N1-guanyl-1,7-diaminoheptane sensitizes bladder cancer cells to doxorubicin by preventing epithelial-mesenchymal transition through inhibition of eukaryotic translation initiation factor 5A2 activation.

Drug resistance greatly reduces the efficacy of doxorubicin-based chemotherapy in bladder cancer treatment; however, the underlying mechanisms are poorly understood. We aimed to investigate whether N1-guanyl-1,7-diaminoheptane (GC7), which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation, exerts synergistic cytotoxicity with doxorubicin in bladder cancer, and whether eIF5A2 is involved in chemoresistance to doxorubicin-based bladder cancer treatment. BIU-87, J82, and UM-UC-3 bladder cancer cells were transfected with eIF5A2 siRNA or negative control siRNA before incubation with doxorubicin alone or doxorubicin plus GC7 for 48 h. Doxorubicin cytotoxicity was enhanced by GC7 in BIU-87, J82, and UM-UC-3 cells. It significantly inhibited activity of eIF5A2, suppressed doxorubicin-induced epithelial-mesenchymal transition in BIU-87 cells, and promoted mesenchymal-epithelial transition in J82 and UM-UC-3 cells. Knockdown of eIF5A2 sensitized bladder cancer cells to doxorubicin, prevented doxorubicin-induced EMT in BIU-87 cells, and encouraged mesenchymal-epithelial transition in J82 and UM-UC-3 cells. Combination therapy with GC7 may enhance the therapeutic efficacy of doxorubicin in bladder cancer by inhibiting eIF5A2 activation and preventing epithelial-mesenchymal transition.

The comparative study on inhibitory effect of natural organic matters on the TiO2 and activated carbon/TiO2 composites for the removal of 17α-ethinylestradiol.

To reduce or eliminate the inhibition effect of natural organic matters (NOMs) in water on TiO2 photocatalysis for removal of emerging contaminants, four activated carbon/titanium dioxide (AC/TiO2) composites with different pore structure were prepared by hydrothermal method. The results showed that anatase TiO2 particles were uniformly distributed in the pores or onto the surface of activated carbons. The total removal rate of 6 mg L-1 17α-ethinylestradiol (EE2) on the four AC/TiO2 composites reached above 90%, 30% higher than that of EE2 on TiO2. The degradation rate constants of EE2 on four kinds of AC/TiO2 were much higher than that on TiO2. Further study indicated that the adsorption removal ratio of EE2 on the composites was slightly reduced mainly because competitive adsorption between hydrophilic NOMs (HA and FA) and EE2 molecules when HA and FA coexisted with EE2 in water. But importantly, the obvious inhibitory effect of FA for TiO2 photocatalysis was eliminated on four composites because the introduction of AC with excellent adsorption capacity can preferentially transfer hydrophobic EE2 molecules onto adsorption sites of TiO2/AC composites.

Persulfate enhanced removal of bisphenol A by copper oxide/reduced graphene oxide foam: Influencing factors, mechanism and degradation pathway.

The CuO/reduced graphene oxide foam (CuO/RGF) with excellent recyclability was prepared via hydrothermal method followed by freeze drying treatment for bisphenol A (BPA) removal via activating peroxydisulfate (PDS). SEM, XRD, XPS, FT-IR, BET, and TG techniques were used to investigate the structure and property of CuO/RGF. The effect of degradation conditions (pH, PDS amount, Cl-, HCO3-, HA and FA) on BPA removal by CuO/RGF were investigated. The result presented that CuO nanosheet was inserted into the RGF carrier with three-dimensional structure. The degradation rate constant of BPA over CuO/RGF (0.00917 min-1) was 1.24 and 6.46 times higher than those of BPA over CuO (0.00714 min-1) and RGF (0.00142 min-1). More importantly, the pore structure of RGF can successfully limit the release of Cu (II) compared to pure CuO. According to quenching test as well as electron spin resonance (EPR) spectra, BPA degradation was triggered by 1O2, •OH and SO4•-, which was the combination of nonradical (1O2) and radical activation of PDS (•OH and SO4•-). The possible degradation route of BPA was proposed based on intermediates obtained by combining solid phase extraction pretreatment technique with high performance liquid-mass spectrometry. After assessing the viability of MCF-7 cells, we can see that the estrogenic activities of treated solution reduced without producing stronger endocrine disruptors.

Left Ventricular Noncompaction Is Associated with Valvular Regurgitation and a Variety of Arrhythmias.

Left ventricular noncompaction (LVNC) is a type of cardiomyopathy characterized anatomically by prominent ventricular trabeculation and deep intertrabecular recesses. The mortality associated with LVNC ranges from 5% to 47%. The etiology of LVNC is yet to be fully understood, although decades have passed since its recognition as a clinical entity globally. Furthermore, critical questions, i.e., whether LVNC represents an acquired pathology or has a congenital origin and whether the reduced contractile function in LVNC patients is a cause or consequence of noncompaction, remain to be addressed. In this study, to answer some of these questions, we analyzed the clinical features of LVNC patients. Out of 9582 subjects screened for abnormal cardiac functions, 45 exhibit the characteristics of LVNC, and 1 presents right ventricular noncompaction (RVNC). We found that 40 patients show valvular regurgitation, 39 manifest reduced systolic contractions, and 46 out of the 46 present different forms of arrhythmias that are not restricted to be caused by the noncompact myocardium. This retrospective examination of LVNC patients reveals some novel findings: LVNC is associated with regurgitation in most patients and arrhythmias in all patients. The thickness ratio of the trabecular layer to compact layer negatively correlates with fractional shortening, and reduced contractility might result from LVNC. This study adds evidence to support a congenital origin of LVNC that might benefit the diagnosis and subsequent characterization of LVNC patients.

Synthesis, structure, and properties of carbon/carbon composites artificial rib for chest wall reconstruction.

In this work, braided carbon fiber reinforced carbon matrix composites (3D-C/C composites) are prepared by chemical vapor infiltration process. Their composite structure, mechanical properties, biocompatibility, and in vivo experiments are investigated and compared with those of traditional 2.5D-C/C composites and titanium alloys TC4. The results show that 3D-C/C composites are composed of reinforced braided carbon fiber bundles and pyrolytic carbon matrix and provide 51% open pores with a size larger than 100 µm for tissue adhesion and growth. The Young's modulus of 3D-C/C composites is about 5 GPa, much smaller than those of 2.5D-C/C composites and TC4, while close to the autogenous bone. 3D-C/C composites have a higher tensile strength (167 MPa) and larger elongation (5.0%) than 2.5D-C/C composites (81 MPa and 0.7%), and do not show obvious degradation after 1 × 106 cyclic tensile loading. The 3D-C/C composites display good biocompatibility and have almost no artifacts on CT imaging. The in vivo experiment reveals that 3D-C/C composites artificial ribs implanted in dogs do not show displacement or fracture in 1 year, and there are no obvious proliferation and inflammation in the soft tissues around 3D-C/C composites implant. Our findings demonstrate that 3D-C/C composites are suitable for chest wall reconstruction and present great potentials in artificial bones.

The comparative study of two kinds of ß-Bi2O3/TiO2 binary composite and their removal of 17ɑ-ethynylestradiol.

In this work, we used TiO2 nanobelts and P25 particles as titanium sources to combine with ß-Bi2O3 to form ß-Bi2O3/TiO2 and ß-Bi2O3/P25 composites. The prepared samples were characterized by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), and UV-vis absorbance spectroscopy and fluorescence spectroscopy. The structure and performance of two composites were comparatively investigated, and the ß-Bi2O3 molar ratios in them were optimized and their roles in them were studied. The results showed that the TiO2 nanobelts and commercial TiO2 (P25) particles combined with ß-Bi2O3 nanosheets. The optimal molar ratios of Bi to Ti element in two kinds of composites are 1:1. The ß-Bi2O3 in P25/ß-Bi2O3 makes more contribution to the improvement of photocatalytic activity of them than that in ß-Bi2O3/TiO2 because P25 particles are distributed on ß-Bi2O3 nanosheet more uniformly. The photocatalytic activities of ß-Bi2O3/TiO2 (0.02275 min-1) and ß-Bi2O3/P25 (0.02382 min-1) are 3.72 times and 3.90 times than that of pure ß-Bi2O3 (0.0061 min-1) for EE2 removal. The enhanced photocatalytic activities of two kinds of composites are ascribed to photo-induced interfacial charge transfer on the heterojunction between ß-Bi2O3 and TiO2 or P25. From the economic view, ß-Bi2O3/P25 composites are better than ß-Bi2O3/TiO2 because TiO2 nanobelts in the ß-Bi2O3/TiO2 composite are obtained from P25 via extra hydrothermal treatment in strong alkaline environment. The free radical capture experiment indicated that the dominant reactive species are h+ and •O-2 for EE2 removal by TiO2/ß-Bi2O3 and P25/ß-Bi2O3 composites.

The TiO2 (B) nano-belts with excellent performance prepared via alkaline stirring hydrothermal method and its application to remove 17α-ethynylestradiol.

In this work, TiO2 (B) nano-belts were synthesized by hydrothermal method under stirring, and static conditions and preparation conditions were optimized. The prepared materials were characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), photoluminescence spectroscopy (PL), and N2 adsorption/desorption measurement. The photocatalytic performance was evaluated by removing synthetic estrogen 17α-ethynylestradiol (EE2), which is the most potent endocrine-disrupting chemical. The results show that the TiO2 nano-belt possesses pure metastable monoclinic TiO2 (B) and has uniform nano-belt shape with 80~120-nm diameters and 62.904 m2 g-1 of specific surface area. Under the best optimal preparation conditions (0.5 g P25, 20 mL 10 mol L-1 NaOH, hydrothermal temperature 180 °C for 18 h under stirring, 400 °C calcination for 2 h), the TiO2 (B) has better catalytic activity with 100.00% removal rate towards 3 mg L-1 EE2 in 120 min. The removal rates of EE2 over catalyst which was prepared under static condition and P25 are 74.66% and 70.71%, respectively. The photocatalytic degradation rate constant of TiO2 (B) prepared under stirring condition (0.0379 min-1) is 4.51 times and 8.42 times than those of TiO2 prepared under static condition (0.0084 min-1) and P25 (0.0045 min-1). The excellent photocatalytic activity is mainly ascribed to longer one-dimensional nano-belt structure and effective suppression of photo-produced electron-hole.

The decreased expression of miR-625 predicts poor prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Previous study has detected the expression of miR-625 in esophageal squamous cell carcinoma (ESCC) and found that miR-625 was related to tumor depth, stage, and metastasis of ESCC. However, the prognostic value of miR-625 in ESCC has not yet been reported. METHODS: Real-time quantitative PCR was employed to measure the expression level of miR-625 in clinical ESCC tissues. Survival curves were made using the Kaplan-Meier method, and the log rank test was used to analyze the differences between clinicopathological characteristics and survival in ESCC patients. RESULTS: The expression level of miR-625 in ESCC tissues was significantly lower than that in adjacent non-tumor tissues (1.00 ± 0.38 vs. 3.25 ± 1.83, P < 0.0001). Low miR-625 expression was observed to be closely correlated with lymph node metastasis (P = 0.01), distant metastasis (P = 0.007), tumor differentiation (P = 0.04), and advanced TNM stage (P = 0.005). The 5-year overall survival rate in the low expression group was 38.1%, compared with 68.8% in the high expression group (log-rank test, P = 0.001). Multivariate Cox regression analysis showed that miR-625 expression level (HR = 3.72, 95% CI: 1.36-8.78, P = 0.005) was an independent factor in predicting the overall survival of ESCC patients. CONCLUSION: Our findings provide the convincing evidence for the first time that the down-regulation of miR-625 may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of ESCC patients.

FBW7 upregulation enhances cisplatin cytotoxicity in non- small cell lung cancer cells.

INTRODUCTION: Lung cancer is extremely harmful to human health and has one of the highest worldwide incidences of all malignant tumors. Approximately 80% of lung cancers are classified as non-small cell lung cancers (NSCLCs). Cisplatin-based multidrug chemotherapy regimen is standard for such lesions, but drug resistance is an increasing problem. F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein family that regulates cell cycle progression, and cell growth and differentiation. FBW7 also functions as a tumor suppressor. METHODS: We used cell viability assays, Western blotting, and immunofluorescence combined with siRNA interference or plasmid transfection to investigate the underlying mechanism of cisplatin resistance in NSCLC cells. RESULTS: We found that FBW7 upregulation significantly increased cisplatin chemosensitivity and that cells expressing low levels of FBW7, such as NCI-H1299 cells, have a mesenchymal phenotype. Furthermore, siRNA-mediated silencing or plasmid-mediated upregulation of FBW7 resulted in altered epithelial-mesenchymal transition (EMT) patterns in NSCLC cells. These data support a role for FBW7 in regulating the EMT in NSCLC cells. CONCLUSION: FBW7 is a potential drug target for combating drug resistance and regulating the EMT in NSCLC cells.