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https://www.readbyqxmd.com/read/28646426/eftrenonacog-alfa-a-review-in-haemophilia-b
#1
Sheridan M Hoy
Eftrenonacog alfa (Alprolix™) is a recombinant fusion protein comprising human factor IX (FIX) covalently linked to the constant region (Fc) domain of human IgG1 (i.e. rFIXFc). The presence of the Fc domain extends the terminal half-life (t½) of rFIXFc, permitting prolonged treatment intervals. rFIXFc is available for intravenous use for the prophylaxis and treatment of bleeding in patients with haemophilia B. In two multinational, phase III studies in previously treated children, adolescents and adults with severe haemophilia B, rFIXFc prophylaxis resulted in low median annualized bleeding rates (ABRs), and was associated with reductions in median weekly factor consumption and dosing frequency compared with pre-study FIX regimens...
June 23, 2017: Drugs
https://www.readbyqxmd.com/read/28641278/astragaloside-iv-alleviates-heat-induced-inflammation-by-inhibiting-endoplasmic-reticulum-stress-and-autophagy
#2
Zhiwei Dong, Jian Zhou, Ying Zhang, Yajie Chen, Zichen Yang, Guangtao Huang, Yu Chen, Zhiqiang Yuan, Yizhi Peng, Tongtong Cao
BACKGROUND: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#3
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28637688/fus-ddit3-fusion-protein-driven-igf-ir-signaling-is-a-therapeutic-target-in-myxoid-liposarcoma
#4
Marcel Trautmann, Jasmin Menzel, Christian Bertling, Magdalene Cyra, Ilka Isfort, Konrad Steinestel, Sandra Elges, Inga Grünewald, Bianca Altvater, Claudia Rossig, Stefan Fröhling, Susanne Hafner, Thomas Simmet, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann
Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS-DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS‑DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634358/hiv-1-gp41-targeting-fusion-inhibitory-peptides-enhance-the-gp120-targeting-protein-mediated-inactivation-of-hiv-1-virions
#5
Qianqian Qi, Qian Wang, Weizao Chen, Lanying Du, Dimiter S Dimitrov, Lu Lu, Shibo Jiang
Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT)...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28633670/preclinical-anti-myeloma-activity-of-edo-s101-a-new-bendamustine-derived-molecule-with-added-hdaci-activity-through-potent-dna-damage-induction-and-impairment-of-dna-repair
#6
Ana-Alicia López-Iglesias, Ana B Herrero, Marta Chesi, Laura San-Segundo, Lorena González-Méndez, Susana Hernández-García, Irena Misiewicz-Krzeminska, Dalia Quwaider, Montserrat Martín-Sánchez, Daniel Primo, Teresa Paíno, P Leif Bergsagel, Thomas Mehrling, Marcos González-Díaz, Jesús F San-Miguel, María-Victoria Mateos, Norma C Gutiérrez, Mercedes Garayoa, Enrique M Ocio
BACKGROUND: Despite recent advances in the treatment of multiple myeloma (MM), the prognosis of most patients remains poor, and resistance to traditional and new drugs frequently occurs. EDO-S101 is a novel therapeutic agent conceived as the fusion of a histone deacetylase inhibitor radical to bendamustine, with the aim of potentiating its alkylating activity. METHODS: The efficacy of EDO-S101 was evaluated in vitro, ex vivo and in vivo, alone, and in combination with standard anti-myeloma agents...
June 20, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28629465/natural-igm-antibodies-that-bind-neoepitopes-exposed-as-a-result-of-spinal-cord-injury-drive-secondary-injury-by-activating-complement
#7
Aarti Narang, Fei Qiao, Carl Atkinson, Hong Zhu, Xiaofeng Yang, Liudmila Kulik, V Michael Holers, Stephen Tomlinson
BACKGROUND: Natural IgM antibodies (Abs) function as innate immune sensors of injury via recognition of neoepitopes expressed on damaged cells, although how this recognition systems function following spinal cord injury (SCI) exposes various neoepitopes and their precise nature remains largely unknown. Here, we investigated the role of two natural IgM monoclonal Abs (mAbs), B4 and C2, that recognize post-ischemic neoepitopes following ischemia and reperfusion in other tissues. METHODS: Identification of post-SCI expressed neoepitopes was examined using previously characterized monoclonal Abs (B4 and C2 mAbs)...
June 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28626744/central-beneficial-effects-of-trimetazidine-on-psychomotor-performance-in-normal-healthy-volunteers
#8
Hayder M Al-Kuraishy, Ali I Al-Gareeb
BACKGROUND: Trimetazidine is a fatty oxidation inhibitor, leading to shifting of energy substrate from fatty acid oxidation toward glucose oxidation that leads to the reduction of oxygen requirement. The aims of the present study were to elucidate the effects of trimetazidine on psychomotor performance and vigilance on normal healthy volunteers. MATERIALS AND METHODS: A total of 234 subjects (age 22-25 years) were recruited in this study. The volunteers were randomizing into two groups with 117 volunteers in each group...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28624412/mild-hypothermia-protects-hippocampal-neurons-against-oxygen-glucose-deprivation-reperfusion-induced-injury-by-improving-lysosomal-function-and-autophagic-flux
#9
Tianen Zhou, Lian Liang, Yanran Liang, Tao Yu, Chaotao Zeng, Longyuan Jiang
Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered...
June 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28624214/further-characterization-of-the-bifunctional-hiv-entry-inhibitor-scd4-fit45
#10
Alexander Falkenhagen, Sadhna Joshi
HIV entry into target cells is a highly sequential and time-sensitive process. In recent years, potent HIV Env-targeting antibodies, such as VRC01, have been identified. However, antibodies bind only to a single epitope, and mutations that confer resistance to antibody-mediated inhibition of HIV entry have been detected. In contrast, HIV cannot escape from binding to soluble CD4 (sCD4) without a fitness disadvantage. sCD4 has the unique ability to induce conformational changes within the HIV envelope glycoproteins (Env) that allow fusion inhibitors to bind...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28615362/drugging-the-catalytically-inactive-state-of-ret-kinase-in-ret-rearranged-tumors
#11
Dennis Plenker, Maximilian Riedel, Johannes Brägelmann, Marcel A Dammert, Rakhee Chauhan, Phillip P Knowles, Carina Lorenz, Marina Keul, Mike Bührmann, Oliver Pagel, Verena Tischler, Andreas H Scheel, Daniel Schütte, Yanrui Song, Justina Stark, Florian Mrugalla, Yannic Alber, André Richters, Julian Engel, Frauke Leenders, Johannes M Heuckmann, Jürgen Wolf, Joachim Diebold, Georg Pall, Martin Peifer, Maarten Aerts, Kris Gevaert, René P Zahedi, Reinhard Buettner, Kevan M Shokat, Neil Q McDonald, Stefan M Kast, Oliver Gautschi, Roman K Thomas, Martin L Sos
Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. We provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors, such as AD80 or ponatinib, that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28609758/a-selection-guide-for-the-new-generation-6-dye-dna-profiling-systems
#12
Sze-Wah Lin, Christina Li, Stephen C Y Ip
The Federal Bureau of Investigation (FBI) has recently expanded the CODIS core loci from the existing 13 to 20 as a new guideline, and laboratories from the US are required to comply with the new regulation before uploading or conducting identity search in the national database. The expanded CODIS format, which shares all the core loci commonly used in the European countries and the US, not only increases international compatibility, but also reduces the number of adventitious matches, and hence facilitates international law enforcement and counterterrorism endeavours...
June 3, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28609659/development-of-peptidomimetic-inhibitors-of-the-erg-gene-fusion-product-in-prostate-cancer
#13
Xiaoju Wang, Yuanyuan Qiao, Irfan A Asangani, Bushra Ateeq, Anton Poliakov, Marcin Cieślik, Sethuramasundaram Pitchiaya, Balabhadrapatruni V S K Chakravarthi, Xuhong Cao, Xiaojun Jing, Cynthia X Wang, Ingrid J Apel, Rui Wang, Jean Ching-Yi Tien, Kristin M Juckette, Wei Yan, Hui Jiang, Shaomeng Wang, Sooryanarayana Varambally, Arul M Chinnaiyan
No abstract text is available yet for this article.
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28608166/abatacept-a-review-in-rheumatoid-arthritis
#14
Hannah A Blair, Emma D Deeks
The biological DMARD (bDMARD) abatacept (Orencia(®)), a recombinant fusion protein, selectively modulates a co-stimulatory signal necessary for T-cell activation. In the EU, abatacept is approved for use in patients with highly active and progressive rheumatoid arthritis (RA) not previously treated with methotrexate. Abatacept is also approved for the treatment of moderate to severe active RA in patients with an inadequate response to previous therapy with at least one conventional DMARD (cDMARD), including methotrexate or a TNF inhibitor...
June 12, 2017: Drugs
https://www.readbyqxmd.com/read/28607007/synergistic-activity-with-notch-inhibition-and-androgen-ablation-in-erg-positive-prostate-cancer-cells
#15
Ahmed A Mohamed, Shyh-Han Tan, Charles P Xavier, Shilpa Katta, Wei Huang, Lakshmi Ravindranath, Muhammad Jamal, Hua Li, Meera Srivastava, Eri S Srivatsan, Taduru L Sreenath, David G McLeod, Alagarsamy Srinivasan, Gyorgy Petrovics, Albert Dobi, Shiv Srivastava
The oncogenic activation of the ETS related gene (ERG) due to gene fusions is present in over half of prostate cancer (CaP) in Western countries. Due to its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for CaP. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with ERG expression status was identified; confirming that NOTCH factors are direct transcriptional targets of ERG...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28606804/a-human-challenge-model-for-respiratory-syncytial-virus-kinetics-the-pharmacological-effect-of-a-novel-fusion-inhibitor-and-the-modeling-of-symptoms-scores
#16
Julia Korell, Bruce Green, John DeVincenzo, Dymphy Huntjens
Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections, and is a major cause of hospital admissions and death in young children. Limited treatments currently exist that can prevent or minimise exacerbation of the disease. The aims of this work were: 1) to develop a population pharmacodynamic model to describe RSV kinetics (RSVK) in nasal lavage, 2) evaluate the impact of an investigational fusion inhibitor, JNJ-53718678, on RSVK, and 3) determine the relationship between RSVK and symptoms scores...
June 9, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28602833/a-novel-il-1ra-pep-fusion-protein-with-enhanced-brain-penetration-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibition-of-oxidative-stress-and-neuroinflammation
#17
Dong-Dong Zhang, Min-Ji Zou, Ya-Tao Zhang, Wen-Liang Fu, Tao Xu, Jia-Xi Wang, Wen-Rong Xia, Zhi-Guang Huang, Xiang-Dong Gan, Xiao-Ming Zhu, Dong-Gang Xu
Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP)...
June 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28596237/the-snare-protein-syntaxin1a-plays-an-essential-role-in-biphasic-exocytosis-of-the-incretin-hormone-glucagon-like-peptide-1
#18
Sarah E Wheeler, Holly M Stacey, Yasaman Nahaei, Stephen J Hale, Alexandre B Hardy, Frank Reimann, Fiona M Gribble, Pierre Larraufie, Herbert Y Gaisano, Patricia L Brubaker
Exocytosis of the hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is essential for the incretin effect after nutrient ingestion, and is critical for the actions of dipeptidylpeptidase IV inhibitors that enhance GLP-1 levels in patients with type 2 diabetes. 2-Photon microscopy revealed that exocytosis of GLP-1 is biphasic, with a 1(st) peak at 1-6min and a 2(nd) peak at 7-12min after stimulation with forskolin. Approximately 75% of the exocytotic events were represented by compound granule fusion, and the remainder were accounted for by full fusion of single granules, under basal and stimulated conditions...
June 8, 2017: Diabetes
https://www.readbyqxmd.com/read/28594408/autophagy-blockade-and-lysosomal-membrane-permeabilization-contribute-to-lead-induced-nephrotoxicity-in-primary-rat-proximal-tubular-cells
#19
Xiang-Bin Song, Gang Liu, Fei Liu, Zhen-Gui Yan, Zhen-Yong Wang, Zong-Ping Liu, Lin Wang
Lead (Pb) is a known nephrotoxicant that causes damage to proximal tubular cells. Autophagy has an important protective role in various renal injuries, but the role of autophagy in Pb-elicited nephrotoxicity remains largely unknown. In this study, Pb promoted the accumulation of autophagosomes in primary rat proximal tubular (rPT) cells, and subsequent findings revealed that this autophagosome accumulation was caused by the inhibition of autophagic flux. Moreover, Pb exposure did not affect the autophagosome-lysosome fusion in rPT cells...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28592067/-combination-of-pp242-and-dasatinib-suppresses-the-progression-of-acute-myeloid-leukemia-in-a-mouse-model
#20
Y H Qu, H T Liu, F C He
Objective: To establish the acute myeloid leukemia (AML) mouse model, and to preliminarily investigate the efficiency of dasatinib, a tryosine kinase inhibitor, and PP242, an inhibitor of PI3K/Akt/mTOR signaling pathway in the development of AML. Methods: The lineage(-) (Lin(-)) cells of C57BL/6J were transduced with retrovirus carrying MSCV-MLL-AF9-IRES-GFP fusion gene. The transduced cells were transplanted into lethally irradiated recipient mice to induce AML, and then the AML mouse model were established...
May 30, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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