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https://www.readbyqxmd.com/read/28239766/up-regulation-of-gbp2-is-associated-with-neuronal-apoptosis-in-rat-brain-cortex-following-traumatic-brain-injury
#1
Qi Miao, Meihong Ge, Lili Huang
Guanylate binding protein 2 (GBP2) is one member of GBP family. Recently, GBP2 has been proposed to be a novel target of anti-cancer drugs. However, the role of GBP2 in the traumatic brain injury (TBI) is very limited. In this study, we sought to define GBP2's role in brain injury. GBP2 protein levels were significantly increased in the brain 3 days after injury, suggesting a functional role for GBP2 in TBI. Neuronal cells overexpressing GBP2 exhibited up-regulation of co-location of GBP2 and NeuN following TBI, suggesting that GBP2 potentiates the neuron apoptosis...
February 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28239687/protein-phosphatase-5-contributes-to-the-overexpression-of-epigenetically-regulated-t-lymphocyte-genes-in-patients-with-lupus
#2
D Patel, G Gorelik, B Richardson
OBJECTIVE: Lupus develops when genetically predisposed people encounter certain drugs or environmental agents causing oxidative stress such as infections and sun exposure, and then typically follows a chronic relapsing course with flares triggered by the exogenous stressors. Current evidence indicates that these environmental agents can trigger lupus flares by inhibiting the replication of DNA methylation patterns during mitosis in CD4(+) T cells, altering the expression of genes suppressed by this mechanism that convert normal "helper" cells into auto reactive cells which promote lupus flares...
December 2016: Lupus (Los Angel)
https://www.readbyqxmd.com/read/28239655/alterations-in-sarcomere-function-modify-the-hyperplastic-to-hypertrophic-transition-phase-of-mammalian-cardiomyocyte-development
#3
Benjamin R Nixon, Alexandra F Williams, Michael S Glennon, Alejandro E de Feria, Sara C Sebag, H Scott Baldwin, Jason R Becker
It remains unclear how perturbations in cardiomyocyte sarcomere function alter postnatal heart development. We utilized murine models that allowed manipulation of cardiac myosin-binding protein C (MYBPC3) expression at critical stages of cardiac ontogeny to study the response of the postnatal heart to disrupted sarcomere function. We discovered that the hyperplastic to hypertrophic transition phase of mammalian heart development was altered in mice lacking MYBPC3 and this was the critical period for subsequent development of cardiomyopathy...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239561/regulation-of-cardiac-cacnb2-by-microrna-499-potential-role-in-atrial-fibrillation
#4
Tian-You Ling, Xiao-Li Wang, Qiang Chai, Tong Lu, John M Stulak, Lyle D Joyce, Richard C Daly, Kevin L Greason, Li-Qun Wu, Win-Kuang Shen, Yong-Mei Cha, Hon-Chi Lee
The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28239551/genome-wide-chromatin-accessibility-dna-methylation-and-gene-expression-analysis-of-histone-deacetylase-inhibition-in-triple-negative-breast-cancer
#5
Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L DiNome, Dave S B Hoon, Diego M Marzese
Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors...
June 2017: Genomics Data
https://www.readbyqxmd.com/read/28239472/analyses-of-the-peripheral-immunome-following-multiple-administrations-of-avelumab-a-human-igg1-anti-pd-l1-monoclonal-antibody
#6
Renee N Donahue, Lauren M Lepone, Italia Grenga, Caroline Jochems, Massimo Fantini, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
BACKGROUND: Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239468/immunotherapy-associated-autoimmune-hemolytic-anemia
#7
Uqba Khan, Farman Ali, Muhammad Siddique Khurram, Awais Zaka, Tarik Hadid
BACKGROUND: Immunotherapy has been widely used in the treatment of several solid and hematologic malignancies. Checkpoint inhibitors have been the forefront of cancer immunotherapy in recent years. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) pathway are the prototypic checkpoint targets for immunotherapy. When combined, CTLA-4 and PD-1 checkpoint inhibitors work synergistically, but with increased probability of toxicity. The following case represents an unusual adverse effect of combined treatment with ipilimumab and nivolumab used for treatment of metastatic melanoma...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239377/pro-inflammatory-signaling-in-a-3d-organotypic-skin-model-after-low-let-irradiation-nf-%C3%AE%C2%BAb-cox-2-activation-and-impact-on-cell-differentiation
#8
Anna Acheva, Giuseppe Schettino, Kevin M Prise
Nearly 85% of radiotherapy patients develop acute radiation dermatitis, which is an inflammatory reaction of the skin at the treatment field and in the surrounding area. The aims of this study were to unravel the mechanisms of radiation-induced inflammatory responses after localized irradiation in a human 3D organotypic skin culture model. This could provide possible inflammatory targets for reduction of skin side effects. 3D organotypic skin cultures were set up and locally irradiated with 225 kVp X-rays, using a combination of full exposure and partial shielding (50%) of the cultures...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28238967/resveratrol-fuels-her2-and-er%C3%AE-positive-breast-cancer-behaving-as-proteasome-inhibitor
#9
Andreani Cristina, Bartolacci Caterina, Wijnant Kathleen, Crinelli Rita, Bianchi Marzia, Magnani Mauro, Hysi Albana, Iezzi Manuela, Amici Augusto, Marchini Cristina
The phytoestrogen resveratrol has been reported to possess cancer chemo-preventive activity on the basis of its effects on tumor cell lines and xenograft or carcinogen-inducible in vivo models. Here we investigated the effects of resveratrol on spontaneous mammary carcinogenesis using Δ16HER2 mice as HER2+/ERα+ breast cancer model. Instead of inhibiting tumor growth, resveratrol treatment (0.0001% in drinking water; daily intake of 4μg/mouse) shortened tumor latency and enhanced tumor multiplicity in Δ16HER2 mice...
February 26, 2017: Aging
https://www.readbyqxmd.com/read/28238947/identification-of-novel-mrp3-inhibitors-based-on-computational-models-and-validation-using-an-in-vitro-membrane-vesicle-assay
#10
Izna Ali, Matthew A Welch, Yang Lu, Peter W Swaan, Kim L R Brouwer
INTRODUCTION: Multidrug resistance-associated protein 3 (MRP3), an efflux transporter on the hepatic basolateral membrane, may function as a compensatory mechanism to prevent the accumulation of anionic substrates (e.g., bile acids) in hepatocytes. Inhibition of MRP3 may disrupt bile acid homeostasis and is one hypothesized risk factor for the development of drug-induced liver injury (DILI). Therefore, identifying potential MRP3 inhibitors could help mitigate the occurrence of DILI. METHODS: Bayesian models were developed using MRP3 transporter inhibition data for 86 structurally diverse drugs...
February 23, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28238906/fibulin-4-reduces-extracellular-matrix-production-and-suppresses-chondrocyte-differentiation-via-dkk1-mediated-canonical-wnt-%C3%AE-catenin-signaling
#11
Lei Shangguan, Guangzhi Ning, Zhuojing Luo, Yue Zhou
Fibulin-4 is an extracellular matrix (ECM) protein implicated in connective tissue development and elastic fiber formation. However, little is known about the underlying function of Fibulin-4 in cartilage development. The aim of this study was to investigate the role and probable mechanism of Fibulin-4 stimulation in ECM production and chondrocyte differentiation. Fibulin-4 has been observed to be abnormally elevated and matrix metalloproteinases 13 (MMP13) level was highly expressed in human osteoarthritis (OA) chondrocytes...
February 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28238890/time-lapse-imaging-of-p65-and-i%C3%AE%C2%BAb%C3%AE-translocation-kinetics-following-ca-2-induced-neuronal-injury-reveals-biphasic-translocation-kinetics-in-surviving-neurons
#12
Robert Schwamborn, Heiko Düssmann, Hans-Georg König, Jochen H M Prehn
The transcription factor nuclear factor-κB (NF-κB) regulates neuronal differentiation, plasticity and survival. It is well established that excitatory neurotransmitters such as glutamate control NF-κB activity. Glutamate receptor overactivation is also involved in ischemic- and seizure-induced neuronal injury and neurodegeneration. However, little is known at the single cell-level how NF-κB signaling relates to neuronal survival during excitotoxic injury. We found that silencing of p65/NF-κB delayed N-methyl-d-aspartate (NMDA)-induced excitotoxic injury in hippocampal neurons, suggesting a functional role of p65 in excitotoxicity...
February 23, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28238848/resveratrol-protects-against-spinal-cord-injury-by-activating-autophagy-and-inhibiting-apoptosis-mediated-by-the-sirt1-ampk-signaling-pathway
#13
Haosen Zhao, Shurui Chen, Kai Gao, Zipeng Zhou, Chen Wang, Zhaoliang Shen, Yue Guo, Zhuo Li, Zhanghui Wan, Chang Liu, Xifan Mei
Spinal cord injury (SCI) is a devastating condition with few effective treatments. Resveratrol, a polyphenolic compound, has exhibited neuroprotective effects in many neurodegenerative diseases. However, the explicit effect and mechanism of resveratrol on SCI is still unclear. Adenosine 5' monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1),the downstream protein, play key roles in metabolizing of energy, resisting of resistance, and cellularprotein homeostasis. In this study, we determined the effects of resveratrol on SCI and their potential relationship with SIRT1/AMPK signaling pathway, autophagy and apoptosis...
February 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28238808/hypophosphatasia-an-overview-for-2017
#14
Michael P Whyte
Hypophosphatasia (HPP) is the inborn-error-of-metabolism that features low serum alkaline phosphatase (ALP) activity (hypophosphatasemia) caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of ALP (TNSALP). Autosomal recessive or autosomal dominant inheritance from among >300 TNSALP (ALPL) mutations largely explains HPP's remarkably broad-ranging severity. TNSALP is a cell-surface homodimeric phosphohydrolase richly expressed in the skeleton, liver, kidney, and developing teeth...
February 24, 2017: Bone
https://www.readbyqxmd.com/read/28238805/pharmacological-inhibition-of-lsd1-and-mtor-reduces-mitochondrial-retention-and-associated-ros-levels-in-the-red-blood-cells-of-sickle-cell-disease
#15
Ramasamy Jagadeeswaran, Benjamin A Vazquez, Muthusamy Thiruppathi, Balaji B Ganesh, Vinzon Ibanez, Shuaiying Cui, James D Engel, Alan M Diamond, Robert E Molokie, Joseph DeSimone, Donald Lavelle, Angela Rivers
Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs) which accelerates their hemolysis...
February 23, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#16
Fucheng Luo, Karl Herrup, Xin Qi, Yan Yang
Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and stems necrosis in primary OLs exposed to TNF-α and H2O2...
February 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28238772/assessment-of-anti-cholinesterase-activity-and-cytotoxicity-of-cagaita-eugenia-dysenterica-leaves
#17
Cristian A Gasca, Willian O Castillo, Catarina Satie Takahashi, Christopher W Fagg, Perola de Oliveira E Magalhães, Yris M Fonseca-Bazzo, Dâmaris Silveira
Eugenia dysenterica ex DC Mart. (Myrtaceae) is a Brazilian tree with pharmacological and biological properties. The aqueous leaf extract, rich in polyphenols, was tested in the human neuroblastoma cell line SHSY5Y to evaluate its effect on cell viability. The extract and two isolated compounds were also assessed for the potential inhibitory activity on acetylcholinesterase, an enzyme related to Alzheimer's disease. A simple chromatographic method using Sephadex LH-20 was developed to separate catechin and quercetin from the aqueous leaf extract of E...
February 23, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28238764/cullin-e3-ligase-activity-is-required-for-myoblast-differentiation
#18
Jordan Blondelle, Paige Shapiro, Andrea A Domenighetti, Stephan Lange
The role of cullin E3-ubiquitin ligases for muscle homeostasis is best known during muscle atrophy, as the cullin-1 substrate adaptor atrogin-1 counts among the most well-characterized muscle atrogins. We investigated, whether cullin activity was also crucial during terminal myoblast differentiation and aggregation of acetylcholine receptors for the establishment of neuromuscular junctions in vitro. The activity of cullin E3-ligases is modulated through posttranslational modification with the small ubiquitin-like modifier nedd8...
February 23, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28238749/persistent-kallikrein5-activation-induces-atopic-dermatitis-like-skin-architecture-independent-of-par2-activity
#19
Yanan Zhu, Joanne Underwood, Derek Macmillan, Leila Shariff, Ryan O'Shaughnessy, John I Harper, Chris Pickard, Peter S Friedmann, Eugene Healy, Wei-Li Di
BACKGROUND: Up-regulation of kallikreins (KLK) including KLK5 has been reported in atopic dermatitis (AD). KLK5 has biological functions which include degrading desmosomal proteins and inducing pro-inflammatory cytokine secretion through protease activated receptor 2 (PAR2). However, due to the complex interactions between various cells in AD inflamed skin, it is difficult to dissect the precise and multiple roles of up-regulated KLK5 in AD skin. OBJECTIVE: We investigated the effect of up-regulated KLK5 on the expression of epidermal related proteins and cytokines in keratinocytes and on skin architecture...
February 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28238728/an-integrative-transcriptomic-analysis-reveals-bisphenol-a-exposure-induced-dysregulation-of-microrna-expression-in-human-endometrial-cells
#20
Wei-Chun Chou, Pei-Hsuan Lee, Yan-Yan Tan, Ho-Chen Lin, Chung-Wei Yang, Kuan-Hsueh Chen, Chun-Yu Chuang
Bisphenol A (BPA) are commonly used in the manufacture of polycarbonate plastics. Higher BPA exposure levels have been found in patients with endometrial hyperplasia that is one of risk factors of endometrial cancer (EC). Aberrant microRNAs (miRNAs) regulation has been observed in the development of cancer. Thus, this study investigated whether BPA exposure can disrupt miRNA regulation and its gene expression regarding to EC carcinogenic progress. Microarray experiments of miRNA and mRNA were performed in human endometrial cancer RL95-2 cells with treatment of low-to-moderate (10, 10(3) and 10(5)nM) BPA to explore the aberrant genes corresponding to human EC progression...
February 23, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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