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https://www.readbyqxmd.com/read/28806770/increasing-creatine-kinase-activity-protects-against-hypoxia-reoxygenation-injury-but-not-against-anthracycline-toxicity-in-vitro
#1
Sevasti Zervou, Hannah J Whittington, Philip J Ostrowski, Fang Cao, Jack Tyler, Hannah A Lake, Stefan Neubauer, Craig A Lygate
The creatine kinase (CK) phosphagen system is fundamental to cellular energy homeostasis. Cardiomyocytes express three CK isoforms, namely the mitochondrial sarcomeric CKMT2 and the cytoplasmic CKM and CKB. We hypothesized that augmenting CK in vitro would preserve cell viability and function and sought to determine efficacy of the various isoforms. The open reading frame of each isoform was cloned into pcDNA3.1, followed by transfection and stable selection in human embryonic kidney cells (HEK293). CKMT2- CKM- and CKB-HEK293 cells had increased protein and total CK activity compared to non-transfected cells...
2017: PloS One
https://www.readbyqxmd.com/read/28806703/nox4-mediated-ros-production-induces-apoptotic-cell-death-via-down-regulation-of-c-flip-and-mcl-1-expression-in-combined-treatment-with-thioridazine-and-curcumin
#2
Seung Un Seo, Tae Hwan Kim, Dong Eun Kim, Kyoung-Jin Min, Taeg Kyu Kwon
Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA...
August 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/28805970/a-novel-free-fatty-acid-receptor-1-gpr40-ffar1-agonist-mr1704-enhances-glucose-dependent-insulin-secretion-and-improves-glucose-homeostasis-in-rats
#3
Naoto Tsuda, Atsuko Kawaji, Toshihiro Sato, Mitsuhiro Takagi, Chika Higashi, Yutaka Kato, Kumiko Ogawa, Hiroyasu Naba, Munetaka Ohkouchi, Masaki Nakamura, Yoshitaka Hosaka, Junichi Sakaki
Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805676/inhibitors-of-deubiquitinating-enzymes-block-hiv-1-replication-and-augment-the-presentation-of-gag-derived-mhc-i-epitopes
#4
Christian Setz, Melanie Friedrich, Pia Rauch, Kirsten Fraedrich, Alina Matthaei, Maximilian Traxdorf, Ulrich Schubert
In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity...
August 12, 2017: Viruses
https://www.readbyqxmd.com/read/28803751/insulin-prevents-aberrant-mitochondrial-phenotype-in-sensory-neurons-of-type-1-diabetic-rats
#5
Mohamad-Reza Aghanoori, Darrell R Smith, Subir Roy Chowdhury, Mohammad Golam Sabbir, Nigel A Calcutt, Paul Fernyhough
Diabetic neuropathy affects approximately 50% of diabetic patients. Down-regulation of mitochondrial gene expression and function has been reported in both human tissues and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin signaling in diabetes contributes to loss of mitochondrial function in DRG neurons and to development of neuropathy. Sensory neurons obtained from age-matched adult control or streptozotocin (STZ)-induced type 1 diabetic rats were cultured with or without insulin before determining mitochondrial respiration and expression of mitochondrial respiratory chain and insulin signaling-linked proteins...
August 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28803390/cancer-clonal-theory-immune-escape-and-their-evolving-roles-in-cancer-multi-agent-therapeutics
#6
REVIEW
Jonathan L Messerschmidt, Prianka Bhattacharya, Gerald L Messerschmidt
PURPOSE OF REVIEW: The knowledge base of malignant cell growth and resulting targets is rapidly increasing every day. Clonal theory is essential to understand the changes required for a cell to become malignant. These changes are then clues to therapeutic intervention strategies. Immune system optimization is a critical piece to find, recognize, and eliminate all cancer cells from the host. Only by administering (1) multiple therapies that counteract the cancer cell's mutational and externally induced survival traits and (2) by augmenting the immune system to combat immune suppression processes and by enhancing specific tumor trait recognition can cancer begin to be treated with a truly targeted focus...
August 12, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28803136/anti-inflammatory-activity-of-natural-stilbenoids-a-review
#7
REVIEW
Marcela Dvorakova, Premysl Landa
Resveratrol and other natural stilbenoids, including piceatannol, pterostilbene, and gnetol, are well-known anti-inflammatory compounds with indisputable activity in vitro as well as in vivo. Their molecular targets include inducible nitric oxide synthase, cyclooxygenases, leukotrienes, nuclear factor kappa B, tumor necrosis factor α, interleukins and many more. This anti-inflammatory activity together with their antioxidant activity is believed to stand behind their other positive health effects against cancer, cardiovascular and neurodegenerative diseases or diabetes...
August 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28803118/complex-interactions-between-the-subject-factors-of-biological-sex-and-prior-histories-of-binge-drinking-and-unpredictable-stress-influence-behavioral-sensitivity-to-alcohol-and-alcohol-intake
#8
Sema G Quadir, Eugenie Guzelian, Mason A Palmer, Douglas L Martin, Jennifer Kim, Karen K Szumlinski
Alcohol use disorders, affective disorders and their comorbidity are sexually dimorphic in humans. However, it is difficult to disentangle the interactions between subject factors influencing alcohol sensitivity in studies of humans. Herein, we combined murine models of unpredictable, chronic, mild stress (UCMS) and voluntary binge-drinking to examine for sex differences in the interactions between prior histories of excessive ethanol-drinking and stress upon ethanol-induced changes in motor behavior and subsequent drinking...
August 9, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28802032/deciphering-critical-amino-acid-residues-to-modify-and-enhance-the-binding-affinity-of-ankyrin-scaffold-specific-to-capsid-protein-of-human-immunodeficiency-virus-type-1
#9
Somphot Saoin, Tanchanok Wisitponchai, Kannaporn Intachai, Koollawat Chupradit, Sutpirat Moonmuang, Sawitree Nangola, Kuntida Kitidee, Kanda Fanhchaksai, Vannajan Sanghiran Lee, Saw-See Hong, Pierre Boulanger, Phimonphan Chuankhayan, Chun-Jung Chen, Chatchai Tayapiwatana
BACKGROUND: AnkGAG1D4 is an artificial ankyrin repeat protein which recognizes the capsid protein (CA) of the human immunodeficiency virus type 1 (HIV-1) and exhibits the intracellular antiviral activity on the viral assembly process. Improving the binding affinity of AnkGAG1D4 would potentially enhance the AnkGAG1D4-mediated antiviral activity. OBJECTIVE: To augment the affinity of AnkGAG1D4 scaffold towards its CA target, through computational predictions and experimental designs...
August 8, 2017: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/28801357/the-autoimmune-risk-variant-ptpn22-c1858t-alters-b-cell-tolerance-at-discrete-checkpoints-and-differentially-shapes-the-naive-repertoire
#10
Genita Metzler, Xuezhi Dai, Christopher D Thouvenel, Socheath Khim, Tania Habib, Jane H Buckner, David J Rawlings
A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28798145/tnf-induces-neutrophil-adhesion-via-formin-dependent-cytoskeletal-reorganization-and-activation-of-%C3%AE-integrin-function
#11
Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Camila Bononi Almeida, Hanan Chweih, Wilson Alves Ferreira, Cristina Pontes Vicente, Fabio Trindade Maranhão Costa, Claudio C Werneck, Fernando Ferreira Costa, Nicola Conran
Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28797553/negative-pressure-wound-therapy
#12
REVIEW
Bryden J Stanley
Open wounds are regularly addressed in veterinary medicine and can be challenging to manage, especially when there is significant loss of full-thickness skin. Traditional wound dressings are being replaced by modern synthetic materials, biologic wound dressings, and mechanical technologies to augment healing. Negative pressure wound therapy (NPWT) is one of the most successful mechanical adjuncts to wound healing. Experience with NPWT in veterinary medicine is not as extensive as in human medicine but reports have been positive...
August 7, 2017: Veterinary Clinics of North America. Small Animal Practice
https://www.readbyqxmd.com/read/28797134/looking-beyond-the-intervertebral-disc-the-need-for-behavioral-assays-in-models-of-discogenic-pain
#13
REVIEW
Grace E Mosley, Thomas W Evashwick-Rogler, Alon Lai, James C Iatridis
Orthopedic research into chronic discogenic back pain has commonly focused on aging- and degeneration-related changes in intervertebral disc structure, biomechanics, and biology. However, the primary spine-related reason for physician office visits is pain. The ambiguous nature of the human condition of discogenic low back pain motivates the use of animal models to better understand the pathophysiology. Discogenic back pain models must consider both emergent behavioral changes following pain induction and changes in the nervous system that mediate such behavior...
August 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28796622/w-fyd-a-wearable-fabric-based-display-for-haptic-multi-cue-delivery-and-tactile-augmented-reality
#14
Simone Fani, Simone Ciotti, Edoardo Battaglia, Alessandro Moscatelli, Matteo Bianchi
Despite the importance of softness, there is no evidence of wearable haptic systems able to deliver controllable softness cues. Here, we present the Wearable Fabric Yielding Display (W-FYD), a fabric-based display for multi-cue delivery that can be worn on user's finger and enables, for the first time, both active and passive softness exploration. It can also induce a sliding effect under the finger-pad. A given stiffness profile can be obtained by modulating the stretching state of the fabric through two motors...
August 7, 2017: IEEE Transactions on Haptics
https://www.readbyqxmd.com/read/28796621/influence-of-secretion-on-airflow-dynamics-of-mechanical-ventilated-respiratory-system
#15
Shuai Ren, Yan Shi, Maolin Cai, Weiqing Xu
Secretions in the airways of mechanical ventilated patients are extremely dangerous to patients' health. In recent studies, the continuous constant airflow is adopted, however it is not consistent with clinical situation. To study respiratory airflow dynamic characteristics with secretion in the airways, a mathematical model based on clinical mechanical ventilation is established in this paper. Through the experimental study, the accuracy and dependability of the model are confirmed. To illustrate the secretion's influence of on the airflow dynamics of mechanical ventilated respiratory system, three key parameters which are cross section area ratio of secretion/ pipe, air-secretion contact area and secretion viscosity are involved in the study...
August 9, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28794024/highly-pathogenic-new-world-arenavirus-infection-activates-the-pattern-recognition-receptor-pkr-without-attenuating-virus-replication-in-human-cells
#16
Cheng Huang, Olga A Kolokoltsova, Elizabeth J Mateer, Takaaki Koma, Slobodan Paessler
The arenavirus family consists of several highly pathogenic viruses including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junín virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. NW JUNV and MACV infections readily induce an IFN response in human cells, while OW LASV infection usually triggers an undetectable or weak IFN response. JUNV induces IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs during infection and activates IFN response...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28793943/decontamination-of-hospital-surfaces-with-multijet-cold-plasma-a-method-to-enhance-infection-prevention-and-control
#17
Orla J Cahill, Tânia Claro, Attilio A Cafolla, Niall T Stevens, Stephen Daniels, Hilary Humphreys
OBJECTIVE To evaluate the efficacy of a multijet cold-plasma system and its efficacy in decontaminating 2 surfaces commonly found in hospitals DESIGN An in vitro study of common causes of healthcare-acquired infection METHODS Log10 9 cultures of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended spectrum β-lactamase-producing Escherichia coli, and Acinetobacter baumannii were applied to 5-cm2 sections of stainless steel and mattress. Human serum albumin (HSA) was used as a proxy marker for organic material, and atomic force microscopy (AFM) was used to study the impact on bacterial cell structure...
August 10, 2017: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/28793349/ligation-of-dectin-2-with-a-novel-microbial-ligand-promotes-adjuvant-activity-for-vaccination
#18
Huafeng Wang, Taek-Jin Lee, Scott J Fites, Richard Merkhofer, Robert Zarnowski, Tristan Brandhorst, Kevin Galles, Bruce Klein, Marcel Wüthrich
The development of vaccines against fungi and other intracellular microbes is impeded in part by a lack of suitable adjuvants. While most current vaccines against infectious diseases preferentially induce production of antibodies, cellular immunity is essential for the resolution of fungal infections. Microbes such as fungi and Mycobacterium tuberculosis require Th17 and Th1 cells for resistance, and engage the C-type lectin receptors including Dectin-2. Herein, we discovered a novel Dectin-2 ligand, the glycoprotein Blastomyces Eng2 (Bl-Eng2)...
August 9, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28793283/trifluoperazine-induced-suicidal-erythrocyte-death-and-s-nitrosylation-inhibition-reversed-by-the-nitric-oxide-donor-sodium-nitroprusside
#19
Mehrdad Ghashghaeinia, Mauro Carlos Wesseling, Elena Ramos, Polina Petkova-Kirova, Sabrina Waibel, Elisabeth Lang, Rosi Bissinger, Kossai Alzoubi, Baerbel Edelmann, Zohreh Hosseinzadeh, Peter Dreischer, Azam Shahvaroughi-Farahani, Ulrich Mrowietz, Martin Köberle, Lars Kaestner, Ingolf Bernhardt, Antonio Martínez-Ruiz, Thomas Wieder, Florian Lang
BACKGROUND AND PURPOSE: The high potency antipsychotic drug trifluoperazine (10-[3-(4-methyl-1-piperazinyl)-propyl]-2-(trifluoromethyl)-(10)H-phenothiazine dihydrochloride; TFP) may either counteract or promote suicidal cell death or apoptosis. Similar to apoptosis, erythrocytes may enter eryptosis, characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis can be stimulated by an increase in cytoplasmic Ca2+ concentration ([Ca2+]i) and inhibited by nitric oxide (NO)...
August 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28793249/network-based-genomic-analysis-of-human-oligodendrocyte-progenitor-differentiation
#20
Suyog U Pol, Jessie J Polanco, Richard A Seidman, Melanie A O'Bara, Hani J Shayya, Karen C Dietz, Fraser J Sim
Impaired human oligodendrocyte progenitor cell (hOPC) differentiation likely contributes to failed remyelination in multiple sclerosis. The characterization of molecular pathways that regulate hOPC differentiation will provide means to induce remyelination. In this study, we determined the gene expression profile of PDGFαR(+) hOPCs during initial oligodendrocyte commitment. Weighted gene coexpression network analysis was used to define progenitor and differentiation-specific gene expression modules and functionally important hub genes...
August 8, 2017: Stem Cell Reports
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