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https://www.readbyqxmd.com/read/29025984/synthesis-and-biological-evaluation-of-a-novel-18-f-labeled-adnectin-as-a-pet-radioligand-for-imaging-pd-l1-expression
#1
David J Donnelly, Ralph Adam Smith, Paul Morin, Dasa Lipovsek, Jochem Gokemeijer, Daniel Cohen, Virginie Lafont, Tritin Tran, Erin Lee Cole, Martin Wright, Joonyoung Kim, Adrienne Pena, Daniel Kukral, Douglas D Dischino, Patrick Chow, Jinping Gan, Olufemi Adelakun, Xi-Tao Wang, Kai Cao, David Lueng, Samuel Bonacorsi, Wendy Hayes
The programmed death protein (PD-1) and its ligand (PD-L1) play critical roles in a checkpoint pathway cancer cells exploit to evade the immune system. A same-day PET imaging agent for measuring PD-L1 status in primary and metastatic lesions could be important for optimizing drug therapy. Herein, we have evaluated the tumor targeting of an anti-PD-L1 Adnectin after (18)F-fluorine labeling. Methods: An anti-PD-L1 Adnectin was labeled with (18)F in two steps. This synthesis featured fluorination of a novel prosthetic group, followed by a copper-free click conjugation to a modified Adnectin to generate (18)F-BMS-986192...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29017779/targeted-inhibition-of-hantavirus-replication-and-intracranial-pathogenesis-by-a-chimeric-protein-delivered-sirna
#2
Jie Yang, Ji-Feng Sun, Ting-Ting Wang, Xiao-Hong Guo, Jun-Xia Wei, Lin-Tao Jia, An-Gang Yang
Hantavirus (HV) infection, which underlies hantavirus hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, remains to be a severe clinical challenge. Here, we synthesized small interfering RNAs (siRNAs) that target the encoding sequences of HV strain 76-118, and validated their inhibitory role in virus replication in HV-infected monkey kidney Vero E6 cells. A chimeric protein, 3G1-Cκ-tP, consisting of a single-chain antibody fragment (3G1) against the HV surface envelop glycoprotein, the constant region of human immunoglobulin κ chain (Cκ), and truncated protamine (amino acids 8-29, tP), was further generated...
October 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28959669/in-vitro-cytotoxicity-of-zinc-oxide-iron-oxide-and-copper-nanopowders-prepared-by-green-synthesis
#3
Saranya S, Vijayaranai K, Pavithra S, Raihana N, Kumanan K
In vitro cytotoxic effects of ZnO, FeO and Cu metallic nanopowders (NPs) on Vero (African green monkey kidney cell line), PK 15 (Pig kidney cell line) and Madin Darby Bovine Kidney (MDBK) cell lines were investigated at different time intervals (24 and 48 h). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine the cytotoxic effects of green synthesized (plant based) nanopowders. The comparative effects of exposure period and concentration of nanopowders on cell viability were studied...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28955630/synthesis-characterization-and-biological-applications-of-mycosynthesized-silver-nanoparticles
#4
Sathiyaseelan Anbazhagan, Shajahan Azeez, Girilal Morukattu, Ramachandran Rajan, Kaviyarasan Venkatesan, Kalaichelvan Puthupalayam Thangavelu
Silver nanoparticles (AgNPs) have been known for their inhibitory and bactericidal effects. In the present study, less toxic AgNPs using Cunninghamella echinulata is reported for the first time. The obtained AgNPs were characterized using UV-Visible spectrophotometer, XRD, FT-IR, FE-SEM with EDAX and HR-TEM. AgNPs showed the maximum absorbance at 420-430 nm. The transmission electron micrograph revealed the formation of considerably uniform-sized AgNPs with an average size of 20-50 nm. The reducing and capping agents responsible for AgNP synthesis were identified by FT-IR...
October 2017: 3 Biotech
https://www.readbyqxmd.com/read/28942525/subcutaneous-ovarian-tissue-transplantation-in-nonhuman-primates-duration-of-endocrine-function-and-normalcy-of-subsequent-offspring-as-demonstrated-by-reproductive-competence-oocyte-production-and-telomere-length
#5
David M Lee, Carrie M Thomas, Fuhua Xu, Richard R Yeoman, Jing Xu, Richard L Stouffer, Don P Wolf, Mary B Zelinski
PURPOSE: The main purposes of the study were to investigate the endocrine function of ovarian tissue transplanted to heterotopic subcutaneous sites and the reproductive competence and telomere length of a nonhuman primate originating from transplanted tissue. METHODS: Ovarian cortex pieces were transplanted into the original rhesus macaques in the arm subcutaneously, in the abdomen next to muscles, or in the kidney. Serum estradiol (E2) and progesterone (P4) concentrations were measured weekly for up to 8 years following tissue transplantation...
September 23, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28918011/nucleic-acid-polymers-with-accelerated-plasma-and-tissue-clearance-for-chronic-hepatitis-b-therapy
#6
Ingo Roehl, Stephan Seiffert, Celia Brikh, Jonathan Quinet, Catherine Jamard, Nadine Dorfler, Jennifer A Lockridge, Lucyna Cova, Andrew Vaillant
REP 2139 is a nucleic acid polymer (NAP) currently under clinical development for chronic hepatitis B (HBV) therapy. This preclinical study investigated different REP 2139 analogs that would display reduced accumulation in the serum and tissues, while retaining an antiviral effect against HBV infection. REP 2139 analogs were evaluated in human plasma, CD-1 mice, cynomolgus monkeys, and Pekin ducks. Discrete ribose transformation to 2'OH in selected riboadenosines resulted in a slow degradation in acidified human plasma that plateaued after 48 hr...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28904298/usefulness-of-urinary-biomarkers-for-nephrotoxicity-in-cynomolgus-monkeys-treated-with-gentamicin-cisplatin-and-puromycin-aminonucleoside
#7
Hiroshi Uchino, Junko Fujishima, Kaori Fukuoka, Teppei Iwakiri, Akira Kamikuri, Hidenori Maeda, Kazuhiro Nakama
The objective of this study was to investigate the availability of novel urinary biomarkers (BMs) such as total protein, albumin, β2-microglobulin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute nephrotoxicity in cynomolgus monkeys. Animals (total 9 males/3 groups) were administered gentamicin (GM) subcutaneously at 40 mg/kg for 7 days, cisplatin (CDDP) intravenously at 3 mg/kg once and puromycin aminonucleoside (PAN) intravenously at 20 mg/kg for 7 days...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904193/mutations-in-the-fusion-protein-of-measles-virus-that-confer-resistance-to-the-membrane-fusion-inhibitors-carbobenzoxy-d-phe-l-phe-gly-and-as-48
#8
Michael N Ha, Sébastien Delpeut, Ryan S Noyce, Gary Sisson, Karen M Black, Liang-Tzung Lin, Darius Bilimoria, Richard K Plemper, Gilbert G Privé, Christopher D Richardson
The inhibitors Z-d-Phe-l-Phe Gly (fusion inhibitor peptide, FIP) and AS-48 have similar efficacy in blocking membrane fusion and syncytia formation mediated by measles virus. Other homologues such as Z-d-Phe are less effective, but may act through the same mechanism. In an attempt to map the site of action of these inhibitors, we generated mutant viruses which were resistant to the inhibitory effects of Z-d-Phe-l-Phe Gly. These 10 mutations were localized to the heptad repeat region (HRB) of the fusion protein and no changes were observed in the viral hemagglutinin, which is the receptor attachment protein...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28898286/structural-investigation-of-c6-36-and-vero-cell-cultures-infected-with-a-brazilian-zika-virus
#9
Debora Ferreira Barreto-Vieira, Fernanda Cunha Jácome, Marcos Alexandre Nunes da Silva, Gabriela Cardoso Caldas, Ana Maria Bispo de Filippis, Patrícia Carvalho de Sequeira, Elen Mello de Souza, Audrien Alves Andrade, Pedro Paulo de Abreu Manso, Gisela Freitas Trindade, Sheila Maria Barbosa Lima, Ortrud Monika Barth
Zika virus (ZIKV) is a member of the flavivirus genus, and its genome is approximately 10.8 kilobases of positive-strand RNA enclosed in a capsid and surrounded by a membrane. Studies on the replication dynamics of ZIKV are scarce, which limits the development of antiviral agents and vaccines directed against ZIKV. In this study, Aedes albopictus mosquito lineage cells (C6/36 cells) and African green monkey kidney epithelial cells (Vero cells) were inoculated with a ZIKV sample isolated from a Brazilian patient, and the infection was characterized by immunofluorescence staining, phase contrast light microscopy, transmission electron microscopy and real-time RT-PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28870343/solvent-solvent-fractionations-of-combretum-erythrophyllum-burch-leave-extract-studies-of-their-antibacterial-antifungal-antioxidant-and-cytotoxicity-potentials
#10
Fanyana M Mtunzi, Ikechukwu P Ejidike, Imelda Ledwaba, Aroke Ahmed, Vusumzi E Pakade, Michael J Klink, Sekomeng J Modise
OBJECTIVE: To evaluate the biological activities of Combretum erythrophyllum (C. erythrophyllum) leaf extracts against infectious diseases' pathogenesis and their cytotoxicity potentials. METHODS: Powdered leaf material (300 g) of C. erythrophyllum was extracted (1:10 w/v) using acetone to obtain the crude extract. Liquid-liquid fractionation was performed on the crude acetone extract (30 g) using solvents of different polarity. The bioautographic method was used to detect the inhibition of bacterial and fungal growth by active compounds present in the crude and fractions...
July 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28855711/potential-antigens-involved-in-delayed-xenograft-rejection-in-a-ggta1-cmah-dko-pig-to-monkey-model
#11
Junfang Zhang, Chongwei Xie, Ying Lu, Ming Zhou, Zepeng Qu, Da Yao, Chuanghua Qiu, Jia Xu, Dengke Pan, Yifan Dai, Hidetaka Hara, David K C Cooper, Shanshan Ma, Mingtao Li, Zhiming Cai, Lisha Mou
When hyperacute rejection is avoided by deletion of Gal expression in the pig, delayed xenograft rejection (DXR) becomes a major immunologic barrier to successful xenotransplantation. This study was to investigate the potential antigens involved in DXR. We isolated primary renal microvascular endothelial cells (RMEC) and aortic endothelial cells (AEC) from a GGTA1/CMAH double-knockout (DKO) pig (and a GGTA1-KO pig) and immunized cynomolgus monkeys with both of these cells. After sensitization, monkey serum antibody binding and cytotoxicity to RMEC was significantly higher than to AEC(p < 0...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706754/smart-release-nano-formulation-of-cytochrome-c-and-hyaluronic-acid-induces-apoptosis-in-cancer-cells
#12
C M Figueroa, B N Suárez, A M Molina, J C Fernández, Z Torres, K Griebenow
Herein we tested a nanosized cancer-cell targeted delivery system based on cytochrome c (Cyt c) and hyaluronic acid. Cyt c was chosen since it is a per se non-toxic protein but causes apoptosis when delivered to the cytoplasm of target cells. Hyaluronic acid was employed to create the nanosized delivery system with passive targeting capability in order to exploit the enhanced permeation and retention (EPR) effect and active targeting capability of hyaluronic acid. In addition, our goal was to incorporate a smart release strategy to only promote protein release upon reaching its target...
February 2017: Journal of Nanomedicine & Nanotechnology
https://www.readbyqxmd.com/read/28694750/in-vitro-and-in-vivo-anticancer-studies-of-2-hydroxy-chalcone-derivatives-exhibit-apoptosis-in-colon-cancer-cells-by-hdac-inhibition-and-cell-cycle-arrest
#13
Aditya Narayan Pande, Subhankar Biswas, Neetinkumar D Reddy, B S Jayashree, Nitesh Kumar, C Mallikarjuna Rao
Considering the therapeutic values of bioflavonoids in colon cancer treatment, six 2'-hydroxy chalcones (C1-C6) were synthesized, characterized and screened for in vitro cytotoxicity on human colon carcinoma (HCT116) and African green monkey kidney epithelial cells (Vero). Only C5 showed selective cytotoxicity against HCT116 cells. Other potent cytotoxic compounds were C1, C2 and C3. Further screening included enzyme inhibition studies on histone deacetylase (HDAC) enzyme where C1 showed lowest IC50 value (105...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28671598/synthesis-and-evaluation-of-n-3-trifluoroacetyl-indol-7-yl-acetamides-for-potential-in-vitro-antiplasmodial-properties
#14
Malose J Mphahlele, Mmakwena M Mmonwa, Yee Siew Choong
A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides with trifluoroacetic anhydride. The prepared compounds were evaluated for potential in vitro antiplasmodial properties. Preliminary results from antiplasmodial activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum revealed that a combination of 2-(4-flurophenyl)- and 5-(4-fluorophenyl) or 2-(4-flurophenyl)- and 4-fluorostyryl groups in compounds 3(a,f) and 4(a,g), for example, is required for biological activity for both series of compounds...
July 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28659807/elucidation-of-arctigenin-pharmacokinetics-and-tissue-distribution-after-intravenous-oral-hypodermic-and-sublingual-administration-in-rats-and-beagle-dogs-integration-of-in-vitro-and-in-vivo-findings
#15
Jie Li, Xin Li, Yu-Shan Ren, Yuan-Yuan Lv, Jun-Sheng Zhang, Xiao-Li Xu, Xian-Zhen Wang, Jing-Chun Yao, Gui-Min Zhang, Zhong Liu
Although arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28637685/milk-oligosaccharides-inhibit-human-rotavirus-infectivity-in-ma104-cells
#16
Daniel R Laucirica, Vassilis Triantis, Ruud Schoemaker, Mary K Estes, Sasirekha Ramani
Background: Oligosaccharides in milk act as soluble decoy receptors and prevent pathogen adhesion to the infant gut. Milk oligosaccharides reduce infectivity of a porcine rotavirus strain; however, the effects on human rotaviruses are less well understood.Objective: In this study, we determined the effect of specific and abundant milk oligosaccharides on the infectivity of 2 globally dominant human rotavirus strains.Methods: Four milk oligosaccharides-2'-fucosyllactose (2'FL), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), and galacto-oligosaccharides-were tested for their effects on the infectivity of human rotaviruses G1P[8] and G2P[4] through fluorescent focus assays on African green monkey kidney epithelial cells (MA104 cells)...
September 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28629354/acetone-leaf-extracts-of-some-south-african-trees-with-high-activity-against-escherichia-coli-also-have-good-antimycobacterial-activity-and-selectivity-index
#17
Ishaku L Elisha, Francien S Botha, Balungile Madikizela, Lyndy J McGaw, Jacobus N Eloff
BACKGROUND: Tuberculosis is a world-wide problem affecting humans and animals. There is increasing development of resistance of the pathogens to current antimycobacterial agents. Many authors have investigated activities of extracts and isolated compounds from plants. The traditional uses of plants have frequently been the criterion to select plants investigated. In this contribution, we investigate whether plant extracts with very good activity against Escherichia coli may also be active against mycobacteria...
June 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28629039/time-dependent-subcellular-structure-injuries-induced-by-nano-micron-sized-calcium-oxalate-monohydrate-and-dihydrate-crystals
#18
Xin-Yuan Sun, Kai Yu, Jian-Ming Ouyang
Comparative studies were conducted to investigate the time effect of cell injury induced by nano-sized (50nm) and micron-sized (10μm) calcium oxalate monohydrate (COM) and dihydrate (COD) crystals in African green monkey renal epithelial (Vero) cells. The effects of nano-/micron-sized COM and COD exposure on Vero cells were investigated by detecting the cell viability, cell morphology, LDH release, reactive oxygen species, mitochondrial membrane potential, cell cycle, and cell apoptosis, as well as the intracellular and extracellular crystal distribution...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28619602/optimized-method-for-isolation-of-immature-intracytoplasmic-retroviral-particles-from-mammalian-cells
#19
Hana Langerová, Tomáš Ruml, Michaela Rumlová
To biochemically and structurally characterize viral intracytoplasmic particles (ICAPs), a sample of high purity and homogeneity is usually required. Production of ICAPs in the system closely related to their natural host cells is crucial for the analysis of host-cell binding proteins involved in ICAPs assembly, transport and budding. However, this approach is often hampered by problems with low yield of the ICAPs due to either low expression or fast release from the host cell. Another obstacle may be a low stability or fragility of the intracellular particles...
October 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28573661/characterization-of-a-pristane-induced-lupus-associated-model-in-the-non-human-primate-cynomolgus-monkey
#20
Jing Wang, Hui Shen, Yuqiang Zhu, Ying Zhu, Lei Cai, Zhiyao Wang, Qin Shi, Yuhua Qiu
BACKGROUND: Lupus is an autoimmune disease with complex syndrome. Rodent models have limitations for recapitulating the spectrum of the disease. A more powerful translational model is desirable. METHOD: Lupus-associated model in cynomolgus monkeys was induced by two intraperitoneal injections of 2, 6, 10, 14-tetramethylpentadecane (PRISTANE). Lupus-specific biomarkers and manifestations over a 246-day period were observed at multilevel. To visualize and quantify kidney function in real time, contrast-enhanced ultrasound was used...
June 2, 2017: Journal of Medical Primatology
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