rss_2.0Endocrine Regulations FeedSciendo RSS Feed for Endocrine Regulations Regulations Feed the accuracy of thyroid sono-elastography vs. ultrasound-guided fine needle aspiration cytology with thyroid malignancy diagnosis histopathology<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>ARTICLEtrue irisin and the brain-derived neurotrophic factor levels in sedentary subjects: effect of 8-weeks lifestyle intervention<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>ARTICLEtrue reticulum stress-dependent regulation of the expression of serine hydroxymethyltransferase 2 in glioblastoma cells<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>ARTICLEtrue verified methods for determining predictors of development of arterial hypertension depending on endothelial nitric oxide synthase T786C gene promoter polymorphism using lipid profile indicators<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>ARTICLEtrue chronic calcific pancreatitis with intraductal calculi associated with secondary diabetes mellitus type 3 and diabetic ketoacidosis – A case report<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>ARTICLEtrue, GABA, and dopamine interplay in autism<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>ARTICLEtrue of lipid profile and obesity in patients with polycystic ovary syndrome<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>ARTICLEtrue of signaling protein ERN1 increases the sensitivity of serine synthesis gene expressions to glucose and glutamine deprivations in U87MG glioblastoma cells<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>ARTICLEtrue relationship between the tumor and its innervation: historical, methodical, morphological, and functional assessments – A minireview<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>ARTICLEtrue knockdown modifies the hypoxic regulation of homeobox gene expression in U87MG glioblastoma cells<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>ARTICLEtrue glycation end products of dietary origin and their association with inflammation in diabetes – A minireview<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>ARTICLEtrue of apolipoprotein E genotypes with a cluster of seven in persons with type 2 diabetes<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>ARTICLEtrue of medicinal plants to ameliorate neovascularization activities in diabetes: A systematic review<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>ARTICLEtrue sorghum ( L.) grain consumption is insufficient to increase adiponectin levels in prediabetic adults<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>ARTICLEtrue controls endoplasmic reticulum stress and hypoxia dependent regulation of insulin receptor and related genes expression in HEK293 cells<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>ARTICLEtrue of malignancy in Thy3 thyroid nodules<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>ARTICLEtrue, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population.</p> <p><bold>Methods.</bold> The study involved 53 obesity cases and 48 non-obesity subjects (controls). The GHRL, LEP, and LEPR genes polymorphism (rs696217, rs7799039, rs1137100, rs1137101, rs1805094) was genotyped using a TaqMan real-time polymerase chain reaction method. Blood hormones (leptin, ghrelin, adiponectin, resistin) were determined with commercially available kits using a Multiskan FC analyzer.</p> <p><bold>Results.</bold> The study of the effect of genotypes of the GHRL (rs696217), LEP (rs7799039), and LEPR (rs1137100, rs1805094) polymorphisms on the level of metabolic hormones (leptin, ghrelin, adiponectin, resistin) in the blood of obese patients did not show reliably significant results. Thus, the presence of the LEPR genes (rs1137101) polymorphism in the Ukrainian population indicates an increased risk of the metabolic syndrome development regardless of the homozygous or heterozygous genotype (genotypes AA, AG, GG).</p> <p><bold>Conclusions.</bold> We established a significant effect of the presence of the A allele and G allele of the LEPR gene polymorphism (rs1137101) on the level of leptin, ghrelin, adiponectin, and resistin in the serum of patients diagnosed with the metabolic syndrome in the Ukrainian population.</p> </abstract>ARTICLEtrue role of kisspeptin in the pathogenesis of a polycystic ovary syndrome<abstract> <title style='display:none'>Abstract</title> <p>Hypothalamic-pituitary gonadal (HPG) axis is responsible for the development and regulation of the female reproductive system. In polycystic ovary syndrome (PCOS), there is a disturbance in the HPG axis. Kisspeptin, a neuropeptide produced by the KISS1 gene, plays a vital role in the regulation of HPG axis by binding with its receptors KISS1R/GPR54, and stimulates gonadotropin secretion from the hypothalamus into pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Polymorphisms or mutations in the KISS1 gene can cause disturbance in the kisspeptin signaling pathway and is thought to disrupt HPG axis. Altered signaling of kisspeptin can cause abnormal secretion of GnRH pulse, which leads to increased LH/FSH ratio, thereby affecting androgen levels and ovulation. The increased levels of androgen worsen the symptoms of PCOS. In the present article, we review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS. The goal of this review article is to provide an overview and metabolic profile of kisspeptin in PCOS patients and the expression of kisspeptin in PCOS animal models. In the present article, we also review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS.</p> </abstract>ARTICLEtrue prevention in diabetes-induced alterations in the rat liver<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> The study was performed to elucidate whether nicotinamide (NAm) can attenuate the diabetes-induced liver damage by correction of ammonia detoxifying function and disbalance of NAD-dependent processes in diabetic rats.</p> <p><bold>Methods.</bold> After four weeks of streptozotocin-induced diabetes, Wistar male rats were treated for two weeks with or without NAm. Urea concentration, arginase, and glutamine synthetase activities, NAD+ levels, and NAD+/NADH ratio were measured in cytosolic liver extracts. Expression of <italic>parp-1</italic> gene in the liver was estimated by quantitative polymerase chain reaction and PARP-1 cleavage evaluated by Western blotting.</p> <p><bold>Results.</bold> Despite the blood plasma lipid peroxidation products in diabetic rats were increased by 60%, the activity of superoxide dismutase (SOD) was reduced. NAm attenuated the oxidative stress, but did not affect the enzyme activity in diabetic rats. In liver of the diabetic rats, urea concentration and arginase activity were significantly higher than in the controls. The glutamine synthetase activity was decreased. Decline in NAD+ level and cytosolic NAD+/NADH ratio in the liver of diabetic rats was observed. Western blot analysis demonstrated a significant up-regulation of PARP-1 expression accompanied by the enzyme cleavage in the diabetic rat liver. However, no correlation was seen between mRNA expression of <italic>parp-1</italic> gene and PARP-1 protein in the liver of diabetic rats. NAm markedly attenuated PARP-1 cleavage induced by diabetes, but did not affect the <italic>parp-1</italic> gene expression.</p> <p><bold>Conclusions.</bold> NAm counteracts diabetes-induced impairments in the rat liver through improvement of its detoxifying function, partial restoration of oxidative stress, NAD+ level, normalization of redox state of free cytosolic NAD+/NADH-couples, and prevention of PARP-1 cleavage.</p> </abstract>ARTICLEtrue of serum adipokines (omentin-1 and visfatin) in coronary artery disease at a North Indian hospital<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Adipose tissue is considered to be an endocrine organ that secretes bioactive substances known as adipokines that contribute to the pathophysiology of metabolic and coronary diseases related to obesity. In this study, various novel biomarkers, such as inflammatory markers that are pro-inflammatory (visfatin) and anti-inflammatory (omentin-1), as prognostic indicators for people with coronary artery disease (CAD) were investigated.</p> <p><bold>Methods.</bold> In this study, 30 diabetic patients with CAD, 30 diabetic patients without CAD, and 30 healthy control counterparts were included. Serum omentin and visfatin concentrations were evaluated by solid-phase enzyme linked immunosorbent assay (ELISA) kit. Patients with established diagnosis of CAD based on angiography, ECG, and elevated cardiac marker level were included into the study. Patients with cardioembolic stroke, cerebral venous sinus thrombosis, CNS vasculitis, and hemorrhage due to trauma, tumor, vascular malformation, and coagulopathy were excluded.</p> <p><bold>Results.</bold> The serum omentin-1 levels were significantly higher in the healthy controls in comparison with the diabetic group (p&lt;0.0001) and serum visfatin levels were significantly higher in the diabetic group in comparison with the healthy controls (p&lt;0.0001). The serum omentin levels were significantly higher in the diabetic group in comparison with the cardio-diabetic group (p&lt;0.0001) and serum visfatin levels were significantly higher in the cardio-diabetic group in comparison with the diabetic group (p&lt;0.0001). The serum omentin-1 showed negative correlation with the serum visfatin in the cardio-diabetic group.</p> <p><bold>Conclusion.</bold> The adipokines, such as omentin and visfatin, may be good therapeutic candidates in preventing or ameliorating CAD.</p> </abstract>ARTICLEtrue