Endocrine regulations最新文献

{"title":"Statistically verified methods for determining predictors of development of arterial hypertension depending on endothelial nitric oxide synthase T786C gene promoter polymorphism using lipid profile indicators.","authors":"Svitlana Pidruchna, Volodimir Shmanko, Roman Hnizdyukh, Andrii Sverstiuk, Petro Lykhatskyy, Iryna Kuzmak, Tetyana Yaroshenko, Iryna Bandas, Nadya Vasylyshyn, Oksana Ostrivka, Alla Mudra, Lylya Palytsia, Nataliya Letnyak, Oleksandr Tokarskyy","doi":"10.2478/enr-2024-0015","DOIUrl":"10.2478/enr-2024-0015","url":null,"abstract":"<p><p><b>Objective.</b> Polymorphism investigation of T786C gene promoter of endothelial nitric oxide synthase (eNOS/NOS3) in the arterial hypertension is a promising field for determining the relationship between heredity, hypertension, and dyslipidemia, which still remains controversial. The purpose of the study was to investigate the lipid profile, which depends on the NOS3 T786C gene promotor region polymorphism in patients with arterial hypertension. <b>Methods.</b> The study involved 86 patients with arterial hypertension. The control group consisted of 30 basically healthy individuals. The lipid profile in the blood serum of the studied patients was measured by commercially available kits using Biochem FC-200 analyzer (HTI, USA). The allelic polymorphism of NOS3 T786C gene promoter was studied using a polymerase chain reaction technique with electrophoretic detection of the results. <b>Results.</b> An increase at the level of all atherogenic fractions in the blood was found in the group of patients carrying the CC genotype compared with carriers of the TT genotype of the NOS3 gene. The total cholesterol serum level in the group of carriers of the CC genotype of NOS3 T786C gene promoter increased by 33.3% compared with carriers of the TT genotype and it was almost twice as high as the control values. In the group of carriers in the CC genotype of the NOS3 gene, the serum level of triglycerides was statistically significantly higher (2.9 times) than in the group of carriers of the TT genotype. The low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) serum levels significantly increased in patients with arterial hypertension with the CC genotype by 1.6 and 4.6 times, respectively, compared with the TT genotype carriers. The high-density lipoprotein (HDL) serum level, as an antiatherogenic factor, was statistically significantly lower (by 45.8%) in the group of the CC genotype carriers of the NOS3 gene than in the group with carriers of the TT genotype (0.58±0.06 vs. 1.07±0.03 mmol/l.) <b>Conclusions.</b> The increase in all atherogenic and decrease in antiatherogenic lipid parameters of the lipidogram of patients with arterial hypertension and the deepening of dyslipidemia in carriers of the CC genotype compared with carriers of the TT genotype of the NOS3 T786C gene promoter is crucial in the development of dyslipidemia.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"138-143"},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress-dependent regulation of the expression of serine hydroxymethyltransferase 2 in glioblastoma cells.","authors":"Oleksandr H Minchenko, Myroslava Y Sliusar, Olena O Khita, Yuliia M Viletska, Olha Y Luzina, Serhiy V Danilovskyi, Dmytro O Minchenko","doi":"10.2478/enr-2024-0016","DOIUrl":"10.2478/enr-2024-0016","url":null,"abstract":"<p><p><b>Objective.</b> Serine hydroxymethyltransferase (SHMT2) plays a multifunctional role in mitochondria (folate-dependent tRNA methylation, translation, and thymidylate synthesis). The endoplasmic reticulum stress, hypoxia, and glucose and glutamine supply are significant factors of malignant tumor growth including glioblastoma. Previous studies have shown that the knockdown of the endoplasmic reticulum to nucleus signaling 1 (ERN1) pathway of endoplasmic reticulum stress strongly suppressed glioblastoma cell proliferation and modified the sensitivity of these cells to hypoxia and glucose or glutamine deprivations. The present study aimed to investigate the regulation of the <i>SHMT2</i> gene in U87MG glioblastoma cells by ERN1 knockdown, hypoxia, and glucose or glutamine deprivations with the intent to reveal the role of ERN1 signaling in sensitivity of this gene expression to hypoxia and nutrient supply. <b>Methods.</b> The control U87MG glioblastoma cells (transfected by an empty vector) and ERN1 knockdown cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) or only ERN1 endoribonuclease (dnrERN1) were used. Hypoxia was introduced by dimethyloxalylglycine (500 ng/ml for 4 h). For glucose and glutamine deprivations, cells were exposed in DMEM without glucose and glutamine, respectively for 16 h. RNA was extracted from cells and reverse transcribed. The expression level of the <i>SHMT2</i> gene was studied by real-time qPCR and normalized to ACTB. <b>Results.</b> It was found that inhibition of ERN1 endoribonuclease and protein kinase in glioblastoma cells led to a down-regulation of <i>SHMT2</i> gene expression in U87MG cells. At the same time, the expression of this gene did not significantly change in cells with inhibited ERN1 endoribonuclease, but tunicamycin strongly increased its expression. Moreover, the expression of the <i>SHMT2</i> gene was not affected in U87MG cells after silencing of XBP1. Hypoxia up-regulated the expression level of the <i>SHMT2</i> gene in both control and ERN1 knockdown U87MG cells. The expression of this gene was significantly up-regulated in glioblastoma cells under glucose and glutamine deprivations and ERN1 knockdown significantly increased the sensitivity of the <i>SHMT2</i> gene to these nutrient deprivation conditions. <b>Conclusion.</b> The results of the present study demonstrate that the expression of the <i>SHMT2</i> gene responsible for serine metabolism and formation of folate one-carbon is controlled by ERN1 protein kinase and induced by hypoxia as well as glutamine and glucose deprivation conditions in glioblastoma cells and reflects the ERN1-mediated reprogramming of sensitivity this gene expression to nutrient deprivation.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"144-152"},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison the accuracy of thyroid sono-elastography vs. ultrasound-guided fine needle aspiration cytology with thyroid malignancy diagnosis histopathology.","authors":"Sarah Abd Elmageed Mahmoud, Mohamed Elsayed Enaba, Mohamed Moustafa Shareef, Yasser Moustafa Hafez, Ibrahim Abbas","doi":"10.2478/enr-2024-0014","DOIUrl":"10.2478/enr-2024-0014","url":null,"abstract":"<p><p><b>Objective.</b> The intend of the present study was to assess the diagnostic performance of strain elastography in investigating the thyroid nodule malignancy taking the surgical biopsy as a gold standard reference test. <b>Methods.</b> The study included 120 patients with 123 thyroid nodules, of which 67 had total thyroidectomy. The American College of Radiology Thyroid Imaging Reporting and Data Systems (ACR-TIRADS) were evaluated for all nodules. All suspicious nodules were referred for a fine needle aspiration cytology (FNAC) if they fulfilled the required size. Strain elastography was performed for each suspicious nodule. Ultrasound-guided FNAC was performed for all suspicious nodules. Total thyroidectomy was performed in those whom the suspicious nodules were proven by FNAC. <b>Results.</b> Strain ratio had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 84%, 81%, 95%, 85%, and 84%, respectively, with a cut point 1.96. Elasticity score had a sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 100%, 80%, 95%, 85% and 87%, respectively, with a cut point 0.96. The elasticity score had a statistically significantly odds ratio for detecting the benignity 3.9 C. I (1.6-9.3). <b>Conclusion.</b> Strain elastography has a high diagnostic performance in detecting the malignant as well as benign nodules, thus it can limit the rate of unneeded FNAC or surgery especially among B3 and B4 groups with indeterminate cytology.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"129-137"},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxytocin, GABA, and dopamine interplay in autism.","authors":"Tomas Havranek, Zuzana Bacova, Jan Bakos","doi":"10.2478/enr-2024-0012","DOIUrl":"10.2478/enr-2024-0012","url":null,"abstract":"<p><p>Oxytocin plays an important role in brain development and is associated with various neurotransmitter systems in the brain. Abnormalities in the production, secretion, and distribution of oxytocin in the brain, at least during some stages of the development, are critical for the pathogenesis of neuropsychiatric diseases, particularly in the autism spectrum disorder. The etiology of autism includes changes in local sensory and dopaminergic areas of the brain, which are also supplied by the hypothalamic sources of oxytocin. It is very important to understand their mutual relationship. In this review, the relationship of oxytocin with several components of the dopaminergic system, gamma-aminobutyric acid (GABA) inhibitory neurotransmission and their alterations in the autism spectrum disorder is discussed. Special attention has been paid to the results describing a reduced expression of inhibitory GABAergic markers in the brain in the context of dopaminergic areas in various models of autism. It is presumed that the altered GABAergic neurotransmission, due to the absence or dysfunction of oxytocin at certain developmental stages, disinhibits the dopaminergic signaling and contributes to the autism symptoms.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"105-114"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of signaling protein ERN1 increases the sensitivity of serine synthesis gene expressions to glucose and glutamine deprivations in U87MG glioblastoma cells.","authors":"Oleksandr H Minchenko, Myroslava Y Sliusar, Olena O Khita, Dmytro O Minchenko, Yuliia M Viletska, Oleh V Halkin, Liudmyla O Levadna, Anastasiia A Cherednychenko, Yevgen P Khikhlo","doi":"10.2478/enr-2024-0010","DOIUrl":"10.2478/enr-2024-0010","url":null,"abstract":"<p><p><b>Objective.</b> Glucose and glutamine supply as well as serine synthesis and endoplasmic reticulum (ER) stress are important factors of glioblastoma growth. Previous studies showed that the knockdown of ERN1 (ER to nucleus signaling 1) suppressed glioblastoma cell proliferation and modified the sensitivity of numerous gene expressions to nutrient deprivations. The present study is aimed to investigate the impact of glucose and glutamine deprivations on the expression of serine synthesis genes in U87MG glioblastoma cells in relation to ERN1 knockdown with the intent to reveal the role of ERN1 signaling pathway on the ER stress-dependent regulation of these gene expressions. Clarification of the regulatory mechanisms of serine synthesis is a great significance for glioblastoma therapy. <b>Methods.</b> The control U87MG glioblastoma cells (transfected by empty vector) and ERN1 knockdown cells (transfected by dominant-negative ERN1) were exposed under glucose and glutamine deprivation conditions for 16 h. RNA was extracted from cells and reverse transcribed. The expression level of <i>PHGDH</i> (phosphoglycerate dehydrogenase), <i>PSAT1</i> (phosphoserine amino-transferase 1), <i>PSPH</i> (phosphoserine phosphatase), <i>ATF4</i> (activating transcription factor 4), and <i>SHMT1</i> (serine hydroxymethyltransferase 1) genes was studied by real-time qPCR and normalized to ACTB. <b>Results.</b> It was found that the expression level of genes responsible for serine synthesis such as <i>PHGDH</i>, <i>PSAT1</i>, <i>PSPH</i>, and transcription factor <i>ATF4</i> was up-regulated in U87MG glioblastoma cells under glucose and glutamine deprivations. Furthermore, inhibition of ERN1 significantly enhances the impact of glucose and especially glutamine deprivations on these gene expressions. At the same time, the expression of the <i>SHMT1</i> gene, which is responsible for serine conversion to glycine, was down-regulated in both nutrient deprivation conditions with more significant changes in ERN1 knockdown glioblastoma cells. <b>Conclusion.</b> Taken together, the results of present study indicate that the expression of genes responsible for serine synthesis is sensitive to glucose and glutamine deprivations in gene-specific manner and that suppression of ERN1 signaling significantly modifies the impact of both glucose and glutamine deprivations on <i>PHGDH</i>, <i>PSAT1</i>, <i>PSPH</i>, <i>ATF4</i>, and <i>SHMT1</i> gene expressions and reflects the ERN1-mediated genome reprograming introduced by nutrient deprivation condition.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"91-100"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of lipid profile and obesity in patients with polycystic ovary syndrome.","authors":"Sadaf Parveen, Saba Khan, Mohammad Mustufa Khan, Bhavana Gupta, Ausaf Ahmad, Roshan Alam","doi":"10.2478/enr-2024-0009","DOIUrl":"10.2478/enr-2024-0009","url":null,"abstract":"<p><p><b>Objective.</b> Abnormal lipid profile and obesity increase the risk of polycystic ovary syndrome (PCOS). PCOS patients may have a greater risk of infertility, metabolic syndrome (MetS) and cardiovascular disease (CVD) due to abnormal lipid profile and obesity. The aim of the study was to find the association between abnormal lipid profile and obesity in patients with PCOS. <b>Methods.</b> In this case-control study, a total of 102 female subjects (51 diagnosed PCOS and 51 age-matched healthy controls) were enrolled, aged between 20-40 years. Biochemical parameters such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were estimated. Anthropometric parameters such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were recorded. A p<0.05 was considered statistically significant. <b>Results.</b> Mean of BMI, WC, WHR, LH, FSH, TC, TG, LDL-C, and VLDL-C was found significantly elevated in patients with PCOS as compared to controls (p<0.01). However, the mean of HDL-C was found significantly reduced in patients with PCOS as compared to controls (p<0.01). BMI has shown a significant positive correlation with WC (r=0.562, p<0.01) and WHR (r=0.580, p<0.01) among PCOS patients. LH has shown a significant positive correlation with FSH (r=0.572, p<0.01) among PCOS patients. TC has shown a significant positive correlation with TG (r=0.687, p<0.01), LDL-C (r=0.917, p<0.01), and VLDL-C (r=0.726, p<0.01) among PCOS patients. <b>Conclusion.</b> The results showed that abnormal lipid profile and obesity have a significant association with PCOS patients. Regular monitoring and treatment of PCOS patients are required to reduce the risk of infertility, MetS, and CVD.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"83-90"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent chronic calcific pancreatitis with intraductal calculi associated with secondary diabetes mellitus type 3 and diabetic ketoacidosis - A case report.","authors":"Gurusha Bahl, Dinesh K Upadhyay, Madhumati Varma, Rajveer Singh, Subhankar Das, Sadique Hussain","doi":"10.2478/enr-2024-0011","DOIUrl":"10.2478/enr-2024-0011","url":null,"abstract":"<p><p>Diabetes mellitus type 3 refers to diabetes secondary to an existing disease or condition of the exocrine pancreas and is an uncommon cause of diabetes occurring due to pancreatogenic pathology. It accounts for 15-20% of diabetic patients in Indian and Southeast Asian continents. This is case report of a rare case of type 3 diabetes mellitus (T3DM) presenting with diabetic ketoacidosis (DKA). The patient was admitted for DKA along with complaint of hyperglycemia, blood glucose of 405 mg/dl with HbA1c level of 13.7%. Computed tomography evidence revealed chronic calcific pancreatitis with intraductal calculi and dilated pancreatic duct.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"101-104"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced glycation end products of dietary origin and their association with inflammation in diabetes - A minireview.","authors":"Adriana Pedreanez, Jorge Robalino, Diego Tene, Patricio Salazar","doi":"10.2478/enr-2024-0007","DOIUrl":"10.2478/enr-2024-0007","url":null,"abstract":"<p><p>Advanced glycation end products (AGEs) are a diverse group of compounds that are formed as a result of the non-enzymatic reaction between a reducing sugar such as glucose and the free NH2 groups of an amino acid in a protein or other biomolecule. The chemical reaction, by which these products are generated, is known as the Maillard reaction and occurs as a part of the body's normal metabolism. Such a reaction is enhanced during diabetes due to hyperglycemia, but it can also occur during the preparation, processing, and preservation of certain foods. Therefore, AGEs can also be obtained from the diet (d-AGE) and contribute to an increase of the total serum pool of these compounds. They have been implicated in a wide variety of pathological processes, mainly because of their ability to induce inflammatory responses and oxidative stress increase. They are extensively accumulated as a part of the normal aging, especially in tissues rich in long half-life proteins, which can compromise the physiology of these tissues. d-AGEs are abundant in diets rich in processed fats and sugars. This review is addressed to the current knowledge on these products and their impact on the immunomodulation of various mechanisms that may contribute to exacerbation of the diabetes pathophysiology.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"57-67"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships of apolipoprotein E genotypes with a cluster of seven in persons with type 2 diabetes.","authors":"Douglas E Barre, Kazimiera A Mizier-Barre, Odette Griscti, Kevin Hafez","doi":"10.2478/enr-2024-0005","DOIUrl":"10.2478/enr-2024-0005","url":null,"abstract":"<p><strong>Objective.: </strong>The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes (2/2, 2/3, 2/4, 3/3, 3/4, and 4/4) for each member of the cluster of seven associated with type 2 diabetes (T2D). The cluster of seven includes abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased plasma levels of triglycerides)), increased low-density lipoprotein (LDL) oxidation, and increased inflammation.</p><p><strong>Methods.: </strong>Forty-six patients with well-controlled T2D participated in the study. Abdominal obesity (assessed by waist circumference), hypertension (measured by manual sphygmomanometry), platelet hyperaggregability (measured by bleeding time), hyperglycemia (by enzymatic kit and spectrophotometry), decreased plasma levels of HDL-C and increased plasma levels of triglycerides (by enzymatic kit and spectrophotometry), increased LDL oxidation (measured by LDL conjugated dienes using spectrophotometry) and increased inflammation measured by C-reactive protein (CRP) (by EIA kit) were determined.</p><p><strong>Results.: </strong>All genotypes, except 2/2 were found in the population studied. Abdominal obesity did not vary significantly across the five genotypes. However, glucose levels trended progressively higher going from 2/3 to 2/4 to 3/4 to 4/4. Systolic blood pressure was higher in 3/4 compared to 2/4 and trended higher in 3/4 compared to 3/3. Diastolic blood pressure trended higher in 3/3 vs 2/4 and significantly higher in 3/4 compared to 2/4. Triglycerides trended higher in 3/4 vs 3/3 while HDL-C came close to trending downward in 4/4 compared to 2/4. Bleeding time was unaffected by genotype. Plasma LDL conjugated dienes trended higher in 3/4 vs 2/4 and were significantly higher in 3/4 vs 3/3. CRP trended higher in 4/4 vs 2/3.</p><p><strong>Conclusion.: </strong>We can conclude that those with at least one 4 allele in the presence of another allele being 2, 3 or 4 is potentially (in the case of trends) deleterious or is deleterious in terms of hyperglycemia, hypertension (systolic and diastolic blood pressure), dyslipidemia, LDL conjugated dienes and CRP levels.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"40-46"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERN1 knockdown modifies the hypoxic regulation of homeobox gene expression in U87MG glioblastoma cells.","authors":"Daria A Krasnytska, Olena O Khita, Yuliia M Viletska, Dmytro O Minchenko, Oleh V Halkin, Olha V Rudnytska, Sofiia L Hoian, Oleksandr H Minchenko","doi":"10.2478/enr-2024-0006","DOIUrl":"10.2478/enr-2024-0006","url":null,"abstract":"<p><strong>Objective.: </strong>Homeobox genes play an important role in health and disease including oncogenesis. The present investigation aimed to study ERN1-dependent hypoxic regulation of the expression of genes encoding homeobox proteins MEIS (zinc finger E-box binding homeobox 2) and LIM homeobox 1 family, SPAG4 (sperm associated antigen 4) and NKX3-1 (NK3 homeobox 1) in U87MG glioblastoma cells in response to inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1) for evaluation of their possible significance in the control of glioblastoma growth.</p><p><strong>Methods.: </strong>The expression level of homeobox genes was studied in control (transfected by vector) and ERN1 knockdown U87MG glioblastoma cells under hypoxia induced by dimethyloxalylglycine (0.5 mM for 4 h) by quantitative polymerase chain reaction and normalized to ACTB.</p><p><strong>Results.: </strong>It was found that hypoxia down-regulated the expression level of <i>LHX2</i>, <i>LHX6</i>, <i>MEIS2</i>, and <i>NKX3</i>-1 genes but up-regulated the expression level of <i>MEIS1</i>, <i>LHX1</i>, <i>MEIS3</i>, and <i>SPAG4</i> genes in control glioblastoma cells. At the same time, ERN1 knockdown of glioblastoma cells significantly modified the sensitivity of all studied genes to a hypoxic condition. Thus, ERN1 knockdown of glioblastoma cells removed the effect of hypoxia on the expression of <i>MEIS1</i> and <i>LHX1</i> genes, but increased the sensitivity of <i>MEIS2</i>, <i>LHX2</i>, and <i>LHX6</i> genes to hypoxia. However, the expression of <i>MEIS3</i>, <i>NKX3</i>-1, and <i>SPAG4</i> genes had decreased sensitivity to hypoxia in ERN1 knockdown glioblastoma cells. Moreover, more pronounced changes under the conditions of ERN1 inhibition were detected for the pro-oncogenic gene <i>SPAG4</i>.</p><p><strong>Conclusion.: </strong>The results of the present study demonstrate that hypoxia affected the expression of homeobox genes <i>MEIS1</i>, <i>MEIS2</i>, <i>MEIS3</i>, <i>LHX1</i>, <i>LHX2</i>, <i>LHX6</i>, <i>SPAG4</i>, and <i>NKX3-1</i> in U87MG glioblastoma cells in gene-specific manner and that the sensitivity of all studied genes to hypoxia condition is mediated by ERN1, the major pathway of the endoplasmic reticulum stress signaling, and possibly contributed to the control of glioblastoma growth. A fundamentally new results of this work is the establishment of the fact regarding the dependence of hypoxic regulation of SPAG4 gene expression on ER stress, in particular ERN1, which is associated with suppression of cell proliferation and tumor growth.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"47-56"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}