Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis
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Oncogenic Role of SFRP2 in P53-Mutant Osteosarcoma Development Via Autocrine and Paracrine Mechanism
Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism Huensuk Kima,b,c, Seungyeul Yood,e, Ruoji Zhouf,g,AnXuf, Jeffrey M. Bernitza,b,c, Ye Yuana,b,c, Andreia M. Gomesa,b,h,i, Michael G. Daniela,b,c, Jie Sua,b,c,j, Elizabeth G. Demiccok,l, Jun Zhud,e, Kateri A. Moorea,b,c, Dung-Fang Leea,b,f,g,m,n,1,2, Ihor R. Lemischkaa,b,c,o,1,3, and Christoph Schaniela,b,c,o,p,1,2 aDepartment of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; bThe Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; cThe Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; dDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; eIcahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; fDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030; gThe University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030; hCentre for Neuroscience and Cell Biology, University of Coimbra, 3030-789 Coimbra, Portugal; iInstitute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal; jCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065; kDepartment of Pathology, Icahn School -
4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4). -
Three Dact Gene Family Members Are Expressed During Embryonic Development
Three Dact Gene Family Members are Expressed During Embryonic Development and in the Adult Brains of Mice Daniel A Fisher, Saul Kivimäe, Jun Hoshino, Rowena Suriben, Pierre -Marie Martin, Nichol Baxter, Benjamin NR Cheyette Department of Psychiatry & Gra duate Programs in Developmental Biology and Neuroscience, University of California, San Francisco, 94143-2611 Correspondence: Benjamin NR Cheyette [email protected] 415.476.7826 Running Title: Mouse Dact Gene Family Expression Key Words: mouse, Dpr, Frodo, Thyex, Dact, Wnt, Dvl, expression, embryo, brain Supported by: NIH: MH01750 K08; NARSAD Young Investigator Award; NAAR award #551. Abstract Members of the Dact protein family were initially identified through binding to Dishevelled (Dvl), a cytoplasmic protein central to Wnt signaling. During mouse development, Dact1 is detected in the presomitic mesoderm and somites during segmentation, in the limb bud mesenchyme and other mesoderm-derived tissues, and in the central nervous system (CNS). Dact2 expression is most prominent during organogenesis of the thymus, kidneys, and salivary glands, with much lower levels in the somites and in the developing CNS. Dact3, not previously described in any organism, is expressed in the ventral region of maturing somites, limb bud and branchial arch mesenchyme, and in the embryonic CNS; of the three paralogs it is the most highly expressed in the adult cerebral cortex. These data are consistent with studies in other vertebrates showing that Dact paralogs have distinct signaling and developmental roles, and suggest they may differentially contribute to postnatal brain physiology. Introduction Signaling downstream of secreted Wnt ligands is a conserved process in multicellular animals that plays important roles during development and, when misregulated, contributes to cancer and other diseases (Polakis, 2000; Moon et al., 2002). -
Multivariate Analysis Reveals Differentially Expressed Genes
www.nature.com/scientificreports OPEN Multivariate analysis reveals diferentially expressed genes among distinct subtypes of difuse astrocytic gliomas: diagnostic implications Nerea González‑García1,2, Ana Belén Nieto‑Librero1,2, Ana Luisa Vital3, Herminio José Tao4, María González‑Tablas2,5,6, Álvaro Otero2, Purifcación Galindo‑Villardón1,2, Alberto Orfao2,5,6 & María Dolores Tabernero2,5,6,7* Diagnosis and classifcation of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profles (GEP) of 268 difuse astrocytic gliomas—33 difuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)—based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratifcation, particularly among inconclusive cases with II–III grade diagnosed, which have diferent prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 difuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identifcation of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identifed a set of 27 genes capable of diferentiating among distinct subtypes of gliomas that might support current histological classifcation. DA + AA showed similar molecular profles with only a few discriminatory genes -
Inhibitory Effects of Phytochemicals on Metabolic Capabilities of CYP2D6*1 and CYP2D6*10 Using Cell-Based Models in Vitro
Acta Pharmacologica Sinica (2014) 35: 685–696 npg © 2014 CPS and SIMM All rights reserved 1671-4083/14 $32.00 www.nature.com/aps Original Article Inhibitory effects of phytochemicals on metabolic capabilities of CYP2D6*1 and CYP2D6*10 using cell-based models in vitro Qiang QU1, 2, Jian QU1, Lu HAN2, Min ZHAN1, Lan-xiang WU3, Yi-wen ZHANG1, Wei ZHANG1, Hong-hao ZHOU1, * 1Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha 410078, China; 2Xiangya Hospital, Central South University, Changsha 410008, China; 3Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China Aim: Herbal products have been widely used, and the safety of herb-drug interactions has aroused intensive concerns. This study aimed to investigate the effects of phytochemicals on the catalytic activities of human CYP2D6*1 and CYP2D6*10 in vitro. Methods: HepG2 cells were stably transfected with CYP2D6*1 and CYP2D6*10 expression vectors. The metabolic kinetics of the enzymes was studied using HPLC and fluorimetry. Results: HepG2-CYP2D6*1 and HepG2-CYP2D6*10 cell lines were successfully constructed. Among the 63 phytochemicals screened, 6 compounds, including coptisine sulfate, bilobalide, schizandrin B, luteolin, schizandrin A and puerarin, at 100 μmol/L inhibited CYP2D6*1- and CYP2D6*10-mediated O-demethylation of a coumarin compound AMMC by more than 50%. Furthermore, the inhibition by these compounds was dose-dependent. Eadie-Hofstee plots demonstrated that these compounds competitively inhibited CYP2D6*1 and CYP2D6*10. However, their Ki values for CYP2D6*1 and CYP2D6*10 were very close, suggesting that genotype- dependent herb-drug inhibition was similar between the two variants. -
List of European Pharmacopoeia Reference Standards Effective From
List of European Pharmacopoeia Reference Standards Effective from 2021/10/6 Order Reference Standard Batch Quantity Sale Information Monograph Storage Shipping Shipment Price Code n° per vial Unit group with DGD Y0001552 Abacavir for peak identification CRS 1 10 mg 1 2589 +5°C+/-3°C A1A 79 € Y0001551 Abacavir for system suitability CRS 1 10 mg 1 2589 +5°C+/-3°C A1A 79 € Y0001561 Abacavir sulfate CRS 1 20 mg 1 2589 +5°C+/-3°C A1A 79 € Y0002199 Acamprosate calcium CRS 1 80 mg 1 See leaflet 1585 +5°C+/-3°C A1A 79 € Y0000055 Acamprosate calcium - reference spectrum 1 n/a 1 This reference standard was officially withdrawn from monograph 1585 L 79 € 01/2017:1585 on 01/01/2021 and replaced by Y0002199 Acamprosate calcium. The reference will however remain available for sale for a further 6 months (subject to stock availability), i.e. until 01/07/2021. The reference will remain visible in the catalogue until 01/01/2022. ; Batch 1 is valid until 1 January 2022 Y0000116 Acamprosate impurity A CRS 2 110 mg 1 3-aminopropane-1-sulfonic acid (homotaurine) 1585 +5°C+/-3°C A1A 79 € Y0000500 Acarbose CRS 3 100 mg 1 See leaflet 2089 +5°C+/-3°C A1A 79 € Y0000354 Acarbose for identification CRS 1 10 mg 1 2089 +5°C+/-3°C A1A 79 € Y0000427 Acarbose for peak identification CRS 4 20 mg 1 2089 +5°C+/-3°C A1A 79 € A0040000 Acebutolol hydrochloride CRS 1 50 mg 1 0871 +5°C+/-3°C A1A 79 € Y0000359 Acebutolol impurity B CRS 2 10 mg 1 N-[3-acetyl-4-[(2RS)-2-hydroxy-3-[(1-methylethyl)amino] 0871 +5°C+/-3°C A1A 79 € propoxy]phenyl]acetamide (diacetolol) Y0000127 Acebutolol -
Alkaloids Used As Medicines: Structural Phytochemistry Meets Biodiversity—An Update and Forward Look
molecules Review Alkaloids Used as Medicines: Structural Phytochemistry Meets Biodiversity—An Update and Forward Look Michael Heinrich 1,2,* , Jeffrey Mah 1 and Vafa Amirkia 1 1 Research Group ‘Pharmacognosy and Phytotherapy’, UCL School of Pharmacy, University of London, 29–39 Brunswick Sq., London WC1N 1AX, UK; [email protected] (J.M.); [email protected] (V.A.) 2 Graduate Institute of Integrated Medicine, College of Chinese Medicine, and Chinese Medicine Research Center, China Medical University, No. 100, Section 1, Jingmao Road, Beitun District, Taichung 406040, Taiwan * Correspondence: [email protected]; Tel.: +44-20-7753-5844 Abstract: Selecting candidates for drug developments using computational design and empirical rules has resulted in a broad discussion about their success. In a previous study, we had shown that a species’ abundance [as expressed by the GBIF (Global Biodiversity Information Facility)] dataset is a core determinant for the development of a natural product into a medicine. Our overarching aim is to understand the unique requirements for natural product-based drug development. Web of Science was queried for research on alkaloids in combination with plant systematics/taxonomy. All alkaloids containing species demonstrated an average increase of 8.66 in GBIF occurrences between 2014 and 2020. Medicinal Species with alkaloids show higher abundance compared to non-medicinal alkaloids, often linked also to cultivation. Alkaloids with high biodiversity are often simple alkaloids found in multiple species with the presence of ’driver species‘ and are more likely to be included in early-stage drug development compared to ‘rare’ alkaloids. Similarly, the success of an alkaloid Citation: Heinrich, M.; Mah, J.; Amirkia, V. -
A Draft Map of the Human Proteome
ARTICLE doi:10.1038/nature13302 A draft map of the human proteome Min-Sik Kim1,2, Sneha M. Pinto3, Derese Getnet1,4, Raja Sekhar Nirujogi3, Srikanth S. Manda3, Raghothama Chaerkady1,2, Anil K. Madugundu3, Dhanashree S. Kelkar3, Ruth Isserlin5, Shobhit Jain5, Joji K. Thomas3, Babylakshmi Muthusamy3, Pamela Leal-Rojas1,6, Praveen Kumar3, Nandini A. Sahasrabuddhe3, Lavanya Balakrishnan3, Jayshree Advani3, Bijesh George3, Santosh Renuse3, Lakshmi Dhevi N. Selvan3, Arun H. Patil3, Vishalakshi Nanjappa3, Aneesha Radhakrishnan3, Samarjeet Prasad1, Tejaswini Subbannayya3, Rajesh Raju3, Manish Kumar3, Sreelakshmi K. Sreenivasamurthy3, Arivusudar Marimuthu3, Gajanan J. Sathe3, Sandip Chavan3, Keshava K. Datta3, Yashwanth Subbannayya3, Apeksha Sahu3, Soujanya D. Yelamanchi3, Savita Jayaram3, Pavithra Rajagopalan3, Jyoti Sharma3, Krishna R. Murthy3, Nazia Syed3, Renu Goel3, Aafaque A. Khan3, Sartaj Ahmad3, Gourav Dey3, Keshav Mudgal7, Aditi Chatterjee3, Tai-Chung Huang1, Jun Zhong1, Xinyan Wu1,2, Patrick G. Shaw1, Donald Freed1, Muhammad S. Zahari2, Kanchan K. Mukherjee8, Subramanian Shankar9, Anita Mahadevan10,11, Henry Lam12, Christopher J. Mitchell1, Susarla Krishna Shankar10,11, Parthasarathy Satishchandra13, John T. Schroeder14, Ravi Sirdeshmukh3, Anirban Maitra15,16, Steven D. Leach1,17, Charles G. Drake16,18, Marc K. Halushka15, T. S. Keshava Prasad3, Ralph H. Hruban15,16, Candace L. Kerr19{, Gary D. Bader5, Christine A. Iacobuzio-Donahue15,16,17, Harsha Gowda3 & Akhilesh Pandey1,2,3,4,15,16,20 The availability of human genome sequence has transformed biomedical research over the past decade. However, an equiv- alent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. -
Atypical Chromosome Abnormalities in Acute Myeloid Leukemia Type M4
Genetics and Molecular Biology, 30, 1, 6-9 (2007) Copyright by the Brazilian Society of Genetics. Printed in Brazil www.sbg.org.br Short Communication Atypical chromosome abnormalities in acute myeloid leukemia type M4 Agnes C. Fett-Conte1, Roseli Viscardi Estrela2, Cristina B. Vendrame-Goloni3, Andréa B. Carvalho-Salles1, Octávio Ricci-Júnior4 and Marileila Varella-Garcia5 1Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil. 2Austa Hospital, São José do Rio Preto, SP, Brazil. 3Departamento de Biologia, Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, SP, Brazil. 4Hemocentro, São José do Rio Preto, SP, Brazil. 5Comprehensive Cancer Center, University of Colorado, Denver, CO, USA. Abstract This study reports an adult AML-M4 patient with atypical chromosomal aberrations present in all dividing bone mar- row cell at diagnosis: t(1;8)(p32.1;q24.2), der(9)t(9;10)(q22;?), and ins(19;9)(p13.3;q22q34) that may have origi- nated transcripts with leukemogenic potential. Key words: acute myeloid leukemia, chromosomal abnormalities, chromosomal translocations. Received: February 10, 2006; Accepted: June 22, 2006. Acute non-lymphocytic or myelogenous leukemia (Mitelman Database of Chromosome Aberration in Cancer (ANLL or AML) represents a hematopoietic malignancy 2006). Karyotype is generally an important prognostic fac- characterized by abnormal cell proliferation and stalled dif- tor in AML, a favorable prognosis being associated with ferentiation leading to the accumulation of immature cells minor karyotypic changes, low frequency of abnormal in the marrow itself, in peripheral blood and eventually in bone marrow cells and changes specifically involving the other tissues. -
Transcriptomic and Epigenomic Characterization of the Developing Bat Wing
ARTICLES OPEN Transcriptomic and epigenomic characterization of the developing bat wing Walter L Eckalbar1,2,9, Stephen A Schlebusch3,9, Mandy K Mason3, Zoe Gill3, Ash V Parker3, Betty M Booker1,2, Sierra Nishizaki1,2, Christiane Muswamba-Nday3, Elizabeth Terhune4,5, Kimberly A Nevonen4, Nadja Makki1,2, Tara Friedrich2,6, Julia E VanderMeer1,2, Katherine S Pollard2,6,7, Lucia Carbone4,8, Jeff D Wall2,7, Nicola Illing3 & Nadav Ahituv1,2 Bats are the only mammals capable of powered flight, but little is known about the genetic determinants that shape their wings. Here we generated a genome for Miniopterus natalensis and performed RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages to decipher the molecular events that underlie bat wing development. Over 7,000 genes and several long noncoding RNAs, including Tbx5-as1 and Hottip, were differentially expressed between forelimb and hindlimb, and across different stages. ChIP-seq analysis identified thousands of regions that are differentially modified in forelimb and hindlimb. Comparative genomics found 2,796 bat-accelerated regions within H3K27ac peaks, several of which cluster near limb-associated genes. Pathway analyses highlighted multiple ribosomal proteins and known limb patterning signaling pathways as differentially regulated and implicated increased forelimb mesenchymal condensation in differential growth. In combination, our work outlines multiple genetic components that likely contribute to bat wing formation, providing insights into this morphological innovation. The order Chiroptera, commonly known as bats, is the only group of To characterize the genetic differences that underlie divergence in mammals to have evolved the capability of flight. -
Expression Profiling of Sexually Dimorphic Genes in the Japanese
www.nature.com/scientificreports OPEN Expression profling of sexually dimorphic genes in the Japanese quail, Coturnix japonica Miki Okuno1,5, Shuntaro Miyamoto2,5, Takehiko Itoh1, Masahide Seki3, Yutaka Suzuki3, Shusei Mizushima2,4 & Asato Kuroiwa2,4* Research on avian sex determination has focused on the chicken. In this study, we established the utility of another widely used animal model, the Japanese quail (Coturnix japonica), for clarifying the molecular mechanisms underlying gonadal sex diferentiation. In particular, we performed comprehensive gene expression profling of embryonic gonads at three stages (HH27, HH31 and HH38) by mRNA-seq. We classifed the expression patterns of 4,815 genes into nine clusters according to the extent of change between stages. Cluster 2 (characterized by an initial increase and steady levels thereafter), including 495 and 310 genes expressed in males and females, respectively, contained fve key genes involved in gonadal sex diferentiation. A GO analysis showed that genes in this cluster are related to developmental processes including reproductive structure development and developmental processes involved in reproduction were signifcant, suggesting that expression profling is an efective approach to identify novel candidate genes. Based on RNA-seq data and in situ hybridization, the expression patterns and localization of most key genes for gonadal sex diferentiation corresponded well to those of the chicken. Our results support the efectiveness of the Japanese quail as a model for studies gonadal sex diferentiation in birds. In birds, males are homogametic (ZZ) and females are heterogametic (ZW). Te sex determination mechanism involving gene(s) on the sex chromosome is highly conserved among birds. In chickens, sex determination is thought to occur afer embryonic day (E) 4.5, corresponding to Hamburger and Hamilton stage1 24 (HH24). -
Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer
life Article Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer Dehua Liu 1 , Chenyu Sun 2 , Nahyun Kim 2 , Chandur Bhan 2, John Pocholo Whitaker Tuason 2, Yue Chen 3, Shaodi Ma 4, Yuting Huang 5 , Ce Cheng 6,7, Qin Zhou 8 and Kaiguang Zhang 1,* 1 The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; [email protected] 2 Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, IL 60657, USA; [email protected] (C.S.); [email protected] (N.K.); [email protected] (C.B.); [email protected] (J.P.W.T.) 3 Department of Clinical Medicine, School of the First Clinical Medicine, Anhui Medical University, Hefei 230032, China; [email protected] 4 Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, China; [email protected] 5 University of Maryland Medical Center Midtown Campus, Baltimore, MD 21201, USA; [email protected] 6 The University of Arizona College of Medicine, Banner University Medical Center at South Campus, Tucson, AZ 85724, USA; [email protected] 7 Banner-University Medical Center South, Tucson, AZ 85713, USA 8 Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA; [email protected] * Correspondence: [email protected]; Tel.: +86-138-5517-0097 Citation: Liu, D.; Sun, C.; Kim, N.; Abstract: Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related Bhan, C.; Tuason, J.P.W.; Chen, Y.; Ma, proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregu- S.; Huang, Y.; Cheng, C.; Zhou, Q.; lated expression is found in multiple cancers.