Endocrine regulationsPub Date : 2024-04-24Print Date: 2024-01-01DOI: 10.2478/enr-2024-0010
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
{"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}
Endocrine regulationsPub Date : 2024-04-24Print Date: 2024-01-01DOI: 10.2478/enr-2024-0009
Sadaf Parveen, Saba Khan, Mohammad Mustufa Khan, Bhavana Gupta, Ausaf Ahmad, Roshan Alam
{"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}
Endocrine regulationsPub Date : 2024-04-02Print Date: 2024-01-01DOI: 10.2478/enr-2024-0007
Adriana Pedreanez, Jorge Robalino, Diego Tene, Patricio Salazar
{"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}
Endocrine regulationsPub Date : 2024-04-02Print Date: 2024-01-01DOI: 10.2478/enr-2024-0005
Douglas E Barre, Kazimiera A Mizier-Barre, Odette Griscti, Kevin Hafez
{"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}
Endocrine regulationsPub Date : 2024-04-02Print Date: 2024-01-01DOI: 10.2478/enr-2024-0006
Daria A Krasnytska, Olena O Khita, Yuliia M Viletska, Dmytro O Minchenko, Oleh V Halkin, Olha V Rudnytska, Sofiia L Hoian, Oleksandr H Minchenko
{"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}
Endocrine regulationsPub Date : 2024-04-02Print Date: 2024-01-01DOI: 10.2478/enr-2024-0008
Filip Blasko, Lubica Horvathova
{"title":"The relationship between the tumor and its innervation: historical, methodical, morphological, and functional assessments - A minireview.","authors":"Filip Blasko, Lubica Horvathova","doi":"10.2478/enr-2024-0008","DOIUrl":"10.2478/enr-2024-0008","url":null,"abstract":"<p><p>The acceptance of the tumor as a non-isolated structure within the organism has opened a space for the study of a wide spectrum of potential direct and indirect interactions, not only between the tumor tissue and its vicinity, but also between the tumor and its macroenvironment, including the nervous system. Although several lines of evidence have implicated the nervous system in tumor growth and progression, for many years, researchers believed that tumors lacked innervation and the notion of indirect neuro-neoplastic interactions via other systems (e.g., immune, or endocrine) predominated. The original idea that tumors are supplied not only by blood and lymphatic vessels, but also autonomic and sensory nerves that may influence cancer progression, is not a recent phenomenon. Although in the past, mainly due to the insufficiently sensitive methodological approaches, opinions regarding the presence of nerves in tumors were inconsistent. However, data from the last decade have shown that tumors are able to stimulate the formation of their own innervation by processes called neo-neurogenesis and neo-axonogenesis. It has also been shown that tumor infiltrating nerves are not a passive, but active components of the tumor microenvironment and their presence in the tumor tissue is associated with an aggressive tumor phenotype and correlates with poor prognosis. The aim of the present review was to 1) summarize the available knowledge regarding the course of tumor innervation, 2) present the potential mechanisms and pathways for the possible induction of new nerve fibers into the tumor microenvironment, and 3) highlight the functional significance/consequences of the nerves infiltrating the tumors.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"68-82"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335205","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":"Risk of malignancy in Thy3 thyroid nodules.","authors":"Emad Mofid Nassif Rezkallah, Ragai Sobhi Hanna, Wael Magdy Elsaify","doi":"10.2478/enr-2024-0003","DOIUrl":"10.2478/enr-2024-0003","url":null,"abstract":"<p><p><b>Objective.</b> Thyroid cancer is the most common endocrine malignancy in humans. Ultrasound guided fine needle aspiration cytology (FNAC) is now considered the best diagnostic tool for the evaluation of any thyroid nodule. Thyroid cytology is graded from Thy1 to Thy5 with Thy3 being the most challenging in diagnosis. Our aim was to identify the risk of malignancy in Thy3 cytology in our centre. This risk should be explained to the patient before taking any decision. <b>Methods.</b> One hundred and one patients were included in our study. All patients had Thy3 cytology on preoperative ultrasound scan guided FNAC. All patients had diagnostic hemithyroidectomy. The results from the histology were compared with the cytology findings and the rates of malignancy were identified. <b>Results.</b> Of the 101 patients, 17 were males and 84 females. Average age for diagnosis was 52.4±15 years of age. Patients were classified into three groups; patient who had completely benign histology (n=70), patients who had incidental finding of micro-carcinoma after diagnostic hemithyroidectomy (n=10), and patients who had thyroid macro-carcinomas (n=21). Total rate of malignancy was 30.7% when combining both the malignant and the incidental groups and 20.8% when excluding the incidental group. <b>Conclusion.</b> Our rates of malignancy in Thy3 cytology are similar to the literature. These rates should be explained clearly to the patient during the preoperative counselling. Future advances in biomarkers technology may help to improve the preoperative diagnostic accuracy and reduce the rate of unnecessary thyroid surgery.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"19-25"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722032","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}
Endocrine regulationsPub Date : 2024-02-12Print Date: 2023-01-01DOI: 10.2478/enr-2024-0001
Dmytro O Minchenko, Olena O Khita, Yuliia M Viletska, Myroslava Y Sliusar, Olha V Rudnytska, Halyna E Kozynkevych, Borys H Bezrodnyi, Yevgen P Khikhlo, Oleksandr H Minchenko
{"title":"Cortisol controls endoplasmic reticulum stress and hypoxia dependent regulation of insulin receptor and related genes expression in HEK293 cells.","authors":"Dmytro O Minchenko, Olena O Khita, Yuliia M Viletska, Myroslava Y Sliusar, Olha V Rudnytska, Halyna E Kozynkevych, Borys H Bezrodnyi, Yevgen P Khikhlo, Oleksandr H Minchenko","doi":"10.2478/enr-2024-0001","DOIUrl":"10.2478/enr-2024-0001","url":null,"abstract":"<p><p><b>Objective.</b> Glucocorticoids are important stress-responsive regulators of insulin-dependent metabolic processes realized through specific changes in genome function. The aim of this study was to investigate the impact of cortisol on insulin receptor and related genes expression in HEK293 cells upon induction the endoplasmic reticulum (ER) stress by tunicamycin and hypoxia. <b>Methods.</b> The human embryonic kidney cell line HEK293 was used. Cells were exposed to cortisol (10 µM) as well as inducers of hypoxia (dimethyloxalylglycine, DMOG; 0.5 mM) and ER stress (tunicamycin; 0.2 µg/ml) for 4 h. The RNA from these cells was extracted and reverse transcribed. The expression level of <i>INSR</i>, <i>IRS2</i>, and <i>INSIG2</i> and some ER stress responsive genes encoding XBP1n, non-spliced variant, XBP1s, alternatively spliced variant of XBP1, and DNAJB9 proteins, was measured by quantitative polymerase chain reaction and normalized to ACTB. <b>Results.</b> We showed that exposure of HEK293 cells to cortisol elicited up-regulation in the expression of <i>INSR</i> and <i>DNAJB9</i> genes and down-regulation of XBP1s, XBP1n, IRS2, and INSIG2 mRNA levels. At the same time, induction of hypoxia by DMOG led to an up-regulation of the expression level of most studied mRNAs: XBP1s and XBP1n, IRS2 and INSIG2, but did not change significantly <i>INSR</i> and <i>DNAJB9</i> gene expression. We also showed that combined impact of cortisol and hypoxia introduced the up-regulation of INSR and suppressed XBP1n mRNA expression levels. Furthermore, the exposure of HEK293 cells to tunicamycin affected the expression of IRS2 gene and increased the level of XBP1n mRNA. At the same time, the combined treatment of these cells with cortisol and inductor of ER stress had much stronger impact on the expression of all the tested genes: strongly increased the mRNA level of ER stress dependent factors XBP1s and DNAJB9 as well as INSR and INSIG2, but down-regulated IRS2 and XBP1n. <b>Conclusion.</b> Taken together, the present study indicates that cortisol may interact with ER stress and hypoxia in the regulation of ER stress dependent <i>XBP1</i> and <i>DNAJB9</i> mRNA expression as well as INSR and its signaling and that this corticosteroid hormone modified the impact of hypoxia and especially tunicamycin on the expression of most studied genes in HEK293 cells. These data demonstrate molecular mechanisms of glucocorticoids interaction with ER stress and insulin signaling at the cellular level.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722029","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}
Endocrine regulationsPub Date : 2024-02-12Print Date: 2023-01-01DOI: 10.2478/enr-2024-0004
Phaik Har Yong, Shin Yee New, Meram Azzani, Yuan Seng Wu, Vi Vien Chia, Zhi Xiang Ng
{"title":"Potential of medicinal plants to ameliorate neovascularization activities in diabetes: A systematic review.","authors":"Phaik Har Yong, Shin Yee New, Meram Azzani, Yuan Seng Wu, Vi Vien Chia, Zhi Xiang Ng","doi":"10.2478/enr-2024-0004","DOIUrl":"10.2478/enr-2024-0004","url":null,"abstract":"<p><p>Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive angiogenesis can cause diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. All of these complications are debilitating, which may lead to an increased susceptibility to lower-limb amputations due to ulcerations and infections. In addition, microvascular alterations, segmental demyelination, and endoneurial microangiopathy may cause progressive deterioration ultimately leading to kidney failure and permanent blindness. Some medicinal plants have potent anti-angiogenic, antioxidant or anti-inflammatory properties that can ameliorate angiogenesis in diabetes. The purpose of this systematic review is to demonstrate the potential of medicinal plants in ameliorating the neovascularization activities in diabetes. Manuscripts were searched from PubMed, Science Direct, and Scopus databases, and Google Scholar was used for searching additional papers. From 1862 manuscripts searched, 1854 were excluded based on inclusion and exclusion criteria and 8 were included into this systematic review, whereas the required information was extracted and summarized. All identified medicinal plants decreased the high blood glucose levels in diabetes, except the aqueous extract of Lonicerae japonicae flos (FJL) and Vasant Kusumakar Ras. They also increased the reduced body weight in diabetes, except the aqueous extract of FL and total lignans from Fructus arctii. However, methanolic extract of Tinospora cordifolia and Vasant Kusumakar Ras were not tested for their ability to affect the body weight. Besides, all medicinal plants identified in this systematic review decreased the vascular endothelial growth factor (VEGF) protein expression and vasculature activity demonstrated by histopathological examination indicating promising anti-angiogenic properties. All medicinal plants identified in this systematic review have a potential to ameliorate neovascularization activities in diabetes by targeting the mechanistic pathways related to oxidative stress, inflammation, and angiogenesis.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"26-39"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722031","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}