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https://www.readbyqxmd.com/read/28637319/matrix-metalloproteinases-their-functional-role-in-lung-cancer
#1
Neha Merchant, Ganji Purnachandra Nagaraju, Balney Rajitha, Saipriya Lammata, Kishore Kumar Jella, Zachary S Buchwald, Sajani S Lakka, Arif N Ali
Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared to non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors which control the tumor microenvironment...
June 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28637243/nanopore-sequencing-data-analysis-state-of-the-art-applications-and-challenges
#2
Alberto Magi, Roberto Semeraro, Alessandra Mingrino, Betti Giusti, Romina D'Aurizio
The nanopore sequencing process is based on the transit of a DNA molecule through a nanoscopic pore, and since the 90s is considered as one of the most promising approaches to detect polymeric molecules. In 2014, Oxford Nanopore Technologies (ONT) launched a beta-testing program that supplied the scientific community with the first prototype of a nanopore sequencer: the MinION. Thanks to this program, several research groups had the opportunity to evaluate the performance of this novel instrument and develop novel computational approaches for analyzing this new generation of data...
June 16, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28637023/cationic-liquid-crystalline-nanoparticles-for-the-delivery-of-synthetic-rnai-based-therapeutics
#3
Emanuela Gentile, Taro Oba, Jing Lin, Ruping Shao, Feng Meng, Xiaobo Cao, Heather Y Lin, Majidi Mourad, Apar Pataer, Veerabhadran Baladandayuthapani, Dong Cai, Jack A Roth, Lin Ji
RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short half-life, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637014/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#4
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636979/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#5
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636951/structure-of-cc-chemokine-receptor-5-with-a-potent-chemokine-antagonist-reveals-mechanisms-of-chemokine-recognition-and-molecular-mimicry-by-hiv
#6
Yi Zheng, Gye Won Han, Ruben Abagyan, Beili Wu, Raymond C Stevens, Vadim Cherezov, Irina Kufareva, Tracy M Handel
CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636912/channeling-of-camp-in-pde-pka-complexes-promotes-signal-adaptation
#7
Nikhil Kumar Tulsian, Srinath Krishnamurthy, Ganesh Srinivasan Anand
Spatiotemporal control of the cAMP signaling pathway is governed by both hormonal stimulation of cAMP generation by adenylyl cyclases (activation phase) and cAMP hydrolysis by phosphodiesterases (PDEs) (termination phase). The termination phase is initiated by PDEs actively targeting the protein kinase A (PKA) R-subunit through formation of a PDE-PKAR-cyclic adenosine monophosphate (cAMP) complex (the termination complex). Our results using PDE8 as a model PDE, reveal that PDEs mediate active hydrolysis of cAMP bound to its receptor RIα by enhancing the enzymatic activity...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636911/direct-conversion-of-an-enzyme-from-native-like-to-amyloid-like-aggregates-within-inclusion-bodies
#8
Francesco Elia, Francesca Cantini, Fabrizio Chiti, Christopher Martin Dobson, Francesco Bemporad
The acylphosphatase from Sulfolobus solfataricus (Sso AcP) is a globular protein able to aggregate in vitro from a native-like conformational ensemble without the need for a transition across the major unfolding energy barrier. This process leads to the formation of assemblies in which the protein retains its native-like structure, which subsequently convert into amyloid-like aggregates. Here, we investigate the mechanism by which Sso AcP aggregates in vivo to form bacterial inclusion bodies after expression in E...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#9
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28636801/water-channels-and-barriers-formed-by-claudins
#10
REVIEW
Rita Rosenthal, Dorothee Günzel, Dian Theune, Carolina Czichos, Jörg-Dieter Schulzke, Michael Fromm
Physiological studies in leaky epithelia, like kidney proximal tubules and the small intestine, have documented water transport via both transcellular and paracellular pathways. The discovery of aquaporin water channels provided a molecular basis for transcellular water movement. In contrast, the contribution, or even existence, of a specific paracellular water pathway has been disputed for a long time, until the cation channel-forming tight junction protein claudin-2 was shown to also permit the paracellular passage of water through its pore...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28636681/thermally-induced-conformational-changes-and-protein-protein-interactions-of-bovine-serum-albumin-in-aqueous-solution-under-different-ph-and-ionic-strengths-as-revealed-by-saxs-measurements
#11
Dmitry Molodenskiy, Evgeny Shirshin, Tatiana Tikhonova, Andrey Gruzinov, Georgy Peters, Francesco Spinozzi
Thermal-induced conformational changes and protein-protein interactions of bovine serum albumin (BSA) in aqueous solution are assessed by small angle X-ray scattering (SAXS) at two pH values (7.4 and 9.0) and two ionic strengths (0.1 and 0.5). We demonstrate that Guinier analysis in two ranges of the modulus of the scattering vector allows protein melting and aggregation to be monitored simultaneously, thus providing insights into the mechanism of thermal-induced BSA aggregation. Results of the analysis suggest that at room temperature monomeric and dimeric BSA fractions are present in solution...
June 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28636670/identification-of-novel-small-molecules-that-inhibit-stat3-dependent-transcription-and-function
#12
Iryna Kolosenko, Yasmin Yu, Sander Busker, Matheus Dyczynski, Jianping Liu, Martin Haraldsson, Caroline Palm Apergi, Thomas Helleday, Katja Pokrovskaja Tamm, Brent D G Page, Dan Grander
Activation of Signal Transducer and Activator of Transcription 3 (STAT3) has been linked to several processes that are critical for oncogenic transformation, cancer progression, cancer cell proliferation, survival, drug resistance and metastasis. Inhibition of STAT3 signaling has shown a striking ability to inhibit cancer cell growth and therefore, STAT3 has become a promising target for anti-cancer drug development. The aim of this study was to identify novel inhibitors of STAT-dependent gene transcription...
2017: PloS One
https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#13
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28636382/development-of-efficient-chemistry-to-generate-site-specific-disulfide-linked-protein-and-peptide-payload-conjugates-application-to-thiomab%C3%A2-antibody-drug-conjugates
#14
Jack David Sadowsky, Thomas H Pillow, Jinhua Chen, Fang Fan, Changrong He, Yanli Wang, Gang Yan, Hui Yao, Zijin Xu, Shanique Martin, Donglu Zhang, Phillip Chu, Josefa Dela Cruz-Chuh, Aimee O'Donohue, Guangmin Li, Geoffrey Del Rosario, Jintang He, Luna Liu, Carl K Ng, Dian Su, Gail D Lewis Phillips, Katherine Ruth Kozak, Shang-Fan Yu, Keyang Xu, Douglas Leipold, John S Wai
Conjugation of small molecule payloads to specific cysteine residues on proteins via a disulfide bond represents an attractive strategy to generate redox-sensitive bioconjugates, which have value as potential diagnostic reagents or therapeutics. Advancement of such "direct-disulfide" bioconjugates to the clinic necessitates chemical methods to form disulfide connections efficiently, without byproducts. The disulfide connection must also be resistant to premature cleavage by thiols prior to arrival at the targeted tissue...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28636368/probing-the-mechanism-of-lal-32-a-gold-nanoparticle-based-antibiotic-discovered-through-small-molecule-variable-ligand-display
#15
Rose Byrne-Nash, Danielle Lucero, Niki Osbaugh, Roberta J Melander, Christian Melander, Daniel L Feldheim
The unrelenting rise of antimicrobial resistant bacteria has necessitated the search for novel antibiotic solutions. Herein we describe further mechanistic studies on a 2.0 nm diameter gold nanoparticle-based antibiotic (designated LAL-32). This antibiotic exhibits bactericidal activity against the Gram-negative bacterium Escherichia coli at 1.0 μΜ, a concentration significantly lower than several clinically available antibiotics (such as ampicillin and gentamicin), and acute treatment with LAL-32 does not give rise to spontaneous resistant mutants...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28636364/charge-shift-corrected-electronegativities-and-the-effect-of-bond-polarity-and-substituents-on-covalent-ionic-resonance-energy
#16
Andrew M James, Croix J Laconsay, John Morrison Galbraith
Bond dissociation energies and resonance energies for HnA-BHm molecules (A, B = H, C, N, O, F, Cl, Li, and Na) have been determined in order to re-evaluate the concept of electronegativity in the context of modern valence bond theory. Following Pauling's original scheme, and using the rigorous definition of the covalent-ionic resonance energy provided by the breathing orbital valence bond method, we have derived a charge-shift corrected electronegativity scale for H, C, N, O, F, Cl, Li, and Na. Atomic charge shift character is defined using a similar approach resulting in values of 0...
June 21, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28636355/semisynthetic-flavone-derived-antimicrobials-with-therapeutic-potential-against-methicillin-resistant-staphylococcus-aureus-mrsa
#17
Shuimu Lin, Jun-Jie Koh, Thet Tun Aung, Wan Ling Wendy Sin, Fanghui Lim, Lin Wang, Rajamani Lakshminarayanan, Lei Zhou, Donald T H Tan, Derong Cao, Roger W Beuerman, Li Ren, Shouping Liu
A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has been designed from natural icaritin to combat drug-resistant Gram-positive bacterial infections. Compound 6 containing two arginine residues exhibited excellent antibacterial activity against Gram-positive bacteria, including MRSA, and very low toxicity to mammalian cells, resulting in a high selectivity of more than 511, comparable to that of several membrane-active antibiotics in clinical trials. Our data show for the first time that icaritin derivatives effectively kill bacteria...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28636330/water-in-ionic-liquid-lubricants-friend-and-foe
#18
Oscar Y Fajardo, Fernando Bresme, Alexei A Kornyshev, Michael Urbakh
To a greater or lesser extent, most room temperature ionic liquids (RTILs) absorb water from humid air. Penetration of water into the lubricating nanoscale film may affect its equilibrium structure and dynamic properties and thus influence the ability of RTILs as lubricants to reduce friction between solid surfaces. Here we investigate the impact of hydration on lubrication using non-equilibrium molecular dynamics simulations. Water adsorption changes both the ionic liquid molecules orientation and the slip conditions at the solid-liquid interfaces, resulting in a reduced resistance against squeezing-out of the lubricant by an external load...
June 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#19
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28636246/stretchable-electrochemical-sensor-for-inducing-and-monitoring-cell-mechanotransduction-in-real-time
#20
Yan-Ling Liu, Yu Qin, Zi-He Jin, Xue-Bo Hu, Miao-Miao Chen, Rong Liu, Christian Amatore, Wei-Hua Huang
Existing methods offer little direct and real-time information about stretch-triggered biochemical responses during cell mechanotransduction. Herein, we report a novel stretchable electrochemical sensor that takes advantage of a hierarchical percolation network of carbon nanotubes and gold nanotubes (CNTs- Au NTs). This hybrid nano-structure provides the sensor with excellent time-reproducible mechanical and electrochemical performances while granting very good cellular compatibility, making it perfectly apt to induce and monitor simultaneously transient biochemical signals...
June 21, 2017: Angewandte Chemie
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