Endocrine regulations最新文献

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.

Objective. Genetic factors contribute to the development of metabolic syndrome and subsequent arterial hypertension (AH). The study of the T786C polymorphism of the endothelial nitric oxide synthase (eNOS) gene in arterial hypertension is important as its correlation with adipokine imbalance is a novelty area to find associations between hypertension development, obesity, and heredity. The purpose of the current study was to investigate serum adipokines levels, depending on the T786C polymorphism of the eNOS in patients with arterial hypertension. Methods. We examined 86 patients with arterial hypertension who underwent the determination of the T786C-gene promoter eNOS allelic polymorphism by PCR with electrophoretic detection. Additionally, the serum adipokines (resistin, leptin, adipoleptin, and ghrelin) levels were determined using enzyme-linked immunosorbent assay. Results. In the patients with arterial hypertension, a significant increase in resistin level was found only in TC and CC genotype carriers of T786C, while adiponectin and leptin levels were significantly higher in all three genotypes (TT, TC, CC) compared to control healthy group. The most severe increase in the adipokine levels was observed in CC genotype, followed by TC geno-type. The antianorexic hormone ghrelin had an opposite trend, with the lowest levels found in CC, followed by TC, and TT genotypes of T786C promoter eNOS gene. Interestingly, ghrelin level in TT genotype patients was not statistically different from control healthy group. Conclusions. We demonstrated that CC and TC, compared with TT genotype carriers of the T786C polymorphism of the promoter eNOS gene, had significantly higher levels of all adipokines, except ghrelin, where an opposite trend was observed, which suggests their higher risk in development of more severe arterial hypertension with concomitant obesity, and other associated disorders.

Objective. For the effective growth of malignant tumors, including glioblastoma, the necessary factors involve endoplasmic reticulum (ER) stress, hypoxia, and the availability of nutrients, particularly glucose. The ER degradation enhancing alpha-mannosidase like protein 1 (EDEM1) is involved in ER-associated degradation (ERAD) targeting misfolded glycoproteins for degradation in an N-glycan-independent manner. EDEM1 was also identified as a new modulator of insulin synthesis and secretion. The present study aims to investigate the regulation of the EDEM1 gene expression in U87MG glioblastoma cells by hypoxia and glucose or glutamine deprivations depending on the knockdown of ERN1 (endoplasmic reticulum to nucleus signaling 1) with the intent to reveal the role of ERN1 signaling in the regulation of this gene expression and function in tumorigenesis. Methods. The U87MG glioblastoma cells (transfected by an empty vector; control) and ERN1 knockdown cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) or only ERN1 endoribonuclease (dnrERN1) were used. Hypoxia was introduced by dimethyloxalylglycine (4 h). For glucose and glutamine deprivations, the cells were exposed to DMEM medium without glucose and glutamine, respectively, for 16 h. The expression level of the EDEM1 gene was studied by quantitative RT-PCR and normalized to the ACTB mRNA. Results. It was found that inhibition of endoribonuclease and protein kinase activities of ERN1 led to down-regulation of EDEM1 gene expression in glioblastoma cells. Moreover, the expression of this gene was also decreased after silencing ERN1 in glioblastoma cells. At the same time, the expression of EDEM1 gene did not significantly change in cells with inhibited ERN1 endoribonuclease only. The expression of the EDEM1 gene was increased under hypoxia in control U87MG cells, but resistant to hypoxia in cells with ERN1 knockdown. Furthermore, the expression of this gene was up-regulated under glucose and glutamine deprivations in control glioblastoma cells. However, the ERN1 knockdown increased the sensitivity of EDEM1 gene expression to glucose and decreased to glutamine deprivations. Conclusion. The results of the present study demonstrate that inhibition of ERN1 down-regulated the expression of the EDEM1 gene through protein kinase activity of ERN1 and that the regulation of this gene expression by hypoxia and nutrient supply, especially glucose, is differently controlled by ERN1 in glioblastoma cells.

Objective. To better understand the role of thyroid hormones in regulating the growth of breast epithelial cells and the estrogen-like effects of these hormones, the present study was conducted to investigate the relationship between breast cancer and thyroid autoimmune disorders in southeast Iran women. Methods. In this case-control study, in the case group, all newly diagnosed breast cancer pa-tients referred to the oncology clinics in Zahedan city in years 2021‒2022 were studied. The num-ber of participants in each group was represented by 40 breast cancer patients. The control group was represented by women without breast cancer. The sampling method was simple or available using the nonprobability method. The presence or absence of thyroid dysfunction was checked using thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase (TPO), and anti-thyroglobulin (Tg) tests. Results. The mean age of participants was 47±11 years. The risk of subclinical hyperthyroid-ism was higher in subjects with breast cancer and about 8 times higher than in the healthy ones (OR=8.27). According to the value of OR=1, the risk of developing autoimmune thyroid disease was the same in individuals with breast cancer as in healthy individuals. The odds ratio of hypothy-roidism could not be calculated because the value in the control group was zero. Conclusion. The results of this study show that there are abnormal characteristics of the thy-roid gland in breast cancer patients compared to the control group. The incidence of subclinical hyperthyroidism was significantly increased in the breast cancer patients. However, there was no difference in the incidence of autoimmune thyroid disease between the two groups.

Objective. Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impaired social interaction and communication, restrictive and repetitive patterns of behavior, interests and activities. The aim of this study was to determine the postnatal levels of thyroid hor-mones and investigate their association with the severity of ASD symptoms. Methods. The study included 56 children (46 boys and 10 girls) with ASD aged 24-42 months. For ASD diagnostics the Autism Diagnostic Observation Schedule - second version (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) - interview with the child's parents or guard-ians were used. Venous blood was drawn right after the diagnostic procedures to analyze serum thyroid-stimulating hormone (s-TSH), free triiodothyronine (s-fT3), and free thyroxine (s-fT4) levels. Linear regression analysis was conducted to assess the relationship between the concentra-tions of thyroid hormones and ASD symptoms severity. Results. Serum concentrations of measured hormones were within normal reference ranges in almost all children. Decline of s-TSH was significantly associated with an increase in the severity of impaired social interaction and impaired communication as rated by parents (ADI-R) and with a higher prevalence of stereotyped behavior as observed in the diagnostic examination (ADOS-2). A decrease in s-fT3 was associated with higher frequency of stereotyped behavior as assessed by parents (ADI-R). Neither sex nor age were significant predictors. Conclusion. Although thyroid hormone levels were normal, we demonstrated an association of thyroid hormones with ASD symptoms.

Objective. Nanographene oxide (nGO) nanoparticles (NPs) have unique properties and are widely used in various fields, including biomedicine. These NPs, however, also exhibit toxic ef-fects and therefore, the understanding of the molecular mechanism of nGO toxicity is very im-portant mainly for the nanomedicine, especially the cancer therapy. This study aimed to examine the impact of nGO NPs on the expression of genes associated with endoplasmic reticulum (ER) stress, proliferation, and cancerogenesis in both normal human astrocytes and U87MG glioblas-toma cells. Methods. Normal human astrocytes line NHA/TS and U87MG glioblastoma cells stable trans-fected by empty vector or dnERN1 (dominant-negative construct of ERN1) were exposed to low doses of nGO (1 and 4 ng/ml) for 24 h. RNA was extracted from the cells and used for cDNA syn-thesis. The expression levels of DNAJB9, EDEM1, DDIT3, ATF3, ATF4, TOB1, and IDH2 mRNAs were measured by quantitative polymerase chain reaction and normalized to ACTB mRNA. Results. We showed that treatment of normal astrocytes and glioblastoma cells by relatively small doses of nGO (1 and 4 ng/ml for 24 h) affected the expression level of DNAJB9, EDEM1, DDIT3, ATF3, ATF4, TOB1, and IDH2 mRNAs, but the sensitivity of all studied mRNA expres-sions to these NPs was significantly higher in normal astrocytes than in glioblastoma cells. The impact of nGO on these gene expressions is mediated by ER stress because ERN1 knockdown sup-presses the effect of these nanoparticles in glioblastoma cells. Conclusion. The data obtained demonstrate that the low doses of nGO disturbed the functional integrity of the genome preferentially through ER stress signaling and exhibit a more pronounced genotoxic effect in the normal astrocytes than the glioblastoma cells.

Objective. We report a case of a 23-year-old pregnant female with five months of amenorrhea. She was referred to us with rapidly developing jaundice, anemia, and dyspnea with hyperthyroidism. Methods. After initial treatment of all the possible causes of progressive jaundice led to no improvement. The treatment was then heavily directed towards managing thyroid storm. Results. Hepatic dysfunction improved with iodine and thionamides. Patient recovered well. This points towards the uncommon association of severe hyperbilirubinemia with thyroid storm a potentially fatal endocrine disorder and its rapid improvement with iodine and thionamides. Conclusions. Our case suggests that severe hyperbilirubinemia can be caused by hyperthyroidism and the etiology of hepatic dysfunction should include thyrotoxicosis as a probable cause. Aggressive treatment should be done with iodine and thionamides for fruition.

Objective. Reduced calciferol (vitamin D) levels in pregnant women have been associated with an increased risk to infant health. Progesterone sustains pregnancy and reduces the risk of premature birth through its metabolites affecting myometrial contractility. Sex hormone-binding globulin protein (SHBG) is a biomarker of premature birth. The present study aimed to find out if early pregnancy levels of vitamin D, SHBG, and progesterone metabolites may predict preterm birth risk. Methods. Five hundred pregnant women aged 18-43 years during their 2nd and 3rd trimesters from multiple civilian regional medical centers in Lahore participated in the study. Blood samples taken from participants were used to determine vitamin D, SHBG, 11-deoxycorticosterone (DOC), and 16α-hydroxyprogesterone (16α-OHP) levels using specific ELISA kits. Statistical analysis was performed by one-way ANOVA using the latest GraphPad Prism software. Results. A significant decrease in vitamin D, DOC, and SHBG levels (p<0.001, p<0.001, and p<0.05, respectively) in the preterm birth cohorts in the 2nd and 3rd trimester was found compared to the corresponding control groups. Furthermore, 16α-OHP levels in the preterm birth cohorts in the 2nd and 3rd trimesters were significantly increased (p<0.001 and p=0.0062, respectively) compared to their control cohorts. Conclusion. The results of our study confirm that calciferol deficiency in pregnant women is associated with an increased risk of premature birth and indicate that SHBG and progesterone metabolites may be useful biomarkers for the early identification and prediction of preterm birth.

Objective. The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes in the responsiveness of members of a cluster of seven measures in older persons with type 2 diabetes mellitus (T2DM) consuming flaxseed lignan complex (FLC). The cluster of seven are abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDLc), and increased plasma levels of triglycerides), increased low-density lipoprotein (LDL) oxidation and increased inflammation. All cluster members exacerbate T2DM. Methods. Sixteen patients with well-controlled T2DM participated in this double-blind randomized, placebo-controlled crossover study consisting of four visits. Apolipoprotein E genotyping was done at visit one. The cluster of seven, diet, exercise, smoking and medication use were assessed at each visit. Results. The 3/4 genotype showed a stronger downward trend in systolic blood pressure compared to the 3/3 genotype with no trend or significant difference in the 2/4 genotype. There was a downward trend in diastolic blood pressure in genotype 3/3 compared genotype 2/4, which showed no significant difference or trend. Only genotype 3/4 showed a significant drop in diastolic pressure compared to genotypes 2/4 and 3/3. HDLc only showed a downward trend in 3/4 relative to genotypes 2/4 and 3/3. LDL apolipoprotein B oxidation (LDL-Box) only showed an upward trend in 3/3 compared to genotypes 2/4 and 3/4. There were no other significant differences or trends by genotype in the cluster of seven. Conclusions. It appears that those with the 2/4 genotype may not benefit from FLC, those with 3/3 and 3/4 genotypes may benefit only in terms of systolic and diastolic pressures, those with the apo E 3/4 genotype should perhaps avoid FLC to manage HDLc, and those with the 3/3 genotype should perhaps avoid FLC to manage LDL apolipoprotein B oxidation.