MiRNA-188-5p alleviates the progression of osteosarcoma via target degrading CCNT2.

OBJECTIVE: The aim of this study was to investigate the biological role of microRNA-188-5p (miRNA-188-5p) in mediating the progression of osteosarcoma by degrading CCNT2. PATIENTS AND METHODS: The relative expression levels of miRNA-188-5p and CCNT2 in osteosarcoma tissues and para-cancerous normal tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, their expression levels in osteosarcoma cell lines were examined. The regulatory effects of miRNA-188-5p on the proliferative ability and cell cycle progression of osteosarcoma cells were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. Dual-Luciferase reporter gene assay was applied to verify the binding relationship between miRNA-188-5p and CCNT2. Furthermore, rescue experiments were conducted to clarify the role of miRNA-188-5p/CCNT2 in mediating the progression of osteosarcoma. RESULTS: MiRNA-188-5p was lowly expressed in osteosarcoma tissues when compared with paracancerous normal tissues. Overexpression of miRNA-188-5p significantly suppressed the proliferative ability and arrested cell cycle progression of osteosarcoma cells. However, knockdown of miRNA-188-5p obtained the opposite trends. The Dual-Luciferase reporter gene assay verified the binding relationship between miRNA-188-5p and CCNT2. The expression level of CCNT2 in HOS and MG-63 cells was markedly downregulated after transfection of miRNA-188-5p mimics. In addition, overexpression of CCNT2 could partially reverse the inhibitory effect of miRNA-188-5p on the proliferative ability and cell cycle progression of osteosarcoma cells. CONCLUSIONS: MiRNA-188-5p is downregulated in osteosarcoma. Furthermore, it suppresses the proliferative ability and cell cycle progression of osteosarcoma cells via target degrading CCNT2.

Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway.

OBJECTIVE: To investigate the relative expression of long non-coding RNA 00673 (lncRNA 00673) in hepatocellular carcinoma (HCC) and HCC cells and study its regulation on the malignant phenotype of HCC cells PATIENTS AND METHODS: Samples of HCC and adjacent tissues from January 2013 to December 2015 were collected. The expression level of lncRNA00673 in HCC tissues and cells was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) assays. lncRNA00673 specific interference sequences were transiently transfected into HCC cells and the effect of HCC cells on the biological behavior of HCC cells was examined by in vitro experiments ((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay), flow cytometry, transwell, etc.). A tumor model of nude mice with HCC was established for the study of tumor growth condition of tumor-bearing mice after the interference with lncRNA00673 expression. Changes in expression levels of molecular markers on Notch signaling pathway after the interference with lncRNA00673 were detected by Western blot. RESULTS: lncRNA00673 was highly expressed in HCC tissues and cells. MTT results showed that interfering with lncRNA00673 inhibited cell proliferation. Flow cytometry results showed that HCC cell cycle was retarded in G1-G0 phase, thus promoting apoptosis after the interference with lncRNA00673. Western blot results showed that expression levels of molecular markers on Notch signaling pathway were changed after the interference with lncRNA00763. CONCLUSIONS: lncRNA00673 is highly expressed in HCC tissues and cells, and can promote the proliferation and metastasis of HCC by the regulation on Notch signaling pathway. lncRNA00673 may be a potential target for the treatment of HCC.

miR-182 selectively targets HOXA10 in goat endometrial epithelium cells in vitro.

Proper HOXA10 expression was essential for endometrial receptivity what was crucial for successful embryo implantation in mammalian. This study confirmed that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR, selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed in the goat endometrium at gestational day 15 (D15) compared with gestational day 5 (D5), suggesting that there were some other factors regulated the expression of HOXA10 during the development of goat endometrium in vivo. What's more, HOXA10 gene silencing (HOXA10-siRNA) resulted in gEECs apoptosis in vitro, and it regulated the protein levels of oestrogen receptor a (ERa), progesterone receptor B (PRb), insulin-like growth factor 1 receptor (IGF1R), BCL-2, pleiotrophin (PTN), AKT and p-JNK in gEECs. Furthermore, HOXA10 might regulate the protein levels of endometrial receptivity biomarker genes, including vascular endothelial growth factor (VEGF), osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in gEECs. In conclusion, miR-182 targeted HOXA10 selectively in EECs in vitro, and HOXA10 played an important role in maintaining the function of EECs in dairy goats.

Knockdown of protein phosphatase 5 (PPP5C) suppresses the growth of leukemic cell line U937.

Serine/threonine protein phosphatase 5 (PPP5C) participates in multiple signaling pathways including cell cycle control and cell growth. PPP5C is involved in the progression of human breast cancer and hepatocellular carcinoma. However, its function in acute myelogenous leukemia (AML) remains unknown. In this study, we constructed a lentivirus system to knock down the expression level of PPP5C in leukemic cell line U937. Cell proliferation and cell cycles were assessed by MTT assay and flow cytometry respectively. Western blot was used to determine the level of caspase-3, PARP (poly ADP-ribose polymerase), CDK4 and CyclinD1. Knockdown of PPP5C suppressed the proliferation ability of U937 cells, and led to G0/G1 phase arrest, inducing cell apoptosis in U937 cells. The apoptosis of the U937 cells was associated with upregulating cleaved caspase-3 and PARP, and downregulating CDK4 and CyclinD1. In conclusions, PPP5C knockdown inhibits U937 cell proliferation and might be used as a potential therapeutic target for the treatment of leukemia.

Universality analysis of the existence of substantia nigra "swallow tail" appearance of non-Parkinson patients in 3T SWI.

OBJECTIVE: To use the 3.0T susceptibility-weighted imaging (SWI) for universality analysis of the "swallow tail" appearance in the substantia nigra of non-Parkinson disease and discuss its lack of the value of imaging diagnosis of Parkinson disease (PD). PATIENTS AND METHODS: Take 3.0TMR SWI in 60 PD patients (Group PD) and non-PD volunteers (Group N-PD), on the map of range analyze morphology and number of "swallow tail" appearance in substantia nigra of N-PD group volunteers, and compare the performance image of the corresponding region of the patients in the PD group. RESULTS: After, 15 patients with lesions in the brain stem and significant motion artifacts were excluded. Forty-nine cases of group N-PD (96.08%) had typical "swallow tail" appearance in the bilateral or unilateral substantia nigra compacta posterolateral. All 54 patients with group PD (100%) lacked the "drop" rear elliptical high signal. CONCLUSIONS: On the 3.0T SWI range map, the "swallow tail" appearance is ubiquitous in the substantia nigra of patients with non-PD. The deficiency of the signs has high sensitivity and specificity for PD diagnosis.

Patients with brain metastases derived from gastrointestinal cancer: clinical characteristics and prognostic factors

Purpose. This study seeks to evaluate the natural history, outcome, and possible prognostic factors in patients with brain metastases derived from gastrointestinal cancers. Methods. The clinical features, prognostic factors, and the effects of different treatment modalities on survival were retrospectively investigated in 103 patients with brain metastases derived from gastrointestinal cancers. Results. The median time from diagnosis of primary tumor to brain metastasis was 22.00 months. The interval between diagnosis of primary tumor relapse and brain metastasis was 8.00 months. The median follow-up time was 7.80 months. The median survival time after diagnosis of brain metastases was 4.10 months for all patients and 1.17 months for patients who received only steroids (36.9 %), 3.97 months for patients who only received whole-brain radiation therapy (WBRT 31.1 %), 11.07 months for patients who received gamma-knife surgery alone or/and WBRT (20.4 %), and 13.70 months for patients who underwent surgery and radiotherapy (12 patients, 11.6 %) (P < 0.001). Multivariate analysis revealed that recursive partitioning analysis (RPA) class, extracranial metastasis, and chemotherapy were independent prognostic factors. Brain metastasis derived from gastrointestinal tract cancer is rare, and overall patient survival is poor. Conclusion. RPA class, chemotherapy after brain metastases, and treatment regimens were independent prognostic factors for the survival of patients with brain metastases derived from gastrointestinal cancers (AU)

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Patients with brain metastases derived from gastrointestinal cancer: clinical characteristics and prognostic factors.

PURPOSE: This study seeks to evaluate the natural history, outcome, and possible prognostic factors in patients with brain metastases derived from gastrointestinal cancers. METHODS: The clinical features, prognostic factors, and the effects of different treatment modalities on survival were retrospectively investigated in 103 patients with brain metastases derived from gastrointestinal cancers. RESULTS: The median time from diagnosis of primary tumor to brain metastasis was 22.00 months. The interval between diagnosis of primary tumor relapse and brain metastasis was 8.00 months. The median follow-up time was 7.80 months. The median survival time after diagnosis of brain metastases was 4.10 months for all patients and 1.17 months for patients who received only steroids (36.9 %), 3.97 months for patients who only received whole-brain radiation therapy (WBRT 31.1 %), 11.07 months for patients who received gamma-knife surgery alone or/and WBRT (20.4 %), and 13.70 months for patients who underwent surgery and radiotherapy (12 patients, 11.6 %) (P < 0.001). Multivariate analysis revealed that recursive partitioning analysis (RPA) class, extracranial metastasis, and chemotherapy were independent prognostic factors. Brain metastasis derived from gastrointestinal tract cancer is rare, and overall patient survival is poor. CONCLUSION: RPA class, chemotherapy after brain metastases, and treatment regimens were independent prognostic factors for the survival of patients with brain metastases derived from gastrointestinal cancers.

Visualization of nigrosomes-1 in 3T MR susceptibility weighted imaging and its absence in diagnosing Parkinson's disease.

OBJECTIVE: To assess the imaging features of nigrosomes-1 in the substantia nigra through 3T MR susceptibility weighted imaging (SWI) and its disease-specific changes for the diagnosis of Parkinson's disease (PD). PATIENTS AND METHODS: A total of 116 subjects were included in this study and allocated into 3 groups: 54 patients diagnosed with PD were assigned to the PD group, 51 age- and sex-matched volunteers without PD served as the control N-PD group, and 11 clinically suspected PD patients were allocated to the undiagnosed (UD) group. All patients received 3.0T superconducting MRI scanning on xxx. The images were analyzed and compared to assess the ability of nigrosomes-1 signals to depict PD pathology. RESULTS: The signals of nigrosomes-1 were strong, droplet-like or oval in shape, and were found in 49 patients from the N-PD group (96.08%), on both sides of the SN (47 cases) and unilaterally (2 cases). In contrast, these signals were absent in all 54 cases from the PD group, and were undetected in 7 out of 11 cases in the UD group, 7 cases without the "drop" and 1 case with narrow strips of hyperintensity were clinically proven to PD, 2 cases with the typical hyperintensity were clinically proven to Parkinson's plus syndrome, 2 cases with slightly wider strip of hyperintensity were less sensitive to the drug levodopa. CONCLUSIONS: The absence of typical droplet-like or oval-shaped nigrosomes-1 signals in 3.0T MR SWI may prove useful in identifying PD and Parkinson's syndrome with high sensitivity and specificity.

Study on the carotid atherosclerotic plaque of patients suffering from ischemic cerebrovascular disease by 64 slices CT.

OBJECTIVE: To explore the correlation between the features of a carotid plaque of patients suffering from carotid atherosclerosis and ischemic cerebrovascular disease by 64 slices computed tomography (CT). PATIENTS AND METHODS: One hundred patients with carotid atherosclerosis were divided into the ischemic event group (n=48) and non-ischemic event group (n=52). The features of the carotid plaque were detected by 64 slices CT. RESULTS: One hundred and thirteen plaques were found in the ischemic event group. The proportions of fatty, calcified, and mixed plaque were 35.4%, 30.1%, and 34.5%. There are 78 plaques found in the non-ischemic event group. The proportions of fatty, calcified, and mixed plaque were 21.8%, 51.3%, and 26.9%. The distribution difference between the three types of plaques was statistically significant (p<0.05). The proportions of mixed plaque composed mainly of fatty plaque were 64.1% and 23.8%. These two constituent ratios are significantly different from those of statistical processing (p<0.01). There are 10 cases of plaque ulceration out of the 100 cases, among which eight are from the ischemic event group and two cases from the other group. After statistical processing, the incidence rates of plaque ulceration from these two groups are significantly different (p<0.05). CONCLUSIONS: The 64 slices CT can accurately present the morphological features of the carotid plaque. It indicates that the fatty plaque, mixed plaque composed mainly of fatty plaque and ulcerative plaque can cause ischemic cerebrovascular events.

A study on lesion pattern of bilateral cerebellar infarct.

OBJECTIVE: To explore the lesion patterns and stroke mechanism of the acute bilateral cerebellar infarct. PATIENTS AND METHODS: Patients admitted to Xiangyang Hospital with acute cerebellar infarcts, confirmed by diffusion-weighted imaging (DWI), were investigated. Patients were divided into two groups by lesions: unilateral cerebellar infarct (UCI) and bilateral cerebellar infarct (BCI). The demographic features, involved territories and concomitant lesions outside the cerebellum (CLOC). The causes were analyzed. RESULTS: Amongst the 115 patients hospitalized with posterior circulation cerebral infarct due to acute stroke, 56 patients had cerebellar infarct. There were 36 (64.3%) cases of unilateral cerebellar infarct and 20 (35.7%) cases of the BCI. The baseline information shows that stroke history (p = 0.002), fibrinogen (p = 0.036) and admission NIHSS score (M) (p = 0.001) for the BCI group are higher than the unilateral cerebellar infarct group. The incidence rate of cerebellar infarct in a posterior inferior cerebellar artery (PICA) blood supplying territory is the highest by divisions of vascular distribution. Unilateral cerebellar infarct occurs more often (p = 0.006); BCI is more common in PICA+SCA blood supplying territory (p = 0.004). The incidence rate of BCI merged with CLOC is much higher than the unilateral cerebellar infarct (p = 0.002). Merged infratentorial lesions are more common (p = 0.022) than BCI with atherosclerosis (p = 0.041). Offending artery diseases are mainly in the V4 segment of the vertebral artery, and in the severe stenosis or occlusion of V4 and BA junction. CONCLUSIONS: BCI was frequently involved in the PICA + SCA territory. Our results support the fact that embolism resulted from large artery atherosclerosis is the important stroke mechanism in the BCI.

Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia.

Glucocorticoids (GCs) are among the most widely prescribed medications in clinical practice. The beneficial effects of GCs in acute lymphoblastic leukemia (ALL) are based on their ability to induce apoptosis, but the underlying transcriptional mechanisms remain poorly defined. Computational modeling has enormous potential in the understanding of biological processes such as apoptosis and the discovery of novel regulatory mechanisms. We here present an integrated analysis of gene expression kinetic profiles using microarrays from GC sensitive and resistant ALL cell lines and patients, including newly generated and previously published data sets available from the Gene Expression Omnibus. By applying time-series clustering analysis in the sensitive ALL CEM-C7-14 cells, we identified 358 differentially regulated genes that we classified into 15 kinetic profiles. We identified GC response element (GRE) sequences in 33 of the upregulated known or potential GC receptor (GR) targets. Comparative study of sensitive and resistant ALL showed distinct gene expression patterns and indicated unexpected similarities between sensitivity-restored and resistant ALL. We found that activator protein 1 (AP-1), Ets related gene (Erg) and GR pathways were differentially regulated in sensitive and resistant ALL. Erg protein levels were substantially higher in CEM-C1-15-resistant cells, c-Jun was significantly induced in sensitive cells, whereas c-Fos was expressed at low levels in both. c-Jun was recruited on the AP-1 site on the Bim promoter, whereas a transient Erg occupancy on the GR promoter was detected. Inhibition of Erg and activation of GR lead to increased apoptosis in both sensitive and resistant ALL. These novel findings significantly advance our understanding of GC sensitivity and can be used to improve therapy of leukemia.

Study on the effect of different oxygen therapies on rats with acute carbon dioxide poisoning.

OBJECTIVE: To study the effect of different oxygen therapies on the rats with carbon dioxide poisoning for screening out the best on-the-spot oxygen-therapy technology for treating acute carbon dioxide poisoning. METHODS: The 60 healthy male Sprague Dawley rats were randomly divided into normal control group (A group), carbon dioxide poisoning group (B group), low-concentration oxygen inhalation treatment group (C group), high-concentration oxygen inhalation treatment group (D group) and hyperbaric oxygen-therapy group (E group). Various kinds of oxygen therapies were given after the contamination. The pH, partial pressure of oxygen (PO(2)) and partial pressure of carbon dioxide (PCO(2)) of arterial blood, serum troponin I (CTNI), creatine kinase (CK), glutamic-oxaloacetic transaminase (AST), γ-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), potassium (K), sodium (Na) and chlorine (Cl) for the rats of each group were inspected. The lung and the brain tissues were taken for observing the pathological changes. RESULTS: There is no significant difference in pH, PO(2) and PCO(2) among all oxygen-therapy groups (p > 0.05). The levels of CTNI, CK and AST in E group are obviously lower than that in B, C and D groups (p < 0.05). The level of serum K in E group is obviously lower than that in B, C and D groups (p < 0.05). The levels of serum Na and Cl in E group are obviously higher than that in B, C and D groups (p < 0.05). The pathological change of lungs in E group is significantly better than that in C and D groups. CONCLUSIONS: We recommend that the medical units with related conditions can give the hyperbaric oxygen therapy to patients as soon as possible.