ACTA ENDOCRINOLOGICA (BUC)

Context. Recent evidence has stressed that many proinflammatory factors are particularly conducive to the progression of diabetic nephropathy, but the mechanisms underlying the changes are poorly understood. Objective. The purpose of this study was to investigate if up-regulated expression of both phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2) is involved in renal damage and micro-inflammatory state in streptozotocin-induced diabetic rats. Animals and methods. Sixteen Sprague Dawley rats were randomly divided into 2 groups: control group and diabetes group. Animals in diabetes group were treated with intraperitoneal injection of streptozotocin. Eight weeks later, rat renal tissue was studied with light and transmission electron microscopes, and PLA2 and COX-2 and their mRNA expression were examined by immunohistochemistry and reverse transcription polymerase chain reaction, respectively. Results. The renal pathological lesions in diabetes group were obvious, including increased amounts of mesangial matrix, thickening of the glomerular and tubular basement membranes and fusion and effacement of the adjacent podocyte foot processes. Infiltrating inflammatory cells were observed in the tubules. Compared with control group, the expression of cytosolic PLA2 and COX-2 was significantly increased in diabetes group. Conclusions. It uncovers that the PLA2-COX-2 pathway may lead to renal inflammation associated with renal damage in streptozotocin- induced diabetic rats.

Aims. This study investigated the relationship between proteinuria levels, clinicopathological features, and renal prognoses in Chinese patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods. Three hundred patients with T2DM and biopsy-proven DN were enrolled. Patients were stratified by 24-h proteinuria levels: Group 1:≤1g/24h); Group 2:1-3g/24h; and Group 3:≥3g/24h. Renal outcomes were defined as having reached end-stage renal disease (ESRD). The proteinuria level’s influence on the renal outcomes was evaluated using Cox regression analysis. Results. Among subgroups stratified by proteinuria levels, systolic blood pressure, serum creatinine, BUN, cholesterol, DR and hypertension incidence, the incidences of patients who progressed to ESRD were the lowest in group 1 (P<0.05). However, eGFR, serum albumin and hemoglobin were highest in group 1. Patients with higher proteinuria levels had much lower five-year renal survival rates. Univariate analyses revealed that higher proteinuria levels were significant clinical predictors of renal prognosis (P<0.05), although they were not independent risk factors for progression to ESRD in the multivariate Cox proportional hazard analysis (P>0.05). Conclusions. The higher the level of proteinuria, the lower the 5-year renal survival rate of DN patients, but there was no significant correlation between proteinuria level and 5-year renal survival rate. Other factors in the proteinuria group may have more significant effects on the 5-year renal survival rate, such as lower baseline eGFR, serum albumin, hemoglobin and higher cholesterol, higher incidences of DR and more severe lesions.

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.

Objective. To study the correlation between neck circumference(NC) and umbilical artery blood flow in physiologic pregnancies. Methods. One hundred and one healthy pregnant woman in the third trimester were enrolled. Anthropometric measurements and ultrasonic testing were done. Results. The women with NC ≥34.7cm had a more elevated umbilical artery pulsatility index(PI) and systolic/diastolic ratio (S/D) than the women with NC <34.7cm (P<0.01). NC were positively correlated with PI(r=0.224,P=0.024) and S/D ratio(r=0.415,P=0.0001). In multivariate analysis, NC was independently associated with PI (β=0.026, P=0.016) and S/D ratio (β=0.132, P=0.0001). Conclusions. Obesity has an adverse impact on feto-placetal vessels, and NC was superior to body mass index.

Aims. To investigate the changes in the miRNAs and mRNAs expressed in the liver upon induction of “hyperresistinemia”. Methods. We identified mRNA and miRNAs that were differentially expressed between normal and resistin-treated liver tissue using microarrays. Expression was validated using quantitative RT-PCR (qRT-PCR). The putative targets and pathways of the differentially expressed miRNAs and mRNAs were investigated, respectively, using various computational algorithms. In addition, the interactions between differentially expressed miRNAs and mRNAs were analyzed. Results. After the filtration of the signals below the threshold level, we identified 34 miRNAs and 875 genes with expression levels different by more than 1.5-fold and 2.0-fold, respectively, between the two groups. These observations were confirmed by qRT-PCR. Bidirectional prediction analyses showed that the differentially expressed miRNAs may be inversely regulated by their predicted targets. Conclusion. Hyperresistinemia results in changes in the miRNAs and mRNAs expressed in the liver.

Aim. To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and threedimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods. 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results. The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion. Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist.

Context and objective. Reactive oxygen species (ROS) produced under oxidative stress is important for osteoclastogenesis. As a major member of the metallothionein (MT) family, metallothionein2 (MT2) can scavenge ROS in osteoblasts. However, the role of MT2 in osteoclastogenesis and ROS production in osteoclast precursors (OCPs) is unknown. Material and methods. In this study, we first investigated MT2 expression level in osteoporotic model mice. Next, we explored the roles of MT2 in osteoclastic differentiation and ROS production in OCPs. Ultimately, via rescue assays based on hydrogen peroxide (H2O2), the significance of ROS in MT-2-regulated osteoclastic differentiation was further elucidated. Results. Compared with sham operated (Sham) mice, ovariectomized (OVX) mice displayed bone marrow primary OCPs (Ly6C+CD11b-) having higher ROS levels and lower MT2 expression. MT2 overexpression inhibited the formation of mature osteoclasts, while MT2 knockdown was contrary. Moreover, MT2 overexpression inhibited ROS production in OCPs, while MT2 knockdown exhibited the opposite effects. Notably, the inhibitory effect of MT2 overexpression on osteoclastogenesis and ROS production was blocked by the addition of H2O2. Conclusion. MT2 inhibits osteoclastogenesis through repressing ROS production in OCPs, which indicates that the strategy of upregulating MT2 in OCPs may be applied to the clinical treatment of osteoclastic bone loss.

Aim. The purpose of this study is to investigate the effect of self-monitoring of blood glucose (SMBG) on glycemic control in insulin-naive type 2 diabetic patients comparing SMBG plus self-regulatory behavioral education, and SMBG plus individual education. Methods. Participants with glycated hemoglobin A1C (HbA1C) of 7.5-12% were enrolled in this 24-week, prospective study. Forty-two and forty participants received SMBG plus selfregulatory behavioral education, and SMBG plus individual education, respectively. The glycemic and behavioral attitudes outcomes were evaluated. Results. The A1C level decreased in both groups, from 9.41± 1.7% to 7.84± 0.83% in the SMBG plus self-regulatory behavioral education and 9.62 ±1.08% to 9.09± 1.1% in the SMBG plus individual education. However, the postprandial glucose (PPG) level sustained more significant decreases from 277.1 ±80.1 to 175.7 ±53.9 mg/dL in the SMBG plus self-regulatory behavioral education, and from 261.2 ±80.5 to 221.6 ±41.2 mg/dL in the SMBG plus individual education. The frequency of PPG monitoring increased from 0.1 ± 0.81 to 3.46 ± 2.81 times/week in SMBG plus self-regulatory behavioral education, whereas it increased from 0.13± 0.78 to 1.01± 0.89 in SMBG plus individual education. The amount of carbohydrates consumed per day decreased and the amount of physical activity performed per week increased significantly in self-regulatory behavioral education group. Conclusions. The use of this model of SMBG plus self-regulatory behavior education appears to have resulted in superior improvements in glycemic control and behavioral outcomes compared with those achieved by SMBG plus individual education.