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https://www.readbyqxmd.com/read/28722515/construction-of-a-plga-based-targeted-sirna-delivery-system-for-treatment-of-osteoporosis
#1
Deniz Sezlev Bilecen, Jose Carlos Rodriguez-Cabello, Hasan Uludag, Vasif Hasirci
Osteoporosis is a systemic skeletal disorder which occurs when the bone turnover balance is disrupted. With the identification of the genes involved in the pathogenesis of the disease, studies on development of new osteoporosis treatments has intensified. RNA interference (RNAi) mechanism uses short interfering RNA (siRNA) to knockdown disease related gene expression as a treatment approach. Targeting while protecting siRNA against hydrolysis by nucleases in vivo is, however, challenging. The maintenance of therapeutic plasma level is also hampered by the clearance of siRNA from the body...
July 19, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28721587/genetically-engineered-cell-lines-for-%C3%AE-1-antitrypsin-expression
#2
Qianqian Ji, Caiping Guo, Chen Xie, Yingdan Wu, Pei Zhang, Hui Li, Yongjun Lu
OBJECTIVES: To establish genetically modified cell lines that can produce functional α1-antitrypsin (AAT), by CRISPR/Cas9-assisted homologous recombination. RESULTS: α1-Antitrypsin deficiency (AATD) is a monogenic heritable disease that often results in lungs and liver damage. Current augmentation therapy is expensive and in short of supply. To develop a safer and more effective therapeutic strategy for AATD, we integrated the AAT gene (SERPINA1, NG_008290.1) into the AAVS1 locus of human cell line HEK293T and assessed the safety and efficacy of CRISPR/Cas9 on producing potential therapeutic cell lines...
July 18, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28718812/therapeutic-efficacy-of-the-novel-stimuli-sensitive-nano-ferritins-containing-doxorubicin-in-a-head-and-neck-cancer-model
#3
Verena Damiani, Elisabetta Falvo, Giulio Fracasso, Luca Federici, Martina Pitea, Vincenzo De Laurenzi, Gianluca Sala, Pierpaolo Ceci
Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS)...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28717202/%C3%AE-caryophyllene-emitted-from-a-transgenic-arabidopsis-or-chemical-dispenser-repels-diaphorina-citri-vector-of-candidatus-liberibacters
#4
Berta Alquézar, Haroldo Xavier Linhares Volpe, Rodrigo Facchini Magnani, Marcelo Pedreira de Miranda, Mateus Almeida Santos, Nelson Arno Wulff, Jose Mauricio Simões Bento, José Roberto Postali Parra, Harro Bouwmeester, Leandro Peña
Production of citrus, the main fruit tree crop worldwide, is severely threatened by Huanglongbing (HLB), for which as yet a cure is not available. Spread of this bacterial disease in America and Asia is intimately connected with dispersal and feeding of the insect vector Diaphorina citri, oligophagous on rutaceous host plants. Effective control of this psyllid is an important component in successful HLB management programs. Volatiles released from the non-host guava have been shown to be repellent to the psyllid and to inhibit its response to citrus odour...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715967/hyperthermia-enhanced-targeted-drug-delivery-using-magnetic-resonance-guided-focussed-ultrasound-a-pre-clinical-study-in-a-genetic-model-of-pancreatic-cancer
#5
Navid Farr, Yak-Nam Wang, Samantha D'Andrea, Frank Starr, Ari Partanen, Kayla M Gravelle, Jeannine S McCune, Linda J Risler, Stella G Whang, Amy Chang, Sunil R Hingorani, Donghoon Lee, Joo Ha Hwang
PURPOSE: The lack of effective treatment options for pancreatic cancer has led to a 5-year survival rate of just 8%. Here, we evaluate the ability to enhance targeted drug delivery using mild hyperthermia in combination with the systemic administration of a low-temperature sensitive liposomal formulation of doxorubicin (LTSL-Dox) using a relevant model for pancreas cancer. MATERIALS AND METHODS: Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre)...
July 17, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28715385/a-genetically-engineered-mouse-model-of-sporadic-colorectal-cancer
#6
Alexander M Betzler, Susan Kochall, Linda Blickensdörfer, Sebastian A Garcia, May-Linn Thepkaysone, Lahiri K Nanduri, Michael H Muders, Jürgen Weitz, Christoph Reissfelder, Sebastian Schölch
Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Genetically engineered mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in large organs such as the colon in which only a single tumor is desired. As a result, an immunocompetent, genetically engineered mouse model of colorectal cancer was developed which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials...
July 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28713247/divergent-roles-of-central-serotonin-in-adult-hippocampal-neurogenesis
#7
REVIEW
Ning-Ning Song, Ying Huang, Xin Yu, Bing Lang, Yu-Qiang Ding, Lei Zhang
The central serotonin (5-HT) system is the main target of selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28710617/steroid-bioconversions
#8
Marina V Donova
Steroid modifications by selected wild-type and engineered strains of microorganisms became an effective tool for the production of high-valued steroidal drugs and their precursors for the pharmaceutical industry. Some microorganisms are effective at the performance of sterol side-chain degradation, oxyfunctionalization of steroid core, and redox reactions at different positions of the steroid molecule. A number of bioprocesses using steroid-transforming microbial strains are well established on an industrial level...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28709932/assessing-glycolytic-flux-alterations-resulting-from-genetic-perturbations-in-e-coli-using-a-biosensor
#9
Christina E Lehning, Solvej Siedler, Mostafa M H Ellabaan, Morten O A Sommer
We describe the development of an optimized glycolytic flux biosensor and its application in detecting altered flux in a production strain and in a mutant library. The glycolytic flux biosensor is based on the Cra-regulated ppsA promoter of E. coli controlling fluorescent protein synthesis. We validated the glycolytic flux dependency of the biosensor in a range of different carbon sources in six different E. coli strains and during mevalonate production. Furthermore, we studied the flux-altering effects of genome-wide single gene knock-outs in E...
July 11, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28709434/integrating-multi-omics-analyses-of-nonomuraea-dietziae-to-reveal-the-role-of-soybean-oil-in-4-oh-meleu-4-csa-overproduction
#10
Huanhuan Liu, Di Huang, Lina Jin, Cheng Wang, Shaoxiong Liang, Jianping Wen
BACKGROUND: Nonomuraea dietziae is a promising microorganism to mediate the region-specific monooxygenation reaction of cyclosporine A (CsA). The main product [(4'-OH)MeLeu](4)-CsA possesses high anti-HIV/HCV and hair growth-stimulating activities while avoiding the immunosuppressive effect of CsA. However, the low conversion efficiency restricts the clinical application. In this study, the production of [(4'-OH)MeLeu](4)-CsA was greatly improved by 55.6% from 182.8 to 284.4 mg/L when supplementing soybean oil into the production medium, which represented the highest production of [(4'-OH)MeLeu](4)-CsA so far...
July 14, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28707113/genetically-engineered-hairy-root-cultures-of-hyoscyamus-senecionis-and-h-muticus-ploidy-as-a-promising-parameter-in-the-metabolic-engineering-of-tropane-alkaloids
#11
Esmaeil Dehghan, Darwin W Reed, Patrick S Covello, Zeinab Hasanpour, Javier Palazon, Kirsi-Marja Oksman-Caldentey, Farajollah Shahriari Ahmadi
Tetraploidy improves overexpression of h6h and scopolamine production of H. muticus, while in H. senecionis, pmt overexpression and elicitation can be used as effective methods for increasing tropane alkaloids. The effects of metabolic engineering in a polyploid context were studied by overexpression of h6h in the tetraploid hairy root cultures of H. muticus. Flow cytometry analysis indicated genetic stability in the majority of the clones, while only a few clones showed genetic instability. Among all the diploid and tetraploid clones, the highest level of h6h transgene expression and scopolamine accumulation was interestingly observed in the tetraploid clones of H...
July 13, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28701395/preferential-targeting-of-conserved-gag-regions-after-vaccination-with-a-heterologous-dna-prime-modified-vaccinia-ankara-mva-boost-hiv-1-vaccine-regimen
#12
Asli Bauer, Lilli Podola, Philipp Mann, Marco Missanga, Antelmo Haule, Lwitiho Sudi, Charlotta Nilsson, Bahati Kaluwa, Cornelia Lueer, Maria Mwakatima, Patricia J Munseri, Leonard Maboko, Merlin L Robb, Sodsai Tovanabutra, Gustavo Kijak, Mary Marovich, Sheena McCormack, Sarah Joseph, Eligius Lyamuya, Britta Wahren, Eric Sandström, Gunnel Biberfeld, Michael Hoelscher, Muhammad Bakari, Arne Kroidl, Christof Geldmacher
Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28700899/pegylated-liposomal-formulation-of-doxorubicin-overcomes-drug-resistance-in-a-genetically-engineered-mouse-model-of-breast-cancer
#13
András Füredi, Kornélia Szebényi, Szilárd Tóth, Mihály Cserepes, Lilla Hámori, Veronika Nagy, Edina Karai, Péter Vajdovich, Tímea Imre, Pál Szabó, Dávid Szüts, József Tóvári, Gergely Szakács
Success of cancer treatment is often hampered by the emergence of multidrug resistance (MDR) mediated by P-glycoprotein (ABCB1/Pgp). Doxorubicin (DOX) is recognized by Pgp and therefore it can induce therapy resistance in breast cancer patients. In this study our aim was to evaluate the susceptibility of the pegylated liposomal formulation of doxorubicin (PLD/Doxil®/Caelyx®) to MDR. We show that cells selected to be resistant to DOX are cross-resistant to PLD and PLD is also ineffective in an allograft model of doxorubicin-resistant mouse B-cell leukemia...
July 9, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28695896/r-spondin-chromosome-rearrangements-drive-wnt-dependent-tumour-initiation-and-maintenance-in-the-intestine
#14
Teng Han, Emma M Schatoff, Charles Murphy, Maria Paz Zafra, John E Wilkinson, Olivier Elemento, Lukas E Dow
Defining the genetic drivers of cancer progression is a key in understanding disease biology and developing effective targeted therapies. Chromosome rearrangements are a common feature of human malignancies, but whether they represent bona fide cancer drivers and therapeutically actionable targets, requires functional testing. Here, we describe the generation of transgenic, inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer-associated EIF3E-RSPO2 and PTPRK-RSPO3 chromosome rearrangements in vivo...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28693571/characterization-of-erythrose-reductase-from-yarrowia-lipolytica-and-its-influence-on-erythritol-synthesis
#15
Tomasz Janek, Adam Dobrowolski, Anna Biegalska, Aleksandra M Mirończuk
BACKGROUND: Erythritol is a natural sweetener that is used in the food industry. It is produced as an osmoprotectant by bacteria and yeast. Due to its chemical properties, it does not change the insulin level in the blood, and therefore it can be safely used by diabetics. Previously, it has been shown that erythrose reductase (ER), which catalyzes the final step, plays a crucial role in erythritol synthesis. ER reduces erythrose to erythritol with NAD(P)H as a cofactor. Despite many studies on erythritol synthesis by Yarrowia lipolytica, the enzymes involved in this metabolic pathway have ever been described...
July 11, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28692815/efficient-generation-of-goats-with-defined-point-mutation-i397v-in-gdf9-through-crispr-cas9
#16
Yiyuan Niu, Xiaoe Zhao, Jiankui Zhou, Yan Li, Yu Huang, Bei Cai, Yutai Liu, Qiang Ding, Shiwei Zhou, Jin Zhao, Guangxian Zhou, Baohua Ma, Xingxu Huang, Xiaolong Wang, Yulin Chen
The recent emergence of the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9 system has attracted significant attention for its potential to improve traits of agricultural importance. However, most applications in livestock species to date have depended on aberrant DNA repair to generate frameshifting indels. Whether this genomic engineering technique involving homology-dependent repair (HDR) can be used to introduce defined point mutations has been less explored. Previously, we reported a G→A point mutation (g...
July 11, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28691927/ubiquitination-of-tumor-suppressor-pml-regulates-prometastatic-and-immunosuppressive-tumor-microenvironment
#17
Ya-Ting Wang, Jocelyn Chen, Chou-Wei Chang, Jayu Jen, Tzu-Yu Huang, Chun-Ming Chen, Roger Shen, Suh-Yuen Liang, I-Cheng Cheng, Shuenn-Chen Yang, Wu-Wei Lai, Kuang-Hung Cheng, Tao-Shih Hsieh, Ming-Zong Lai, Hung-Chi Cheng, Yi-Ching Wang, Ruey-Hwa Chen
The tumor microenvironment plays an important role in tumor growth and metastasis. However, the mechanism by which tumor cells regulate the cell and non-cell constituents of surrounding stroma remains incompletely understood. Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in tumor microenvironment regulation is poorly characterized. PML is frequently downregulated in many cancer types, including lung cancer. Here, we identify a PML ubiquitination pathway that is mediated by WD repeat 4-containing cullin-RING ubiquitin ligase 4 (CRL4WDR4)...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28691262/metabolic-modelling-to-identify-engineering-targets-for-komagataella-phaffii-the-effect-of-biomass-composition-on-gene-target-identification
#18
Ayca Cankorur-Cetinkaya, Duygu Dikicioglu, Stephen G Oliver
Genome-scale metabolic models are valuable tools for the design of novel strains of industrial microorganisms, such as Komagataella phaffii (syn. Pichia pastoris). However, as is the case for many industrial microbes, there is no executable metabolic model for K. phaffiii that confirms to current standards by providing the metabolite and reactions IDs, to facilitate model extension and reuse, and gene-reaction associations to enable identification of targets for genetic manipulation. In order to remedy this deficiency, we decided to reconstruct the genome-scale metabolic model of K...
July 10, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28689971/effect-of-substitution-of-photo-cross-linker-in-photochemical-cytosine-to-uracil-transition-in-dna
#19
Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto
Genome editing is an important technique for protein engineering, treatment of genetic disorders, and production of non-native proteins. A shortcoming of current enzymatic and chemical methods for genome editing is their limited applicability for in vivo studies. In addition, non-enzymatic methods, such as photochemical DNA editing using 3-cyanovinylcarbazole ((CNV)K), require high temperatures to affect cytosine to uracil transformations. To overcome this limitation, we developed new photo-cross-linkers based on (CNV)K, 3-methoxycarbonlycarbazole, 3-carboxyvinylcarbazole, and 3-carbonylamidevinylcarbazole...
June 16, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28689336/v79-fibroblasts-are-protected-against-reactive-oxygen-species-by-flax-fabric
#20
Katarzyna Skórkowska-Telichowska, Anna Kulma, Tomasz Gębarowski, Wioleta Wojtasik, Kamil Kostyn, Helena Moreira, Anna Szyjka, Aleksandra Boba, Marta Preisner, Justyna Mierziak, Malgorzata Arendt, Anna Kostyn, Michał Szatkowski, Jan Szopa, Kazimierz Gąsiorowski
Chinese hamster pulmonary fibroblasts (V79 cells) pre-treated with flax fabrics derived from non-modified or genetically engineered flax fibres and treated with H2O2 revealed a markedly lower level of intracellular reactive oxygen species (ROS) than control, non-pre-treated cells. The fabrics were prepared from fibres derived from two kinds of transgenic plants: W92 plants, which overproduce flavonoids, and M type plants, which produce hydroxybutyrate polymer in their vascular bundles and thus in fibres. Incubating the V79 cells with the flax fabrics prior to H2O2 treatment also reduced the amount of DNA damage, as established using the comet assay (also known as alkaline single-cell gel electrophoresis) and pulsed-field electrophoresis of intact cellular DNA...
July 8, 2017: Applied Biochemistry and Biotechnology
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