Carbon and phosphorus co-doped carbon nitride hollow tube for improved photocatalytic hydrogen evolution.

Graphitic carbon nitride, regarded as a charming conjugated polymer, has been a visible light photocatalyst. Bulk carbon nitride endures the limited light absorption ability, few surface active sites and slow separation of photoinduced charge carriers, leading to the poor catalytic activity. Herein, a new carbon (C) and phosphorus (P) co-doped carbon nitride hollow tube with adjustable optical property (CPCN) was developed by applying melamine and polyacrylic amide as the precursors and phosphoric acid as the P source via a hydrothermal-thermal copolymerization way. The effects of polyacrylic amide content on the morphology and photocatalytic performance were intensively investigated. The special hollow tube favors the improvement of active sites and visible light harvesting ability. Meantime, C and P co-doping results in the narrow band gap and rapid charge transfer, thus enabling an enhanced catalytic activity under visible light irradiation. Particularly, CPCN-50 exhibits a remarkable H2 generation rate of 4485.7 µmol h-1 g-1 under λ > 400 nm, which is higher than pure carbon nitride CN (902.3 µmol h-1 g-1), C doped sample CCN-50 (3741.1 µmol h-1 g-1) and P doped sample CNP (2280.0 µmol h-1 g-1). It implies that C, P co-doping exhibits a synergistic effect on boosting photoinduced charge transfer and hindering the recombination. Moreover, CPCN-50 illustrates a higher H2 generation rate (3024.5 µmol h-1 g-1) than CN (400.8 µmol h-1 g-1) under λ > 420 nm irradiation. This way developed in this work might exhibit utility for synthesizing highly effective photocatalysts for the CO2 reduction, H2 evolution and so on.

LncRNA NEAT1 promotes malignant phenotypes and TMZ resistance in glioblastoma stem cells by regulating let-7g-5p/MAP3K1 axis.

Glioblastoma multiforme (GBM) is one of the most malign brain tumors in adults. Temozolomide (TMZ) is an oral chemotherapy drug constituting the backbone of chemotherapy regimens utilized as first-line treatment of GBM. However, resistance to TMZ often leads to treatment failure. In the present study, we explored the expression and related mechanisms of nuclear enriched abundant transcript 1 (NEAT1) in glioma stem cells (GSCs). Quantitative real-time PCR (qRT-PCR) showed that NEAT1 was up-regulated in serum samples of GBM patients and GSCs isolated from U87, U251 cell lines. Functional experiments showed that NEAT1 knockdown restrained malignant behaviors of GSC, including proliferation, migration and invasion. Dual-luciferase assays identified let-7g-5p was a downstream target and negatively adjusted by NEAT1. Restoration of let-7g-5p impeded tumor progression by inhibiting proliferation, migration and invasion. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1), as a direct target of let-7g-5p, was positively regulated by NEAT1 and involved to affect the regulation of NEAT1 on GSCs' behaviors. In conclusion, our results suggested that NEAT1 promoted GSCs progression via NEAT1/let-7g-5p/MAP3K1 axis, which provided a depth insight into TMZ resistance mechanism.

Construction of three-dimensional mesoporous carbon nitride with high surface area for efficient visible-light-driven hydrogen evolution.

Carbon nitride, as an outstanding photocatalyst for hydrogen production, displays a limited photocatalytic performance on account of the insufficient light absorption and low surface area. Herein, three-dimensional mesoporous carbon nitride with large surface area was prepared by using freeze-dried cyanuric acid-melamine supramolecular aggregates and ionic liquid as precursor and template, respectively. The results find that as-prepared carbon nitride materials possess the 3D interconnected open-framework with porous channels owing to the decomposition of ionic liquid and precursor under high temperature calcination, which in favor of the contact between active sites and reactants as well as the improvement of charge carrier transport rate. Compared to the pure carbon nitride, the obtained CNF-0.005 was endowed with the ultrathin nanosheets, broaden light adsorption, high separation rate of photogenerated carriers and improved photocatalytic activity. Especially, the above-mentioned sample exhibits a superior visible light driven photocatalytic H2 production capability and excellent durability, as high as 129.5 µmol/h, which is about 27.6 times and 1.8 times than that of the bulk CN and pure CNF, respectively. This work opens up an ingenious strategy towards the fabrication of high-performance carbon nitride with controllable structure and improved surface area for efficient hydrogen production.

Ag-Based nanocomposites: synthesis and applications in catalysis.

Ag-Based nanocomposites, including supported Ag nanocomposites and bimetallic Ag nanocomposites, have been intensively investigated as highly efficient catalysts because of their high activity and stability, easy preparation, low cost, and low toxicity. Herein, we systematically summarize and comprehensively evaluate versatile synthetic strategies for the preparation of Ag-based nanocomposites, and outline their recent advances in catalytic oxidation, catalytic reduction, photocatalysis and electrocatalysis. In addition, the challenges and prospects related to Ag-based nanocomposites for various catalytic applications are also discussed. In light of the most recent advances in Ag-based nanocomposites for catalysis applications, this review provides a comprehensive assessment on the material selection, synthesis and catalytic characteristics of these catalysts, which offers a strategic guide to build a close connection between Ag nanocomposites and catalysis applications.

Hierarchical Honeycomb Br-, N-Codoped TiO2 with Enhanced Visible-Light Photocatalytic H2 Production.

The halogen elements modification strategy of TiO2 encounters a bottleneck in visible-light H2 production. Herein, we have for the first time reported a hierarchical honeycomb Br-, N-codoped anatase TiO2 catalyst (HM-Br,N/TiO2) with enhanced visible-light photocatalytic H2 production. During the synthesizing process, large amounts of meso-macroporous channels and TiO2 nanosheets were fabricated in massive TiO2 automatically, constructing the hierarchical honeycomb structure with large specific surface area (464 m2 g-1). cetyl trimethylammonium bromide and melamine played a key role in constructing the meso-macroporous channels. Additionally, HM-Br,N/TiO2 showed a high visible-light H2 production rate of 2247 µmol h-1 g-1, which is far more higher than single Br- or N-doped TiO2 (0 or 63 µmol h-1 g-1, respectively), thereby demonstrating the excellent synergistic effects of Br and N elements in H2 evolution. In HM-Br,N/TiO2 catalytic system, the codoped Br-N atoms could reduce the band gap of TiO2 to 2.88 eV and the holes on acceptor levels (N acceptor) can passivate the electrons on donor levels (Br donor), thereby preventing charge carriers recombination significantly. Furthermore, the proposed HM-Br,N/TiO2 fabrication strategy had a wide range of choices for N source (e.g., melamine, urea, and dicyandiamide) and it can be applied to other TiO2 materials (e.g., P25) as well, thereby implying its great potential application in visible-light H2 production. Finally, on the basis of experimental results, a possible photocatalytic H2 production mechanism for HM-Br,N/TiO2 was proposed.

CdS nanosphere-decorated hollow polyhedral ZCO derived from a metal-organic framework (MOF) for effective photocatalytic water evolution.

Semiconductor nanostructures have received considerable attention in the field of photocatalytic hydrogen evolution. However, eco-friendly, high efficiency, and low-cost semiconductor materials are still desired. In consideration of this, herein, we design a new and economic noble-metal-free CdS/ZnxCo3-xO4 (CdS/ZCO) nanohybrid photocatalyst using a metal-organic framework (MOF) template, which is a framework structure composed of organic ligands and metal ion nodes with different numbers of connections. The as-prepared CdS/ZCO composites with a large specific surface area and porous hollow structure exhibit remarkable catalytic activity and high stability for hydrogen generation. The hydrogen evolution rate is about 3978.6 µmol g-1 h-1 with lactic acid as the sacrificial agent when the optimized amount of CdS nanoparticles (30 wt%) is decorated on the ZCO frame, and the production efficiency of H2 for CdS/ZCO is 4 times higher than that for CdS nanospheres or CdS/Co3O4. The significantly enhanced photocatalytic activity of CdS/ZCO is attributed to the efficient charge separation and transfer between the phase boundary of CdS and ZCO. In addition, the composites exhibit better hydrogen production in lactic acid than in methanol, and the remarkable catalytic activity and high stability of the CdS/ZCO composites for hydrogen evolution indicate that MOF-based composite materials have potential application prospects in energy conversion.

Visible-light photo-Fenton oxidation of phenol with rGO-α-FeOOH supported on Al-doped mesoporous silica (MCM-41) at neutral pH: Performance and optimization of the catalyst.

In this study, α-FeOOH on reduced graphene oxide (rGO-α-FeOOH) supported on an Al-doped MCM-41 catalyst (RFAM) was optimized for the visible-light photo-Fenton oxidation of phenol at neutral pH. The stability of the catalysts, effect of bubbling aeration, and degradation intermediates were investigated. Results indicated that RFAM with a large Brunauer-Emmett-Teller (BET) area and mesoporous structure displayed excellent catalytic activity for the visible-light-driven (VLD) photo-Fenton process. Phenol degradation was well described by a pseudo-first-order reaction kinetics model. Raman analysis demonstrated that an rGO-α-FeOOH (RF) composite is formed during the ferrous-ion-induced self-assembly process. Al-MCM-41 could uniformly disperse RF nanosheets and promote the mobility and diffusion of matter. The activity of the main catalyst α-FeOOH was enhanced after the incorporation of rGO nanosheets. The α-FeOOH crystal in RFAM showed catalytic activity superior to those of Fe3O4 and Fe2O3. The RFAM catalyst, with an optimal GO-Fe2+mass ratio of 2.33, exhibited a larger BET area, pore size, and pore volume, and thus exhibited high performance and energy utilization efficiency in the VLD photo-Fenton reaction with remarkable stability. Bubbling N2 inhibited catalytic performance, while bubbling O2 or air only slightly accelerated the phenol degradation. Visible light played an important role in accelerating the formation of reactive oxygen species (·OH) for the highly efficient phenol degradation. Analysis of degradation intermediates indicated a high phenol mineralization level and the formation of low-molecular-weight organic acids. This work would be helpful in providing an insight into a new type of catalyst assembly and a possible route to a promising heterogeneous catalyst applicable in the visible light photo-Fenton process for effective wastewater remediation at neutral pH.

Synthesis of ordered mesoporous La2O3-ZrO2 composites with encapsulated Pt NPs and the effect of La-dopping on catalytic activity.

In this work, we report a feasible approach to synthesize a ternary nanocomposites, Pt/lanthanum doped mesoporous zirconium oxide (Pt/La2O3-ZrO2), via an effective two-step method. Ordered mesoporous La2O3-ZrO2 composites were firstly fabricated with mesoporous silica KIT-6 as a hard template. Subsequently, uniform Pt nanoparticles encapsulated by 4 hydroxyl-terminated poly (amidoamine) (G4-OH PAMAM) dendrimers were deposited on the La2O3-ZrO2 composites. The as-prepared samples were characterized by transmission electron microscope (TEM), N2 adsorption-desorption isotherm analysis, energy dispersion X-ray analysis (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and temperature programmed reduction (H2-TPR). The average size of PtDENs was found to be 1.48nm in diameter. Furthermore, the introduction of La could improve the structure of the supports which was confirmed by XRD and H2-TPR analysis. The reduction of p-nitrophenol to p-aminophenol by NaBH4 was utilized to evaluate the catalytic performances of catalysts. Results indicated that the Pt/La2O3-ZrO2 catalyst calcined in nitrogen at 550°C exhibited the highest catalytic performance and still kept the high catalytic activity even after six cycles. This phenomenon suggests that synergistic effect among Pt-Zr-La could enhance the catalytic efficiency. Finally, reaction mechanism was proposed for the reduction of p-nitrophenol.

Fabrication of Ellipsoidal Silica Yolk-Shell Magnetic Structures with Extremely Stable Au Nanoparticles as Highly Reactive and Recoverable Catalysts.

A novel strategy was reported for the fabrication of yolk-shell magnetic MFSVmS-Au nanocomposites (NCs) consisting of double-layered ellipsoidal mesoporous silica shells, numerous sub-4 nm Au nanoparticles (NPs), and magnetic Fe central cores. The hierarchical FSVmS NCs with ellipsoidal α-Fe2O3@mSiO2/mSiO2 as yolks/shells were first prepared through the facile sol-gel template-assisted method, and plenty of extremely stable ultrafine Au NPs were postencapsulated within interlayer cavities through the unique deposition-precipitation method mediated with Au(en)2Cl3 compounds. Notably, ethylenediamine ligands were used to synthesize the stable cationic complexes, [Au(en)2]3+, that readily underwent the deprotonation reaction to chemically modify negatively charged mesoporous silica under alkaline conditions. The subsequent two-stage programmed hydrogen annealing initiated the in situ formation of Au NPs and the reduction of α-Fe2O3 to magnetic Fe, where the synthesized Au NPs were highly resistant to harsh thermal sintering even at 700 °C. Given its structural superiority and magnetic nature, the MFSVmS-Au was demonstrated to be a highly efficient and recoverable nanocatalyst with superior activity and reusability toward the reduction of 4-nitrophenol to 4-aminophenol, and the pristine morphology was retained after six recycling tests.

Synthesis and characterization of hollow ZrO(2)TiO(2)/Au spheres as a highly thermal stability nanocatalyst.

A novel binary-metal-oxide-coated hollow microspheres-titanium dioxide-zirconium dioxide-coated Au nanocatalyst was prepared via a facile hydrothermal synthesis method. SEM, TEM, EDX, FTIR, XRD, UV-vis and XPS analyses were employed to characterize the composition, structure, and morphology of ZrO2-TiO2 hollow spheres. The size of Au nanoparticles was found to be 3-5nm in diameter before being immobilized on the aforementioned mesoporous ZrO2-TiO2 layer and used as catalysts in the reduction of 4-nitrophenol to 4-aminophenol by NaBH4. Compared with TiO2/Au and ZrO2/Au, ZrO2-TiO2/Au NPs showed a higher catalytic activity because of due to mixed oxide synergistic effect. Besides, the sample gets the highest thermal stability and reactivity at 550°C, after calcining the hollow ZT/Au NPs at 550°C, 300°C and room temperature, respectively. Finally, a possible reaction mechanism was also proposed to explain the reduction of 4-nitrophenol to 4-aminophenol over ZrO2-TiO2/Au catalyst.

Novel RGO/α-FeOOH supported catalyst for Fenton oxidation of phenol at a wide pH range using solar-light-driven irradiation.

A novel solar-light-driven (SLD) Fenton catalyst was developed by reducing the ferrous-ion onto graphene oxide (GO) and forming reduced graphene oxide/α-FeOOH composites (RF) via in-situ induced self-assembly process. The RF was supported on several mesoporous supports (i.e., Al-MCM-41, MCM-41 and γ-Al2O3). The activity, stability and energy use for phenol oxidation were systematically studied for a wide pH range. Furthermore, the catalytic mechanism at acid and alkaline aqueous conditions was also elucidated. The results showed that Fe(II) was reduced onto GO nanosheets and α-FeOOH crystals were formed during the self-assembly process. Compared with Fenton reaction without SLD irradiation, the visible light irradiation not only dramatically accelerated the rate of Fenton-based reactions, but also extended the operating pH for the Fenton reaction (from 4.0 to 8.0). The phenol oxidation on RF supported catalysts was fitting well with the pseudo-first-order kinetics, and needed low initiating energy, insensitive to the reacting temperature changes (273-318K). The Al-MCM-41 supported RF was a more highly energy-efficient catalyst with the prominent catalytic activity at wide operating pHs. During the reaction, OH radicals were generated by the SLD irradiation from H2O2 reduction and H2O oxidation in the FeⅡ/FeⅢ and FeⅢ/FeⅣ cycling processes.

Double-Shelled TiO2 Hollow Spheres Assembled with TiO2 Nanosheets.

High-quality double-shelled TiO2 hollow spheres (DHS-Ti) assembled with TiO2 nanosheets have been synthesized for the first time through a simple hydrothermal treatment of sSiO2 @TiO2 (TiO2 -coated solid SiO2 spheres). The double-shelled structure shows a high BET surface area up to 417.6 m2 g-1 . Anatase DHS-Ti of high crystallinity can be obtained without structural collapse by calcination treatment. The effects of cetyl trimethylammonium bromide (CTAB) concentration, pH, and hydrothermal reaction temperature have also been investigated with a series of contrast experiments. A formation mechanism involving the in situ growth of amorphous TiO2 nanosheets followed by the redeposition of dissolved silica species is proposed. Lastly, the DHS-Ti forming strategy can be extended as a general strategy to fabricate various morphological hollow nanostructures and double-shelled Pt nanocatalysts by rationally selecting functional sSiO2 nanoparticles as core materials. This work could open up a new strategy for controllable synthesis of complex hollow structures and other functional materials.

In-situ formation of supported Au nanoparticles in hierarchical yolk-shell CeO2/mSiO2 structures as highly reactive and sinter-resistant catalysts.

A novel strategy was described to construct Au-based yolk-shell SCVmS-Au nanocomposites (NCs), which combined the sol-gel template-assisted process for the assembly of hierarchical SCVmS NCs with modified CeO2/mSiO2 as yolks/shells, and the unique deposition-precipitation (DP) process mediated with Au(en)2Cl3 compounds for the synthesis of extremely stable supported Au nanoparticles (NPs). Characterization results indicated that the obtained SCVmS-Au NCs featured mesoporous silica shells, tunable interlayer voids, movable CeO2-modified cores and numerous sub-5nm Au NPs. Notably, the Au(en)2Cl3 was employed as gold precursors to chemically modify into the modulated yolk-shell structure through the DP process and the subsequent low-temperature hydrogen reduction induced the in-situ formation of abundant supported Au NPs, bestowing these metal NPs with ultrafine grain size and outstanding sinter-resistant properties that endured harsh thermal conditions up to 750°C. Benefiting from the structural advantages and enhanced synergy of CeO2-Au/mSiO2-Au yolks/shells, the SCVmS-Au was demonstrated as markedly efficient catalysts with superior activity and reusability in catalyzing the reduction of 4-nitrophenol to 4-aminophenol, and its pristine morphology still maintained after eight recycling tests.

Different expression of miR-29b and VEGFA in glioma.

Glioma is one of the most common carcinomas in terms of both incidence and mortality worldwide. This is a case-control study with 240 cases and age- and gender-matched controls in the rate of 1:1. The results of this present word indicated that the expressions of both miR-29b and VEGFA in blood were significantly different compared with the control group, and thus may help to differentiate glioma cases from the controls. In addition, the diagnostic role of miR-29b and VEGFA was important for the clinical application. In conclusion, circulating miR-29b and VEGFA could be used as diagnosis biomarkers.

Decreased expression of the SPOP gene is associated with poor prognosis in glioma.

This study suggests that speckle-type POZ protein (SPOP) may be a tumor suppressor gene and its prognostic value in human glioma. Real-time quantitative RT-PCR (qRT­PCR), western blotting, and immunohistochemical staining were used to examine SPOP expression in glioma tissues and normal brain (NB) tissues. The relationships between the SPOP expression levels, the clinicopathological factors, and patient survival were investigated. The molecular mechanisms of SPOP expression and its effects on cell viability, migration and invasion were also explored by MTT assay, wound-healing assays and Transwell assay. SPOP mRNA and protein levels were downregulated in glioma tissues compared to NB. Immunohistochemical staining results showed low expression in 62.2% (61/98) of glioma samples, while high expression in 75% (9/12) of NB samples, and the difference was statistically significant (P=0.014). In addition, decreased SPOP was associated disease progression in glioma samples, the expression level of SPOP was positively correlated with mean tumor diameter (MTD) (P=0.021) and the status of tumor grade and histological type (WHO I, II, III and IV) (P=0.032) in glioma patients. Additionally, the overall survival of patients with low SPOP expression was significantly worse than that of SPOP-high patients (P=0.001). In vitro overexpression of SPOP markedly inhibited cell viability, migration and invasion in vitro. These findings suggest that SPOP has potential use as novel biomarker of glioma and may serve as an independent predictive factor for prognosis of glioma patients.

miR-155 Regulates Glioma Cells Invasion and Chemosensitivity by p38 Isforms In Vitro.

The critical role of microRNAs in cancer development has been extensively described. miRNAs are both specific markers and putative therapy targets. miR-155 has been identified to be an oncomiRNA and is highly expressed in several solid cancers, including glioblastoma. In this study, we found that miR-155 is a good potential therapy target. Knockdown of miR-155 sensitizes glioma cells to the chemotherapy of temozolomide (TMZ) by targeting the p38 isoforms mitogen-activated protein kinase 13 [MAPK13, also known as p38 MAPKδ or stress-activated protein kinase 4 (SAPK4)] and MAPK14 (also known as p38 MAPKα). As tumor suppressor genes, MAPK13 and MAPK14 play important roles in lowering the accumulation of reactive oxygen species (ROS), inducing cell apoptosis, and slowing the progression of cancer. Knockdown of miR-155 enhanced the anticancer effect of TMZ on glioma by targeting the MAPK13 and MAPK14-mediated oxidative stress and apoptosis, but did not affect the secretion of MMP2 and MMP9.

Comparison of administration routes for adipose-derived stem cells in the treatment of middle cerebral artery occlusion in rats.

Given that adult adipose tissue is an abundant, accessible and safe source of stem cells, the use of adipose-derived stem cells (ADSCs) provides a promising approach in ischemic stroke. The delivery route, however, for transplantation of ADSCs in clinical application remains controversial regarding the time window, cell type, safety issues, 'first pass' effect and therapeutic effect. To determine the optimal administration route in transplantation of ADSCs, we compared the therapeutic effect of the three mainly used administration routes of ADSCs in a middle cerebral artery occlusion (MCAO) rat model. Cells isolated from the adipose tissue of adult rodents were differentiated and characterized in vitro, and further transplanted in vivo by intravenous, intra-arterial or intra-ventricular delivery. The infarct volume, expression of neurotrophic factors and the neurobehavioral improvements were evaluated after the equal dose of BrdU labeled ADSCs transplantation. Our results indicated that the equal dose of ADSCs delivered intravenously were effective in improving the neurological outcome and reducing the infarct volume after ischemic brain injury in long term duration in contrast to intra-arterial and intra-ventricular delivery. At 1-7 days after transplantation, the increased expression levels of BDNF, VEGF, bFGF, Bcl-2, IL-10 and decreased levels of caspase-3 and TNF-α in the intra-ventricular and intra-arterial groups were significant in contrast to the intravenous group. There was no significant difference among the three groups after 7 days. Our findings suggest that compared with the intra-ventricular delivery, intravascular injection allows higher dose injection with fewer invasions and appears to be optimal in application with regard to therapeutic efficacy, safety and feasibility.

Schwann cells differentiated from adipose­derived stem cells for the treatment of brain contusion.

Rapid development of tissue engineering techniques has led to the possibility of treating central nervous injuries with Schwann cells (SCs). However, certain characteristics of SCs, such as a low proliferation ability, greatly restrict their use. The aim of the present study was to investigate whether SCs differentiated from adipose­derived stem cells (ADSC­SCs) could used to promote functional recovery in brain contusion in rat. ADSCs were isolated and expanded from the groin of Sprague­Dawley rats and differentiated into SCs. The ADSC­SCs were transplanted into the contused rat brain and the locomotor function of the rats was assessed. Significant locomotor function recovery was observed in hemiparalyzed rats treated with ADSCs­SCs. In conclusion, transplantation of ADSC­SCs significantly promoted functional recovery following brain contusion.

Role of podocalyxin in astrocytoma: Clinicopathological and in vitro evidence.

The present study examined the expression of podocalyxin (PODX) in surgically-resected astrocytomas, associated the levels of PODX expression with the clinicopathological characteristics and survival outcomes of astrocytoma and assessed how PODX affected the viability of astrocytoma cells following the administration of chemotherapeutic agents. The immunohistochemical analysis of 102 patient samples revealed that a high expression of PODX was significantly associated with high-grade astrocytomas (P<0.001) and a high Ki-67 labeling index (LI; P<0.001). A Kaplan-Meier survival analysis demonstrated that the high PODX expression group had significantly shorter disease-free survival (DFS) and overall survival (OS) rates compared with the low expression group (P<0.001). The multivariate analysis using the Cox's proportional hazards model revealed that a high expression of PODX, a high World Health Organization grade and a high Ki-67 LI were independent factors for shorter DFS and OS times. A subsequent in vitro study using SW1783 and U-87 human astrocytoma cell lines revealed that knocking down PODX decreased astrocytoma cell viability against temozolomide-induced apoptotic stress through the inhibition of the Akt survival signaling pathway. In conclusion, the in vivo findings indicated that a high expression of PODX is predictive of a poor survival outcome and, thus, may be used as a prognostic factor to predict the survival outcomes of astrocytoma patients. The in vitro findings indicated that PODX may promote astrocytoma cell viability against chemotherapeutic agent-induced apoptotic stress through the Akt pathway, indicating that PODX may be a novel target for overcoming chemoresistance in astrocytomas.

Let-7b expression determines response to chemotherapy through the regulation of cyclin D1 in glioblastoma.

BACKGROUND: Glioblastoma is the most common type of primary brain tumors. Cisplatin is a commonly used chemotherapeutic agent for Glioblastoma patients. Despite a consistent rate of initial responses, cisplatin treatment often develops chemoresistance, leading to therapeutic failure. Cellular resistance to cisplatin is of great concern and understanding the molecular mechanisms is an utter need. METHODS: Glioblastoma cell line U251 cells were exposed to increasing doses of cisplatin for 6 months to establish cisplatin-resistant cell line U251R. The differential miRNA expression profiles in U251 and U251R cell lines were identified by microarray analysis and confirmed by Q-PCR. MiRNA mimics were transfected into U251R cells, and cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. RESULTS: U251R cells showed 3.1-fold increase in cisplatin resistance compared to its parental U251 cells. Microarray analysis identified Let-7b and other miRNAs significantly down-regulated in U251R cells compared to U251 cells. Transfection of Let-7b mimics greatly re-sensitized U251R cells to cisplatin, while transfection of other miRNAs has no effect or slightly effect. Cyclin D1 is predicted as a target of Let-7b through bioinformatics analysis. Over-expression of Let-7b mimics suppressed cyclin D1 protein expression and inhibited cyclin D1-3'-UTR luciferase activity. Knockdown of cyclin D1 expression significantly increased cisplatin-induced G1 arrest and apoptosis. CONCLUSIONS: Collectively, our results indicated that cisplatin treatment leads to Let-7b suppression, which in turn up-regulates cyclin D1 expression. Let-7b may serve as a marker of cisplatin resistance, and can enhance the therapeutic benefit of cisplatin in glioblastoma cells.