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https://www.readbyqxmd.com/read/29166707/-establishment-of-myocardial-targeted-nanoparticles-and-preliminary-evaluation-of-its-effects-on-prevention-and-treatment-of-myocardial-injury
#1
Y Y Liu, C Wang, P F Luo, Z F Xia
Objective: To establish 3-{4-[2-hydroxyl-(1-methylethylamino) propoxy] phenyl} propionic acid cetylesters (PAC) modified nanoparticles, and preliminarily explore its cardiomyocyte-targeting function and protection effects on myocardium. Methods: (1) HL-1 myocardial cells were divided into cyanidin-3 (Cy3) marked non-targeted small interference RNA (Cy3-siNC) group and Cy3 marked small interference RNA designed for the nuclear factor kappa B (NF-κB)-p65 gene (Cy3-si435) group according to the random number table, with 3 wells in each group...
November 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29166616/the-aryl-hydrocarbon-receptor-preferentially-marks-and-promotes-gut-regulatory-t-cells
#2
Jian Ye, Ju Qiu, John W Bostick, Aki Ueda, Hilde Schjerven, Shiyang Li, Christian Jobin, Zong-Ming E Chen, Liang Zhou
The local environment may affect the development and function of tissue-resident T regulatory cells (Tregs), which are crucial for controlling inflammation. Although the aryl hydrocarbon receptor (Ahr), an environmental sensor, is expressed by Tregs, its role in Treg cell development and/or function remains elusive. Here, we generated mouse genetic models to ablate or activate Ahr expression specifically in Tregs. We showed that Ahr was expressed more abundantly by peripherally induced Tregs (pTregs) in the gut and that its expression was independent of microbiota...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166604/capture-of-dense-core-vesicles-at-synapses-by-jnk-dependent-phosphorylation-of-synaptotagmin-4
#3
Vinita Bharat, Michael Siebrecht, Katja Burk, Saheeb Ahmed, Carsten Reissner, Mahdokht Kohansal-Nodehi, Vicky Steubler, Markus Zweckstetter, Jonathan T Ting, Camin Dean
Delivery of neurotrophins and neuropeptides via long-range trafficking of dense core vesicles (DCVs) from the cell soma to nerve terminals is essential for synapse modulation and circuit function. But the mechanism by which transiting DCVs are captured at specific sites is unknown. Here, we discovered that Synaptotagmin-4 (Syt4) regulates the capture and spatial distribution of DCVs in hippocampal neurons. We found that DCVs are highly mobile and undergo long-range translocation but switch directions only at the distal ends of axons, revealing a circular trafficking pattern...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166591/a-cd103-conventional-dendritic-cell-surveillance-system-prevents-development-of-overt-heart-failure-during-subclinical-viral-myocarditis
#4
Xavier Clemente-Casares, Siyavash Hosseinzadeh, Iulia Barbu, Sarah A Dick, Jillian A Macklin, Yiming Wang, Abdul Momen, Crystal Kantores, Laura Aronoff, Maylis Farno, Tiffany M Lucas, Joan Avery, Dorrin Zarrin-Khat, Heidi J Elsaesser, Babak Razani, Kory J Lavine, Mansoor Husain, David G Brooks, Clinton S Robbins, Myron Cybulsky, Slava Epelman
Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103(+) and CD11b(+), which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166588/regulatory-t-cell-migration-is-dependent-on-glucokinase-mediated-glycolysis
#5
Madhav Kishore, Kenneth C P Cheung, Hongmei Fu, Fabrizia Bonacina, Guosu Wang, David Coe, Eleanor J Ward, Alessandra Colamatteo, Maryam Jangani, Andrea Baragetti, Giuseppe Matarese, David M Smith, Robert Haas, Claudio Mauro, David C Wraith, Klaus Okkenhaug, Alberico L Catapano, Veronica De Rosa, Giuseppe D Norata, Federica M Marelli-Berg
Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK)...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166577/cell-cycle-related-kinase-regulates-mammalian-eye-development-through-positive-and-negative-regulation-of-the-hedgehog-pathway
#6
Floria I Lupu, Jacob B Burnett, Jonathan T Eggenschwiler
Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the role of CCRK in mouse eye development. Ccrk mutants show dramatic patterning defects, with an expansion of the optic stalk domain into the optic cup, as well as an expansion of the retinal pigment epithelium (RPE) into neural retina (NR) territory. In addition, Ccrk mutants display a shortened optic stalk...
November 19, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29166179/imbalance-between-subpopulations-of-regulatory-t-cells-in-patients-with-acute-exacerbation-of-copd
#7
Xia Yang, Bo Huo, Xiaoning Zhong, Wenyan Su, Wenting Liu, Yumei Li, Zhiyi He, Jing Bai
Human regulatory T cells (Tregs) have been reported to be not significantly different in the peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Recent research has identified some new markers for Tregs and indicated that Tregs are composed of distinct subpopulations. The aim of the study was to describe the changing patterns of circulating Treg subpopulations in patients with acute exacerbation of COPD (AECOPD) and healthy controls, and to explore their potential roles in AECOPD pathogenesis...
November 22, 2017: COPD
https://www.readbyqxmd.com/read/29165988/bioconjugate-strategies-for-the-induction-of-antigen-specific-tolerance-in-autoimmune-diseases
#8
Chunsong Yu, Jingchao Xi, Meng Li, Myunggi An, Haipeng Liu
Antigen-specific immunotherapy (ASI) holds great promise for the treatment of autoimmune diseases. In mice, administration of major histocompatibility complex (MHC) binding synthetic peptides which modulate T cell receptor (TCR) signaling under subimmunogenic conditions induces selective tolerance without suppressing the global immune responses. However, clinical translation has yielded limited success. It has become apparent that the TCR signaling pathway via synthetic peptide antigen alone is inadequate to induce an effective tolerogenic immunity in autoimmune diseases...
November 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29165554/the-effect-of-1-5%C3%A2-t-cardiac-magnetic-resonance-on-human-circulating-leucocytes
#9
William R Critchley, Anna Reid, Julie Morris, Josephine H Naish, John P Stone, Alexandra L Ball, Triin Major, David Clark, Nick Waldron, Christien Fortune, Jakub Lagan, Gavin A Lewis, Mark Ainslie, Erik B Schelbert, Daniel M Davis, Matthias Schmitt, James E Fildes, Christopher A Miller
Aims: Investigators have proposed that cardiovascular magnetic resonance (CMR) should have restrictions similar to those of ionizing imaging techniques. We aimed to investigate the acute effect of 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, and in a large cohort of patients in vivo. Methods and results: In vitro study: peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers, and histone H2AX phosphorylation (γ-H2AX) expression, leucocyte counts, and functional parameters were quantified using flow cytometry under the following conditions: (i) immediately following PBMC isolation, (ii) after standing on the benchside as a temperature and time control, (iii) after a standard CMR scan...
November 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29165232/functional-analysis-of-the-esab-component-of-the-staphylococcus-aureus-type-vii-secretion-system
#10
M Guillermina Casabona, Grant Buchanan, Martin Zoltner, Catriona P Harkins, Matthew T G Holden, Tracy Palmer
Type VII secretion systems (T7SS) are found in many bacteria and secrete proteins involved in virulence and bacterial competition. In Staphylococcus aureus the small ubiquitin-like EsaB protein has been previously implicated as having a regulatory role in the production of the EsxC substrate. Here we show that in the S. aureus RN6390 strain, EsaB does not genetically regulate production of any T7 substrates or components, but is indispensable for secretion activity. Consistent with EsaB being an essential component of the T7SS, loss of either EsaB or EssC are associated with upregulation of a common set of iron acquisition genes...
November 22, 2017: Microbiology
https://www.readbyqxmd.com/read/29165229/na%C3%A3-ve-t-cells-are-activated-by-autologous-hcmv-infected-endothelial-cells-through-nkg2d-and-can-control-hcmv-transmission-in-vitro
#11
Narmadha Subramanian, Zeguang Wu, Frank Reister, Kerstin Laib Sampaio, Giada Frascaroli, Luka Cicin-Sain, Thomas Mertens
Apart from classical antigen-presenting cells (APCs) like dendritic cells and macrophages, there are semiprofessional APCs such as endothelial cells (ECs) and Langerhans' cells. Human cytomegalovirus (HCMV) infects a wide range of cell types including the ECs which are involved in the trafficking and homing of T cells. By investigating the interaction of naïve T cells obtained from HCMV-seronegative umbilical cord blood with autologous HCMV-infected human umbilical vein ECs (HUVECs), we could show that the activation of naïve T cells occurred after 1 day of peripheral blood mononuclear cell (PBMC) exposure to HCMV-infected HUVECs...
November 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29165150/search-for-biomarkers-of-asbestos-exposure-and-asbestos-induced-cancers-in-investigations-of-the-immunological-effects-of-asbestos
#12
REVIEW
Hidenori Matsuzaki, Naoko Kumagai-Takei, Suni Lee, Megumi Maeda, Nagisa Sada, Tamayo Hatayama, Shoko Yamamoto, Miho Ikeda, Kei Yoshitome, Yu Min, Yasumitsu Nishimura, Takemi Otsuki
The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells...
June 9, 2017: Environmental Health and Preventive Medicine
https://www.readbyqxmd.com/read/29165089/a-novel-method-to-synthesize-phosphocreatine-and-phosphocreatine-prodrugs
#13
Maria Arkel, Patrizia Garbati, Annalisa Salis, Gianluca Damonte, Nara Liessi, Enrico Adriano, Umberto Benatti, Maurizio Balestrino, Enrico Millo
Background Adenosine triphosphate (ATP) is the energy currency of the body; it takes part in various and indispensable metabolic processes for the maintenance of cell homeostasis, degrading to its hydrolysis product, adenosine diphosphate (ADP). Efficient ways to restore ATP are therefore necessary in the cells. When the cell lacks energy due to ischemic conditions or high ATP demand, phosphocreatine gives its phosphate group to ADP that converts to ATP, in a reaction catalyzed by the enzyme creatine kinase...
November 20, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/29165070/bortezomib-in-kidney-transplant-current-use-and-perspectives
#14
Erika B Rangel, Lucio R Requião-Moura, Taina V de Sandes-Freitas, Gessika Marcelo-Gomes
BACKGROUND: Despite major advances in transplant medicine, antibody-mediated rejection (AMR) continues to have severe clinical implications and adversely affect graft survival. Therefore, the search for alternative drugs to treat AMR is widely pursued. The first-in-class proteasome inhibitor bortezomib (BZ) is a selective inhibitor of the 26S proteasome, which was initially approved for the treatment of malignant plasma cell disorders. METHODS: This review encompasses how our understanding of inhibiting proteasome pathway created the basis of BZ research and important milestones accomplished in AMR treatment in the transplant setting...
November 20, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29164814/a-thrombin-receptor-derived-imaging-agent-detects-subclinical-arthritis-in-mice
#15
Beth Friedman, Michael A Whitney, Elamprakash N Savariar, Christa Caneda, Paul Steinbach, Qing Xiong, Dina V Hingorani, Jessica Crisp, Stephen R Adams, Michael Kenner, Csilla N Lippert, Quyen T Nguyen, Monica Guma, Roger Y Tsien, Maripat Corr
OBJECTIVE: Functional imaging of synovitis could improve both early detection of rheumatoid arthritis (RA) and long-term outcomes. Motivated by the intersection of inflammation with coagulation protease activation, we examine coagulation protease activities in arthritic mice with a dual fluorescent Ratiometric thrombin-Activatable Cell Penetrating Peptide (RACPPNleTPRSFL ). METHOD: Mice with chronic transgenic K/BxN arthritis, or with arthritis on Day 1 of passive serum transfer induced arthritis (STIA), were imaged in vivo for Cy5 em: Cy7 em ratiometric fluorescence from proteolytic cleavage and activation of RACPPNleTPRSFL ...
November 22, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29164616/protection-against-%C3%AE-amyloid-neurotoxicity-by-a-non-toxic-endogenous-n-terminal-%C3%AE-amyloid-fragment-and-its-active-hexapeptide-core-sequence
#16
Kelly H Forest, Naghum Alfulaij, Komal Arora, Ruth Taketa, Tessi Sherrin, Cedomir Todorovic, James L M Lawrence, Gene T Yoshikawa, Ho-Leung Ng, Victor J Hruby, Robert A Nichols
High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164598/vitamin-c-modulates-glutamate-transport-and-nmda-receptor-function-in-the-retina
#17
Ivan Domith, Renato Socodato, Camila C Portugal, Andressa F Munis, Aline T Duarte-Silva, Roberto Paes-de-Carvalho
Vitamin C (in the reduced form ascorbate or in the oxidized form dehydroascorbate) is implicated in signaling events throughout the central nervous system (CNS). In the retina, a high-affinity transport system for ascorbate has been described and glutamatergic signaling has been reported to control ascorbate release. Here we investigated the modulatory role played by vitamin C upon glutamate uptake and N-methyl-D-aspartate (NMDA) receptor activation in cultured retinal cells or in intact retinal tissue using biochemical and imaging techniques...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164585/expression-and-clinical-significance-of-mir-181a-and-mir-203-in-systemic-lupus-erythematosus-patients
#18
H-S Li, Y Ning, S-B Li, P-Y Shao, S-J Chen, Q Ye, X Heng
OBJECTIVE: MiR-181a plays a critical role in modulating T cell and B cell differentiation, as well as immune response. Its abnormal expression probably participates in the pathogenesis of systemic lupus erythematosus (SLE). MiR-203 is involved in regulating Toll-like receptor and inducing immune tolerance. Abnormal expression or function of miR-203 is related to multiple auto-immune diseases but its role in SLE remains unclear. This study, thus, investigated the serum level of miR-181a and miR-203, to analyze their roles in diagnosing and evaluating SLE...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29164561/study-of-prevalence-and-influencing-factors-of-depression-in-tumor-patients-and-the-therapeutic-effects-of-fluoxetine
#19
J Dai, N Liao, J Shi, J-Q Tao
OBJECTIVE: To observe the depression in patients with malignant tumor and influencing factors of the disease, as well as to investigate the effects of fluoxetine on depressive symptoms in cancer patients and the immune function. PATIENTS AND METHODS: 262 patients with malignant tumors, confirmed by pathological and radiological diagnosis as malignant tumor were randomly divided into 2 groups: the control group with chemotherapy; the treatment group with chemotherapy and 20 mg/d fluoxetine for six weeks...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29163806/interferon-inducible-cxc-chemokines-are-crucial-immune-modulators-and-survival-predictors-in-colorectal-cancer
#20
Larissa Kistner, Dietrich Doll, Anne Holtorf, Ulrich Nitsche, Klaus-Peter Janssen
Tumor-infiltrating T-cells are strongly associated with prognosis in colorectal cancer, but the mechanisms governing intratumoral lymphocyte recruitment are unclear. We investigated the clinical relevance and functional contribution of interferon-regulated CXC-chemokines CXCL9, CXCL10, and CXCL11, described as T-cells attractants. Their expression was significantly elevated in tumors as compared to normal colon in 163 patients with colon cancer, represented an independent positive predictor of post-operative survival, and was highly significantly correlated with the presence of tumor-infiltrating cytotoxic CD8(+) T-cells and CD4(+) TH1-effector cells...
October 27, 2017: Oncotarget
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