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https://www.readbyqxmd.com/read/29332251/clinical-pharmacokinetics-and-pharmacodynamics-of-telavancin-compared-with-the-other-glycopeptides
#1
REVIEW
Valentin Al Jalali, Markus Zeitlinger
Telavancin was discovered by modifying the chemical structure of vancomycin and belongs to the group of lipoglycopeptides. It employs its antimicrobial potential through two distinct mechanisms of action: inhibition of bacterial cell wall synthesis and induction of bacterial membrane depolarization and permeabilization. In this article we review the clinically relevant pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the pharmacokinetic and pharmacodynamic data of the other glycopeptides are presented...
January 13, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29323879/malaria-derived-gpi-anchor-enhances-anti-pfs25-functional-antibodies-that-block-malaria-transmission
#2
Neeraj Kapoor, Ivana Vanjak, James Rozzelle, Aym Berges, Wei Chan, Gang Yin, Cuong Tran, Aaron K Sato, Alexander R Steiner, Thao P Pham, Ashley J Birkett, Carole Long, Jeff Fairman, Kazutoyo Miura
Malaria, one of the most common vector borne human diseas-es, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429,000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts towards development of vaccines to prevent transmission are still needed. Pfs25, a post-fertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidyl-inositol (GPI) linker, which itself possesses proinflammatory properties...
January 11, 2018: Biochemistry
https://www.readbyqxmd.com/read/29322283/rational-design-of-engineered-microbial-cell-surface-multi-enzyme-co-display-system-for-sustainable-nadh-regeneration-from-low-cost-biomass
#3
Lei Han, Bo Liang, Jianxia Song
As an important cofactor, NADH is essential for most redox reactions and biofuel cells. However, supply of exogenous NADH is challenged, due to the low production efficiency and high cost of NADH regeneration system, as well as low stability of NADH. Here, we constructed a novel cell surface multi-enzyme co-display system with ratio- and space-controllable manner as exogenous NADH regeneration system for the sustainable NADH production from low-cost biomass. Dockerin-fused glucoamylase (GA) and glucose dehydrogenase (GDH) were expressed and assembled on the engineered bacterial surfaces, which displayed protein scaffolds with various combinations of different cohesins...
January 10, 2018: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29321239/comparative-genomic-analysis-of-the-pseudofungus-hyphochytrium-catenoides
#4
Guy Leonard, Aurélie Labarre, David S Milner, Adam Monier, Darren Soanes, Jeremy G Wideman, Finlay Maguire, Sam Stevens, Divya Sain, Xavier Grau-Bové, Arnau Sebé-Pedrós, Jason E Stajich, Konrad Paszkiewicz, Matthew W Brown, Neil Hall, Bill Wickstead, Thomas A Richards
Eukaryotic microbes have three primary mechanisms for obtaining nutrients and energy: phagotrophy, photosynthesis and osmotrophy. Traits associated with the latter two functions arose independently multiple times in the eukaryotes. The Fungi successfully coupled osmotrophy with filamentous growth, and similar traits are also manifested in the Pseudofungi (oomycetes and hyphochytriomycetes). Both the Fungi and the Pseudofungi encompass a diversity of plant and animal parasites. Genome-sequencing efforts have focused on host-associated microbes (mutualistic symbionts or parasites), providing limited comparisons with free-living relatives...
January 2018: Open Biology
https://www.readbyqxmd.com/read/29313666/carbon-1-versus-carbon-3-linkage-of-d-galactose-to-porphyrins-synthesis-uptake-and-photodynamic-efficiency
#5
Patrícia Manuela Ribeiro Pereira, Waqar Rizvi, Naga Venkata Satya Dinesh Kumar Bhupathiraju, Naxhije Berisha, Rosa Fernandes, Joao P C Tome, Charles Michael Michael Drain
The use of glycosylated compounds is actively pursued as a therapeutic strategy for cancer due to the overexpression of various types of sugar receptors and transporters on most cancer cells. Conjugation of saccharides to photosensitizers such as porphyrins provides a promising strategy to improve the selectivity and cell uptake of the photosensitizers, enhancing the overall photosensitizing efficacy. Most porphyrin-carbohydrate conjugates are linked via the carbon-1 position of the carbohydrate because this is the most synthetically accessible approach...
January 9, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29313428/biosynthesis-of-silver-nanoparticles-using-novel-bacillus-sp-sbt8
#6
Tuğçe Yurtluk, Fikriye Alev Akçay, Ayşe Avcı
Biosynthesis of silver nanoparticles (AgNPs) using microorganisms is an important application of nano-biotechnology and green chemistry because of interest by pharmaceutical and food manufacturers. In this study, biosynthesis of AgNPs by a novel Bacillus strain isolated from a soil sample from Sakarya district in Turkey was investigated. Biosynthesis was performed using cell-free supernatant of the bacterium following 24 h growth. Effects of varying AgNO3 concentration (1-10 mM), pH (5-10), and temperature (30-40°C) on the synthesis of AgNPs were determined...
January 9, 2018: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/29313227/apolipoprotein-a-i-stimulates-cell-proliferation-in-bone-marrow-cell-culture
#7
I F Usynin, A N Dudarev, A Yu Gorodetskaya, S M Miroshnichenko, T A Tkachenko, V I Tkachenko
Culturing of bone marrow cells in serum-free RPMI-1640 medium led to a decrease in the rate of DNA biosynthesis. Addition of HDL or their main protein component apolipoprotein A-I to the culture medium dose-dependently increased the rate of [3H]-thymidine incorporation into DNA. The maximum stimulation was achieved at HDL concentration of 80 μg/ml and apolipoprotein A-I concentration of 20 μg/ml. To identify the target-cells of apolipoprotein A-I, we used thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU) that incorporates into cell DNA at the stage of replicative DNA synthesis (S phase) and can be detected by fluorescence microscopy...
January 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29310250/rational-synthesis-of-mos2-based-immobilized-trypsin-for-rapid-and-effective-protein-digestion
#8
Chaoshuang Xia, Heping Wang, Fenglong Jiao, Fangyuan Gao, Qiong Wu, Yehua Shen, Yangjun Zhang, Xiaohong Qian
In this work, a novel MoS2-based immobilized trypsin reactor was designed and prepared. Pyrene-1-butyric acid was first assembled onto MoS2 nanosheets via the strong π-π stacking and then trypsin was covalently immobilized onto the nanocomposite supports through amidation reaction. Compared with traditional in-solution digestion, higher sequence coverage (84%) and shorter time (5min) could be achieved by the novel trypsin reactor during the digestion of BSA. The excellent performances of as-prepared trypsin reactor can be mainly attributed to the designed novel structure of the composites with high surface area resulting in high enzyme loading...
March 1, 2018: Talanta
https://www.readbyqxmd.com/read/29305670/bioactive-chylomicrons-for-oral-lymphatic-targeting-of-berberine-chloride-novel-flow-blockage-assay-in-tissue-based-and-caco-2-cell-line-models
#9
Manal A Elsheikh, Yosra S R Elnaggar, Dina Y Otify, Ossama Y Abdallah
PURPOSE: To develop novel bioactive-chylomicrons to solve oral delivery obstacles of Berberine chloride and target the lymphatic system. METHODS: Berberine-loaded bioactive-chylomicrons were prepared and underwent full in vitro characterization. Intestinal permeability was appraised via both non-everted gut sac model and Caco-2 cell model. Furthermore, Bioactive-chylomicrons' cellular uptake and distribution were examined by laser scanning confocal microscopy. Finally, a novel chylomicron flow-blockage assay on tissue and cellular levels were elaborated to assess the lymphatic targeting ability...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29300865/crispr-cas9-mediated-tspo-gene-mutations-lead-to-reduced-mitochondrial-membrane-potential-and-steroid-formation-in-ma-10-mouse-tumor-leydig-cells
#10
Jinjiang Fan, Kevin Wang, Barry Zirkin, Vassilios Papadopoulos
The outer mitochondrial membrane translocator protein (TSPO) binds cholesterol with high affinity and is involved in mediating its delivery into mitochondria, the rate-limiting step in hormone-induced steroidogenesis. Specific ligand binding to TSPO has been shown to initiate steroid formation. However, recent studies of the genetic deletion of Tspo have provided conflicting results. Here we address and extend previous studies by examining the effects of Tspo - specific mutations on steroid formation in the hormone- and cAMP-responsive MA-10 cells, using the CRISPR/Cas9 system...
December 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/29295615/the-locational-impact-of-site-specific-pegylation-streamlined-screening-with-cell-free-protein-expression-and-coarse-grain-simulation
#11
Kristen M Wilding, Addison K Smith, Joshua W Wilkerson, Derek B Bush, Thomas Allen Knotts, Bradley Charles Bundy
Although polyethylene glycol (PEG) is commonly used to improve protein stability and therapeutic efficacy, the optimal location for attaching PEG onto proteins is not well understood. Here, we present a cell-free protein synthesis-based screening platform which facilitates site-specific PEGylation and efficient evaluation of PEG attachment efficiency, thermal stability, and activity for different variants of PEGylated T4 lysozyme, including a di-PEGylated variant. We also report developing a computationally-efficient coarse-grain simulation model as a potential tool to narrow experimental screening candidates...
January 2, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29274292/butyrate-and-docosahexaenoic-acid-interact-in-alterations-of-specific-lipid-classes-in-differentiating-colon-cancer-cells
#12
Zuzana Tylichová, Josef Slavík, Miroslav Ciganek, Petra Ovesná, Pavel Krčmář, Nicol Straková, Miroslav Machala, Alois Kozubík, Jiřina Hofmanová, Jan Vondráček
Docosahexaenoic acid (DHA) and sodium butyrate (NaBt) exhibit a number of interactive effects on colon cancer cell growth, differentiation or apoptosis; however, the molecular mechanisms responsible for these interactions and their impact on cellular lipidome are still not fully clear. Here, we show that both dietary agents together induce dynamic alterations of lipid metabolism, specific cellular lipid classes and fatty acid composition. In HT-29 cell line, a model of differentiating colon carcinoma cells, NaBt supported incorporation of free DHA into non-polar lipids and their accumulation in cytoplasmic lipid droplets...
December 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29248802/eef1a1-overexpression-enhances-tumor-progression-and-indicates-poor-prognosis-in-hepatocellular-carcinoma
#13
Shi-Lu Chen, Shi-Xun Lu, Li-Li Liu, Chun-Hua Wang, Xia Yang, Zhi-Yi Zhang, Hui-Zhong Zhang, Jing-Ping Yun
Liver is a major contributor of protein production physiologically. The aberrant state of protein synthesis leads to tumor progression. Eukaryotic elongation factor 1 alpha 1 (eEF1A1) is a major member of the eukaryotic elongation factor family that regulates protein synthesis. Although eEF1A1 plays an essential role in controlling the cell fate, its clinical significance in tumor development and progression has not been reported. Here, we aimed to uncover the expression and prognostic significance of eEF1A1 in hepatocellular carcinoma (HCC)...
December 14, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29246861/ribosome-biogenesis-protein-urb1-acts-downstream-of-mtor-complex-1-to-modulate-digestive-organ-development-in-zebrafish
#14
Jia He, Yun Yang, Junren Zhang, Jinzi Chen, Xiangyong Wei, Jianbo He, Lingfei Luo
Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in zebrafish urb1, which encodes an essential ribosome biogenesis protein. The urb1cq31 mutant exhibits hypoplastic digestive organs, which is caused by impaired cell proliferation with the differentiation of digestive organ progenitors unaffected. Knockdown of mtor or raptor leads to similar hypoplastic phenotypes and reduced expression of urb1 in the digestive organs...
November 29, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/29243822/nrf2-promotes-oesophageal-cancer-cell-proliferation-via-metabolic-reprogramming-and-detoxification-of-reactive-oxygen-species
#15
Yuki Kitano, Yoshifumi Baba, Shigeki Nakagawa, Keisuke Miyake, Masaaki Iwatsuki, Takatsugu Ishimoto, Yo-Ichi Yamashita, Naoya Yoshida, Masayuki Watanabe, Mitsuyoshi Nakao, Hideo Baba
Cancer cells consume a large amount of energy and maintain high levels of anabolism to promote cell proliferation via metabolic reprogramming. Nuclear factor erythroid 2-related factor 2 (Nrf2; NFE2L2) is a master transcription regulator of stress responses and promotes metabolic reprogramming to support cell proliferation in various types of cancer. As oesophageal cancer is one of the most aggressive gastrointestinal cancers, we aimed to clarify the effect of Nrf2 on metabolic reprogramming in oesophageal cancer...
December 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29235215/cloning-free-template-dna-preparation-for-cell-free-protein-synthesis-via-two-step-pcr-using-versatile-primer-designs-with-short-3-utr
#16
Mika Nomoto, Yasuomi Tada
Cell-free protein synthesis (CFPS) systems largely retain the endogenous translation machinery of the host organism, making them highly applicable for proteomics analysis of diverse biological processes. However, laborious and time-consuming cloning procedures hinder progress with CFPS systems. Herein, we report the development of a rapid and efficient two-step polymerase chain reaction (PCR) method to prepare linear DNA templates for a wheat germ CFPS system. We developed a novel, effective short 3'-untranslated region (3'-UTR) sequence that facilitates translation...
December 13, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29232946/huntingtin-polyglutamine-dependent-protein-aggregation-in-reconstituted-cells
#17
Kodai Machida, Kuru Kanzawa, Tomoaki Shigeta, Yuki Yamamoto, Kanta Tsumoto, Hiroaki Imataka
One of the aims of synthetic biology is bottom-up construction of reconstituted human cells for medical uses. To that end, we generated giant unilamella vesicles (GUVs) that contained a HeLa cell extract, which comprises a cell-free protein synthesis (CFPS) system. Then we expressed Huntingtin protein fragments that contained polyglutamine (polyQ) sequences (Htt-polyQ), a hallmark of Huntington's disease. That system produced polyQ-dependent protein aggregates, as previously demonstrated in living cells. We next simplified the system by generating GUVs that contained purified human factors, which reconstituted a CFPS system...
December 12, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29228574/microfluidic-hydrodynamic-focusing-synthesis-of-polymer-lipid-nanoparticles-for-sirna-delivery
#18
Xueqin Huang, Robert J Lee, Yuhang Qi, Yujing Li, Jiahui Lu, Qingfan Meng, Lesheng Teng, Jing Xie
Small interfering RNAs (siRNAs) are promising as therapeutics for intractable diseases such as cancer. However, efficient and safe delivery of siRNAs in vivo remains a challenge. Polymer-lipid hybrid nanoparticles (P/LNPs) have been evaluated for therapeutic delivery of siRNA. In this study, a microfluidic hydrodynamic focusing (MF) system was used to prepare P/LNPs loaded with VEGF siRNA. P/LNPs made by MF were smaller in particle size and had narrower size distribution compared to P/LNPs formed by bulk mixing (BM)...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228426/lncrna-hotair-contributes-to-the-tumorigenesis-of-nasopharyngeal-carcinoma-via-up-regulating-fasn
#19
D-D Ma, L-L Yuan, L-Q Lin
OBJECTIVE: The therapeutic options for nasopharyngeal carcinoma (NPC) treatment have been restricted mainly to radiotherapy or chemotherapy, and the clinical treatment effect remains unsatisfactory. The primary purpose of this study was to investigate the molecular mechanisms of NPC and to find effective novel therapeutic targets for NPC. PATIENTS AND METHODS: In order to analyze the expression level of lncRNA HOTAIR and FASN in human NPC clinical tissues or NPC cells, total RNA was extracted with TRIzol and the relative mRNA expression levels were detected by quantitative Real-time PCR...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29221924/unraveling-co-translational-protein-folding-concepts-and-methods
#20
REVIEW
Anton A Komar
Advances in techniques such as nuclear magnetic resonance spectroscopy, cryo-electron microscopy, and single-molecule and time-resolved fluorescent approaches are transforming our ability to study co-translational protein folding both in vivo in living cells and in vitro in reconstituted cell-free translation systems. These approaches provide comprehensive information on the spatial organization and dynamics of nascent polypeptide chains and the kinetics of co-translational protein folding. This information has led to an improved understanding of the process of protein folding in living cells and should allow remaining key questions in the field, such as what structures are formed within nascent chains during protein synthesis and when, to be answered...
December 5, 2017: Methods: a Companion to Methods in Enzymology
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