MicroRNA-137 inhibits pituitary prolactinoma proliferation by targeting AKT2.

PURPOSE: Prolactinoma is the most common type of pituitary adenoma. Most prolactinoma need medical treatment, but some of them are aggressive and require surgery. In previous decades, some miRNAs have been manifested as oncogenes or tumor suppressors. Consequently, miRNAs' abnormal expression involves tumorigenesis, invasion, and metastasis of different types of tumors, including pituitary tumors. The current study aim to explore the aggressiveness-associated miRNAs in prolactinoma and underlying molecular mechanisms based on the bioinformatic analysis and fundamental experiment studies. METHODS: GSE46294 miRNA expression profile from the Gene Expression Omnibus (GEO) database was downloaded. Differentially expressed miRNAs (DEMs) were filtered from this data. Subsequently, the target genes of downregulated miRNAs were analyzed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RT-qPCR, western blot, and CCK-8 assays were used to validate the effect of miR-137 on the proliferation of MMQ cells through AKT2. Finally, the binding site of rat miR-137 to AKT2 were predicted by Targetscan and Bibiserv database, and verified by double luciferase reporter assay. RESULTS: Twenty-four changed DEMs (fourteen upregulated and ten downregulated) were identified. Target genes of downregulated DEMs were classified into three groups by GO terms. KEGG pathway enrichment analysis revealed these target genes enriched in the PI3K-Akt pathway. We also confirmed that miR-137 can target AKT2 and inhibit the proliferation of MMQ cells induced by AKT2. CONCLUSION: MiR-137 suppressed prolactinomas' aggressive behavior by targeting AKT2.

Protective effect of icariin on kidney in 5/6 nephrectomized rats and its mechanism.

The aim of this study was to investigate the renal protective effect of icariin in 5/6 nephrectomized rats and the molecular mechanisms involved. Forty male Sprague-Dawley rats were randomly divided into 5 groups: sham-operated group, 5/6 nephrectomy model group, icariin groups (20 and 40 mg/kg), and benazepril group. After 12-weeks treatment, 24-h urine and serum were collected, and urine protein, serum creatinine, and blood urea nitrogen were determined. The rats were then sacrificed and fresh kidney tissues were prepared to obtain single cell suspensions. Cell cycle distribution and cell apoptosis were determined by annexin V-FITC/propidium iodide (PI) double staining using a flow cytometer. mRNA expression of Bcl-2 and Bax was examined using quantitative real-time PCR. After 12-weeks treatment, urinary protein, serum creatinine, and blood urea nitrogen in the icariin-treated group were much lower than in the untreated group compared with 5/6 nephrectomy model. Icariin reduced the percentage of S phase cells, increased the percentage of G0/M phase cells, and inhibited apoptosis in the renal cells. mRNA expression of Bcl-2 and Bax was decreased. In conclusion, icariin has a renal protective effect in 5/6 nephrectomized rats, which may be related mainly to alterations in cell cycle distribution and expression of apoptotic genes.

[A comparative study of the efficacy of customized titanium plates versus conventional maxillary protraction in the treatment of skeletal class â ¢ patients].

Objective: To compare the clinical efficacy of customized titanium plate and conventional maxillary protraction treatment in patients with skeletal class Ⅲ malocclusion during growth spurt. Methods: During growth spurt, skeletal class Ⅲ patients with maxillary hypoplasia who were treated in the Department of Orthodontics, Capital Medical University School of Stomatology from August 2018 to July 2021 were prospectively enrolled. They were treated with maxillary protraction using customized titanium plates (customized titanium plate group) and conventional methods (conventional protraction group), respectively. Lateral cephalometric radiographs were collected before and after treatment for conventional cephalometric analysis, including SNA angle (angle between Sella, Nasion and A point), ANB angle (angle between A point, Nasion, and B point), FH-MP angle (mandibular plane angle), Y-axis angle, U1-L1 angle (upper to lower central incisor angle), U1-SN angle (upper incisor to SN plane angle), anterior and lower height, maxillary length, etc. The stable basicranial line (SBL) was used as the reference line to measure the distance from each reference point (ANS point, A point, Prn point, Sn point, UL point etc.) to the stable basicranial vertical line (VerT, the perpendicular line of the skull base line at the intersection point of the anterior wall of the sella image and the inferior edge of the anterior bed process). Paired t-tests were performed on the cephalometric data before and after maxillary protraction treatment in the two groups, and two independent samples t-tests were performed to compare the differences in the efficacy of the two maxillary protraction methods. Results: A total of 20 patients (9 males and 11 females), aged (10.8±1.3) years, were included in the personalized titanium plate group. A total of 20 patients (8 males and 12 females), aged (10.5±1.1) years, were included in the conventional protraction group. The SNA angle, ANB angle, FH-MP angle, Y-axis angle, anterior lower height, maxillary length, ANS-VerT distance, A-VerT distance, Prn-VerT distance, Sn-VerT distance, and UL-VerT distance were significantly higher than those before treatment in the two groups (P<0.05). The changes of SNA angle, ANB angle and A-VerT before and after treatment in the personalized titanium plate group [3.15°±2.28°, 4.64°±1.40°, (4.41±3.43) mm, respectively] were significantly higher than those in the traditional group [2.13°±2.69°, 2.81°±1.10°, (3.13±4.76) mm, respectively](P<0.05), and the changes of U1-L1 angle and U1-SN angle before and after treatment (-0.76°±7.42° and 1.74°±6.38°, respectively) was significantly lower than that of the control group (-5.14°±6.62° and 4.57°±5.24°, respectively, P<0.05). Conclusions: Maxillary protraction can effectively improve skeletal class Ⅲ relationships in growing patients. The linear measurements using the SBL line as a reference plane visualize the sagittal improvement in sagittal relationship after maxillary protraction. The customized titanium plate maxillary protraction treatment has a clear therapeutic effect on patients with skeletal class Ⅲ deformities, and its dental effect is relatively small.

[Three-dimensional printed miniplate used for maxillary protraction].

The miniplate was designed and three-dimensional (3D) printed according to the positions of roots and tooth germs and then it was used as skeletal anchorage to protract the maxilla. The maxilla moved forward obviously after treatment. Custom designed and 3D printed miniplate could be used for maxillary protraction.

Nonmalignant respiratory disease among hematite mine workers in China.

The mortality risk of nonmalignant respiratory disease among hematite workers in the Longyan and Taochong mines of China was investigated in a retrospective cohort study covering the period 1970-1982. The cohort was limited to men and consisted of 5406 underground miners, of whom 1335 (25%) were diagnosed as having silicosis. Among those with silicosis, 560 (42%) were diagnosed as having silicotuberculosis. Among the 490 underground miners who died, 278 (57%) died of nonmalignant respiratory disease. The relative risk for death due to nonmalignant respiratory disease for stage III silicotics compared to nonsilicotics was almost 100-fold. High dust exposure was associated with a statistically significant increase in risk of death due to nonmalignant respiratory disease (relative risk 5.3). The relative risk associated with jobs with high dust exposure before the introduction of industrial hygiene controls was 7.7, and the corresponding value for after their introduction was 2.3. There is a need for continued close monitoring of industrial hygiene in these mines.

Mortality experience of haematite mine workers in China.

The mortality risk of iron ore (haematite) miners between 1970 and 1982 was investigated in a retrospective cohort study of workers from two mines, Longyan and Taochong, in China. The cohort was limited to men and consisted of 5406 underground miners and 1038 unexposed surface workers. Among the 490 underground miners who died, 205 (42%) died of silicosis and silicotuberculosis and 98 (20%) of cancer, including 29 cases (5.9%) of lung cancer. The study found an excess risk of non-malignant respiratory disease and of lung cancer among haematite miners. The standardised mortality ratio for lung cancer compared with nationwide male population rates was significantly raised (SMR = 3.7), especially for those miners who were first employed underground before mechanical ventilation and wet drilling were introduced (SMR = 4.8); with jobs involving heavy exposure to dust, radon, and radon daughters (SMR = 4.2); with a history of silicosis (SMR = 5.3); and with silicotuberculosis (SMR = 6.6). No excess risk of lung cancer was observed in unexposed workers (SMR = 1.2). Among current smokers, the risk of lung cancer increased with the level of exposure to dust. The mortality from all cancer, stomach, liver, and oesophageal cancer was not raised among underground miners. An excess risk of lung cancer among underground mine workers which could not be attributed solely to tobacco use was associated with working conditions underground, especially with exposure to dust and radon gas and with the presence of non-malignant respiratory disease. Because of an overlap of exposures to dust and radon daughters, the independent effects of these factors could not be evaluated.