We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. ...PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.
We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR.
CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-β signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients.
PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.
Cocaine is one of the most frequently used illicit drug in the world. Therefore, the development of simple and fast methods for the detection of cocaine and common adulterants, diluents and ...impurities are extremely important in forensic investigations. The present study describes, for the first time, a method based on capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) for the rapid (2.5 min) and simultaneous quantification of cocaine, levamisole, lidocaine, carbonate, borate, chloride, nitrate, nitrite and sulphate. In the experiment, anions were separated in co-electroosmotic mode and cations in counter-electroosmotic mode employing a buffer solution composed by 10.0 mmol L−1 TAPS, 12 mmol L−1 NaOH and 0.2 mmol L−1 CTAB as the background electrolyte (pH = 8.8). The developed CE method demonstrated some interesting analytical characteristics such as: (i) a simple sample pretreatment step (only dilution in water and filtering), (ii) high-throughput screening (24 injections h−1), (iii) proper recovery values (between 72 and 118%), and (iv) an inter-day precision of less than 7% for all analytes. The procedure was successfully applied in the analysis of seized cocaine samples collected by the Integrated Forensics Post (PPI) of the Minas Gerais Civil Police (Uberaba, Minas Gerais State, Brazil), during the year of 2018.
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•CE-C4D for rapid (2.5 min) and simultaneous quantification of adulterants in seized cocaine samples.•Cocaine, levamisole, lidocaine, CO32−, BO33−, Cl−, NO2−, NO3−, and SO42− peaks in a single run.•The procedure exhibits high-throughput screening, specificity and wide linear range.•The cationic and anionic profile performed on CE-C4D can be used as a screening tool to aid the Police investigations.
Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in breast cancer. However, the function of PRRX1 in colorectal cancer (CRC) has not ...been elucidated.
We utilised ectopic PRRX1-expressing cell lines to analyse the function of PRRX1 in CRC. The clinical significance of PRRX1 was also examined on three independent CRC case sets.
PRRX1 induced EMT and the stem-like phenotype in CRC cells. In contrast to studies of breast cancer, abundant expression of PRRX1 was significantly associated with metastasis and poor prognosis in CRC.
PRRX1 is an indicator of metastasis and poor prognosis in CRC cases. Further investigation is required to uncover the signalling network regulating PRRX1.
Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This ...work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats.
An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured.
Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats.
The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.
Endoscopic hydro-mastoidectomy, in which mastoidectomy is performed underwater, can be employed during transcanal endoscopic ear surgery for cholesteatoma removal. It was hypothesised that endoscopic ...hydro-mastoidectomy might take less time than endoscopic non-underwater mastoidectomy because the endoscope does not need to be removed for cleaning.
This study compared the mastoidectomy and total operative durations between the endoscopic hydro-mastoidectomy (
= 25) and endoscopic non-underwater drilling (control,
= 8) groups. Moreover, it compared the size of resected areas of the external auditory canal between the two groups.
The mastoidectomy time of the endoscopic hydro-mastoidectomy group was significantly shorter than that of the control group (
< 0.01). The total operative time did not differ significantly between the endoscopic hydro-mastoidectomy and control groups (
= 0.17). The resected area was significantly larger in the endoscopic hydro-mastoidectomy group than in the control group (
< 0.05).
Endoscopic hydro-mastoidectomy enables more extensive bone resection within a shorter period.
The dipole polarizability of stable even-mass tin isotopes 112,114,116,118,120,124Sn was extracted from inelastic proton scattering experiments at 295MeV under very forward angles performed at RCNP. ...Predictions from energy density functionals cannot account for the present data and the polarizability of 208Pb simultaneously. The evolution of the polarizabilities in neighboring isotopes indicates a kink at 120Sn while all model results show a nearly linear increase with mass number after inclusion of pairing corrections.
The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) ...expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC).
Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated.
High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced.
Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.
Aggressive periodontitis (AgP) is characterized by rapid alveolar bone destruction and tooth loss early in life, and its etiology remains unclear. To explore the genetic risk factors of AgP, we ...performed genome-wide single-nucleotide polymorphism genotyping for identity-by-descent mapping and identified 32 distinct candidate loci, followed by whole exome sequencing with 2 pedigrees of AgP consisting of 3 cases and 1 control in 1 family and 2 sibling cases in the other. After variant filtering procedures and validation by targeted Sanger sequencing, we identified 2 missense mutations at 16q12 in NOD2 (p.Ala110Thr and p.Arg311Trp), which encodes nucleotide-binding oligomerization domain protein 2. We further examined 94 genetically unrelated AgP patients by targeted sequencing of NOD2 and found that 2 patients among them also carried the p.Arg311Trp variant. Furthermore, we found 3 additional missense mutations in this gene (p.His370Tyr, p.Arg459Cys, and p.Ala868Thr). These mutations either had not been previously observed or are extremely rare (frequency <0.001) in Asian populations. NOD2 plays a crucial role in innate immunity as an intracellular receptor initiating nuclear factor κB–dependent and mitogen-activated protein kinase–dependent gene transcription. These results demonstrated NOD2 as a novel gene involved in AgP.
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