Pub Date : 2024-11-01Epub Date: 2024-05-11DOI: 10.1007/s40618-024-02362-x
M Marconi, M T Pagano, J Ristori, S Bonadonna, R Pivonello, M C Meriggiola, G Motta, F Lombardo, M Mosconi, A Oppo, C Cocchetti, A Romani, S Federici, L Bruno, N Verde, A Lami, C M Crespi, L Marinelli, L Giordani, P Matarrese, A Ruocco, C Santangelo, B Contoli, M Masocco, V Minardi, F Chiarotti, A D Fisher, M Pierdominici
Purpose: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population.
Methods: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP).
Results: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity.
Conclusions: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.
{"title":"Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.","authors":"M Marconi, M T Pagano, J Ristori, S Bonadonna, R Pivonello, M C Meriggiola, G Motta, F Lombardo, M Mosconi, A Oppo, C Cocchetti, A Romani, S Federici, L Bruno, N Verde, A Lami, C M Crespi, L Marinelli, L Giordani, P Matarrese, A Ruocco, C Santangelo, B Contoli, M Masocco, V Minardi, F Chiarotti, A D Fisher, M Pierdominici","doi":"10.1007/s40618-024-02362-x","DOIUrl":"10.1007/s40618-024-02362-x","url":null,"abstract":"<p><strong>Purpose: </strong>Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population.</p><p><strong>Methods: </strong>A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP).</p><p><strong>Results: </strong>TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity.</p><p><strong>Conclusions: </strong>Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-05-15DOI: 10.1007/s40618-024-02388-1
J Lu, X Liu, A Cen, Y Hong, Y Wang
Background: Papillary thyroid carcinoma (PTC) is one of the most common subtypes of thyroid carcinoma. Exosomal miR-181a plays an important role in the development of PTC. This study examined the regulatory mechanism of miR-181a under conditions of hypoxia and its impact on angiogenesis.
Methods: A ribonucleoprotein immunoprecipitation (RIP) experiment was conducted to verify the interaction between HOTAIR and RELA. The relationship between RELA and the miR-181a promoter was detected by ChIP-qPCR. Short hairpin (sh) RNA was designed to knock down HOTAIR in TPC cells. The underlying mechanism of miR-181a was verified by use of dual-luciferase assays and rescue experiments. The regulatory effect of GATA6 on angiogenesis was studied using CCK8, EdU, Transwell, and western blot assays.
Results: A RIP assay showed that HOTAIR could bind to RELA under hypoxic conditions. ChIP-qPCR and dual luciferase assays showed RELA could interact with the miR181a promoter and upregulate miR-181a. Knockdown of HOTAIR downregulated miR-181a in TPC-1 cells, and the downregulation could be rescued by RELA overexpression. MiR-181a downregulated GATA6 in HUVEC cells. Overexpression of GATA6 inhibited HUVEC proliferation, migration, tube formation, and EGFR expression. Exosomal miR-181a promoted angiogenesis by downregulating GATA6 expression.
Conclusion: HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.
{"title":"HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis.","authors":"J Lu, X Liu, A Cen, Y Hong, Y Wang","doi":"10.1007/s40618-024-02388-1","DOIUrl":"10.1007/s40618-024-02388-1","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid carcinoma (PTC) is one of the most common subtypes of thyroid carcinoma. Exosomal miR-181a plays an important role in the development of PTC. This study examined the regulatory mechanism of miR-181a under conditions of hypoxia and its impact on angiogenesis.</p><p><strong>Methods: </strong>A ribonucleoprotein immunoprecipitation (RIP) experiment was conducted to verify the interaction between HOTAIR and RELA. The relationship between RELA and the miR-181a promoter was detected by ChIP-qPCR. Short hairpin (sh) RNA was designed to knock down HOTAIR in TPC cells. The underlying mechanism of miR-181a was verified by use of dual-luciferase assays and rescue experiments. The regulatory effect of GATA6 on angiogenesis was studied using CCK8, EdU, Transwell, and western blot assays.</p><p><strong>Results: </strong>A RIP assay showed that HOTAIR could bind to RELA under hypoxic conditions. ChIP-qPCR and dual luciferase assays showed RELA could interact with the miR181a promoter and upregulate miR-181a. Knockdown of HOTAIR downregulated miR-181a in TPC-1 cells, and the downregulation could be rescued by RELA overexpression. MiR-181a downregulated GATA6 in HUVEC cells. Overexpression of GATA6 inhibited HUVEC proliferation, migration, tube formation, and EGFR expression. Exosomal miR-181a promoted angiogenesis by downregulating GATA6 expression.</p><p><strong>Conclusion: </strong>HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-05-23DOI: 10.1007/s40618-024-02381-8
G Jones, M Kaufmann, R St-Arnaud
Infantile hypercalcemia type 1 (HCINF1), formerly known as Lightwood syndrome, is a subtype of hypercalcemia caused by loss-of-function biallelic mutations in the vitamin D catabolic enzyme, CYP24A1, which 24-hydroxylates the hormone 1,25-(OH)2D3. This short review focuses on the main features of the HCINF1 disease; emerging knowledge of the structure and function of the cytochrome P450, CYP24A1 and the location of inactivating mutations; the development of a rapid LC-MS/MS-based laboratory test for defective 24-hydroxylation; and future implications for bioanalytical assay and treatment of all types of vitamin D-related hypercalcemic conditions.
婴儿高钙血症 1 型(HCINF1),以前称为 Lightwood 综合征,是高钙血症的一种亚型,由维生素 D 分解酶 CYP24A1(24-羟基化激素 1,25-(OH)2D3)的功能缺失双重突变引起。这篇简短的综述主要介绍了 HCINF1 疾病的主要特征;对细胞色素 P450、CYP24A1 结构和功能以及失活突变位置的新认识;基于 LC-MS/MS 的 24- 羟基化缺陷快速实验室检测方法的开发;以及未来对生物分析检测和治疗各类维生素 D 相关高血钙症的影响。
{"title":"Infantile hypercalcemia type 1 (HCINF1): a rare disease resulting in nephrolithiasis and nephrocalcinosis caused by mutations in the vitamin D catabolic enzyme, CYP24A1.","authors":"G Jones, M Kaufmann, R St-Arnaud","doi":"10.1007/s40618-024-02381-8","DOIUrl":"10.1007/s40618-024-02381-8","url":null,"abstract":"<p><p>Infantile hypercalcemia type 1 (HCINF1), formerly known as Lightwood syndrome, is a subtype of hypercalcemia caused by loss-of-function biallelic mutations in the vitamin D catabolic enzyme, CYP24A1, which 24-hydroxylates the hormone 1,25-(OH)<sub>2</sub>D<sub>3</sub>. This short review focuses on the main features of the HCINF1 disease; emerging knowledge of the structure and function of the cytochrome P450, CYP24A1 and the location of inactivating mutations; the development of a rapid LC-MS/MS-based laboratory test for defective 24-hydroxylation; and future implications for bioanalytical assay and treatment of all types of vitamin D-related hypercalcemic conditions.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-05-06DOI: 10.1007/s40618-024-02384-5
M Coskun, H N Sendur, A Babayeva, M N Cerit, E T Cerit, M M Yalcin, A E Altinova, M Akturk, M A Karakoc, F B Toruner
Purpose: The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly.
Methods: This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA.
Results: The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness.
Conclusion: This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.
{"title":"Quantitative ultrasound techniques and biochemical markers to assess liver steatosis and fibrosis in newly diagnosed acromegaly.","authors":"M Coskun, H N Sendur, A Babayeva, M N Cerit, E T Cerit, M M Yalcin, A E Altinova, M Akturk, M A Karakoc, F B Toruner","doi":"10.1007/s40618-024-02384-5","DOIUrl":"10.1007/s40618-024-02384-5","url":null,"abstract":"<p><strong>Purpose: </strong>The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly.</p><p><strong>Methods: </strong>This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA.</p><p><strong>Results: </strong>The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness.</p><p><strong>Conclusion: </strong>This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-08-14DOI: 10.1007/s40618-024-02441-z
I Caruso, L Di Gioia, S Di Molfetta, M Caporusso, A Cignarelli, G P Sorice, L Laviola, F Giorgino
Purpose: Randomized controlled trials with tirzepatide (TZP) displayed unprecedented glucose and body weight lowering efficacy in individuals with type 2 diabetes and/or obesity and a safety profile similar to that of glucagon-like peptide-1 receptor agonists (GLP-1RA), mainly characterized by gastrointestinal (GI) adverse events (AE). Concerns on diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer were also addressed. We aimed to investigate whether the same safety issues emerged from the FDA Adverse Event Reporting System (FAERS) post-marketing surveillance database.
Methods: OpenVigil 2.1-MedDRA-v24 and AERSMine (data 2004Q1-2023Q3) were used to query the FAERS database. Reports of GI AE, diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer were investigated. The analysis was then filtered for age, gender, and designation as primary suspect. AE occurrence with TZP was compared to insulin, sodium-glucose cotransporter-2 inhibitors, metformin, and GLP-1RA.
Results: Disproportionate reporting of GI [i.e., nausea (ROR 4.01, 95% CI 3.85-4.19)] and pancreato-biliary disorders [i.e., pancreatitis (ROR 3.63, 95% CI 3.15-4.19)], diabetic retinopathy (ROR 4.14, 95% CI 2.34-7.30), and medullary thyroid cancer (ROR 13.67, 95% CI 4.35-42.96) was detected. TZP exhibited a similar risk of GI AE and medullary thyroid cancer and a lower risk of most pancreato-biliary AE and diabetic retinopathy vs. GLP-1RA.
Conclusions: TZP was associated with an increased risk of specific AE. However, its safety profile was similar to that of GLP-1RA, without increased risk of pancreato-biliary AE, diabetic retinopathy, and medullary thyroid cancer.
研究目的使用替扎帕肽(TZP)的随机对照试验显示,该药对 2 型糖尿病和/或肥胖症患者具有前所未有的降低血糖和体重的疗效,其安全性与胰高血糖素样肽-1 受体激动剂(GLP-1RA)相似,主要表现为胃肠道(GI)不良事件(AE)。糖尿病视网膜病变、胰胆功能紊乱和甲状腺髓样癌等问题也受到关注。我们旨在调查 FDA 不良事件报告系统(FAERS)上市后监测数据库中是否也出现了同样的安全性问题:方法:使用 OpenVigil 2.1-MedDRA-v24 和 AERSMine(2004Q1-2023Q3 数据)查询 FAERS 数据库。对消化道 AE、糖尿病视网膜病变、胰胆管疾病和甲状腺髓样癌的报告进行了调查。然后根据年龄、性别和主要疑似病例进行筛选分析。将 TZP 的 AE 发生率与胰岛素、钠-葡萄糖共转运体-2 抑制剂、二甲双胍和 GLP-1RA 进行了比较:结果:发现胃肠道疾病[即恶心(ROR 4.01,95% CI 3.85-4.19)]和胰胆疾病[即胰腺炎(ROR 3.63,95% CI 3.15-4.19)]、糖尿病视网膜病变(ROR 4.14,95% CI 2.34-7.30)和甲状腺髓样癌(ROR 13.67,95% CI 4.35-42.96)的报告比例偏高。与GLP-1RA相比,TZP发生消化道AE和甲状腺髓样癌的风险相似,而发生大多数胰胆管AE和糖尿病视网膜病变的风险较低:结论:TZP 与特定 AE 风险增加有关。结论:TZP 会增加特定 AE 的风险,但其安全性与 GLP-1RA 相似,不会增加胰胆管 AE、糖尿病视网膜病变和甲状腺髓样癌的风险。
{"title":"The real-world safety profile of tirzepatide: pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database.","authors":"I Caruso, L Di Gioia, S Di Molfetta, M Caporusso, A Cignarelli, G P Sorice, L Laviola, F Giorgino","doi":"10.1007/s40618-024-02441-z","DOIUrl":"10.1007/s40618-024-02441-z","url":null,"abstract":"<p><strong>Purpose: </strong>Randomized controlled trials with tirzepatide (TZP) displayed unprecedented glucose and body weight lowering efficacy in individuals with type 2 diabetes and/or obesity and a safety profile similar to that of glucagon-like peptide-1 receptor agonists (GLP-1RA), mainly characterized by gastrointestinal (GI) adverse events (AE). Concerns on diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer were also addressed. We aimed to investigate whether the same safety issues emerged from the FDA Adverse Event Reporting System (FAERS) post-marketing surveillance database.</p><p><strong>Methods: </strong>OpenVigil 2.1-MedDRA-v24 and AERSMine (data 2004Q1-2023Q3) were used to query the FAERS database. Reports of GI AE, diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer were investigated. The analysis was then filtered for age, gender, and designation as primary suspect. AE occurrence with TZP was compared to insulin, sodium-glucose cotransporter-2 inhibitors, metformin, and GLP-1RA.</p><p><strong>Results: </strong>Disproportionate reporting of GI [i.e., nausea (ROR 4.01, 95% CI 3.85-4.19)] and pancreato-biliary disorders [i.e., pancreatitis (ROR 3.63, 95% CI 3.15-4.19)], diabetic retinopathy (ROR 4.14, 95% CI 2.34-7.30), and medullary thyroid cancer (ROR 13.67, 95% CI 4.35-42.96) was detected. TZP exhibited a similar risk of GI AE and medullary thyroid cancer and a lower risk of most pancreato-biliary AE and diabetic retinopathy vs. GLP-1RA.</p><p><strong>Conclusions: </strong>TZP was associated with an increased risk of specific AE. However, its safety profile was similar to that of GLP-1RA, without increased risk of pancreato-biliary AE, diabetic retinopathy, and medullary thyroid cancer.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-05-02DOI: 10.1007/s40618-024-02377-4
S Heydarzadeh, A A Moshtaghie, M Daneshpour, M Hedayati
Aims and background: The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake.
Material methods: The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, ''GOD-PAP'' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting.
Results: According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group.
Conclusion: Multiple mechanisms point to Rutin's role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment.
{"title":"Regulation of iodine-glucose flip-flop in SW1736 anaplastic thyroid cancer cell line.","authors":"S Heydarzadeh, A A Moshtaghie, M Daneshpour, M Hedayati","doi":"10.1007/s40618-024-02377-4","DOIUrl":"10.1007/s40618-024-02377-4","url":null,"abstract":"<p><strong>Aims and background: </strong>The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake.</p><p><strong>Material methods: </strong>The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, ''GOD-PAP'' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting.</p><p><strong>Results: </strong>According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group.</p><p><strong>Conclusion: </strong>Multiple mechanisms point to Rutin's role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1007/s40618-024-02492-2
Laura Dery, Ilan Shimon, Yaron Rudman, Hiba Masri Iraqi, Shiri Kushnir, Tzipora Shochat, Odelia Cooper, Amit Akirov
Purpose: Given prolactin's (PRL) multifaceted roles in mammary tissue, an association between hyperprolactinemia and breast cancer has been hypothesized. Despite previous studies not identifying this risk, we aimed to investigate whether a connection exists.
Methods: This retrospective cohort study compared breast cancer incidence in patients with dopamine agonist (DA)-treated hyperprolactinemia versus matched controls in a 1:5 ratio. The primary outcome was a breast cancer diagnosis following hyperprolactinemia diagnosis.
Results: The cohort consisted of 1484 female patients with DA-treated hyperprolactinemia matched to 7418 female controls (mean age at diagnosis 32.70 ± 11.12 years; BMI 25.60 ± 5.84 kg/m2). Breast cancer was diagnosed in 27 patients with hyperprolactinemia (1.82%) and 97 controls (1.31%) (HR 1.40, 95% CI 0.91-2.14, p = 0.12). Patients who developed breast cancer were diagnosed with hyperprolactinemia later in life than those who did not (median age 42.63 vs. 29.79 years; p < 0.0001). Patients with PRL < 5× upper limit of normal (ULN) at diagnosis developed breast cancer at a higher rate than controls (2.25% vs. 1.33%; HR 1.73, 95% CI 1.09-2.75), but the difference was not significant in patients with PRL ≥ 5×ULN. Patients who exhibited longer times to PRL normalization had higher incidence of breast cancer (median 2.60 vs. 1.41 years in those who did not develop breast cancer; p = 0.03).
Conclusion: Overall, patients with DA-treated hyperprolactinemia did not show an increased risk for breast cancer compared to controls. However, the risk was significantly higher among those whose PRL levels were < 5×ULN, had advanced age of diagnosis, or prolonged time to PRL normalization.
{"title":"Breast Cancer risk in patients with dopamine agonist-treated hyperprolactinemia.","authors":"Laura Dery, Ilan Shimon, Yaron Rudman, Hiba Masri Iraqi, Shiri Kushnir, Tzipora Shochat, Odelia Cooper, Amit Akirov","doi":"10.1007/s40618-024-02492-2","DOIUrl":"https://doi.org/10.1007/s40618-024-02492-2","url":null,"abstract":"<p><strong>Purpose: </strong>Given prolactin's (PRL) multifaceted roles in mammary tissue, an association between hyperprolactinemia and breast cancer has been hypothesized. Despite previous studies not identifying this risk, we aimed to investigate whether a connection exists.</p><p><strong>Methods: </strong>This retrospective cohort study compared breast cancer incidence in patients with dopamine agonist (DA)-treated hyperprolactinemia versus matched controls in a 1:5 ratio. The primary outcome was a breast cancer diagnosis following hyperprolactinemia diagnosis.</p><p><strong>Results: </strong>The cohort consisted of 1484 female patients with DA-treated hyperprolactinemia matched to 7418 female controls (mean age at diagnosis 32.70 ± 11.12 years; BMI 25.60 ± 5.84 kg/m<sup>2</sup>). Breast cancer was diagnosed in 27 patients with hyperprolactinemia (1.82%) and 97 controls (1.31%) (HR 1.40, 95% CI 0.91-2.14, p = 0.12). Patients who developed breast cancer were diagnosed with hyperprolactinemia later in life than those who did not (median age 42.63 vs. 29.79 years; p < 0.0001). Patients with PRL < 5× upper limit of normal (ULN) at diagnosis developed breast cancer at a higher rate than controls (2.25% vs. 1.33%; HR 1.73, 95% CI 1.09-2.75), but the difference was not significant in patients with PRL ≥ 5×ULN. Patients who exhibited longer times to PRL normalization had higher incidence of breast cancer (median 2.60 vs. 1.41 years in those who did not develop breast cancer; p = 0.03).</p><p><strong>Conclusion: </strong>Overall, patients with DA-treated hyperprolactinemia did not show an increased risk for breast cancer compared to controls. However, the risk was significantly higher among those whose PRL levels were < 5×ULN, had advanced age of diagnosis, or prolonged time to PRL normalization.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1007/s40618-024-02473-5
Z M Song, Y D Wang, F Chai, J Zhang, S Lv, J X Wang, Y Xi
Background: Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development.
Methods: The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING.
Results: Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway.
Conclusions: Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.
{"title":"Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis.","authors":"Z M Song, Y D Wang, F Chai, J Zhang, S Lv, J X Wang, Y Xi","doi":"10.1007/s40618-024-02473-5","DOIUrl":"https://doi.org/10.1007/s40618-024-02473-5","url":null,"abstract":"<p><strong>Background: </strong>Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development.</p><p><strong>Methods: </strong>The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING.</p><p><strong>Results: </strong>Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway.</p><p><strong>Conclusions: </strong>Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1007/s40618-024-02474-4
Eman A Mostafa, Nagwa Abdallah Ismail, Abeer M Nour El Din Abd El Baky, Tarek F ElShaer, Ingy Ashmawy, Aliaa Ahmed Wahby, Mai Magdy Abdel Wahed, Shereen Hamdy Abd El Aziz
Purpose: Type 1 diabetes (T1D) is a chronic autoimmune illness that results in loss of pancreatic beta cells and insulin insufficiency. MicroRNAs (miRNAs) are linked to immune system functions contributing to the pathophysiology of T1D, miRNA-375 is significantly expressed in the human pancreas and its circulatory levels might correspond to beta cell alterations. Pancreatic islet cell antibodies (ICA) and Glutamic acid decarboxylase antibodies (GADA) have roles in autoimmune pathogenesis and are predictive markers of T1D. The aim of this work was to detect serum level changes of miRNA-375, ICA, and GADA in T1D patients, and their siblings compared to healthy controls and correlate them with T1D biochemical parameters.
Methods: The study included 66 T1D patients (32 males and 34 females; age range 3-18 years), 22 patients' siblings (13 males and 9 females; age range 4-17 years), and 23 healthy controls (7 males and 16 females; age range 4-17 years). MiRNA-375 levels were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR), while ICA and GADA levels were measured using enzyme-linked immunosorbent assay (ELISA). Data analysis was done utilizing SPSS-17 software.
Results: MiR-375 levels were downregulated in T1D patients and further decreased in their siblings when compared to healthy controls. Furthermore, miR-375 exhibited inverse correlations with HbA1c levels but no correlations with Total Insulin Dose, disease duration, or autoantibodies (GADA & ICA).
Conclusion: Our study indicates that miR-375 is significantly downregulated in children with T1D and their siblings, suggesting its potential role as a biomarker for beta-cell function and glycemic control.
{"title":"MiR-375: it could be a general biomarker of metabolic changes and inflammation in type 1 diabetes patients and their siblings.","authors":"Eman A Mostafa, Nagwa Abdallah Ismail, Abeer M Nour El Din Abd El Baky, Tarek F ElShaer, Ingy Ashmawy, Aliaa Ahmed Wahby, Mai Magdy Abdel Wahed, Shereen Hamdy Abd El Aziz","doi":"10.1007/s40618-024-02474-4","DOIUrl":"https://doi.org/10.1007/s40618-024-02474-4","url":null,"abstract":"<p><strong>Purpose: </strong>Type 1 diabetes (T1D) is a chronic autoimmune illness that results in loss of pancreatic beta cells and insulin insufficiency. MicroRNAs (miRNAs) are linked to immune system functions contributing to the pathophysiology of T1D, miRNA-375 is significantly expressed in the human pancreas and its circulatory levels might correspond to beta cell alterations. Pancreatic islet cell antibodies (ICA) and Glutamic acid decarboxylase antibodies (GADA) have roles in autoimmune pathogenesis and are predictive markers of T1D. The aim of this work was to detect serum level changes of miRNA-375, ICA, and GADA in T1D patients, and their siblings compared to healthy controls and correlate them with T1D biochemical parameters.</p><p><strong>Methods: </strong>The study included 66 T1D patients (32 males and 34 females; age range 3-18 years), 22 patients' siblings (13 males and 9 females; age range 4-17 years), and 23 healthy controls (7 males and 16 females; age range 4-17 years). MiRNA-375 levels were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR), while ICA and GADA levels were measured using enzyme-linked immunosorbent assay (ELISA). Data analysis was done utilizing SPSS-17 software.</p><p><strong>Results: </strong>MiR-375 levels were downregulated in T1D patients and further decreased in their siblings when compared to healthy controls. Furthermore, miR-375 exhibited inverse correlations with HbA1c levels but no correlations with Total Insulin Dose, disease duration, or autoantibodies (GADA & ICA).</p><p><strong>Conclusion: </strong>Our study indicates that miR-375 is significantly downregulated in children with T1D and their siblings, suggesting its potential role as a biomarker for beta-cell function and glycemic control.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1007/s40618-024-02480-6
T Piticchio, C Luongo, P Trimboli, D Salvatore, F Frasca
Purpose: Hypothalamic-pituitary thyrotropic activity (HPta) is crucial since TSH is the mainstay for evaluating primary hypothyroidism (hT) and replacement therapy in clinical practice. Despite TSH values, some patients experience symptoms and metabolic alterations, raising several issues about hT. The aim of the study was to investigate factors influencing the TSH values achieved after a period of hT induced in a standardized and controlled manner (TSH_time1).
Methods: Our institutional database was searched to extract records of differentiated thyroid cancer (DTC) patients undergoing a LT4 withdrawal protocol prior to radioiodine (RAI) administration. We collected clinical and biochemical parameters before LT4 discontinuation and after one month of induced hT. We performed Mann-Whitney U-test and linear regression analyses.
Results: We included 102 patients, with a median age of 44 years. In univariate analyses, TSH_time1 was correlated with age (p 0.005) and the dose pro Kg/die of LT4 assumed until the discontinuation of LT4 (LT4_dose) (p 0.023). The higher the age, the lower the TSH_time1 level. The higher the LT4_dose, the higher the TSH_time1 level. After multivariate analysis, the fittest model included age, BMI, LT4_dose, and systemic inflammation response index with an adjusted R2 of 0.4.
Conclusion: The study highlights new mechanisms that influence HPta. HPta progressively reduces with age, and this must be considered when evaluating TSH values in the elderly. Furthermore, we report for the first time a rebound effect of HPta, determined by the dose pro Kg/die of LT4 taken prior to its discontinuation. Inflammation and metabolic status also affect these phenomena.
{"title":"Rebound effect of hypothalamic-pituitary thyreotropic activity: a new model to better understand hypothyroidism.","authors":"T Piticchio, C Luongo, P Trimboli, D Salvatore, F Frasca","doi":"10.1007/s40618-024-02480-6","DOIUrl":"https://doi.org/10.1007/s40618-024-02480-6","url":null,"abstract":"<p><strong>Purpose: </strong>Hypothalamic-pituitary thyrotropic activity (HPta) is crucial since TSH is the mainstay for evaluating primary hypothyroidism (hT) and replacement therapy in clinical practice. Despite TSH values, some patients experience symptoms and metabolic alterations, raising several issues about hT. The aim of the study was to investigate factors influencing the TSH values achieved after a period of hT induced in a standardized and controlled manner (TSH_time1).</p><p><strong>Methods: </strong>Our institutional database was searched to extract records of differentiated thyroid cancer (DTC) patients undergoing a LT4 withdrawal protocol prior to radioiodine (RAI) administration. We collected clinical and biochemical parameters before LT4 discontinuation and after one month of induced hT. We performed Mann-Whitney U-test and linear regression analyses.</p><p><strong>Results: </strong>We included 102 patients, with a median age of 44 years. In univariate analyses, TSH_time1 was correlated with age (p 0.005) and the dose pro Kg/die of LT4 assumed until the discontinuation of LT4 (LT4_dose) (p 0.023). The higher the age, the lower the TSH_time1 level. The higher the LT4_dose, the higher the TSH_time1 level. After multivariate analysis, the fittest model included age, BMI, LT4_dose, and systemic inflammation response index with an adjusted R<sup>2</sup> of 0.4.</p><p><strong>Conclusion: </strong>The study highlights new mechanisms that influence HPta. HPta progressively reduces with age, and this must be considered when evaluating TSH values in the elderly. Furthermore, we report for the first time a rebound effect of HPta, determined by the dose pro Kg/die of LT4 taken prior to its discontinuation. Inflammation and metabolic status also affect these phenomena.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}