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https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#1
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28742076/altered-neurite-morphology-and-cholinergic-function-of-induced-pluripotent-stem-cell-derived-neurons-from-a-patient-with-kleefstra-syndrome-and-autism
#2
J Nagy, J Kobolák, S Berzsenyi, Z Ábrahám, H X Avci, I Bock, Z Bekes, B Hodoscsek, A Chandrasekaran, A Téglási, P Dezső, B Koványi, E T Vörös, L Fodor, T Szél, K Németh, A Balázs, A Dinnyés, B Lendvai, G Lévay, V Román
The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells...
July 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28741923/codelivery-of-trichosanthin-and-albendazole-by-nano-self-assembly-for-overcoming-tumor-multidrug-resistance-and-metastasis
#3
Yisi Tang, Jianming Liang, Aihua Wu, Yingzhi Chen, Pengfei Zhao, Tingting Lin, Meng Zhang, Qin Xu, Jianxin Wang, Yongzhuo Huang
Multidrug resistance (MDR) and metastasis are the major obstacles in cancer chemotherapy. Nanotechnology-based combination therapy is a useful strategy. Recently, the combination of biologics and small drugs has attracted much attention in cancer therapy. Yet, the treatment outcomes are often compromised by the different pharmacokinetics profiles of the co-administered drugs, thus leading to inconsistent drug uptake and suboptimal drug combination at the tumor sites. Nanotechnology-based codelivery offers a promising method to address this problem, which is well demonstrated in the use of small drugs combination...
July 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28741710/il-33-expanded-human-v%C3%AE-9v%C3%AE-2-t-cells-have-anti-lymphoma-effect-in-a-mouse-tumor-model
#4
Caroline Duault, Delphine Betous, Christine Bezombes, Stéphane Roga, Corinne Cayrol, Jean-Philippe Girard, Jean-Jacques Fournié, Mary Poupot
From several years, the anticancer effects of Vγ9 T lymphocytes make these cells good candidates for cancer immunotherapies. However, the proved efficacy of γδ Τ cell-based cancer immunotherapies in some clinical trials was minimized due to the inherent toxicity of IL-2, which is essential for the combination therapy with Phosphoantigen (PAg). Recently, we showed that IL-33, a γ chain receptor-independent cytokine, was able to induce the in vitro proliferation of PAg-activated Vγ9 T cells, which were fully functional expressing IFN-γ and TNF-α and showing in vitro anti-tumor cytotoxicity...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28740578/clinical-performance-of-e2fs-1-3-in-kidney-clear-cell-renal-cancer-evidence-from-bioinformatics-analysis
#5
Bin Liang, Jianying Zhao, Xuan Wang
Extensive research on the E2F transcription factor family has led to numerous insights that E2Fs were involved not only in proliferation and tumorigenesis but also in apoptosis and differentiation. In the present study, we analyzed the differential expression of E2Fs1-3 genes, and also evaluated the impact of E2Fs 1-3 genes expression on clinical outcome from the Cancer Genome Atlas (TCGA) database. The results showed that E2F1, E2F2 and E2F3 expression was increased in KIRC tissues than matched normal tissues (E2F1, P < 0...
May 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28740504/2-4-thiazolidinedione-treatment-improves-the-innate-immune-response-in-dairy-goats-with-induced-subclinical-mastitis
#6
Fernanda Rosa, Johan S Osorio, Erminio Trevisi, Francisco Yanqui-Rivera, Charles T Estill, Massimo Bionaz
Mastitis is a major disease in dairy cows resulting in significant economic losses. In vitro works suggest that ruminants peroxisome proliferator-activated receptor gamma (PPARγ) can aid in improving the response to mastitis and can control milk fat synthesis. The objectives of the present experiment were to test if treatment with the putative PPARγ agonist 2,4-thiazolidinedione (TZD) improves (1) the response to subclinical mastitis and (2) milk fat production. Lactating goats received daily injections of 8 mg/kg BW of TZD or saline for 3 weeks...
2017: PPAR Research
https://www.readbyqxmd.com/read/28740382/dual-linker-gold-nanoparticles-as-adjuvanting-carriers-for-multivalent-display-of-recombinant-influenza-hemagglutinin-trimers-and-flagellin-improve-the-immunological-responses-in-vivo-and-in-vitro
#7
Chao Wang, Wandi Zhu, Bao-Zhong Wang
Vaccination is the most cost-effective means of infectious disease control. Although current influenza vaccines are effective in battling closely matched strains, such vaccines have major limitations such as the requirement to produce new vaccines every season, an egg-dependent production system, long production periods, uncertainty in matching the vaccine to circulating strains, and the inability to react to new influenza pandemics resulting from genetic drift or shift. To overcome the intrinsic limitations of the conventional influenza vaccine, we have designed dual-linker gold nanoparticles (AuNPs) conjugated with both recombinant trimetric A/Aichi/2/68 (H3N2), hemagglutinin (HA) and TLR5 agonist flagellin (FliC) as a novel vaccine approach...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28739829/inherent-oxidative-stress-in-lewis-rat-is-associated-with-resistance-to-toxoplasmosis
#8
William H Witola, Chi Yong Kim, Xuejin Zhang
The course of Toxoplasma gondii infection in rats closely resembles that in humans. However, compared to the Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii infection. Thus, we performed RNA sequencing analysis of the LEW versus BN rat, with or without T. gondii infection, in order to unravel molecular factors directing robust and rapid early T. gondii-killing mechanisms in the LEW rat. We found that, compared to the uninfected BN rat, the uninfected LEW rat has inherently higher transcript levels of cytochrome enzymes [Cyp2d3, Cyp2d5 and Cybrd1 that catalyze generation of reactive oxygen species (ROS)], with concomitant higher levels of ROS...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28739727/mir-141-inhibits-proliferation-and-migration-of-colorectal-cancer-sw480-cells
#9
Zhi H Long, Zhi G Bai, Jian N Song, Zhi Zheng, Jun Li, Jun Zhang, Jun Cai, Hong W Yao, Jin Wang, Ying C Yang, Jie Yin, Zhong T Zhang
BACKGROUND: This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). MATERIALS AND METHODS: SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739688/cyclooxygenase-2-inhibition-enhances-proliferation-of-nkt-cells-derived-from-patients-with-laryngeal-cancer
#10
Janusz Klatka, Ewelina Grywalska, Anna Hymos, Małgorzata Guz, Krzysztof Polberg, Jacek Roliński, Andrzej Stepulak
BACKGROUND/AIM: The aim of this study was to analyze whether inhibition of cyclooxygenase-2 by celecoxib and the subsequent enhancement in the proliferation of natural killer T (NKT) cells could play a role in dendritic cell (DC)-based laryngeal cancer (LC) immunotherapy. PATIENTS AND METHODS: Peripheral blood mononuclear cells were obtained from 48 male patients diagnosed with LC and 30 control patients without cancer disease. Neoplastic cell lysate preparations were made from cancer tissues obtained after surgery and used for in vitro DCs generation...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739115/a-recombinant-protein-of-salmonella-typhi-induces-humoral-and-cell-mediated-immune-responses-including-memory-responses
#11
Sayan Das, Rimi Chowdhury, Shubhamoy Ghosh, Santasabuj Das
Gram negative enteric bacteria, Salmonella enterica serovar Typhi (S. Typhi), the etiological agent of typhoid fever is a major public health problem in developing countries. While a permanent solution to the problem would require improved sanitation, food and water hygiene, controlling the infection by vaccination is urgently required due to the emergence of multidrug resistant strains in multiple countries. The currently licensed vaccines are moderately efficacious with limited applicability, and no recommended vaccines exist for younger children...
July 21, 2017: Vaccine
https://www.readbyqxmd.com/read/28738424/use-of-high-throughput-in-vitro-toxicity-screening-data-in-cancer-hazard-evaluations-by-iarc-monograph-working-groups
#12
Weihsueh A Chiu, Kathryn Z Guyton, Matthew T Martin, David M Reif, Ivan Rusyn
Evidence regarding carcinogenic mechanisms serves a critical role in International Agency for Research on Cancer (IARC) Monograph evaluations. Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Monograph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112 -113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream...
July 24, 2017: ALTEX
https://www.readbyqxmd.com/read/28738416/conditionally-immortal-slc4a11-mouse-corneal-endothelial-cell-line-recapitulates-disrupted-glutaminolysis-seen-in-slc4a11-mouse-model
#13
Wenlin Zhang, Diego G Ogando, Edward T Kim, Moon-Jung Choi, Hongde Li, Jason M Tenessen, Joseph A Bonanno
Purpose: To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11-/- mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy. Methods: We intercrossed H-2Kb-tsA58 mice (Immortomouse) expressing an IFN-γ dependent and temperature-sensitive mutant of the SV40 large T antigen (tsTAg) with Slc4a11+/+ and Slc4a11-/- C57BL/6 mice...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28738084/the-dkk3-gene-encodes-a-vital-intracellular-regulator-of-cell-proliferation
#14
Jack L Leonard, Deborah M Leonard, Scot A Wolfe, Jilin Liu, Jaime Rivera, Michelle Yang, Ryan T Leonard, Jacob P S Johnson, Prashant Kumar, Kate L Liebmann, Amanda A Tutto, Zhongming Mou, Karl J Simin
Members of the Dickkopf (Dkk) family of Wnt antagonists interrupt Wnt-induced receptor assembly and participate in axial patterning and cell fate determination. One family member, DKK3, does not block Wnt receptor activation. Loss of Dkk3 expression in cancer is associated with hyperproliferation and dysregulated ß-catenin signaling, and ectopic expression of Dkk3 halts cancer growth. The molecular events mediating the DKK3-dependent arrest of ß-catenin-driven cell proliferation in cancer cells are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28737510/lymphocytes-transiently-expressing-virus-specific-t-cell-receptors-reduce-hepatitis-b-virus-infection
#15
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lütgehetmann, Antonio Bertoletti, Maura Dandri
Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28736524/immune-and-metabolic-regulation-mechanism-of-dangguiliuhuang-decoction-against-insulin-resistance-and-hepatic-steatosis
#16
Hui Cao, Lingling Tuo, Yali Tuo, Ziyun Xia, Rong Fu, Yang Liu, Yihong Quan, Jue Liu, Zhihong Yu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28736303/the-good-and-the-bad-collagens-of-fibrosis-their-role-in-signaling-and-organ-function
#17
M A Karsdal, S H Nielsen, D J Leeming, L L Langholm, M J Nielsen, T Manon-Jensen, A Siebuhr, N S Gudmann, S Rønnow, J M Sand, S J Daniels, J H Mortensen, D Schuppan
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or toxic liver injury, with reticular, chicken wire and bridging fibrosis. Importantly, the overall composition of the ECM, especially the relative amounts of the many types of collagens, which represent the most abundant ECM molecules and which centrally modulate cellular functions and physiological processes, changes dramatically during fibrosis progression...
July 20, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28735813/atypical-memory-b-cells-in-human-chronic-infectious-diseases-an-interim-report
#18
Silvia Portugal, Nyamekye Obeng-Adjei, Susan Moir, Peter D Crompton, Susan K Pierce
Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28735672/cutaneous-angiolymphoid-hyperplasia-in-a-dog
#19
M Michishita, Y Katori, H Sasaki, R D Obara, R Furumoto, M Kato, R Nakahira, H Yoshimura, S Soeta, T Ishiwata, K Takahashi
A 5-year-old male miniature dachshund was presented with a dermal nodule on the left forelimb that increased to 5 mm in diameter over a 2-month period. Grossly, the nodule was firm, and both the external and cut surfaces were homogeneously pale pink in colour. Microscopically, the nodule was comprised of mainly plump endothelial cells and inflammatory cells; among the latter, lymphocytes were predominant, with few scattered plasma cells, mast cells and macrophages. Lymphoid follicles with germinal centres were often observed...
July 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28735665/prevalence-of-foxp3-cells-does-not-correlate-with-ki67-expression-in-canine-diffuse-large-b-cell-lymphoma
#20
C F Muir, S L Priestnall, A Hibbert, C Brown, O A Garden, T Scase
Diffuse large B-cell lymphoma (DLBCL) is the most common type of canine lymphoma and survival times are currently <1 year. Manipulation of the tumour microenvironment, of which the regulatory T cell (Treg) is a principal player, represents a potentially exciting way to curb the rapid proliferation of neoplastic cells. Tregs, characterized by the stable expression of the transcription factor FoxP3, suppress innate and adaptive arms of the immune response and represent a potential therapeutic target within neoplastic lymph nodes...
July 2017: Journal of Comparative Pathology
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