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https://www.readbyqxmd.com/read/29139136/tilmicosin-and-florfenicol-loaded-hydrogenated-castor-oil-solid-lipid-nanoparticles-to-pigs-combined-antibacterial-activities-and-pharmacokinetics
#1
Z Ling, L Yonghong, L Junfeng, Z Li, L Xianqiang
The combined antibacterial effects of tilmicosin (TIL) and florfenicol (FF) against Actinobacillus pleuropneumoniae (APP) (n = 2), Streptococcus suis (S. suis) (n = 2), and Haemophilus parasuis (HPS) (n = 2) were evaluated by chekerboard test and time-kill assays. The pharmacokinetics (PKs) of TIL- and FF-loaded hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) were performed in healthy pigs. The results indicated that TIL and FF showed synergistic or additive antibacterial activities against APP, S...
November 15, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29128308/oxidative-stress-and-dna-damage-after-cerebral-ischemia-potential-therapeutic-targets-to-preserve-the-genome-and-improve-stroke-recovery
#2
REVIEW
Peiying Li, R Anne Stetler, Rehana K Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V L Bennett, Jun Chen
The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ)...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29121987/sequence-analysis-and-characterization-of-pyruvate-kinase-from-clonorchis-sinensis-a-53-1-kda-homopentamer-implicated-immune-protective-efficacy-against-clonorchiasis
#3
Tingjin Chen, Hongye Jiang, Hengchang Sun, Zhizhi Xie, Pengli Ren, Lu Zhao, Huimin Dong, Mengchen Shi, Zhiyue Lv, Zhongdao Wu, Xuerong Li, Xinbing Yu, Yan Huang, Jin Xu
BACKGROUND: Clonorchis sinensis, the causative agent of clonorchiasis, is classified as one of the most neglected tropical diseases and affects more than 15 million people globally. This hepatobiliary disease is highly associated with cholangiocarcinoma. As key molecules in the infectivity and subsistence of trematodes, glycolytic enzymes have been targets for drug and vaccine development. Clonorchis sinensis pyruvate kinase (CsPK), a crucial glycolytic enzyme, was characterized in this research...
November 9, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29112783/toblerols-cyclopropanol-containing-modulators-of-methylobacterial-antibiosis-generated-by-an-unusual-polyketide-synthase
#4
Reiko Ueoka, Miriam Bortfeld-Miller, Brandon Isamu Morinaka, Julia Anne Vorholt, Jörn Piel
Trans-AT polyketide synthases (PKSs) are biosynthetically versatile enzymes that generate bioactive polyketides of high structural diversity. In this study, we detected in the genome of several bacteria a cryptic, unusual trans-AT PKS gene cluster that eluded automated PKS prediction. Genomic mining of one of these strains, the model methylotroph Methylobacterium extorquens AM1, revealed epoxide-cyclopropanol-containing polyketides named toblerols. The stereochemistry was determined by NMR, chemical derivatization, and the comparison of CD data with those of a synthesized model compound...
November 7, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29108355/a-phase-i-clinical-trial-of-binimetinib-in-combination-with-folfox-in-patients-with-advanced-metastatic-colorectal-cancer-who-failed-prior-standard-therapy
#5
May Cho, Jun Gong, Paul Frankel, Timothy W Synold, Dean Lim, Vincent Chung, Joseph Chao, Daneng Li, Yuan Chen, Stephen Sentovich, Kurt Melstrom, Gagandeep Singh, Eloise Luevanos, Marwan Fakih
Background: This was a first in-human, open-label, dose-escalation phase I study conducted to evaluate the maximum tolerated dose (MTD), safety, and efficacy of the combination of oral binimetinib and FOLFOX. Materials and Methods: Patients with metastatic colorectal cancer (mCRC) who progressed on prior standard therapies received twice daily binimetinib continuously or intermittently with FOLFOX. Dose-limiting toxicities (DLTs) were assessed in the first 2 cycles of study treatment...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108108/antibacterial-aryl-crowned-polyketide-from-bacillus-subtilis-associated-with-seaweed-anthophycus-longifolius
#6
Kajal Chakraborty, Bini Thilakan, Vinaya Kizhakkepatt Kizhakkekalam
AIMS: Microbiological, biotechnological and chemical characterization of a previously undescribed aryl-crowned polyketide from Bacillus subtilis MTCC 10403 isolated from brown seaweed Anthophycus longifolius with activity against opportunistic Gram-negative food-borne pathogenic bacterial strains. METHODS AND RESULTS: A culture-dependent method was used to isolate heterotrophic B. subtilis associated with A. longifolius, and assessed for its antimicrobial properties...
November 6, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29104824/comparative-genomic-analysis-of-the-pks-genes-in-five-species-and-expression-analysis-in-upland-cotton
#7
Xueqiang Su, Xu Sun, Xi Cheng, Yanan Wang, Muhammad Abdullah, Manli Li, Dahui Li, Junshan Gao, Yongping Cai, Yi Lin
Plant type III polyketide synthase (PKS) can catalyse the formation of a series of secondary metabolites with different structures and different biological functions; the enzyme plays an important role in plant growth, development and resistance to stress. At present, the PKS gene has been identified and studied in a variety of plants. Here, we identified 11 PKS genes from upland cotton (Gossypium hirsutum) and compared them with 41 PKS genes in Populus tremula, Vitis vinifera, Malus domestica and Arabidopsis thaliana...
2017: PeerJ
https://www.readbyqxmd.com/read/29101453/endophytic-paraconiothyrium-sp-from-zingiber-officinale-rosc-displays-broad-spectrum-antimicrobial-activity-by-production-of-danthron
#8
C Anisha, P Sachidanandan, E K Radhakrishnan
The bioactivity spectrum of fungal endophytes isolated from Zingiber officinale was analyzed against clinical pathogens and against the phytopathogen Pythium myriotylum, which causes Pythium rot in ginger. One of the isolates GFM13 showed broad bioactivity against various pathogens tested including P. myriotylum. The spore suspension as well as the culture filtrate of the endophytic fungal isolate was found to effectively protect ginger rhizomes from Pythium rot. By molecular identification, the fungal endophyte was identified as Paraconiothyrium sp...
November 3, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29097006/kisspeptin-recombinant-oral-vaccine-a-master-gene-vaccine-inhibiting-the-reproductive-physiology-and-behavior-of-ram-lambs
#9
Birhanu Tesema, Jia-Yu Zhao, Xun-Pin Jiang, Gui-Qiang Liu, Yan-Guo Han, Teketay Wassie
The KISS1 gene product, kisspeptin, stimulates gonadotrophic steroid hormone (GNRH) neuronal signaling through the G-protein coupled receptor, kiss1r. Disturbance of this signaling pathway causes hypogonadotropic hypogonadism in mammals. As part of this cutting-edge research project, we analyzed the efficacy of an oral kisspeptin recombinant vaccine on the reproductive physiology and behavior of ram lambs. Ten 56-day old ram lambs were randomly divided into treatment and control groups to receive the experimental recombinant vaccines, C500/pKS-asd or C500/pVAX-asd (aspartate-β semialdehyde dehydrogenase), respectively...
October 31, 2017: Vaccine
https://www.readbyqxmd.com/read/29073267/comparative-genomics-of-geographically-distant-fusarium-fujikuroi-isolates-revealed-two-distinct-pathotypes-correlating-with-secondary-metabolite-profiles
#10
COMPARATIVE STUDY
Eva-Maria Niehaus, Hee-Kyoung Kim, Martin Münsterkötter, Slavica Janevska, Birgit Arndt, Svetlana A Kalinina, Petra M Houterman, Il-Pyung Ahn, Ilaria Alberti, Stefano Tonti, Da-Woon Kim, Christian M K Sieber, Hans-Ulrich Humpf, Sung-Hwan Yun, Ulrich Güldener, Bettina Tudzynski
Fusarium fujikuroi causes bakanae ("foolish seedling") disease of rice which is characterized by hyper-elongation of seedlings resulting from production of gibberellic acids (GAs) by the fungus. This plant pathogen is also known for production of harmful mycotoxins, such as fusarins, fusaric acid, apicidin F and beauvericin. Recently, we generated the first de novo genome sequence of F. fujikuroi strain IMI 58289 combined with extensive transcriptional, epigenetic, proteomic and chemical product analyses. GA production was shown to provide a selective advantage during infection of the preferred host plant rice...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29066863/pharmacokinetic-and-safety-evaluation-of-mb12066-an-nqo1-substrate
#11
Hae Won Lee, Sook Jin Seong, Boram Ohk, Woo Youl Kang, Mi-Ri Gwon, Bo Kyung Kim, Hyun-Ju Kim, Young-Ran Yoon
OBJECTIVE: This study evaluated the pharmacokinetics (PKs) and safety of a newly developed β-lapachone (MB12066) tablet, a natural NAD(P)H:quinone oxidoreductase 1 (NQO1) substrate, in healthy male volunteers. METHODS: In a randomized, double-blind, multiple-dose, two-treatment study, 100 mg MB12066 or placebo was given twice daily for 8 days to groups of eight or three fasted healthy male subjects, respectively, followed by serial blood sampling. Plasma concentrations for β-lapachone were determined using liquid chromatography-tandem mass spectrometry...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29049321/determination-and-production-of-antimicrobial-compounds-by-aspergillus-clavatonanicus-strain-mj31-an-endophytic-fungus-from-mirabilis-jalapa-l-using-uplc-esi-ms-ms-and-td-gc-ms-analysis
#12
Vineet Kumar Mishra, Ajit Kumar Passari, Preeti Chandra, Vincent Vineeth Leo, Brijesh Kumar, Sivakumar Uthandi, Sugitha Thankappan, Vijai Kumar Gupta, Bhim Pratap Singh
Endophytic fungi associated with medicinal plants are reported as potent producers of diverse classes of secondary metabolites. In the present study, an endophytic fungi, Aspergillus clavatonanicus strain MJ31, exhibiting significant antimicrobial activity was isolated from roots of Mirabilis jalapa L., was identified by sequencing three nuclear genes i.e. internal transcribed spacers ribosomal RNA (ITS rRNA), 28S ribosomal RNA (28S rRNA) and translation elongation factor 1- alpha (EF 1α). Ethyl acetate extract of strain MJ31displayed significant antimicrobial potential against Bacillus subtilis, followed by Micrococccus luteus and Staphylococcus aureus with minimum inhibitory concentrations (MIC) of 0...
2017: PloS One
https://www.readbyqxmd.com/read/29040649/clustercad-a-computational-platform-for-type-i-modular-polyketide-synthase-design
#13
Clara H Eng, Tyler W H Backman, Constance B Bailey, Christophe Magnan, Héctor García Martín, Leonard Katz, Pierre Baldi, Jay D Keasling
ClusterCAD is a web-based toolkit designed to leverage the collinear structure and deterministic logic of type I modular polyketide synthases (PKSs) for synthetic biology applications. The unique organization of these megasynthases, combined with the diversity of their catalytic domain building blocks, has fueled an interest in harnessing the biosynthetic potential of PKSs for the microbial production of both novel natural product analogs and industrially relevant small molecules. However, a limited theoretical understanding of the determinants of PKS fold and function poses a substantial barrier to the design of active variants, and identifying strategies to reliably construct functional PKS chimeras remains an active area of research...
October 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29032001/efficacy-of-self-retained-cryopreserved-amniotic-membrane-for-treatment-of-neuropathic-corneal-pain
#14
Melina I Morkin, Pedram Hamrah
PURPOSE: Treatment of neuropathic corneal pain (NCP) remains intricate, and involves a long-term combined multistep approach. The self-retained cryopreserved amniotic membrane (PROKERA(®), Bio-Tissue, Miami,FL) has been utilized for multiple ocular surface disorders. We evaluate the efficacy, safety, and tolerability of ProKera(®) Slim [PKS] and ProKera(®) Clear [PKC] in the treatment of NCP. METHODS: Retrospective case series of 9 patients who received PKS/PKC for the acute treatment of NCP...
October 12, 2017: Ocular Surface
https://www.readbyqxmd.com/read/29028314/heterologous-gene-expression-of-n-terminally-truncated-variants-of-lippks1-suggests-a-functionally-critical-structural-motif-in-the-n-terminus-of-modular-polyketide-synthase
#15
Satoshi Yuzawa, Constance B Bailey, Tatsuya Fujii, Renee Jocic, Jesus F Barajas, Veronica T Benites, Edward E K Baidoo, Yan Chen, Christopher J Petzold, Leonard Katz, Jay D Keasling
Streptomyces genomes have a high G + C content and typically use an ATG or GTG codon to initiate protein synthesis. Although gene-finding tools perform well in low GC genomes, it is known that the accuracy in predicting a translational start site (TSS) is much less for high GC genomes. LipPks1 is a Streptomyces-derived, well-characterized modular polyketide synthase (PKS). Using this enzyme as a model, we experimentally investigated the effects of alternative TSSs using a heterologous host, Streptomyces venezuelae...
November 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29024493/pharmacokinetics-and-pharmacodynamics-of-meloxicam-in-east-asian-populations-the-role-of-ethnicity-on-drug-response
#16
T Aoyama, Y Ishida, M Kaneko, A Miyamoto, Y Saito, M Tohkin, S Kawai, Y Matsumoto
We aimed to reanalyze the differences in the pharmacokinetics (PKs) of meloxicam in East Asian populations based on a population approach using previously published data and to investigate the factors found in population pharmacokinetic (PK) analysis that affect the pharmacodynamics (PDs) of meloxicam. Population PK analysis was performed in 119 healthy male subjects (30 Japanese, 30 Chinese, 29 Korean, and 30 Caucasian) under strictly controlled trial conditions with regulated meals and a single lot of the drug...
October 12, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29019409/genome-mining-and-activation-of-a-silent-pks-nrps-gene-cluster-direct-the-production-of-totopotensamides
#17
Ruidong Chen, Qingbo Zhang, Bin Tan, Liujuan Zheng, Huixian Li, Yiguang Zhu, Changsheng Zhang
A 92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in marine-derived Streptomyces pactum SCSIO 02999 was activated by genetically manipulating the regulatory genes, including the knockout of two negative regulators (totR5 and totR3) and overexpression of a positive regulator totR1, to direct the production of the known totopotensamides (TPMs) A (1) and B (3) and a novel sulfonate-containing analogue TPM C (2). Inactivation of totG led to accumulation of TPM B (3) lacking the glycosyl moiety, which indicated TotG as a dedicated glycosyltransferase in the biosynthesis of 1 and 2...
October 11, 2017: Organic Letters
https://www.readbyqxmd.com/read/29018999/population-pharmacokinetics-of-gabapentin-in-healthy-korean-subjects-with-influence-of-genetic-polymorphisms-of-abcb1
#18
Phuong Tran, Hee-Doo Yoo, Lien Ngo, Hea-Young Cho, Yong-Bok Lee
The objective of this study was to perform population pharmacokinetic (PK) analysis of gabapentin in healthy Korean subjects and to investigate the possible effect of genetic polymorphisms (1236C > T, 2677G > T/A, and 3435C > T) of ABCB1 gene on PK parameters of gabapentin. Data were collected from bioequivalence studies, in which 173 subjects orally received three different doses of gabapentin (300, 400, and 800 mg). Only data from reference formulation were used. Population pharmacokinetics (PKs) of gabapentin was estimated using a nonlinear mixed-effects model (NONMEM)...
October 10, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28993611/natural-product-diversity-associated-with-the-nematode-symbionts-photorhabdus-and-xenorhabdus
#19
Nicholas J Tobias, Hendrik Wolff, Bardya Djahanschiri, Florian Grundmann, Max Kronenwerth, Yi-Ming Shi, Svenja Simonyi, Peter Grün, David Shapiro-Ilan, Sacha J Pidot, Timothy P Stinear, Ingo Ebersberger, Helge B Bode
Xenorhabdus and Photorhabdus species dedicate a large amount of resources to the production of specialized metabolites derived from non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS). Both bacteria undergo symbiosis with nematodes, which is followed by an insect pathogenic phase. So far, the molecular basis of this tripartite relationship and the exact roles that individual metabolites and metabolic pathways play have not been well understood. To close this gap, we have significantly expanded the database for comparative genomics studies in these bacteria...
October 9, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28990182/effect-of-chronic-kidney-disease-on-nonrenal-elimination-pathways-a-systematic-assessment-of-cyp1a2-cyp2c8-cyp2c9-cyp2c19-and-oatp
#20
Ming-Liang Tan, Kenta Yoshida, Ping Zhao, Lei Zhang, Thomas D Nolin, Micheline Piquette-Miller, Aleksandra Galetin, Shiew-Mei Huang
Our recent studies have shown that chronic kidney disease (CKD) affects the pharmacokinetics (PKs) of cytochrome P450 (CYP)2D6-metabolized drugs, whereas effects were less evident on CYP3A4/5. Therefore, the effect of CKD on the disposition of CYP1A2-metabolized, CYP2C8-metabolized, CYP2C9-metabolized, CYP2C19-metabolized, and organic anion-transporting polypeptide (OATP)-transported drugs was investigated. We identified dedicated CKD studies with 6, 5, 6, 4, and 12 "model" substrates for CYP1A2, CYP2C8, CYP2C9, CYP2C19, and OATP, respectively...
October 9, 2017: Clinical Pharmacology and Therapeutics
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