Pub Date : 2021-08-01Epub Date: 2021-03-11DOI: 10.1080/07435800.2021.1895829
Mamoun Ahram, Randa Bawadi, Mohammad S Abdullah, Dana B Alsafadi, Haneen Abaza, Sallam Abdallah, Ebtihal Mustafa
Purpose The cellular and molecular dynamics of DHT-induced EMT in MDA-MB-453 cells were investigated.Methods:PCR arrays were used to examine the expression of EMT-regulatory genes. Immunoblotting was used to detect protein levels and confirm protein-protein interaction following immunoprecipitation. Immunofluorescence was used to observe rearrangement of the actin cytoskeleton and cell morphology. Cell migration was assessed by transwell assayResults: Change of cell morphology was concomitant with increased cell migration after treating cells with DHT. Exposure of cells to DHT for one hour was sufficient to induce changes in cell morphology and actin cytoskeleton after 72 hours indicating altered gene expression. A long-term lasting nuclear translocation of AR was observed after a short exposure of cells to DHT. Investigating the expression of 84 EMT-related genes revealed down-expression of β-catenin, N-cadherin, and TCF-4 and increased expression of Slug, all of which were confirmed at the protein level. Yet, not only early interaction of AR and β-catenin was observed following AR activation, inhibition of β-catenin blocked DHT-induced mesenchymal transition and migration. Wnt signaling was found to be partially important in DHT-induced morphological alteration. The mesenchymal transition of cells could be induced by treating cells with an inhibitor of glycogen synthase kinase-3β, an enzyme that inhibits β-catenin; this morphological transition could be reversed by antagonizing AR suggesting that AR functions downstream of β-catenin.Conclusions: These results suggest that MDA-MB-453 cells undergo partial EMT induced by DHT, β-catenin is critical for this phenotypic change, and AR probably reciprocally mediates the mesenchymal transition of these cells upon activation of GSK-3 β.
{"title":"Involvement of β-catenin in Androgen-induced Mesenchymal Transition of Breast MDA-MB-453 Cancer Cells.","authors":"Mamoun Ahram, Randa Bawadi, Mohammad S Abdullah, Dana B Alsafadi, Haneen Abaza, Sallam Abdallah, Ebtihal Mustafa","doi":"10.1080/07435800.2021.1895829","DOIUrl":"https://doi.org/10.1080/07435800.2021.1895829","url":null,"abstract":"<p><p><b>Purpose</b> The cellular and molecular dynamics of DHT-induced EMT in MDA-MB-453 cells were investigated.<b>Methods</b>:PCR arrays were used to examine the expression of EMT-regulatory genes. Immunoblotting was used to detect protein levels and confirm protein-protein interaction following immunoprecipitation. Immunofluorescence was used to observe rearrangement of the actin cytoskeleton and cell morphology. Cell migration was assessed by transwell assay<b>Results:</b> Change of cell morphology was concomitant with increased cell migration after treating cells with DHT. Exposure of cells to DHT for one hour was sufficient to induce changes in cell morphology and actin cytoskeleton after 72 hours indicating altered gene expression. A long-term lasting nuclear translocation of AR was observed after a short exposure of cells to DHT. Investigating the expression of 84 EMT-related genes revealed down-expression of β-catenin, N-cadherin, and TCF-4 and increased expression of Slug, all of which were confirmed at the protein level. Yet, not only early interaction of AR and β-catenin was observed following AR activation, inhibition of β-catenin blocked DHT-induced mesenchymal transition and migration. Wnt signaling was found to be partially important in DHT-induced morphological alteration. The mesenchymal transition of cells could be induced by treating cells with an inhibitor of glycogen synthase kinase-3β, an enzyme that inhibits β-catenin; this morphological transition could be reversed by antagonizing AR suggesting that AR functions downstream of β-catenin.<b>Conclusions:</b> These results suggest that MDA-MB-453 cells undergo partial EMT induced by DHT, β-catenin is critical for this phenotypic change, and AR probably reciprocally mediates the mesenchymal transition of these cells upon activation of GSK-3 β.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2021.1895829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25462902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skeletal muscle functions as a locomotory system and maintains whole-body metabolism. Sex differences in such skeletal muscle morphology and function have been documented; however, their underlying mechanisms remain elusive. Glucocorticoids are adrenocortical hormones maintaining homeostasis, including regulating whole-body energy metabolism in addition to stress response. In skeletal muscle, glucocorticoids can reduce the synthesis of muscle proteins and simultaneously accelerate the breakdown of proteins to regulate skeletal muscle mass and energy metabolism via a transcription factor glucocorticoid receptor (GR). We herein evaluated the related contributions of the GR to sex differences of gene expression profiles in skeletal muscle using GR-floxed (GRf/f) and skeletal muscle-specific GR knockout (GRmKO) mice. There were no differences in GR mRNA and protein expression levels in gastrocnemius muscle between males and females. A DNA microarray analysis using gastrocnemius muscle from GRf/f and GRmKO mice revealed that, although most gene expression levels were identical in both sexes, genes related to cholesterol and apolipoprotein synthesis and fatty acid biosynthesis and the immunological system were predominantly expressed in males and females, respectively, in GRf/f but not in GRmKO mice. Moreover, many genes were up-regulated in response to starvation in GRf/f but not in GRmKO mice, many of which were sex-independent and functioned to maintain homeostasis, while genes that showed sex dominance related to a variety of functions. Although the genes expressed in skeletal muscle may be predominantly sex-independent, sex-dominant genes may relate to sex differences in energy metabolism and the immune system and could be controlled by the GR.
{"title":"The Influence of Glucocorticoid Receptor on Sex Differences of Gene Expression Profile in Skeletal Muscle.","authors":"Noritada Yoshikawa, Aya Oda, Hiroki Yamazaki, Motohisa Yamamoto, Akiko Kuribara-Souta, Masaaki Uehara, Hirotoshi Tanaka","doi":"10.1080/07435800.2021.1884874","DOIUrl":"https://doi.org/10.1080/07435800.2021.1884874","url":null,"abstract":"<p><p>Skeletal muscle functions as a locomotory system and maintains whole-body metabolism. Sex differences in such skeletal muscle morphology and function have been documented; however, their underlying mechanisms remain elusive. Glucocorticoids are adrenocortical hormones maintaining homeostasis, including regulating whole-body energy metabolism in addition to stress response. In skeletal muscle, glucocorticoids can reduce the synthesis of muscle proteins and simultaneously accelerate the breakdown of proteins to regulate skeletal muscle mass and energy metabolism via a transcription factor glucocorticoid receptor (GR). We herein evaluated the related contributions of the GR to sex differences of gene expression profiles in skeletal muscle using GR-floxed (GRf/f) and skeletal muscle-specific GR knockout (GRmKO) mice. There were no differences in GR mRNA and protein expression levels in gastrocnemius muscle between males and females. A DNA microarray analysis using gastrocnemius muscle from GRf/f and GRmKO mice revealed that, although most gene expression levels were identical in both sexes, genes related to cholesterol and apolipoprotein synthesis and fatty acid biosynthesis and the immunological system were predominantly expressed in males and females, respectively, in GRf/f but not in GRmKO mice. Moreover, many genes were up-regulated in response to starvation in GRf/f but not in GRmKO mice, many of which were sex-independent and functioned to maintain homeostasis, while genes that showed sex dominance related to a variety of functions. Although the genes expressed in skeletal muscle may be predominantly sex-independent, sex-dominant genes may relate to sex differences in energy metabolism and the immune system and could be controlled by the GR.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2021.1884874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25372524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-08-01Epub Date: 2021-04-17DOI: 10.1080/07435800.2021.1914079
Danial Jahantigh, Fariba Mirani Sargazi, Saman Sargazi, Ramin Saravani, Saeedeh Ghazaey Zidanloo, Milad Heidari Nia, Maryam Piri
Purpose: To investigate the link between two variants (rs4705342 and rs4705343) in the promoter of the miR-143/145 cluster with Type 2 diabetes mellitus (T2DM) risk. Methods:A total of 1200 subjects were genotyped using the ARMS-PCR method. Results: The rs4705342 variant enhanced the risk of T2DM under codominant CC (OR = 3.24; 95% CI: 1.89-5.60), recessive TT+TC (OR = 3.02; 95% CI: 1.77-5.17), and dominant TC+CC (OR = 1.35; 95% CI: 1.08-1.71) genetic models. Individuals carrying the C allele of rs4705342 conferred a 1.43 fold increased risk of T2DM. As regards rs4705343, decreased risk of T2DM was observed under codominant TC (OR = 0.53; 95% CI: 0.42-0.67), over-dominant TT+CC (OR = 0.51; 95% CI: 0.40-0.64), and dominant TC+CC (OR = 0.59; 95% CI: 0.48-0.75) models. Haplotype analysis of the variants showed a 1.941-fold increased risk of T2DM regarding the C T combination. Significant associations were noticed between different haplotypes and lipid indices of T2DM patients. There were no notable changes in p-values after adjustment for BMI. Computational analysis revealed that miR143 and/or miR145 target important genes involved in glucose and lipid metabolism. Conclusions: Functional miR-143/145 variants might influence the risk of T2DM. Hence, clarifying the precise regulatory mechanisms of gene expression in the development of T2DM will significantly guide researchers to find a novel target for therapeutic intervention.
{"title":"Relationship between Functional <i>miR-143/145</i> Cluster Variants and Susceptibility to Type 2 Diabetes Mellitus: A Preliminary Case-Control Study and Bioinformatics Analyses.","authors":"Danial Jahantigh, Fariba Mirani Sargazi, Saman Sargazi, Ramin Saravani, Saeedeh Ghazaey Zidanloo, Milad Heidari Nia, Maryam Piri","doi":"10.1080/07435800.2021.1914079","DOIUrl":"https://doi.org/10.1080/07435800.2021.1914079","url":null,"abstract":"<p><p><b>Purpose:</b> To investigate the link between two variants (rs4705342 and rs4705343) in the promoter of the <i>miR-143/145</i> cluster with Type 2 diabetes mellitus (T2DM) risk. <b>Methods:</b>A total of 1200 subjects were genotyped using the ARMS-PCR method. <b>Results:</b> The rs4705342 variant enhanced the risk of T2DM under codominant CC (OR = 3.24; 95% CI: 1.89-5.60), recessive TT+TC (OR = 3.02; 95% CI: 1.77-5.17), and dominant TC+CC (OR = 1.35; 95% CI: 1.08-1.71) genetic models. Individuals carrying the C allele of rs4705342 conferred a 1.43 fold increased risk of T2DM. As regards rs4705343, decreased risk of T2DM was observed under codominant TC (OR = 0.53; 95% CI: 0.42-0.67), over-dominant TT+CC (OR = 0.51; 95% CI: 0.40-0.64), and dominant TC+CC (OR = 0.59; 95% CI: 0.48-0.75) models. Haplotype analysis of the variants showed a 1.941-fold increased risk of T2DM regarding the C T combination. Significant associations were noticed between different haplotypes and lipid indices of T2DM patients. There were no notable changes in <i>p</i>-values after adjustment for BMI. Computational analysis revealed that miR143 and/or miR145 target important genes involved in glucose and lipid metabolism. <b>Conclusions:</b> Functional miR-143/145 variants might influence the risk of T2DM. Hence, clarifying the precise regulatory mechanisms of gene expression in the development of T2DM will significantly guide researchers to find a novel target for therapeutic intervention.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2021.1914079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38887822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01Epub Date: 2020-10-12DOI: 10.1080/07435800.2020.1827263
Rong Chen, Shuying Liu, Meng Huang, Yangna Ou, Wei Liu, Rongrong Cui, Lingqing Yuan, Zhongjian Xie, Zhifeng Sheng, Hong Liu
Objectives: The diagnosis and management of osteoporosis and osteoporotic fractures are challenging in rural and underdeveloped areas of China because medical resources are inaccessible; thus, a simple and accurate method is essential for the detection of vertebral fractures. We aimed to examine the relationship between historical height loss (HHL) and vertebral fractures in postmenopausal Chinese women.
Material and methods: A cross-sectional study of 255 postmenopausal women aged 50 years or older was conducted in September 2017. Demographic data, including self-reported tallest historical height and current height were analyzed. Vertebral fractures were assessed using X-ray radiography and HHL thresholds were examined using specificity and sensitivity testing.
Results: The average age of the 255 participants was 66.3 ± 9.0 years and their mean HHL was 3.5 ± 2.8 cm. The 24 women who were found to have vertebral fractures were older, had more years since menopause (YSM), and a larger HHL compared to those without vertebral fractures. Logistic regression analysis showed that age was a better predictor of vertebral fractures than HHL was, and the cutoff age for detecting vertebral fractures was 71 years, with an area under the receiver operating characteristic curve of 0.750.
Conclusions: Although the women in this study with vertebral fractures had a greater height loss than those without fractures, it was apparent that age, rather than HHL, is the best way to determine who is most likely to develop vertebral fractures.
{"title":"The Value of Historical Height Loss for Detecting Vertebral Fractures in Postmenopausal Women in China.","authors":"Rong Chen, Shuying Liu, Meng Huang, Yangna Ou, Wei Liu, Rongrong Cui, Lingqing Yuan, Zhongjian Xie, Zhifeng Sheng, Hong Liu","doi":"10.1080/07435800.2020.1827263","DOIUrl":"https://doi.org/10.1080/07435800.2020.1827263","url":null,"abstract":"<p><strong>Objectives: </strong>The diagnosis and management of osteoporosis and osteoporotic fractures are challenging in rural and underdeveloped areas of China because medical resources are inaccessible; thus, a simple and accurate method is essential for the detection of vertebral fractures. We aimed to examine the relationship between historical height loss (HHL) and vertebral fractures in postmenopausal Chinese women.</p><p><strong>Material and methods: </strong>A cross-sectional study of 255 postmenopausal women aged 50 years or older was conducted in September 2017. Demographic data, including self-reported tallest historical height and current height were analyzed. Vertebral fractures were assessed using X-ray radiography and HHL thresholds were examined using specificity and sensitivity testing.</p><p><strong>Results: </strong>The average age of the 255 participants was 66.3 ± 9.0 years and their mean HHL was 3.5 ± 2.8 cm. The 24 women who were found to have vertebral fractures were older, had more years since menopause (YSM), and a larger HHL compared to those without vertebral fractures. Logistic regression analysis showed that age was a better predictor of vertebral fractures than HHL was, and the cutoff age for detecting vertebral fractures was 71 years, with an area under the receiver operating characteristic curve of 0.750.</p><p><strong>Conclusions: </strong>Although the women in this study with vertebral fractures had a greater height loss than those without fractures, it was apparent that age, rather than HHL, is the best way to determine who is most likely to develop vertebral fractures.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2020.1827263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38579621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of atypical vs typical anorexia nervosa (AN) might be explained by the genetic background. We assessed the link between the subtypes of AN and the genetic polymorphisms of the thrombotic panel and the methyltetrahydrofolate reductase (MTHFR) gene. This cross-sectional pilot study recruited 48 girls with AN and 10 age-matched control girls with normal menstruation. We recorded anthropometric parameters and obtained blood samples for genotyping and hormonal assessment. Classification of AN was performed according to the DSM-V criteria. Girls with AN had 2.66 times higher odds of carrying at least one genetic polymorphism from the MTHFR panel (C677T and A1298C) compared with girls without AN (OR = 2.660, p-value = 0.041; CI 95% 1.057-6.720). The presence of atypical vs typical AN was associated independently with the presence of any of the assessed MTHFR polymorphisms (C677T, OR = 4.929, 95% CI 1.076-22.579, p-value = 0.040; A1298C, OR = 0.097, 95% CI 0.011-0.866, p-value = 0.037) in age and estrogen adjusted models. The atypical presentation of AN is mainly linked with higher prevalence of the MTHFR C677T and lower prevalence of the A1298C polymorphism.
非典型神经性厌食症与典型神经性厌食症的发生可能与遗传背景有关。我们评估了AN亚型与血栓形成面板和甲基四氢叶酸还原酶(MTHFR)基因遗传多态性之间的联系。这项横断面试点研究招募了48名患有AN的女孩和10名月经正常的年龄匹配的对照女孩。我们记录了人体测量参数,并采集了血液样本进行基因分型和激素评估。根据DSM-V标准对AN进行分类。患有AN的女孩携带至少一种MTHFR基因多态性(C677T和A1298C)的几率是没有AN的女孩的2.66倍(OR = 2.660, p值= 0.041;Ci 95% 1.057-6.720)。非典型AN和典型AN的存在与任何评估的MTHFR多态性的存在独立相关(C677T, OR = 4.929, 95% CI 1.076-22.579, p值= 0.040;A1298C, OR = 0.097, 95% CI 0.011-0.866, p值= 0.037)。AN的非典型表现主要与MTHFR C677T的高患病率和A1298C多态性的低患病率有关。
{"title":"MTHFR Polymorphisms in Girls with Anorexia Nervosa: Implications on Body Weight.","authors":"Areti Augoulea, Eleni Armeni, Evangelia Deligeoroglou, Stavroula A Paschou, Georgios Papadimitriou, Evgenia Stergioti, Vassilios Karountzos, Artemis Tsitsika, Konstantinos Panoulis, Emmanuel Economou, Irene Lambrinoudaki","doi":"10.1080/07435800.2021.1879845","DOIUrl":"https://doi.org/10.1080/07435800.2021.1879845","url":null,"abstract":"<p><p>The development of atypical vs typical anorexia nervosa (AN) might be explained by the genetic background. We assessed the link between the subtypes of AN and the genetic polymorphisms of the thrombotic panel and the methyltetrahydrofolate reductase (MTHFR) gene. This cross-sectional pilot study recruited 48 girls with AN and 10 age-matched control girls with normal menstruation. We recorded anthropometric parameters and obtained blood samples for genotyping and hormonal assessment. Classification of AN was performed according to the DSM-V criteria. Girls with AN had 2.66 times higher odds of carrying at least one genetic polymorphism from the MTHFR panel (C677T and A1298C) compared with girls without AN (OR = 2.660, <i>p</i>-value = 0.041; CI 95% 1.057-6.720). The presence of atypical vs typical AN was associated independently with the presence of any of the assessed MTHFR polymorphisms (C677T, OR = 4.929, 95% CI 1.076-22.579, <i>p</i>-value = 0.040; A1298C, OR = 0.097, 95% CI 0.011-0.866, <i>p</i>-value = 0.037) in age and estrogen adjusted models. The atypical presentation of AN is mainly linked with higher prevalence of the MTHFR C677T and lower prevalence of the A1298C polymorphism.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2021.1879845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38870416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01Epub Date: 2020-09-02DOI: 10.1080/07435800.2020.1810064
Lauren Buehler, Alireza Movahed, Keren Zhou, M Cecilia Lansang
Background: Thyroid uptake and scan (TUS) is a clinical tool used for differentiation of thyrotoxicosis etiologies. Although guidelines recommend ordering a TUS for evaluation of low TSH levels, no specific value is defined. This study aimed to determine a TSH cutoff at which TUSs yield a greater likelihood of successful determination of etiology to avoid unnecessary testing.
Methods: This was a retrospective study on 137 patients seen by an endocrinologist who underwent TUS for evaluation of low TSH (<0.4 μU/mL). A receiver operating curve analysis was performed to determine the TSH cutoff with maximal sensitivity and specificity for prediction of diagnostic utility.
Results: Ninety percent of TUSs (n = 123) led to a diagnosis, while 10% (n = 14) were inconclusive or normal. Diagnoses included Graves' diseases (52%), toxic multinodular goiter (19%), thyroiditis (12%), and solitary toxic adenoma (7%). The median TSH value was 0.008 μU/mL (IQR 0.005, 0.011), and the median free T4 value was 1.7 μU/mL (IQR 1.3, 2.8). The ROC analysis produced an area under the curve of 0.86. The optimal TSH cutoff value was 0.02 μU/mL (sensitivity 80%, specificity 93%) for prediction of diagnostic yield.
Conclusion: This study demonstrates that TSH is a useful predictor of the utility of TUS in yielding an etiology of thyrotoxicosis. Our analysis showed that TUS had a greater likelihood of determining an etiology when TSH was ≤0.02 μU/mL. This information can help clinicians avoid unnecessary cost and patient time burden when TUS is unlikely to aid in determining the etiology of thyrotoxicosis.
{"title":"Serum thyroid stimulating hormone level for predicting utility of thyroid uptake and scan.","authors":"Lauren Buehler, Alireza Movahed, Keren Zhou, M Cecilia Lansang","doi":"10.1080/07435800.2020.1810064","DOIUrl":"https://doi.org/10.1080/07435800.2020.1810064","url":null,"abstract":"<p><strong>Background: </strong>Thyroid uptake and scan (TUS) is a clinical tool used for differentiation of thyrotoxicosis etiologies. Although guidelines recommend ordering a TUS for evaluation of low TSH levels, no specific value is defined. This study aimed to determine a TSH cutoff at which TUSs yield a greater likelihood of successful determination of etiology to avoid unnecessary testing.</p><p><strong>Methods: </strong>This was a retrospective study on 137 patients seen by an endocrinologist who underwent TUS for evaluation of low TSH (<0.4 μU/mL). A receiver operating curve analysis was performed to determine the TSH cutoff with maximal sensitivity and specificity for prediction of diagnostic utility.</p><p><strong>Results: </strong>Ninety percent of TUSs (n = 123) led to a diagnosis, while 10% (n = 14) were inconclusive or normal. Diagnoses included Graves' diseases (52%), toxic multinodular goiter (19%), thyroiditis (12%), and solitary toxic adenoma (7%). The median TSH value was 0.008 μU/mL (IQR 0.005, 0.011), and the median free T4 value was 1.7 μU/mL (IQR 1.3, 2.8). The ROC analysis produced an area under the curve of 0.86. The optimal TSH cutoff value was 0.02 μU/mL (sensitivity 80%, specificity 93%) for prediction of diagnostic yield.</p><p><strong>Conclusion: </strong>This study demonstrates that TSH is a useful predictor of the utility of TUS in yielding an etiology of thyrotoxicosis. Our analysis showed that TUS had a greater likelihood of determining an etiology when TSH was ≤0.02 μU/mL. This information can help clinicians avoid unnecessary cost and patient time burden when TUS is unlikely to aid in determining the etiology of thyrotoxicosis.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2020.1810064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38335796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01Epub Date: 2020-08-13DOI: 10.1080/07435800.2020.1804928
Zhihua Zuo, Ling Liu, Bin Song, Juan Tan, Dafa Ding, Yibing Lu
Purpose: This study aimed to investigate the role and mechanism of lncRNA ENST00000606790.1 (ENST) in promoting the progression of papillary thyroid carcinoma (PTC).
Methods: The expression of ENST in human PTC and normal para-cancerous thyroid (NPTC) tissues or cell lines was determined by RT-qPCR. Cell growth was determined by CCK8 assay. Cell colony formation was determined by cell colony formation assay. Cell cycle analysis was performed by staining cells with PI (Propidium Iodide). Cell invasion was assessed by transwell assay. Protein expression was examined by western-blot. siRNA was constructed to inhibit the expression of ENST. 740-Y-P was used to activate PI3K. The correlation between ENST expression and clinical outcomes was analyzed.
Results: ENST was significantly up-regulated in PTC tissues or PTC cell lines (PTC and IHH4 cell lines), compared to NPTC tissues or normal cell lines, respectively. High expression of ENST was strongly correlated to lymph node metastasis and tumor size at diagnosis. Silencing of ENST significantly inhibited cell growth and colony formation, arrested the cell cycle at G2/M phase, upregulated the expression of CHK1, downregulated the expression of CDC25C, and inhibited cell invasion. Silencing of ENST significantly down-regulated the expression of PI3K, p-PI3K, AKT, and p-AKT in IHH4 cells. Furthermore, treatment with the PI3K activator 740-Y-P partially abolished the effect of silencing of ENST on PTC cells.
Conclusions: Overall, our results demonstrated that ENST can promote PTC progression by activating the PI3K/AKT signaling pathway, suggesting that ENST can serve as a potential biomarker and new therapeutic target for patients with PTC.
{"title":"Silencing of Long Non-coding RNA ENST00000606790.1 Inhibits the Malignant Behaviors of Papillary Thyroid Carcinoma through the PI3K/AKT Pathway.","authors":"Zhihua Zuo, Ling Liu, Bin Song, Juan Tan, Dafa Ding, Yibing Lu","doi":"10.1080/07435800.2020.1804928","DOIUrl":"https://doi.org/10.1080/07435800.2020.1804928","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the role and mechanism of lncRNA ENST00000606790.1 (ENST) in promoting the progression of papillary thyroid carcinoma (PTC).</p><p><strong>Methods: </strong>The expression of ENST in human PTC and normal para-cancerous thyroid (NPTC) tissues or cell lines was determined by RT-qPCR. Cell growth was determined by CCK8 assay. Cell colony formation was determined by cell colony formation assay. Cell cycle analysis was performed by staining cells with PI (Propidium Iodide). Cell invasion was assessed by transwell assay. Protein expression was examined by western-blot. siRNA was constructed to inhibit the expression of ENST. 740-Y-P was used to activate PI3K. The correlation between ENST expression and clinical outcomes was analyzed.</p><p><strong>Results: </strong>ENST was significantly up-regulated in PTC tissues or PTC cell lines (PTC and IHH4 cell lines), compared to NPTC tissues or normal cell lines, respectively. High expression of ENST was strongly correlated to lymph node metastasis and tumor size at diagnosis. Silencing of ENST significantly inhibited cell growth and colony formation, arrested the cell cycle at G2/M phase, upregulated the expression of CHK1, downregulated the expression of CDC25C, and inhibited cell invasion. Silencing of ENST significantly down-regulated the expression of PI3K, p-PI3K, AKT, and p-AKT in IHH4 cells. Furthermore, treatment with the PI3K activator 740-Y-P partially abolished the effect of silencing of ENST on PTC cells.</p><p><strong>Conclusions: </strong>Overall, our results demonstrated that ENST can promote PTC progression by activating the PI3K/AKT signaling pathway, suggesting that ENST can serve as a potential biomarker and new therapeutic target for patients with PTC.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2020.1804928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38259894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01Epub Date: 2021-03-08DOI: 10.1080/07435800.2021.1894821
Shayan Riahi, Kevin Bryan Lo, Catherine Anastasopoulou, Janani Rangaswami
Our study looked at the relationship between insulin use and clinical outcomes in COVID-19. A response to our article, written by Dr. Chia Sing Kow and Dr. Syed Shahzad Hasan raised a few questions. They mentioned our use of hemoglobin A1c may be inaccurate as the patients in our study had high rates of CKD or ESRD which could alter the hemoglobin A1c levels. However due to the limitations of our patient population and perhaps in a lot of other sample populations in the real-world setting, it was the most feasible way to represent glucose control.The writers also suggested that the use of metformin, a potential confounder, was also not adjusted for. This should be considered in future research but addition of too many variables in a regression model may lead to less reliability of results for our study.The letter writers also suggested that the results of our paper may lead to misinterpretation by readers and may influence providers to not use insulin therapy for their patients when necessary due to fear of worse outcomes in the setting of COVID-19. We reiterated that it is very important that the data not be misinterpreted, and that nowhere in our paper did we imply or suggest that patients who need insulin therapy to treat their diabetes should not receive proper therapy due to the association we delineated in our paper. Instead, more careful surveillance of patients with advanced diabetes is needed especially when admitted with COVID-19.
我们的研究着眼于COVID-19中胰岛素使用与临床结果之间的关系。对于我们的文章,Chia Sing Kow博士和Syed Shahzad Hasan博士提出了一些问题。他们提到我们使用的血红蛋白A1c可能是不准确的,因为我们研究的患者CKD或ESRD的发病率很高,这可能会改变血红蛋白A1c水平。然而,由于我们的患者群体的局限性,也许在现实世界的许多其他样本群体中,这是最可行的方法来表示血糖控制。作者还建议,二甲双胍的使用,一种潜在的混杂因素,也没有调整。在未来的研究中应该考虑到这一点,但是在回归模型中加入太多的变量可能会导致我们研究结果的可靠性降低。这封信的作者还建议,我们论文的结果可能会导致读者的误解,并可能影响提供者在必要时不为患者使用胰岛素治疗,因为他们担心在COVID-19的背景下会出现更糟糕的结果。我们重申,数据不被误解是非常重要的,我们在论文中没有任何地方暗示或建议需要胰岛素治疗的糖尿病患者不应该接受适当的治疗,因为我们在论文中描述的关联。相反,需要对晚期糖尿病患者进行更仔细的监测,特别是在患有COVID-19的患者入院时。
{"title":"Insulin Use and Poor COVID-19 Outcomes among Diabetes Patients: Association Not Necessarily Causation.","authors":"Shayan Riahi, Kevin Bryan Lo, Catherine Anastasopoulou, Janani Rangaswami","doi":"10.1080/07435800.2021.1894821","DOIUrl":"https://doi.org/10.1080/07435800.2021.1894821","url":null,"abstract":"<p><p>Our study looked at the relationship between insulin use and clinical outcomes in COVID-19. A response to our article, written by Dr. Chia Sing Kow and Dr. Syed Shahzad Hasan raised a few questions. They mentioned our use of hemoglobin A1c may be inaccurate as the patients in our study had high rates of CKD or ESRD which could alter the hemoglobin A1c levels. However due to the limitations of our patient population and perhaps in a lot of other sample populations in the real-world setting, it was the most feasible way to represent glucose control.The writers also suggested that the use of metformin, a potential confounder, was also not adjusted for. This should be considered in future research but addition of too many variables in a regression model may lead to less reliability of results for our study.The letter writers also suggested that the results of our paper may lead to misinterpretation by readers and may influence providers to not use insulin therapy for their patients when necessary due to fear of worse outcomes in the setting of COVID-19. We reiterated that it is very important that the data not be misinterpreted, and that nowhere in our paper did we imply or suggest that patients who need insulin therapy to treat their diabetes should not receive proper therapy due to the association we delineated in our paper. Instead, more careful surveillance of patients with advanced diabetes is needed especially when admitted with COVID-19.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2021.1894821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25449860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01Epub Date: 2020-11-04DOI: 10.1080/07435800.2020.1843877
{"title":"Expression of Concern: The effects of vitamin D and evening primrose oil co-supplementation on lipid profiles and biomarkers of oxidative stress in vitamin D-deficient women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.","authors":"","doi":"10.1080/07435800.2020.1843877","DOIUrl":"https://doi.org/10.1080/07435800.2020.1843877","url":null,"abstract":"","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2020.1843877","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38565421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01Epub Date: 2021-02-26DOI: 10.1080/07435800.2021.1892748
Chia Siang Kow, Syed Shahzad Hasan
Previous study reported that preadmission insulin treatment in patients with coronavirus disease 2019 (COVID-19) and concurrent diabetes was associated with a significantly increased odds of mortality. However, such association may be modified by possible baseline differences in glycemic control between insulin users and non-insulin users. Misinterpretation of the association between insulin treatment and mortality could lead to confusion in clinical practice and hospitalized patients with COVID-19 for whom insulin treatment is appropriately indicated may be omitted from such treatment. However, requirement for insulin during hospitalization for COVID-19 may be a marker of poor prognosis and as such could be used to identify patient population who require more aggressive treatments to prevent mortality.
{"title":"Insulin Treatment May Not Be Associated with Increased Mortality in Patients with COVID-19 and Concurrent Diabetes.","authors":"Chia Siang Kow, Syed Shahzad Hasan","doi":"10.1080/07435800.2021.1892748","DOIUrl":"https://doi.org/10.1080/07435800.2021.1892748","url":null,"abstract":"<p><p>Previous study reported that preadmission insulin treatment in patients with coronavirus disease 2019 (COVID-19) and concurrent diabetes was associated with a significantly increased odds of mortality. However, such association may be modified by possible baseline differences in glycemic control between insulin users and non-insulin users. Misinterpretation of the association between insulin treatment and mortality could lead to confusion in clinical practice and hospitalized patients with COVID-19 for whom insulin treatment is appropriately indicated may be omitted from such treatment. However, requirement for insulin during hospitalization for COVID-19 may be a marker of poor prognosis and as such could be used to identify patient population who require more aggressive treatments to prevent mortality.</p>","PeriodicalId":11601,"journal":{"name":"Endocrine Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07435800.2021.1892748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25408650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}