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https://www.readbyqxmd.com/read/28322844/a-harmine-derived-beta-carboline-displays-anti-cancer-effects-in-vitro-by-targeting-protein-synthesis
#1
Annelise Carvalho, Jennifer Chu, Céline Meinguet, Robert Kiss, Guy Vandenbussche, Bernard Masereel, Johan Wouters, Alexander Kornienko, Jerry Pelletier, Véronique Mathieu
Growing evidence indicates that protein synthesis is deregulated in cancer onset and progression and targeting this process might be a selective way to combat cancers. While harmine is known to inhibit DYRK1A and intercalate into the DNA, tri-substitution was shown previously to modify its activity profile in favor of protein synthesis inhibition. In this study, we thus evaluated the optimized derivative CM16 in vitro anti-cancer effects unfolding its protein synthesis inhibition activity. Indeed, the growth inhibitory profile of CM16 in the NCI 60-cancer-cell-line-panel correlated with those of other compounds described as protein synthesis inhibitors...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322160/an-efficient-transient-expression-system-for-enhancing-generation-of-monoclonal-antibodies-in-293-suspension-cells
#2
Guoquan Zhang, Jie Liu, Wanting Fan, Qianyi Chen, Bin Shi
BACKGROUND: Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAb in mammalian cells. However, though a few commercial expression systems of mAbs can be listened, the high expense often impedes academia researches. METHODS: In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contains internal ribosome entry site (IRES) and enhancer elements to express IgG1 light chain (LC) and heavy chain (HC) in one transcript...
March 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28320882/contributions-of-the-n-terminal-and-c-terminal-domains-of-initiation-factor-3-towards-its-functions-in-the-fidelity-of-initiation-and-anti-association-of-the-ribosomal-subunits
#3
Shreya Ayyub, Divya Dobriyal, Umesh Varshney
Initiation factor 3 (IF3) is one of the three conserved prokaryotic translation initiation factors essential for protein synthesis and cellular survival. Bacterial IF3 is composed of a conserved architecture of N- and C- terminal globular domains (NTD and CTD) joined by a linker region. IF3 is a ribosome anti-association factor which also modulates selection of start codon and initiator tRNA. All the functions of IF3 have been attributed to its CTD by in vitro studies. However, in vivo relevance of these findings has not been investigated...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28315697/the-role-of-the-tor-pathway-in-mediating-the-link-between-nutrition-and-longevity
#4
REVIEW
Oleh Lushchak, Olha Strilbytska, Veronika Piskovatska, Kenneth B Storey, Alexander Koliada, Alexander Vaiserman
The target of rapamycin (TOR) pathway integrates signals from extracellular and intracellular agents, such as growth factors, nutrients, mediators of energy balance, oxygen availability and other environmental cues. It allows the regulation of multiple cellular processes including protein and lipid synthesis, ribosome biogenesis, autophagy and metabolic processes. Being conserved across different phyla, TOR regulates longevity of various organisms in response to dietary conditions. In this review we described the main components of the TOR pathway and its upstream effectors and downstream processes in relation to aging...
March 15, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28303005/ligand-co-crystallization-of-aminoacyl-trna-synthetases-from-infectious-disease-organisms
#5
Spencer O Moen, Thomas E Edwards, David M Dranow, Matthew C Clifton, Banumathi Sankaran, Wesley C Van Voorhis, Amit Sharma, Colin Manoil, Bart L Staker, Peter J Myler, Donald D Lorimer
Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#6
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28283558/gene-expression-profiling-with-cre-conditional-pseudorabies-virus-reveals-a-subset-of-midbrain-neurons-that-participate-in-reward-circuitry
#7
Lisa E Pomeranz, Mats I Ekstrand, Kaamashri N Latcha, Gregory A Smith, Lynn W Enquist, Jeffrey M Friedman
The mesolimbic dopamine pathway receives inputs from numerous regions of the brain as part of a neural system that detects rewarding stimuli and coordinates a behavioral response. The capacity to simultaneously map and molecularly define the components of this complex multisynaptic circuit would thus advance our understanding of the determinants of motivated behavior. To accomplish this, we have constructed pseudorabies virus (PRV) strains in which viral propagation and fluorophore expression are activated only after exposure to Cre recombinase...
March 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28263991/selective-inhibition-of-rna-polymerase-i-transcription-as-a-potential-approach-to-treat-african-trypanosomiasis
#8
Louise E Kerry, Elaine E Pegg, Donald P Cameron, James Budzak, Gretchen Poortinga, Katherine M Hannan, Ross D Hannan, Gloria Rudenko
Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High VSG expression within an expression site body (ESB) is mediated by RNA polymerase I (Pol I), which in other eukaryotes exclusively transcribes ribosomal RNA genes (rDNA). As T. brucei is reliant on Pol I for VSG transcription, we investigated Pol I transcription inhibitors for selective anti-trypanosomal activity. The Pol I inhibitors quarfloxin (CX-3543), CX-5461, and BMH-21 are currently under investigation for treating cancer, as rapidly dividing cancer cells are particularly dependent on high levels of Pol I transcription compared with nontransformed cells...
March 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28263311/a-subset-of-platinum-containing-chemotherapeutic-agents-kills-cells-by-inducing-ribosome-biogenesis-stress
#9
Peter M Bruno, Yunpeng Liu, Ga Young Park, Junko Murai, Catherine E Koch, Timothy J Eisen, Justin R Pritchard, Yves Pommier, Stephen J Lippard, Michael T Hemann
Cisplatin and its platinum analogs, carboplatin and oxaliplatin, are some of the most widely used cancer chemotherapeutics. Although cisplatin and carboplatin are used primarily in germ cell, breast and lung malignancies, oxaliplatin is instead used almost exclusively to treat colorectal and other gastrointestinal cancers. Here we utilize a unique, multi-platform genetic approach to study the mechanism of action of these clinically established platinum anti-cancer agents, as well as more recently developed cisplatin analogs...
February 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28260497/improved-protein-toxin-delivery-based-on-attempts-systems
#10
Yongzhuo Huang, Victor C Yang, Feng Li, Meong Cheol Shin, Huiyuan Wang, Kyoung Ah Min, Meng Zhang, Yingzhi Chen
Ribosome-inactivating proteins (RIPs) are wildly found in multiple species of plants, bacteria and fungi. As a special family of protein toxins, RIPs can inhibit protein synthesis and induce cell death via inactivating ribosome in eukaryotic cells. Thus, RIPs have been applied for anti-tumor therapy in the past two decades. However, because of poor cell permeability, nonselective mode of action for tumor cells, poor pharmacokinetic profiles and immunogenicity, their clinical application has been severely constrained...
March 1, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28260147/establishment-and-characterization-of-a-squamous-cell-carcinoma-cell-line-designated-hzk-1-derived-from-a-metastatic-lymph-node-tumor-of-the-tongue
#11
Tetsuya Hirabayashi, Haruka Takahashi, Miho Watanabe, Toshiaki Tachibana
The hZK-1 cell line was successfully established from the metastatic foci of a lymph node of an 82-year-old Japanese woman with squamous cell carcinoma of the tongue. The pathological diagnosis of the tumor was moderately to well-differentiated squamous cell carcinoma. The hZK-1 cells were angular in shape, and had neoplastic and pleomorphic features. Adjacent hZK-1 cells were joined by desmosomes and well-developed microvilli, and many free ribosomes were observed in the cytoplasm. The doubling time of the hZK-1 cells was approximately 36, 33, and 29 h at the 10th, 20th, and 30th passages, respectively...
March 4, 2017: Human Cell
https://www.readbyqxmd.com/read/28249746/the-evaluation-of-cultivable-microbiota-profile-in-patients-with-secondary-endodontic-infection-before-and-after-photo-activated-disinfection
#12
Maryam Pourhajibagher, Roghayeh Ghorbanzadeh, Steven Parker, Nasim Chiniforush, Abbas Bahador
BACKGROUND: Secondary/persistent endodontic infection can be the outcome of failure of endodontic treatment. Photo-activated disinfection (PAD) can be a useful adjunct to mechanical and antimicrobial agents in eliminating endopathogenic microorganisms. In this study, we evaluated the effect of PAD on diversity and count of microbiota related to secondary/persistent endodontic infections. MATERIALS AND METHODS: Root canal samples were taken using sterile paper points from the root canals of 14 patients with secondary/persistent endodontic infections after removing the root-canal filling materials...
February 26, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28209400/multidrug-resistant-enterococcal-infections-new-compounds-novel-antimicrobial-therapies
#13
REVIEW
Roel M van Harten, Rob J L Willems, Nathaniel I Martin, Antoni P A Hendrickx
Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E...
February 13, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28205545/octreotide-attenuates-acute-kidney-injury-after-hepatic-ischemia-and-reperfusion-by-enhancing-autophagy
#14
Huiping Sun, Shuangfa Zou, Keith A Candiotti, Yanhua Peng, Qinya Zhang, Weiqiang Xiao, Yiyun Wen, Jiao Wu, Jinfeng Yang
Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194024/regnase-1-a-rapid-response-ribonuclease-regulating-inflammation-and-stress-responses
#15
REVIEW
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28192480/mtor-activity-in-aids-related-diffuse-large-b-cell-lymphoma
#16
Sara H Browne, Julio A Diaz-Perez, Michael Preziosi, Charles C King, George A Jones, Sonia Jain, Xiaoying Sun, Erin G Reid, Scott VandenBerg, Huan-You Wang
BACKGROUND: Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28170113/helicoverpa-zea-gut-associated-bacteria-indirectly-induce-defenses-in-tomato-by-triggering-a-salivary-elicitor-s
#17
Jie Wang, Michelle Peiffer, Kelli Hoover, Cristina Rosa, Rensen Zeng, Gary W Felton
Insect gut-associated microbes modulating plant defenses have been observed in beetles and piercing-sucking insects, but the role of caterpillar-associated bacteria in regulating plant induced defenses has not been adequately examined. We identified bacteria from the regurgitant of field-collected Helicoverpa zea larvae using 16S ribosomal RNA (rRNA) gene sequencing and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. A combination of biochemical, molecular, and confocal electron microscopy methods were used to determine the role of caterpillar-associated bacteria in mediating defenses in Solanum lycopersicum (tomato)...
February 7, 2017: New Phytologist
https://www.readbyqxmd.com/read/28164609/anti-cytoplasmic-autoantibodies-in-hodgkin-s-lymphoma
#18
Joachim Sennekamp, Hans-Peter Seelig
BACKGROUND: A 42-year old male patient with anamnesis of bronchial asthma presented himself with exertional dyspnea. High titer antibodies of cytoplasmic pattern in the indirect immunofluorescence test (IIFT) on HEp-2cells, not attributable to common specificities like anti-tRNA-synthetases, anti-signal recognition particle (SRP) or anti-ribosomal proteins (RPs) prompted the molecular biological approach for determination of antigen specificity. In-depth investigation of the patient's clinical settings revealed a lymphocyte predominant Hodgkin's lymphoma, which could be brought to complete remission by chemotherapy...
August 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28150900/discovery-of-antimicrobial-and-antitubercular-molecules-from-fusarium-solani-an-endophyte-of-glycyrrhiza-glabra
#19
Aiyatullah Shah, Muzafar Ahmad Rather, Parvaiz H Qazi, Mushtaq A Aga, Saleem Mushtaq, Aabid Manzoor Shah, Aehtesham Hussain, Shoib A Baba, Zahoor Ahmad
AIM: Glycyrrhiza glabra is a high value medicinal plant thriving in biodiversity rich Kashmir Himalaya. The present study was designed to explore the fungal endophytes from G glabra as a source of bioactive molecules. METHODS AND RESULTS: The extracts prepared from the isolated endophytes were evaluated for antimicrobial activities using broth micro-dilution assay. The endophytic strain coded as A2 exhibiting promising antibacterial as well as antituberculosis activity was identified as Fusarium solani by ITS-5...
February 2, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28100663/leveraging-genome-wide-datasets-to-quantify-the-functional-role-of-the-anti-shine-dalgarno-sequence-in-regulating-translation-efficiency
#20
Adam J Hockenberry, Adam R Pah, Michael C Jewett, Luís A N Amaral
Studies dating back to the 1970s established that sequence complementarity between the anti-Shine-Dalgarno (aSD) sequence on prokaryotic ribosomes and the 5' untranslated region of mRNAs helps to facilitate translation initiation. The optimal location of aSD sequence binding relative to the start codon, the full extents of the aSD sequence and the functional form of the relationship between aSD sequence complementarity and translation efficiency have not been fully resolved. Here, we investigate these relationships by leveraging the sequence diversity of endogenous genes and recently available genome-wide estimates of translation efficiency...
January 2017: Open Biology
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