Endocrine regulations最新文献

Objective. IgG4-related disease is a fibro-inflammatory multisystemic condition with lesions mimicking tumors. Involvement of the hypophysis is rare and the first case of IgG4-related hypophysitis was described in 2004. Typically, it is revealed by sellar mass effects, hypopituitarism, and diabetes insipidus. In the present paper, we report a case of IgG4-related hypophysitis revealed by submandibular sialadenitis. Case Report. The subject was a 52-year-old patient presented with swelling of the submandibular gland. His complaints were decreased libido, anorexia, and weight loss for three months. Hormonal assessment found mild hyperprolactinemia, hypogonadotropic hypogonadism, and central hypothyroidism. Pituitary magnetic resonance imaging showed heterogeneous enlargement of the pituitary gland with diffuse gadolinium enhancement. The submandibular gland biopsy revealed submandibular sialadenitis with positive immunohistochemistry to IgG4. Diagnosis of IgG4-related hypophysitis was made based on Leporati criteria 2 and 3. Glucocorticoid therapy was prescribed for this patient, but without improvement of the pituitary function. In fact, the effectiveness of steroid therapy on the pituitary swelling is proven and already represents the fifth diagnostic criterion of Leporati. However, the improvement of the pituitary functions is uncertain. Conclusion. The present case illustrates an atypical presentation of IgG4-related hypophysitis without tumor syndrome or diabetes insipidus. Continuous monitoring of the pituitary function is needed during the long-term follow up given that improvement of the hormonal deficiencies is uncertain.

Objective. Hashimoto's thyroiditis (HT) is a prevalent condition characterized by increased thyroid antibody titers (TAT) in non-celiac disease. The emergence of a gluten-free diet (GFD) as a potential treatment for reducing TAT and HT symptoms is a promising development. However, the potential benefits of gluten withdrawal in HT are not fully understood and the overall evidence is inconclusive. The aim of this review article is to present a systematic protocol for evaluating the effects of a GFD intervention in the treatment of HT in non-celiac disease. Methods. Randomized controlled trials in adults and older people with HT and non-celiac disease following the GFD intervention compared to any gluten dietary and no dietary interventions or placebo (as long as it contains gluten) will be included. We will use Cochrane Central, Medline, Lilacs, Embase, Scopus, and Web of Science for the search. Free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), TAT - anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg), C-reactive protein (CRP), vitamin D, adverse effects, body weight, body mass index (BMI), diet adherence and health-related quality of life will be used as the outcomes. We will present the results in a narrative format and if possible, we will conduct a meta-analysis using a random effects model. The certainty of the evidence using the Grading of Recommendations Assessment Development and Evaluation (GRADE) will be assessed. Conclusion. We will disseminate the results through peer-reviewed publications, social networks, and educational talks. The systematic review will provide valuable information on the effects of the GFD in the treatment of HT in non-celiac disease verifying its impact mainly on TAT.

Objective. Cholestasis is a disorder with accumulation of bile acids in the liver that can lead to toxicity and impairment in liver function and heart. In current study, we investigated the protective effect of ginger extract on the liver and heart damages in cholestatic rats. Methods. Thirty-six male Wistar rats were randomly divided into 6 groups (n=6). Cholestasis was induced in the rats by ligating the bile ducts. The animals were treated with different doses of methanol extract of ginger (100, 200, 400 mg/kg/day) for 28 days. Serum factors including ala-nine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin, and the oxidative stress indices, glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), and total antioxidant capacity in the liver and heart tissues were measured. Histopathological changes were also investigated. Results. The results showed that ligating the bile ducts in rats was associated with an increase in the serum factors including ALT, AST, ALP, and bilirubin. It also increased the amount of ROS, MDA, and decreased the GSH and total antioxidant capacity. On the other hand, severe histo-pathological changes were seen in the liver and heart tissues. The results show that ginger extract reduced the amount of serum factors, modulated the antioxidant indices and improved the histo-pathological changes. Conclusions. According to the results of this study, it can be concluded that the administration of ginger extract can be a new strategy to treat the complication of liver and heart damage caused by cholestasis. The protective effects of ginger against cholestasis and its complications may be mediated by the antioxidant activity of its components.

Objective. Endoplasmic reticulum stress and glucose supply are significant factors in glioblastoma growth. The present study aims to investigate the impact of glucose-dependent control of IGF2BP2, TOB1, HBEGF, TWIST1, CCNH, and E2F1 gene expression in U87MG glioblastoma cells in response to the inhibition of both enzymatic activities of signaling protein ERN1. Methods. The U87MG glioblastoma cells with inhibited both enzymatic activities of ERN1 (endoribonuclease and protein kinase; dnERN1) were used. Cells transfected with an empty vector served as a control. The expression level of the IGF2BP2 and other genes was studied by quantitative RT-PCR. Results. It was shown that the expression level of the IGF2BP2 gene is up-regulated, while that of TOB1 and E2F1 genes is down-regulated in control glioblastoma cells treated with glucose deprivation. Nevertheless, the ERN1 knockdown modified the sensitivity of IGF2BP2 and TOB1 genes to reduced glucose supply. At the same time, the expression of HBEGF, TWIST1, and CCNH genes in control glioblastoma cells was resistant to glucose deprivation conditions. However, inhibition of the enzymatic activities of ERN1 signaling protein strongly increased the impact of glucose deprivation on HBEGF gene expression, but down-regulated the expression of the TWIST1 gene. Conclusion. These results demonstrate that the enzymatic activity of signaling protein ERN1 controls the sensitivity of almost all studied genes to glucose deprivation in U87MG glioblastoma cells in a gene-specific manner. This is important for elucidating the endoplasmic reticulum stress-mediated sensitivity of key regulatory gene expression in glioblastoma cells to glucose supply, a significant factor in tumor growth.

Objective. Diabetes is a chronic disease that causes insulin resistance and destruction of β-cells in pancreas. It is highly associated with hyperglycemia and hyperlipidemia, which can cause microvascular and macrovascular complications. The aim of this systematic review was to evaluate the beneficial effects of medicinal plant extracts on ameliorating glucose levels and lipid profile in diabetic rats. Methods. A systematic review search was conducted using PubMed, Scopus, Google Scholar and ScienceDirect databases using combined terms. The data were extracted and selected by two reviewers under the PRISMA guidelines, which included 25 articles. These 25 articles were selected by the inclusion and exclusion criteria. The quality assessments of the articles were carried out by using the Risk of Bias tool and animal intervention studies. Results. A total of 4651 articles were identified by searching the databases. Articles in the amount of 4505 were then excluded after screening the title and abstract. The remaining 146 articles proceeded to eligibility analysis and finally 25 articles were included into systemic review studies. From the 25 articles reviewed, Clerodendrum volubile showed the highest reducing effect on the blood glucose levels and lipid profile in diabetic rats. Solena amplexicaulis showed the lowest effect on ameliorating glucose levels, while Myrtus communis demonstrated the lowest effect on improving lipid profile in diabetic rats. Conclusion. The reviewed medicinal plant extracts reviewed demonstrated promising efficacy in ameliorating the blood glucose and lipid levels in diabetic rats.

Objective. Polycystic ovary syndrome (PCOS) is one of the commonest endocrinopathies in women characterized by hyperandrogenism, ovulatory dysfunction, and insulin resistance affecting 5-20% of reproductive-aged women worldwide. Recent studies have emphasized the role of the fat mass and obesity-associated (FTO) gene in the development of PCOS, specifically the rs9939609 A/T polymorphism, which is linked to an increased risk of PCOS. The study aimed to investigate the levels of FTO protein and its association with luteinizing hormone (LH), follicle-stimulating hormone (FSH) and anthropometric parameters in patients with PCOS compared to healthy controls. Materials. A total of 298 women, comprising 149 patients and 149 healthy controls, enrolled in the study. Anthropometric parameters (body mass index, BMI; waist circumference, WC; hip circumference, HC; waist-to-hip ratio, WHR), and hormonal assays (LH, FSH, LH/FSH ratio) were performed. FTO protein levels were measured by ELISA kit and their association with these parameters was analyzed. A receiver operator characteristic (ROC) curve analysis was performed to evaluate the discriminatory power of FTO protein levels in distinguishing PCOS cases and controls. A value p<0.05 was considered statistically significant. Results. FTO protein levels were significantly elevated in PCOS women with increased BMI, WC, HC, and WHR (p=<0.05). The mean of BMI showed a positive correlation with both WC (r=0.367, p<0.001) and HC (r=0.395, p<0.001). WC strongly correlated with HC (r=0.780, p<0.001) and WHR (r=0.465, p<0.001). LH significantly correlated with FSH (r=0.543, p<.001), and LH/FSH (r=0.553, p<.001). FTO protein showed a positive correlation with LH (r=0.364, p<0.001), and FSH (r=0.166, p<0.001). Additionally, a negative correlation of FTO protein with BMI (r=-0.190, p<0.05), WC (r=-0.277, p<0.05), and WHR (r=-0.408 p<0.001) was observed. The levels of FTO protein were significantly higher in PCOS patients compared to controls. Significant correlations were also found between FTO protein levels and the anthropometric or hormonal parameters. The AUC for FTO protein levels was 0.624 (p=0.550), indicating moderate discriminatory power, but lacking statistical significance. Conclusion. The study found that FTO protein levels are significantly higher in PCOS women correlating with anthropometric and hormonal parameters (increased LH, decreased FSH). This highlights potential involvement of FTO protein in the hormonal and metabolic disturbances characteristics of the syndrome indicating its biomarker character for the condition.

Objective. Endoplasmic reticulum (ER) stress and hypoxia are key factors for the effective growth of malignant tumors, including glioblastoma. The phosphoserine aminotransferase 1 (PSAT1) is an ER stress-responsive enzyme responsible for serine synthesis and necessary for tumor cell proliferation. The present study aims to investigate the regulation of the PSAT1 gene expression in U87MG glioblastoma cells and normal human astrocytes by ER stress and hypoxia depending on hydrocortisone, a native stress hormone used for co-treatment of glioblastoma and other malignant tumors. Methods. The U87MG glioblastoma cells and normal human astrocytes were used. Hypoxia was introduced by dimethyloxalylglycine. Tunicamycin was used for the induction of ER stress. Further, the cells were treated with hydrocortisone. RNA was extracted from cells after 4 h exposure to hydrocortisone, tunicamycin, and hypoxia. The expression level of the PSAT1 gene was studied by quantitative RT-PCR and normalized to ACTB mRNA. Results. We found that treatment of normal human astrocytes with hydrocortisone resulted in a decreased expression of the PSAT1 gene, but its expression in glioblastoma cells was resistant to this hormone action. However, hypoxia did not significantly change the expression of the PSAT1 gene in normal astrocytes, but strongly modified the effect of hydrocortisone on this gene expression. At the same time, hypoxia increased the expression of the PSAT1 gene in glioblastoma cells independently of hydrocortisone. Tunicamycin decreased the expression of this gene in normal astrocytes, but increased it in glioblastoma cells. In addition, the impact of tunicamycin on PSAT1 gene expression was suppressed by hypoxia in both normal astrocytes and glioblastoma cells and by hydrocortisone only in normal astrocytes. At the same time, the combined effect of hypoxia and hydrocortisone greatly enhanced the expression of the PSAT1 gene in tunicamycin-treated normal astrocytes and especially glioblastoma cells. Conclusion. The results of this study showed that hydrocortisone differentially controls the regulation of PSAT1 gene expression by ER stress and hypoxia in normal astrocytes and glioblastoma cells and that the combined effect of hydrocortisone and hypoxia greatly enhanced PSAT1 gene expression in tunicamycin-treated cells.

Objective. In this retrospective observational study, we aimed to evaluate the impact of insulin degludec/insulin aspart (IDegAsp) treatment on glycemic status, metabolic parameters, and weight/body mass index (BMI) change at a single tertiary diabetes center in Turkey. Methods. We conducted a retrospective cohort study of patients with type 2 diabetes who received IDegAsp treatment between October 2018 and November 2019 at the diabetes outpatient clinic. The patients who had inadequate responses (HbA1c ≥8%) to at least 3 months of experienced insulin (± oral antidiabetic drug [OAD]) treatment were included into the study. Results. One hundred patients (61% females) with a mean age of 61.7±10.0 years (range; 39-88 years) were analyzed. Mean fasting plasma glucose and HbA1c levels decreased by 3rd, 6th, 9th, and 12th months (p=0.010, p=0.007, p=0.027, and p=0.090, respectively and p<0.001, p<0.001, p<0.001, and p=0.001, respectively). Mean body weight and BMI values increased in the 3rd (83.1±15.6 kg and 31.6±5.7 kg/m2, repecitvely) and 6th (87.0±15.4 kg and 32.3±5.3 kg/m2, resepctively) months, although the changes were not statistically significant (p=0.10 and p=0.08, respectively). However, mean body weight returned to baseline levels by the 9th (80.8±17.0 kg and 30.5±6.4 kg/m2, respectively) and 12th (79.5±13.5 kg and 30.5±5.7 kg/m2, respectively) months (p=0.074 and p=0.400, respectively). Conclusions. IDegAsp can provide a significant decrease in HbA1c in a real-life setting. Although weight gain was observed in the first months of the treatment, this effect disappeared over time and decreased to the baseline levels.

Objective. Pituitary neuroendocrine tumors (PitNETS) are common intracranial tumors, but extrasellar or ectopic PitNETS are very rare and supposed to originate from some pituitary remnants. They are mostly found in sphenoidal sinus. But particularly, ectopic clival PitNETS are highly aggressive and can cause bone invasion and can be misdiagnosed as other lesions of the skull base such as chordomas. Case Report. We report a challenging case of an ectopic prolactin-secreting PitNET arising in the clivus in a young female presenting with secondary amenorrhea and sellar mass effect symptoms. On magnetic resonance imaging (MRI), the tumor showed osteolytic features that firstly oriented towards chordoma. Regarding the very high levels of prolactin that constantly exceeded 200 ng/mL, prolactinoma was indeed very presumable. Dopamine agonist treatment was progressively introduced to its maximal tolerated dose, but with neither hormonal response nor size reduction. Hence, surgical resection was decided and the patient underwent an endoscopic transsphenoidal resection of the tumor that was purely ectopic to the clivus. The diagnosis of prolactinoma was confirmed by pathological examination and immunohistochemical staining was intensely and diffusely positive for prolactin and focally for follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The surgery succeeded to normalize prolactin level, but with residual tumor on the fourth month MRI control. Conclusion. Management of these rare tumors should be individualized with multidisciplinary collaboration.

Objective. It is known that inhibition of the endoplasmic reticulum transmembrane signaling protein (ERN1) suppresses the glioblastoma cells proliferation. The present study aims to investigate the impact of inhibition of ERN1 endoribonuclease and protein kinase activities on the TOB1, HBEGF, and TWIST1 gene expression in U87MG glioblastoma cells with an intent to reveal the role of ERN1 signaling in the regulation of expression of these genes. Methods. The U87MG glioblastoma cells with inhibited ERN1 endoribonuclease (dnrERN1) or both enzymatic activities of ERN1 (endoribonuclease and protein kinase; dnERN1) were used. Cells transfected with empty vector served as controls. Wild-type glioblastoma cells were used for mRNA silencing. The expression level of the TOB1, HBEGF, and TWIST1 genes and microRNA were studied by quantitative RT-PCR. Results. We found that inhibition of ERN1 endoribonuclease activity led to a strong down-regulation of HBEGF gene expression in glioblastoma cells and did not significantly change the expression of TOB1 and TWIST1 genes. At the same time, inhibition of both enzymatic activities of ERN1 strongly increased the expression of the TOB1 gene and down-regulated HBEGF and TWIST1 genes in glioblastoma cells. The expression of TWIST1 gene increased, but HBEGF and TOB1 genes significantly decreased in cells with silencing of ERN1 mRNA by specific siRNA. At the same time, silencing of XBP1 mRNA reduced the expression of HBEGF gene only. In addition, in glioblastoma cells with ERN1 knockdown, the level of miR-96-5p was suppressed, but miR-182-5p was increased and could promote post-transcriptional expression of TWIST1, HBEGF, and TOB1 mRNAs. Conclusion. The results of the present study demonstrate that inhibition of ERN1 strongly up-regulated the expression of the anti-proliferative TWIST1 gene through protein kinase activity of ERN1 and that decreased HBEGF and TOB1 genes expression was also controlled preferentially by ERN1 protein kinase activity. These changes in the expression level of TWIST1, HBEGF, and TOB1 genes may also contribute to ERN1 knockdown-mediated suppression of glioblastoma cells proliferation.