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https://www.readbyqxmd.com/read/28734141/new-dinuclear-palladium-ii-complexes-studies-of-the-nucleophilic-substitution-reactions-dna-bsa-interactions-and-cytotoxic-activity
#1
Dušan Ćoćić, Snežana Jovanović, Marija Nišavić, Dejan Baskić, Danijela Todorović, Suzana Popović, Živadin D Bugarčić, Biljana Petrović
Six new dinuclear Pd(II) complexes, [{Pd(2,2'-bipy)Cl}2(μ-pz)](ClO4)2 (Pd1), [{Pd(dach)Cl}2(μ-pz)](ClO4)2 (Pd2), [{Pd(en)Cl}2(μ-pz)](ClO4)2 (Pd3), [{Pd(2,2'-bipy)Cl}2(μ-4,4'-bipy)](ClO4)2 (Pd4), [{Pd(dach)Cl}2(μ-4,4'-bipy)](ClO4)2 (Pd5) and [{Pd(en)Cl}2(μ-4,4'-bipy)](ClO4)2 (Pd6) (where 2,2'-bipy=2,2'-bipyridyl, pz=pyrazine, dach=trans-(±)-1,2-diaminocyclohexane, en=ethylenediamine, 4,4'-bipy=4,4'-bipyridyl) have been synthesized and characterized by elemental microanalysis, IR, (1)H NMR and MALDI-TOF mass spectrometry...
July 16, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-tregs-prevent-gvhd-while-allowing-a-powerful-t-cell-dependent-gvl-effect-in-murine-models
#2
B Del Papa, L Ruggeri, E Urbani, S Baldoni, D Cecchini, T Zei, R Iacucci Ostini, B Crescenzi, A Carotti, A Pierini, P Sportoletti, P Di Bartolomeo, F Falzetti, C Mecucci, A Velardi, M F Martelli, M Di Ianni
We developed a GMP-compatible expansion protocol, to improve number and purity of Tregs available for clinical trials. Six clinical grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation and rapamycin for 19 days achieving a median of 8.5 fold (6.25-13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong MLR inhibition...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28726923/robust-manufacturing-of-lipid-polymer-nanoparticles-through-feedback-control-of-parallelized-swirling-microvortices
#3
Michael J Toth, Taeyoung Kim, YongTae Kim
A variety of therapeutic and/or diagnostic nanoparticles (NPs), or nanomedicines, have been formulated for improved drug delivery and imaging applications. Microfluidic technology enables continuous and highly reproducible synthesis of NPs through controlled mixing processes at the micro- and nanoscale. Yet, the inherent low-throughput remains a critical roadblock, precluding the probable applications of new nanomedicines for clinical translation. Here we present robust manufacturing of lipid-polymer NPs (LPNPs) through feedback controlled operation of parallelized swirling microvortex reactors (SMRs)...
July 20, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28726567/possible-mechanisms-involved-in-the-anti-nociceptive-effects-of-hydro-ethanolic-leaf-extract-of-ziziphus-abyssinica
#4
Eric Boakye-Gyasi, Isaac Tabiri Henneh, Wonder Kofi Mensah Abotsi, Elvis Ofori Ameyaw, Eric Woode
CONTEXT: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to support the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. PURPOSE: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28725053/cyclic-di-gmp-regulates-mycobacterium-tuberculosis-resistance-to-ethionamide
#5
Hai-Nan Zhang, Zhao-Wei Xu, He-Wei Jiang, Fan-Lin Wu, Xiang He, Yin Liu, Shu-Juan Guo, Yang Li, Li-Jun Bi, Jiao-Yu Deng, Xian-En Zhang, Sheng-Ce Tao
Tuberculosis is still on the top of infectious diseases list on both mobility and mortality, especially due to drug-resistance of Mycobacterium tuberculosis (M.tb). Ethionamide (ETH) is one of effective second line anti-TB drugs, a synthetic compound similar to isoniazid (INH) structurally, with existing severe problem of ETH resistance. ETH is a prodrug, which is activated by Etha inside M.tb, and etha is transcriptionally repressed by Ethr. We found that c-di-GMP could bind Ethr, enhanced the binding of Ethr to the promoter of etha, and then repressed the transcription of etha, thus caused resistance of M...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722676/comparative-proteomic-analysis-of-virulent-and-avirulent-strains-of-toxoplasma-gondii-reveals-strain-specific-patterns
#6
Dong-Hui Zhou, Ze-Xiang Wang, Chun-Xue Zhou, Shuai He, Hany M Elsheikha, Xing-Quan Zhu
Research exploring the proteome of Toxoplasma gondii oocysts has gained momentum over the past few years. However, little is known about the oocyst's protein repertoires that contribute to differential virulence among T. gondii strains. Here, we used isobaric tag for relative and absolute quantitation-based proteomic analysis of oocysts of two T. gondii strains exhibiting the virulent PYS (ToxoDB#9) phenotype versus the less virulent PRU (Type II, ToxoDB#1) phenotype. Our aim was to determine protein expression patterns that contribute to the virulence of a particular phenotype...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721831/transient-production-of-recombinant-pharmaceutical-proteins-in-plants-evolution-and-perspectives
#7
Lilya Kopertekh, Joachim Schiemann
During the last two decades the production of pharmaceutical proteins in plants evolved from proof of concept to established technology adopted by several biotechnological companies. This progress is particularly based on intensive research starting stable genetic transformation and moving to transient expression. Due to its advantages in yield and speed of protein production transient expression platforms became leading plant-based manufacturing technology. Current transient expression methods rely on Agrobacterium-mediated delivery of expression vectors into plant cells...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721305/fully-automated-gmp-production-of-68-ga-ga-do3a-vs-cys-40-exendin-4-for-clinical-use
#8
Irina Velikyan, Ulrika Rosenstrom, Olof Eriksson
[(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4/PET-CT targeting glucagon like peptide-1 receptor (GLP-1R) has previously demonstrated its potential clinical value for the detection of insulinomas. The production and accessibility of this radiopharmaceutical is one of the critical factors in realization of clinical trials and routine clinical examinations. Previously, the radiopharmaceutical was prepared manually, however larger scale of clinical trials and healthcare requires automation of the production process in order to limit the operator radiation dose as well as improve tracer manufacturing robustness and on-line documentation for enhanced good manufacturing practice (GMP) compliance...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28708802/characterization-and-expansion-of-autologous-gmp-ready-regulatory-t-cells-for-treg-based-cell-therapy-in-patients-with-ulcerative-colitis
#9
Caroline J Voskens, Anika Fischer, Susanne Roessner, Carmen Lorenz, Simon Hirschmann, Raja Atreya, Clemens Neufert, Imke Atreya, Markus F Neurath, Gerold Schuler
BACKGROUND: A local imbalance between regulatory (Treg) and effector T cells is believed to play a major role in gut-specific inflammation, including ulcerative colitis (UC). Restoration of this balance through an adoptive Treg transfer is an attractive new treatment approach in patients who are refractory to current standard therapies. It was our goal to develop a Good Manufacturing Practices (GMP)-conform protocol for expansion of UC Treg cells as a rational backbone for future studies on Treg therapy in UC...
August 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28707320/homology-model-of-the-human-trna-splicing-ligase-rtcb
#10
Argha Nandy, Patricia Saenz-Mendez, Adrienne M Gorman, Afshin Samali, Leif A Eriksson
RtcB is an essential human tRNA ligase required for ligating the 2',3'-cyclic phosphate and 5'-hydroxyl termini of cleaved tRNA halves during tRNA splicing and XBP1 fragments during endoplasmic reticulum stress. Activation of XBP1 has been implicated in various human tumors including breast cancer. Here we present, for the first time, a homology model of human RtcB (hRtcB) in complex with manganese and covalently bound GMP built from the Pyrococcus horikoshii RtcB (bRtcB) crystal structure, PDB ID 4DWQA. The structure is analyzed in terms of stereochemical quality, folding reliability, secondary structure similarity with bRtcB, druggability of the active site binding pocket and its metal-binding microenvironment...
July 13, 2017: Proteins
https://www.readbyqxmd.com/read/28704171/a-bioluminescent-pseudomonas-aeruginosa-wound-model-reveals-increased-mortality-of-type-1-diabetic-mice-to-biofilm-infection
#11
Agostinho Hunt A M, Gibson J A, Larrivee C L, O'Reilly S, Navitskaya S, Needle D B, Abramovitch R B, Busik J V, Waters C M
OBJECTIVE: To examine how bacterial biofilms, as contributing factors in the delayed closure of chronic wounds in patients with diabetes, affect the healing process. METHOD: We used daily microscopic imaging and the IVIS Spectrum in vivo imaging system to monitor biofilm infections of bioluminescent Pseudomonas aeruginosa and evaluate healing in non-diabetic and streptozotocin-induced diabetic mice. RESULTS: Our studies determined that diabetes alone did not affect the rate of healing of full-depth murine back wounds compared with non-diabetic mice...
July 1, 2017: Journal of Wound Care
https://www.readbyqxmd.com/read/28702321/a-high-content-small-molecule-screen-identifies-novel-inducers-of-definitive-endoderm
#12
Alexander Korostylev, Pallavi U Mahaddalkar, Oliver Keminer, Kamyar Hadian, Kenji Schorpp, Philip Gribbon, Heiko Lickert
OBJECTIVES: Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can generate any given cell type in the human body. One challenge for cell-replacement therapy is the efficient differentiation and expansion of large quantities of progenitor cells from pluripotent stem cells produced under good manufacturing practice (GMP). FOXA2 and SOX17 double positive definitive endoderm (DE) progenitor cells can give rise to all endoderm-derived cell types in the thymus, thyroid, lung, pancreas, liver, and gastrointestinal tract...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28701538/differential-expression-of-long-term-potentiation-among-identified-inhibitory-inputs-to-dopamine-neurons
#13
DeNard V Simmons, Alyssa K Petko, Carlos Antonio Paladini
The in vivo firing pattern of ventral tegmental area (VTA) dopamine neurons is controlled by GABA afferents originating primarily from the nucleus accumbens (NAc), rostromedial tegmental nucleus (RMTg), and from local GABA neurons within the VTA. Although different forms of plasticity have been observed from GABA inputs to VTA dopamine neurons - one dependent on cyclic GMP synthesis, the other dependent on adenylyl cyclase activation - it is unknown whether plasticity is differentially expressed in each. Using an optogenetic strategy, we show that identified inhibitory postsynaptic currents (IPSCs) from local VTA GABA neurons and NAc afferents exhibit a cyclic GMP-dependent long-term potentiation (LTP) that is capable of inhibiting the firing activity of dopamine neurons...
July 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28699788/allogeneic-cell-therapy-manufacturing-process-development-technologies-and-facility-design-options
#14
Saeed Abbasalizadeh, Mohammad Pakzad, Joaquim M S Cabral, Hossein Baharvand
Currently, promising outcomes from clinical trials of allogeneic cells, especially allogeneic mesenchymal stromal cells, fibroblasts, keratinocytes, and human cardiac stem cells, have encouraged research institutions, small and medium enterprises (SMEs), and big pharmaceutical companies to invest and focus on developing allogeneic cell therapy products. Commercial and large-scale production of allogeneic cell therapy products requires unique capabilities to develop technologies that generate safe and effective allogeneic cells/cell lines and their fully characterized master/working banks...
July 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28695374/impact-of-aromaticity-on-anticancer-activity-of-polypyridyl-ruthenium-ii-complexes-synthesis-structure-dna-protein-binding-lipophilicity-and-anticancer-activity
#15
Petar Čanović, Ana Rilak Simović, Snežana Radisavljević, Ioannis Bratsos, Nicola Demitri, Marina Mitrović, Ivanka Zelen, Živadin D Bugarčić
With the aim of assessing how the aromaticity of the inert chelating ligand can influence the activity of ruthenium(II) polypyridyl complexes, two new monofunctional ruthenium(II) complexes, [Ru(Cl-Ph-tpy)(phen)Cl]Cl (1) and [Ru(Cl-Ph-tpy)(o-bqdi)Cl]Cl (2) (where Cl-Ph-tpy = 4'-(4-chlorophenyl)-2,2':6',2″-terpyridine, phen = 1,10-phenanthroline, o-bqdi = o-benzoquinonediimine), were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR, XRD)...
July 10, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28682554/-effects-of-cytosolic-bacteria-on-cyclic-gmp-amp-synthase-expression-in-human-gingival-tissues-and-periodontal-ligament-cells
#16
Yang Xiaojun, Tan Yongmei, Tian Zhihui, Zhou Ting, Zhao Wanghong, Hou Jin
OBJECTIVE: This work aims to determine the effect of cytosolic bacteria on the expression of cyclic GMP-AMP synthase (cGAS) in human periodontal ligament cells (hPDLCs) and gingival tissues. METHODS: The ability of Porphyromonas gingivalis (P. gingivalis) to invade hPDLCs was detected using laser scanning confocal microscope assay at a multiplicity of infection of 10. P. gingivalis-infected cells were sorted by fluorescence-activated cell sorting (FACS). Then, quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect cGAS expression in infected cells...
April 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28682478/water-bridged-h-bonding-network-contributes-to-the-catalysis-of-a-sam-dependent-c-methyltransferase-hcgc
#17
Liping Bai, Tristan Wagner, Tao Xu, Xile Hu, Ulrich Ermler, Seigo Shima
[Fe]-hydrogenase contains the iron-guanylylpyridinol (FeGP) cofactor 1. The FeGP cofactor contains a pyridinol ring substituted by GMP, two methyl and an acylmethyl groups. HcgC, an enzyme of FeGP biosynthesis, catalyzes the methyl transfer from S-adenosylmethionine (SAM) to C3 of 6-carboxymethyl-5-methyl-4-hydroxy-2-pyridinol 2. Here, we report on the ternary structure of HcgC-S-adenosylhomocysteine (SAH, the demethylated product of SAM) and 2 at 1.7 Å resolution. The proximity of C3 of 2 and S of SAH indicates a catalytically productive geometry...
July 6, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28682064/a-very-rare-example-of-a-structurally-characterized-3-gmp-metal-complex-nmr-and-synthetic-assessment-of-adducts-formed-by-guanine-derivatives-with-pt-l-tri-cl-cl-complexes-with-an-n-n-n%C3%A2-tridentate-ligand-l-tri-terminated-by-imidazole-rings
#18
Kokila Ranasinghe, Svetlana Pakhomova, Patricia A Marzilli, Luigi G Marzilli
[Pt(N(R)-1,1'-Me2dma)Cl]Cl complexes with tridentate ligands (bis(1-methyl-2-methylimidazolyl)amine, R = H; N-(methyl)bis(1-methyl-2-methylimidazolyl)amine, R = Me) were prepared in order to investigate Pt(N(R)-1,1'-Me2dma)G adducts (G = monodentate N9-substituted guanine or hypoxanthine derivative). Solution NMR spectroscopy is the primary tool for studying metal complexes of nucleosides and nucleotides because such adducts rarely crystallize. However, [Pt(N(H)-1,1'-Me2dma)(3'-GMPH)]NO3·5H2O (5) was crystallized, allowing, to our knowledge, the first crystallographic molecular structure determination for a 3'-GMP platinum complex...
July 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28681205/dietary-substitution-of-fishmeal-by-alternative-protein-with-guanosine-monophosphate-supplementation-influences-growth-digestibility-blood-chemistry-profile-immunity-and-stress-resistance-of-red-sea-bream-pagrus-major
#19
Md Sakhawat Hossain, Shunsuke Koshio
We determined the effects of complete fishmeal (FM) replacement by alternative protein (soy protein concentrate, SPC) with guanosine monophosphate (GMP) supplementation on growth, digestibility, immunity, blood chemistry profile, and stress resistance of juvenile red sea bream, Pagrus major. FM protein of a FM-based control diet (FM0) was replaced with 33.3 (FM33.3), 66.6 (FM66.7), and 100% (FM100) by SPC protein, and each replacement group was supplemented with 0.4% GMP to formulate four experimental diets...
July 5, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28680857/cyclic-dinucleotides-in-oral-bacteria-and-in-oral-biofilms
#20
Ulvi K Gürsoy, Mervi Gürsoy, Eija Könönen, Herman O Sintim
Oral cavity acts as a reservoir of bacterial pathogens for systemic infections and several oral microorganisms have been linked to systemic diseases. Quorum sensing and cyclic dinucleotides, two "decision-making" signaling systems, communicate to regulate physiological process in bacteria. Discovery of cyclic dinucleotides has a long history, but the progress in our understanding of how cyclic dinucleotides regulate bacterial lifestyle is relatively new. Oral microorganisms form some of the most intricate biofilms, yet c-di-GMP, and c-di-AMP signaling have been rarely studied in oral biofilms...
2017: Frontiers in Cellular and Infection Microbiology
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