Endocrine regulations最新文献

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. 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. 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. 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.

The present minireview traces the road leading to discovery of selenium, formerly appointed as a toxic element that became later a bioelement, which is necessary for the proper functioning of living organisms. Selenium occurs in human and animal bodies either in the form of seleno-Lcysteine or its dimeric form seleno-L-cystine as a crucial component of selenoenzymes or selenoproteins. Selenium atom represents an integral component of the enzyme active site of different forms of glutathione peroxidase, which catalyzes conversion of hydrogen peroxide and organic hydroperoxides into the water and corresponding alcohols. A revolutionary breakthrough in the field of endocrinology came with the identification of different forms of iodothyronine deiodinase as selenoenzymes, which play an important role in the metabolism of thyroid hormone. The role of selenium in immune function and autoimmune thyropathies that might be associated with selenium deficiency are reported and discussed. This minireview also brings forward novel directions of organoselenium compounds or selenium nanoparticles in cancer therapy. Based on the update of available literature and the author's experimental experience, the minireview can be devoted to clinicians and medical students.

Objective. The aim of this study was to evaluate the association of the α-adducin-1 gene (ADD1) (Gly460Trp [rs4961]) polymorphism and its expression in association with renal dysfunction and sodium sensitivity in hypertensive patients in western Ukrainian population. Methods. One-hundred patients with essential arterial hypertension (EAH) and hypertensive-mediated target organ damage (stage 2), moderate, high, and very high cardiovascular risk were enrolled in case-control study. Sixty healthy individuals were assigned as controls. Sodium sensitivity and sodium resistance were determined by salt load reaction. The ADD1 (rs4961) genotyping was performed in RT-PCR. Results. The expression of the quantitative trait loci (eQTL) of ADD1 gene (rs4961) (chr4:2906707 [hg19]) was confirmed in 37 tissues and organs with 23 phenotypic traits. Two hundred eQTL associations revealed - all cis-variants (cis-QTL); 73 methylation QTL (mQTL), 34 splicing QTL (sQTL), 14 histone modification QTL (hQTL), 2 protein QTL (pQTL), 23 transcript utilization QTL (tuQTL), and 4 loci of incorporated long noncoding areas of RNA (lncRNA). GG-genotype unreliably enhances EAH risk (OR=1.92; 95%CI: 0.90-4.10; p=0.066). Sodium sensitivity was observed in 54.0% of patients and in 20.0% of controls (c2=17.89; p<0.001). Sodium sensitivity in T-allele carriers of the ADD1 gene (1378G>T; rs4961) dominated 12-fold in general (OR 95%CI: 2.24-64.29; p=0.001), in women - 4.71 times (OR 95%CI: 1.92-11.56; p<0.001), and in men - 4.09 times (OR 95%CI: 1.03-16.28; p=0.041). Sodium sensitivity elevated the likelihood of severe EAH twice (OR=2.19; OR 95%CI: 1.00-5.05; p=0.049). Conclusion. T-allele associates with sodium sensitivity in essential arterial hypertension patients and increases the risk of hypertension regardless the gender. Sodium sensitivity enhances the probability of severe essential arterial hypertension in observed population.

Objective. Carboxypeptidase E (CPE) plays an important role in the biosynthesis of neurotransmitters and peptide hormones including insulin. It also promotes cell proliferation, survival, and invasion of tumor cells. The endoplasmic reticulum stress, hypoxia, and nutrient supply are significant factors of malignant tumor growth including glioblastoma. There are data indicating that the knockdown of the endoplasmic reticulum to nucleus signaling 1 (ERN1) suppressed glioblastoma cell proliferation and increased invasiveness of these cells. The present study aims to investigate the regulation of the CPE gene in U87MG glioblastoma cells by ERN1 knockdown, hypoxia, and glucose or glutamine deprivations with the intent to reveal the role of ERN1 signaling in the regulation of this gene expression and function in tumorigenesis. Methods. Human glioblastoma cells U87MG (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; for glucose and glutamine deprivations, the cells were cultured in DMEM medium without glucose or glutamine for 16 h, respectively. The expression level of the CPE gene was studied by quantitative RT-PCR and normalized to ACTB. Results. It was found that inhibition of endoribonuclease and protein kinase activities of ERN1 led to a strong up-regulation of CPE gene expression in glioblastoma cells. The expression of this gene also increased in glioblastoma cells after silencing ERN1. At the same time, the expression of this gene did not significantly change in cells with inhibited ERN1 endoribonuclease only. The expression of the CPE gene was resistant to hypoxia in control U87MG cells, but increased in cells with ERN1 knockdown. The expression of this gene was up-regulated under glutamine deprivation in control glioblastoma cells, but decreased upon ERN1 knockdown. However, glucose deprivation decreased the expression of CPE gene in both types of used cells, but ERN1 inhibition enhanced this effect. Conclusion. The results of the present study demonstrate that inhibition of ERN1 strongly up-regulated the expression of pro-oncogenic CPE gene through protein kinase activity of ERN1 and that increased CPE gene expression possibly participates in ERN1 knockdown-mediated invasiveness of glioblastoma cells.

Objective. CoolSeal is a new vessel sealing system for dissection and hemostasis during surgery. No clinical studies have investigated safety, advantages or disadvantages regarding the use of this device. The aim of the present study was to investigate the safety of CoolSeal and compare it with conventional ligation technique or LigaSure during the total thyroidectomy. We hypothesized that the use of CoolSeal would reduce the operating time and bleeding without complications increase. Study design represents a retrospective cohort study with a tertiary reference center setting. Methods. We analyzed total thyroidectomy data from January 2021 to June 2023. We recorded patients' characteristics, surgical information, and postoperative outcome. Results. We performed 221 total thyroidectomies in the study period. Analysis was restricted to 171 patients operated by only two surgeons. Hemostasis was secured by conventional ligation in 117 patients (68%), LigaSure in 34 patients (20%) and CoolSeal in 20 patients (12%). Median thyroid weight and bleeding were 67 g and 50 ml, respectively. Procedures using LigaSure or Cool-Seal were on larger glands (median 205 g) without increased bleeding (50 ml). Operating time was shortest with CoolSeal (96 min, p=0.003) compared with LigaSure (117 min) or conventional ligation (115 min). Bleeding was reduced with CoolSeal compared with LigaSure (45 vs. 100 ml, p=0.003). With CoolSeal, median hospitalization was one postoperative day, no patients required re-operation. There was no palsy of recurrent laryngeal nerves and no permanent hypoparathyroidism. Conclusion. In our first clinical experience, CoolSeal was safe and efficient for total thyroidectomy. With a small sample size, we saw a clinical benefit with reduced operating time without post-operative complications increase.