those of the EH group. A circadian change in relation to PAC was observed in both groups. A correlation between PAC and BP was statistically nonsignificant in most study patients in either group. Our data indicated that the circadian BP pattern was not associated with a change in PAC levels in patients with APA. Hai Li, Jianbin Liu, Juan Liu, Liehua Liu, Minmin Huang, Guohong Wei, Wanping Deng, Zhimin Huang, Xiaopei Cao, Haipeng Xiao, and Yanbing Li Copyright © 2019 Hai Li et al. All rights reserved. Ginsenoside Rg1 Ameliorates Palmitic Acid-Induced Hepatic Steatosis and Inflammation in HepG2 Cells via the AMPK/NF-B Pathway Sun, 28 Jul 2019 07:05:03 +0000 Nonalcoholic fatty liver disease (NAFLD) is one of the common diseases in the world, and it can progress from simple lipid accumulation to sustained inflammation. The present study was designed to investigate the effects and underlying mechanisms of ginsenoside Rg1 (G-Rg1) treatment on NAFLD in vitro. HepG2 cells were treated with palmitic acid (PA) to induce steatosis and inflammation and then successively incubated with G-Rg1. Lipids accumulation was analyzed by Oil Red O staining and intracellular triglyceride (TG) quantification. Inflammatory conditions were examined by quantifying the levels of cell supernatant alanine transaminase/aspartate aminotransferase (ALT/AST) and secretory proinflammatory cytokines, including IL-1β, IL-6, and TNF-α in the cell supernatants. Quantitative RT-PCR and western blotting were used to measure the expressions of genes and proteins associated with lipogenic synthesis and inflammation, including AMP-activated protein kinase (AMPK) and nuclear factor-kappa B (NF-κB) pathways. HepG2 cells were pretreated with an AMPK inhibitor; then, Oil Red O staining and TG quantification were performed to study the lipid deposition. Phospho-AMPK (Thr172) (p-AMPK) and phospho-acetyl-CoA carboxylase (Ser79) (p-ACCα) were quantified by immunoblotting. Immunofluorescence was performed to demonstrate the nuclear translocation of NF-κB P65. The present study showed that PA markedly increased the intracellular lipid droplets accumulation and TG levels, but decreased AMPK phosphorylation and the expressions of its downstream lipogenic genes. However, G-Rg1 alleviated hepatic steatosis and reduced the intracellular TG content; these changes were accompanied by the activation of the AMPK pathway. In addition, blocking AMPK by using the AMPK inhibitor markedly abolished the G-Rg1-mediated protection against PA-induced lipid deposition in HepG2 cells. Furthermore, G-Rg1 reduced the ALT/AST levels and proinflammatory cytokines release, which were all enhanced by PA. These effects were correlated with the inactivation of the NF-κB pathway and translocation of P65 from the cytoplasm to the nucleus. Overall, these results suggest that G-Rg1 effectively ameliorates hepatic steatosis and inflammation, which might be associated with the AMPK/NF-κB pathway. Qing Xiao, Shujun Zhang, Cheng Yang, Ruoyang Du, Jinqiu Zhao, Jiajun Li, Yashu Xu, Yuanyuan Qin, Yue Gao, and Wenxiang Huang Copyright © 2019 Qing Xiao et al. All rights reserved. The Role of Occupational Therapy in Secondary Prevention of Diabetes Wed, 24 Jul 2019 08:05:13 +0000 Diabetes mellitus is becoming a global health concern due to its prevalence and projected growth. Despite a growing number of interventions for secondary prevention of diabetes, there is a persistent poor glycemic control and poor adherence to the prescribed diabetes management regimen. In light of the tremendous costs of diabetes to both individuals and the society, it is pressing to find effective ways to improve diabetes self-management (DSM) and treatment adherence. Occupational therapists can bring values to the diabetes care team by evaluating multiple levels of influence on DSM, addressing personal and environmental barriers to well-being and DSM, and supporting patients to develop of a highly complex competences and skills to satisfactorily self-manage diabetes. This article summarizes two evidence-based, well-structured occupational therapy (OT) programs that use activity-based treatments and psychosocial strategies, respectively, to improve DSM abilities and to enhance quality of life. As the needs of adolescents with diabetes are quite different from other diabetic populations, this article also provides a summary of pediatric OT interventions that aim to facilitate autonomy and development of DSM ability among adolescents with diabetes. Evidence indicates that OT interventions can improve the quality of life and treatment adherence in patients with diabetes and hence should be continued and built on to address the increasing needs of diabetic populations. Xizi Shen and Xingping Shen Copyright © 2019 Xizi Shen and Xingping Shen. All rights reserved. A Prospective Study Comparing Two-Time Points of Thyroid Hormone Replacement during the Holy Month of Ramadan Mon, 22 Jul 2019 00:05:17 +0000 Background. Muslims all over the world fast during the month of Ramadan from dawn until dusk. There is little data regarding the best timing of levothyroxine intake during the month of Ramadan where taking it on an empty stomach represents a challenge to most patients. Our study aims to compare two-time points of levothyroxine intake during Ramadan in terms of change in thyroid stimulating hormone (TSH), compliance, and convenience. Study Design and Methods. This was an open-label, randomized, prospective trial. Adult patients known to have primary hypothyroidism with stable TSH for the last 6 months who intended to fast during the month of Ramadan were invited to participate in this prospective study. The study took place during Ramadan of H1438 (May-June 2017). All patients were randomly assigned to two groups. In group A (n= 50) patients took levothyroxine 30 minutes before breaking the fast at sunset (iftar), and in group B (n= 46) patients took it 30 minutes before an early morning meal before sunrise (suhour). Results. TSH levels increased in both group A (from 1.99 to 3.28 mIU/L) and group B (from 1.54 to 3.28 mIU/L) after Ramadan fasting. There was no difference between the two groups. Compliance with intake instructions, all of the time, was reported in 41.6% of group A and 35.7% of group B patients. In both the groups, 95% of patients said it was convenient for them to take the medication at the assigned time. Conclusion. Choosing an optimal time for levothyroxine intake during the month of Ramadan remains a challenge. The current study did not provide any evidence on ideal time and dose of levothyroxine administration during fasting to manage hypothyroidism. Studies with a larger number of patients need to be done to further explore this issue. Zeinab Dabbous, Buthaina Alowainati, Sara Darwish, Hamda Ali, Seleena Farook, Mariam Al Malaheem, Abeir Abdalrubb, Wajiha Gul, and Wajiha Abu Haliqa Copyright © 2019 Zeinab Dabbous et al. All rights reserved. Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS) in Rats with Thyroid Dysfunction Thu, 18 Jul 2019 13:05:18 +0000 Background and Objectives. Thyroid hormones have an important role in the growth and development of various tissues including the kidney, which is the major site of renin release and the consequent angiotensin and aldosterone formation. Therefore any derangement in thyroid function can result in abnormal functioning in the renin-angiotensin-aldosterone system. The current study was undertaken to find the impact of using a direct renin inhibitor (Aliskiren) and an angiotensin-converting enzyme inhibitor (Fosinopril) on the components of the renin-angiotensin-aldosterone system (RAAS) in rats with thyroid dysfunctions. Method. Forty-two male albino rats were divided into three subgroups. First group (6 rats) served as control. Second group (18 rats) served as hyperthyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Third group (18 rats) served as hypothyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Induction of hyperthyroidism and hypothyroidism was done through daily oral administration of L-Thyroxine and Propylthiouracil, respectively. On day 40 of the study, the rats were sacrificed and blood was collected for estimation of renin, angiotensin I, angiotensin II, aldosterone, TSH, T3, and T4. The collected blood samples were also used for estimation of levels blood urea, serum creatinine, liver enzymes, and serum electrolytes. Blood pressure and urine collection were done on days 1 and 40. The collected urine was used for estimation of urine flow, sodium excretion, and potassium excretion rates. Results. In hypothyroid induced rats, serum renin level dropped as expected, while the use of Aliskiren and Fosinopril on these hypothyroid rats raised renin level due to the feedback mechanism. Both angiotensin I and II were significantly (P <0.05) lower than normal levels in the hypothyroid rats, unlike the level of aldosterone, which was higher than normal level. There was nonsignificant lowering in BP (systolic, diastolic, and mean BP) in the hypothyroid rats. Treatment of these rats with Aliskiren and Fosinopril did not lower the blood pressure more than normal when compared to the hypothyroid group. The hypothyroid rats also showed a decrease in level of serum creatinine. In hyperthyroid rats, there was a rise in levels of serum renin, angiotensin II, and aldosterone; nevertheless, the increase in angiotensin I level was significant. The use of Aliskiren and Fosinopril increased the level of renin nonsignificantly (decreased angiotensin I significantly). Hyperthyroid rats showed a significant increase in systolic, diastolic, and mean blood pressure. Both Aliskiren and Fosinopril increased urine flow, Na+   excretion, and K+ excretion rates. Aliskiren was better at reducing the high blood pressure. Conclusion. Aliskiren and Fosinopril in hyperthyroid rats decreased serum angiotensin I, angiotensin II, and aldosterone. Blockade of renin and inhibition of angiotensin-converting enzyme both resulted in a rebound increase in level of renin in hypothyroid rats. Aliskiren is better at controlling blood pressure in hyperthyroid rats. Urine flow, sodium excretion, and potassium excretion rates were improved by the use of Aliskiren and Fosinopril in hyperthyroid rats. Susan A. S. Farhadi and Kawa F. Dizaye Copyright © 2019 Susan A. S. Farhadi and Kawa F. Dizaye. All rights reserved. Identification of Serum miRNA-423-5p Expression Signature in Somatotroph Adenomas Wed, 17 Jul 2019 10:05:14 +0000 Circulating miRNAs are novel disease biomarkers that are valuable for diagnosis and prognosis. But the circulating miRNAs profile in somatotroph adenomas is still unknown. Therefore, serum exosomal miRNAs expression profiling in somatotroph adenomas was performed on 6 somatotroph adenomas and 6 normal controls. From the exosomal miRNAs expression profiling, we found 169 miRNAs differently expressed between somatotroph adenomas and healthy pituitary samples (p< 0.05, FC > 2). Among the 169 miRNAs, miR-423-5p was expressed lower in somatotroph adenomas than in healthy pituitary samples, which was proved by miRSCan Panel Chip™ qPCR. PTTG1 and SYT1 were the target mRNAs of miR-423-5p, and transcriptomics and proteomics profile both indicated the high expression of PTTG1 and SYT1 in somatotroph adenomas. H-scores were 223.1 ± 34.7 for PTTG1 and 163.4 ± 42.3 for SYT1 in 62 somatotroph adenomas specimens and 84.2 ± 21.3 for PTTG1 and 47.4 ± 17.2 for SYT1 in 6 healthy pituitary specimens by IHC. miR-423-5p inhibited the expression of SYT1 and PTTG1 at the mRNA and protein levels. Dual luciferase reporter gene assay shown was significantly reduced in the presence of miR-423-5p in GH3 cells transfected with wild-type PTTG1 3'UTR luciferase reporter plasmid but not reduced when transfected with the mutation PTTG1 3'UTR luciferase reporter plasmid (p<0.01). In vitro experiments showed that miR-423-5p induced cell apoptosis, inhibited cell proliferation, and reduced growth hormone release and migration of GH3 cells. The activity of miR-423-5p in GH3 cell was nearly blocked by its inhibitor. These results verified the central role of low miR-423-5p in promoting tumorigenesis in somatotroph adenomas. PTTG1 may act as biomarkers for clinical treatment of somatotroph adenomas. Sida Zhao, Jianhua Li, Jie Feng, Zhenye Li, Qian Liu, Peng Lv, Fei Wang, Hua Gao, and Yazhuo Zhang Copyright © 2019 Sida Zhao et al. All rights reserved. Increased Circulating Chemerin in Relation to Chronic Microvascular Complications in Patients with Type 2 Diabetes Tue, 16 Jul 2019 08:05:12 +0000 Objective. Type 2 diabetes (T2DM) is a global epidemic and increases mortality due to its vascular complications. Chemerin has been found to exert a major role in glucose and lipid metabolism. The aim of this study was to explore the correlation between plasma chemerin levels and microangiopathy in patients with T2DM. Methods. A total of 598 T2DM patients were classified into two groups: with and without microvascular complications. Anthropometric parameters and blood pressure were taken. The amounts of glycosylated hemoglobin, glucose, lipid profiles, creatinine, and chemerin concentrations in the blood were determined. The presence and severity of nephropathy, retinopathy, and neuropathy were also evaluated by specific tests. Results. Plasma levels of chemerin in diabetic subjects with microvascular complications were markedly elevated compared to those without. The number of microvascular complications increased with high plasma chemerin levels. Patients with high chemerin levels had an increased incidence of nephropathy and retinopathy. Furthermore, the chemerin plasma concentrations increased with the progression of diabetic nephropathy with highest values in macroalbuminuria groups. In contrast, no significant difference was observed in plasma chemerin levels between subjects with and without peripheral neuropathy. Pearson correlation analysis showed that plasma chemerin levels were positively related to duration of diabetes, serum creatinine, and 24-hour urine albumin excretion, even after multiple adjustments. Using logistic regression analysis, plasma chemerin concentrations were independently associated with the presence of nephropathy and retinopathy, not neuropathy. Conclusion. This study elucidated a positive correlation between increased chemerin levels and the development of some subtypes of diabetic microangiopathy. Ping Gu, Wei Wang, Yue Yao, Yixin Xu, Liping Wang, Pu Zang, Jian Ma, Cuihua Yang, Junya Liang, Bin Lu, and Jiaqing Shao Copyright © 2019 Ping Gu et al. All rights reserved. Maternal Vitamin D Status and Its Effect on Vitamin D Levels in Early Infancy in a Tertiary Care Centre in Sri Lanka Tue, 09 Jul 2019 09:05:08 +0000 Epidemiologic studies from South Asian countries have reported vitamin D deficiency among all age groups. However, there is very little information on vitamin D levels, especially in the vulnerable populations (pregnant/breast feeding mother and infants) in Sri Lanka. More data on vitamin D status of such populations will be important for policy decisions to be made at a national level. Similarly, it will be valuable for healthcare programs in other countries (e.g., United States, Australia, Europe, and Canada) as Sri Lankans are a fast-growing migrant population to those countries. The purpose of this study was to investigate maternal vitamin D status and its effects on infants in a state sector tertiary care centre in Sri Lanka. This prospective cohort study was conducted on 140 healthy pregnant mothers in the third trimester (mean gestational age 39±1 weeks). Blood was collected for 25(OH)D and parathyroid hormone (PTH). Sun exposure and feeding patterns of the infants were recorded based on maternal reporting. Mean age of the infants at follow-up visit was 36±7 days. Vitamin D (25 (OH)D) deficiency (<25 nmol/L) was observed in 12% pregnant mothers, 5% lactating mothers, and 63% infants. Insufficiency (<50 nmol/L) was found in an additional 51% and 43% in pregnant and lactating mothers and 25% of infants. Mean 25(OH)D was higher in pregnant (46.4±17.5 nmol/L) and lactating (51.9±17.0 nmol/L) mothers than infants (28.1±13.7 nmol/L). Maternal vitamin D level during pregnancy was a significant risk factor (OR: 6.00, 95%CI: 1.522-23.655) for infant deficiency and insufficiency. Sun exposure of infants showed a significant positive correlation with vitamin D level (OR: 3.23, 95%CI: 1.19-8.68). In conclusion, the presence of Vitamin D deficiency/insufficiency is higher in infants compared to pregnant/lactating mothers. Low maternal 25(OH)D during pregnancy was a risk factor for deficiency in infants. Although majority of lactating mothers had sufficient vitamin D, most of their exclusively breastfed offspring were deficient. Kaneshapillai Anusha, Usha Hettiaratchi, Dulani Gunasekera, Shamini Prathapan, and Guwani Liyanage Copyright © 2019 Kaneshapillai Anusha et al. All rights reserved. Polymorphisms in Adipokines in Mexican Children with Obesity Mon, 01 Jul 2019 12:05:20 +0000 The high prevalence of childhood obesity in Mexico is alarming in the health-science field. We propose to investigate the contribution of adipokines and cytokines polymorphisms and common BMI/obesity-associated loci, revealed in genome-wide association studies in Caucasian adult cohorts, with childhood obesity. This study included 773 Mexican-Mestizo children (5-15 years old) in a case-control study. The polymorphisms included were ADIPOQ (rs6444174), TNF-α (rs1800750), IL-1β (rs1143643), IL-6 (rs1524107; rs2069845), NEGR1 (rs34305371), SEC16B-RASAL2 (rs10913469), TMEM18 (rs6548238; rs7561317), GNPDA2 (rs16857402), LEP (rs2167270), MTCH2 (rs10838738), LGR4-LIN7C-BDNF (rs925946), BCDIN3D-FAIM2 (rs7138803), FTO (rs62033400), MC4R (rs11872992), MC4R (rs17782313), and KCTD15 (rs29942). No significant contribution was found with adipokines and cytokines polymorphisms in this study. Only both TMEM18 (rs6548238; rs7561317) polymorphisms were found associated with obesity (OR=0.5, P=0.008) and were in linkage disequilibrium (r2=0.87). The linear regression showed that the rs7561317 polymorphism of TMEM18 is negatively associated with obesity. This report highlights the influence of TMEM18 in Mexican-Mestizo children obesity, while adipokine and cytokine polymorphisms were not associated with it. Angélica Saraí Jiménez-Osorio, Alma Olivia Aguilar-Lucio, Helios Cárdenas-Hernández, Claudette Musalem-Younes, Jacqueline Solares-Tlapechco, Paula Costa-Urrutia, Oscar Medina-Contreras, Julio Granados, and Martha Eunice Rodríguez-Arellano Copyright © 2019 Angélica Saraí Jiménez-Osorio et al. All rights reserved. Effect of Social Factors and the Natural Environment on the Etiology and Pathogenesis of Diabetes Mellitus Tue, 25 Jun 2019 13:05:36 +0000 Type 2 diabetes mellitus (T2DM) is currently a public health problem worldwide and a threat to human health and social development. The incidence rate of the disease is steadily increasing. Various genetic and environmental factors have been established as influencing the pathogenesis of this disease. However, the influence of social factors and the natural environment on DM incidence should also be considered. Low-grade inflammation could represent a central point of connection integrating all these potential triggers, being partly responsible for the development of insulin resistance. This paper aims to elaborate on the impact of the natural environment and social factors on DM development, with a special focus on six aspects of the pathogenesis of DM: pollution, radiation, psychology, drink, sleep, and exercise. We identified a two-way relationship between T2DM and social and natural environments. Changes in these environments may lead to low-grade inflammation, which in turn induces or aggravates T2DM and vice versa. Poor lifestyle may lead to increased insulin resistance and promote DM development. Improvements in blood glucose control can be achieved through nonenvironmental and behavioral interventions. Guangtong Dong, Lianlian Qu, Xuefeng Gong, Bing Pang, Weitian Yan, and Junping Wei Copyright © 2019 Guangtong Dong et al. All rights reserved.