WITHDRAWN: Application of Chemotherapeutic Drugs and Convectionenhanced Delivery Technology in Glioma

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the website of the journal Anti-Cancer Agents in Medicinal Chemistry.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorialpolicies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Research progress of anti-glioma chemotherapeutic drugs (Review).

Glioma is the most common primary intracranial malignancy in the central nervous system. At present, the most important treatment option is surgical resection of the tumor combined with radiotherapy and chemotherapy. The principle of operation is to remove the tumor to the maximal extent on the basis of preserving brain function. However, prominent invasive and infiltrative proliferation of glioma tumor cells into the surrounding normal tissues frequently reduces the efficacy of treatment. This in turn worsens the prognosis, because the tumor cannot be completely removed, which can readily relapse. Chemotherapeutic agents when applied individually have demonstrated limited efficacy for the treatment of glioma. However, multiple different chemotherapeutic agents can be used in combination with other treatment modalities to improve the efficacy while circumventing systemic toxicity and drug resistance. Therefore, it is pivotal to unravel the inhibitory mechanism mediated by the different chemotherapeutic drugs on glioma cells in preclinical studies. The aim of the present review is to provide a summary for understanding the effects of different chemotherapeutic drugs in glioma, in addition to providing a reference for the preclinical research into novel chemotherapeutic agents for future clinical application.

Advances in metformin­based metabolic therapy for non­small cell lung cancer (Review).

Therapeutic approaches that target the metabolism of tumor cells have been a popular research topic in recent years. Previous studies have demonstrated that glycolysis inhibitors reduce the proliferation of non­small cell lung cancer (NSCLC) cells by interfering with the aerobic glycolytic pathway. However, the mitochondrial oxidative phosphorylation (OXPHOS) pathway in tumor cells has also been implicated in lung cancer metabolism. Metformin, a known inhibitor of mitochondrial OXPHOS, has been indicated to reduce NSCLC morbidity and mortality in clinical studies. The present article reviewed the therapeutic effects of metformin against NSCLC, both as a single agent and combined with other anticancer treatments, in order to provide a theoretical basis for its clinical use in adjuvant therapy for NSCLC.

Superhydrophobic and Flexible Silver Nanowire-Coated Cellulose Filter Papers with Sputter-Deposited Nickel Nanoparticles for Ultrahigh Electromagnetic Interference Shielding.

Superhydrophobic, flexible, and ultrahigh-performance electromagnetic interference (EMI) shielding papers are of paramount importance to safety and long-term service under external mechanical deformations or other harsh service environments because they fulfill the growing demand for multipurpose materials. Herein, we fabricated multifunctional papers by incorporating sputter-deposited nickel nanoparticles (NiNPs) and a fluorine-containing coating onto cellulose filter papers coated with silver nanowires (AgNWs). AgNW networks with sputter-deposited NiNPs provide outstanding magnetic properties, electrical conductivity, and EMI shielding performance. At an AgNW content of 0.109 vol % and a NiNP content of 0.013 mg/cm2, the resultant papers exhibit a superior EMI shielding effectiveness (SE) of 88.4 dB. Additionally, the fluorine-containing coating endows the resultant papers with a high contact angle of 149.7°. Remarkably, the obtained papers still maintain a high EMI SE even after 1500 bending cycles or immersion in water, salt, or strong alkaline solutions for 2 h, indicating their outstanding mechanical robustness and chemical durability. This work opens a new window for designing and implementing ultrahigh-performance EMI shielding materials.

Robust, flexible, and high-performance electromagnetic interference shielding films with long-lasting service.

It is of great significance for electromagnetic interference (EMI) shielding materials to fulfill long-lasting service requirements. Here, waterborne polyurethane (WPU) was coated on the surface of a silver nanowire (AgNW) network with sputter-deposited nickel nanoparticles (NiNPs) by dip-coating technology to improve their durability. After five dip-coating cycles, a WPU layer nearly coated the whole surface of the hybrid papers, and only a fraction of the metal filler is bare. The resultant hybrid papers exhibit an electrical conductivity of ∼3500 S m-1, remnant magnetization of 0.03 emu g-1, saturation magnetization of 0.10 emu g-1, and coercivity of 256 Oe. On the one hand, the presence of the WPU coating does not affect the shielding effectiveness (SE) of the hybrid papers; on the other hand, the WPU coating enhances the ability to resist tape peeling. Moreover, the resultant hybrid papers still maintain the original SE value (∼80 dB), even after exposure to air for 5 months owing to the isolation effect of the WPU coating, implying long-lasting durability. The results confirm that the obtained hybrid papers can meet the requirements of practical applications.

Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein.

The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered. Next, we investigated whether the reduction in NK cells within HCV mouse livers might elicit an effect on immune-mediated liver injury. HCV mice were subjected to acute liver injury models upon ConA administration. We observed that HCV mice developed more severe ConA-induced immune-mediated hepatitis, which was dependent on the accumulated intrahepatic NK cells. Our results indicated that after the administration of ConA, NK cells not only mediated liver injury through the production of immunoregulatory cytokines (IFN-γ, TNF-α and perforin) with direct antiviral activity, but they also killed target cells directly through the TRAIL/DR5 and NKG2D/NKG2D ligand signaling pathway in HCV mice. Our findings suggest a critical role for NK cells in oversensitive liver injury during chronic HCV infection.

Bioluminescence imaging of caspase-3 activity in mouse liver.

Apoptosis is an essential process for the maintenance of liver physiology. The ability to noninvasively image apoptosis in livers would provide unique insights into its role in liver disease processes. In the present work, we established a stable mouse model by hydrodynamics methods to study the activity of caspase-3 and evaluate the effect of the apoptosis inhibitors in mouse livers under true physiological conditions by bioluminescence imaging. The reporter plasmid attB-ANLuc(DEVD)BCLuc that contains fragment of attB and ANLuc(DEVD)BCLuc was codelivered with the mouse-codon optimized φC31 (φC31o) integrase plasmids specifically to mouse liver by hydrodynamic injection procedure. Then, φC31o integrase mediated intramolecular recombination between wild-type attB and attP site in mice, and thus the reporter expression cassette attB-ANLuc(DEVD)BCLuc was integrated permanently into mouse liver chromosome. We used these mice to characterize in vivo activation of caspase-3 upon treatment with LPS/D-GalN. Our data show that liver apoptosis could be reflected by the activity of luciferase. The shRNA targeting caspase-3 protein or apoptosis inhibitors could effectively downregulate luciferase activity in vivo. Also, this model could be used to measure caspase-3 activation during inflammatory and infectious events in vivo as verified by infected with MHV-3. This model could be used for screening anti-apoptosis compounds target mouse livers.

Screening compounds against HCV based on MAVS/IFN-ß pathway in a replicon model.

AIM: To develop a sensitive assay for screening compounds against hepatitis C virus (HCV). METHODS: The proteolytic cleavage of NS3/4A on enhanced yellow fluorescent protein (eYFP)-mitochondrial antiviral signaling protein (MAVS) was examined by reporter enzyme secreted placental alkaline phosphatase (SEAP), which enabled us to perform ongoing monitoring of anti-HCV drugs through repeated chemiluminescence. Subcellular localization of eYFP-MAVS was assessed by fluorescence microscopy. Cellular localization and protein levels were examined by Western blotting. RESULTS: HCV NS3/4A protease cleaved eYFP-MAVS from mitochondria to block the activation of interferon (IFN)-ß promoter, thus resulting in downregulation of SEAP activity. The decrease in SEAP activity was proportional to the dose of active NS3/4A protease. Also this reporter assay was used to detect anti-HCV activity of IFN-α and cyclosporine A. CONCLUSION: Our data show that this reporter system is a sensitive and quantitative reporter of anti-HCV inhibitors. This system will constitute a new tool to allow the efficient screening of HCV inhibitors.

Bioluminescence imaging of Hepatitis C virus NS3/4A serine protease activity in cells and living animals.

The lack of robust small animal models has been an obstacle to the screening of Hepatitis C virus (HCV) NS3/4A protease inhibitors in vivo. Here, we described a reporter assay system for in vivo noninvasive imaging of NS3/4A serine protease activity using split firefly luciferase complementation strategy. The reporter construct ANluc(NS5A/B)BCluc constitutes the split N- and C-terminal fragments of luciferase, fused to interacting peptides, pepA and pepB, respectively, with an intervening HCV NS3/4A cleavage motif of NS5A/B. We proved that the reporter molecule could be proteolytically cleaved by NS3/4A at the NS5A/B motif in cells and living animals. Association of pepA and pepB brought inactive fragments of luciferase into close proximity, thereby restoring bioluminescence activity. The increase in luciferase activity was proportional to the dose of active NS3/4A protease. The ANluc(NS5A/B)BCluc reporter also could be used to detect the activity of NS3/4A-specific shRNA and IFN-alpha. Therefore, the reporter assay system using split firefly luciferase complementation strategy should prove useful for evaluating NS3/4A protease activity in cells and living animals.