rss_2.0Sciendo RSS Feed for Endocrine Regulationshttps://sciendo.com/journal/ENRhttps://www.sciendo.comhttps://sciendo-parsed.s3.eu-central-1.amazonaws.com/65ca3079c8e724130865a035/cover-image.jpghttps://sciendo.com/journal/ENR140216https://sciendo.com/article/10.2478/enr-2024-0017<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Genetic factors substantially contribute to the development and duration of arterial hypertension. The study of the A1166C polymorphism of the angiotensin II type 1 receptor gene (<italic>AGTR1</italic>) in arterial hypertension is an auspicious area for assessing the relationship between heredity, hypertension development, and adipokines, but it still remains debatable. The purpose of the current study was to investigate serum adipokines levels depending on the <italic>AGTR1</italic> A1166C polymorphism.</p> <p><bold>Methods.</bold> A total of 86 patients with arterial hypertension were examined, who underwent the evaluation of the allelic A1166C polymorphism of <italic>AGTR1</italic> by polymerase chain reaction with electrophoretic detection and determination of serum adipokines levels using enzyme-linked immunosorbent assay.</p> <p><bold>Results.</bold> In the group of patients with arterial hypertension, a significant increase in serum adipokines (resistin, adiponectin, and leptin) levels was found against the background of a decrease in the antianorexic hormone ghrelin with a predominance of CC genotype carriers compared with AA genotype carriers of the <italic>AGTR1</italic>. A statistically significant decrease in ghrelin and an increase in serum adipokines (resistin, adiponectin, and leptin) in CC genotype carriers compared with AA genotype carriers of the <italic>AGTR1</italic> were found suggesting that CC genotype carriers may be predictors of the development of arterial hypertension in our patients.</p> <p><bold>Conclusions.</bold> Statistically significant decrease in ghrelin and increase in serum adipokines (resistin, adiponectin, and leptin) were found in CC genotype carriers compared with AA genotype carriers of the <italic>AGTR1</italic>, which suggests that carriers of the CC genotype are predictors of the arterial hypertension development in our patients.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00172024-08-09T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0020<abstract> <title style='display:none'>Abstract</title> <p>In preovulatory follicles, after the endogenous gonadotropin surge, the oocyte-cumulus complexes (OCCs) produce hyaluronan (HA) in a process called “cumulus expansion”. During this process, the heavy chains (HCs) of the serum-derived inter-alpha-trypsin inhibitor (IαI) family bind covalently to synthesized HA and form a unique structure of the expanded cumulus HA-rich extracellular matrix. Understanding the biochemical mechanism of the covalent linkage between HA and the HCs of the IαI family is one of the most significant discoveries in reproductive biology, since it explains basis of the cumulus expansion process running in parallel with the oocyte maturation, both essential for ovulation. Two recent studies have supported the above-mentioned findings: in the first, seven components of the extracellular matrix were detected by proteomic, evolutionary, and experimental analyses, and in the second, the essential role of serum in the process of cumulus expansion in vitro was confirmed. We have previously demonstrated the formation of unique structure of the covalent linkage of HA to HCs of IαI in the expanded gonadotropin-stimulated OCC, as well as interactions with several proteins produced by the cumulus cells: tumor necrosis factor-alpha-induced protein 6, pentraxin 3, and versican. Importantly, deletion of these genes in the mice produces female infertility due to defects in the oocyte-cumulus structure.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00202024-08-09T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0018<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> The hormonal balance is dependent on the internal and external stimuli. The baseline cortisol (BC) and thyroid stimulating hormone (TSH) levels have been observed to vary and have a predictive value in critical illness settings. Few reports have studied their variation in non-severe acute illness. The present study aims to describe the variation of BC and TSH levels and to determine the factors influencing BC and TSH levels in patients admitted with non-severe acute illness.</p> <p><bold>Patients and Methods.</bold> This is a cross-sectional study of patients admitted to Infectious Diseases and Endocrinology units at the Department of Endocrinology-Diabetology and Internal Medicine at Tahar Sfar University Hospital between March 15th and September 15th, 2020. BC and TSH levels were obtained during the hospitalization.</p> <p><bold>Results.</bold> A total of 143 patients were included in this study with 75 presenting with infection. All infections were community-acquired and predominantly non-severe. The BC levels were higher in patients with infection (p=0.004), especially those admitted via the emergency department (p=0.009) with a fever (p=0.015). The BC positively correlated with the temperature (p=0.002, r’=0.350), CRP levels (p=0.002, r’=0.355), neutrophil to lymphocyte ratio (p=0.045, r’=0.235), and SOFA score (p=0.023, r’=0.262). On the other hand, TSH levels were comparable in the presence of infection (p=0.400). TSH levels did not correlate with the fever, the severity of infection, or inflammation biomarkers. Both BC and TSH did not predict unfavorable outcomes in non-severe infected patients.</p> <p><bold>Conclusion.</bold> In patients admitted with critical acute infections, the BC levels seem to indicate a relatively more severe infectious state. On the other hand, TSH levels did not show significant variations in these patients.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00182024-08-09T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0019<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Myocardial fibrosis is a devastating condition causing millions of deaths yearly. Several factors, such as aging, cause myocardial fibrosis. The Wnt/β-catenin pathway is one of the critical intracellular signaling for the development of cardiac fibrosis. Molecular and cellular mechanism of myocardial fibrosis induced by intensive exercise is not well-understood. The current study evaluates the effects of short- and long-term intensive exercise on the <italic>Wnt1</italic> gene expression in a heart left ventricle in an animal model.</p> <p><bold>Methods.</bold> Twenty-one male Wistar rats (mean weight 250±50 g) were divided into three groups (n=7): 1) control group (C); 2) short-term regular intensive exercise group (S-RIE, high-intensity exercise for one month six days weekly for 60 min with speed of 35 m/min), and 3) long-term regular intensive exercise group (L-RIE, high-intensity exercise for six months six days daily for 60 min with speed of 35 m/min). The heart left ventricle was isolated at the end of the experiment, and the relative gene expression of the <italic>Wnt1</italic> gene was measured by the Real-Time PCR.</p> <p><bold>Results.</bold> The L-RIE group showed a significant increase in the <italic>Wnt1</italic> expression compared to the S-RIE and the control group. Although no difference was observed in the <italic>Wnt1</italic> mRNA level in the S-RIE group compared to the control group, <italic>Wnt1</italic> mRNA level increased in the L-RIE group compared to the S-RIE group.</p> <p><bold>Conclusion.</bold> The exercise duration was of a great importance in the <italic>Wnt1</italic> gene expression. Regular intensive exercise may be involved in the formation of the myocardial fibrosis by increasing the expression of the <italic>Wnt1</italic> gene.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00192024-08-09T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0014<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> 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.</p> <p><bold>Methods.</bold> 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.</p> <p><bold>Results.</bold> 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).</p> <p><bold>Conclusion.</bold> 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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00142024-06-11T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0013<abstract> <title style='display:none'>Abstract</title> <p><bold>Objectives.</bold> Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2 diabetes, hyper-tension, dyslipidemia, and others. Physical inactivity together with an imbalance in caloric intake and expenditure leads to a loss of muscle mass, reduced insulin sensitivity, and accumulation of the visceral fat. Organokines (adipokines, myokines, hepatokines, etc.) serve in the organism for inter-organ communication. However, human studies focused on the exercise-related changes in plasma levels of certain myokines have produced contradictory results. In the present study, we verified a hypothesis that myokine irisin, which is expected to increase in response to physical activity, induces brain-derived neurotrophic factor (BDNF) production and by this way mediates the beneficial effect of exercise on several brain functions.</p> <p><bold>Subjects and Methods.</bold> Women (n=27) and men (n=10) aged 44.5±12.0 years, who were sedentary and overweight/obese (men ≥25%, women ≥28% body fat), participated in the study. The effect of an 8-week intensive lifestyle intervention (150 minutes of moderate physical activity per week, diet modification, and reduction of caloric intake) on the selected organokines (irisin, BDNF) in the context of an expected improvement in cardiometabolic status was examined.</p> <p><bold>Results.</bold> The 8-week lifestyle intervention resulted in a significant (p&lt;0.05) reduction in body mass index, body fat, blood pressure, insulin resistance, lipid and liver parameters, and irisin levels (p&lt;0.001). However, BDNF increase in the whole group did not reach statistical significance. After the improvement of cardiometabolic parameters, a significant decrease in irisin and increase in BDNF levels were also observed in the subgroup with unsatisfactory (≤5%) body weight reduction. Neither relationship between irisin and BDNF levels, nor effect of age or sex on their levels was observed.</p> <p><bold>Conclusions.</bold> We cannot confirm the hypothesis that exercise-induced irisin may increase the BDNF levels, whereas, the organokine levels in the periphery may not completely reflect the processes in the brain compartments. The observed decrease in irisin levels after 8-week intensive lifestyle intervention program, which was in contrary to its supposed mechanisms of action and dynamics, suggests the presence of several yet undiscovered impacts on the secretion of irisin.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00132024-06-11T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0016<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> 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 <italic>SHMT2</italic> 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.</p> <p><bold>Methods.</bold> 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 <italic>SHMT2</italic> gene was studied by real-time qPCR and normalized to ACTB.</p> <p><bold>Results.</bold> It was found that inhibition of ERN1 endoribonuclease and protein kinase in glioblastoma cells led to a down-regulation of <italic>SHMT2</italic> 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 <italic>SHMT2</italic> gene was not affected in U87MG cells after silencing of XBP1. Hypoxia up-regulated the expression level of the <italic>SHMT2</italic> 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 <italic>SHMT2</italic> gene to these nutrient deprivation conditions.</p> <p><bold>Conclusion.</bold> The results of the present study demonstrate that the expression of the <italic>SHMT2</italic> 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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00162024-06-11T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0015<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> 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.</p> <p><bold>Methods.</bold> 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.</p> <p><bold>Results.</bold> 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.)</p> <p><bold>Conclusions.</bold> 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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00152024-06-11T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0011<abstract> <title style='display:none'>Abstract</title> <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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00112024-04-24T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0012<abstract> <title style='display:none'>Abstract</title> <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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00122024-04-24T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0009<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> 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.</p> <p><bold>Methods.</bold> 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&lt;0.05 was considered statistically significant.</p> <p><bold>Results.</bold> 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&lt;0.01). However, the mean of HDL-C was found significantly reduced in patients with PCOS as compared to controls (p&lt;0.01). BMI has shown a significant positive correlation with WC (r=0.562, p&lt;0.01) and WHR (r=0.580, p&lt;0.01) among PCOS patients. LH has shown a significant positive correlation with FSH (r=0.572, p&lt;0.01) among PCOS patients. TC has shown a significant positive correlation with TG (r=0.687, p&lt;0.01), LDL-C (r=0.917, p&lt;0.01), and VLDL-C (r=0.726, p&lt;0.01) among PCOS patients.</p> <p><bold>Conclusion.</bold> 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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00092024-04-24T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0010<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> 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.</p> <p><bold>Methods.</bold> 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 <italic>PHGDH</italic> (phosphoglycerate dehydrogenase), <italic>PSAT1</italic> (phosphoserine amino-transferase 1), <italic>PSPH</italic> (phosphoserine phosphatase), <italic>ATF4</italic> (activating transcription factor 4), and <italic>SHMT1</italic> (serine hydroxymethyltransferase 1) genes was studied by real-time qPCR and normalized to ACTB.</p> <p><bold>Results.</bold> It was found that the expression level of genes responsible for serine synthesis such as <italic>PHGDH</italic>, <italic>PSAT1</italic>, <italic>PSPH</italic>, and transcription factor <italic>ATF4</italic> 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 <italic>SHMT1</italic> 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.</p> <p><bold>Conclusion.</bold> 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 <italic>PHGDH</italic>, <italic>PSAT1</italic>, <italic>PSPH</italic>, <italic>ATF4</italic>, and <italic>SHMT1</italic> gene expressions and reflects the ERN1-mediated genome reprograming introduced by nutrient deprivation condition.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00102024-04-24T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0008<abstract><title style='display:none'>Abstract</title> <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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00082024-04-02T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0006<abstract><title style='display:none'>Abstract</title> <sec><title style='display:none'>Objective.</title> <p>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> </sec> <sec><title style='display:none'>Methods.</title> <p>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> </sec> <sec><title style='display:none'>Results.</title> <p>It was found that hypoxia down-regulated the expression level of <italic>LHX2</italic>, <italic>LHX6</italic>, <italic>MEIS2</italic>, and <italic>NKX3</italic>-1 genes but up-regulated the expression level of <italic>MEIS1</italic>, <italic>LHX1</italic>, <italic>MEIS3</italic>, and <italic>SPAG4</italic> 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 <italic>MEIS1</italic> and <italic>LHX1</italic> genes, but increased the sensitivity of <italic>MEIS2</italic>, <italic>LHX2</italic>, and <italic>LHX6</italic> genes to hypoxia. However, the expression of <italic>MEIS3</italic>, <italic>NKX3</italic>-1, and <italic>SPAG4</italic> 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 <italic>SPAG4</italic>.</p> </sec> <sec><title style='display:none'>Conclusion.</title> <p>The results of the present study demonstrate that hypoxia affected the expression of homeobox genes <italic>MEIS1</italic>, <italic>MEIS2</italic>, <italic>MEIS3</italic>, <italic>LHX1</italic>, <italic>LHX2</italic>, <italic>LHX6</italic>, <italic>SPAG4</italic>, and <italic>NKX3-1</italic> 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> </sec> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00062024-04-02T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0007<abstract><title style='display:none'>Abstract</title> <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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00072024-04-02T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0005<abstract><title style='display:none'>Abstract</title> <sec><title style='display:none'>Objective.</title> <p>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> </sec> <sec><title style='display:none'>Methods.</title> <p>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> </sec> <sec><title style='display:none'>Results. </title> <p>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> </sec> <sec><title style='display:none'>Conclusion.</title> <p>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> </sec> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00052024-04-02T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0004<abstract> <title style='display:none'>Abstract</title> <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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00042024-02-12T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0002<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Adiponectin is an internally produced bioactive compound with a protective role against the insulin resistance-related diseases. Finding an adiponectin modifier can play a beneficial role in preventing the progression of the diseases, particularly in the prediabetic patients, as a high-risk population. This study was undertaken to examine the effect of dietary sorghum grain for a week on the plasma adiponectin levels in prediabetic patients.</p> <p><bold>Methods.</bold> The study involved 26 (13+13) participants in both control and intervention groups. The control group maintained their habitual diet of white rice, while the intervention group replaced their habitual diet of white rice with sorghum grain for seven consecutive days. In all participants, the adiponectin concentration was measured before and after the intervention period.</p> <p><bold>Results.</bold> Most study subjects had central obesity and dyslipidemia. Adiponectin levels after the intervention period decreased from the baseline in the control and sorghum groups including in all BMI groups. The change of decreasing adiponectin level was greater in the control than the sorghum group and in line with greater BMI in the sorghum group, but statistically insignificant. No significant difference in adiponectin concentrations was found among BMI groups.</p> <p><bold>Conclusion.</bold> Sorghum grain consumption for a week is insufficient to increase adiponectin levels in the prediabetic patients. Insulin resistance, central obesity, and dyslipidemia may be the confounding variables that alter the favorable effect of sorghum on adiponectin. Longer sorghum consumption or other interventions may be needed to increase the adiponectin levels in people under these conditions.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00022024-02-12T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0001<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> 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.</p> <p><bold>Methods.</bold> 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 <italic>INSR</italic>, <italic>IRS2</italic>, and <italic>INSIG2</italic> 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.</p> <p><bold>Results.</bold> We showed that exposure of HEK293 cells to cortisol elicited up-regulation in the expression of <italic>INSR</italic> and <italic>DNAJB9</italic> 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 <italic>INSR</italic> and <italic>DNAJB9</italic> 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.</p> <p><bold>Conclusion.</bold> Taken together, the present study indicates that cortisol may interact with ER stress and hypoxia in the regulation of ER stress dependent <italic>XBP1</italic> and <italic>DNAJB9</italic> 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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00012024-02-12T00:00:00.000+00:00https://sciendo.com/article/10.2478/enr-2024-0003<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> 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.</p> <p><bold>Methods.</bold> 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.</p> <p><bold>Results.</bold> 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.</p> <p><bold>Conclusion.</bold> 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> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/enr-2024-00032024-02-12T00:00:00.000+00:00en-us-1