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Egisto Boschetti, Lorenzo E Hernández-Castellano, Pier Giorgio Righetti
The present review covers proteomics discoveries in farm animals using combinatorial peptide ligand libraries (CPLLs). These libraries enhance the identification of low-abundance proteins by compressing the dynamic range of the protein concentration. This technology can be applied in multiple biological fluids, such as plasma or serum, follicular and cerebrospinal fluids, urine, saliva, tears seminal fluid, milk whey and even lymph. The discovery of low-abundance proteins contributes to the continuous monitoring for animal pathologies, which allows early treatment and disease prevention...
February 11, 2019: Journal of Proteomics
Carolina Abril-Sánchez, Adrián Matencio, Silvia Navarro-Orcajada, Francisco García-Carmona, José Manuel López-Nicolás
In this work we used natural and modified cyclodextrins (β-CD and HP-β-CD) as encapsulating agents to improve citronellal properties. Using fluorimetric techniques, its aggregation behavior was studied for the first time. Its critical micellar concentration was seen to vary with the presence of cyclodextrins, which form 1:1 stoichiometry complexes with citronellal. The encapsulation constants and the scores obtained by Molecular Docking were correlated. Chromatographic (GC-MS) and sensory analysis confirmed that cyclodextrins improve the persistence of the aroma...
February 11, 2019: Chemistry and Physics of Lipids
Yucheng Guo, Chen Bao, Dacheng Ma, Yubing Cao, Yanda Li, Zhen Xie, Shao Li
Tumorigenesis is a complex process that is driven by a combination of the networks of genes and environmental factors; however, efficient approaches for identifying functional networks that are perturbed by the process of tumorigenesis is poorly understood. Then, the identification of functional synergistic modules and pathways is often limited by computational method and experiment measures. Here, we propose an integrated network-based approach for the systematic discovery of functional synergistic modules that are causal determinants of inflammation-induced tumorigenesis, by prioritizing candidate genes of integrating clinical-based and network-based genome-wide gene prediction methods and identify functional synergistic modules based on combinatorial CRISPR-Cas9 screens...
February 14, 2019: ACS Synthetic Biology
Tadeo Enrique Velazquez-Caldelas, Sergio Antonio Alcalá-Corona, Jesús Espinal-Enríquez, Enrique Hernandez-Lemus
Inflammation has been recognized as an important driver in the development and growth of malignancies. Inflammatory signaling in cancer emerges from the combinatorial interaction of several deregulated pathways. Pathway deregulation is often driven by changes in the underlying gene regulatory networks. Confronted with such complex scenario, it can be argued that a closer analysis of the structure of such regulatory networks will shed some light on how gene deregulation led to sustained inflammation in cancer...
2019: Frontiers in Immunology
Daniel Schulz, Yannik Severin, Vito Riccardo Tomaso Zanotelli, Bernd Bodenmiller
Phagocytosis is a process in which target cells or particles are engulfed and taken up by other cells, typically professional phagocytes; this process is crucial in many physiological processes and disease states. The detection of targets for phagocytosis is directed by a complex repertoire of cell surface receptors. Pattern recognition receptors directly detect targets for binding and uptake, while opsonic and complement receptors detect objects coated by soluble factors. However, the importance of single and combinatorial surface marker expression across different phenotypes of professional phagocytes is not known...
February 13, 2019: Scientific Reports
Takeo K Maeda, Daisuke Sugiura, Il-Mi Okazaki, Takumi Maruhashi, Taku Okazaki
T cell activation is tightly regulated by both stimulatory and inhibitory co-receptors and has been a focus in the development of interventions for managing cancer or autoimmune diseases. Targeting the inhibitory co-receptors programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has successfully eradicated tumors but induced immune-related adverse-events in human and mice. The beneficial and adverse effects of targeting these co-receptors highlight their importance in cancer immunity and also autoimmunity...
February 13, 2019: Journal of Biological Chemistry
Yide Zhang, Evan L Nichols, Abigail M Zellmer, Ian H Guldner, Cody Kankel, Siyuan Zhang, Scott S Howard, Cody J Smith
Super-resolution microscopy is broadening our in-depth understanding of cellular structure. However, super-resolution approaches are limited, for numerous reasons, from utilization in longer-term intravital imaging. We devised a combinatorial imaging technique that combines deconvolution with stepwise optical saturation microscopy (DeSOS) to circumvent this issue and image cells in their native physiological environment. Other than a traditional confocal or two-photon microscope, this approach requires no additional hardware...
February 13, 2019: Development
Trisha Tucholski, Samantha Knott, Bifan Chen, Paige Pistono, Ziqing Lin, Ying Ge
Mass spectrometry (MS)-based top-down proteomics provides rich information about proteoforms arising from combinatorial amino acid sequence variations and post-translational modifications (PTMs). Fourier transform ion cyclotron resonance (FT-ICR) MS affords ultra-high resolving power and provides high-accuracy mass measurements, presenting a powerful tool for top-down MS characterization of proteoforms. However, detection and characterization of large proteins from complex mixtures remain challenging due to the exponential decrease in S:N with increasing molecular weight (MW) and co-eluting low-MW proteins; thus, size-based fractionation of complex protein mixtures prior to MS analysis is necessary...
February 13, 2019: Analytical Chemistry
Chanjuan Liu, Changping Ruan, Rui Shi, Bang-Ping Jiang, Shichen Ji, Xing-Can Shen
Indocyanine green (ICG), a multifunctional near-infrared (NIR) imaging agent approved by the FDA, has been extensively used in clinical cancer theranosis, but limited by its inherent instability, short plasma half-life and lack of targeting ability. Herein, an in situ formed photothermal network based thermosensitive hydrogel (PNT-gel) constructed by using supramolecular cross-linking conjugated polymers was developed for the stabilization of ICG and efficient combinatorial photothermal/photodynamic antitumor therapy...
February 13, 2019: Biomaterials Science
Qimeng Song, Marc Steuber, Sergey I Druzhinin, Holger Schönherr
A novel concept to obtain cell microenvironments by microobject assembly at the water/air interface is reported. Since the orientation of 30 μm sized polymer cubes and their capillary force assembly is found to be controlled by surface wettability, afforded by coating the initially exposed surfaces by gold and self-assembled monolayers, unique niches in closely packed arrays of cubes with vertex up orientation can be realized. The random assembly of distinctly different cubes, pre-functionalized or surface-structured exclusively on their top surface, facilitates the massively parallel generation of different microenvironments in a combinatorial manner, which paves the way to future systematic structure-property relationship studies with cells...
February 13, 2019: Angewandte Chemie
Aryadne L de Almeida, Katiany R Caleffi-Ferracioli, Regiane B de L Scodro, Vanessa P Baldin, Débora C Montaholi, Luiza F Spricigo, Sandra S Nakamura-Vasconcelos, Laíse A Hegeto, Eloísa G Sampiron, Giovana F Costacurta, Diego A Dos S Yamazaki, Gisele de F Gauze, Vera Ld Siqueira, Rosilene F Cardoso
AIM:  To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity. MATERIALS & METHODS:  Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter...
February 13, 2019: Future Microbiology
Bowen Sun, Nathaniel R Jensen, Dongjun Chung, Meixiang Yang, Amanda C LaRue, Hiu Wing Cheung, Qi Wang
The scaffold/adaptor growth factor receptor bound 2 (GRB2)-associated binding protein 2 (GAB2) is frequently amplified and/or overexpressed in primary high-grade serous ovarian cancers (HGSOCs). Here we investigate a novel treatment strategy by targeting SHP2 and PI3K signaling in HGSOCs with GAB2 amplification/overexpression (GAB2High ). The expression of GAB2 was analyzed in primary HGSOCs and ovarian cancer cell lines. In vitro and in vivo assays were performed to demonstrate the effect of SHP2 and PI3K-mediated GAB2High HGSOC progression...
2019: American Journal of Cancer Research
Jong Woo Lee, Janaki Parameswaran, Teresa Sandoval-Schaefer, Kyung Jin Eoh, Dong-Hua Yang, Fang Zhu, Ranee Mehra, Roshan Sharma, Stephen G Gaffney, Elizabeth B Perry, Jeffrey P Townsend, Ilya G Serebriiskii, Erica A Golemis, Natalia Issaeva, Wendell G Yarbrough, Ja Seok Koo, Barbara A Burtness
PURPOSE: Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in TP53, resulting in treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed and an oncogenic driver, its inhibition has only modest clinical effects in HPV-negative HNSCC. We explored a novel combination of AURKA and WEE1 inhibition to overcome intrinsic resistance to AURKA inhibition...
February 12, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hongyue Chen, Jing Qin, Yi Hu
Hyaluronic acid (HA) was depolymerized by a combination of ultrasound, hydrogen peroxide and copper ion. The structures of high-molecular-weight hyaluronic acid (HMW-HA) and low-molecular-weight hyaluronic acid (LMW-HA) were determined by Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD) spectroscopy, and UV-VIS absorption spectroscopy. The degradations of HMW-HA using a physical method, a chemical method, and a combination of physical and chemical method were compared. The results show that HA can be effectively degraded by a combinatorial method involving ultrasound, hydrogen peroxide, and copper ion...
February 11, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Christoph M Griessinger, Andreas M Schmid, Dominik Sonanini, Barbara F Schörg, Mohamed Ali Jarboui, Daniel Bukala, Natalie Mucha, Birgit Fehrenbacher, Julia Steinhilber, Manuela Martella, Ursula Kohlhofer, Martin Schaller, Lars Zender, Hans-Georg Rammensee, Leticia Quintanilla-Martinez, Martin Röcken, Manfred Kneilling, Bernd J Pichler
Cancer treatment with adoptively transferred tumor-associated antigen-specific CD4+ T-helper cells is a promising immunotherapeutic approach. In the pancreatic cancer model RIP-Tag2, the intraperitoneal (i.p.) application of Tag-specific TH1 cells exhibited a profound antitumoral efficiency. We investigated, whether an intravenous (i.v.) application of Tag-TH1 cells induces an equivalent therapeutic effect. Adoptively transferred fluorescent Tag-TH1 cells revealed a pronounced homing to the tumors after either i...
February 7, 2019: Carcinogenesis
Shivashankar Damodaran, Joshua M Lang, David F Jarrard
PURPOSE: Androgen deprivation therapy(ADT) alone has been the standard of care for metastatic hormone sensitive prostate cancer(mHSPC) for the last 75 years. This review focuses on recent trials and mechanisms that highlight a new paradigm, combining ADT with other agents, changing the management of prostate cancer patients with advanced disease. METHODS: A PubMed and Web of Science database search on peer-reviewed literature was performed through January 2018 using the keywords "metastatic hormone sensitive prostate cancer", " metastatic castration sensitive prostate cancer", "docetaxel", "abiraterone" and "senescence in cancer"...
February 7, 2019: Journal of Urology
Krishnan Balasubramanian
We review various mathematical and computational techniques for drug discovery exemplifying some recent works pertinent to group theory of nested structures of relevance to phylogeny, topological, computational and combinatorial methods for drug discovery for multiple viral infections. We have reviewed techniques from topology, combinatorics, graph theory and knot theory that facilitate topological and mathematical characterizations of protein-protein interactions, molecular-target interactions, proteomics, genomics and statistical data reduction procedures for a large set of starting chemicals in drug discovery...
February 8, 2019: Current Topics in Medicinal Chemistry
Amita Ajit, Santhoshkumar Thankayyan Retnabai, Lissy K Krishnan
Biotechnological interventions to engineer favorable biochemical environments that facilitate wound repair through quick attainment of vasculature are of immense demand. Potential of angiogenic factors (AF), notably vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (Hif-1α) and the paracrine role of human adipose derived mesenchymal stromal cells (hADMSCs) in establishing vasculature has been reported. Independent application of AF or hADMSCs has led to clinical failure, pertaining to poor means of delivery, deprived bioavailability and insufficiency to drive adequate angiogenesis, respectively...
February 12, 2019: Tissue Engineering. Part C, Methods
Andy I Nguyen, Ryan K Spencer, Christopher L Anderson, Ronald N Zuckermann
Synthesis of biomimetic multimetallic clusters is sought after for applications such as efficient storage of solar energy and utilization of greenhouse gases. However, synthetic efforts are hampered by a dearth of ligands that are developed for multimetallic clusters due to current limitations in rational design and organic synthesis. Peptoids, a synthetic sequence-defined oligomer, enable a biomimetic strategy to rapidly synthesize and optimize large, multifunctional ligands by structural design and combinatorial screening...
December 21, 2018: Chemical Science
Yingying Zhang, Luhui Wang, Yafei Dong
Due to structual polymorphism, excellent binding activity and functional significances in biological regulation, G-quadruplex has become the focus of research as an innovated module for analytical chemistry and biomedicine. Meanwhile, in the biosensor fields, new nanomaterial graphene oxide (GO) has also received extensive attention due to its brilliant physical and chemical properties. Herein, we propose a non-label and enzyme-free logic operation platform based on G-quadruplex structure and GO instead of any expensive modification...
2019: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
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