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https://www.readbyqxmd.com/read/28351040/macular-edema-definition-and-basic-concepts
#1
Gabriel Coscas, José Cunha-Vaz, Gisèle Soubrane
Macular edema is the result of an accumulation of fluid in the retinal layers around the fovea. It contributes to vision loss by altering the functional cell relationship in the retina and promoting an inflammatory reparative response. Macular edema may be intracellular or extracellular. Intracellular accumulation of fluid, also called cytotoxic edema, is an alteration of the cellular ionic distribution. Extracellular accumulation of fluid, which is more frequent and clinically more relevant, is directly associated with an alteration of the blood-retinal barrier (BRB)...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28351000/targeted-superparamagnetic-nanoparticles-coated-with-2-deoxy-d-gloucose-and-doxorubicin-more-sensitize-breast-cancer-cells-to-ionizing-radiation
#2
Jalil Pirayesh Islamian, Milad Hatamian, Negar Abbasi Aval, Mohammad Reza Rashidi, Asghar Mesbahi, Mohammad Mohammadzadeh, Mohammad Asghari Jafarabadi
INTRODUCTION: Nanoparticles are promising as a new approach to enhance chemo- radiotherapy efficiency in breast cancer mainly via targeted therapy. MATERIALS & METHODS: SKBR3 and T47D breast cancer cells were treated with superparamagnetic mesoporous hydroxyapatite nanocomposites (SPmHANs)conjugated with 1 μM doxorubicin and 0.5 mM 2-Deoxy-d-Glucose and irradiated with 1 and 2 Gy gamma rays in vitro. The treatment toxicity and also the apoptosis/necrosis ratio were measured by MTT assay and also ELISA cell death detection PLUS, respectively...
March 25, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28350947/traumatic-spinal-cord-injury-repair-and-regeneration
#3
Christopher S Ahuja, Satoshi Nori, Lindsay Tetreault, Jefferson Wilson, Brian Kwon, James Harrop, David Choi, Michael G Fehlings
BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery. PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28350865/multi-drug-loaded-micelles-delivering-chemotherapy-and-targeted-therapies-directed-against-hsp90-and-the-pi3k-akt-mtor-pathway-in-prostate-cancer
#4
Bao Le, Ginny L Powers, Yu Tong Tam, Nicholas Schumacher, Rita L Malinowski, Laura Steinke, Glen Kwon, Paul C Marker
BACKGROUND: Advanced prostate cancers that are resistant to all current therapies create a need for new therapeutic strategies. One recent innovative approach to cancer therapy is the simultaneous use of multiple FDA-approved drugs to target multiple pathways. A challenge for this approach is caused by the different solubility requirements of each individual drug, resulting in the need for a drug vehicle that is non-toxic and capable of carrying multiple water-insoluble antitumor drugs...
2017: PloS One
https://www.readbyqxmd.com/read/28350454/structural-optimizations-of-thieno-3-2-b-pyrrole-derivatives-for-the-development-of-metabolically-stable-inhibitors-of-chikungunya-virus
#5
Kuan Chieh Ching, Thi Ngoc Quy Tran, Siti Naqiah Amrun, Yiu Wing Kam, Lisa F P Ng, Christina Li Lin Chai
Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus and there is no approved effective antiviral treatment currently available for CHIKV. We previously reported the discovery of thieno[3,2-b]pyrrole 1b that displayed good antiviral activity against CHIKV infection in vitro. However, it has a short half-life in the presence of human liver microsomes (HLMs) (T1/2 = 2.91 min). Herein, we report further optimization studies in which potential metabolically labile sites on compound 1b were removed or modified, resulting in the identification of thieno[3,2-b]pyrrole 20 and pyrrolo[2,3-d]thiazole 23c possessing up to 17-fold increase in metabolic half-lives in HLMs and good in vivo pharmacokinetic properties...
March 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28350442/engineered-polymer-transferrin-conjugates-as-self-assembling-targeted-drug-delivery-systems
#6
Hiteshri Makwana, Francesca Mastrotto, Johannes Pall Magnusson, Darrell Sleep, Joanna Hay, Karl J Nicholls, Stephanie Allen, Cameron Alexander
Polymer-protein conjugates can be engineered to self-assemble into discrete and well-defined drug delivery systems which combine the advantages of receptor targeting and controlled drug release. We designed specific conjugates of the iron-binding and transport protein, transferrin (Tf), to combine the advantages of this serum-stable protein as a targeting agent for cancer cells with self-assembling polymers to act as carriers of cytotoxic drugs. Tf variants were expressed with cysteine residues at sites spanning different regions of the protein surface and the polymer conjugates grown from these variants were compared with polymer conjugates grown from non-selectively derivatised sites on native Tf...
March 28, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28346994/gc-ms-analysis-and-potential-cytotoxic-activity-of-calyptranthes-grandifolia-o-berg-calyptranthes-tricona-d-legrand-and-myrciaria-plinioides-d-legrand-essential-oil-in-raw264-7-and-cho-k1-cells
#7
D Faleiro, S M Immich, F Majolo, L Mayer, E M Ethur, M I Goettert
The search for new bioactive substances derived from natural products is daily growing. Among biologically active products used in therapeutic approaches, essential oils are described with wide range of therapeutic and pharmacological potential. Plants from Myrtaceae family have the presence of essential oils in its composition. Calyptranthes grandifolia, Calyptranthes tricona and Myrciaria plinioides species belong to this family and are used by the local population. However, there are no reports in the literature describing relevant characteristics about the potential and possible activities of these species...
March 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28346872/5-bromo-2-aryl-benzimidazole-derivatives-as-non-cytotoxic-potential-dual-inhibitors-of-%C3%AE-glucosidase-and-urease-enzymes
#8
Tanzila Arshad, Khalid Mohammed Khan, Najma Rasool, Uzma Salar, Shafqat Hussain, Humna Asghar, Mohammed Ashraf, Abdul Wadood, Muhammad Riaz, Shahnaz Perveen, Muhammad Taha, Nor Hadiani Ismail
On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM)...
March 20, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28346797/substituted-borosilicate-glasses-with-improved-osteogenic-capacity-for-bone-tissue-engineering
#9
João S Fernandes, Piergiorgio Gentile, Aileen Crawford, Ricardo A Pires, Paul V Hatton, Rui L Reis
Borosilicate bioactive glasses (BBGs) have shown the capacity to promote higher formation of new bone when compared with silicate bioactive glasses. Herein, we assessed the capacity of BBGs to induce osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) as a function of their substituted divalent cations (Mg(2+), Ca(2+), Sr(2+)). To this purpose, we synthesized BBG particles by melt quenching. The cell viability, proliferation, and morphology (i.e., PrestoBlue(®), PicoGreen(®), and DAPI and Phalloidin stainings, respectively), as well as protein expression (i...
March 27, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28346428/autophagy-is-required-for-cell-survival-under-l-asparaginase-induced-metabolic-stress-in-acute-lymphoblastic-leukemia-cells
#10
H Takahashi, J Inoue, K Sakaguchi, M Takagi, S Mizutani, J Inazawa
L-asparaginase has been used for more than three decades in acute lymphoblastic leukemia (ALL) patients and remains an essential drug in the treatment of ALL. Poor response to L-asparaginase is associated with increased risk of therapeutic failure in ALL. However, both the metabolic perturbation and molecular context of L-asparaginase-treated ALL cells has not been fully elucidated. Here we identify that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346393/choerosponins-a-and-b-two-new-cytotoxic-bridged-ring-ketones-and-the-determination-of-their-absolute-configurations
#11
Chang-Wei Li, Bing Han, Bing Cai, Cheng-Bin Cui
Bioactivity-directed fractionation of antitumor compounds from the stem barks of Choerospondias axillaries (Roxb.) Burtt et Hill (Anacardiaceae) afforded two new cytotoxic bridged-ring ketones, choerosponins A (1) and B (2), and their structures were elucidated by spectroscopic methods; their stereochemistry was determined by NOE difference experiments, CD spectra and the modified Mosher's method. Compound 1 has a rare dioxatricyclo skeleton. Flow cytometry and SRB methods were employed to evaluate the antitumor activity of the two compounds against tsFT210, HCT-15, HeLa, A2780 and MCF-7 cell lines, and both of them showed strong cytotoxicity...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346389/artesunate-enhances-the-cytotoxicity-of-5-aminolevulinic-acid-based-sonodynamic-therapy-against-mouse-mammary-tumor-cells-in-vitro
#12
Tomohiro Osaki, Yoshihiro Uto, Masahiro Ishizuka, Tohru Tanaka, Nobuyasu Yamanaka, Tsukasa Kurahashi, Kazuo Azuma, Yusuke Murahata, Takeshi Tsuka, Norihiko Itoh, Tomohiro Imagawa, Yoshiharu Okamoto
Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346380/constituents-of-the-roots-of-dichapetalum-pallidum-and-their-anti-proliferative-activity
#13
Dorcas Osei-Safo, Godwin Akpeko Dziwornu, Regina Appiah-Opong, Mary Anti Chama, Isaac Tuffour, Reiner Waibel, Richard Amewu, Ivan Addae-Mensah
As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A (2) and X (3). Also isolated were the known compounds friedelin-2,3-lactone (4), friedelan-3-one (6), friedelan-3β-ol (7) and pomolic (8), as well as the dipeptide aurantiamide acetate (5). The compounds were characterized by direct interpretation of their IR, 1D NMR and 2D NMR spectral data and by comparison of their physico-chemical data, including their chromatographic profiles, with the literature and authentic samples in our compound library for the genus Dichapetalum...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346364/new-benzimidazole-1-2-4-triazole-hybrid-compounds-synthesis-anticandidal-activity-and-cytotoxicity-evaluation
#14
Hülya Karaca Gençer, Ulviye Acar Çevik, Serkan Levent, Begüm Nurpelin Sağlık, Büşra Korkut, Yusuf Özkay, Sinem Ilgın, Yusuf Öztürk
Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR, (13)C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346319/effect-of-combination-antiretroviral-therapy-on-hiv-1-specific-antibody-dependent-cellular-cytotoxicity-responses-in-subtype-b-and-subtype-c-infected-cohorts
#15
Vijaya Madhavi, Archana Kulkarni, Ashwini Shete, Wen Shi Lee, Milla R Mclean, Anne B Kristensen, Manisha Ghate, Bruce D Wines, P Mark Hogarth, Matthew S Parsons, Anthony Kelleher, David A Cooper, Janaki Amin, Sean Emery, Madhuri Thakar, Stephen J Kent
BACKGROUND: There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC) and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored. METHODS: The effect of cART on HIV-1- and influenza-specific ADCC was analyzed in two cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after two years of cART...
March 23, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28346096/a-novel-multiparametric-drug-scoring-method-for-high-throughput-screening-of-3d-multicellular-tumor-spheroids-using-the-celigo-image-cytometer
#16
Scott Cribbes, Sarah Kessel, Scott McMenemy, Jean Qiu, Leo Li-Ying Chan
Three-dimensional (3D) tumor models have been increasingly used to investigate and characterize cancer drug compounds. The ability to perform high-throughput screening of 3D multicellular tumor spheroids (MCTS) can highly improve the efficiency and cost-effectiveness of discovering potential cancer drug candidates. Previously, the Celigo Image Cytometer has demonstrated a novel method for high-throughput screening of 3D multicellular tumor spheroids. In this work, we employed the Celigo Image Cytometer to examine the effects of 14 cancer drug compounds on 3D MCTS of the glioblastoma cell line U87MG in 384-well plates...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346088/a-1536-well-3d-viability-assay-to-assess-the-cytotoxic-effect-of-drugs-on-spheroids
#17
Franck Madoux, Allison Tanner, Michelle Vessels, Lynsey Willetts, Shurong Hou, Louis Scampavia, Timothy P Spicer
Evaluation of drug cytotoxicity traditionally relies on use of cell monolayers, which are easily miniaturized to the 1536-well plate format. Three-dimensional (3D) cell culture models have recently gained popularity thanks to their ability to better mimic the complexity of in vivo systems. Despite growing interest in these more physiologically relevant and highly predictive cell-based models for compound profiling and drug discovery, 3D assays are currently performed in a medium- to low-throughput format, either in 96-well or 384-well plates...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345939/macrophilone-a-structure-elucidation-total-synthesis-and-functional-evaluation-of-a-biologically-active-iminoquinone-from-the-marine-hydroid-macrorhynchia-philippina
#18
Katherine Zlotkowski, William M Hewitt, Pengcheng Yan, Heidi R Bokesch, Megan L Peach, Marc C Nicklaus, Barry R O'Keefe, James B McMahon, Kirk R Gustafson, John S Schneekloth
A previously uncharacterized pyrroloiminoquinone natural product, macrophilone A, was isolated from the stinging hydroid Macrorhynchia philippina. The structure was assigned utilizing long-range NMR couplings and DFT calculations and proved by a concise, five-step total synthesis. Macrophilone A and a synthetic analogue displayed potent biological activity, including increased intracellular reactive oxygen species levels and submicromolar cytotoxicity toward lung adenocarcinoma cells.
March 27, 2017: Organic Letters
https://www.readbyqxmd.com/read/28345897/a-smart-molecule-for-selective-sensing-of-nitric-oxide-conversion-of-no-to-hsno-relevance-of-biological-hsno-formation
#19
Abu Saleh Musha Islam, Rahul Bhowmick, Kaberi Pal, Atul Katarkar, Keya Chaudhuri, Mahammad Ali
A smart molecule, QT490, containing thiosemicarbazide moiety acts as a highly selective turn-on in vitro NO sensor through the unprecedented NO-induced transformation of thiosemicarbazide moiety to 1,3,4-oxadiazole heterocycle with the concomitant release of HSNO, thereby eliminating any interference from various endogenous biomolecules including dehydroascorbic acid, ascorbic acid, etc. The kinetic studies of the reactions between QT490 and NO provide a mechanistic insight into formation of HSNO/RSNO from the reaction between H2S/RSH and NO in the biological system...
March 27, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28345838/ercc1-expression-in-metastatic-triple-negative-breast-cancer-patients-treated-with-platinum-based-chemotherapy
#20
Mohamed Ali EL Baiomy, Wagdi F El Kashef
Background: Possible targeted therapies for metastatic triple negative breast cancer (TNBC) include cytotoxic chemotherapy that causes interstrand breaks (platinum-based drugs). The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway, removing platinum-induced DNA adducts and contributing to cisplatin resistance. Detecting ERCC1 overexpression is important in considering treatment options for metastatic TNBC, including individualized approaches to therapy, and may facilitate improved responses or reduction of unnecessary toxicity...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
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