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https://www.readbyqxmd.com/read/28091582/androgen-mediated-regulation-of-endoplasmic-reticulum-associated-degradation-and-its-effects-on-prostate-cancer
#1
Yalcin Erzurumlu, Petek Ballar
The endoplasmic reticulum (ER) comprises thirty percent of the newly translated proteins in eukaryotic cells. The quality control mechanism within the ER distinguishes between properly and improperly folded proteins and ensures that unwanted proteins are retained in the ER and subsequently degraded through ER-associated degradation (ERAD). Besides cleaning of misfolded proteins ERAD is also important for physiological processes by regulating the abundance of normal proteins of the ER. Thus it is important to unreveal the regulation patterns of ERAD...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089350/rickettsia-prowazekii-methionine-aminopeptidase-as-a-promising-target-for-the-development-of-antibacterial-agents
#2
Travis R Helgren, Congling Chen, Phumvadee Wangtrakuldee, Thomas E Edwards, Bart L Staker, Jan Abendroth, Banumathi Sankaran, Nicole A Housley, Peter J Myler, Jonathon P Audia, James R Horn, Timothy J Hagen
Methionine aminopeptidase (MetAP) is a class of ubiquitous enzymes essential for the survival of numerous bacterial species. These enzymes are responsible for the cleavage of N-terminal formyl-methionine initiators from nascent proteins to initiate post-translational modifications that are often essential to proper protein function. Thus, inhibition of MetAP activity has been implicated as a novel antibacterial target. We tested this idea in the present study by targeting the MetAP enzyme in the obligate intracellular pathogen Rickettsia prowazekii...
November 10, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28088004/a-catechin-nanoformulation-inhibits-wm266-melanoma-cell-proliferation-migration-and-associated-neo-angiogenesis
#3
Nicoletta di Leo, Matteo Battaglini, Liron Berger, Martina Giannaccini, Luciana Dente, Silke Hampel, Orazio Vittorio, Giuseppe Cirillo, Vittoria Raffa
We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The anticancer potential of the resulting nanohybrid was validated on an aggressive melanoma cell line, in vitro and in zebrafish xenotransplants...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28087003/in%C3%A2-vitro-generation-of-renal-tubular-epithelial-cells-from-fibroblasts-implications-for-precision-and-regenerative-medicine-in-nephrology
#4
Christina M Wyatt, Nicole Dubois
Prior efforts to generate renal epithelial cells in vitro have relied on pluripotent or bone marrow-derived mesenchymal stem cells. A recent publication in Nature Cell Biology describes the generation of induced tubular epithelial cells from fibroblasts, potentially offering a novel platform for personalized drug toxicity screening and in vitro disease modeling. This report serves as a promising proof of principle study and opens future research directions, including the optimization of the reprogramming process, efficient translation to adult human fibroblasts, and the generation of highly specific functional renal cell types...
February 2017: Kidney International
https://www.readbyqxmd.com/read/28079309/bioactive-injectable-aggregates-with-nanofibrous-microspheres-and-human-dental-pulp-stem-cells-a-translational-strategy-in-dental-endodontics
#5
I Garzón, M A Martin-Piedra, V Carriel, M Alaminos, X Liu, R D Souza
Regeneration of the pulp-dentin complex with stem cells is a potential alternative to conventional root canal treatments. Human dental pulp stem cells (hDPSCs) have been extensively studied because of their ability to proliferate and differentiate into mineralized dental and nondental tissues. In this work we combined hDPSCs with two types of injectable poly-L-lactic acid (PLLA) microspheres with a nanofibrous or smooth surface to form bioactive injectable aggregates, and examined their ability to promote pulp regeneration in the root canal in an in vivo model...
January 12, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28078426/calreticulin-is-required-for-calcium-homeostasis-and-proper-pollen-tube-tip-growth-in-petunia
#6
Anna Suwińska, Piotr Wasąg, Przemysław Zakrzewski, Marta Lenartowska, Robert Lenartowski
Calreticulin is involved in stabilization of the tip-focused Ca (2+) gradient and the actin cytoskeleton arrangement and function that is required for several key processes driving Petunia pollen tube tip growth. Although the precise mechanism is unclear, stabilization of a tip-focused calcium (Ca(2+)) gradient seems to be critical for pollen germination and pollen tube growth. We hypothesize that calreticulin (CRT), a Ca(2+)-binding/buffering chaperone typically residing in the lumen of the endoplasmic reticulum (ER) of eukaryotic cells, is an excellent candidate to fulfill this role...
January 11, 2017: Planta
https://www.readbyqxmd.com/read/28077628/the-creatininase-homolog-mfte-from-mycobacterium-smegmatis-catalyzes-a-peptide-cleavage-reaction-in-the-biosynthesis-of-a-novel-ripp
#7
Nathan A Bruender, Vahe Bandarian
Most ribosomally-synthesized and post-translationally modified peptide (RiPP) natural products are processed by tailoring enzymes to create complex natural products that are still recognizably peptide-based. However, some tailoring enzymes dismantle the peptide en route to synthesis of small molecules. The biosynthesis of a small-molecule natural product of as yet unknown structure, mycofactocin, is thought to be synthesized in this way, via the mft gene cluster found in many strains of Mycobacteria. This cluster harbors at least six genes, which appear to be conserved across species...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28075493/joint-stability-after-canine-cranial-cruciate-ligament-graft-reconstruction-varies-among-femoral-fixation-sites
#8
Louisa K Ho-Eckart, Masahiro Seki, Lindsey M Luizza, Michael T Kearney, Mandi J Lopez
OBJECTIVE: To quantify stability in cranial cruciate ligament (CrCL) deficient canine stifles with hamstring grafts affixed at 3 femoral locations. STUDY DESIGN: Canine stifle motion study using a multi-cohort, repeated measures design. SAMPLE POPULATION: 27 canine cadaver stifles. METHODS: Hamstring grafts (HG) were affixed at the gracilis-semitendinosus insertion and on the lateral femur (1) proximal trochlear ridge (TR), (2) craniodistal to fabella (F), or (3) condyle center (CC)...
January 11, 2017: Veterinary Surgery: VS
https://www.readbyqxmd.com/read/28074350/a-comparative-study-of-the-bone-regenerative-effect-of-chemically-modified-rna-encoding-bmp-2-or-bmp-9
#9
Behnoush Khorsand, Satheesh Elangovan, Liu Hong, Alexander Dewerth, Michael S D Kormann, Aliasger K Salem
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2...
January 10, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28074342/the-presence-of-modified-nucleosides-in-extracellular-fluids-leads-to-the-specific-incorporation-of-5-chlorocytidine-into-rna-and-modulates-the-transcription-and-translation
#10
Caroline Noyon, Thierry Roumeguère, Cédric Delporte, Damien Dufour, Melissa Cortese, Jean-Marc Desmet, Christophe Lelubre, Alexandre Rousseau, Philippe Poelvoorde, Jean Nève, Luc Vanhamme, Karim Zouaoui Boudjeltia, Pierre Van Antwerpen
Myeloperoxidase (MPO) is able to promote several kinds of damage and is involved in mechanisms leading to various diseases such as atherosclerosis or cancers. An example of these damages is the chlorination of nucleic acids, which is considered as a specific marker of the MPO activity. Since 5-chlorocytidine has been recently shown in healthy donor plasmas, this study aimed at discovering if these circulating modified nucleosides could be incorporated into RNA and DNA and if their presence impacts the ability of enzymes involved in the incorporation, transcription, and translation processes...
January 10, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28073938/sonic-hedgehog-guides-axons-via-zipcode-binding-protein-1-mediated-local-translation
#11
Lea Lepelletier, Sébastien D Langlois, Christopher B Kent, Kristy Welshhans, Steves Morin, Gary J Bassell, Patricia T Yam, Frédéric Charron
: Sonic hedgehog (Shh) attracts spinal cord commissural axons toward the floorplate. How Shh elicits changes in the growth cone cytoskeleton that drive growth cone turning is unknown. We find that the turning of rat commissural axons up a Shh gradient requires protein synthesis. In particular, Shh stimulation increases β-actin protein at the growth cone, even when the cell bodies have been removed. Thus Shh induces the local translation of β-actin at the growth cone. We hypothesised that this requires zipcode binding protein 1 (ZBP1), an mRNA binding protein that transports β-actin mRNA and releases it for local translation upon phosphorylation...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28073841/activation-of-eif4e-by-aurora-kinase-a-depicts-a-novel-druggable-axis-in-everolimus-resistant-cancer-cells
#12
Ahmed Katsha, Lihong Wang, Janet Arras, Omar M Omar, Jeffrey A Ecsedy, Abbes Belkhiri, Wael El-Rifai
PURPOSE: In this study, we investigated the role of Aurora kinase A (AURKA) in regulating EIF4E, cap-dependent translation, and resistance to mTOR inhibitor, RAD001 (everolimus). EXPERIMENTAL DESIGN: Tumor xenografts and in vitro cell models of upper gastrointestinal adenocarcinomas (UGCs) were used to determine the role of AURKA in activation of EIF4E and cap-dependent translation. Overexpression, knockdown, and pharmacologic inhibition of AURKA were used in vitro and in vivo...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28073086/human-neural-progenitors-derived-from-integration-free-ipscs-for-sci-therapy
#13
Ying Liu, Yiyan Zheng, Shenglan Li, Haipeng Xue, Karl Schmitt, Georgene W Hergenroeder, Jiaqian Wu, Yuanyuan Zhang, Dong H Kim, Qilin Cao
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28069877/bone-seeking-matrix-metalloproteinase-2-inhibitors-prevent-bone-metastatic-breast-cancer-growth
#14
Marilena Tauro, Gemma Shay, Samer S Sansil, Antonio Laghezza, Paolo Tortorella, Anthony M Neuger, Hatem Soliman, Conor C Lynch
Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor or host derived MMP-2 contributes to breast cancer growth and does so by processing substrates including type I collagen and transforming growth factorβ (TGFβ) latency proteins. These data provide strong rationale for the application of MMP-2 inhibitors to treat the disease. However, in vivo, MMP-2 is systemically expressed...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28069737/mtorc1-plays-an-important-role-in-skeletal-development-by-controlling-pre-osteoblast-differentiation
#15
Stephen Fitter, Mary P Matthews, Sally K Martin, Jianling Xie, Soo Siang Ooi, Carl R Walkley, John D Codrington, Markus A Ruegg, Michael N Hall, Christopher G Proud, Stan Gronthos, Andrew C W Zannettino
The mammalian target of rapamycin complex 1 (mTORC1) is activated by extracellular factors that control bone accrual. However, the direct role of this complex in osteoblast biology remains to be determined. To investigate this question, we disrupted mTORC1 function in pre-osteoblasts by targeted deletion of Raptor (Rptor) in Osterix-expressing cells. Deletion of Rptor resulted in reduced limb length that was associated with smaller epiphyseal growth plates in the postnatal skeleton. Rptor deletion caused a marked reduction in pre- and post-natal bone accrual, which was evident in skeletal elements derived from both intramembranous and endochondrial ossification...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069522/myeloperoxidase-mediated-protein-lysine-oxidation-generates-2-aminoadipic-acid-and-lysine-nitrile-in-vivo
#16
Hongqiao Lin, Bruce S Levison, Jennifer A Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A DiDonato, Stanley L Hazen
Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2-AAA during inflammatory diseases are unknown...
January 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28069382/antibiotic-tigecycline-enhances-cisplatin-activity-against-human-hepatocellular-carcinoma-through-inducing-mitochondrial-dysfunction-and-oxidative-damage
#17
Jun Tan, Meijun Song, Mi Zhou, Yaoren Hu
Targeting mitochondrial metabolism has been recently demonstrated to be a promising therapeutic strategy for the treatment of various cancer. In this work, we demonstrate that antibiotic tigecycline is selectively against hepatocellular carcinoma (HCC) through inducing mitochondrial dysfunction and oxidative damage. Tigecycline is more effective in inhibiting proliferation and inducing apoptosis of HCC than normal liver cells. Importantly, tigecycline significantly enhances the inhibitory effects of chemotherapeutic drug cisplatin in HCC in vitro and in vivo...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28068081/peptide-decorated-nanofibrous-niche-augments-in-vitro-directed-osteogenic-conversion-of-human-pluripotent-stem-cells
#18
Yi Deng, Yuanyi Yang, Shicheng Wei
Realization of clinical potential of human pluripotent stem cells (hPSCs) in bone regenerative medicine requires development of simple and safe biomaterials for expansion of hPSCs followed by directing their lineage commitment to osteoblasts. In the present study, a chemically defined peptide-decorated polycaprolactone (PCL) nanofibrous microenvironment was prepared through electrospinning technology and subsequent conjugation with vitronectin peptide to promote the culture and osteogenic potential of hPSCs in vitro...
January 9, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28063987/a-mathematical-model-for-the-determination-of-forming-tissue-moduli-in-needled-nonwoven-scaffolds
#19
Joao S Soares, Will Zhang, Michael S Sacks
Formation of engineering tissues (ET) remains an important scientific area of investigation for both clinical translational and mechanobiological studies. Needled-nonwoven (NNW) scaffolds represent one of the most ubiquitous biomaterials based on their well-documented capacity to sustain tissue formation and the unique property of substantial construct stiffness amplification, the latter allowing for very sensitive determination of forming tissue modulus. Yet, their use in more fundamental studies is hampered by the lack of (1) substantial understanding of the mechanics of the NNW scaffold itself under finite deformations and means to model the complex mechanical interactions between scaffold fibers, cells, and de novo tissue; and (2) rational models with reliable predictive capabilities describing their evolving mechanical properties and their response to mechanical stimulation...
January 4, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28063918/simultaneous-in-vivo-receptor-occupancy-assays-for-serotonin-1a-2a-and-dopamine-2-receptors-with-the-use-of-non-radiolabelled-tracers-proposed-method-in-screening-antipsychotics
#20
Jagadeesh Babu Thentu, Ramakrishna Nirogi, Gopinadh Bhyrapuneni, Devender Reddy Ajjala, Raghupathi Reddy Aleti, Veera Raghava Choudary Palacharla
INTRODUCTION: Conventionally, receptor occupancy assays employ radiolabelled tracer.However, recent advances with non-radiolabelled tracers brought a revolution in target engagement assays.Non-radiolabelled tracer based receptor occupancy uses LC-MS/MS based quantification.It offers simultaneous quantification of more than one tracer; thus, provides the feasibility of evaluating multiple targets in a single animal.In the present study, we demonstrated simultaneous measurement of serotonin 1A, serotonin 2A, and dopamine 2 receptor occupancy using non-radiolabelled tracers in rats...
January 4, 2017: Journal of Pharmacological and Toxicological Methods
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