<abstract><title style='display:none'>Abstract</title>MODY (Maturity Onset Diabetes of the Young) is a type of diabetes resulting from a pathogenic effect of gene mutations. Up to date, 13 MODY genes are known. Gene HNF1A is one of the most common causes of MODY diabetes (HNF1A-MODY; MODY3). This gene is polymorphic and more than 1200 pathogenic and non-pathogenic HNF1A variants were described in its UTRs, exons and introns. For HNF1A-MODY, not just gene but also phenotype heterogeneity is typical. Although there are some clinical instructions, HNF1A-MODY patients often do not meet every diagnostic criteria or they are still misdiagnosed as type 1 and type 2 diabetics. There is a constant effort to find suitable biomarkers to help with in distinguishing of MODY3 from Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). DNA sequencing is still necessary for unambiguous confirmation of clinical suspicion of MODY. NGS (Next Generation Sequencing) methods brought discoveries of multiple new gene variants and new instructions for their pathogenicity classification were required. The most actual problem is classification of variants with uncertain significance (VUS) which is a stumbling-block for clinical interpretation. Since MODY is a hereditary disease, DNA analysis of family members is helpful or even crucial. This review is updated summary about HNF1A-MODY genetics, pathophysiology, clinics functional studies and variant classification.</abstract>

Novel insights into genetics and clinics of the HNF1A-MODY

<abstract><title style='display:none'>Abstract</title>Pheochromocytomas are rare tumors originating in the adrenal medulla. They may be sporadic or in the context of a hereditary syndrome. A considerable number of pheochromocytomas carry germline or somatic gene mutations, which are inherited in the autosomal dominant way. All patients should undergo genetic testing. Symptoms are due to catecholamines over production or to a mass effect. Diagnosis is confirmed by raised plasma or urine metanephrines or normetanephrines. Radiology assists in the tumor location and any local invasion or metastasis. All the patients should have preoperative preparation with α-blockers and/or other medications to control hypertension, arrhythmia, and volume expansion. Surgery is the definitive treatment. Follow up should be life-long.</abstract>

Pheochromocytoma

<abstract><title style='display:none'>Abstract</title> The maintenance of the body weight at a stable level is a major determinant in keeping the higher animals and mammals survive. Th e body weight depends on the balance between the energy intake and energy expenditure. Increased food intake over the energy expenditure of prolonged time period results in an obesity. Th e obesity has become an important worldwide health problem, even at low levels. The obesity has an evil effect on the health and is associated with a shorter life expectancy. A complex of central and peripheral physiological signals is involved in the control of the food intake. Centrally, the food intake is controlled by the hypothalamus, the brainstem, and endocannabinoids and peripherally by the satiety and adiposity signals. Comprehension of the signals that control food intake and energy balance may open a new therapeutic approaches directed against the obesity and its associated complications, as is the insulin resistance and others. In conclusion, the present review summarizes the current knowledge about the complex system of the peripheral and central regulatory mechanisms of food intake and their potential therapeutic implications in the treatment of obesity.</abstract>

Physiology Department, Faculty of Medicine, MAHSA University, Malaysia

Physiology Department, Faculty of Medicine, Minia University,

Central and peripheral control of food intake

<abstract><title style='display:none'>Abstract</title><bold>Objective.</bold> We conducted an extensive review of the literature and tried to cite the most recent recommendations concerning the pheochromocytoma (PHEO).<bold>Methods.</bold> Pub Med and Google Scholar databases were searched systematically for studies concerning pheochromocytomas (intra-adrenal paragangliomas) from 1980 until 2016. Bibliographies were searched to find additional articles.<bold>Results.</bold> More than four times elevation of plasma fractionated metanephrines or elevated 24-h urinary fractionated metanephrines are keys to diagnosing pheochromocytoma. If the results are equivocal then we perform the clonidine test. If we have not done it already, we preferably do a CT scan and/or an MRI scan. The patient needs pre-treatment with α1-blockers at least 10–14 days before operation. Alternatives or sometimes adjuncts are Calcium Channels Blockers and/or β-Blockers. Several familial syndromes are associated with PHEO and genetic testing should be considered.<bold>Conclusions.</bold> The biggest problem for pheochromocytoma is to suspect it in the first place. Elevated metanephrines establish the diagnosis. With the proper preoperative preparation the risks during operation and the postoperative period are minimal. If there is a risk of the hereditable mutation, it is strongly suggested that all the patients with pheochromocytoma need clinical genetic testing.</abstract>

Pheochromocytoma, diagnosis and treatment: Review of the literature

<abstract><title style='display:none'>Abstract</title><bold>Objective.</bold> There is no reliable treatment for men with idiopathic infertility, but the relationship between severe sperm production and the ratio of estrogen to testosterone levels has been shown. Aromatase is an enzyme that plays an important role in converting testosterone to estradiol and androstenedione to estrogen. Aromatase inhibitors can increase testosterone and androgen production without increasing the amount of estrogen in circulation. The aim of this study was to evaluate the effect of aromatase inhibitor letrozole on the male infertility.<bold>Method.</bold> This pre- and post-quasi-experimental clinical trial was carried out on 41 men with an infertility diagnosis. The basic hormonal profile included FSH, LH, testosterone, and estradiol. The ratio of testosterone to serum estradiol was also calculated and recorded. The sperm analysis was performed before the treatment and the seminal parameters were evaluated and recorded. Patients were then treated with letrozole 2.5 mg daily for 4 months. At the end of 4th months, the hormonal profile was studied and seminal analysis performed and recorded.<bold>Results.</bold> The levels of FSH, LH, testosterone, and estradiol, and the ratio of testosterone to estradiol increased significantly after letrozole treatment. The sperm concentration, sperm motility, and sperm forward motion significantly increased after letrozole treatment. Sperm morphology only lightly altered.<bold>Conclusion.</bold> The ratio of testosterone to estradiol levels in infertile men treated with aromatase inhibitor improved and caused changes in sperm parameters. Letrozole may be used to improve sperm parameters in infertile men with low serum testosterone to estradiol ratio.</abstract>

Effect of letrozole on spermogram parameters and hormonal profile in infertile men: A clinical trial study

<abstract>
<title style='display:none'>Abstract</title>
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women associated with cardiovascular disease and obesity. The possible benefits of omega-3 supplementation in this syndrome have been discussed much. This study is aimed to verify, based on the scientific data published, if there are any benefits in the omega-3 supplementation in the treatment of PCOS and to indicate its possible dosages for the treatment of polycystic ovary. The work consists of a systematic review of clinical trials and cohort of the MEDLINE/PubMed database from 2009 to October 2019. All studies that analyzed the omega-3 supplementation in women with PCOS were included. Cross-sectional studies, review articles, systematic reviews, meta-analysis, duplicates, studies in animals or cell culture, studies with omega-3 supplementation via food or associated with other supplementations were not included, except those involving vitamin E. In total, 21 articles were selected. Despite the heterogeneity of the studies selected, indirect benefits were observed mainly regarding the glycemic profile, such as insulin resistance reduction, lipid profile modulation (i.e. decrease in total cholesterol, triglycerides, and elevation of high-density lipoprotein), and the regulation of the androgenic profile. As for the anthropometric profile, the studies were scarce and most of them had no significant meaning. Regarding the antioxidant profile and inflammatory biomarkers, the findings differ among studies, but promising results were observed with different doses over 12 weeks of use, such as C-reactive protein (CRP) reduction. Thus, omega-3 fatty acids promote indirect benefits in the treating of women with PCOS. However, to reveal well-defined standards for dosage and supplementation time, further studies are needed.
</abstract>

Omega-3 supplementation in the treatment of polycystic ovary syndrome (PCOS) – a review of clinical trials and cohort

<abstract>
<title style='display:none'>Abstract</title>
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.
</abstract>

Oxytocin, GABA, and dopamine interplay in autism

<abstract>
<title style='display:none'>Abstract</title>
<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.
<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.
<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.
<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.
</abstract>

Association of lipid profile and obesity in patients with polycystic ovary syndrome

<abstract>
<title style='display:none'>Abstract</title>
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.
</abstract>

Persistent 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>
<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.
<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.
<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.
<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.
</abstract>

Inhibition 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>
<sec><title style='display:none'>Objective.</title>
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.
</sec>
<sec><title style='display:none'>Methods.</title>
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.
</sec>
<sec><title style='display:none'>Results.</title>
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>.
</sec>
<sec><title style='display:none'>Conclusion.</title>
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.
</sec>
</abstract>

ERN1 knockdown modifies the hypoxic regulation of homeobox gene expression in U87MG glioblastoma cells

<abstract><title style='display:none'>Abstract</title>
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.
</abstract>

The relationship between the tumor and its innervation: historical, methodical, morphological, and functional assessments – A minireview

Instructions for Reviewers

Open Access License

Instructions to Authors

Editorial Policy

Endocrine Regulations

 Endocrine Regulations (from 1967 to 1990 as Endocrinologia Experimentalis), an open access, peer reviewed international journal, welcomes the submission of original research papers and...

Cite Score

SNIP

MNiSW

Google Scholar h5-index

Google Scholar h5-median

 Endocrine Regulations (from 1967 to 1990 as Endocrinologia Experimentalis), an open access, peer reviewed international journal, welcomes the...