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https://www.readbyqxmd.com/read/28340182/novel-targets-and-future-strategies-for-acute-cardioprotection-position-paper-of-the-european-society-of-cardiology-working-group-on-cellular-biology-of-the-heart
#1
Derek J Hausenloy, David Garcia-Dorado, Hans Erik Bøtker, Sean M Davidson, James Downey, Felix B Engel, Robert Jennings, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Michel Ovize, Cinzia Perrino, Fabrice Prunier, Rainer Schulz, Joost P G Sluijter, Linda W Van Laake, Jakob Vinten-Johansen, Derek M Yellon, Kirsti Ytrehus, Gerd Heusch, Péter Ferdinandy
Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury. During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic - however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing...
March 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#2
Yong Hwan Kim, Mi-Jung Kim, Se-Woon Choe, Dennis Sprecher, Young Jae Lee, S Paul Oh
BACKGROUND: Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult onset arteriovenous malformations (AVMs). OBJECTIVES: The goal of this study is to evaluate potential therapeutic effects of oral delivery of four anti-angiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult onset AVMs in a murine model of HHT...
March 24, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28339027/su6668-modulates-prostate-cancer-progression-by-downregulating-mtdh-akt-signaling-pathway
#3
Benjiang Qian, Yi Yao, Changming Liu, Jiabing Zhang, Huihong Chen, Huizhang Li
Prostate cancer is the second leading cause of cancer deaths among men in Western counties and has increased in incidence also in China in recent years. Although diagnosis modalities for primary prostate cancer have markedly improved, there are still no effective therapies for metastatic prostate cancer. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2, PDGFRβ and FGFR1. There is strong experimental evidence that SU6668 can induce growth inhibition of various primary tumors...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28339018/role-of-autophagy-in-the-progression-of-osteoarthritis-the-autophagy-inhibitor-3-methyladenine-aggravates-the-severity-of-experimental-osteoarthritis
#4
Ni-Tao Cheng, Hai Meng, Li-Feng Ma, Liang Zhang, Hao-Miao Yu, Zhen-Zhong Wang, Ai Guo
Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA)...
March 23, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28339015/protection-of-fk506-against-neuronal-apoptosis-and-axonal-injury-following-experimental-diffuse-axonal-injury
#5
Ting-Qin Huang, Jin-Ning Song, Feng-Wei Zheng, Hong-Gang Pang, Yong-Lin Zhao, Hua Gu, Jun-Jie Zhao
Diffuse axonal injury (DAI) is the most common and significant pathological features of traumatic brain injury (TBI). However, there are still no effective drugs to combat the formation and progression of DAI in affected individuals. FK506, also known as tacrolimus, is an immunosuppressive drug, which is widely used in transplantation medicine for the reduction of allograft rejection. Previous studies have identified that FK506 may play an important role in the nerve protective effect of the central nervous system...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338622/phosphodiesterase-inhibitors-as-a-therapeutic-approach-to-neuroprotection-and-repair
#6
REVIEW
Eric P Knott, Mazen Assi, Sudheendra N R Rao, Mousumi Ghosh, Damien D Pearse
A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28338008/noninvasive-measurement-of-transdermal-drug-delivery-by-impedance-spectroscopy
#7
Pasquale Arpaia, Umberto Cesaro, Nicola Moccaldi
The effectiveness in transdermal delivery of skin permeation strategies (e.g., chemical enhancers, vesicular carrier systems, sonophoresis, iontophoresis, and electroporation) is poorly investigated outside of laboratory. In therapeutic application, the lack of recognized techniques for measuring the actually-released drug affects the scientific concept itself of dosage for topically- and transdermally-delivered drugs. Here we prove the suitability of impedance measurement for assessing the amount of drug penetrated into the skin after transdermal delivery...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337955/examining-the-in-vitro-efficacy-of-the-iap-antagonist-birinapant-as-a-single-agent-or-in-combination-with-dacarbazine-to-induce-melanoma-cell-death
#8
Vesna Vetma, Jan Rožanc, Emilie M Charles, Christian T Hellwig, Leonidas G Alexopoulos, Markus Rehm
Antagonists of inhibitor of apoptosis proteins (IAPs), alone or in combination with genotoxic therapeutics, have been shown to efficiently induce cell death in various solid tumours. The IAP antagonist birinapant is currently being tested in phase II clinical trials. We herein aimed to investigate the in vitro anti-tumour efficacy of dacarbazine, both as a single agent and in combination with birinapant, in melanoma cell lines. Covering clinically relevant drug concentration ranges, we conducted a total of 5400 measurements in a panel of 12 human melanoma cell lines representing different stages of disease progression...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28337258/neuroprotective-effect-of-win55-212-2-against-3-nitropropionic-acid-induced-toxicity-in-the-rat-brain-involvement-of-cb1-and-nmda-receptors
#9
Marisol Maya-López, Ana Laura Colín-González, Gabriela Aguilera, María Eduarda de Lima, Ana Colpo-Ceolin, Edgar Rangel-López, Juana Villeda-Hernández, Daniel Rembao-Bojórquez, Isaac Túnez, Armando Luna-López, Roberto Lazzarini-Lechuga, Viridiana Yazmín González-Puertos, Pedro Posadas-Rodríguez, Alejandro Silva-Palacios, Mina Königsberg, Abel Santamaría
The endocannabinoid system (ECS), and agonists acting on cannabinoid receptors (CBr), are known to regulate several physiological events in the brain, including modulatory actions on excitatory events probably through N-methyl-D-aspartate receptor (NMDAr) activity. Actually, CBr agonists can be neuroprotective. The synthetic CBr agonist WIN55,212-2 acts mainly on CB1 receptor. In turn, the mitochondrial toxin 3-nitropropionic acid (3-NP) produces striatal alterations in rats similar to those observed in the brain of Huntington's disease patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337226/tetramethylpyrazine-protects-against-early-brain-injury-after-experimental-subarachnoid-hemorrhage-by-affecting-mitochondrial-dependent-caspase-3-apoptotic-pathway
#10
Shaoxue Li, Xiaolan Xiao, Xiaojia Ni, Zhennan Ye, Junjie Zhao, Chunhua Hang
This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28337127/nlrp3-inflammasome-in-neurological-diseases-from-functions-to-therapies
#11
REVIEW
Limin Song, Lei Pei, Shanglong Yao, Yan Wu, You Shang
Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28336257/a-novel-pyrazole-containing-indolizine-derivative-suppresses-nf-%C3%AE%C2%BAb-activation-and-protects-against-tnbs-induced-colitis-via-a-ppar-%C3%AE-dependent-pathway
#12
Yong Fu, Junting Ma, Xiafei Shi, Xiang-Yun Song, Yaping Yang, Shuke Xiao, Jiahuang Li, Wei-Jin Gu, Zhen Huang, Junfeng Zhang, Jiangning Chen
The nuclear factor-κB (NF-κB)-mediated activation of macrophages plays a key role in mucosal immune responses in Crohn's disease (CD). Moreover, increasing evidence shows that the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) exerts satisfactory anti-inflammatory effects in experimental colitis models, mostly by suppressing NF-κB-mediated macrophage activation. Therefore, exploring therapeutic strategies to activate PPAR-γ and inhibit the NF-κB pathway in colonic macrophages holds great promise for the treatment of CD...
March 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28335576/genome-wide-identification-and-evolutionary-analysis-of-sarcocystis-neurona-protein-kinases
#13
Edwin K Murungi, Henry M Kariithi
The apicomplexan parasite Sarcocystis neurona causes equine protozoal myeloencephalitis (EPM), a degenerative neurological disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions, such as host cell invasion, cell cycle progression and host immune response evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans...
March 21, 2017: Pathogens
https://www.readbyqxmd.com/read/28334762/missense-uros-mutations-causing-congenital-erythropoietic-porphyria-reduce-uros-homeostasis-that-can-be-rescued-by-proteasome-inhibition
#14
Jean-Marc Blouin, Ganeko Bernardo-Seisdedos, Emma Sasso, Julie Esteve, Cécile Ged, Magalie Lalanne, Arantza Sanz-Parra, Pedro Urquiza, Hubert de Verneuil, Oscar Millet, Emmanuel Richard
Congenital erythropoietic porphyria (CEP) is an inborn error of heme biosynthesis characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in deleterious porphyrin accumulation in blood cells responsible for hemolytic anemia and cutaneous photosensitivity. We analyzed here the molecular basis of UROS impairment associated with twenty nine UROS missense mutations actually described in CEP patients. Using a computational and biophysical joint approach we predicted that most disease-causing mutations would affect UROS folding and stability...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334334/p53-and-its-mutants-on-the-slippery-road-from-stemness-to-carcinogenesis
#15
Alina Molchadsky, Varda Rotter
Normal development, tissue homeostasis and regeneration following injury rely on the proper functions of wide repertoire of stem cells (SCs) persisting during embryonic period and throughout the adult life. Therefore, SCs employ robust mechanisms to preserve their genomic integrity and avoid heritage of mutations to their daughter cells. Importantly, propagation of SCs with faulty DNA as well as dedifferentiation of genomically altered somatic cells may result in derivation of cancer SCs, which are considered to be the driving force of the tumorigenic process...
March 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28334263/pathogenesis-of-meningococcal-purpura-fulminans
#16
H Lécuyer, D Borgel, X Nassif, M Coureuil
Purpura fulminans (PF) is a dreadful and frequent complication of Neisseria meningitidis invasive infection, and is associated with a high mortality rate. This syndrome begins with dermal microvessels thrombosis that rapidly lead to hemorrhagic skin necrosis. In this review, we discuss the prothrombotic events occurring during meningococcal infection. Moreover, recent data from an experimental mouse model have highlighted the critical role of the meningococcus adhesion to the endothelium in the development of PF lesions, thus opening new therapeutic perspectives...
March 9, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28333959/fnc-efficiently-inhibits-mantle-cell-lymphoma-growth
#17
Yan Zhang, Rong Zhang, Xixi Ding, Bangan Peng, Ning Wang, Fang Ma, Youmei Peng, Qingduan Wang, Junbiao Chang
FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, is a novel cytidine analogue, that has shown strong antiproliferative activity in human lymphoma, lung adenocarcinoma and acute myeloid leukemia. In this study, we investigated the effects of FNC on mantle cell lymphoma (MCL) and the underlying mechanisms. In in vitro experiments, cell viability was detected by the CCK8 assay, and cell cycle progression and apoptosis were assessed by flow cytometry, and the expression of relative apoptosis proteins were detected by Western Blot...
2017: PloS One
https://www.readbyqxmd.com/read/28333689/computational-modelling-of-the-cerebral-cortical-microvasculature-effect-of-x-ray-microbeams-versus-broad-beam-irradiation
#18
Andreas Merrem, Stefan Bartzsch, Jean Laissue, Uwe Oelfke
Microbeam Radiation Therapy is an innovative pre-clinical strategy which uses arrays of parallel, tens of micrometre wide kilo-voltage photon beams to treat tumours. These X-ray beams are typically generated on a synchrotron source. It was shown that these beam geometries allow exceptional normal tissue sparing from radiation damage while still being effective in tumour ablation. A final biological explanation for this enhanced therapeutic ratio has still not been found, some experimental data support an important role of the vasculature...
March 23, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28332488/parkinson-disease
#19
REVIEW
Werner Poewe, Klaus Seppi, Caroline M Tanner, Glenda M Halliday, Patrik Brundin, Jens Volkmann, Anette-Eleonore Schrag, Anthony E Lang
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability...
March 23, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28332424/neuroprotective-effect-of-dl-3-n-butylphthalide-on-patients-with-radiation-induced-brain-injury-a-clinical-retrospective-cohort-study
#20
Xiaoni Zhang, Yi Li, Xiangpen Li, Xiaoming Rong, Yamei Tang, Ying Peng
PURPOSE: To evaluate the neuroprotective effects of Dl-3-n-butylphthalide (NBP) on patients with radiation-induced brain injury, a hospital-based, clinical retrospective cohort study was conducted. PATIENTS AND METHODS: Data was collected on patients diagnosed with radiation-induced brain injury from January 2009 to January 2015 in Department of Neurology, Sun Yat-Sen Memorial Hospital. All patients enrolled have received cranial radiotherapy and were diagnosed with radiation-induced brain injury...
March 23, 2017: International Journal of Neuroscience
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