Published Title QUALIFIER NAME AFC Tnfa/ DMSO Tumor Necrosis
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
CD40 Signaling Synergizes with TLR-2 in the BCR Independent Activation of Resting B Cells
CD40 Signaling Synergizes with TLR-2 in the BCR Independent Activation of Resting B Cells Shweta Jain, Sathi Babu Chodisetti, Javed N. Agrewala* Immunology Laboratory, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, India Abstract Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB) cells, by involving TLR-2 and CD40 - molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID), signifying class switch recombination (CSR). Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response. Citation: Jain S, Chodisetti SB, Agrewala JN (2011) CD40 Signaling Synergizes with TLR-2 in the BCR Independent Activation of Resting B Cells. PLoS ONE 6(6): e20651. doi:10.1371/journal.pone.0020651 Editor: Leonardo A. Sechi, Universita di Sassari, Italy Received April 14, 2011; Accepted May 6, 2011; Published June 2, 2011 Copyright: ß 2011 Jain et al. -
An Overview of the Role of Hdacs in Cancer Immunotherapy
International Journal of Molecular Sciences Review Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy Debarati Banik, Sara Moufarrij and Alejandro Villagra * Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, 800 22nd St NW, Suite 8880, Washington, DC 20052, USA; [email protected] (D.B.); [email protected] (S.M.) * Correspondence: [email protected]; Tel.: +(202)-994-9547 Received: 22 March 2019; Accepted: 28 April 2019; Published: 7 May 2019 Abstract: Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration. -
Polymorphisms with Late-Onset Alzheimer Disease in Han Chinese
172 Original Article on Translational Neurodegeneration Page 1 of 8 Association of lectin-like oxidized low density lipoprotein receptor 1 (OLR1) polymorphisms with late-onset Alzheimer disease in Han Chinese Zuo-Teng Wang1#, Xiao-Ling Zhong2#, Meng-Shan Tan1, Hui-Fu Wang1, Chen-Chen Tan1, Wei Zhang1, Zhan-Jie Zheng3, Ling-Li Kong3, Lan Tan1, Li Sun2 1Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China; 2Department of Neurology, Qingdao Central Hospital, Qingdao University, Qingdao 266042, China; 3Department of Geriatric, Qingdao Mental Health Center, Qingdao 266034, China Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: All authors; (VI) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. #These authors should be regarded as co-first authors. Correspondence to: Dr. Lan Tan, MD, PhD. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Qingdao 266071, China. Email: [email protected]; Dr. Li Sun, MD, PhD. Department of Neurology, Qingdao Central Hospital, Qingdao University, Qingdao 266042, China. Email: [email protected]. Background: Lectin-like oxidized low density lipoprotein receptor 1 (OLR1) locates within the area of chromosome 12p, which has been identified as the AD-susceptible region, and plays a role in lipid metabolism. Therefore, it has been suggested to be a good candidate gene for Alzheimer’s disease (AD). Several SNPs within OLR1 have been reported to have association with AD among Caucasians. Methods: We selected and genotyped three SNPs (rs1050283, rs1050286, rs17808009) in OLR1 to investigate its possible relationship with the onset of late-onset Alzheimer disease(LOAD) in 984 LOAD cases and 1,354 healthy controls among northern Han Chinese. -
Genome Wide Analysis of TLR1/2- and TLR4-Activated SZ95 Sebocytes
RESEARCH ARTICLE Genome wide analysis of TLR1/2- and TLR4- activated SZ95 sebocytes reveals a complex immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands DaÂniel ToÈ rőcsik1,2*, DoÂra KovaÂcs1, SzilaÂrd PoÂliska3, Zita Szentkereszty-KovaÂcs1, a1111111111 Marianna LovaÂszi1, Katalin Hegyi1, Andrea Szegedi1,4, Christos C. Zouboulis5, a1111111111 Mona Ståhle2 a1111111111 a1111111111 1 Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 2 Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, a1111111111 Stockholm, Sweden, 3 Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatics Core Facility, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 4 Division of Dermatological Allergology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 5 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau, Germany OPEN ACCESS * [email protected] Citation: ToÈrőcsik D, KovaÂcs D, PoÂliska S, Szentkereszty-KovaÂcs Z, LovaÂszi M, Hegyi K, et al. (2018) Genome wide analysis of TLR1/2- and TLR4-activated SZ95 sebocytes reveals a complex Abstract immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands. Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in PLoS ONE 13(6): e0198323. https://doi.org/ the development of acne. Still, there is only limited knowledge on their effect on sebocytes. 10.1371/journal.pone.0198323 In this work we performed global gene expression profile analysis with functional clustering Editor: Mauro Picardo, San Gallicano Dermatologic of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide Institute, ITALY [LPS])-activated SZ95 sebocytes. -
Basic Science * Drug X Is Used for Ongoing IP/Patent Assessment Heart: First Published As 10.1136/Heartjnl-2021-BCS.199 on 4 June 2021
Abstracts Basic science * Drug X is used for ongoing IP/patent assessment Heart: first published as 10.1136/heartjnl-2021-BCS.199 on 4 June 2021. Downloaded from Conflict of Interest No BS1 REPROGRAMMING HUMAN MACROPHAGES WITH DRUG X: POTENTIAL MECHANISMS FOR STABILISATION OF ATHEROSCLEROTIC PLAQUES BS2 MECHANOSENSOR PIEZO1 IN SKELETAL MUSCLE PERICYTES 1Klaudia Kocsy, 1Endre Kiss-Toth, 2Jessica Redgrave, 2Arshad Majid, 3Sheila Francis. 1Department of Infection, Immunity & Cardiovascular Disease, The University of Sheffield, 1Yilizila Abudushalamu, 1Hema Viswambharan, 2Romana Mughal, 1Richard Cubbon, Sheffield, UK; 2Department of Neuroscience, The University of Sheffield, Sheffield, UK; 3The 1Mark Kearney, 1David Beech, 1Piruthivi Sukumar. 1Discovery and Translational Science University of Sheffield, Sheffield, UK Department Leeds Institute of Cardiovascular and Metabolic Medic, Leeds, UK; 2Department of Optometry and Vision Sciences School of Applied Sciences University of Huddersfield 10.1136/heartjnl-2021-BCS.199 10.1136/heartjnl-2021-BCS.200 Introduction Ischemic stroke is commonly caused by large artery atherosclerosis. Patients with a high atherosclerotic bur- Introduction Pericytes (PC) are mural cells which are present den (stenosis) and inflamed or ulcerated plaque are at in blood microvessels. They play an important part in the for- increased risk of early recurrent ischaemic events. Treatment mation and stabilization of new blood vessels. They are essen- with anti-inflammatory agents may therefore reduce stroke tial for vascular development and cardiovascular homeostasis. incidence and recurrence in patients with this condition, but They wrap around the endothelial cells (EC) and endothelial- in vitro human studies of the possible mechanisms are lacking. pericyte communication is both via physical contact and para- 1 We hypothesised that an anti-inflammatory compound crine signalling. -
The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis
Page 1 of 53 Diabetes The metabolic regulator histone deacetylase 9 contributes to glucose homeostasis abnormality induced by hepatitis C virus infection Jizheng CHEN2, Ning WANG1, Mei DONG1, Min GUO2, Yang ZHAO3, Zhiyong ZHUO3, Chao ZHANG3, Xiumei CHI4, Yu PAN4, Jing JIANG4, Hong TANG2, Junqi NIU4, Dongliang YANG5, Zhong LI1, Xiao HAN1, Qian WANG1* and Xinwen Chen2 1 Jiangsu Province Key Lab of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, China 2 State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China 3 Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China 4 Department of Hepatology, The First Hospital of Jilin University, Changchun, 130021, China 5 Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, China 1 Diabetes Publish Ahead of Print, published online September 29, 2015 Diabetes Page 2 of 53 *Correspondence: Qian WANG, Ph.D. Jiangsu Province Key Lab of Human Functional Genomics Department of Biochemistry and Molecular Biology Nanjing Medical University Nanjing 210029, China E-mail: [email protected] Fax: +86-25-8362 1065 Tel: +86-25-8686 2729 2 Page 3 of 53 Diabetes ABSTRACT Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7 provide critical mechanisms for regulating glucose homeostasis. Here we report HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1, together with HDAC3. Specifically, HDAC9 expression can be strongly induced upon hepatitis C virus (HCV) infection. -
(P -Value<0.05, Fold Change≥1.4), 4 Vs. 0 Gy Irradiation
Table S1: Significant differentially expressed genes (P -Value<0.05, Fold Change≥1.4), 4 vs. 0 Gy irradiation Genbank Fold Change P -Value Gene Symbol Description Accession Q9F8M7_CARHY (Q9F8M7) DTDP-glucose 4,6-dehydratase (Fragment), partial (9%) 6.70 0.017399678 THC2699065 [THC2719287] 5.53 0.003379195 BC013657 BC013657 Homo sapiens cDNA clone IMAGE:4152983, partial cds. [BC013657] 5.10 0.024641735 THC2750781 Ciliary dynein heavy chain 5 (Axonemal beta dynein heavy chain 5) (HL1). 4.07 0.04353262 DNAH5 [Source:Uniprot/SWISSPROT;Acc:Q8TE73] [ENST00000382416] 3.81 0.002855909 NM_145263 SPATA18 Homo sapiens spermatogenesis associated 18 homolog (rat) (SPATA18), mRNA [NM_145263] AA418814 zw01a02.s1 Soares_NhHMPu_S1 Homo sapiens cDNA clone IMAGE:767978 3', 3.69 0.03203913 AA418814 AA418814 mRNA sequence [AA418814] AL356953 leucine-rich repeat-containing G protein-coupled receptor 6 {Homo sapiens} (exp=0; 3.63 0.0277936 THC2705989 wgp=1; cg=0), partial (4%) [THC2752981] AA484677 ne64a07.s1 NCI_CGAP_Alv1 Homo sapiens cDNA clone IMAGE:909012, mRNA 3.63 0.027098073 AA484677 AA484677 sequence [AA484677] oe06h09.s1 NCI_CGAP_Ov2 Homo sapiens cDNA clone IMAGE:1385153, mRNA sequence 3.48 0.04468495 AA837799 AA837799 [AA837799] Homo sapiens hypothetical protein LOC340109, mRNA (cDNA clone IMAGE:5578073), partial 3.27 0.031178378 BC039509 LOC643401 cds. [BC039509] Homo sapiens Fas (TNF receptor superfamily, member 6) (FAS), transcript variant 1, mRNA 3.24 0.022156298 NM_000043 FAS [NM_000043] 3.20 0.021043295 A_32_P125056 BF803942 CM2-CI0135-021100-477-g08 CI0135 Homo sapiens cDNA, mRNA sequence 3.04 0.043389246 BF803942 BF803942 [BF803942] 3.03 0.002430239 NM_015920 RPS27L Homo sapiens ribosomal protein S27-like (RPS27L), mRNA [NM_015920] Homo sapiens tumor necrosis factor receptor superfamily, member 10c, decoy without an 2.98 0.021202829 NM_003841 TNFRSF10C intracellular domain (TNFRSF10C), mRNA [NM_003841] 2.97 0.03243901 AB002384 C6orf32 Homo sapiens mRNA for KIAA0386 gene, partial cds. -
Evaluating the Effect of TLR4-Overexpressing on The
Guo et al. J of Biol Res-Thessaloniki (2020) 27:13 https://doi.org/10.1186/s40709-020-00124-3 Journal of Biological Research-Thessaloniki RESEARCH Open Access Evaluating the efect of TLR4-overexpressing on the transcriptome profle in ovine peripheral blood mononuclear cells Xiaofei Guo1†, Jinlong Zhang1,2†, Yao Li2, Jing Yang1, Yihai Li1, Chunxiao Dong1, Guoshi Liu2, Zhengxing Lian2 and Xiaosheng Zhang1* Abstract Background: Toll-like receptor 4 (TLR4) plays an important role in the elimination of Gram-negative bacteria infec- tions and the initiation of antiinfammatory response. Using the technology of pronuclear microinjection, genetically modifed (GM) sheep with TLR4 overexpression were generated. Previous studies have shown that these GM sheep exhibited a higher infammatory response to Gram-negative bacteria infection than wild type (WT) sheep. In order to evaluate the gene expression of GM sheep and study the co-expressed and downstream genes for TLR4, peripheral blood mononuclear cells (PBMC) from TLR4-overexpressing (Tg) and wild type (WT) sheep were selected to discover the transcriptomic diferences using RNA-Seq. Result: An average of 18,754 and 19,530 known genes were identifed in the Tg and WT libraries, respectively. A total of 338 known genes and 85 novel transcripts were found to be diferentially expressed in the two libraries (p < 0.01). A diferentially expressed genes (DEGs) enrichment analysis showed that the GO terms of infammatory response, cell recognition, etc. were signifcantly (FDR < 0.05) enriched. Furthermore, the above DEGs were signifcantly (FDR < 0.05) enriched in the sole KEGG pathway of the Phagosome. Real-time PCR showed the OLR1, TLR4 and CD14 genes to be diferentially expressed in the two groups, which validated the DEGs data. -
Modulation of Cell-Mediated Immunity by HIV-1 Infection of Macrophages
Modulation of cell-mediated immunity by HIV-1 infection of macrophages Lucy Caitríona Kiernan Bell Division of Infection and Immunity University College London PhD Supervisor: Dr Mahdad Noursadeghi A thesis submitted for the degree of Doctor of Philosophy University College London August 2014 Declaration I, Lucy Caitríona Kiernan Bell, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Abstract Cell-mediated immunity (CMI) is central to the host response to intracellular pathogens such as Mycobacterium tuberculosis (Mtb). The function of CMI can be modulated by human immunodeficiency virus (HIV)-1 via its pleiotropic effects on the immune response, including modulation of macrophages, which are parasitized by both HIV-1 and Mtb. HIV-1 infection is associated with increased risk of tuberculosis (TB), and so in this thesis I sought to explore the host/pathogen interactions through which HIV-1 dysregulates CMI, and thus changes the natural history of TB. Using an in vitro model of human monocyte-derived macrophages (MDMs), I characterise a phenotype wherein HIV-1 specifically attenuates production of the immunoregulatory cytokine interleukin (IL)-10 in response to Mtb and other innate immune stimuli. I show that this phenotype requires HIV-1 integration and gene expression, and may result from a function of the HIV-1 accessory proteins. I identify that the phosphoinositide 3-kinase (PI3K) pathway specifically regulates IL-10 production in human MDMs, and thus may be a target for HIV-1 to mediate IL-10 attenuation. -
Genetic Testing Policy Number: PG0041 ADVANTAGE | ELITE | HMO Last Review: 04/11/2021
Genetic Testing Policy Number: PG0041 ADVANTAGE | ELITE | HMO Last Review: 04/11/2021 INDIVIDUAL MARKETPLACE | PROMEDICA MEDICARE PLAN | PPO GUIDELINES This policy does not certify benefits or authorization of benefits, which is designated by each individual policyholder terms, conditions, exclusions and limitations contract. It does not constitute a contract or guarantee regarding coverage or reimbursement/payment. Paramount applies coding edits to all medical claims through coding logic software to evaluate the accuracy and adherence to accepted national standards. This medical policy is solely for guiding medical necessity and explaining correct procedure reporting used to assist in making coverage decisions and administering benefits. SCOPE X Professional X Facility DESCRIPTION A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to a heritable or acquired disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing). Clinical genetic tests are those in which specimens are examined and results reported to the provider or patient for the purpose of diagnosis, prevention or treatment in the care of individual patients. Genetic testing is performed for a variety of intended uses: Diagnostic testing (to diagnose disease) Predictive -
Critical Role of Oxidized LDL Receptor-1 in Intravascular
www.nature.com/scientificreports OPEN Critical role of oxidized LDL receptor‑1 in intravascular thrombosis in a severe infuenza mouse model Marumi Ohno1, Akemi Kakino2, Toshiki Sekiya1, Naoki Nomura1, Masashi Shingai1, Tatsuya Sawamura2 & Hiroshi Kida1* Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single‑ or multiple‑organ dysfunction in severe infuenza, the detailed mechanisms have yet been clarifed. This study evaluated infuenza‑associated abnormal blood coagulation utilizing a severe infuenza mouse model. After infecting C57BL/6 male mice with intranasal applications of 500 plaque‑forming units of infuenza virus A/Puerto Rico/8/34 (H1N1; PR8), an elevated serum level of prothrombin fragment 1 + 2, an indicator for activated thrombin generation, was observed. Also, an increased gene expression of oxidized low‑density lipoprotein (LDL) receptor‑1 (Olr1), a key molecule in endothelial dysfunction in the progression of atherosclerosis, was detected in the aorta of infected mice. Body weight decrease, serum levels of cytokines and chemokines, viral load, and infammation in the lungs of infected animals were similar between wild‑type and Olr1 knockout (KO) mice. In contrast, the elevation of prothrombin fragment 1 + 2 levels in the sera and intravascular thrombosis in the lungs by PR8 virus infection were not induced in KO mice. Collectively, the results indicated that OLR1 is a critical host factor in intravascular thrombosis as a pathogeny of severe infuenza. Thus, OLR1 is a promising novel therapeutic target for thrombosis during severe infuenza. Infuenza is a respiratory disease and remains a major health concern, causing approximately half a million deaths per year globally1. -
Impaired Autophagy Triggered by HDAC9 in Mesenchymal Stem Cells Accelerates Bone Mass Loss
Impaired autophagy triggered by HDAC9 in mesenchymal stem cells accelerates bone mass loss Running title: HDAC9 impairs MSCs differentiation via autophagy. Zhang Liqiang1,2,4, Qi Meng1, 4, Chen Ji1,4,Zhao Jiangdong3, Li Liya2, Hu Jiachen1, Jin Yan1,2*, Liu Wenjia1,2* 1. State Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases&Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China. 2. Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China. 3. The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China. 4. These authors contributed equally to this work. Correspondence Wenjia Liu & Yan Jin, Center for Tissue Engineering, Fourth Military Medical University, No. 145 West Changle Road, Xi’an, Shaanxi, China. Emails: [email protected] or [email protected];[email protected]; Abstract Background: Bone mass loss in aging is linked with imbalanced lineage differentiation of bone marrow mesenchymal stem cells (BMMSCs). Recent studies have proved that histone deacetylases (HDACs) are regarded as key regulators of bone remodeling. However, HDACs involve in regulating BMMSCs bio-behaviors remain elusive. Here, we investigated ability of HDAC9 on modulation of autophagy and its significance in lineage differentiation of BMMSCs. Methods: The effects of HDAC9 on lineage differentiation of BMMSCs and autophagic signalling were assessed by various biochemical (Western blot and ChIP assay), morphological (TEM and confocal microscopy) and microCT assays. Results : 16-month mice manifested obvious bone mass loss and marrow fat increase, accompanied with the decreased osteogenic differentiation and increased adipogenic differentiation of BMMSCs.