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https://www.readbyqxmd.com/read/29458146/enhanced-anticancer-effects-of-scutellaria-barbata-d-don-in-combination-with-traditional-chinese-medicine-components-on-non-small-cell-lung-cancer-cells
#1
Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells...
February 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29458108/the-relaxin-receptor-as-a-therapeutic-target-perspectives-from-evolution-and-drug-targeting
#2
REVIEW
Ross A D Bathgate, Martina Kocan, Daniel J Scott, M Akhter Hossain, Sara V Good, Sergey Yegorov, Jan Bogerd, Paul Gooley
The peptide relaxin was first identified as an important circulating hormone during pregnancy over 90 years ago. Research over many years defined the numerous biological roles that relaxin plays throughout pregnancy in many mammalian species. These important biological actions have led to the testing of relaxin as a therapeutic agent for a number of indications. The discovery of the relaxin receptor, RXFP1, in 2002 facilitated the better understanding of the cellular targets of relaxin, its mechanism of action and enabled the development of relaxin mimetics and screening for small molecule agonists...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29458099/using-near-infrared-spectroscopy-to-predict-the-lignin-content-and-monosaccharide-compositions-of-pinus-radiata-wood-cell-walls
#3
Leona M Fahey, Michél K Nieuwoudt, Philip J Harris
Near infrared (NIR) spectroscopy coupled with partial least squares (PLS-1) regression was used to predict the lignin contents and monosaccharide compositions of milled wood of Pinus radiata. The effects of particle size and moisture content were investigated by collecting NIR spectra of four sample types: large (<0.422 mm) and small (<0.178 mm) particles, in both ambient and dry conditions. PLS-1 models were constructed using mixtures of compression wood (CW) and opposite wood (OW) that provided a linear range of cell-wall compositions...
February 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29458097/topographical-memory-analyzed-in-mice-using-the-hamlet-test-a-novel-complex-maze
#4
Lucie Crouzier, Damien Gilabert, Mireille Rossel, Françoise Trousse, Tangui Maurice
The Hamlet test is an innovative device providing a complex environment for testing topographic memory in mice. Animals were trained in groups for weeks in a small village with a central agora, streets expanding from it towards five functionalized houses, where they can drink, eat, hide, run, interact with a stranger mouse. Memory was tested by depriving mice from water or food and analyzing their ability to locate the Drink/Eat house. Exploration and memory were analysed in different strains, gender, and after different training periods and delays...
February 16, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29458089/structural-and-biophysical-insight-into-dual-site-binding-of-the-protoberberine-alkaloid-palmatine-to-parallel-g-quadruplex-dna-using-nmr-fluorescence-and-circular-dichroism-spectroscopy
#5
Kumar Padmapriya, Ritu Barthwal
Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4 , has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by1 H and31 P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra...
February 16, 2018: Biochimie
https://www.readbyqxmd.com/read/29458079/autofluorescence-a-potential-pitfall-in-immunofluorescence-based-inflammation-grading
#6
Jonas Wizenty, Muhammad Imtiaz Ashraf, Nadine Rohwer, Martin Stockmann, Sascha Weiss, Matthias Biebl, Johann Pratschke, Felix Aigner, Tilo Wuensch
Immunofluorescence (IF) staining of paraffin-embedded tissues is a frequently used method to answer research questions or even detect the abundance of a certain protein for diagnostic use. However, the signal originating from specific antibody-staining might be distorted by autofluorescence (AF) of the assessed tissue. Although the AF phenomenon is well known, its presence is often neglected by insufficient staining controls. In this study, we describe the existence of cellular AF in paraffin-embedded healthy and inflamed human and murine colonic tissues and present ways to reduce AF...
February 16, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29458077/reciprocal-regulation-of-the-cadherin-11-stat3-axis-by-caveolin-1-in-mouse-fibroblasts-and-lung-carcinoma-cells
#7
M Geletu, R Mohan, R Arulanandam, A Berger-Becvar, I R Nabi, P T Gunning, L Raptis
Caveolin-1 (Cav1) is an integral plasma membrane protein and a complex regulator of signal transduction. The Signal Transducer and Activator of Transcription-3 (Stat3) is activated by a number of receptor and non-receptor tyrosine kinases and is positively implicated in cancer. Despite extensive efforts, the relationship between Cav1 and Stat3 has been a matter of controversy. We previously demonstrated that engagement of E- or N-cadherin or cadherin-11 cell to cell adhesion molecules, as occurs with confluence of cultured cells, triggers a dramatic increase in the levels of tyr705 phosphorylated ie activated Stat3, by a mechanism requiring the cRac1 small GTPase...
February 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29458026/knockdown-of-fascin-1-expression-suppresses-cell-migration-and-invasion-of-non-small-cell-lung-cancer-by-regulating-the-mapk-pathway
#8
Da Zhao, Tao Zhang, Xiao-Ming Hou, Xiao-Ling Ling
Fascin-1 is a cytoskeletal protein and it can specifically bind to F-actin, it can be abnormally expressed in a variety of solid tumors. Fascin-1 was identified as a factor for poor prognosis in non-small cell lung cancer (NSCLC). However, the relevant molecular mechanisms are not yet fully understood. In this study, the fascin-1 knockdown cells were produced by lentivirus infection, and then cell proliferation, invasion and cell migration assay were used to investigate the role of fascin-1 in NSCLC cells. The MAPK pathway related proteins were determined by western blot...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458023/structural-characterization-of-the-hcov-229e-fusion-core
#9
Wei Zhang, Qianqian Zheng, Mengrong Yan, Xiaobo Chen, Haitao Yang, Weihong Zhou, Zihe Rao
HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458013/ago2-rna-immunoprecipitation-reveals-distinct-mirna-targetomes-of-primary-burkitt-lymphoma-tumors-and-normal-b-cells
#10
Agnieszka Dzikiewicz-Krawczyk, Arjan Diepstra, Bea Rutgers, Gertrud Kortman, Debora de Jong, Jasper Koerts, Marian Bulthuis, Tineke van der Sluis, Annika Seitz, Lydia Visser, Klaas Kok, Joost Kluiver, Anke van den Berg
MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression. Deregulated miRNA levels have been linked to Burkitt lymphoma (BL) pathogenesis. To date, the number of known pathogenesis-related miRNA-target gene interactions is limited. Here, we determined for the first time the miRNA targetomes of primary BL tumors and normal B cells. AGO2-RNA immunoprecipitation (AGO2-RIP) of two frozen diagnostic BL tissue samples and three CD19+ B-cell samples isolated from routinely removed tonsils revealed distinct miRNA targetomes of BL and normal B cells...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29458008/trefoil-factor-2-promotes-type-2-immunity-and-lung-repair-through-intrinsic-roles-in-hematopoietic-and-non-hematopoietic-cells
#11
Li-Yin Hung, Taylor K Oniskey, Debasish Sen, Matthew F Krummel, Andrew E Vaughan, Noam A Cohen, De'Broski R Herbert
Trefoil factors are small secreted proteins that regulate tissue integrity and repair at mucosal surfaces, particularly in the gastrointestinal tract. However, their relative contribution(s) to controlling baseline lung function or the extent of infection-induced lung injury are unknown issues. Using irradiation bone marrow chimeras, we found that Trefoil factor 2 (TFF2) produced from both hematopoietic- and non-hematopoietic-derived cells is essential for host protection, proliferation of alveolar type 2 cells, and restoration of pulmonary gas exchange following infection with the hookworm parasite Nippostrongylus brasiliensis...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29457857/towards-structural-studies-of-self-assembled-subviral-particles-combining-cell-free-expression-with-100-khz-mas-nmr
#12
Guillaume David, Marie-Laure Fogeron, Maarten Schledorn, Roland Montserret, Uta Haselmann, Susanne Penzel, Aurelie Badillo, Lauriane Lecoq, Patrice André, Michael Nassal, Ralf Bartenschlager, Beat H Meier, Anja Böckmann
Viral membrane proteins are prime targets in the combat against infection. Still, their structure determination remains a challenge, both with respect to sample preparation, and the need for structural methods allowing analysis in a native-like lipid environment. Cell-free protein synthesis and solid-state NMR are promising approaches in this context, one with respect to its high potential of native expression of complex proteins, and the other for its ability to analyze membrane proteins in lipids. We here show that milligram amounts of the small envelope protein of the duck hepatitis B virus (DHBV) can be produced using cell-free expression, and that the protein self-assembles into subviral particles...
February 19, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29457838/bax-inhibitor-1-protects-from-non-alcoholic-steatohepatitis-by-limiting-ire1%C3%AE-signaling
#13
Cynthia Lebeaupin, Déborah Vallée, Déborah Rousseau, Stéphanie Patouraux, Stéphanie Bonnafous, Gilbert Adam, Frederic Luciano, Carmelo Luci, Rodolphe Anty, Antonio Iannelli, Sandrine Marchetti, Guido Kroemer, Sandra Lacas-Gervais, Albert Tran, Philippe Gual, Béatrice Bailly-Maitre
Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29457796/h3b-8800-an-orally-available-small-molecule-splicing-modulator-induces-lethality-in-spliceosome-mutant-cancers
#14
Michael Seiler, Akihide Yoshimi, Rachel Darman, Betty Chan, Gregg Keaney, Michael Thomas, Anant A Agrawal, Benjamin Caleb, Alfredo Csibi, Eckley Sean, Peter Fekkes, Craig Karr, Virginia Klimek, George Lai, Linda Lee, Pavan Kumar, Stanley Chun-Wei Lee, Xiang Liu, Crystal Mackenzie, Carol Meeske, Yoshiharu Mizui, Eric Padron, Eunice Park, Ermira Pazolli, Shouyong Peng, Sudeep Prajapati, Justin Taylor, Teng Teng, John Wang, Markus Warmuth, Huilan Yao, Lihua Yu, Ping Zhu, Omar Abdel-Wahab, Peter G Smith, Silvia Buonamici
Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells...
February 19, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29457675/oocyte-activating-capacity-of-fresh-and-frozen-thawed-spermatids-in-the-common-marmoset-callithrix-jacchus
#15
Narumi Ogonuki, Hiroki Inoue, Shogo Matoba, Yoko Kakino Kurotaki, Hidetoshi Kassai, Yukiko Abe, Erika Sasaki, Atsu Aiba, Atsuo Ogura
The common marmoset (Callithrix jacchus) represents a promising nonhuman primate model for the study of human diseases because of its small size, ease of handling, and availability of gene-modified animals. Here, we aimed to devise reproductive technology for marmoset spermatid injection using immature males for a possible rapid generational turnover. Spermatids at each step could be identified easily by their morphology under differential interference microscopy: thus, early round spermatids had a round nucleus with a few nucleolus-like structures and abundant cytoplasm, as in other mammals...
February 19, 2018: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29457608/redox-responsive-ucnps-dpa-conjugated-ngo-peg-bpei-dox-for-imaging-guided-ptt-and-chemotherapy-for-cancer-treatment
#16
Arif Gulzar, Jiating Xu, Liangge Xu, Piaoping Yang, Fei He, Dan Yang, Guanghui An, Mohd Bismillah Ansari
The disulfide bond (-S-S-) is an enormously valuable functional group in a variety of chemical and biological agents that display effective reactivity or biological activities (e.g., antitumor activities). The disulfide bonds prevalent in proteins are somewhat oxidizing in the extracellular space; however, such disulfide bonds can rarely be found inside cells because of disulfide cleavage reactions facilitated by abundant free cellular thiols, including glutathione (GSH), which is the most important common thiol-containing small molecule...
February 19, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#17
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457531/shedding-new-light-on-rhoa-signalling-as-a-drug-target-in-vivo-using-a-novel-rhoa-fret-biosensor-mouse
#18
Max Nobis, David Herrmann, Sean C Warren, Douglas Strathdee, Thomas R Cox, Kurt I Anderson, Paul Timpson
The small GTPase RhoA is a master regulator of signalling in cell-extracellular matrix interactions. RhoA signalling is critical to many cellular processes including migration, mechanotransduction, and is often disrupted in carcinogenesis. Investigating RhoA activity in a native tissue environment is challenging using conventional biochemical methods; we therefore developed a RhoA-FRET biosensor mouse, employing the adaptable nature of intravital imaging to a variety of settings. Mechnotransduction was explored in the context of osteocyte processes embedded in the calvaria responding in a directional manner to compression stress...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457313/modeling-the-hematocrit-distribution-in-microcirculatory-networks-a-quantitative-evaluation-of-a-phase-separation-model
#19
Peter M Rasmussen, Timothy W Secomb, Axel R Pries
OBJECTIVE: Theoretical models are essential tools for studying microcirculatory function. Recently, the validity of a well-established phase separation model was questioned and it was claimed that it produces problematically low hematocrit predictions and lack of red cells in small diameter vessels. We conducted a quantitative evaluation of this phase separation model to establish common ground for future research. METHODS: Model predictions were validated against a comprehensive data base with measurements from four mesenteric networks...
February 19, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29457051/signet-ring-cell-carcinoma-ileal-crohn-disease-or-both-a-case-of-diagnostic-challenge
#20
Joana R Carvalho, Joana Tavares, Inês Goulart, Paula Moura Dos Santos, Emília Vitorino, Cristina Ferreira, Fátima Serejo, José Velosa
Signet ring cell carcinoma is a rare form of adenocarcinoma that predominantly affects the stomach. Signet ring cell carcinoma originated from the ileum is extremely rare and the prognosis is poor. We present a case of small bowel obstruction with features suggesting Crohn disease of the ileum. The symptoms were chronic diarrhea and abdominal pain with a family history of inflammatory bowel disease. The patient underwent surgery and histopathology revealed both aspects of signet ring cell carcinoma and Crohn disease of the ileum...
January 2018: GE Portuguese Journal of Gastroenterology
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