28,533 results match your criteria Combinatorial Chemistry & High Throughput Screening[Journal]


Clinical Implications of Single Nucleotide Polymorphisms in Diagnosis of Asthma and its Subtypes.

Yonsei Med J 2019 Jan;60(1):1-9

Department of Interdisciplinary Program in Biomedical Science, Graduate School, Soonchunhyang University, Bucheon, Korea.

For the past three decades, a large number of genetic studies have been performed to examine genetic variants associated with asthma and its subtypes in hopes of gaining better understanding of the mechanisms underlying disease pathology and to identify genetic biomarkers predictive of disease outcomes. Various methods have been used to achieve these objectives, including linkage analysis, candidate gene polymorphism analysis, and genome-wide association studies (GWAS); however, the degree to which genetic variants contribute to asthma pathogenesis has proven to be much less significant than originally expected. Subsequent application of GWAS to well-defined phenotypes, such as occupational asthma and non-steroidal anti-inflammatory drugexacerbated respiratory diseases, has overcome some of these limitations, although with only partial success. Read More

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January 2019

Testosterone- and vitamin-grafted cellulose ethers for sustained release of camptothecin.

Carbohydr Polym 2019 Feb 19;206:641-652. Epub 2018 Nov 19.

Institute of Polymer Chemistry, Johannes Kepler University Linz, 4040 Linz, Austria.

Camptothecin (CPT), a potent anticancer drug with known antiviral activity, is halted of clinical use. Few drug delivery systems of CPT are approved for therapy. Hereby, we propose the encapsulation of hydrophobic CPT in the inner core of cellulose nanoaggregates for sustained release with retaining of antiproliferative activity. Read More

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February 2019

A decade of Nucleic Acid Programmable Protein Arrays (NAPPA) availability: News, actors, progress, prospects and access.

J Proteomics 2018 Dec 12. Epub 2018 Dec 12.

Proteomics Unit, Cancer Research Centre (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, Spain; Department of Medicine and General Cytometry Service-Nucleus, Cancer Research Centre (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, Spain. Electronic address:

Understanding the dynamic of the proteome is a critical challenge because it requires high sensitive methodologies in high-throughput formats in order to decipher its modifications and complexity. While molecular biology provides relevant information about cell physiology that may be reflected in post-translational changes, High-Throughput (HT) experimental proteomic techniques are essential to provide valuable functional information of the proteins, peptides and the interconnections between them. Hence, many methodological developments and innovations have been reported during the last decade. Read More

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December 2018

Tight control of genomic phosphorothioate modification by the ATP-modulated autoregulation and reusability of DndB.

Mol Microbiol 2018 Dec 15. Epub 2018 Dec 15.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.

DNA phosphorothioate (PT) modification was recently identified to occur naturally in diverse bacteria and to be governed by DndABCDE proteins. The nuclease resistance as well as the redox and nucleophilic properties of PT sulfur make PT modification a versatile player in restriction-modification (R-M) defense, epigenetic regulation, environmental fitness, and the maintenance of cellular redox homeostasis. In this study, we discovered that tight control of PT levels is mediated by the ATPase activity of DndB. Read More

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December 2018

Rational combination of cancer immunotherapy in melanoma.

Virchows Arch 2018 Dec 14. Epub 2018 Dec 14.

Maria Sklodowska-Curie Institute, Oncology Center, Warsaw, Poland.

The recent advances in cancer immunotherapy with unprecedented success in therapy of advanced melanoma represent a turning point in the landscape of melanoma treatment. Given the complexity of activation of immunological system and the physiologic multifactorial homeostatic mechanisms controlling immune responses, combinatorial strategies are eagerly needed in melanoma therapy. Nevertheless, rational selection of immunotherapy combinations should be more biomarker-guided, including not only the cancer immunogram, PD-L1 expression, interferon gene expression signature, mutational burden, and tumor infiltration by CD8+ T cells but also intratumoral T cell exhaustion and microbiota composition. Read More

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December 2018
1 Read

A combination of linalool, vitamin C, and copper synergistically trigger Reactive Oxygen Species, DNA damage and inhibits subsp. serovar Typhi and .

Appl Environ Microbiol 2018 Dec 14. Epub 2018 Dec 14.

Chemical Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Uttarakhand 247 667, India.

Inappropriate and disproportionate use of antibiotics is contributing immensely to the development of antibiotic resistance in bacterial species associated with food contamination. Use of natural products in combination can be a potent alternative hurdle strategy to inactivate foodborne pathogens. Here, we explored pro-oxidant properties of essential oil inalool and itamin C in combination with opper (LVC) in combating foodborne pathogens and a subsp. Read More

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December 2018

Near-infrared AIEgens as transformers to enhance tumor treatment efficacy with controllable self-assembled redox-responsive carrier-free nanodrug.

Biomaterials 2018 Dec 10;193:12-21. Epub 2018 Dec 10.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, PR China. Electronic address:

Nanosized drug delivery systems (nDDS) have been extensively exploited to achieve improved therapeutic performance of chemotherapeutic drugs in cancer treatment. Carrier-free nanodrugs have recently emerged as a promising generation of nDDS. In this work, a carrier-free theranostic nanodrug was fabricated by incorporating near-infrared (NIR) emission AIEgens (NPAPF) with redox responsive camptothecin-gemcitabine amphiphilic prodrug (CPT-ss-GEM) to form self-assembled nanoparticles (NCssG NPs). Read More

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December 2018
2 Reads

Combinatorial Utilization of Murine Embryonic Stem Cells and In Vivo Models to Study Human Congenital Heart Disease.

Curr Protoc Stem Cell Biol 2018 Dec 12:e75. Epub 2018 Dec 12.

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.

We have established an in vitro model of the human congenital heart defect (CHD)-associated mutation NKX2.5 R141C. We describe the use of the hanging drop method to differentiate Nkx2. Read More

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December 2018
1 Read

Deconstructing Retinal Organoids: Single cell RNA-Seq reveals the cellular components of human pluripotent stem cell-derived retina.

Stem Cells 2018 Dec 12. Epub 2018 Dec 12.

Institute of Genetic Medicine, Newcastle University, Newcastle, UK.

The rapid improvements in single cell sequencing technologies and analyses afford greater scope for dissecting organoid cultures composed of multiple cell types and create an opportunity to interrogate these models to understand tissue biology, cellular behaviour and interactions. To this end, retinal organoids generated from human embryonic stem cells (hESCs) were analysed by single cell RNA-sequencing (scRNA-Seq) at three time points of differentiation. Combinatorial data from all time points revealed the presence of nine clusters, five of which corresponded to key retinal cell types: retinal pigment epithelium (RPE), retinal ganglion cells (RGCs), cone and rod photoreceptors and Müller glia. Read More

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December 2018

Multi-modal optimization of bismuth vanadate photoanodes via combinatorial alloying and hydrogen processing.

Chem Commun (Camb) 2018 Dec 14. Epub 2018 Dec 14.

Joint Center for Artificial Photosynthesis, California Institute of Technology, Pasadena CA 91125, USA.

Alloying transition metals, such as Mo, into BiVO4 has emerged as the primary mechanism for improving carrier transport in this photoanode for solar fuels production. The present work establishes the generality of improving photoelectrochemical performance through co-alloying with a transition metal electron donor and a structure-modulating rare earth. Further improvement for all such alloys is obtained by annealing the oxide materials in H2, ultimately producing photoanodes with above 3 mA cm-2 photocurrent density under AM 1. Read More

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December 2018

Tuning of delta-protocadherin adhesion through combinatorial diversity.

Elife 2018 Dec 14;7. Epub 2018 Dec 14.

Department of Biomedical Sciences, Cornell University, Ithaca, United States.

The delta-protocadherins (δ-Pcdhs) play key roles in neural development, and expression studies suggest they are expressed in combination within neurons. The extent of this combinatorial diversity, and how these combinations influence cell adhesion, is poorly understood. We show that individual mouse olfactory sensory neurons express 0-7 δ-Pcdhs. Read More

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December 2018

BRAF and MEK inhibitors differentially affect nivolumab-induced T cell activation by modulating the TCR and AKT signaling pathways.

Oncoimmunology 2019 29;8(1):e1512456. Epub 2018 Oct 29.

Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.

Immune checkpoint inhibitors (ICIs) such as the anti-PD-1 antibody Nivolumab, achieve remarkable clinical efficacy in patients with late stage cancers. However, only a small subset of patients benefit from this therapy. Numerous clinical trials are underway testing whether combining ICIs with other anti-cancer therapies can increase this response rate. Read More

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October 2018

Does Size Really Matter? Probing the Efficacy of Structural Reduction in the Optimization of Bioderived Compounds - A Computational "Proof-of-Concept".

Comput Struct Biotechnol J 2018 23;16:573-586. Epub 2018 Nov 23.

Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa.

Over the years, numerous synthetic approaches have been utilized in drug design to improve the pharmacological properties of naturally derived compounds and most importantly, minimize toxic effects associated with their transition to drugs. The reduction of complex bioderived compounds to simpler bioactive fragments has been identified as a viable strategy to develop lead compounds with improved activities and minimal toxicities. Although this 'reductive' strategy has been widely exemplified, underlying biological events remain unresolved, hence the unanswered question remains how does the fragmentation of a natural compound improve its bioactivity and reduce toxicities? Herein, using a combinatorial approach, we initialize a computational "proof-of- concept" to expound the differential pharmacological and antagonistic activities of a natural compound, Anguinomycin D, and its synthetic fragment, SB640 towards Exportin Chromosome Region Maintenance 1 (CRM1). Read More

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November 2018

Novel Clofarabine-Based Combinations with Polyphenols Epigenetically Reactivate Retinoic Acid Receptor Beta, Inhibit Cell Growth, and Induce Apoptosis of Breast Cancer Cells.

Int J Mol Sci 2018 Dec 10;19(12). Epub 2018 Dec 10.

Faculty of Medicine, Lazarski University, 02-662 Warsaw, Poland.

An epigenetic component, especially aberrant DNA methylation pattern, has been shown to be frequently involved in sporadic breast cancer development. A growing body of literature demonstrates that combination of agents, i.e. Read More

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December 2018

The stability and oncogenic function of LIN28A are regulated by USP28.

Biochim Biophys Acta Mol Basis Dis 2018 Dec 10. Epub 2018 Dec 10.

Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea; College of Medicine, Hanyang University, Seoul 04763, South Korea. Electronic address:

RNA-binding protein LIN28A is often highly expressed in human malignant tumors and is involved in tumor metastasis and poor prognosis. Knowledge about post-translational regulatory mechanisms governing LIN28A protein stability and function is scarce. Here, we investigated the role of ubiquitination and deubiquitination on LIN28A protein stability and report that LIN28A protein undergoes ubiquitination. Read More

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December 2018

The sp. PCC 6803 Genome Encodes Up to Four 2-Phosphoglycolate Phosphatases.

Front Plant Sci 2018 27;9:1718. Epub 2018 Nov 27.

Department of Plant Physiology, University of Rostock, Rostock, Germany.

Photorespiratory phosphoglycolate (2PG) metabolism is essential for cyanobacteria, algae, and plants. The first enzyme of the pathway, 2PG phosphatase (PGPase), is known from plants and algae but was scarcely investigated in cyanobacteria. analysis revealed four candidate genes (, , , and ) in the genome of the model cyanobacterium sp. Read More

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November 2018

Exploitation of Synthetic mRNA To Drive Immune Effector Cell Recruitment and Functional Reprogramming In Vivo.

J Immunol 2018 Dec 12. Epub 2018 Dec 12.

Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853;

Therapeutic strategies based on in vitro-transcribed mRNA (IVT) are attractive because they avoid the permanent signature of genomic integration that is associated with DNA-based therapy and result in the transient production of proteins of interest. To date, IVT has mainly been used in vaccination protocols to generate immune responses to foreign Ags. In this "proof-of-principle" study, we explore a strategy of combinatorial IVT to recruit and reprogram immune effector cells to acquire divergent biological functions in mice in vivo. Read More

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December 2018

Anti-PD1 'SHR-1210' aberrantly targets pro-angiogenic receptors and this polyspecificity can be ablated by paratope refinement.

MAbs 2018 Dec 12:1-19. Epub 2018 Dec 12.

a UltraHuman Limited, Codebase , Edinburgh , UK.

Monoclonal anti-programmed cell death 1 (PD1) antibodies are successful cancer therapeutics, but it is not well understood why individual antibodies should have idiosyncratic side-effects. As the humanized antibody SHR-1210 causes capillary hemangioma in patients, a unique toxicity amongst anti-PD1 antibodies, we performed human receptor proteome screening to identify nonspecific interactions that might drive angiogenesis. This screen identified that SHR-1210 mediated aberrant, but highly selective, low affinity binding to human receptors such as vascular endothelial growth factor receptor 2 (VEGFR2), frizzled class receptor 5 and UL16 binding protein 2 (ULBP2). Read More

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December 2018

The application of NIPT using combinatorial probe-anchor synthesis to identify sex chromosomal aneuploidies (SCAs) in a cohort of 570 pregnancies.

Mol Cytogenet 2018 3;11:59. Epub 2018 Dec 3.

1Women's Hospital, School of Medicine Zhejiang University, 1, Xueshi Road, Hangzhou Zhejiang, 310006 People's Republic of China.

Background: Non-invasive prenatal testing (NIPT) as alternative screening method had been proven to have very high sensitivity and specificity for detecting common aneuploidies such as T21, T18, and T13, with low false positive and false negative rates. Unfortunately, recent studies suggested that the NIPT achieved lower accuracy in sex chromosomal aneuploidies (SCAs) detection than autosomal aneuploidies detection. BGISEQ-500 powered by Combinatorial Probe-Anchor Synthesis (CPAS) and DNA Nanoballs (DNBs) technology that combined linear amplification and rolling circle replication to reduce the error rate while enhancing the signal. Read More

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December 2018

The Effects of Combined Abiotic and Pathogen Stress in Plants: Insights From Salinity and pv Interaction in Cucumber.

Front Plant Sci 2018 20;9:1691. Epub 2018 Nov 20.

Department of Plant Biotechnology and Cytogenetics, Plant Breeding and Acclimatization Institute - National Research Institute, Radzików, Poland.

Plants are often challenged by abiotic and biotic stresses acting in combination and the response to combinatorial stress differs from that triggered by each factor individually. Although salinity and pathogens are major stressors limiting plant growth and productivity worldwide, their interaction is poorly understood. The reactions to pathogens overlap with those to abiotic stresses, and reactive oxygen species (ROS) and stress hormones represent central nodes in the interacting signaling pathways. Read More

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November 2018

Energy-modulated X-ray fluorescence and luminescence emissions from therapeutic nanoparticles.

Phys Med Biol 2018 Nov 6. Epub 2018 Nov 6.

Department of Nuclear, Plasma and Radiological Engineering, University of Illinois - Urbana-Champaign, 214 Nuclear Engineering Laboratory, 103 South Goodwin Avenue, Urbana IL 61801-2984, USA, Urbana, Illinois, UNITED STATES.

In this study, we have investigated the possibility of modulating X-ray fluorescence (XF) and X-ray luminescence (XL) emissions from therapeutic nanoparticles (NPs) by fine-tuning the energy of incident X-rays from benchtop X-ray sources. We have carried out detailed experimental studies to determine the strength of XF and XL emissions from Y2O3:Eu3+ and LaF3:Tb3+ NPs being irradiated with X-rays from benchtop X-ray sources operated with different tube-voltages and coupled to various filter configurations. These studies demonstrated that low-energy X-rays with average energy at around 10-15 keV are the most efficient to stimulate XL emission from the Y2O3:Eu3+ and LaF3:Tb3+ NPs. Read More

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November 2018

Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies.

SLAS Discov 2018 Dec 7:2472555218812657. Epub 2018 Dec 7.

1 Department of Chemistry, American University, Washington, DC, USA.

Over the past century, a multitude of derivatives of structural scaffolds with established antimicrobial potential have been prepared and tested, and a variety of new scaffolds have emerged. The effectiveness of antibiotics, however, is in sharp decline because of the emergence of drug-resistant microorganisms. The prevalence of drug resistance, both in clinical and community settings, is a consequence of bacterial ingenuity in altering pathways and/or cell morphology, making it a persistent threat to human health. Read More

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December 2018

Adequate evidence to support improved outcomes in depression by primary care physicians compared to psychiatrists when using combinatorial pharmacogenomics.

J Psychiatr Res 2018 Nov 15. Epub 2018 Nov 15.

Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Molecular Brain Science Research Department, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address:

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November 2018

CASMAP: Detection of statistically significant combinations of SNPs in association mapping.

Bioinformatics 2018 Dec 12. Epub 2018 Dec 12.

Department of Biosystems Science and Engineering, ETH Zurich, Basel, 4058, Switzerland SIB Swiss Institute of Bioinformatics.

Summary: Combinatorial association mapping aims to assess the statistical association of higher-order interactions between genetic markers with a phenotype of interest. This paper presents CASMAP, a software package that leverages recent advances in significant pattern mining to overcome the statistical and computational challenges that have hindered combinatorial association mapping. CASMAP can be used to perform region-based association studies and to detect higher-order epistatic interactions of genetic variants. Read More

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December 2018

Combinatorial effect of curcumin and tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in induction of apoptosis via inhibition of nuclear factor kappa activity and enhancement of caspase-3 activity in chronic myeloid cells: An study.

J Cancer Res Ther 2018 Dec;14(Supplement):S1193-S1200

Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India.

Background: Nuclear factor kappa B (NFkB-light-chain-enhancer of activated B-cells) expression and its regulation is a key role in the development of number of malignancies, as NFkB mediates the balance between cell death and its survival. Therefore, NFkB regulation constitutes an attractive target to overcome the resistance to chemotherapeutic agents in anticancer therapy. Curcumin, as a chemopreventive agent, has a potential role in inhibiting cell growth in a variety of malignancies. Read More

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December 2018

Radioprotective effect of melatonin on expression of and genes in rat peripheral blood.

J Cancer Res Ther 2018 Dec;14(Supplement):S1070-S1075

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Objective: Ionizing radiation is a critical threat to biomolecules, especially DNA. Various combinatorial compounds have been studied to protect this biomolecule. Melatonin has been reported as a direct and indirect free radical scavenger, but in this study, we explored the effect of melatonin on assisting in DNA repair by expression of Cdkn1a and Rad50; both of these genes are involved in DNA repair signaling, induced by radiation in rat peripheral blood. Read More

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December 2018
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Osthole Synergizes With HER2 Inhibitor, Trastuzumab in HER2-Overexpressed N87 Gastric Cancer by Inducing Apoptosis and Inhibition of AKT-MAPK Pathway.

Front Pharmacol 2018 27;9:1392. Epub 2018 Nov 27.

School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

Although trastuzumab has shown considerable activity in the treatment of HER2-positive breast and gastric cancers, a significant proportion of patients do not respond to trastuzumab. Recent studies revealed that osthole, an active coumarin isolated from (L.) Cusson possesses potent anti-tumor activity. Read More

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November 2018

Desperately seeking…Models to find the right partner and the best use for checkpoint inhibitors.

Br J Cancer 2018 Dec 11. Epub 2018 Dec 11.

Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.

Immune checkpoint inhibitors have shown unprecedented clinical activity in a variety of cancer types, but only in a fraction of patients. Promising in vivo synergies have been demonstrated between checkpoint inhibitors and other drugs and/or chemotherapy or radiotherapy, and effective models are now needed to select the best combinatorial regimen and disease setting. Read More

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December 2018
1 Read

Histone Acetylation Cooperating with AREB1 Transcription Factor Regulates Drought Response and Tolerance in Populus trichocarpa.

Plant Cell 2018 Dec 11. Epub 2018 Dec 11.

Northeast Forestry University CITY: Harbin POSTAL_CODE: 150040 China [CN]

Plants develop tolerance to drought by activating genes with altered levels of epigenetic modifications. Specific transcription factors (TFs) are involved in this activation, but the molecular connections within the regulatory system are unclear. Here, we analyzed genome-wide H3K9ac enrichment and examined its association with transcriptomes in Populus trichocarpa under drought stress. Read More

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December 2018
5 Reads
9.338 Impact Factor

Resistance to Epigenetic-Targeted Therapy Engenders Tumor Cell Vulnerabilities Associated with Enhancer Remodeling.

Cancer Cell 2018 Dec;34(6):922-938.e7

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Read More

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December 2018
23.523 Impact Factor

Functional Characterization of LIKE HETEROCHROMATIN PROTEIN 1 in the moss Physcomitrella patens: its conserved protein interactions in land plants.

Plant J 2018 Dec 7. Epub 2018 Dec 7.

University School of Biotechnology, Guru Gobind Singh Indraprastha University, Sector 16C, Dwarka, New, Delhi-110078, India.

In flowering plants LIKE HETEROCHROMATIN PROTEIN 1 (LHP1)/TERMINAL FLOWER 2 (TFL2) is known to interact with polycomb group (PcG) and non-PcG proteins and control developmental programs. LHP1/TFL2 is an ancient protein and has been characterized in the early-divergent plant Physcomitrella patens. However, interacting partners of PpLHP1 other than the chromomethylase PpCMT have not been identified to date. Read More

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December 2018

On hormonal regulation of the dynamic apical hook development.

New Phytol 2018 Dec 7. Epub 2018 Dec 7.

Institute of Plant and Food Science, Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.

To deal with the ever-changing environment, sessile plants adapt diverse and plastic organ structures during postembryonic development. Among these, the apical hook forms shortly after seed germination of most dicots, protects the delicate shoot meristem from mechanical damage during soil emergence. For decades, this structure has been taken as an excellent model for investigating the mechanisms underlying differential growth of plant tissues. Read More

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December 2018
3 Reads

Expression of PD-L1 in tumor-associated nerves correlates with reduced CD8 tumor-associated lymphocytes and poor prognosis in prostate cancer.

Int J Cancer 2018 Dec 11. Epub 2018 Dec 11.

Department of Urology and Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.

To investigate immune profile consisting of stromal PD-L1 expression, inhibitory or non-T-cell inflamed tumor microenvironment that may predict response to anti-PD-L1/PD-1 immunotherapy in prostate cancer, we validated the specificity of a PD-L1 monoclonal antibody (E1L3N) and identified PD-L1 specific expression in prostatic stromal nerve cells. PD-L1 expression was analyzed in 73 primary prostate cancers and 7 castration-resistant prostate cancers (CRPC) by IHC and resulting data from primary prostate cancers were correlated with tumor-associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD-L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. Read More

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December 2018
1 Read

MiRNA influences in mesenchymal stem cell commitment to neuroblast lineage development.

Noncoding RNA Res 2018 Dec 15;3(4):232-242. Epub 2018 Nov 15.

Centre for Molecular Medicine and Biobanking, University of Malta, Msida MSD2080, Malta.

Mesenchymal Stem Cells (MSCs) are widely used in therapeutic applications. Their plasticity and predisposition to differentiate into a variety of cell types, including those of the neuronal lineage, makes them ideal to study whether a selection of miRNAs may direct the differentiation of MSCs into neuroblasts or neuroblastoma to mature neurons. Following a short-listing, miR-107, 124 and 381 were selected as the most promising candidates for this differentiation. Read More

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December 2018

The anticancer activity of genistein is increased in estrogen receptor beta 1-positive breast cancer cells.

Onco Targets Ther 2018 14;11:8153-8163. Epub 2018 Nov 14.

Department of Breast and Thyroid Surgery, Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China,

Background: Most breast cancers are estrogen dependent and were sensitive to endocrine therapy, and genistein (GEN) shows strong affinity with human oestrogen receptor beta (ERβ).

Purpose: The present study aimed to investigate the anticancer activity of GEN in breast cancer cell lines that constitutively expressing ERβ1 in vitro and in vivo.

Methods: MCF-7/ERβ1 and MDA-MB-231/ERβ1 cell sub-lines were established through lentiviral infection. Read More

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November 2018

Rapamycin-inspired macrocycles with new target specificity.

Nat Chem 2018 Dec 10. Epub 2018 Dec 10.

Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Rapamycin and FK506 are macrocyclic natural products with an extraordinary mode of action, in which they form binary complexes with FK506-binding protein (FKBP) through a shared FKBP-binding domain before forming ternary complexes with their respective targets, mechanistic target of rapamycin (mTOR) and calcineurin, respectively. Inspired by this, we sought to build a rapamycin-like macromolecule library to target new cellular proteins by replacing the effector domain of rapamycin with a combinatorial library of oligopeptides. We developed a robust macrocyclization method using ring-closing metathesis and synthesized a 45,000-compound library of hybrid macrocycles (named rapafucins) using optimized FKBP-binding domains. Read More

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December 2018
25.325 Impact Factor

Combinatorial therapies for spinal cord injury: strategies to induce regeneration.

Neural Regen Res 2019 Jan;14(1):69-71

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, Braga; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.

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January 2019

Rapid proteolytic digestion and peptide separation using monolithic enzyme microreactor coupled with capillary electrophoresis.

J Pharm Biomed Anal 2018 Dec 1;165:129-134. Epub 2018 Dec 1.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China. Electronic address:

Proteolytic digestion and peptide separation are key steps in proteomic study, which has attracted much attention. A novel immobilized trypsin microreactor based on monolithic capillary column was developed for rapid proteolytic digestion in this work. The monolithic support was prepared using itaconic acid as functional monomer within a silanized fused-silica capillary. Read More

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December 2018

Dynamics of protein complex components.

Curr Opin Chem Biol 2018 Dec 4;48:81-85. Epub 2018 Dec 4.

University of British Columbia, Michael Smith Laboratories, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.

Identifying protein-protein interactions (PPIs) is necessary to understand the molecular mechanisms behind cellular processes. This task is complicated by the facts that many proteins can interact simultaneously (i.e. Read More

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December 2018

Molecular characterisation of immunological memory following homologous or heterologous challenges in the schistosomiasis vector snail, Biomphalaria glabrata.

Dev Comp Immunol 2018 Dec 4;92:238-252. Epub 2018 Dec 4.

Univ. Perpignan Via Domitia, Interactions Hôtes Pathogènes Environments UMR 5244, CNRS, IFREMER, Univ. Montpellier, F-66860, Perpignan, France. Electronic address:

Invertebrate immune response may be primed by a current infection in a sustained manner, leading to the failure of a secondary infection with the same pathogen. The present study focuses on the Schistosomiasis vector snail Biomphalaria glabrata, in which a specific genotype-dependent immunological memory was demonstrated as a shift from a cellular to a humoral immune response. Herein, we investigate the complex molecular bases associated with this genotype-dependant immunological memory response. Read More

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December 2018

Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis.

J Hepatol 2018 Dec 5. Epub 2018 Dec 5.

Aix Marseille Univ, CNRS, Developmental Biology Institute of Marseille (IBDM) UMR 7288, Parc Scientifique de Luminy, Marseille France. Electronic address:

Background & Aims: The variety of alterations found in hepatocellular carcinoma (HCC) challenges the identification of functionally relevant genes and their combinatorial actions in tumorigenesis. Deregulation of Receptor Tyrosine Kinases (RTKs) is frequent in HCC, yet little is known about the molecular events that cooperate with RTKs and whether these cooperative events play an active role at the root of liver tumorigenesis.

Methods: A forward genetic screen was performed using Sleeping Beauty transposon insertional mutagenesis to accelerate liver tumour formation in a genetic context in which subtly increased MET RTK levels predispose towards tumorigenesis. Read More

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December 2018

Degron mediated BRM/SMARCA2 depletion uncovers novel combination partners for treatment of BRG1/SMARCA4-mutant cancers.

Biochem Biophys Res Commun 2018 Nov 20. Epub 2018 Nov 20.

Oncology, Novartis Institutes for Biomedical Research, Cambridge, MA, USA. Electronic address:

Recent studies have highlighted that cancer cells with a loss of the SWI/SNF complex catalytic subunit BRG1 are dependent on the remaining ATPase, BRM, making it an attractive target for cancer therapy. However, an understanding of the extent of target inhibition required to arrest cell growth, necessary to develop an appropriate therapeutic strategy, remains unknown. Here, we utilize tunable depletion of endogenous BRM using the SMASh degron, and interestingly observe that BRG1-mutant lung cancer cells require near complete depletion of BRM to robustly inhibit growth both in vitro and in vivo. Read More

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November 2018
1 Read

Dynamic Generation of G-quadruplex DNA Ligands by Target-Guided Combinatorial Chemistry on a Magnetic Nano-platform.

J Med Chem 2018 Dec 11. Epub 2018 Dec 11.

Dynamic combinatorial chemistry (DCC) has emerged as a promising strategy for template-driven selection of high-affinity ligands for biological targets from equilibrating combinatorial libraries. However, only a few examples using disulphide exchange based DCC are reported for nucleic acid targets. Herein, we have demonstrated that gold-coated magnetic nanoparticle conjugated DNA targets can be used as templates for dynamic selection of ligands from an imine-based combinatorial library. Read More

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December 2018

Combinatorial Peptide Array Synthesis Based on Microfluidic Impact Printing.

ACS Comb Sci 2018 Dec 6. Epub 2018 Dec 6.

In this paper, a novel inkjet printing technique, micro impact printing (MI printing), is applied for the first time to combinatorial peptide array synthesis on amine functionalized micro disc arrays through standard Fmoc chemistry. MI printing shows great advantages in combinatorial peptide array synthesis compared with other printing techniques, including 1) a disposable cartridge; 2) a small spot size (80 μm) increases array density; 3) minimal loading volume (0.6 μL) and dead volume (<0. Read More

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December 2018
1 Read

Computer vision-based phenotyping for improvement of plant productivity: A machine learning perspective.

Gigascience 2018 Dec 6. Epub 2018 Dec 6.

Department of Information Engineering and Computer Science, University of Trento, Via Sommarive 9, 38123 Trento, Italy.

Employing computer vision to extract useful information from images and videos is becoming a key technique for identifying phenotypic changes in plants. In this report, we review the emerging aspects of computer vision for automated plant phenotyping. Recent advances in image analysis empowered by machine learning-based techniques, including convolutional neural network-based modeling, have expanded their application to assist high-throughput plant phenotyping. Read More

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December 2018
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Sense of Smell: Structural, Functional, Mechanistic Advancements and Challenges in Human Olfactory Research.

Curr Neuropharmacol 2018 Dec 5. Epub 2018 Dec 5.

Department of Applied Science, Indian Institute of Information Technology, Allahabad, Uttar Pradesh. India.

Olfaction, the sense of smell detects and discriminate odors as well as social cues which influence our innate responses. The olfactory system in human beings is found to be weak as compare to other animals; however, it seems to be very precise. It can detect and discriminate millions of chemical moieties (odorants) even in minuscule quantities. Read More

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December 2018

Predicting Drug Interactions From Chemogenomics Using INDIGO.

Methods Mol Biol 2019 ;1888:219-231

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.

Designing effective antibiotic combination regimens is critical for countering drug resistance in pathogens. Yet the large combinatorial search-space makes the identification of effective combinations a significant challenge. There is a great need for computational approaches that can rapidly prioritize potential combination regimens based on the antagonistic and synergistic interactions among the constituent antibiotics. Read More

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January 2019
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Integrated Analysis of Drug Sensitivity and Selectivity to Predict Synergistic Drug Combinations and Target Coaddictions in Cancer.

Methods Mol Biol 2019 ;1888:205-217

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

High-throughput drug sensitivity testing provides a powerful phenotypic profiling approach to identify effective drug candidates for individual cell lines or patient-derived samples. Here, we describe an experimental-computational pipeline, named target addiction scoring (TAS), which mathematically transforms the drug response profiles into target addiction signatures, and thereby provides a ranking of potential therapeutic targets according to their functional importance in a particular cancer sample. The TAS pipeline makes use of drug polypharmacology to integrate the drug sensitivity and selectivity profiles through systems-wide interconnection networks between drugs and their targets, including both primary protein targets as well as secondary off-targets. Read More

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January 2019

Crosstalk Between PD-1/PD-L1 Blockade and Its Combinatorial Therapies in Tumor Immune Microenvironment: A Focus on HNSCC.

Front Oncol 2018 21;8:532. Epub 2018 Nov 21.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide with a poor prognosis and high mortality. More than two-thirds of HNSCC patients still have no effective control of clinical progression, and the five-year survival rate is < 50%. Moreover, patients with platinum-refractory HNSCC have a median survival of < 6 months. Read More

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November 2018
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Penetration and efficacy of transdermal NSAIDs in a model of acute joint inflammation.

J Pain Res 2018 13;11:2809-2819. Epub 2018 Nov 13.

InterVivo Solutions Inc, Toronto, ON, Canada.

Purpose: Prescription and OTC non-steroidal anti-inflammatory drugs (NSAIDs) are ubiquitous treatments for pain and inflammation; however, oral administration of these drugs may produce gastrointestinal (GI) side effects. Transdermal (TD) administration of NSAIDs circumvents these adverse events by avoiding the GI tract and, presumably, achieves regional drug levels of therapeutic effect and thereby, fewer off-target complications.

Methods: A drug quantification method was developed for ibuprofen and celecoxib in canine plasma and synovial fluid using liquid chromatography and mass spectrometry. Read More

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November 2018
2 Reads