首页 > 最新文献

Journal of Endocrinological Investigation最新文献

英文 中文
Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population. 意大利变性和性别多元化成年人群的社会人口概况、健康相关行为和就医体验。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-11-01 Epub Date: 2024-05-11 DOI: 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.

目的:有关变性者和性别多元化者(TGD)总体健康状况的信息仍然缺乏。为了填补这一空白,意大利国家卫生研究院(National Institute of Health)与国家反种族歧视办公室(National Office against Racial Discriminations)、临床中心和变性者组织共同开展了一项横断面研究,以确定意大利变性者成年人群的社会人口概况、健康相关行为和获得医疗保健的经历:方法:采用计算机辅助网络访谈(CAWI)技术进行了一项全国性调查。方法:采用计算机辅助网络访谈(CAWI)技术进行了一次全国性调查,对收集到的数据在 TGD 亚群内部进行了比较,并在 TGD人群和意大利普通人群(IGP)之间进行了比较:959 名 TGD 受访者中,65% 出生时被分配为女性(AFAB),35% 出生时被分配为男性(AMAB)。91.8%和 8.2%的受访者为二元和非二元 TGD。据报告,超过 20% 的 TGD 人口处于失业状态,其中,AMAB 和非二元人群的失业率最高。与 IGP 相比,TGD 人群中吸烟和酗酒的比例更高(p 结论:我们的研究结果是了解 TGD 人群中吸烟和酗酒情况的第一步:我们的研究结果为更好地了解意大利 TGD 人口的健康需求迈出了第一步,以便为更具包容性的公共卫生规划最佳政策选择。
{"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}
引用次数: 0
HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis. HYPOXIA诱导lncRNA HOTAIR招募甲状腺乳头状癌细胞中的RELA,从而上调miR-181a并促进血管生成。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-11-01 Epub Date: 2024-05-15 DOI: 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.

背景:甲状腺乳头状癌(PTC)是甲状腺癌最常见的亚型之一。外泌体miR-181a在PTC的发展过程中起着重要作用。本研究探讨了缺氧条件下miR-181a的调控机制及其对血管生成的影响:方法:通过核糖核蛋白免疫沉淀(RIP)实验验证了HOTAIR与RELA之间的相互作用。通过 ChIP-qPCR 检测 RELA 与 miR-181a 启动子之间的关系。设计了短发夹(sh)RNA 来敲除 TPC 细胞中的 HOTAIR。利用双荧光素酶测定和拯救实验验证了 miR-181a 的内在机制。利用 CCK8、EdU、Transwell 和 Western 印迹实验研究了 GATA6 对血管生成的调控作用:RIP试验表明,在缺氧条件下,HOTAIR能与RELA结合。ChIP-qPCR和双荧光素酶检测表明,RELA能与miR181a启动子相互作用并上调miR-181a。敲除 HOTAIR 会下调 TPC-1 细胞中的 miR-181a,而 RELA 的过表达可以挽救这种下调。MiR-181a 下调了 HUVEC 细胞中的 GATA6。过表达 GATA6 可抑制 HUVEC 的增殖、迁移、管形成和表皮生长因子受体的表达。外泌体 miR-181a 通过下调 GATA6 的表达促进血管生成:结论:缺氧时,HOTAIR 激活 RELA 上调 miR-181a。外泌体miR-181a通过下调GATA6促进肿瘤血管生成。
{"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}
引用次数: 0
Infantile hypercalcemia type 1 (HCINF1): a rare disease resulting in nephrolithiasis and nephrocalcinosis caused by mutations in the vitamin D catabolic enzyme, CYP24A1. 婴儿高钙血症 1 型(HCINF1):一种罕见疾病,由维生素 D 分解酶 CYP24A1 基因突变引起,可导致肾炎和肾钙化。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-11-01 Epub Date: 2024-05-23 DOI: 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}
引用次数: 0
Quantitative ultrasound techniques and biochemical markers to assess liver steatosis and fibrosis in newly diagnosed acromegaly. 用定量超声技术和生化指标评估新诊断的肢端肥大症患者的肝脏脂肪变性和纤维化。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-11-01 Epub Date: 2024-05-06 DOI: 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.

目的:众所周知,在高GH/IGF-1的影响下,肝脏可免受脂肪变性的影响。细胞角蛋白 18 (CK18) 和胰岛素样生长因子结合蛋白 7 (IGFBP7) 在肝脏脂肪变性和纤维化时会增加。本研究旨在使用定量超声技术和生化指标评估新诊断的肢端肥大症患者的肝脏脂肪变性和肝纤维化情况:这项单中心横断面研究包括23名新确诊的肢端肥大症患者和46名年龄、性别、体重指数(BMI)和腰围(WC)匹配的对照组。采用组织衰减成像(TAI)评估肝脏脂肪变性,采用剪切波弹性成像(SWE)评估表明肝纤维化的硬度。血清 IGFBP7 和 CK18 通过酶联免疫吸附进行研究:结果:与对照组相比,肢端肥大症组的肝脏脂肪变性(p = 0.006)明显降低,肝脏硬度(p = 0.004)、血清 IGFBP7(p = 0.048)和 CK18(p = 0.005)水平明显升高。肢端肥大症组的纤维化程度(p = 0.012)明显高于对照组。此外,CK18与肝脏硬度、体重、HOMA-IR、血红蛋白A1c和甘油三酯呈正相关。在肢端肥大症组,肝脏脂肪变性与 GH 水平呈负相关。逐步多元线性回归分析显示,体重指数(P = 0.008)和 CK18(P = 0.015)是肝硬变增加的独立风险因素:本研究表明,在新诊断的肢端肥大症患者中,肝纤维化的存在与肝脂肪变性无关。血清CK18似乎是肢端肥大症肝纤维化增加的潜在标志物。
{"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}
引用次数: 0
The real-world safety profile of tirzepatide: pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database. Tirzepatide 的真实世界安全概况:对 FDA 不良事件报告系统 (FAERS) 数据库的药物警戒分析。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-11-01 Epub Date: 2024-08-14 DOI: 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}
引用次数: 0
Regulation of iodine-glucose flip-flop in SW1736 anaplastic thyroid cancer cell line. SW1736无性甲状腺癌细胞系中碘-葡萄糖翻转的调控。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-11-01 Epub Date: 2024-05-02 DOI: 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.

目的和背景:在不同类型的甲状腺癌中发现了碘和葡萄糖摄取的另一种方式,即 "翻转"(flip-flop)。ATC 细胞碘摄取量低而葡萄糖摄取量高,缺乏分化良好肿瘤的形态和遗传特征,侵袭性越来越强。发现创新的多靶点药物来抑制癌症中失调的信号传导,具有重要意义。在这项研究中,我们旨在根据碘化物和葡萄糖的摄取,阐明芦丁作为一种植物药对无性甲状腺癌细胞株的分子机制:材料方法:采用MTT试验检测细胞活力。碘吸收检测采用分光光度法,根据桑德尔-科尔索夫反应测定 SW1736 细胞对碘的吸收。葡萄糖吸收检测采用 "GOD-PAP "酶比色法,直接测定细胞内的葡萄糖水平。采用 qRT-PCR 技术检测 SW1736 细胞中 NIS、GLUT1 和 3 mRNA 的表达。用 Western 印迹法测定 SW1736 细胞中 NIS、GLUT1 和 3 蛋白水平:结果:芦丁对 SW1736 细胞活力的抑制具有时间和剂量依赖性。Real-time RT-PCR 定量分析显示,与对照组相比,芦丁处理组的 NIS mRNA 水平升高。相应地,Western 印迹显示芦丁处理的 SW1736 细胞株中 NIS 蛋白高表达,而 GLUT 1 和 3 低表达。与对照组相比,芦丁提高了甲状腺癌细胞株 SW1736 的碘摄取量,降低了葡萄糖摄取量:多种机制表明,芦丁是碘摄取的主要刺激剂和葡萄糖摄取的抑制剂,包括在 mRNA 和蛋白质水平分别对 NIS 和 GLUTs 产生影响。在这里,我们将翻转现象描述为一种可能的 ATC 治疗靶点。此外,本文首次证实芦丁是一种 NIS 表达诱导剂,能够恢复 SW1736 细胞系的细胞分化。由此也可以得出结论,芦丁可以特异性地阻断作为代谢靶点的GLUTs,从而达到预防和治疗甲状腺癌的目的。
{"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}
引用次数: 0
Breast Cancer risk in patients with dopamine agonist-treated hyperprolactinemia. 多巴胺受体激动剂治疗的高泌乳素血症患者患乳腺癌的风险。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-10-30 DOI: 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.

目的:鉴于催乳素(PRL)在乳腺组织中的多方面作用,人们假设高催乳素血症与乳腺癌之间存在关联。尽管之前的研究并未发现这种风险,但我们仍希望调查两者之间是否存在联系:这项回顾性队列研究比较了多巴胺受体激动剂(DA)治疗的高泌乳素血症患者与匹配对照组的乳腺癌发病率,两者的比例为 1:5。主要结果是确诊高泌乳素血症后的乳腺癌诊断结果:研究对象包括1484名经DA治疗的高泌乳素血症女性患者和7418名女性对照组患者(诊断时平均年龄为32.70 ± 11.12岁;体重指数为25.60 ± 5.84 kg/m2)。27名高泌乳素血症患者(1.82%)和97名对照组患者(1.31%)被确诊为乳腺癌(HR 1.40,95% CI 0.91-2.14,P = 0.12)。与未患乳腺癌的患者相比,患乳腺癌的患者被诊断出患有高泌乳素血症的时间较晚(中位年龄为 42.63 岁对 29.79 岁;P 结论:高泌乳素血症患者的中位年龄为 42.63 岁对 29.79 岁:总体而言,与对照组相比,经 DA 治疗的高催乳素血症患者罹患乳腺癌的风险并没有增加。但是,PRL 水平达到中位数的患者罹患乳腺癌的风险明显较高。
{"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}
引用次数: 0
Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis. 雌激素通过ERα/KRT19信号轴增强甲状腺乳头状癌的增殖、迁移和侵袭。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-10-25 DOI: 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.

背景:雌激素被认为是生育期妇女甲状腺乳头状癌(PTC)发病率较高的原因;然而,要完全理解雌激素如何在细胞水平上影响PTC的发展还需要更多的研究。因此,我们结合牛津纳米孔技术(ONT)测序来探索PTC的分子标记物,并研究雌激素促进PTC发展的分子机制:通过Ualcan在线分析了ESR1(ERα)和KRT19在正常甲状腺组织和癌组织中的表达水平,以及在TCGA数据库中不同癌症分期、种族、性别、年龄组、组织学亚型和结节转移状态中的表达水平;分析了ESR1、KRT19与THCA患者生存期的关系。建立了PTC异种移植肿瘤模型。使用ERα特异性抑制剂(MPP)和EDU细胞增殖试验来验证雌激素对PTC增殖的影响。在 KTC-1 细胞中敲除 KRT19,并使用 CCK-8、免疫荧光标记、EMT 相关蛋白 Western 印迹、划痕试验和 Transwell 试验测定 PTC 细胞的增殖、迁移和侵袭能力。通过 Western 印迹和免疫荧光研究了 ERα 与 KRT19 的关系。利用 EDU 细胞增殖试验和 Transwell 试验评估了 ERα/KRT19 信号轴对 PTC 细胞增殖、迁移和侵袭能力的影响。通过 ONT 测序,收集了 15 对 PTC 组织和癌旁组织样本。结合生物特征分析构建了PPI网络以验证KRT19的差异表达,并利用STRING验证了KRT19与ESR1之间的蛋白相互作用:结果:Ualcan显示ESR1和KRT19在THCA组织中的表达高于正常甲状腺组织。ERα 的 E2 激活促进了 PTC 细胞和组织的生长,而 si-KRT19 则抑制了 PTC 细胞的增殖、迁移和侵袭。KRT19与ERα共同组成了ERα/KRT19信号轴。E2激活ERα/KRT19信号轴促进了PTC细胞的增殖、迁移和侵袭。ONT测序和STRING网站验证了KRT19在PTC中有显著差异表达,ESR1和KRT19有蛋白相互作用,与雌激素信号通路有关:利用公共数据库、RNA测序和生物信息学,我们发现E2刺激ERα/KRT19信号轴,从而刺激PTC的增殖、迁移和侵袭。
{"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}
引用次数: 0
MiR-375: it could be a general biomarker of metabolic changes and inflammation in type 1 diabetes patients and their siblings. MiR-375:它可能是 1 型糖尿病患者及其兄弟姐妹代谢变化和炎症的一般生物标志物。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-10-25 DOI: 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.

目的:1 型糖尿病(T1D)是一种慢性自身免疫性疾病,会导致胰岛β细胞丧失和胰岛素分泌不足。微小核糖核酸(miRNAs)与免疫系统功能有关,有助于 T1D 的病理生理学,miRNA-375 在人类胰腺中显著表达,其循环水平可能与β细胞的改变相对应。胰岛细胞抗体(ICA)和谷氨酸脱羧酶抗体(GADA)在自身免疫发病机制中发挥作用,是 T1D 的预测标志物。本研究旨在检测 T1D 患者及其兄弟姐妹与健康对照组相比血清中 miRNA-375、ICA 和 GADA 水平的变化,并将其与 T1D 生化指标相关联:研究对象包括 66 名 T1D 患者(32 名男性和 34 名女性;年龄范围为 3-18 岁)、22 名患者的兄弟姐妹(13 名男性和 9 名女性;年龄范围为 4-17 岁)和 23 名健康对照者(7 名男性和 16 名女性;年龄范围为 4-17 岁)。MiRNA-375 的水平采用定量反转录聚合酶链反应(RT-qPCR)法测定,而 ICA 和 GADA 的水平则采用酶联免疫吸附试验(ELISA)法测定。数据分析采用 SPSS-17 软件:结果:与健康对照组相比,T1D 患者体内的 MiR-375 水平下调,其兄弟姐妹体内的 MiR-375 水平进一步下降。此外,miR-375 与 HbA1c 水平呈反相关,但与胰岛素总剂量、病程或自身抗体(GADA 和 ICA)无相关性:我们的研究表明,miR-375 在 T1D 儿童及其兄弟姐妹中明显下调,这表明它可能成为β细胞功能和血糖控制的生物标志物。
{"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}
引用次数: 0
Rebound effect of hypothalamic-pituitary thyreotropic activity: a new model to better understand hypothyroidism. 下丘脑-垂体促甲状腺激素活动的反弹效应:更好地理解甲状腺功能减退症的新模型。
IF 5.4 2区 医学 Q1 Medicine Pub Date : 2024-10-21 DOI: 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.

目的:下丘脑-垂体促甲状腺激素活性(HPta)至关重要,因为 TSH 是评估原发性甲状腺功能减退症(hT)和临床替代疗法的主要依据。尽管存在 TSH 值,但一些患者仍会出现症状和新陈代谢改变,这就提出了有关 hT 的几个问题。本研究的目的是调查影响以标准化和受控方式(TSH_time1)诱导 hT 一段时间后 TSH 值的因素:我们搜索了本机构的数据库,提取了在使用放射性碘(RAI)前接受LT4停药方案的分化型甲状腺癌(DTC)患者的记录。我们收集了停用LT4前和诱导hT一个月后的临床和生化指标。我们进行了曼-惠特尼 U 检验和线性回归分析:我们共纳入 102 名患者,中位年龄为 44 岁。在单变量分析中,TSH_time1 与年龄(P 0.005)和停用 LT4 前的 LT4 剂量(LT4_dose)(P 0.023)相关。年龄越大,TSH_time1 水平越低。LT4_剂量越大,TSH_time1水平越高。经过多变量分析,最适合的模型包括年龄、体重指数、LT4_剂量和全身炎症反应指数,调整后的R2为0.4:该研究强调了影响 HPta 的新机制。HPta会随着年龄的增长而逐渐降低,在评估老年人的促甲状腺激素值时必须考虑到这一点。此外,我们首次报告了 HPta 的反弹效应,该效应由停药前服用的 LT4 剂量 pro Kg/die 决定。炎症和代谢状态也会影响这些现象。
{"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}
引用次数: 0
期刊
Journal of Endocrinological Investigation
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1