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Li Cheng, Jun Zhang, Xin-Yi Li, Li Yuan, Yan-Fang Pan, Xiao-Rong Chen, Tian-Ming Gao, Jian-Tian Qiao, Jin-Shun Qi
Amyloid β protein (Aβ) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in Aβ molecule is an effective active center responsible for Aβ neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid β protein, and investigated the neuroprotection of the anti-Aβ31-35 antibody against Aβ1-42 -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats...
October 26, 2016: Hippocampus
Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
Begüm Nurpelin Sağlık, Sinem Ilgın, Yusuf Özkay
Donepezil (DNP), an acetylcholinesterase (AChE) inhibitor, is one of the most preferred choices in Alzheimer diseases (AD) therapy. In the present study, 38 new DNP analogues were synthesized. Structures of the synthesized compounds (1-38) were elucidated by IR, (1)H NMR, (13)C NMR and HRMS spectroscopic methods and elemental analysis. Inhibitory potential of the compounds on cholinesterase enzymes was investigated. None of the compounds displayed significant activity on butyrylcholinesterase (BChE) enzyme...
October 19, 2016: European Journal of Medicinal Chemistry
Vanessa I S Mendes, Geoffrey A Bartholomeusz, Mary Ayres, Varsha Gandhi, Jorge A R Salvador
No abstract text is available yet for this article.
October 23, 2016: European Journal of Medicinal Chemistry
Min Ma, Fuwei Pi, Jiasheng Wang, Jian Ji, Xiulan Sun
Humans are most likely to be exposed to microcystins (MCs) combined with other water pollutants rather than to individual compounds through the consumption of contaminated drinking water or through recreational activities, such as swimming. However, the combined effects of MC-LR, estradiol (EST), and ractopamine (RAC) have not been extensively researched. The goal of this study was to investigate the combined effects of these compounds. For this purpose, cytotoxicity was evaluated in HepG2 cells treated with single or combined doses of MC-LR, EST, and RAC based on concentration addition (CA), independent action (IA), and Chou-Talalay's combination-index (CI) methods...
October 23, 2016: Chemosphere
T J Mai, R Ma, Z Li, S C Bi
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Vicente Rodríguez-González, Ruth B Domínguez-Espíndola, Sergio Casas-Flores, Olga A Patrón-Soberano, Roberto Camposeco Solis, Soo Wohn Lee
Antifungal silver nanocomposites inspired by titanate nanotubes (AgTNTs) were successfully evaluated for the effective inactivation of the phytopathogenic fungus Botrytis Cinerea within 20 minutes. One dimensional H2Ti3O7 nanotubes functionalized with silver nanoparticles (AgNPs) exhibit unique surface and antifungal properties for the photoinactivation of B. Cinerea. Nanostructured titanates were synthesized by the eco-friendly, practical, microwave-induced, hydrothermal method followed by a highly monodispersive AgNP UV-photodeposition...
October 26, 2016: ACS Applied Materials & Interfaces
Cenk Daglioglu, Burcu Okutucu
PURPOSE: Resistance to chemotherapy is one of the major problems facing current cancer research. Enhancing tumor cell response to anticancer agents increases chemotherapeutic effectiveness. We have recently addressed this issue and reported on producing multifunctional nanoparticles (Fe3O4@SiO2(FITC)-FA/AICAR/DOX) aiming to overcome chemoresistance with synergetic effect of AICAR and DOX. In the present study, we demonstrated that these nanoparticles not only show enhanced cellular uptake and cytotoxic effect but can also show enhanced pro-apoptotic and anti-proliferative effects in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat and MIA PaCa-2)...
October 25, 2016: Pharmaceutical Research
E P Kopantsev, M B Kostina, E V Grankina, M R Kopantseva, V I Egorov, E D Sverdlov
Hybrid therapeutic gene FCU1 gene was cloned into a lentiviral expression vector and the therapeutic effect of its expression was studied in three pancreatic cancer cell lines. Expression of FCU1 gene sensitized cells of two of three studied pancreatic cancer cell lines to 5-fluorocytosine. In addition, uracil phosphoribosyl transferase activity of the hybrid FCU1 protein increased sensitivity of transfected cells of all three studied pancreatic cancer cell lines to 5-fluorouracil, a standard chemotherapeutic agent...
October 26, 2016: Bulletin of Experimental Biology and Medicine
Clement Cochain, Alma Zernecke
Although infiltration of CD8(+) T cells in human atherosclerotic lesions has been described 30 years ago, the role of these cells in lesion development has long remained enigmatic. While experimental models hinted at their pro-atherogenic role based on circumstantial evidence, genetic mouse models of cytotoxic CD8(+) T cell-specific immune deficiency suggested no crucial role of these cells in lesion development. However, in recent years, more refined models of adoptive cell transfer, disruption of specific immune regulatory pathways or monoclonal antibody-mediated cell depletion have proposed both atheroprotective and pro-atherogenic functions for CD8(+) T cells in atherosclerosis...
November 2016: Basic Research in Cardiology
John P Veluchamy, A Marijne Heeren, Jan Spanholtz, Jaap D H van Eendenburg, Daniëlle A M Heideman, Gemma G Kenter, Henk M Verheul, Hans J van der Vliet, Ekaterina S Jordanova, Tanja D de Gruijl
Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK)...
October 25, 2016: Cancer Immunology, Immunotherapy: CII
María de Lourdes Mora-García, Rosario García-Rocha, Omar Morales-Ramírez, Juan José Montesinos, Benny Weiss-Steider, Jorge Hernández-Montes, Luis Roberto Ávila-Ibarra, Christian Azucena Don-López, Marco Antonio Velasco-Velázquez, Vianey Gutiérrez-Serrano, Alberto Monroy-García
BACKGROUND: In recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other "classic" sources have been described. However, the phenotypic and functional properties of tumor MSCs are poorly understood. The aim of this study was to analyze the immunosuppressive capacity of cervical cancer-derived MSCs (CeCa-MSCs) on effector T lymphocytes through the purinergic pathway. METHODS: We determined the expression and functional activity of the membrane-associated ectonucleotidases CD39 and CD73 on CeCa-MSCs and normal cervical tissue-derived MSCs (NCx-MSCs)...
October 26, 2016: Journal of Translational Medicine
Eun-Sang Cho, Jin-Mu Yi, Jong-Shik Park, You Jin Lee, Chae Jun Lim, Ok-Sun Bang, No Soo Kim
BACKGROUND: Oxaliplatin can induce peripheral neuropathy (OXIPN) as an adverse side effect in cancer patients. Until now, no effective preventive or therapeutic drug has been developed; therefore, the dose-limiting factor of OXIPN is still an obstacle in the use of oxaliplatin to treat cancer patients. In the present study, we report for the first time that the aqueous extract of Lithospermi radix (WLR) can attenuate the OXIPN in both in vitro and in vivo neuropathic models. METHODS: The protective effect of WLR on OXIPN was evaluated in vitro by quantifying nerve growth factor (NGF)-stimulated neurite outgrowth in PC12 cells treated with a combination of oxaliplatin and WLR...
October 26, 2016: BMC Complementary and Alternative Medicine
Nimmy Kumar, Subhankar Biswas, Asha Elizabeth Mathew, Subin Varghese, Jessy Elizabeth Mathew, K Nandakumar, Jesil Mathew Aranjani, Richard Lobo
BACKGROUND: Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Current treatment modality for HCC is marginally effective. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. The present study was aimed at exploring the anti-proliferative, pro-oxidant and pro-apoptotic potential of stem of Elytranthe parasitica (L.) Danser (EP), a parasitic shrub belonging to Loranthaceae...
October 26, 2016: BMC Complementary and Alternative Medicine
Subhajit Ghosh, Saswat Mohapatra, Anisha Thomas, Debmalya Bhunia, Abhijit Saha, Gaurav Das, Batakrishna Jana, Surajit Ghosh
An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics, competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find out such a unique nanocarrier and engineer all the above-mentioned features into it. In this manuscript, we have shown for the first time that Apoferritin (Apf) can carry and deliver high dose of doxorubicin (Dox), docetaxel (Doc) and combination of both Dox and Doc specifically into the cancer cell and enhances killing compared to free drug without any functionalization or property modulation...
October 26, 2016: ACS Applied Materials & Interfaces
Admar Verschoor, Christian M Karsten, Steven P Broadley, Yves Laumonnier, Jörg Köhl
The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes...
November 2016: Immunological Reviews
Valentina Tabanelli, Vanessa Santiago-Pacheco, Mario Corbellino, Angelica Calleri, Claudio Agostinelli, Carlo Parravicini, Stefano A Pileri
AIMS: A new subtype of granzyme B (GrB) producing "regulatory B cells" (Bregs) has been recently described; these peculiar cytotoxic B-cells are significantly increased in interleukin-21 (IL-21)-rich settings, and in particular during HIV and EBV infection. Our aim is to report a unique case of an EBV-positive diffuse large B-cell lymphoma (DLBCL) with cytotoxic features arisen in an HIV+ patient, and to understand if this lesion may represent a proliferation of neoplastic cytotoxic Bregs...
October 26, 2016: Histopathology
Soumen Chakraborty, Gaurav Das, Surajit Ghosh, Dipakranjan Mal
An efficient and regioselective synthetic route to naphthoquinone/naphthoquinol-carbohydrate hybrids has been developed. It is based upon anionic annulation of 3-nucleofugalphthalides with an acrylate appended sugar moiety. In each of the annulations studied, the arene-carbohydrate hybrids were obtained in good to excellent yields. The in vitro cytotoxic activity of the synthetic naphthoquinone/naphthonol-carbohydrate hybrids were evaluated against the human cervical cancer cell line (HeLa), and a few of them were found to exhibit potent anticancer activity against the cell line...
October 26, 2016: Organic & Biomolecular Chemistry
João Luiz Silva-Filho, Celso Caruso-Neves, Ana Acacia Sá Pinheiro
Angiotensin II (Ang II) and its receptor AT1 (AT1R), an important effector axis of renin-angiotensin system (RAS), have been demonstrated to regulate T-cell responses. However, these studies characterized Ang II and AT1R effects using pharmacological tools, which do not target only Ang II/AT1R axis. The specific role of AT1R expressed by antigen-specific CD8(+) T cells is unknown. Then we immunized transgenic mice expressing a T-cell receptor specific for SIINFEKL epitope (OT-I mice) with sporozoites of the rodent malaria parasite Plasmodium berghei expressing the cytotoxic epitope SIINFEKL...
October 26, 2016: Scientific Reports
Nicole Maeding, Thomas Verwanger, Barbara Krammer
Photodynamic therapy (PDT) is a cancer treatment with a long-standing history. It employs the application of nontoxic components, namely a light-sensitive photosensitizer and visible light, to generate reactive oxygen species (ROS). These ROS lead to tumor cell destruction, which is accompanied by the induction of an acute inflammatory response. This inflammatory process sends a danger signal to the innate immune system, which results in activation of specific cell types and release of additional inflammatory mediators...
October 6, 2016: Cancers
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