rss_2.0Endocrine Regulations FeedSciendo RSS Feed for Endocrine Regulations Regulations Feed, 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 stress in liver of streptozotocin-induced diabetic mice fed a high-fat diet: A treatment role of L.<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> The aim of this study was the investigation of a treatment role of Artemisia annua L. (AA) on liver dysfunction and oxidative stress in high-fat diet/streptozotocin-induced diabetic (HFD/STZ) mice.</p> <p><bold>Methods.</bold> Sixty mice were divided into 12 groups including control, untreated diabetic, and treated diabetic ones with metformin (250 mg/kg), and doses of 100, 200, and 400 mg/kg of water (hot and cold) and alcoholic (methanol) extracts of AA. Type 2 diabetes mellitus (T2DM) was induced in mice by high-fat diet for 8 weeks and STZ injection in experimental animals. After treatment with doses of 100, 200 or 400 mg/kg of AA extracts in HFD/STZ diabetic mice for 4 weeks, oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and free radicals (ROS) were determined in the liver tissue in all groups.</p> <p><bold>Results.</bold> Diabetic mice treated with metformin and AA extracts showed a significant decrease in ROS and MDA concentrations and a notable increase in GSH level in the liver. Effectiveness of higher doses of AA extracts (200 and 400 mg/kg), especially in hot-water and alcoholic ones, were similar to and/or even more effective than metformin.</p> <p><bold>Conclusion.</bold> Therapeutic effects of AA on liver dysfunction showed that antioxidant activity of hot-water and alcoholic AA extracts were similar or higher than of metformin.</p> </abstract>ARTICLEtrue controls the expression of genes responsible for serine synthesis in U87MG cells on ERN1-dependent manner<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Serine synthesis as well as endoplasmic reticulum stress and hypoxia are important factors of malignant tumor growth including glioblastoma. Previous studies have shown that the knockdown of ERN1 (endoplasmic reticulum to nucleus signaling) significantly suppressed the glioblastoma cell proliferation and modified the hypoxia regulation. The present study is aimed to investigate the impact of hypoxia on the expression of <italic>PHGDH</italic> (phosphoglycerate dehydrogenase), <italic>PSAT1</italic> (phosphoserine aminotransferase 1), <italic>PSPH</italic> (phosphoserine phosphatase), <italic>ATF4</italic> (activating transcription factor 4), and <italic>SHMT1</italic> (serine hydroxymethyltransferase 1) in U87MG glioblastoma cells in relation to knockdown of ERN1 with the intent to reveal the role of ERN1 signaling pathway on the endoplasmic reticulum stress-dependent regulation of expression of these genes.</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 to hypoxia introduced by dimethyloxalylglycine for 4 h. RNA was extracted from cells and reverse transcribed. The expression level of <italic>PHGDH</italic>, <italic>PSAT1</italic>, <italic>PDPH</italic>, <italic>SHMT1</italic>, and <italic>ATF4</italic> genes was studied by real-time qPCR and normalized to ACTB.</p> <p><bold>Results.</bold> It was found that hypoxia up-regulated the expression level of <italic>PHGDH</italic>, <italic>PSAT1</italic>, and <italic>ATF4</italic> genes in control U87MG cells, but <italic>PSPH</italic> and <italic>SHMT1</italic> genes expression was down-regulated. The expression of <italic>PHGDH</italic>, <italic>PSAT1</italic>, and <italic>ATF4</italic> genes in glioblastoma cells with knockdown of ERN1 signaling protein was more sensitive to hypoxia, especially <italic>PSAT1</italic> gene. At the same time, the expression of <italic>PSPH</italic> gene in ERN1 knockdown cells was resistant to hypoxia. The expression of <italic>SHMT1</italic> gene, encoding the enzyme responsible for conversion of serine to glycine, showed similar negative sensitivity to hypoxia in both control and ERN1 knockdown glioblastoma cells.</p> <p><bold>Conclusion.</bold> The results of the present study demonstrate that the expression of genes responsible for serine synthesis is sensitive to hypoxia in gene-specific manner and that ERN1 knockdown significantly modifies the impact of hypoxia on the expression of <italic>PHGDH</italic>, <italic>PSAT1</italic>, <italic>PSPH</italic>, and <italic>ATF4</italic> genes in glioblastoma cells and reflects the ERN1-mediated reprograming of hypoxic regulation at gene expression level.</p> </abstract>ARTICLEtrue of leucocyte and platelet indices in patients with type 2 diabetes mellitus with microvascular complications at a tertiary care hospital in south India – A prospective cross-sectional study<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> The present study was directed to assess the correlation between leukocyte and platelet indices and microvascular complications in patients with type 2 diabetes mellitus (T2DM).</p> <p><bold>Methods.</bold> A prospective cross-sectional study was conducted between January 2020 and May 2021 at a tertiary healthcare center. Sixty T2DM patients, who fulfilled the inclusion and exclusion criteria, were included into the study and divided into 2 groups: T2DM patients with microvascular complications and T2DM patients without vascular complications. Clinical history was taken and examinations (routine complete blood count) were done to obtain platelet indices, neutrophillymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were obtained and tabulated. A correlation was statistically analyzed from the obtained data, p value &lt;0.05 was considered to be statistically significant.</p> <p><bold>Results.</bold> From the patients with microvascular complications, 18 cases suffered from retinopathy and nephropathy. Majority of the participants suffered from moderate non-proliferative retinopathy. The creatine median and absolute neutrophil count (ANC) were significantly higher in T2DM patients with microvascular complications (p&lt;0.0001 and p&lt;0.0054, respectively) compared to T2DM patients without vascular complications. No significant correlation was found between platelet indices, NLR, PLR with regard to fasting blood sugar, post prandial blood sugar, HbA1C in T2DM patients.</p> <p><bold>Conclusions.</bold> Since no significant correlation was found between the different platelet indices and microvascular complications, it is evident that these markers cannot be used as the predictors of microvascular complications in T2DM patients.</p> </abstract>ARTICLEtrue of DNA methylation of gene changes in the patients with type 2 diabetes mellitus as a predictive biomarker instead of HbA1c, random blood sugar, lipid profile, kidney function test, and some risk factors<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Nowadays, type 2 diabetes mellitus (T2DM) is the most common chronic endocrine disorder, affecting an estimated 5–10% of adults worldwide and this disease rapidly increases in the Kurdistan region population. This research aims to identify DNA methylation change in the <italic>CPAN10</italic> gene as a predictive biomarker in T2DM and the association between DNA methylation status with lipid profile and kidney function test.</p> <p><bold>Methods.</bold> The participants (113) were divided into three groups: diabetes group (47), prediabetes group (36), and control group (30). The study was carried out on patients who visited the private clinical sectors between August and December 2021 in the Koya city Kurdistan region of Iraq. To determine DNA methylation status, methylation-specific PCR (MPS) with paired primer for each methylated and unmethylated region was used. The Mann-Whitney U test and Spearman’s correlation were performed for statistical analysis of data and a value of p&lt;0.05 was considered significant.</p> <p><bold>Results.</bold> The obtained results show that DNA hypermethylation was recorded in the promoter region in the samples of the diabetes and prediabetes groups compared to the healthy group (control). Various factors also affected the level of DNA methylation, such as HbA1c in prediabetes group and body mass index in the control group.</p> <p><bold>Conclusion.</bold> These results indicate that DNA methylation changes in the <italic>CAPN10</italic> gene promoter region may be used as a potential predictive biomarker to diagnose T2DM; however, this study requires further data to support this evidence.</p> </abstract>ARTICLEtrue of liver parameters in diabetes mellitus – a narrative review<abstract> <title style='display:none'>Abstract</title> <p>Diabetes mellitus is characterized by hyperglycemia and abnormalities in insulin secretion and function. This review article focuses on various liver parameters, including albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alpha fetoprotein (AFP), alpha 1 antitrypsin (AAT), ammonia, bilirubin, bile acid, gamma-glutamyl transferase (GGT), immunoglobulin, lactate dehydrogenase (LDH), and total protein. These parameters play significant roles in the development of different types of diabetes such as type 1 diabetes (T1DM), type 2 diabetes (T2DM) and gestational diabetes (GDM). The article highlights that low albumin levels may indicate inflammation, while increased ALT and AST levels are associated with liver inflammation or injury, particularly in non-alcoholic fatty liver disease (NAFLD). Elevated ALP levels can be influenced by liver inflammation, biliary dysfunction, or bone metabolism changes. High bilirubin levels are independently linked to albuminuria in T1DM and an increased risk of T2DM. Elevated GGT levels are proposed as markers of oxidative stress and liver dysfunction in T2DM. In GDM, decreased serum AFP levels may indicate impaired embryo growth. Decreased AFP levels in T2DM can hinder the detection of hepatocellular carcinoma. Hyperammonemia can cause encephalopathy in diabetic ketoacidosis, and children with T1DM and attention deficit hyperactivity disorder often exhibit higher ammonia levels. T2DM disrupts the regulation of nitrogen-related metabolites, leading to increased blood ammonia levels. Bile acids affect glucose regulation by activating receptors on cell surfaces and nuclei, and changes in bile acid metabolism are observed in T2DM. Increased LDH activity reflects metabolic disturbances in glucose utilization and lactate production, contributing to diabetic complications. Poor glycemic management may be associated with elevated levels of IgA and IgG serum antibodies, and increased immunoglobulin levels are also associated with T2DM.</p> </abstract>ARTICLEtrue of the GHRL gene (rs696217) polymorphism on the metabolic disorders in patients with obesity in the Ukrainian population<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Over the past four decades, the prevalence of obesity has tripled and limited genetic studies with specific SNPs have been conducted, but no investigations using ghrelin and obestatin prepropeptide (GHRL) gene have been reported in the Ukrainians population. The aim of this study was to evaluate changes in the level of metabolic hormones in the blood of obese patients in relation to the GHRL (rs696217) polymorphism.</p> <p><bold>Methods.</bold> The study involved 53 obesity cases and 48 non-obesity subjects (controls). The GHRL (rs696217) polymorphism was genotyped using a TaqMan real-time polymerase chain reaction method. Blood hormones were determined with commercially available kits using a Multi-skan FC analyzer.</p> <p><bold>Results.</bold> Carriers of the T allele of the GHRL (rs696217) polymorphism were statistically significantly more in patients diagnosed with obesity compared to controls indicating a genetically determined cause of obesity. We also established a significant effect of the presence of the T allele of the GHRL (rs696217) polymorphism on the decrease in the adiponectin level and the increase of resistin level in obese patients. The study of the effect of genotypes (TT, GT, GG) of the GHRL (rs696217) polymorphism on the metabolic hormone levels in the blood of obese patients did not show reliably significant differences.</p> <p><bold>Conclusions.</bold> The presence of the T allele of the GHRL (rs696217) polymorphism in Ukrainian population indicates an increased risk of the obesity development regardless on the homozygous or heterozygous genotype.</p> </abstract>ARTICLEtrue of selected nuclear receptors in human epithelial ovarian cell line Caov3 exposed to bisphenol derivatives<abstract> <title style='display:none'>Abstract</title> <p><bold>Objectives.</bold> Bisphenol A (BPA) is an indispensable industrial chemical. However, as a proven endocrine disruptor, it may be associated with several health disturbances, including the reproductive functions impairment and cancer. Due to the restriction of BPA usage, many bisphenol derivatives gradually substitute BPA. However, studies have reported adverse biological effects of BPA analogs, but the specific sites of their action remain largely unknown. Nuclear receptors (NRs) appear to play significant roles in various types of cancer. In addition, they are considered relevant targets of bisphenols. In the present study, we investigated the effects of BPA and its analogs bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) on mRNA expression of selected NRs in the human ovarian epithelial cell line Caov3. The NRs examined included retinoic acid receptor α (<italic>RARA</italic>), retinoid X receptor α (<italic>RXRA</italic>), peroxisome proliferator activating receptor β/δ (<italic>PPARD</italic>), chicken ovalbumin upstream promoter-transcription factor 2 (<italic>COUPTFII</italic>), and nuclear receptor-related protein 1 (<italic>NURR1</italic>).</p> <p><bold>Methods.</bold> Caov3 cells were treated with the bisphenols at the concentrations of 1 nM, 100 nM, 10 µM and 100 µM. After 24 h and 72 h of incubation, cell viability was determined by the MTS assay, and the selected genes expression was analyzed using RT-qPCR.</p> <p><bold>Results.</bold> Bisphenol treatment did not affect Caov3 cell viability, except the significant impairment after exposure to the highest BPAF dose (100 µM). At lower doses, neither bisphenol analog altered the expression of the NRs. However, at the highest concentration (100 µM), BPAF and BPA altered the mRNA levels of <italic>PPARD</italic>, <italic>COUPTFII</italic>, and <italic>NURR1</italic> in a time- and receptor-specific manner.</p> <p><bold>Conclusions.</bold> The effects of bisphenols on the specific NRs in the epithelial ovarian cancer cells were addressed for the first time by the present study. Although generally we did not find that bisphenols may provoke significant alterations in the expression of the selected NRs in Caov3 cells, they may alter mRNA expression of certain NRs at high concentrations.</p> </abstract>ARTICLEtrue between the size of pheochromocytoma and the level of metanephrines<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Pheochromocytomas (PHEO) and paraganglioma (PGLs) are rare neuroendocrine catecholamine-producing tumors that arise from the chromaffin cells of either the adrenal medulla or extra-adrenal paraganglionic tissues. Despite the recent advances in imaging technologies, biochemical evidence of excessive catecholamine production by the tumor is considered the most important test for the diagnosis of these tumors. The aim of the present study is to investigate the role of the catecholamine metabolites (normetanephrine and metanephrine) levels in the diagnosis of PHEO/PGLs and to evaluate if their levels correlate with the size of these tumors.</p> <p><bold>Patients and Methods.</bold> Twenty-five patients were included in the study during the time period of 10 years. Their data were compared with another set of 25 patients to obtain the sensitivity and specificity of metanephrine and normetanephrine in the diagnosis of PHEO/PGLs. The tumor size was reviewed in every patient to obtain the correlation coefficient between the tumor sizes and the plasma/24-hour urinary metanephrine levels.</p> <p><bold>Results.</bold> The sensitivity and specificity rates for plasma metanephrine were 80–92% and 92–96%, respectively; while for 24-hour urinary metanephrine were 80–90% and 95–100%, respectively. We found a strong positive relationship between the tumor size and the plasma levels of normetanephrine (r=0.518, p&lt;0.01), and metanephrine (r=0.577, p&lt;0.01). While the relation with the 24-hour urinary concentrations of normetanephrine (r=0.384, p=0.01) and 24-h urinary meta-nephrine (r=0.138, p&lt;0.01) was low.</p> <p><bold>Conclusion.</bold> The determination of plasma and 24-hour urinary levels of metanephrines is a reliable test for the diagnosis of PHEO, as they are continuously produced by the tumor cells in contrast to catecholamines.</p> </abstract>ARTICLEtrue disorders during endogenous Cushing’s syndrome: prevalence, associated factors, and outcome after remission<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> The prognosis of Cushing’s syndrome (CS) is related to a higher cardiovascular morbidity and mortality. This study aimed to determine the prevalence of metabolic disorders in patients with CS, the associated factors, and the rate of remission of these disorders after the remission from CS.</p> <p><bold>Methods.</bold> It is a retrospective study including 75 cases of CS followed up at the university hospital La Rabta of Tunis from 1987 to 2018. Clinical and paraclinical data were collected from medical files.</p> <p><bold>Results.</bold> The mean age of the patients was 44.1±18.9 years and the sex ratio was 0.39. At CS diagnosis, the frequencies of obesity, hypertension, diabetes, dyslipidemia, and metabolic syndrome were 52, 75, 43, 83, and 73%, respectively. The age, gender, body mass index, waist circumference, and baseline serum cortisol level were not associated with the presence of diabetes, hypertension or dyslipidemia. Forty-eight patients were operated on. At one year, 38 patients were in remission from CS. The remission rates of hypertension, diabetes, and dyslipidemia were respectively 58% (p&lt;0.001), 76% (p&lt;0.001), and 17% (NS).</p> <p><bold>Conclusion.</bold> Metabolic disorders were frequent during CS and their frequencies decreased after the remission from the syndrome.</p> </abstract>ARTICLEtrue of antipsychotics, haloperidol and olanzapine, on the expression of apoptosis-related genes in mouse mHippoE-2 cells and rat hippocampus<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Modified levels of pro- (caspase3, Bax) and anti-apoptotic (Bcl-2) regulatory proteins have been detected in certain brain areas of schizophrenic patients indicating a possible dysregulation of apoptosis. In the present study, effects of antipsychotics, haloperidol (HAL) and olanzapine (OLA), on the gene expression of caspase3 (<italic>casp3</italic>), <italic>Bax</italic> and <italic>Bcl-2</italic> were studied <italic>in vitro</italic> in mouse hippocampal mHippoE-2 cell line and <italic>in vivo</italic> in the hippocampus of MK-801 animal schizophrenia model with the aim to provide evidence that antipsychotics may affect the activity of apoptosis-related markers.</p> <p><bold>Methods.</bold> mHippoE-2 cells were incubated with MK-801 (20 µM), HAL (10 µM), and OLA (10 µM) alone or combined, MK-801+HAL/OLA, for 24, 48, and 72 h. Male Sprague Dawley rats were injected with saline or MK-801 (0.5 mg/kg) for 6 days and since the 7th day, they were treated with vehicle (VEH), HAL (1 mg/kg) or OLA (2 mg/kg) for the next 7 days. The <italic>casp3</italic>, <italic>Bax</italic> and <italic>Bcl-2</italic> gene expression in mHippoE-2 cells and rat hippocampus was measured by RT-PCR.</p> <p><bold>Results.</bold> In mHippoE-2 cells, <italic>casp3</italic> gene expression was increased by MK-801 and OLA treatments alone for 48 h, HAL treatment alone for 24 and 72 h, and co-treatment with MK-801+OLA for 24 and 72 h compared to controls. HAL and OLA suppressed the stimulatory effect of MK-801 on <italic>casp3</italic> mRNA levels in cells after 48 h of incubation. <italic>Bax</italic> mRNA levels in mHippoE-2 cells were decreased after HAL treatment for 24 and 48 h, and also after co-treatment with MK-801+HAL for 72 h. <italic>In vivo</italic>, MK-801 decreased mRNA levels of both pro-apoptotic markers, <italic>casp3</italic> and <italic>Bax</italic>, in hippocampus of VEH-treated rats and <italic>Bax</italic> mRNA levels in hippocampus of HAL-treated animals. OLA reversed the inhibitory effect of MK-801 on <italic>casp3</italic> expression in the VEH-treated animals. Neither MK-801 nor antipsychotics induced changes in the gene expression of anti-apoptotic marker <italic>Bcl-2</italic> in mHippoE-2 cells as well as hippocampus of rats.</p> <p><bold>Conclusions.</bold> The results of the present study demonstrate that antipsychotics, HAL and OLA, may affect mRNA levels of pro-apoptotic markers in hippocampal cells <italic>in vitro</italic>, but not <italic>in vivo</italic>. The obtained data do not clearly support the assumed potentiating role of MK-801 in inducing apoptosis in specific brain areas and a possible protective role of antipsychotics against induction of apoptosis. The obtained data may contribute to a deeper insight into the neurodevelopmental changes connected with schizophrenia.</p> </abstract>ARTICLEtrue of DNAJB9 and some other genes is more sensitive to SWCNTs in normal human astrocytes than glioblastoma cells<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Single-walled carbon nanotubes (SWCNTs) are considered to be one of the nanomaterials attractive for biomedical applications, particularly in the health sciences as imaging probes and drug carriers, especially in the field of cancer therapy. The increasing exploitation of nanotubes necessitates a comprehensive evaluation of the potential impact of these nanomaterials, which purposefully accumulate in the cell nucleus, on the human health and the function of the genome in the normal and tumor tissues. The aim of this study was to investigate the sensitivity of the expression of <italic>DNAJB9</italic> and some other genes associated with the endoplasmic reticulum (ER) stress and cell proliferation to low doses of SWCNTs in normal human astrocytes (NHA/TS) and glioblastoma cells (U87MG) with and without an inhibition of ERN1 signaling pathway of the ER stress.</p> <p><bold>Methods.</bold> Normal human astrocytes, line NHA/TS and U87 glioblastoma cells stable transfected by empty vector or dnERN1 (dominant-negative construct of ERN1) were exposed to low doses of SWCNTs (2 and 8 ng/ml) for 24 h. RNA was extracted from the cells and used for cDNA synthesis. The expression levels of DNAJB9, TOB1, BRCA1, DDX58, TFPI2, CLU, and P4HA2 mRNAs were measured by a quantitative polymerase chain reaction and normalized to ACTB mRNA.</p> <p><bold>Results.</bold> It was found that the low doses of SWCNTs up-regulated the expression of <italic>DNAJB9</italic>, <italic>TOB1</italic>, <italic>BRCA1</italic>, <italic>DDX58</italic>, <italic>TFPI2</italic>, <italic>CLU</italic>, and <italic>P4HA2</italic> genes in normal human astrocytes in dose-dependent (2 and 8 ng/ml) and gene-specific manner. These nanotubes also increased the expression of most studied genes in control (transfected by empty vector) U87 glioblastoma cells, but with much lesser extent than in NHA/TS. However, the expression of <italic>CLU</italic> gene in control U87 glioblastoma cells treated with SWCNTs was down-regulated in a dose-dependent manner. Furthermore, the expression of <italic>TOB1</italic> and <italic>P4HA2</italic> genes did not significantly change in these glioblastoma cells treated by lower dose of SWCNTs only. At the same time, inhibition of ERN1 signaling pathway of ER stress in U87 glioblastoma cells led mainly to a stronger resistance of <italic>DNAJB9</italic>, <italic>TOB1</italic>, <italic>BRCA1</italic>, <italic>DDX58</italic>, <italic>TFPI2</italic>, and <italic>P4HA2</italic> gene expression to both doses of SWCNTs.</p> <p><bold>Conclusion.</bold> The data obtained demonstrate that the low doses of SWCNTs disturbed the genome functions by changing the levels of key regulatory gene expressions in gene-specific and dose-dependent manner, but their impact was much stronger in the normal human astrocytes in comparison with the tumor cells. It is possible that ER stress, which is constantly present in tumor cells and responsible for multiple resistances, also created a partial resistance to the SWCNTs action. Low doses of SWCNTs induced more pronounced changes in the expression of diverse genes in the normal human astrocytes compared to glioblastoma cells indicating for a possible both genotoxic and neurotoxic effects with a greater extent in the normal cells.</p> </abstract>ARTICLEtrue and safety of SGLT2 inhibitors in individuals with type 1 diabetes under continuous subcutaneous insulin infusion: a real-world study<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII.</p> <p><bold>Methods.</bold> Retrospective study includes 34 T1D adult individuals under CSII, who started SGLT2i until 30th June 2021. Data regarding the glycemic control and acute diabetes complications at the moment of introduction of SGLT2i and after 3, 6, and 12 months of use were collected.</p> <p><bold>Results.</bold> Twenty-three individuals were included. Comparing with the moment of SGLT2i introduction after 3, 6, and 12 months of use, there was a statistically significant increase of time in range (TIR) (∆<sub>T3M</sub>=12.8%; ∆<sub>T6M</sub>=11.5%; ∆<sub>T12M</sub>=11.1%), and a decrease in time above range (∆<sub>T3M</sub>=13.6%; ∆T6M=11.9%; ∆<sub>T12M</sub>=10.5%). There were no significant differences in time below the range. Mean glucose and mean glucose management indicator significantly reduced in the 3 evaluated moments. A significant reduction in median weight was also observed (∆<sub>T6M</sub>=2 kg; ∆<sub>T12M</sub>=4.5 kg). Two patients (8.7%) developed mild euglycemic DKA during SGLT2i treatment, both were women and had body mass index (BMI) &lt;27 kg/m<sup>2</sup>. One of them had a total daily insulin dose (TDDI) reduction of 26.9% after 3 months of use.</p> <p><bold>Conclusions.</bold> The use of SGLT2i, as an adjuvant treatment in T1D individuals under CSII, was associated with a significant increase of TIR without increasing time in hypoglycemia. It also had a weight benefit. Careful use in selected participants is necessary to reduce the occurrence of DKA.</p> </abstract>ARTICLEtrue narrative review on pathogenetic mechanisms of hyperinsulinemic hypoglycemia in Kabuki syndrome<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Kabuki syndrome (KS) is associated with hyperinsulinemic hypoglycemia (HH) in 0.3–4% of patients, thus exceeding the prevalence in the general population. HH association is stronger for KS type 2 (KDM6A-KS, OMIM #300867) than KS type 1 (KMT2D-KS, OMIM #147920). Both the disease-associated genes, KMD6A and KMT2D, modulate the chromatin dynamic. As such, KS is considered to be the best characterized pediatric chromatinopathy. However, the exact pathogenetic mechanisms leading to HH in this syndrome remain still unclear.</p> <p><bold>Methods.</bold> We selected on the electronic database PubMed all articles describing or hypothesizing the mechanisms underlying the dysregulated insulin secretion in KS.</p> <p><bold>Results.</bold> The impact on the gene expression due to the KDM6A or KMT2D function loss may lead to a deregulated pancreatic β-cell differentiation during embryogenesis. Moreover, both KMT2D gene and KDM6A gene are implicated in promoting the transcription of essential pancreatic β-cell genes and in regulating the metabolic pathways instrumental for insulin release. Somatic KMT2D or KDM6A mutations have also been described in several tumor types, including insulinoma, and have been associated with metabolic pathways promoting pancreatic cell proliferation.</p> <p><bold>Conclusions.</bold> The impact of pathogenic variants in KDM6A and KDM2D genes on β-cell insulin release remains to be fully clarified. Understanding this phenomenon may provide valuable insight into the physiological mechanisms of insulin release and into the pathological cascade causing hyperinsulinism in KS. The identification of these molecular targets may open new therapeutic opportunities based on epigenetic modifiers.</p> </abstract>ARTICLEtrue of aspartate aminotransferase platelet ratio index score and insulin resistance in type 2 diabetes mellitus with non-alcoholic fatty liver disease<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases characterized by the presence of ectopic fat in the liver and steatosis, which cannot be explained by alcohol consumption. The association between NAFLD and type 2 diabetes mellitus (T2DM) is well established. As liver fibrosis progresses in a patient with NAFLD, insulin resistance (IR) increases and may worsen diabetes control. The aspartate aminotransferase platelet ratio index (APRI) score is a simple and inexpensive bedside marker that can detect liver fibrosis and cirrhosis. Several studies have shown an association between APRI and NAFLD. However, there is a gap in correlation with IR in patients with diabetes. In this study, we sought to correlate IR and NAFLD in diabetes using the APRI score.</p> <p><bold>Methods.</bold> This observational hospital-based cross-sectional study was conducted in the Department of General Medicine, one of the tertiary care hospitals in North India, from February 2019 to July 2020. A total of 70 patients were taken for the study. Patients with T2DM, aged &gt;30 years, who had no history of alcohol use and who had or were newly diagnosed with NAFLD were enrolled in the study.</p> <p><bold>Results.</bold> Significant differences in mean HbAc1, AST, serum insulin, APRI score and homeo-static model assessment-2 (HOMA2) IR between NAFLD grade 1, grade 2, and grade 3 groups were found. Pearson correlation between APRI score and HOMA2 IR total values revealed a significant positive correlation between them.</p> <p><bold>Conclusions.</bold> The data of the present study indicate that the APRI score can be used to assess the IR degree and provide important information for improving glycemic control in T2DM patients with NAFLD.</p> </abstract>ARTICLEtrue types in hypothyroid patients in a Coimbatore tertiary care hospital: A prospective observational study<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Hypothyroidism is a syndrome characterized by clinical manifestations associated with thyroid hormone deficiency. The thyroid hormone plays a pivotal role in the hematopoietic system and stimulates precursors of erythropoietin gene expression. Therefore, anemia is a common clinical manifestation in hypothyroid individuals. The goal of this study was to carry out a prospective analysis of the prevalence of anemia, its types, and the etiology behind the differing anemia morphology among hypothyroid patients.</p> <p><bold>Methods.</bold> The study was conducted with a sample size of 100 patients suffering from hypothyroidism. The methodology of the study included a questionnaire and consent filling for general information followed by a complete blood test for assessment of blood count, peripheral smear, FT3/FT4 (free triiodothyronine/thyroxine), anemia profile, vitamin B12, folate, LDH (lactate dehydrogenase), reticulocyte count, and thyroid stimulating hormone (TSH).</p> <p><bold>Results.</bold> The results of the study are in line with the previous studies and showed severe anemia and prevalence among women of reproductive age. Microcyte hypochromic anemia was found to be the most common type of morphological anemia, which was validated with low hemoglobin (Hb) levels, vitamin B12, FT3, and FT4. Additionally, TSH showed a positive correlation with reticulocyte count, LDH, and Hb in Pearson’s correlation test.</p> <p><bold>Conclusion.</bold> The study summarizes the need to investigate the underlying etiological agent responsible for better therapy and management of hypothyroidism and anemia suggesting also the use of oral iron supplements along with levothyroxine therapy.</p> </abstract>ARTICLEtrue associated with a succinate dehydrogenase subunit B mutation: A minireview and a case report<abstract> <title style='display:none'>Abstract</title> <p><bold>Objective.</bold> Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that arise from the chromaffin cells of the adrenal medulla or extra-adrenal tissues. These tumors are characterized by an excessive secretion of catecholamines, which are responsible for the clinical manifestation of the disease. Although most of these tumors are sporadic, underlying genetic abnormalities may be present in up to 24% of the cases. A succinate dehydrogenase subunit B (SDHB) mutation represents one of the rare presentations of the disease. In this study, we represent a rare case of pheochromocytoma associated with SDHB mutation.</p> <p><bold>Methods.</bold> We performed a retrospective review of our case in addition to reviewing the available literature on the same topic.</p> <p><bold>Results.</bold> A 17-year-old patient presented with sustained hypertension. Clinical, laboratory, and radiological evaluations confirmed the diagnosis of catecholamine-secreting tumor. Laparoscopic adrenalectomy was performed. Histopathological and genetic testing confirmed a pheochromocytoma associated with SDHB mutation. No recurrence was detected on two-years of follow up.</p> <p><bold>Conclusion.</bold> Pheochromocytoma associated with SDHB mutation is a rare presentation. Genetic testing for suspecting cases is essential to help to establish the appropriate follow-up plan.</p> </abstract>ARTICLEtrue