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https://www.readbyqxmd.com/read/28724261/development-of-a-sandwich-enzyme-linked-immunosorbent-assay-for-dtmp-gh-fusion-protein-by-rational-immunogen-selection
#1
Song Wang, Mingqiang Shen, Shilei Chen, Cheng Wang, Fang Chen, Mo Chen, Gaomei Zhao, Xinze Ran, Tianmin Cheng, Yongping Su, Yang Xu, Junping Wang
dTMP-GH is a chimeric protein containing a tandem dimer of thrombopoietin mimetic peptide (dTMP) fused to human growth hormone (hGH) prepared previously by our team. It shows significant bioactivity in promoting thrombocytopoiesis, but detection of intact dTMP-GH in plasma is still a challenge due to the presence of endogenous hGH. In this study, a rabbit polyclonal antibody with high affinity to dTMP was obtained with a BSA-conjugated immunogen composed of 20 amino acids sequence spanning two TMP and the linker...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28724258/lldt-288-a-novel-triptolide-analogue-exhibits-potent-antitumor-activity-in-vitro-and-in-vivo
#2
Hongtao Xu, Xiaoting Fan, Guanjun Zhang, Xiaoyu Liu, Zhihong Li, Yuanchao Li, Biao Jiang
(14S)-14β-(1-(2-morpholinoethyl)-1H-indazol-5-ylamino)mthylepitriptolide (LLDT-288) was a novel C14β-heterocycle aminomethyl substituent triptolide analogue, which showed comparable cytotoxicity to triptolide. Here we demonstrated that LLDT-288 displayed broad-spectrum, potent antitumor activity, effectively against drug-resistance cancer cells, and induced apoptosis in vitro, but exerted low toxicity. Moreover, it exhibited a remarkable microsomal stability, and showed no inhibitory effects on different cytochrome P450 isoforms...
July 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28724203/huprine-x-attenuates-the-neurotoxicity-induced-by-kainic-acid-especially-brain-inflammation
#3
J Relat, B Pérez, P Camps, D Muñoz-Torrero, A Badia, M V Clos
Huprine X (HX) is a synthetic anticholinesterasic compound that exerts a potent inhibitory action on acetylcholinesterase (AChE) activity, an agonist effect on cholinergic receptors, neuroprotective activity in different neurotoxicity models in vivo and in vitro and cognition enhancing effects in non-transgenic (C57BL/6) and transgenic (3xTg-AD, APPswe) mice. In the present study, we assessed the ability of HX (0.8 mg/kg, 21 days) to prevent the damage induced by kainic acid (KA; 28 mg/kg) regarding apoptosis, glia reactivity and neurogenesis in mouse brain...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28723961/dysfunctional-gpr40-ffar1-signaling-exacerbates-pain-behavior-in-mice
#4
Kazuo Nakamoto, Fuka Aizawa, Kei Miyagi, Takuya Yamashita, Mitsumasa Mankura, Yutaka Koyama, Fumiyo Kasuya, Akira Hirasawa, Takashi Kurihara, Atsuro Miyata, Shogo Tokuyama
We previously showed that activation of G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) signaling modulates descending inhibition of pain. In this study, we investigated the involvement of fatty acid-GPR40/FFAR1 signaling in the transition from acute to chronic pain. We used GPR40/FFAR1-knockout (GPR40KO) mice and wild-type (WT) mice. A plantar incision was performed, and mechanical allodynia and thermal hyperalgesia were evaluated with a von Frey filament test and plantar test, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28723951/cd8-t-cells-provide-immune-protection-against-murine-disseminated-endotheliotropic-orientia-tsutsugamushi-infection
#5
Guang Xu, Nicole L Mendell, Yuejin Liang, Thomas R Shelite, Yenny Goez-Rivillas, Lynn Soong, Donald H Bouyer, David H Walker
Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i...
July 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28723950/high-affinity-anti-tim-3-and-anti-kir-monoclonal-antibodies-cloned-from-healthy-human-individuals
#6
Stefan Ryser, Angeles Estellés, Edgar Tenorio, Lawrence M Kauvar, Mikhail L Gishizky
We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs) from peripheral blood mononuclear cells (PBMC) of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK)...
2017: PloS One
https://www.readbyqxmd.com/read/28723938/gender-differences-in-cerebral-metabolism-for-color-processing-in-mice-a-pet-mri-study
#7
Philip C Njemanze, Mathias Kranz, Mario Amend, Jens Hauser, Hans Wehrl, Peter Brust
INTRODUCTION: Color processing is a central component of mammalian vision. Gender-related differences of color processing revealed by non-invasive functional transcranial Doppler ultrasound suggested right hemisphere pattern for blue/yellow chromatic opponency by men, and a left hemisphere pattern by women. MATERIALS AND METHODS: The present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) with statistical parametric mapping (SPM) during light stimulation with blue and yellow filters compared to darkness condition...
2017: PloS One
https://www.readbyqxmd.com/read/28723918/heterogeneity-of-p53-dependent-genomic-responses-following-ethanol-exposure-in-a-developmental-mouse-model-of-fetal-alcohol-spectrum-disorder
#8
Maria Camargo Moreno, Sandra M Mooney, Frank A Middleton
Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#9
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723889/distinct-timescales-of-population-coding-across-cortex
#10
Caroline A Runyan, Eugenio Piasini, Stefano Panzeri, Christopher D Harvey
The cortex represents information across widely varying timescales. For instance, sensory cortex encodes stimuli that fluctuate over few tens of milliseconds, whereas in association cortex behavioural choices can require the maintenance of information over seconds. However, it remains poorly understood whether diverse timescales result mostly from features intrinsic to individual neurons or from neuronal population activity. This question remains unanswered, because the timescales of coding in populations of neurons have not been studied extensively, and population codes have not been compared systematically across cortical regions...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723727/longitudinal-analysis-of-motor-symptoms-and-histopathology-in-woozy-mice-a-model-of-cerebellar-ataxia
#11
Takemitsu Hayashi, Tomoya Onozato, Isao Wanajo, Morimichi Hayashi, Hiroo Takeda, Yoshikazu Fujimori
Woozy (wz) mice develop ataxia and carry a mutation in the Sil1 gene. Homozygous wz mice have been characterized histopathologically, but no details of their motor function have been reported. In the present study, to comprehensively understand the relationship between symptomatic progression and pathological feature, we evaluated motor function and neurodegeneration with age from presymptomatic to terminal stages. We evaluated the motor function of homozygous and heterozygous wz mice aged from 5 to 71 weeks...
July 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/28723693/upregulation-of-microrna-876-induces-endothelial-cell-apoptosis-by-suppressing-bcl-xl-in-development-of-atherosclerosis
#12
Kaicheng Xu, Peng Liu, Yue Zhao
BACKGROUND/AIMS: The injury and apoptotic cell death of endothelial cells hallmark the development of atherosclerosis (AS), characterized by dysregulation of lipid homeostasis, immune responses, and formation of coronary plaques. However, the mechanisms underlying the initiation of endothelial cell apoptosis remain ill-defined. Recent evidence suggests a role of microRNAs in the processes of AS-associated endothelial cell apoptosis. Thus, we studied this question in the current study...
July 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28723688/trigonelline-inhibits-inflammation-and-protects-%C3%AE-cells-to-prevent-fetal-growth-restriction-during-pregnancy-in-a-mouse-model-of-diabetes
#13
Ji-Yin Zhou, Xiao-Huang Du, Zuo Zhang, Gui-Sheng Qian
BACKGROUND: As an active component from traditional Chinese medicine, trigonelline has a protective effect on diabetes. This study evaluated the protective effects of trigonelline on diabetic mice during pregnancy. METHODS: Diabetes was induced in female mice by intraperitoneal injection for continuous 5-day of 40 mg/kg/day streptozotocin. Female mice were divided into 4 groups after they were allowed to mate with normal male mice: nondiabetic, nondiabetic treated with trigonelline (70 mg/kg) for 18 days, diabetic, and diabetic treated with trigonelline (70 mg/kg)...
July 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28723681/inhibition-of-necroptosis-attenuates-kidney-inflammation-and-interstitial-fibrosis-induced-by-unilateral-ureteral-obstruction
#14
Xia Xiao, Chunyang Du, Zhe Yan, Yonghong Shi, Huijun Duan, Yunzhuo Ren
BACKGROUND: Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury...
July 20, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28723671/qishenyiqi-pill-attenuates-atherosclerosis-by-promoting-regulatory-t-cells-inhibiting-t-helper-17-cells-and-accelerating-cholesterol-excretion
#15
Li Peng, Chong-Shan Lv, Yun Zhao, Shao-Dong Chen, Yang Huang, Da-Wei Lu, Shu-Qiong Huang, Zong-Bao Yang, Lin-Chao Qian, Lei Wen
OBJECTIVE: The aim of this study was to explore potential immunoregulatory mechanisms underlying the suppressive effect on atherosclerosis of QiShenYiQi pill (QSYQ). METHODS AND RESULTS: Male ApoE-/- mice were maintained on a Western-type diet and QSYQ treatment for eight weeks. Determination of atherosclerosis demonstrated that QSYQ attenuated plaque formation and decreased the level of blood low-density lipoproteins-cholesterol. QSYQ treatment did not affect body weight but reduced the ratio of liver weight and body weight...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#16
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723662/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#17
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723652/a-patient-derived-orthotopic-xenograft-pdox-mouse-model-of-a-cisplatinum-resistant-osteosarcoma-lung-metastasis-that-was-sensitive-to-temozolomide-and-trabectedin-implications-for-precision-oncology
#18
Kentaro Igarashi, Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Yong Zhang, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara A Russell, Arun S Singh, Hiroyuki Tsuchiya, Irmina Elliott, Fritz C Eilber, Robert M Hoffman
In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723644/fir-haplodeficiency-promotes-splicing-to-pyruvate-kinase-m2-in-mice-thymic-lymphoma-tissues-revealed-by-six-plex-tandem-mass-tag-quantitative-proteomic-analysis
#19
Asako Kimura, Kouichi Kitamura, Guzhanuer Ailiken, Mamoru Satoh, Toshinari Minamoto, Nobuko Tanaka, Fumio Nomura, Kazuyuki Matsushita
The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723642/suppression-of-microrna-384-enhances-autophagy-of-airway-smooth-muscle-cells-in-asthmatic-mouse
#20
Zhe Cheng, Xi Wang, Lingling Dai, Liuqun Jia, Xiaogang Jing, Ying Liu, Huan Wang, Pengfei Li, Lin An, Meng Liu
Injury to airway smooth muscle (ASM) cells hallmarks the pathological progression of asthma, a chronic inflammatory airway disease. MicroRNAs (miRNAs) play essential roles in the development of asthma as well as airway remodeling. Here we studied the involvement of miRNAs in the regulation of autophagic survival of ASM cells and airway disorder. We analyzed autophagy-associated factors LC3 and Beclin-1 by RT-qPCR and protein blotting in purified airway smooth muscle cells from ovalbumin (OVA)-induced asthmatic mice...
July 1, 2017: Oncotarget
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