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https://www.readbyqxmd.com/read/29777913/the-tp53-induced-glycolysis-and-apoptosis-regulator-mediates-cooperation-between-htlv-1-p30-ii-and-the-retroviral-oncoproteins-tax-and-hbz-and-is-highly-expressed-in-an-in-vivo-xenograft-model-of-htlv-1-induced-lymphoma
#1
Tetiana Hutchison, Aditi Malu, Laçin Yapindi, Rachel Bergeson, Kendra Peck, Megan Romeo, Carolyn Harrod, Jordan Pope, Louisa Smitherman, Wesleigh Gwinn, Lee Ratner, Courtney Yates, Robert Harrod
The human T-cell leukemia virus type-1 (HTLV-1) is an oncoretrovirus that infects and transforms CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATLL) -an aggressive lymphoproliferative disease that is highly refractive to most anticancer therapies. The HTLV-1 proviral genome encodes several regulatory products within a conserved 3' nucleotide sequence, known as pX; however, it remains unclear how these factors might cooperate or dynamically interact in virus-infected cells. Here we demonstrate that the HTLV-1 latency-maintenance factor p30II induces the TP53-induced glycolysis and apoptosis regulator (TIGAR) and counters the oxidative stress, mitochondrial damage, and cytotoxicity caused by the viral oncoproteins Tax and HBZ...
May 16, 2018: Virology
https://www.readbyqxmd.com/read/29777805/design-of-carboxymethyl-chitosan-based-heparin-mimicking-cross-linked-beads-for-safe-and-efficient-blood-purification
#2
Yilin Wang, Xuelian Huang, Chao He, YuPei Li, Weifeng Zhao, Changsheng Zhao
Safe and efficient carboxymethyl chitosan (CMC)-based heparin-mimicking cross-linked beads (CMC/PAMPS) as adsorbents for the clearance of low-density lipoprotein-cholesterol (LDL-c) in blood purification were prepared through hydrogen bonding interactions followed with in situ cross-linking with 2-acrylamido-2-methyl-1-propanesulfonicacid (AMPS). Fourier transform infrared spectra (FTIR), two-dimensional correlation FTIR spectroscopy (2D IR), thermal gravimetric analysis (TGA) and energy dispersive X-ray spectrometer (EDS) demonstrated the successful synthesis of CMC/PAMPS beads...
May 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29777794/regulatory-t-cell-targeted-hybrid-nanoparticles-combined-with-immuno-checkpoint-blockage-for-cancer-immunotherapy
#3
Wenquan Ou, Raj Kumar Thapa, Liyuan Jiang, Soe Zar Chi, Milan Gautam, Jae-Hoon Chang, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29777765/in-vitro-and-in-vivo-evaluation-of-an-oral-sustained-release-hepatoprotective-caffeine-loaded-w-o-pickering-emulsion-formula-containing-wheat-germ-oil-and-stabilized-by-magnesium-oxide-nanoparticles
#4
Heba Elmotasem, Hala K Farag, Abeer A A Salama
The objective of this study was to innovate an effective oral sustained release hepatoprotective formula for - the water soluble drug - caffeine. Caffeine is rapidly absorbed and eliminated which dictates frequent administration to achieve adequate therapeutic effect. A w/o Pickering emulsion incorporating caffeine in the internal phase was primed. It contained wheat germ oil and was stabilized by synthesized magnesium oxide nanoparticles (MgO NPs). Components selection was based on their antioxidant, hepatoprotective and anticarcinogenic effects...
May 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29777762/astrocyte-elevated-gene-1-is-a-novel-regulator-of-astrogliosis-and-excitatory-amino-acid-transporter-2-via-interplaying-with-nuclear-factor-%C3%AE%C2%BAb-signaling-in-astrocytes-from-amyotrophic-lateral-sclerosis-mouse-model-with-hsod1-g93a-mutation
#5
Xiang Yin, Shuyu Wang, Yan Qi, Xudong Wang, Hongquan Jiang, Tianhang Wang, Yueqing Yang, Ying Wang, Chunting Zhang, Honglin Feng
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A -positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29777694/gapdh-targeted-therapy-a-new-approach-for-secondary-damage-after-traumatic-brain-injury-on-rats
#6
Vladimir F Lazarev, Elizaveta A Dutysheva, Elena Y Komarova, Elena R Mikhaylova, Irina V Guzhova, Boris A Margulis
Massive neuronal death caused by a neurodegenerative pathology or damage due to ischaemia or traumatic brain injury leads to the appearance of cytosolic proteins in the extracellular space. We found that one of the most abundant cellular polypeptides, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), appearing in the medium of dying cells or body fluids is able to form aggregates that are cytotoxic to adjacent cells. Since we previously showed that the hydrocortisone derivative RX624 can inhibit the ability of GAPDH to transport the enzyme complex with polyglutamine and reduce the cytotoxicity of the complex, we explored the effects of GAPDH on SH-SY5Y neuroblastoma cells...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777637/thymol-inhibits-oral-squamous-cell-carcinoma-growth-via-mitochondria-mediated-apoptosis
#7
Jorge J De La Chapa, Prajjal Kanti Singha, Debbie R Lee, Cara B Gonzales
BACKGROUND: Thymol is a Transient Receptor Potential Ankyrin Subtype 1 channel, (TRPA1) agonist found in thyme and oregano. Thymol has antioxidant, anti-inflammatory, and antimicrobial properties; thus thymol is added to many commercially available products including Listerine mouthwash. Thymol is also cytotoxic to HL-60 (acute promyelotic leukemia) cells in vitro. Therefore, we evaluated the effects of thymol against oral squamous cell carcinoma (OSCC) and its anticancer mechanism-of-action...
May 19, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29777389/iron-based-metal-organic-frameworks-as-a-theranostic-carrier-for-local-tuberculosis-therapy
#8
Gabriela Wyszogrodzka, Przemysław Dorożyński, Barbara Gil, Wieslaw J Roth, Maciej Strzempek, Bartosz Marszałek, Władysław P Węglarz, Elżbieta Menaszek, Weronika Strzempek, Piotr Kulinowski
PURPOSE: The purpose of the study was initial evaluation of applicability of metal organic framework (MOF) Fe-MIL-101-NH2 as a theranostic carrier of antituberculous drug in terms of its functionality, i.e. drug loading, drug dissolution, magnetic resonance imaging (MRI) contrast and cytotoxic safety. METHODS: Fe-MIL-101-NH2 was characterized using X-ray powder diffraction, FTIR spectrometry and scanning electron microscopy. The particle size analysis was determined using laser diffraction...
May 18, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29777335/a-trisubstituted-pyrazole-derivative-reduces-dmba-induced-mammary-tumor-growth-in-rats-by-inhibiting-estrogen-receptor-%C3%AE-expression
#9
Hanumappa Ananda, Kothanahally S Sharath Kumar, Muddenahalli S Sudhanva, Shobith Rangappa, Kanchugarakoppal S Rangappa
Aberrant expression of estrogen receptor alpha (ER-α) is observed in many pathological complications like breast cancer, endometrial cancer, and in osteoporosis. ER-α plays a vital role in the initiation and progression of breast cancer and confers chemo and radioresistance to the cancer cells by upregulating expression of anti-apoptotic proteins. The synthetic pyrazole derivative 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl)pyridine (compound 5d) displays significant cytotoxicity against mammary carcinoma cells...
May 18, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29777330/down-regulating-il-6-gp130-targets-improved-the-anti-tumor-effects-of-5-fluorouracil-in-colon-cancer
#10
Sanhong Li, Jilai Tian, Hongming Zhang, Shoubing Zhou, Xiyong Wang, Lei Zhang, Jiapeng Yang, Zhigang Zhang, Zhenling Ji
Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors...
May 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29777275/overexpression-of-abcb4-contributes-to-acquired-doxorubicin-resistance-in-breast-cancer-cells-in-vitro
#11
Jia-Feng Huang, Chun-Jie Wen, Guo-Zhi Zhao, Yi Dai, Ying Li, Lan-Xiang Wu, Hong-Hao Zhou
PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29777149/stretching-reduces-tumor-growth-in-a-mouse-breast-cancer-model
#12
L Berrueta, J Bergholz, D Munoz, I Muskaj, G J Badger, A Shukla, H J Kim, J J Zhao, H M Langevin
There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary and secondary cancer prevention. Recent studies have shown that gentle daily stretching for 10 minutes can reduce local connective tissue inflammation and fibrosis. Because mechanical factors within the stroma can influence the tumor microenvironment, we hypothesized that stretching would reduce the growth of tumors implanted within locally stretched tissues and tested this hypothesis in a mouse orthotopic breast cancer model...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777118/pdr18-is-involved-in-yeast-response-to-acetic-acid-stress-counteracting-the-decrease-of-plasma-membrane-ergosterol-content-and-order
#13
Cláudia P Godinho, Catarina S Prata, Sandra N Pinto, Carlos Cardoso, Narcisa M Bandarra, Fábio Fernandes, Isabel Sá-Correia
Saccharomyces cerevisiae has the ability to become less sensitive to a broad range of chemically and functionally unrelated cytotoxic compounds. Among multistress resistance mechanisms is the one mediated by plasma membrane efflux pump proteins belonging to the ABC superfamily, questionably proposed to enhance the kinetics of extrusion of all these compounds. This study provides new insights into the biological role and impact in yeast response to acetic acid stress of the multistress resistance determinant Pdr18 proposed to mediate ergosterol incorporation in plasma membrane...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776993/tumor-immune-evasion-arises-through-loss-of-tnf-sensitivity
#14
Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
https://www.readbyqxmd.com/read/29776323/low-frequency-sensorineural-hearing-loss-in-familial-hemophagocytic-lymphohistiocytosis-type-5
#15
Aren Bezdjian, Hanneke Bruijnzeel, Julia Pagel, Sam J Daniel, Hans G X M Thomeer
INTRODUCTION: Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disease affecting the cytotoxic pathway. Due to the recent advances in molecular diagnosis, immuno-chemo therapy, and hematopoietic stem cell transplantation treatment, FHL survival rates have drastically increased. CASE PRESENTATION: Herein, we describe a case of FHL type 5 presenting with low-frequency sensorineural hearing loss. Alongside our reported case, 6 additional patients were identified in the literature...
June 2018: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/29776311/phospholipid-block-copolymer-hybrid-vesicles-with-lysosomal-escape-ability
#16
Wei Zong, Bo Thingholm, Fabian Itel, Philipp Sebastian Schattling, Edit Brodszkij, Daniel Mayer, Steffen Stenger, Kenneth N Goldie, Xiaojun Han, Brigitte Städler
The success of nanoparticulate formulations in drug delivery depends on various aspects including their toxicity, internalization and intracellular location. Vesicular assemblies consisting of phospholipid and amphiphilic block copolymers are an emerging platform, which combines the benefits from liposomes and polymersomes while overcoming their challenges. We report the synthesis of poly(cholesteryl methacrylate)-block-poly(2-(dimethylamino) ethyl methacrylate) (pCMA-b-pDMAEMA) block copolymers and their assembly with phospholipids into hybrid vesicles...
May 18, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29775949/design-and-synthesis-of-some-new-carboxamide-and-propanamide-derivatives-bearing-phenylpyridazine-as-a-core-ring-and-the-investigation-of-their-inhibitory-potential-on-in-vitro-acetylcholinesterase-and-butyrylcholinesterase
#17
Burcu Kilic, Hayrettin O Gulcan, Fatma Aksakal, Tugba Ercetin, Nihan Oruklu, E Umit Bagriacik, Deniz S Dogruer
A series of new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring were designed, synthesized and evaluated for their ability to inhibit both cholinesterase enzymes. In addition, a series of carboxamide and propanamide derivatives bearing biphenyl instead of phenylpyridazine were also synthesized to examine the inhibitory effect of pyridazine moiety on both cholinesterase enzymes. The inhibitory activity results revealed that compounds 5b, 5f, 5h, 5j, 5l pyridazine-3-carboxamide derivative, exhibited selective acetylcholinesterase (AChE) inhibition with IC50 values ranging from 0...
May 8, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29775894/positive-effects-of-antitumor-drugs-in-combination-with-propolis-on-canine-osteosarcoma-cells-spos-2-and-mesenchymal-stem-cells
#18
Pedro Negri Bernardino, Paulo Ricardo Oliveira Bersano, João Ferreira Lima Neto, José Maurício Sforcin
The combination of lower concentrations of antitumor drugs (carboplatin - CARB, doxorubicin - DOX, and methotrexate - MET) with propolis was investigated against canine osteosarcoma (spOS-2) and mesenchymal stem cells (MSC) in vitro. The mechanism of action in the combinations was analyzed. spOS-2 cells were incubated up to 72 h with propolis (50 μg/ml) alone or in combination with CARB (10-400 μmol/l), DOX (0.5-2 μmol/l) or MET (50-200 μmol/l). Cell viability was assessed by MTT assay, apoptosis/necrosis by flow cytometry, and MSC was incubated with the optimum combination...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775868/cytotoxic-and-other-withanolides-from-aeroponically-grown-physalis-philadelphica
#19
Ya-Ming Xu, E M Kithsiri Wijeratne, Alan D Brooks, Poonam Tewary, Li-Jiang Xuan, Wen-Qiong Wang, Thomas J Sayers, A A Leslie Gunatilaka
Eleven withanolides including six previously undescribed compounds, 16β-hydroxyixocarpanolide, 24,25-dihydroexodeconolide C, 16,17-dehydro-24-epi-dioscorolide A, 17-epi-philadelphicalactone A, 16-deoxyphiladelphicalactone C, and 4-deoxyixocarpalactone A were isolated from aeroponically grown Physalis philadelphica. Structures of these withanolides were elucidated by the analysis of their spectroscopic (HRMS, 1D and 2D NMR, ECD) data and comparison with published data for related withanolides. Cytotoxic activity of all isolated compounds was evaluated against a panel of five human tumor cell lines (LNCaP, ACHN, UO-31, M14 and SK-MEL-28), and normal (HFF) cells...
May 15, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29775867/phytochemical-profiles-phototoxic-and-antioxidant-properties-of-eleven-hypericum-species-a-comparative-study
#20
Edoardo Napoli, Laura Siracusa, Giuseppe Ruberto, Alessandra Carrubba, Silvia Lazzara, Antonio Speciale, Francesco Cimino, Antonella Saija, Mariateresa Cristani
Hypericum is one out of the nine genera belonging to the botanical family Clusiaceae Lindl (syn. Hypericaceae Juss.; APG III, 2009). The genus contains 484 species spread worldwide, one of which, Hypericum perforatum, is largely used in folk medicine. The aim of this study was to evaluate the chemical composition, along with the antioxidant and phototoxic activity, of 11 Hypericum species grown in Sicily (H. perforatum L., H. aegypticum L., H. androsaemum L., H. calycinum L., H. hircinum L., H. hirsutum L...
May 15, 2018: Phytochemistry
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