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https://www.readbyqxmd.com/read/28526447/toxicity-screening-of-a-novel-poly-methylmethacrylate-eudragit-nanocarrier-on-l929-fibroblasts
#1
Diogo Graça, Henriqueta Louro, Joana Santos, Kamila Dias, Lídia Gonçalves, António Almeida, Maria João Silva, Ana Bettencourt
Toxicity screening of a novel poly(methylmethacrylate)-Eudragit nanocarrier on L929 fibroblasts Translation of innovative drug delivery nanosystems into the market involves an early toxicity screening in the development phase. Previously, we showed that inclusion of the polymer (Eudragit, EUD) into poly(methylmethacrylate) (PMMA) nanoparticles (NP) resulted in a novel nanocarrier (PMMA-EUD) with an improved biomedical performance. The safety of this novel nanoparticulate system (PMMA-EUDNPs) was assessed in this work and compared to that of the original PMMANPs by using an integrated approach, comprising in vitro toxicity assessment and NPs physicochemical characterization in water and cell medium...
May 16, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28524929/xeno-free-cultivation-of-mesenchymal-stem-cells-from-the-corneal-stroma
#2
Steffi Matthyssen, Sorcha Ní Dhubhghaill, Veerle Van Gerwen, Nadia Zakaria
Purpose: The human cornea has recently been described as a source of corneal stroma-derived mesenchymal stem cells (hMSCs). In vitro expansion of these cells involves basal medium supplemented with fetal bovine serum (FBS). As animal-derived serum can confer a risk of disease transmission and can be subject to considerable lot-to-lot variability, it does not comply with newer Good Manufacturing Practice (GMP)-required animal component-free culture protocols for clinical translation. Methods: This study investigated animal-free alternatives to FBS for cultivation of human corneal stromal MSCs...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28523560/stem-cell-technology-for-epi-genetic-brain-disorders
#3
Renzo J M Riemens, Edilene S Soares, Manel Esteller, Raul Delgado-Morales
Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28522696/apolipoprotein-a-i-mimetic-peptides-discordance-between-in-vitro-and-in-vivo-properties
#4
Michael Ditiatkovski, Jonatan Palsson, Jaye Chin-Dusting, Alan T Remaley, Dmitri Sviridov
OBJECTIVE: Apolipoprotein A-I (apoA-I) mimetic peptides have antiatherogenic properties of high-density lipoprotein in vitro and have been shown to inhibit atherosclerosis in vivo. It is unclear, however, if each in vitro antiatherogenic property of these peptides translates to a corresponding activity in vivo, and if so, which of these contributes most to reduce atherosclerosis. APPROACH AND RESULTS: The effect of 7 apoA-I mimetic peptides, which were developed to selectively reproduce a specific component of the antiatherogenic properties of apoA-I, on the development of atherosclerosis was investigated in apolipoprotein E-deficient mice fed a high-fat diet for 4 or 12 weeks...
May 18, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28521475/microrna-1258-an-invasion-and-metastasis-regulator-that-targets-heparanase-in-gastric-cancer
#5
Jinxin Shi, Ping Chen, Jingxu Sun, Yongxi Song, Bin Ma, Peng Gao, Xiaowan Chen, Zhenning Wang
Numerous microRNAs (miRNAs/miRs) are involved in suppressing or promoting the formation of cancer. However, to the best of our knowledge, the role of miRNA-1258 in gastric cancer (GC) has not previously been investigated. Our previous study demonstrated an increased expression of heparanase (HPSE) in GC tissues and HPSE-facilitated invasion and metastasis of GC cells. Consequently, in the present study, the function of miR-1258 in the invasion and metastasis of GC cells was investigated to determine whether miR-1258 is associated with GC through HPSE...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520932/translational-control-and-rho-dependent-transcription-termination-are-intimately-linked-in-riboswitch-regulation
#6
Laurène Bastet, Adrien Chauvier, Navjot Singh, Antony Lussier, Anne-Marie Lamontagne, Karine Prévost, Eric Massé, Joseph T Wade, Daniel A Lafontaine
Riboswitches are regulatory elements that control gene expression by altering RNA structure upon the binding of specific metabolites. Although Bacillus subtilis riboswitches have been shown to control premature transcription termination, less is known about regulatory mechanisms employed by Escherichia coli riboswitches, which are predicted to regulate mostly at the level of translation initiation. Here, we present experimental evidence suggesting that the majority of known E. coli riboswitches control transcription termination by using the Rho transcription factor...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520920/methylation-of-human-eukaryotic-elongation-factor-alpha-eef1a-by-a-member-of-a-novel-protein-lysine-methyltransferase-family-modulates-mrna-translation
#7
Magnus E Jakobsson, Jedrzej Malecki, Benedikt S Nilges, Anders Moen, Sebastian A Leidel, Pål Ø Falnes
Many cellular proteins are methylated on lysine residues and this has been most intensively studied for histone proteins. Lysine methylations on non-histone proteins are also frequent, but in most cases the functional significance of the methylation event, as well as the identity of the responsible lysine (K) specific methyltransferase (KMT), remain unknown. Several recently discovered KMTs belong to the so-called seven-β-strand (7BS) class of MTases and we have here investigated an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520526/kir3dl1-hl-a-b-subtypes-govern-acute-myelogenous-leukemia-relapse-after-hematopoietic-cell-transplantation
#8
Jeanette E Boudreau, Fabio Giglio, Ted A Gooley, Philip A Stevenson, Jean-Benoît Le Luduec, Brian C Shaffer, Raja Rajalingam, Lihua Hou, Carolyn Katovich Hurley, Harriet Noreen, Elaine F Reed, Neng Yu, Cynthia Vierra-Green, Michael Haagenson, Mari Malkki, Effie W Petersdorf, Stephen Spellman, Katharine C Hsu
Purpose Disease relapse remains a major challenge to successful outcomes in patients who undergo allogeneic hematopoietic cell transplantation (HCT). Donor natural killer (NK) cell alloreactivity in HCT can control leukemic relapse, but capturing alloreactivity in HLA-matched HCT has been elusive. HLA expression on leukemia cells-upregulated in the post-HCT environment-signals for NK cell inhibition via inhibitory killer immunoglobulin-like (KIR) receptors and interrupts their antitumor activity. We hypothesized that varied strengths of inhibition among subtypes of the ubiquitous KIR3DL1 and its cognate ligand, HLA-B, would titrate NK reactivity against acute myelogenous leukemia (AML)...
May 18, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28518085/analysis-of-chromosome-segregation-histone-acetylation-and-spindle-morphology-in-horse-oocytes
#9
Federica Franciosi, Irene Tessaro, Rozenn Dalbies-Tran, Cecile Douet, Fabrice Reigner, Stefan Deleuze, Pascal Papillier, Ileana Miclea, Valentina Lodde, Alberto M Luciano, Ghylene Goudet
The field of assisted reproduction has been developed to treat infertility in women, companion animals, and endangered species. In the horse, assisted reproduction also allows for the production of embryos from high performers without interrupting their sports career and contributes to an increase in the number of foals from mares of high genetic value. The present manuscript describes the procedures used for collecting immature and mature oocytes from horse ovaries using ovum pick-up (OPU). These oocytes were then used to investigate the incidence of aneuploidy by adapting a protocol previously developed in mice...
May 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28517015/genetic-incorporation-of-4-fluorohistidine-into-peptides-enables-selective-affinity-purification
#10
Christine M Ring, Emil S Iqbal, David E Hacker, Matthew C T Hartman, T Ashton Cropp
Due to the lowered pKa of 4-fluorohistidine relative to histidine, peptides and proteins containing this amino acid are potentially endowed with novel properties. We report here the optimized synthesis of 4-fluorohistidine and show that it can efficiently replace histidine in in vitro translation reactions. Moreover, peptides containing 6×-fluorohistidine tags are able to be selectively captured and eluted from nickel resin in the presence of his-tagged protein mixtures.
May 18, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28516119/affinity-pulldown-of-biotinylated-rna-for-detection-of-protein-rna-complexes
#11
Amaresh C Panda, Jennifer L Martindale, Myriam Gorospe
RNA-binding proteins (RBPs) have recently emerged as crucial players in the regulation of gene expression. The interactions of RBPs with target mRNAs control the levels of gene products by altering different regulatory steps, including pre-mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and translation (Glisovic et al., 2008). There are several methodologies available today to identify RNAs bound to specific RBPs; some detect only recombinant molecules in vitro, others detect recombinant and endogenous molecules, while others detect only endogenous molecules...
December 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515792/mesenchymal-stem-cell-therapy-in-type-2-diabetes-mellitus
#12
REVIEW
Li Zang, Haojie Hao, Jiejie Liu, Yijun Li, Weidong Han, Yiming Mu
Type 2 diabetes mellitus (T2DM), which is characterized by the combination of relative insulin deficiency and insulin resistance, cannot be reversed with existing therapeutic strategies. Transplantation of insulin-producing cells (IPCs) was once thought to be the most promising strategy for treating diabetes, but the pace from the laboratory to clinical application has been obstructed due to its drawbacks. Mesenchymal stem cells (MSCs) harbor differentiation potential, immunosuppressive properties, and anti-inflammatory effects, and they are considered an ideal candidate cell type for treatment of DM...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28515298/crimean-congo-hemorrhagic-fever-virus-nucleocapsid-protein-augments-mrna-translation
#13
Subbiah Jeeva, Erdong Cheng, Safder S Ganaie, Mohammad A Mir
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' UTR with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28515001/in-vitro-extracellular-matrix-accumulation-of-nasal-and-articular-chondrocytes-for-intervertebral-disc-repair
#14
S Vedicherla, C T Buckley
Chondrocyte based regenerative therapies for intervertebral disc repair such as Autologous Disc Cell Transplantation (ADCT, CODON) and allogeneic juvenile chondrocyte implantation (NuQu(®), ISTO Technologies) have demonstrated good outcomes in clinical trials. However concerns remain with the supply demand reconciliation and issues surrounding immunoreactivity which exist for allogeneic-type technologies. The use of stem cells is challenging due to high growth factor requirements, regulatory barriers and differentiation towards a stable phenotype...
May 8, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28514734/inflammatory-microrna-194-and-515-attenuate-the-biosynthesis-of-chondroitin-sulfate-during-human-intervertebral-disc-degeneration
#15
Bo Hu, Chen Xu, Ye Tian, Changgui Shi, Ying Zhang, Lianfu Deng, Hongyu Zhou, Peng Cao, Huajiang Chen, Wen Yuan
Intervertebral disc degeneration (IDD) is characterized by dehydration and loss of extracellular matrixes in the nucleus pulposus region. Chondroitin sulfate has been found to be the water-binding molecule that played a key role in IDD. Although investigators have reported that inflammatory cytokines are involved in the reduction of chondroitin sulfate in IDD, but the underlying mechanism is unrevealed. Since chondroitin sulfate synthesis is controlled by chondroitin sulfate glycosyltransferases CHSY-1/2/3 and CSGALNACT-1/2, their functional role and regulatory mechanism in IDD is not fully studied...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512690/translational-studies-on-a-ready-to-use-intramuscular-injection-of-penethamate-for-bovine-mastitis
#16
I G Tucker, R Jain, F Alawi, K Nanjan, O Bork
Bovine mastitis caused by bacterial infections of the mammary gland (udder) of dairy cows is a costly pathology for the dairy industry due to direct and indirect losses in production. Penethamate, a pro-drug of benzylpenicillin, is used by intramuscular injection (IM). The existing products are powders which must be reconstituted in water-for-injection and this presents difficulties in the field. Penethamate is too unstable to be formulated as an aqueous formulation but a chemically stable suspension formulation was possible in certain oils; however, some literature suggests that such formulations would have unacceptable prolonged release...
May 16, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28510127/negative-sense-virion-rna-of-segment-8-ns-of-influenza-a-virus-is-able-to-translate-in-vitro-a-new-viral-protein
#17
O P Zhirnov, K A Akulich, A V Lipatova, E V Usachev
It was shown that full-length virion RNA of segment 8 of influenza virus A/Aichi/2/68 (H3N2) can initiate the synthesis of two major polypeptides with molecular weights of 23 and 13 kD and a minor polypeptide with a molecular weight of 19 kDa, which specifically reacted with the antibodies to the 30-membered peptide of the central part of the NSP protein of influenza A virus. Thus, the genomic-polarity RNA of segment 8 of influenza virus A has a translational template function. These data provide further confirmation of the concept of the bipolar (ambisens) strategy of functioning of the influenza A virus genome...
March 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28509685/modelling-acute-traumatic-haemorrhagic-shock-injury-challenges-and-guidelines-for-preclinical-studies
#18
Jordi L Tremoleda, Sarah A Watts, Penny S Reynolds, Christoph Thiemermann, Karim Brohi
Trauma is responsible for a large proportion of the world's burden of disease, and is by far the biggest killer of young adults. Haemorrhage is the leading cause of preventable death and its effects are directly correlated with the incidence multi-organ failure in survivors. Trauma research is challenging due to patient heterogeneity, limited randomised controlled trials, and in vitro studies that fail to mimic the systemic injury response. Preclinical research remains essential for mechanistic and therapeutic discovery...
May 15, 2017: Shock
https://www.readbyqxmd.com/read/28507812/a-barf1-specific-mab-as-a-new-immunotherapeutic-tool-for-the-management-of-ebv-related-tumors
#19
Riccardo Turrini, Anna Merlo, Debora Martorelli, Damiana Antonia Faè, Roberta Sommaggio, Isabella Monia Montagner, Vito Barbieri, Oriano Marin, Paola Zanovello, Riccardo Dolcetti, Antonio Rosato
The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507282/p53-suppresses-ribonucleotide-reductase-via-inhibiting-mtorc1
#20
Zhengfu He, Xing Hu, Weijin Liu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055...
April 26, 2017: Oncotarget
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