keyword
MENU ▼
Read by QxMD icon Read
search

pk

keyword
https://www.readbyqxmd.com/read/28918591/platform-model-describing-pharmacokinetic-properties-of-vc-mmae-antibody-drug-conjugates
#1
Matts Kågedal, Leonid Gibiansky, Jian Xu, Xin Wang, Divya Samineni, Shang-Chiung Chen, Dan Lu, Priya Agarwal, Bei Wang, Ola Saad, Neelima Koppada, Bernard M Fine, Jin Y Jin, Sandhya Girish, Chunze Li
Antibody-drug conjugates (ADCs) developed using the valine-citrulline-MMAE (vc-MMAE) platform, consist of a monoclonal antibody (mAb) covalently bound with a potent anti-mitotic toxin (MMAE) through a protease-labile vc linker. Recently, clinical data for a variety of vc-MMAE ADCs has become available. The goal of this analysis was to develop a platform model that simultaneously described antibody-conjugated MMAE (acMMAE) pharmacokinetic (PK) data from eight vc-MMAE ADCs, against different targets and tumor indications; and to assess differences and similarities of model parameters and model predictions, between different compounds...
September 16, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28918589/isolated-pancreas-rejections-do-not-have-an-adverse-impact-on-kidney-graft-survival-whereas-kidney-rejections-are-associated-with-adverse-pancreas-graft-survival%C3%A2-in-simultaneous-pancreas-kidney-transplantation
#2
Irfan Moinuddin, Muhammad Sohail Yaqub, Tim Taber, John Powelson, Jonathan Fridell, Asif Sharfuddin
BACKGROUND AND OBJECTIVES: Diabetic Kidney Disease is associated with excessive mortality and morbidity. Simultaneous pancreas kidney transplantation (SPK) significantly improves quality of life and increases life expectancy of uremic diabetic patients. It is not known whether pancreas and kidney rejections in these transplant patients is concordant or discordant. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We analyzed clinical data on all SPK transplants performed between 2003 and 2014 at Indiana University to assess the impact of isolated or combined pancreas and kidney rejections on patient and allograft outcomes...
September 16, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28918554/genome-wide-identification-classification-evolutionary-analysis-and-gene-expression-patterns-of-the-protein-kinase-gene-family-in-wheat-and-aegilops-tauschii
#3
Jun Yan, Peisen Su, Zhaoran Wei, Eviatar Nevo, Lingrang Kong
In this study we systematically identified and classified PKs in Triticum aestivum, Triticum urartu and Aegilops tauschii. Domain distribution and exon-intron structure analyses of PKs were performed, and we found conserved exon-intron structures within the exon phases in the kinase domain. Collinearity events were determined, and we identified various T. aestivum PKs from polyploidizations and tandem duplication events. Global expression pattern analysis of T. aestivum PKs revealed that some PKs might participate in the signaling pathways of stress response and developmental processes...
September 16, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28918505/purification-and-characterization-of-skeletal-muscle-pyruvate-kinase-from-the-hibernating-ground-squirrel-urocitellus-richardsonii-potential-regulation-by-posttranslational-modification-during-torpor
#4
Ryan A V Bell, Kenneth B Storey
Ground squirrel torpor during winter hibernation is characterized by numerous physiological and biochemical changes, including alterations to fuel metabolism. During torpor, many tissues switch from carbohydrate to lipid catabolism, often by regulating key enzymes within glycolytic and lipolytic pathways. This study investigates the potential regulation of pyruvate kinase (PK), a key member of the glycolytic pathway, within the skeletal muscle of hibernating ground squirrels. PK was purified from the skeletal muscle of control and torpid Richardson's ground squirrels, and PK kinetics, structural stability, and posttranslational modifications were subsequently assessed...
September 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28918129/where-do-substrates-of-diacylglycerol-kinases-come-from-diacylglycerol-kinases-utilize-diacylglycerol-species-supplied-from-phosphatidylinositol-turnover-independent-pathways
#5
REVIEW
Fumio Sakane, Satoru Mizuno, Daisuke Takahashi, Hiromichi Sakai
Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). Mammalian DGK comprises ten isozymes (α-κ) and regulates a wide variety of physiological and pathological events, such as cancer, type II diabetes, neuronal disorders and immune responses. DG and PA consist of various molecular species that have different acyl chains at the sn-1 and sn-2 positions, and consequently, mammalian cells contain at least 50 structurally distinct DG/PA species. Because DGK is one of the components of phosphatidylinositol (PI) turnover, the generally accepted dogma is that all DGK isozymes utilize 18:0/20:4-DG derived from PI turnover...
September 9, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28918124/polyphenols-reported-to-shift-apap-induced-changes-in-mapk-signaling-and-toxicity-outcomes
#6
REVIEW
Ngoc Uy Nguyen, Brendan David Stamper
Due to its widespread availability, acetaminophen (APAP) is the leading cause for drug-induced liver injury in many countries including United States and United Kingdom. When used as recommended, APAP is relatively safe. However, in overdose cases, increased metabolism of APAP to N-acetyl-para-benzoquinoneimine (NAPQI), a reactive metabolite, leads to glutathione (GSH) depletion, oxidative stress, and cellular injury. Throughout this process, a variety of factors play important roles in propagating toxicity, including c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family...
September 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28918029/activation-of-ampk-attenuated-cardiac-fibrosis-by-inhibiting-cdk2-via-p21-p27-and-mir-29-family-pathways-in-rats
#7
Hanping Qi, Yan Liu, Shuzhi Li, Yunping Chen, Lei Li, Yonggang Cao, Mingyao E, Pilong Shi, Chao Song, Baiyan Li, Hongli Sun
Cardiac fibrosis is pathological damage associated with nearly all forms of heart disease. AMP-activated protein kinase (AMPK) is an evolutionary conserved energy-sensing enzyme. Emerging evidences indicate that AMPK plays an important role in cardiac fibrosis and cell proliferation. However, less is known about the detailed mechanism of AMPK activation on cardiac fibrosis. In this study, we found the AMPK activation improved the impaired cardiac function of cardiac fibrosis rats and decreased interstitial fibrosis...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917973/inhibitory-effects-of-dianthi-herba-ethanolic-extract-on-inflammatory-and-nociceptive-responses-in-murine-macrophages-and-mouse-models-of-abdominal-writhing-and-ear-edema
#8
You-Chang Oh, Yun Hee Jeong, Won-Kyung Cho, Youn-Hwan Hwang, Jin Yeul Ma
ETHNOPHARMACOLOGICAL RELEVANCE: Dianthi Herba is a traditional herbal medicine used to treat inflammatory-related diseases including acute pyelonephritis, cystitis, laryngopharyngitis, and urethritis. AIM OF THE STUDY: We investigated the effects of Dianthi Herba ethanolic extract (DH) on lipopolysaccharide (LPS)-mediated inflammatory responses in murine macrophages as well as nociceptive and edema mouse models. MATERIALS AND METHODS: The biological effects of DH on inflammatory cytokine, mediator, and related protein production were assessed using enzyme-linked immunosorbent assay (ELISA), Western blotting, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR)...
September 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28917667/amyloid-%C3%AE-42-clearance-and-neuroprotection-mediated-by-x-box-binding-protein-1-signaling-decline-with-aging-in-the-drosophila-brain
#9
María S Marcora, Lautaro F Belfiori-Carrasco, Nadia I Bocai, Laura Morelli, Eduardo M Castaño
The unfolded protein response (UPR) may be pathogenically related to Alzheimer's disease. Yet, the effects of chronic amyloid-β42 (Aβ42) accumulation and UPR activation upon neurotoxicity remain unclear. Here, we show that neuronal Aβ42 expression in Drosophila activated the inositol-requiring protein-1/X-box binding protein 1 (XBP1) UPR branch before the onset of behavioral impairment and persisted with aging. Early upregulation of hsc3/BiP, a target of XBP1 and activating transcription factor 6 pathways, was also sustained in old animals...
August 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28917150/efficient-delivery-of-signal-responsive-gene-carriers-for-disease-specific-gene-expression-via-bubble-liposomes-and-sonoporation
#10
Akira Tsuchiya, Jeong-Hun Kang, Takeshi Mori, Yuki Naritomi, Satoshi Kushio, Takuro Niidome, Katsuro Tachibana, Yoko Takahashi, Yoichi Negishi, Yusuke Oda, Ryo Suzuki, Kazuo Maruyama, Yoshiki Katayama
Sonoporation is a promising method to intracellularly deliver synthetic gene carriers that have lower endocytotic uptake than viral carriers. Here, we applied sonoporation to deliver genes via polyethylene glycol (PEG)-grafted polymeric carriers that specifically respond to hyperactivated protein kinase A (PKA). PEG-grafted polymeric carrier/DNA polyplexes were not efficiently delivered into cells via the endocytotic pathway because of the hydrophilic PEG layer surrounding the polyplexes. However, the delivery of polyplexes into cells was significantly increased by sonoporation...
September 9, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28917142/reactions-of-tobacco-genotypes-with-different-antioxidant-capacities-to-powdery-mildew-and-tobacco-mosaic-virus-infections
#11
Gábor Gullner, Csilla Juhász, Adél Németh, Balázs Barna
The interactions of powdery mildew (Golovinomyces orontii) and Tobacco mosaic virus (TMV) with tobacco lines having down or upregulated antioxidants were investigated. Xanthi-nc, its salicylic acid-deficient NahG mutant, a paraquat-sensitive Samsun (PS) and its paraquat tolerant (PT) mutant were used. Cell membrane damage caused by H2O2 was significantly higher in NahG than Xanthi, whereas it was lower in PT than in PS. Leakage of ions from PT was reduced by the powdery mildew infection. On the other hand TMV inoculation led to a 6-fold and 2-fold elevation of ion leakage from hypersensitive resistant NahG and Xanthi leaves, respectively, whereas ion leakage increased slightly from susceptible PS leaves...
September 8, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28916830/the-effects-of-different-enrofloxacin-dosages-on-clinical-efficacy-and-resistance-development-in-chickens-experimentally-infected-with-salmonella-typhimurium
#12
Jun Li, Haihong Hao, Guyue Cheng, Xu Wang, Saeed Ahmed, Muhammad Abu Bakr Shabbir, Zhenli Liu, Menghong Dai, Zonghui Yuan
To investigate the optimal dosage which can improve clinical efficacy and minimize resistance, pharmacokinetics/pharmacodynamics model of enrofloxacin was established. Effect of enrofloxacin treatments on clearance of Salmonella in experimentally infected chickens and simultaneously resistance selection in Salmonella and coliforms were evaluated in three treatment groups (100, PK/PD designed dosage of 4, 0.1 mg/kg b.w.) and a control group. Treatment duration was three rounds of 7-day treatment alternated with 7-day withdrawal...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916822/ampk-phosphorylation-of-ulk1-is-required-for-targeting-of-mitochondria-to-lysosomes-in-exercise-induced-mitophagy
#13
Rhianna C Laker, Joshua C Drake, Rebecca J Wilson, Vitor A Lira, Bevan M Lewellen, Karen A Ryall, Carleigh C Fisher, Mei Zhang, Jeffrey J Saucerman, Laurie J Goodyear, Mondira Kundu, Zhen Yan
Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3-12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916724/a-novel-mechanism-for-ca-2-calmodulin-dependent-protein-kinase-ii-targeting-to-l-type-ca-2-channels-that-initiates-long-range-signaling-to-the-nucleus
#14
Xiaohan Wang, Christian R Marks, Tyler L Perfitt, Terunaga Nakagawa, Amy Lee, David A Jacobson, Roger J Colbran
Neuronal excitation can induce new mRNA transcription, a phenomenon called excitation-transcription (E-T) coupling. Among several pathways implicated in E-T coupling, activation of voltage-gated L-type Ca(2+) channels (LTCCs) in the plasma membrane can initiate a signaling pathway that ultimately increases nuclear CREB phosphorylation and, in most cases, expression of immediate early genes. Initiation of this long-range pathway has been shown to require recruitment of Ca(2+)-sensitive enzymes to a nanodomain in the immediate vicinity of the LTCC by an unknown mechanism...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916722/phosphoproteomics-reveals-that-glycogen-synthase-kinase-3-phosphorylates-multiple-splicing-factors-and-is-associated-with-alternative-splicing
#15
Mansi Y Shinde, Simone Sidoli, Katarzyna Kulej, Michael J Mallory, Caleb M Radens, Amanda Reicherter, Rebecca L Myers, Yoseph Barash, Kristen W Lynch, Benjamin A Garcia, Peter S Klein
Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif (pS/pTXXXS/T), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry (MS) techniques to analyze the repertoire of GSK-3-dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ~2...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916378/clinical-pharmacology-of-anti-angiogenic-drugs-in-oncology
#16
REVIEW
P Gougis, J Wassermann, J P Spano, N Keynan, C Funck-Brentano, J E Salem
Abnormal vasculature proliferation is one of the so-called hallmarks of cancer. Angiogenesis inhibitor therapies are one of the major breakthroughs in cancer treatment in the last two decades. Two types of anti-angiogenics have been approved: monoclonal antibodies and derivatives, which are injected and target the extracellular part of a receptor, and protein kinase inhibitors, which are orally taken small molecules targeting the intra-cellular Adenosine Triphosphate -pocket of different kinases. They have become an important part of some tumors' treatment, both in monotherapy or in combination...
September 1, 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28916374/amp-activated-protein-kinase-protects-against-anoxia-in-drosophila-melanogaster
#17
Justin J Evans, Chengfeng Xiao, R Meldrum Robertson
During anoxia, proper energy maintenance is essential in order to maintain neural operation. Starvation activates AMP-activated protein kinase (AMPK), an evolutionarily conserved indicator of cellular energy status, in a cascade which modulates ATP production and consumption. We investigated the role of energetic status on anoxia tolerance in Drosophila and discovered that starvation or AMPK activation increases the speed of locomotor recovery from an anoxic coma. Using temporal and spatial genetic targeting we found that AMPK in the fat body contributes to starvation-induced fast locomotor recovery, whereas, under fed conditions, disrupting AMPK in oenocytes prolongs recovery...
September 12, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28916300/distinct-neuronal-populations-in-the-basolateral-and-central-amygdala-are-activated-with-acute-pain-conditioned-fear-and-fear-conditioned-analgesia
#18
Ryan K Butler, Sarah Ehling, Megan Barbar, Jess Thomas, Mary A Hughes, Charles E Smith, Vladimir M Pogorelov, Dipendra K Aryal, William C Wetsel, B Duncan X Lascelles
Fear-conditioned analgesia (FCA) is modulated by brain areas involved in the descending inhibitory pain pathway such as the basolateral (BLA) and central amygdala (CEA). The BLA contains Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and parvalbumin (PV) neurons. CEA neurons are primarily inhibitory (GABAergic) that comprise enkephalin (ENK) interneurons and corticotropin-releasing factor (CRF) - neurons that project to the periaqueductal grey. The purpose of our experiment was to determine the pattern of activation of CaMKII/PV and ENK/CRF neurons following the expression of acute pain, conditioned fear, and FCA...
September 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28916266/grass-carp-ctenopharyngodon-idella-stat3-regulates-the-eif2%C3%AE-phosphorylation-through-interaction-with-pkr
#19
Liqiang Wang, Zhen Wu, Qingli Huang, Keyi Huang, Guoqin Qi, Chuxin Wu, Huiling Mao, Xiaowen Xu, Haizhou Wang, Chengyu Hu
In mammals, STAT3 (Signal transducer and activator of transcription 3) plays an important role in growth, multiplication, differentiation and participates in inflammation, tumorigenesis, metabolic disorders and immune response. STAT3 is a protein that shuttles between the nucleus and cytoplasm. Compared to the STAT3 in cell nucleus, we did not know the function of STAT3 in cytoplasm for a long time. Some recent studies have shown that cytoplasmic STAT3 regulates autophagy through the interaction with the double-stranded RNA-activated protein kinase (PKR), which plays an important role in cellular antiviral response...
September 12, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28916189/phosphoinositide-5-phosphatase-activities-control-cell-motility-in-glioblastoma-two-phosphoinositides-pi-4-5-p2-and-pi-3-4-p2-are-involved
#20
REVIEW
Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes...
September 5, 2017: Advances in Biological Regulation
keyword
keyword
31858
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"