Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/ß-Catenin Signaling Pathway.

INTRODUCTION: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS: Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/ß-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/ß-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.

Vitamin D regulates microflora and ameliorates LPS-induced placental inflammation in rats.

Preeclampsia is a pregnancy-specific disease, which has become an essential cause of perinatal and neonatal death. Gut microflora becomes the regulator of host immunity through the metabolic pathway. Epidemiological studies provide convincing evidence that vitamin D supplementation can prevent the onset of preeclampsia. However, research on the microbial mechanisms and effective treatment strategies for placental inflammation induced by lipopolysaccharide is lacking. In this study, pregnant rats were induced by LPS to establish a rat model of preeclampsia. Sixteen-sequence analysis was used to determine the composition of microflora in feces. In addition, the protective effect of vitamin D supplementation on LPS-preeclampsia rats was evaluated. The results showed that the blood pressure and creatinine of pregnant rats in the LPS group were significantly higher than those in the control group. In addition, LPS disturbed the intestinal microbial community and reduced microbial diversity. Vitamin D supplementation improves the symptoms of preeclampsia, increases the abundance of intestinal beneficial flora, normalizes the level of inflammatory factors LPS-induced by inhibiting the TLR4/MYD88/NF-κB pathway, and effectively resists the disturbance of uterine spiral artery remodeling induced by LPS. This study established that vitamin D-mediated microbial mechanisms and their inhibition are potential therapeutic targets for the treatment of preeclampsia.

Triglyceride glucose index is a significant predictor of severe disturbance of consciousness and all-cause mortality in critical cerebrovascular disease patients.

OBJECTIVE: The association of the triglyceride-glucose (TyG) index with severe consciousness disturbance and in-hospital mortality in patients with cerebrovascular disease in the intensive care unit (ICU) is unclear. This study aimed to investigate the TyG index's predictive ability on the severity of impaired consciousness and in-hospital mortality in patients with cerebrovascular disease in the ICU. METHOD: Patients diagnosed with non-traumatic cerebral hemorrhage and cerebral infarction were extracted from the MIMIC-IV database and analyzed as two cohorts. The association between the TyG index and the severity of patients' impairment of consciousness and in-hospital mortality was analyzed using logistic regression models. Using restricted cubic spline curves, we analyzed potential nonlinear relationships between TyG indices and outcome indicators. receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of the TyG index for outcome indicators. RESULT: The study's last two cohorts comprised 537 patients with traumatic cerebral hemorrhage and 872 patients with cerebral infarction. TyG index was a significant predictor of the severity of impaired consciousness and in-hospital mortality in patients with cerebrovascular disease, as determined by logistic regression. The risk of severe consciousness impairment and in-hospital mortality increased roughly linearly with increasing TyG index. CONCLUSION: The TyG index was found to be a significant predictor for severe impairment of consciousness and in-hospital death in patients with cerebrovascular disease in the ICU, and it provides some predictive value for the severity of consciousness disturbances and in-hospital mortality in cerebrovascular disease patients.

Overexpression of Sugarcane ScDIR Genes Enhances Drought Tolerance in Nicotiana benthamiana.

Dirigent proteins (DIRs) are known to function in lignin biogenesis and to be involved in stress resistance in plants. However, the sugarcane DIRs have not been functionally characterized. In this study, we investigated the DIR-protein-encoding genes in Saccharum spp. (ScDIR) by screening collections of sugarcane databases, monitoring the responses of these genes to drought stress by real-time quantitative PCR, and identifying their heterologous expression in tobacco. Of the 64 ScDIRs identified, four belonging to the DIR-b/d (ScDIR5 and ScDIR11) and DIR-c (ScDIR7 and ScDIR40) subfamilies showed a significant transcriptional response when subjected to drought stress. ScDIR5, ScDIR7, and ScDIR11 are localized in the cell membrane, whereas ScDIR40 is found in the cell wall. The overexpression of these ScDIR genes in tobacco generally increased the drought tolerance of the transgenic lines, with ScDIR7 conferring the highest degree of drought tolerance. The characterization of the physiological and biochemical indicators (superoxide dismutase, catalase, malondialdehyde, and H2O2) confirmed that the ScDIR-overexpressing lines outperformed the wild type. These results demonstrated that specific ScDIRs in sugarcane respond and contribute to tolerance of drought stress, shedding light on potential means of improving drought tolerance in this crop.

Relationship between atherosclerotic burden and depressive symptoms in hypertensive patients: A cross-sectional study based on the NHANES database.

OBJECTIVE: The relationship between atherosclerotic burden, depressive symptoms, and clinically relevant depression (CRD) in hypertensive patients is unclear. In this study, we used the atherosclerotic index of plasma (AIP) to quantify atherosclerotic burden and explore its association with depressive symptoms and CRD in hypertensive patients. METHODS: Hypertension-diagnosed patients were extracted from the National Health and Nutrition Examination Survey (NHANES) database. The relationships between AIP and depressive symptoms and CRD risk in patients were examined through the weighted logistic regression and the weighted linear regression models. Restrictive cubic spline curves were employed to analyze potential nonlinear associations between AIP and outcome indicators. Additionally, subgroup analyses and intergroup interaction tests were conducted. RESULTS: The AIP was considerably associated with the severity of depressive symptoms in hypertensive patients, according to the findings of weighted linear regression. Weighted logistic regression analysis showed that high AIP was significantly associated with a high risk of clinically relevant depression in hypertensive patients. This trend was consistent across various subgroups within the population. CONCLUSION: AIP was observed to be a significant risk factor for clinically relevant depression in hypertensive patients. Atherosclerotic burden in hypertensive patients was significantly associated with the severity of their depressive symptoms.

Unveiling immune tolerance pathways in preeclampsia placenta: implications for molecular targets and discovery of potential biomarkers.

During pregnancy, there is a link between disruption of maternal immune tolerance and preeclampsia, but the molecular mechanisms that regulate maternal and fetal immune tolerance remain unclear. This study employs bioinformatics to identify new markers related to placental immune tolerance and explore their potential role in predicting preeclampsia. Analyzing preeclampsia-related gene expression profiles in the Gene Expression Omnibus (GEO) dataset reveals 211 differentially expressed genes (DEGs) in the placenta, mainly influencing immune cell differentiation and response pathways. Employing weighted gene co-expression network analysis (WGCNA) and lasso regression, four potential target genes (ANKRD37, CRH, LEP, SIGLEC6) are identified for potential prediction of preeclampsia. Validation using the GSE4707 dataset confirmed the diagnostic and predictive potential of these candidate genes. RT-qPCR verified up-regulation in the placenta, while ELISA showed their correlation with immune tolerance factors associated with placental immune tolerance. As a result of this study, identifies potential biomarkers associated with placental immunity and contributes to understanding the molecular mechanism of preeclampsia.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

The maximum tolerated dose of gamma radiation to the optic nerve during γ knife radiosurgery in an animal study.

BACKGROUND: The safety of gamma knife radiosurgery should be considered when treating pituitary adenomas. OBJECTIVES: To determine the maximum tolerated dose of radiation delivered by gamma knife radiosurgery to optic nerves. METHODS: An animal model designed to establish prolonged balloon compression of the optic chiasm and parasellar region was developed to mimic the optic nerve compression caused by pituitary adenomas. Twenty cats underwent surgery to place a balloon for compression effect and 20 cats in a sham operation group received microsurgery without any treatment. The effects of gamma knife irradiation at 10-13 Gy on normal (sham operation group) and compressed (optic nerve compression group) optic nerves were investigated by pattern visual evoked potential examination and histopathology. RESULTS: Gamma knife radiosurgery at 10 Gy had almost no effect. At 11 Gy, P100 latency was significantly prolonged and P100 amplitude was significantly decreased in compressed optic nerves, but there was little change in the normal optic nerves. Doses of 11 Gy and higher induced significant electrophysiological variations and degeneration of the myelin sheath and axons in both normal and compressed optic nerves. CONCLUSIONS: Compressed optic nerves are more sensitive to gamma knife radiosurgery than normal optic nerves. The minimum dose of gamma knife radiosurgery that causes radiation injury in normal optic nerves is 12 Gy; however, the minimum dose is 11 Gy in compressed optic nerves.

Association between VDR genetic polymorphisms and risk of gestational diabetes mellitus in the Chinese population.

BACKGROUND AND AIMS: Abnormal metabolism of vitamin D was the primary mechanism in many pregnancy diseases. Our study was the first to examine the hypothesis that VDR gene polymorphisms contribute to the risk of gestational diabetes mellitus (GDM) in the Chinese population at high altitudes. MATERIALS AND METHODS: One hundred and eighteen women with GDM and 104 women with normal glucose tolerance (NGT) were included in this study using a case-control design. Four single nucleotide polymorphisms (g.47879112G > A, g.47846052C > T, g.47844974A > G, and g.47845054C > A) of mother and fetus were genotyped. RESULTS: Maternal and fetal frequency of the A allele of g.47879112G > A was significantly increased in women with GDM than in those with NGT (p < .05). A correlation between the AA homozygous genotype of g.47879112G > A and GDM was noted. Compared with non-carriers, A allele carriers showed higher fasting plasma insulin and two-hour post-challenge plasma glucose (2h-PPG), and lower levels of vitamin D. Furthermore, both maternal and fetal 4-marker haplotype ACCG were found to be significantly associated with GDM (p < .05). CONCLUSIONS: Association and haplotype analysis indicated that the A allele of g.47879112G > A could be a risk factor for GDM development in the Chinese population at high altitudes. Additionally, the VDR gene polymorphism of the fetus and mother may have a synergistic effect. The VDR polymorphism is associated with an increased risk of GDM and may be useful for predicting the development of the disease.

Identification of Gene Modules and Hub Genes Associated with Sporisorium scitamineum Infection Using Weighted Gene Co-Expression Network Analysis.

Sporisorium scitamineum is a biotrophic fungus responsible for sugarcane smut disease. To investigate the key genes involved in S. scitamineum infection, we conducted RNA sequencing of sugarcane sprouts inoculated with S. scitamineum teliospores. A weighted gene co-expression network analysis (WGCNA) showed that two co-expressed gene modules, MEdarkturquoise and MEpurple-containing 66 and 208 genes, respectively-were associated with S. scitamineum infection. The genes in these two modules were further studied using Gene Ontology (GO) enrichment analysis, pathogen-host interaction (PHI) database BLASTp, and small secreted cysteine-rich proteins (SCRPs) prediction. The top ten hub genes in each module were identified using the Cytohubba plugin. The GO enrichment analysis found that endoplasmic reticulum-related and catabolism-related genes were expressed during S. scitamineum infection. A total of 83 genes had homologs in the PHI database, 62 of which correlated with pathogen virulence. A total of 21 proteins had the characteristics of small secreted cysteine-rich proteins (SCRPs), a common source of fungal effectors. The top ten hub genes in each module were identified, and seven were annotated as Mig1-Mig1 protein, glycosyl hydrolase, beta-N-acetylglucosaminidase, secreted chorismate mutase, collagen, mRNA export factor, and pleckstrin homology domain protein, while the remaining three were unknown. Two SCRPs-SPSC_06609 and SPSC_04676-and three proteins-SPSC_01958, SPSC_02155, and SPSC_00940-identified in the PHI database were also among the top ten hub genes in the MEdarkturquoise and MEpurple modules, suggesting that they may play important roles in S. scitamineum infection. A S. scitamineum infection model was postulated based on current findings. These findings help to deepen the current understanding of early events in S. scitamineum infection.

1,25(OH)2D3 alleviates LPS-induced preeclampsia-like rats impairment in the protective effect by TLR4/NF-kB pathway.

INTRODUCTION: Accumulating epidemiological studies support that Vitamin D deficiency is associated with the pathogenesis of preeclampsia. However, it is unknown whether vitamin D can be used as a treatment for preeclampsia. This study aimed to explore whether vitamin D supplementation could improve the rat model of preeclampsia. METHODS: LPS was used to establish a rat model of preeclampsia. Inflammatory cytokines were examined by QRT-PCR and ELISA assays, and the concentration of sfit-1 and NO was assessed by ELISA. Analyzing the pathological features of the placenta with hematoxylin-eosin. The spatial learning and memory abilities of offspring were evaluated by the Morris water maze. Immune histology and western blot were performed to evaluate the expression levels of inflammatory pathway-associated Factor and vascular endothelium-associated Factor in the placenta. RESULTS: Vitamin D treatment reduced the blood pressure and urine protein of PE model rats, alleviated pathological damage to the placenta and pregnancy outcomes, and protected PE offspring from impaired memory and learning abilities. Moreover, TLR4 signaling pathway in the placenta was inhibited. Furthermore, vitamin D supplementation increased the expression of endothelial growth factor and vascular relaxing factor, and there was no significant difference compared with the control group. DISCUSSION: We generated the result that Vitamin D supplementation significantly improved the phenotype of preeclampsia and adverse pregnancy outcome caused by an abnormal inflammatory reaction and endothelial dysfunction in the placenta, and improved the learning and cognitive ability of offspring.

LncRNA LINC00473 is involved in the progression of invasive pituitary adenoma by upregulating KMT5A via ceRNA-mediated miR-502-3p evasion.

Long noncoding RNAs (lncRNAs) and their crosstalks with other RNAs have been revealed to be closely related to tumorigenesis and development, but their role in invasive pituitary adenoma (IPA) remains largely unclear. In our study, LINC00473 was identified as the most upregulated lncRNA in IPA by whole transcriptome RNA sequencing (RNA-Seq). Further, its related signaling pathway LINC00473/miR-502-3p/KMT5A was obtained by constructing a competing endogenous RNA (ceRNA) regulatory network. Their expression in IPA and non-invasive pituitary adenoma (NIPA) tissues was verified by qRT-PCR. Then the effects and mechanisms of LINC00473 and its ceRNA network on the proliferation of pituitary adenoma (PA) cells were confirmed by gene overexpression or silencing techniques combined with CCK-8 assay, EdU staining, flow cytometry assay, and double luciferase reporter gene assay in PA cell lines AtT-20 and GT1-1 in vitro and in a xenograft model in vivo. LINC00473 is overexpressed in IPA and can promote PA cells proliferation. Mechanistically, overexpression of LINC00473 restricts miR-502-3p through the ceRNA mechanism, upregulates KMT5A expression, and promotes the expression of cyclin D1 and CDK2, which is conducive to the cell cycle process, thereby promoting the proliferation of PA cells, involving IPA progression.

Risk factors for the incidence of apoplexy in pituitary adenoma: a single-center study from southwestern China.

BACKGROUND: Although the incidence and clinical manifestations of pituitary apoplexy were reported by a few researches, the results are not consistent. This study aimed to explore the risk factors associated with an incidence of apoplexy in pituitary adenomas. METHODS: The clinical information of 843 patients with pituitary adenoma from the Department of Neurological Surgery, 1st Affiliated Hospital of Kunming Medical University, was reviewed. The incidence, clinical manifestation, and potential risk factors for pituitary apoplexy were analyzed by a case-control study. RESULTS: In total, 121 patients (14.4%) with macroadenoma were suffered from pituitary apoplexy. Headache, vomiting, and visual impairment are the top 3 symptoms for the pituitary apoplexy.Logistic regression results showed that the hypertension(hypertension vs non-hypertension OR = 2.765, 95%CI:1.41~5.416), tumor type (negative staining vs. positive staining, OR = 1.501, 95%CI:1.248~5.235), and tumor size (diameter > 2 cm vs. diameter ≤ 2 cm, OR = 3.952, 95%CI:2.211~7.053) are independent factors associated with pituitary apoplexy. CONCLUSION: Our results indicate that the risk factors for the incidence of pituitary apoplexy depend mainly on properties of the tumor itself (tumor size and pathologic type) and the blood pressure of patients.

Hypoxia promotes proliferation of pituitary adenomas by HIF-1α/ALKBH5 signaling in vitro.

Hypoxia is a common phenomenon in pituitary adenomas (PAs). The role and mechanism of hypoxia in the PAs remains elusive. This work aimed to explore the effect of hypoxia on PAs in vitro. PA cells GT1-1 were cultured and treated under hypoxic condition. Cell proliferation assay showed the proliferation of PA cells was increased significantly by hypoxia treatment, with a peak at 12 hours. qPCR and western blot indicated that the expression of HIF-1α, ALKBH5, and Nanog were elevated by hypoxia stimuli. In conclusion, our funding demonstrated that hypoxia could increase Nanog expression through HIF-1α/ALKBH5 signaling, thereby promoting the proliferation of PA cells.

Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson's disease.

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson's disease, but its specific mechanism of action is still unclear. Stromal cell-derived factor-1 and its receptor, chemokine receptor 4 (CXCR4), are important regulators of cell migration. We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson's disease. A Parkinson's disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway, and then treated with 5 µL of neural stem cell suspension (1.5 × 104/L) in the right substantia nigra. Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation. Parkinson-like behavior in rats was detected using apomorphine-induced rotation. Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase, CXCR4, and stromal cell-derived factor-1 in the brain. Using quantitative real-time polymerase chain reaction, the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured. In addition, western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4. Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation, increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra, and enhanced the immunoreactivity of tyrosine hydroxylase, CXCR4, and stromal cell-derived factor-1 in the brain. Injection of AMD3100 inhibited the aforementioned effects. These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson's disease. This study was approved by the Animal Care and Use Committee of Kunming Medical University, China (approval No. SYXKK2015-0002) on April 1, 2014.

Transplantation of Nurr1-overexpressing neural stem cells and microglia for treating parkinsonian rats.

BACKGROUND: Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment. METHODS: In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence analysis. RESULTS: The behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months. CONCLUSIONS: The results suggested that transplantation of Nurr1-overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be  a new potential strategy for the cell replacement therapy in PD.

Superparamagnetic iron oxide labeling of spinal cord neural stem cells genetically modified by nerve growth factor-beta.

This study established superparamagnetic iron oxide (SPIO)-labeled nerve growth factor-beta (NGF-beta) gene-modified spinal cord-derived neural stem cells (NSCs). The E14 rat embryonic spinal cord-derived NSCs were isolated and cultured. The cells of the third passage were transfected with plasmid pcDNA3-hNGFbeta by using FuGENE HD transfection reagent. The expression of NGF-beta was measured by immunocytochemistry and Western blotting. The positive clones were selected, allowed to proliferate and then labeled with SPIO, which was mediated by FuGENE HD transfection reagent. Prussian blue staining and transmission electron microscopy (TEM) were used to identify the SPIO particles in the cells. The distinctive markers for stem cells (nestin), neuron (beta-III-tubulin), oligodendrocyte (CNPase) and astrocyte (GFAP) were employed to evaluate the differentiation ability of the labeled cells. The immunocytochemistry and western blotting showed that NGF-beta was expressed in spinal cord-derived NSCs. Prussian blue staining indicated that numerous blue-stained particles appeared in the cytoplasma of the labeled cells. TEM showed that SPIO particles were found in vacuolar structures of different sizes and the cytoplasma. The immunocytochemistry demonstrated that the labeled cells were nestin-positive. After differentiation, the cells expressed beta-III-tubulin, CNPase and GFAP. It was concluded that the SPIO-labeled NGF-beta gene-modified spinal cord-derived NSC were successfully established, which are multipotent and capable of self-renewal.

Analysis of whole genome-wide microRNA transcriptome profiling in invasive pituitary adenomas and non-invasive pituitary adenomas.

BACKGROUND: Dysregulation of microRNAs (miRNAs) plays a critical role during the occurrence and progress of pituitary adenomas (PAs). However, the roles of miRNAs in the invasiveness of PA are poorly understood. This study aims to more comprehensively and specific define the relationship between altered miRNA and PA invasion. METHODS: The differential expression of miRNAs (DEMs) between invasive PAs (IPAs) and non-invasive PAs (NPAs) was explored by RNA sequencing and which functions were analyzed by gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG). The miRNA-mRNA network was predicted with bioinformatics. RESULTS: We identified 31 upregulated miRNAs and 24 downregulated miRNAs in IPAs compared with NPAs. GO analysis and KEGG pathway analysis showed the DEMs were mainly associated with cell proliferation and cell cycle pathway. In addition, on the count of predicted miRNA-mRNA network, two hub miRNAs were identified. CONCLUSIONS: Our results demonstrate the miRNA-mRNA network in detail, which suggest that miRNA may be a promising target in diagnosis and therapy for IPAs.

Analysis of whole genome-wide methylation and gene expression profiles in visceral omental adipose tissue of pregnancies with gestational diabetes mellitus.

BACKGROUND: DNA methylation is the most extensively studied epigenetic modification which had been suspected to be involved in the progress of gestational diabetes mellitus（GDM）. It is vital to investigate the expression profile and methylation profile in the GDM adipose tissue samples to learn more about the relationship between the two profiles. METHODS: Illumina Human Methylation 450 k DNA Analysis Beadchip and whole Human Gene Expression Array were selected to screen for methylation and gene expression in the omental visceral adipose tissue of pregnant women. Validation of methylation of DMGs was conducted by bisulfate pyrosequencing and expression of DEGs by q RT-PCR. RESULTS: Global gene methylation profiling and whole genome expression profiling were conducted in visceral omental adipose tissue (VOAT) between GDM and normal pregnancies. Compared with controls, 935 genes were commonly dysregulated in the GDM group, including 450 down-regulated DEGs and 485 up-regulated DEGs. The Seven overlapping genes between DEGs and DMGs were extracted, including C10orf10, FSTL1, GSTT1, HLA-DPB1, HLA-DRB5, HSPA6 and MSLN. Among them, C10orf10, FSTL1, GSTT1, HLA-DPB1, HLA-DRB5 showed hypermethylation and up-regulated expression, while HSPA6 show hypomethylation and down-regulated expression. Typical negative correlation between gene expression and DNA methylation level was only found in MSLN with significant hypermethylation in the CpG island and downregulated transcription. No gene was found to be significantly hypomethylated in the CpG islands and unregulated transcription. CONCLUSION: We found that antigen processing and presentation pathway and immune-related genes were closely associated with gestational diabetes mellitus in the visceral omental adipose tissue of Chinese pregnant women, based on the integration analysis of expression and methylation profiles. These results may be valuable for the prognostic biomarkers and future therapeutic targets.

Inhibition of tumor growth and angiogenesis by 2-(4-aminophenyl) benzothiazole in orthotopicglioma C6 rat model.

In the present study antitumor effect of 2-(4-aminophenyl) benzothiazole (BTZ) was evaluated against human U251 and rat C6 glioma cell lines using MTT assay. It was observed that BTZ exhibited significant antitumor effect with IC50 of 3.5 and 4 µM against human U251 and rat C6 glioma cells respectively. To gain in-depth insights about the antitumor effect of BTZ, glioma xenograft rat model was prepared. The rats were treated with 10 mg and 15 mg/kg body weight doses of BTZ daily for 21 days after C6 cell administration. Treatment of the rats with BTZ reduced the tumor volume to 12% compared to 100% in the untreated rats. TUNEL assay showed a remarkable increase in the proportion of apoptotic cells in the BTZ treated rats than those in the untreated rats. The increase in the population of apoptotic cells was 23-fold compared to control. Immuno-histological staining revealed marked reduction (16%) in the proportion of CD31-stained vessels in the BTZ treated rats than those of the untreated rats. These changes were accompanied with decreased transcript levels of vascular endothelial growth factor (VEGF) and the VEGF receptor Flt1 as well as ERK1/2 and matrix metalloproteinase-2 (MMP2). Moreover, BTZ altered the expression of several cell cycle control proteins. While as pRb protein expression decreased, E2F1 remained unaltered and cyclin D1 protein and p53 expression was enhanced. Taken together, the results indicate that BTZ is a potent inhibitor of glioma cell proliferation in vivo and exerts its effects on cell cycle control and angiogenesis related proteins.