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https://www.readbyqxmd.com/read/28432946/design-and-synthesis-of-sulfonamide-substituted-diphenylpyrimidines-sfa-dppys-as-potent-bruton-s-tyrosine-kinase-btk-inhibitors-with-improved-activity-toward-b-cell-lymphoblastic-leukemia
#1
He Liu, Menghua Qu, Lina Xu, Xu Han, Changyuan Wang, Xiaohong Shu, Jihong Yao, Kexin Liu, Jinyong Peng, Yanxia Li, Xiaodong Ma
A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC50 values of 1.18 nM, 0.92 nM, 0.42 nM and 1.05 nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430970/helicobacter-pylori-outer-membrane-vesicles-inhibit-human-t-cell-responses-via-induction-of-monocyte-cox-2-expression
#2
Barry D Hock, Judith L McKenzie, Jacqueline I Keenan
The modulation of T cell responses by Helicobacter pylori is thought to potentiate both H. pylori persistence and development of gastric pathologies including cancer. Release of outer membrane vesicles (OMV) by H. pylori provides a potential vehicle for modulation of the immune system. Although OMV are thought to have T cell suppressive activity this has not yet been demonstrated. Their suppressive activity was investigated in this study using the responses of peripheral blood mononuclear cells (PBMC) to T cell stimuli as a readout...
April 18, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28428745/decreased-levels-of-foldase-and-chaperone-proteins-are-associated-with-an-early-onset-amyotrophic-lateral-sclerosis
#3
Melania Filareti, Silvia Luotti, Laura Pasetto, Mauro Pignataro, Katia Paolella, Paolo Messina, Elisabetta Pupillo, Massimiliano Filosto, Christian Lunetta, Jessica Mandrioli, Giuseppe Fuda, Andrea Calvo, Adriano Chiò, Massimo Corbo, Caterina Bendotti, Ettore Beghi, Valentina Bonetto
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration. One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors. We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset. This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#4
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425472/label-free-single-cell-separation-and-imaging-of-cancer-cells-using-an-integrated-microfluidic-system
#5
Maria Antfolk, Soo Hyeon Kim, Saori Koizumi, Teruo Fujii, Thomas Laurell
The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420440/immune-response-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes-mellitus
#6
Lei Ye, Li Li, Bing Wan, Minglan Yang, Jie Hong, Weiqiong Gu, Weiqing Wang, Guang Ning
BACKGROUND: This study explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus. METHODS: Peripheral blood mononuclear cells (PBMCs) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in PBMC culture supernatants were assessed...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28420387/effects-of-host-restriction-factors-and-the-htlv-1-subtype-on-susceptibility-to-htlv-1-associated-myelopathy-tropical-spastic-paraparesis
#7
Satoshi Nozuma, Eiji Matsuura, Daisuke Kodama, Yuichi Tashiro, Toshio Matsuzaki, Ryuji Kubota, Shuji Izumo, Hiroshi Takashima
BACKGROUND: Although human T-lymphotropic virus type 1 (HTLV-1) infection is a prerequisite for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), specific provirus mutations in HAM/TSP have not yet been reported. In this study, we examined whether HAM/TSP patients had the disease-specific genomic variants of HTLV-1 by analyzing entire sequences of HTLV-1 proviruses in these patients, including familial cases. In addition, we investigated the genetic variants of host restriction factors conferring antiretroviral activity to determine which mutations may be related to resistance or susceptibility to HAM/TSP...
April 19, 2017: Retrovirology
https://www.readbyqxmd.com/read/28420279/responses-of-blood-mononucleated-cells-and-clinical-outcome-of-non-celiac-gluten-sensitive-pediatric-patients-to-various-cereal-sources-a-pilot-study
#8
Patrizia Alvisi, Luigia De Fazio, Maria Chiara Valerii, Elena Cavazza, Angela Salerno, Doriana Lacorte, Giovanni Dinelli, Enzo Spisni
Non-celiac gluten sensitivity (NCGS) is a clinical entity recently documented by the scientific community in pediatric patients. Nevertheless, its triggering mechanisms remain largely unsettled. We studied 11 children with NCGS who were diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease (CD) and wheat allergy, matched with 18 children with active CD. Sixteen pediatric patients were also enrolled as controls. Cultured peripheral blood mononucleated cells (PBMCs) obtained from NCGS, CD and control patients were cultured in the presence of wheat proteins extracted from ancient and modern cultivars...
April 19, 2017: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/28420272/resveratrol-suppresses-hyperoxia-induced-nucleocytoplasmic-shuttling-of-sirt1-and-ros-production-in-pbmc-from-preterm-infants-in-vitro
#9
Xi Yang, Wen-Bin Dong, Xiao-Ping Lei, Qing-Ping Li, Lian-Yu Zhang, Ling-Ping Zhang
OBJECTIVE: By assessing silent mating-type information regulation 2 homolog 1 (SIRT1) nucleocytoplasmic shuttling and reactive oxygen species (ROS) levels in peripheral blood mononuclear cells (PBMCs), this study aimed to explore the role of SIRT1 in premature infants after exposure to hyperoxia and assess the protective effects of resveratrol (Res). METHODS: Firstly, ROS levels as well as SIRT1 translocation and expression in PBMCs samples were evaluated from 40 premature infants with different oxygen amounts received at birth...
April 18, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28419653/hcv-viremia-associates-with-nk-cell-activation-and-dysfunction-in-anti-retroviral-hiv-hcv-co-infected-subjects
#10
E Papasavvas, L Azzoni, X Yin, Q Liu, J Joseph, A Mackiewicz, B Ross, K M Lynn, J M Jacobson, K Mounzer, J R Kostman, L J Montaner
The impact of Hepatitis C virus (HCV) RNA levels on immune status in chronically HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy (ART) remains poorly understood. A total of 78 African American subjects HCV viremic/naïve to HCV treatment (33 HCV genotype 1 mono-infected, 45 HCV genotype 1/HIV co-infected on ART) were studied. Clinical and liver enzymes measurements were performed. Whole blood was analyzed for immune subset changes by flow-cytometry. Peripheral blood mononuclear cells (PBMC) were used for same-day constitutive and in vitro Interferon (IFN)-α-induced Signal Transducer and Activator of Transcription (STAT) phosphorylation, K562 target cell lysis and K562 target cell recognition-mediated IFN-γ production...
April 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28416006/leishmania-major-large-rab-gtpase-is-highly-immunogenic-in-individuals-immune-to-cutaneous-and-visceral-leishmaniasis
#11
Rym Chamakh-Ayari, Mehdi Chenik, Ahmed Sahbi Chakroun, Narges Bahi-Jaber, Karim Aoun, Amel Meddeb-Garnaoui
BACKGROUND: We previously identified a Leishmania (L.) major large RAB GTPase (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania species while displaying low level of homology with mammalian homologues. Leishmania small RAB GTPases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large RAB GTPases proteins has not been characterized yet. We report here the immunogenicity of both recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L...
April 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28414780/sensitive-quantification-of-the-hiv-1-reservoir-in-gut-associated-lymphoid-tissue
#12
Sara Morón-López, Maria C Puertas, Cristina Gálvez, Jordi Navarro, Anna Carrasco, Maria Esteve, Josep Manyé, Manel Crespo, Maria Salgado, Javier Martinez-Picado
BACKGROUND: The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As reported in the so called "Boston Patients", despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption...
2017: PloS One
https://www.readbyqxmd.com/read/28412745/neutrophil-count-is-associated-with-myeloid-derived-suppressor-cell-level-and-presents-prognostic-value-of-for-hepatocellular-carcinoma-patients
#13
Xing Li, Yan-Fang Xing, Ai-Hua Lei, Qiang Xiao, Zhi-Huan Lin, Ying-Fen Hong, Xiang-Yuan Wu, Jie Zhou
Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC)...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411882/in-vitro-generation-of-interleukin-10-secreting-b-regulatory-cells-from-donor-adipose-tissue-derived-mesenchymal-stem-cells-and-recipient-peripheral-blood-mononuclear-cells-for-potential-cell-therapy
#14
Kunal S Gupte, Aruna V Vanikar, Hargovind L Trivedi, Chetan N Patel, Jignesh V Patel
BACKGROUND: Interleukin-10 secreting B-cells are a major subset of B-regulatory cells (B-regs), commonly recognized as CD19(+)/38(hi)/24(hi)/IL10(+). They carry out immunomodulation by release of specific cytokines and/or cell-to-cell contact. We have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear cells (PBMC) for potential cell therapy. MATERIAL AND METHODS: Mononuclear cells separated by density gradient centrifugation from 50 ml anti-coagulated blood of 15-RAR and respective donors were analysed for baseline B-regs using appropriate antibodies...
February 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28411413/sexual-intimacy-in-couples-is-associated-with-longer-telomere-length
#15
Tomás Cabeza de Baca, Elissa S Epel, Theodore F Robles, Michael Coccia, Amanda Gilbert, Eli Puterman, Aric A Prather
High-quality relationships have been shown to be beneficial for physical and mental health. This study examined overall relationship satisfaction and perceived stress as well as daily reports of partner support, partner conflict, and physical intimacy obtained over the course of one week in a sample of 129 high and low stress mothers. Telomere length was examined in whole blood, as well as the two cell subpopulations: peripheral blood mononuclear cells (PBMCs) and granulocytes. Telomerase activity was measured in PBMCs...
March 25, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28410455/diallyl-polysulfides-from-allium-sativum-as-immunomodulators-hepatoprotectors-and-antimycobacterial-agents
#16
Carel Oosthuizen, Miriam Arbach, Debra Meyer, Chris Hamilton, Namrita Lall
Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC)...
April 14, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28407320/role-of-tlr4-and-mir-155-in-peripheral-blood-mononuclear-cell-mediated-inflammatory-reaction-in-coronary-slow-flow-and-coronary-arteriosclerosis-patients
#17
Jiangyan Huang, Qin Yang, Longmiao He, Jun Huang
BACKGROUND: To study the role of toll-like receptor 4 (TLR4) and MicroRNA-155 (miR-155) in the peripheral blood mononuclear cell (PBMC)-mediated inflammation in coronary slow flow (CSF) and coronary arteriosclerosis. METHODS: Patients were divided into acute coronary syndrome (ACS), stable angina pectoris (SAP), CSF, and healthy control (HC) groups. The isolated PBMCs were treated with lipopolysaccharide (LPS)/and antagomiR-155. TLR4, miR-155, and the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1, and IL-10 were measured...
April 13, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28405494/overcoming-resistance-to-her2-targeted-therapy-with-a-novel-her2-cd3-bispecific-antibody
#18
Andres Lopez-Albaitero, Hong Xu, Hongfen Guo, Linlin Wang, Zhihao Wu, Hoa Tran, Sarat Chandarlapaty, Maurizio Scaltriti, Yelena Janjigian, Elisa de Stanchina, Nai-Kong V Cheung
T-cell-based therapies have emerged as one of the most clinically effective ways to target solid and non-solid tumors. HER2 is responsible for the oncogenesis and treatment resistance of several human solid tumors. As a member of the HER family of tyrosine kinase receptors, its over-activity confers unfavorable clinical outcome. Targeted therapies directed at this receptor have achieved responses, although development of resistance is common. We explored a novel HER2/CD3 bispecific antibody (HER2-BsAb) platform that while preserving the anti-proliferative effects of trastuzumab, it recruits and activates non-specific circulating T-cells, promoting T cell tumor infiltration and ablating HER2(+) tumors, even when these are resistant to standard HER2-targeted therapies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28402970/the-genotyping-resistance-profile-of-the-pol-gene-detected-in-blood-of-newly-diagnosed-hiv-positive-men-is-durably-archived-in-the-gut-whatever-the-time-of-initiation-of-cart
#19
Anne Emmanuelle Depincé, Elodie Dussert, Delphine Vergnon-Miszczycha, Abdelaye Keita, Sylvie Pillet, Elisabeth Botelho-Nevers, Anne Frésard, Amandine Gagneux-Brunon, Frédéric R Lucht, Xavier Roblin, Bruno Pozzetto, Stéphane Paul, Thomas Bourlet
OBJECTIVE: To evaluate the mutational patterns on the pol gene of the main HIV-1 strain archived in cell genome of 10 chronically infected men according to their clinical and therapeutic history. The genotyping resistance profiles were compared between the first blood plasma available at the time of HIV diagnosis and rectal biopsies and PBMC sampled 1-5 years after the initiation of combined antiretroviral therapy (cART). METHODS: HIV-1 RNA and cell-associated HIV-1 DNA were quantified by Abbott Real-Time HIV-1 and Generic HIV® DNA cell (Biocentric) assays...
April 13, 2017: Intervirology
https://www.readbyqxmd.com/read/28398808/isolation-methods-of-peripheral-blood-mononuclear-cells-in-spanish-biobanks-an-overview
#20
Irene Consuegra, Clara Rodríguez-Aierbe, Inés Santiuste, Anna Bosch, Rosario Martínez-Marín, Ma Antonia Fortuto, Tatiana Díaz, Salvador Martí, Ma Ángeles Muñoz-Fernández
The Spanish Hematic Derivatives Group, consisting of 26 biobanks, was established in 2011. We describe here the viability results of our publically available standard operating procedure to freeze and thaw peripheral blood mononuclear cells (PBMCs). Our protocol maximizes PBMC viability while avoiding where possible interbiobank and intrabiobank assay variability.
February 22, 2017: Biopreservation and Biobanking
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