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https://www.readbyqxmd.com/read/28716651/significance-of-a-to-i-rna-editing-of-transcripts-modulating-pharmacokinetics-and-pharmacodynamics
#1
REVIEW
Masataka Nakano, Miki Nakajima
RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts to generate transcriptome diversity. Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. Inosine forms a base pair with cytidine as if it were guanosine; therefore, the conversion may affect the amino acid sequence, splicing, microRNA targeting, and miRNA maturation...
July 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#2
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28711565/new-aspects-of-molecular-imaging-in-prostate-cancer
#3
Francesco Ceci, Paolo Castellucci, Juliano J Cerci, Stefano Fanti
Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging...
July 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28710530/proteomic-characterisation-reveals-active-wnt-signalling-by-human-multipotent-stromal-cells-as-a-key-regulator-of-beta-cell-survival-and-proliferation
#4
Miljan Kuljanin, Gillian I Bell, Stephen E Sherman, Gilles A Lajoie, David A Hess
AIMS/HYPOTHESIS: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. METHODS: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC(R)) vs nonregenerative (MSC(NR)) capacity...
July 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28709077/phytonanotherapy-for-management-of-diabetes-using-green-synthesis-nanoparticles
#5
K Anand, C Tiloke, Pragalathan Naidoo, A A Chuturgoon
The world has a rich diversity of indigenous medicinal plants. The World Health Organization (WHO) gives high priority to eco-friendly, non-hazardous and cost effective healthcare such as the use of medicinal plants to treat various illnesses, including Human immunodeficiency virus (HIV) infection and Acquired immune deficiency syndrome (AIDS), tuberculosis (TB), diabetes mellitus (DM), malaria, and cancer. In developing countries, a high proportion of the population tends to use complementary and alternative medicines (CAM) together with conventional prescription drugs...
June 27, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28708592/a-peptidomimetic-with-a-chiral-switch-is-an-inhibitor-of-epidermal-growth-factor-receptor-heterodimerization
#6
Shanthi P Kanthala, Yong-Yu Liu, Sitanshu Singh, Rushikesh Sable, Sandeep Pallerla, Seetharama D Jois
Among different types of EGFR dimers, EGFR-HER2 and HER2-HER3 are well known in different types of cancers. Targeting dimerization of EGFR will have a significant impact on cancer therapies. A symmetric peptidomimetic was designed to inhibit the protein-protein interaction of EGFR. The peptidomimetic (Cyclo(1,10)PpR (R) Anapa-FDDF-(R)-Anapa)R, compound 18) was shown to exhibit antiproliferative activity with an IC50 of 194 nM in HER2-expressing breast cancer cell lines and 18 nM in lung cancer cell lines. The peptidomimetic has a Pro-Pro sequence in the structure to stabilize the β-turn and a β-amino acid, amino napthyl propionic acid...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704807/high-sensitivity-troponin-t-and-nt-probnp-kinetics-in-breast-cancer-chemotherapy
#7
Pooja Advani, Jonathan Hoyne, Alvaro Moreno-Aspita, Marcia Dubin, Shelly Brock, Caroline Harlow, Saranya Chumsri, Thomas Suter, Joseph L Blackshear
BACKGROUND/AIMS: Doxorubicin (DOX) and trastuzumab (TRA) are associated with cardiac dysfunction. METHOD: High-sensitivity troponin T (hs-TnT) and brain natriuretic peptide attached to the amino acid N-terminal fragment in the prohormone (NT-proBNP) were measured before and on days +1, +2, +3, and +7 during cycles 1 and 2 of therapy with DOX or TRA in breast cancer patients. RESULTS: Five of eleven DOX-treated women, compared with 2/11 TRA-treated women, had undetectable baseline hs-TnT...
July 14, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28700715/the-pharmacological-and-non-pharmacological-treatment-of-attention-deficit-hyperactivity-disorder-in-children-and-adolescents-a-systematic-review-with-network-meta-analyses-of-randomised-trials
#8
Ferrán Catalá-López, Brian Hutton, Amparo Núñez-Beltrán, Matthew J Page, Manuel Ridao, Diego Macías Saint-Gerons, Miguel A Catalá, Rafael Tabarés-Seisdedos, David Moher
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. METHODS AND FINDINGS: We performed a systematic review with network meta-analyses...
2017: PloS One
https://www.readbyqxmd.com/read/28699354/drug-mediated-intracellular-donation-of-nitric-oxide-potently-inhibits-5-lipoxygenase-a-possible-key-to-future-anti-leukotriene-therapy
#9
Jessica Roos, Marcus Peters, Isabelle V Maucher, Benjamin Kühn, Jasmin Fettel, Nadine Hellmuth, Camilla Brat, Benita Sommer, Anja Urbschat, Matthias Piesche, Anja Vogel, Ewgenij Proschak, René Blöcher, Estel la Buscato, Ann-Kathrin Häfner, Carmela Matrone, Oliver Werz, Juliana Heidler, Ilka Wittig, Carlo Angioni, Gerd Geisslinger, Michael J Parnham, Kai Zacharowski, Dieter Steinhilber, Thorsten Jürgen Maier
AIMS: 5-lipoxygenase (5-LO) is the key enzyme of leukotriene biosynthesis and is critically involved in a number of inflammatory diseases such as arthritis, gout, bronchial asthma, atherosclerosis and cancer. Because 5-LO contains critical nucleophilic amino acids, which are sensitive to electrophilic modifications, we determined the consequences of a drug-mediated intracellular release of nitric oxide (NO) on 5-LO product formation by human granulocytes and on 5-LO-dependent pulmonary inflammation in vivo...
July 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28698587/a-novel-dual-eigen-analysis-of-mouse-multi-tissues-expression-profiles-unveils-new-perspectives-into-type-2-diabetes
#10
Lei M Li, Xiuxiu Liu, Lin Wang, Yong Wang, Xiuqin Liu, Xue Tian, Fuzhou Gong, Li Shen, Xiao-Ding Peng
Type 2 diabetes (T2D) is a complex and polygenic disease yet in need of a complete picture of its development mechanisms. To better understand the mechanisms, we examined gene expression profiles of multi-tissues from outbred mice fed with a high-fat diet (HFD) or regular chow at weeks 1, 9, and 18. To analyze such complex data, we proposed a novel dual eigen-analysis, in which the sample- and gene-eigenvectors correspond respectively to the macro- and micro-biology information. The dual eigen-analysis identified the HFD eigenvectors as well as the endogenous eigenvectors for each tissue...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696185/in-vitro-evaluation-of-antisense-oligonucleotide-functionalized-core-shell-nanoparticles-loaded-with-%C3%AE-tocopherol-succinate
#11
Ebru Kilicay, Zeynep Karahaliloglu, Pınar Alpaslan, Baki Hazer, Emir Baki Denkbas
Antisense oligonucleotide (ASO)-conjugated-α-tocopherol succinate (TCS)-loaded-poly(lactic acid)-g-poly(ethylene glycol) nanoparticles (ASO-TCS-PLA-PEG NPs), with the ratio of polymer/TCS of 10:2.5, 10:5, 10:7 (w/w) were prepared for targeting cancer therapy. The amphiphilic PLA, amino terminated PEG graft copolymers were synthesized by ring opening polymerization reaction. Nanoparticles were produced by using double emulsion (w/o/w) solvent evaporation method. ASO-TCS-PLA-PEG NPs demonstrated satisfactory encapsulation and loading efficiency and size distribution...
July 11, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28694566/antifungal-resistance-metabolic-routes-as-drug-targets-and-new-antifungal-agents-an-overview-about-endemic-dimorphic-fungi
#12
REVIEW
Juliana Alves Parente-Rocha, Alexandre Melo Bailão, André Correa Amaral, Carlos Pelleschi Taborda, Juliano Domiraci Paccez, Clayton Luiz Borges, Maristela Pereira
Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28694032/biodegradable-brain-penetrating-dna-nanocomplexes-and-their-use-to-treat-malignant-brain-tumors
#13
Panagiotis Mastorakos, Clark Zhang, Eric Song, Young Eun Kim, Hee Won Park, Sneha Berry, Won Kyu Choi, Justin Hanes, Jung Soo Suk
The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats...
July 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28687338/replicative-dna-polymerase-defects-in-human-cancers-consequences-mechanisms-and-implications-for-therapy
#14
REVIEW
Stephanie R Barbari, Polina V Shcherbakova
The fidelity of DNA replication relies on three error avoidance mechanisms acting in series: nucleotide selectivity of replicative DNA polymerases, exonucleolytic proofreading, and post-replicative DNA mismatch repair (MMR). MMR defects are well known to be associated with increased cancer incidence. Due to advances in DNA sequencing technologies, the past several years have witnessed a long-predicted discovery of replicative DNA polymerase defects in sporadic and hereditary human cancers. The polymerase mutations preferentially affect conserved amino acid residues in the exonuclease domain and occur in tumors with an extremely high mutation load...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28686288/distribution-of-cyp2c8-and-cyp2c9-amino-acid-substitution-alleles-in-south-indian-diabetes-patients-a-genotypic-and-computational-protein-phenotype-study
#15
Durga Koteswara Rao, Dwarakanath K Murthy, Nazia Sultana Shaik, Babajan Banaganapalli, Kumar Swami Konda, Hanumantha P Rao, Eswar Ganti, Ahmed A Zuheir, Ashraf El-Harouni, Ramu Elango, Imran Ali Khan, Noor Ahmad Shaik
The CYP2C8 and CYP2C9 are two major isoforms of the cytochrome P450 enzyme family, which is involved in drug response, detoxification, and disease development. This study describes the differential distribution of amino acid substitution variants of CYP2C8 (*2-I269F & *3-R139K) and CYP2C9 (*2-C144R & *3-L359A) genes in 234 type 2 diabetes mellitus (T2DM) patients and 218 healthy controls from Andhra Pradesh, South India. Single locus genotype analysis has revealed that homozygous recessive genotypes of 2C8*2-TT (p=<0...
July 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28685675/the-beneficial-effects-of-sulfur-containing-amino-acids-on-cisplatin-induced-cardiotoxicity-and-neurotoxicity-in-rodents
#16
Gvozden Rosic, Jovana Joksimovic, Dragica Selakovic, Vladimir Jakovljevic, Vladimir Zivkovic, Ivan Srejovic, Marko Djuric, Dragan Djuric
Cisplatin is one the most frequently used chemotherapeutic drugs for several decades. Although its antineoplastic effect has been reported in treatment of numerous malignances, various adverse effects seem to be the crucial limiting factor for its administration. Beside the most commonly described nephro- and hepatotoxicity, cisplatin therapy is also accompanied with gastrointestinal, reproductive, hematological, cardiovascular and neurological side effects. Since it has been reported that cisplatin induce oxidative damage in various tissues (by means of altered ROS production, as well as by depletion of antioxidants), it seems reasonable that huge efforts had been put in the investigations of antioxidant supplementation as potential therapeutical approach for attenuation of cisplatin toxicities...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28683086/phosphorylation-of-the-hiv-1-capsid-by-melk-triggers-uncoating-to-promote-viral-cdna-synthesis
#17
Hiroaki Takeuchi, Hideki Saito, Takeshi Noda, Tadashi Miyamoto, Tomokazu Yoshinaga, Kazutaka Terahara, Hiroshi Ishii, Yasuko Tsunetsugu-Yokota, Shoji Yamaoka
Regulation of capsid disassembly is crucial for efficient HIV-1 cDNA synthesis after entry, yet host factors involved in this process remain largely unknown. Here, we employ genetic screening of human T-cells to identify maternal embryonic leucine zipper kinase (MELK) as a host factor required for optimal uncoating of the HIV-1 core to promote viral cDNA synthesis. Depletion of MELK inhibited HIV-1 cDNA synthesis with a concomitant delay of capsid disassembly. MELK phosphorylated Ser-149 of the capsid in the multimerized HIV-1 core, and a mutant virus carrying a phosphorylation-mimetic amino-acid substitution of Ser-149 underwent premature capsid disassembly and earlier HIV-1 cDNA synthesis, and eventually failed to enter the nucleus...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28679290/gene-therapy-using-a-minicep290-fragment-delays-photoreceptor-degeneration-in-a-mouse-model-of-leber-congenital-amaurosis-lca
#18
Wei Zhang, Linjing Li, Qin Su, Guangping Gao, Hemant Khanna
Mutations in the cilia-centrosomal protein CEP290 are most frequently observed in autosomal recessive childhood blindness disorder Leber congenital amaurosis (LCA). No treatment or cure currently exists for this disorder. The Cep290rd16 (retinal degeneration 16) (a mouse model of LCA) carries a mutation in the Cep290 gene, which leads to shorter cilia formation and defective photoreceptor structure and function. A roadblock to developing a gene replacement strategy for CEP290 using conventional Adeno-associated Virus (AAV) vectors is its large size...
July 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28670936/identification-and-characterization-of-erbb4-kinase-inhibitors-for-effective-breast-cancer-therapy
#19
Ankita Sahu, P K Patra, Manoj Kumar Yadav, Meena Varma
The overexpression of ErbB4 is associated with aggressive disease biology and reduced the survival of breast cancer patients. We have used ErbB4 receptor as a novel drug target to spearhead the rational drug design. The present study is divided into two parts. In the first part, we have exploited the hidden information inside ErbB4 kinase receptor both at sequence and structural level. PSI-BLAST algorithm is used to search similar sequences against ErbB4 kinase sequence. Top 15 sequences with high identity were selected for finding conserved and variable regions among sequences using multiple sequence alignment...
July 3, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28670301/a-novel-approach-for-combating-klebsiella-pneumoniae-biofilm-using-histidine-functionalized-silver-nanoparticles
#20
Sanjay Chhibber, Vijay S Gondil, Samrita Sharma, Munish Kumar, Nishima Wangoo, Rohit K Sharma
Treating pathogens is becoming challenging because of multidrug resistance and availability of limited alternative therapies which has further confounded this problem. The situation becomes more alarming when multidrug resistant pathogens form a 3D structure known as biofilm. Biofilms are formed in most of the infections especially in chronic infections where it is difficult to eradicate them by conventional antibiotic therapy. Chemically synthesized nanoparticles are known to have antibiofilm activity but in the present study, an attempt was made to use amino acid functionalized silver nanoparticles alone and in combination with gentamicin to eradicate Klebsiella pneumoniae biofilm...
2017: Frontiers in Microbiology
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