Long noncoding RNA RP11-626G11.3 promotes the progression of glioma through miR-375-SP1 axis.

Gliomas are the most common malignant tumor in the central nervous system and are also one of the leading causes of death in cancer patients. Recently, mounting evidence suggested that both long noncoding RNAs (lncRNAs) and microRNAs play important roles in the proliferation and invasion of cancers, including gliomas. However, the role of lncRNA RP11-626G11.3 in glioma-genesis is still uncovered. Results indicated that lncRNA RP11-626G11.3 was up-regulated in glioma tissues and cell lines, moreover, its overexpression positively correlated with the poor prognosis and advanced pathological stages. Gain and loss of functional experiments demonstrated that lncRNA RP11-626G11.3 promoted the proliferation and invasion of glioma cells in vitro. The knockdown of lncRNA RP11-626G11.3 repressed the tumor growth in vivo. Mechanistically, lncRNA RP11-626G11.3 positively regulated the SP1 expression via competitively sponging with miR-375. Overall, our study shows that lncRNA RP11-626G11.3 promotes glioma progression by sponging miR-375 to regulate SP1 expression, which may provide a novel therapeutic strategy for glioma.

Magnesium regulates neural stem cell proliferation in the mouse hippocampus by altering mitochondrial function.

In the adult brain, neural stem cells from the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the cortex progress through the following five developmental stages: radial glia-like cells, neural progenitor cells, neuroblasts, immature neurons, and mature neurons. These developmental stages are linked to both neuronal microenvironments and energy metabolism. Neurogenesis is restricted and has been demonstrated to arise from tissue microenvironments. We determined that magnesium, a key nutrient in cellular energy metabolism, affects neural stem cell (NSC) proliferation in cells derived from the embryonic hippocampus by influencing mitochondrial function. Densities of proliferating cells and NSCs both showed their highest values at 0.8 mM [Mg(2+) ]o , whereas lower proliferation rates were observed at 0.4 and 1.4 mM [Mg(2+) ]o . The numbers and sizes of the neurospheres reached the maximum at 0.8 mM [Mg(2+) ]o and were weaker under both low (0.4 mM) and high (1.4 mM) concentrations of magnesium. In vitro experimental evidence demonstrates that extracellular magnesium regulates the number of cultured hippocampal NSCs, affecting both magnesium homeostasis and mitochondrial function. Our findings indicate that the effect of [Mg(2+) ]o on NSC proliferation may lie downstream of alterations in mitochondrial function because mitochondrial membrane potential was highest in the NSCs in the moderate [Mg(2+) ]o (0.8 mM) group and lower in both the low (0.4 mM) and high (1.4 mM) [Mg(2+) ]o groups. Overall, these findings demonstrate a new function for magnesium in the brain in the regulation of hippocampal neural stem cells: affecting their cellular energy metabolism.

Correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia in Alzheimer's disease and vascular dementia.

OBJECTIVE: To discuss the correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) and vascular dementia (VD). METHOD: AD cases, VD cases and healthy control cases totaling 237, 255 and 234 were recruited, respectively. The mini-mental state examination (MMSE) was performed to evaluate cognitive impairment. Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were adopted to evaluate BPSD. Apolipoprotein E (APOE) and Low-density lipoprotein receptor-related protein gene (LRP) genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: (1) Frequencies of APOEε4 allele in AD group and VD group were significantly higher than that of the control (P<0.05); (2) MMSE scores of APOEε4 carriers in AD group and VD group were lower than that of non-APOEε4 carriers in the same group (P<0.05); (3) The proportion of APOEε4 carriers presenting with BPSD in AD group was considerably higher that of non-APOEε4 carriers (P<0.05). CONCLUSION: APOEε4 may be the common risk factor for cognitive impairment in AD and VD and the risk factor for BPSD in AD.

PGC-1-related coactivator (PRC) is an important regulator of microglia M2 polarization.

Microglia can be driven to adopt M1 and M2 phenotypes. While the distinct functions of M1 and M2 microglia have been intensively studied, the former are considered proinflammatory and the latter anti-inflammatory. PGC-1-related coactivator (PRC), an important member in the peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family, plays an essential role in metabolic regulation and cell proliferation. The effects of PRC on microglia M2 polarization are still unknown. In this study, we found that PRC expression was robustly induced in M2 microglia. Overexpression of PRC promotes microglia M2 polarization by increasing the expression of arginase-1 (Arg1), resistin-like α (Retnla, Fizz1), and chitinase 3-like 3 (Chi3l3, Ym1). In contrast, the silence of PRC attenuates microglia M2 polarization. Mechanistically, PRC was found to cooperate with signal transducer and activator of transcription 6 (STAT6) to induce an M2 genetic program. Overall, our findings identify PRC as what we believe to be a novel regulator of microglia M2 polarization.

The characteristics of acromegalic patients with hyperprolactinemia and the differences in patients with merely GH-secreting adenomas: clinical analysis of 279 cases.

OBJECTIVE: The aim of this study is to evaluate clinical data from a large cohort of acromegalic patients with and without hyperprolactinemia. DESIGN AND METHODS: Between January 2002 and June 2010, a set of data on 279 acromegalic patients undergoing transsphenoidal surgery was available. Based on preoperative GH and prolactin (PRL) levels, patients were divided into GH and GH+PRL groups. A stabilization or a further improvement of postoperative changes in clinical, hormonal, immunohistochemical, and magnetic resonance imaging parameters was observed in all patients throughout the follow-up period. RESULTS: The GH group had significantly more coarse facial features, large hands and feet, hypertension, and diabetes mellitus compared with the GH+PRL group but significantly less menstrual disorders (13.8 vs 54.3%, P<0.001) and galactorrhea (3.1 vs 22.4%, P<0.001). The GH group had a higher age at diagnosis compared with the GH+PRL group (45.6 ± 13.9 vs 40.4 ± 11.4 years, P=0.001). The GH group had a smaller mean maximal diameter of the adenomas (2.2 ± 0.9 vs 2.6 ± 1.1 cm, P=0.004). There were no significant correlations between hormone levels and the immunohistochemical results. According to the criteria for hormonal cure of acromegaly, the surgical control rates in the GH and GH+PRL groups were 68.4 and 59.7% respectively (P=0.187). Tumor size was an important factor that affected the results of the operations. The rates of surgical control in GH and GH+PRL groups were 80.7 and 69.1% respectively (P=0.037), and the recurrence rates in the two groups were 7.1 and 11.3% respectively (P=0.185). CONCLUSIONS: Compared with patients with merely GH-secreting adenomas, acromegalic patients with hyperprolactinemia are characterized by an earlier onset of disease, lesser acromegalic features, lower GH levels, but larger tumor sizes, whereas in female patients, GH-PRL secreting adenomas are associated with higher incidences of menstrual disorders and galactorrhea.

Transsphenoidal pseudocapsule-based extracapsular resection for pituitary adenomas.

BACKGROUND: In the past several years, increasing attention has been paid to the utility of a pseudocapsule in transphenoidal surgery for pituitary adenomas. However, prior studies focused more on the histological structure of the pseudocapsule and surgical technique. The objective of this study was to evaluate the overall therapeutic effectiveness of transsphenoidal pseudocapsule-based extracapsular resection for pituitary adenomas. METHODS: Between January 2004 and October 2007, 78 patients with pituitary adenomas underwent transsphenoidal pseudocapsule-based extracapsular removal surgery (extracapsular resection group, ER group). During the same period, 64 patients underwent transsphenoidal intracapsular resection operations (intracapsular resection group, IR group). RESULTS: Complete resection rates were achieved in 90.6%, 84.6% and 65.5%, 52.6% of modified Hardy types II and III in the ER and IR groups, showing a significant difference (both P < 0.05). Statistical significance in the remission rates was also found between the two groups with modified Hardy types II and III, respectively (both P < 0.05). Complications occurred in 29.5% of the ER group and 26.6% of the IR group, with no difference between groups (P > 0.05). The recurrence rate of the ER group (2.56%) was lower than that of the IR group (14.06%). CONCLUSION: The transsphenoidal pseudocapsule-based extracapsular resection approach provides a more effective and safe alternative compared to the traditional intracapsular one because of its higher tumor removal and remission rates, and lower recurrence rate.

Surgical outcomes and prognostic factors of transsphenoidal surgery for prolactinoma in men: a single-center experience with 87 consecutive cases.

Context Little systematic data on male prolactinomas treated with surgery are available. Objective To clarify the clinical features and confirm the efficacy of transsphenoidal surgery for male prolactinomas and predictive factors after initial surgery. Patients and methods This retrospective study included 87 male patients with prolactinoma treated by transsphenoidal surgery at an academic medical center. Hormonal and visual status, remission rates, and the rate of tumor relapse, as well as predictive factors, were evaluated. Results Postoperative initial remission was achieved in 52.9% of patients. The remission rate was markedly higher in microadenomas (83.3%) than in macroadenomas (44.9%). Logistic regression analysis showed that the predictive factors of the early negative outcomes were high preoperative prolactin (PRL) levels and tumor invasion. After a median follow-up of 45 months, the long-term remission rate was 42.5%, and relapse of hyperprolactinemia occurred in 19.6% of the cured patients. The 5-year recurrence-free survival was 78.2% (95% confidence interval, 62.3-88.1%). When surgery was followed by adjuvant treatment in uncured and recurrent patients, 78.8% of patients in the entire group in the absence of dopamine agonists obtained biochemical remission at the end of follow-up. Conclusion Transsphenoidal surgery is a viable treatment alternative for male prolactinomas. The remission rates of male patients with microadenomas and/or intrasellar macroprolactinomas by surgery alone remain excellent, and surgery followed by adjuvant therapy as necessary is required for optimizing management of male prolactinomas, especially for extrasellar macroprolactinomas. The early negative results are associated with preoperative PRL levels and tumor invasion.

Clinical features and immunohistochemical changes of pituitary apoplexy.

The clinical features of 426 pituitary adenomas were retrospectively analyzed, focusing on the factors that affect the development of pituitary apoplexy. Immunohistochemical analysis was used to define the different hormone types of the tumors and the expression of various immunologic targets, including the pituitary tumor transforming gene, basic fibroblast growth factor-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and proliferating cell nuclear antigen. Of the 426 patients, 83 presented with pituitary apoplexy (19.48%). Among them, 43 patients (43/83, 51.82%) developed apoplexy in the absence of any obvious precipitating factor. Clinical manifestations included headaches (80/83, 96.38%), vision loss (69/83, 83.13%), pituitary function change (51/83, 61.45%), visual field defects (41/83, 49.39%), and nausea and vomiting (34/83, 40.96%). Male patients and patients with functional adenoma had a higher probability of developing apoplexy. Complicated immunological expression patterns were found in adenomas associated with pituitary apoplexy, with adenomas of different hormone types identified.