ACTA ENDOCRINOLOGICA (BUC)

Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF- 1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

Background. Type 1 diabetes mellitus is a common disorder which causes a variety of complications such as cognitive deficits in central nervous system. Auditory P300 event related potential is a wellestablished neurophysiologic approach in the assessment of cognitive performance. In this study, we aimed to evaluate the cognitive performance in insulin dependent diabetic patients by auditory event related potentials. Methods. In this descriptive analytical and non-interventional study, auditory P300 event related potential was measured in oddball paradigm by using two tone burst stimuli (1000 & 2000 Hz) on 25 diabetic patients and 25 age, education and sex matched healthy controls, with mean age 28.76±4.1 in patients and 29.68±3.6 in controls. Results. The mean P300 latency of the diabetic patients was significantly prolonged and the mean P300 amplitude of the diabetic patients was significantly lower when compared with that of controls at all electrode sites (p<0.01). Also there was a strong correlation between P300 latency and glucose level, HbA1c and diabetes duration (p<0.01). Conclusion. Auditory information processing is slower and the speed of information categorizing is lower in diabetic patients than in controls.

Background. Diabetes mellitus (DM) is considered as an important health confounder in our world, which necessitates its better management by new methods. In this study, we have evaluated the effects of oral Arnebia Euchroma (AE) extract on different stereological parameters of the pancreas as well as blood glucose in Streptozotocin (STZ)-induced diabetes in rats. Methods. We divided 48 Wistar rats into 4 groups: C1 including normal rats, C2 not-treated diabetic rats, E1 with diabetic rats receiving 100 mg/kg AE extract orally, and E2 including diabetic rats treated with 300 mg/kg AE extract. Stereological study was done and the levels of blood glucose were also estimated and compared between experimental and control groups. Results. There were significant differences in volumes of pancreatic islets, β cell populations, blood glucose levels in AE treated groups compared with nottreated diabetic group. Conclusion. Although AE did not completely prevent or heal the pancreatic damage, its oral administration showed promising effects on maintaining the population of beta cells, the main insulin secreting cells, after STZ-induced injury and also lowered blood glucose levels compared to the not-treated diabetic group.

Objective. ARMC5 mutations are responsible for the development of primary bilateral macronodular adrenal hyperplasia (PBMAH). In this study, we aimed to report a novel ARMC5 germline variant in a PBMAH patient family. Method. CT examination and dexamethasone suppression test (DST) were used in the diagnosis of PBMAH. Sanger sequencing was used to validate the familial heredity. For the novel variant, protein predictive analysis was performed to study the changes of secondary and tertiary structures and hydrophobicity. Results. A 45 years old male (proband, III-1) was diagnosed as PBMAH. Whole-exome sequencing (WES) was performed, finding one mutation: c.719_ 724dup, p Arg240_ Pro241dup. Sanger sequencing showed the II-2, III-1, IV-1 with heterozygous gene, confirming the familial heredity. For protein predictive analysis, the predicted secondary structure of variants has one alpha–helix structure incomplete compared with normal ARMC5. The tertiary structure could draw the same conclusion, that hydrophobicity decreases after mutation. Conclusion. We reported a new-found ARMC5 germline variant in PBMAH using WES and protein predictive analysis. With the help of WES, early diagnosis of PBMAH could help variant carriers to prevent the occurrence of cancer by lifetime follow-up.

recently. However, the nature of the signals that may connect body fat/muscle tissues with the central nervous system governing energy homeostasis remains to be elucidated. Objective. The present study was designed to investigate the effects of peripheral kisspeptin-10 administration on irisin release in human males. Subjects and methods. Kisspeptin-10 was administered to normal weight (n=8) and obese (n=8) men. Sequential blood sampling was performed for 30 minutes pre and 210 minutes post kisspeptin injection at 30 minutes interval. ELISA kit was used to detect plasma irisin levels. Results. There is a significant (P<0.0001) effect of Kisspeptin-10 administration on irisin release in both normal weight and obese participants. Mean irisin levels (96.24 ± 1.351 ng/mL) at 210 minutes were significantly (P<0.0001) enhanced as compared to pre-kisspeptin (59.18 ± 4.815 ng/ mL) in normal weight subjects. In obese subjects mean irisin levels (75.76 ± 4.06 ng/mL) were significantly (P<0.0001) elevated at 180 minutes post-kisspeptin when compared with pre-kisspeptin irisin levels (41.28 ± 2.89 ng/mL). Conclusion. Our findings suggest that kisspeptin may have a novel therapeutic potential to induce irisin release in humans which may have anti-obesity effects.

Objective. To investigate the effect of puerarin (Pue) on the proliferation and differentiation of osteoblasts and the expression of type I collagen(Coll I) mRNA in a high-glucose (HG) environment, and to provide evidence for the clinical treatment of diabetic osteoporosis(DOP). Subjects and Methods. The proliferation of osteoblasts from three groups – the control group, the HS group, and the HG+Pue (10-8-10-6 M) group – was cultivated for 72 h and evaluated using the methyl thiazolyltetrazolium (MTT) assay. Results. The MTT values and the ALP activities in all experimental groups were significantly lower than those in the control group, and the MTT values and the ALP activities in the HG+Pue group were significantly higher than those in the HS group. Coll I mRNA expression in all experimental groups was significantly lower than that in the control group, while that in the HG+Pue group was significantly higher than that in the HG group. Conclusions. The proliferation and differentiation of osteoblasts and the expression of Coll I mRNA were inhibited by high glucose, but Pue can increase the proliferation and differentiation as well as the expression of Coll I mRNA in the osteoblasts, indicating that Pue could be therapeutically beneficial against DOP.

Context. Peripheral nerve lesions are a major complication of diabetes mellitus, the main clinical manifestations of which are numbness and pain involving the limbs. Objective. To determine the correlation between pregabalin treatment and diabetic peripheral neuropathic pain. Design. An experimental animal study in BALB/c mice. Subjects and Methods. Diabetes models are established by injecting streptozotocin (STZ) into the abdominal cavities of mice. The correlation between the treatment effect, time, and dosage of pregabalin was determined. The effect of a type 1 organic cation transporter (Octn1) in the absorption of pregabalin was evaluated. Results. Pregabalin reduced tactile allodynia in diabetic mice. The best analgesic effect occurred when intestinal absorption was increased. Octn1 mediated pregabalin entry into intestinal epithelial cells, which influenced the absorption of pregabalin with a timedependent fluctuation in the small intestine. Peripheral nerve damage caused by diabetes was dependent on time and dose of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium. Conclusions. Peripheral nerve damage caused by diabetes was dependent on time and dosage of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium.

Aim. To compare the red blood cell (RBC) diffusional water permeability (Pd) in elderly human subjects and mature\r\nsubjects.\r\nPatients and methods. 58 apparently healthy subjects, aged 65-80 years, were divided into two groups: 44 mature (35-64.9 years) and 14 elderly subjects (65-80 years). The morphological characteristics of RBCs were determined from light microscopic measurements and their Pd was measured\r\nby a NMR method. The inhibition of Pd induced by p-chloromercuribenzoate (PCMB) and the activation energy (Ea,d) of water diffusion across the RBC membrane\r\nwere also determined.\r\nResults. No significant differences between the RBCs of the two groups were found in regard with morphological parameters. Pd (10-3 cm/s) was in case of mature subjects ~ 3.1 at 15?C, 3.6 at 20?C, 4.2 at 25?C, 5.0? at 30?C, 6.1 at 37?C and 7.3 at 42?C, while for elderly subjects Pd was ~ 3.4 at 15?C, 3.9 at 20?C, 4.5 at 25?C, 5.3 at 30?C, 6.6 at 37?C and 7.9 at 42?C. Although rather small these differences were statistically significant: p<0.004 to p <0.04 at various temperatures. This means that RBCs from\r\nelderly people have a higher Pd. In agreement with this suggestion, the values of inhibition of water permeability induced by PCMB were higher for the RBCs from elderly individuals; however, the differences were not statistically significant. Ea,d was the same (~23 kJ/mol) for the RBCs from both groups. After incubation with PCMB Ea,d was ~ 37 kJ/mol for the mature individuals and ~ 31 kJ/mol for\r\nelderly individuals; however, the differences were not statistically significant.\r\nConclusion. A small, but statistically significant, increase in Pd of RBCs from elderly individuals was observed. This can be correlated with peculiarities of a less physically active organism.

Objectives. This work aimed to study the influences of carbonated beverages (CBs) on the testis growth and the expression levels of androgen receptor (AR) of mice. Methods. Two experimental groups of 30 mice each PEP-1 and PEP-2 drank 50% and 100% Pepsi-Cola, respectively for 15 days. Other 2 experimental groups of 30 mice each COC-1 and COC-2 drank 50% and 100% Coca- Cola, respectively for 15 days. The control group (CG) of 30 mice drank water. Bilateral testes were harvested aseptically on days 0, 5, 7, 10, 13 and 15. Real-time PCR and Western blot were implemented to detect levels of androgen receptor (AR) mRNA and protein in testis tissues. Results. Testes masses of PEP-2, COC-1 and COC-2 were greater than those of PEP-1 and CG (P < 0.05). On day 15, testis longitudinal diameter (TLD) of CBs-treated mice was increased as compared to CG. TLD, testes transverse diameters (TTD) and AR proteins levels of PEP-2 and COC-2 were increased in comparison with CG (P<0.05). Serum testosterone concentrations of PEP-2 were higher than that of COC-1 and CG (P < 0.05). Levels of AR mRNAs of four CBs-treated mice were increased by 60.18%, 67.26%, 65.93% and 78.76%. Conclusions. A high concentration of Coca-Cola and Pepsi-Cola could raise TLD and TDD, enhance testosterone secretion, and increase serum EGF concentrations.

Objective. To analyze the clinical value of dissection parathyroidectomy (DP) in patients with chronic kidney disease (CKD) complicated by refractory secondary hyperparathyroidism (HPT). Subjects and Methods. Patients with CKD complicated by refractory secondary HPT were included as the research subjects. Among them, 42 patients who received DP were assigned as the study group, while another 42 patients who underwent conventional total parathyroidectomy were assigned as the control group. Results. The average operative time and postoperative average length of hospital stay of the study group were lower than those of the control group (P<0.05). The study group showed lower levels of parathyroid hormone (PTH) compared to the control group 1 day postoperatively, 7 days postoperatively, 6 months postoperatively, and 12 months postoperatively (P<0.05). The study group exhibited lower serum calcium levels than the control group 1 day postoperatively, 7 days postoperatively, 1 month postoperatively, and 6 months postoperatively (P<0.05). Additionally, the study group demonstrated lower serum phosphorus levels compared to the control group 1 day postoperatively, 7 days postoperatively, and 6 months postoperatively (P<0.05). Conclusions. The application of DP in patients with CKD complicated by refractory secondary HPT holds definite clinical value.