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https://www.readbyqxmd.com/read/29187590/selective-cannabinoid-2-receptor-stimulation-reduces-tubular-epithelial-cell-damage-following-renal-ischemia-reperfusion-injury
#1
Jeffrey D Pressly, Suni M Mustafa, Ammaar Abidi, Sahar Alghamdi, Pankaj Pandey, Kuldeep K Roy, Robert Doerksen, Bob M Moore, Frank Park
Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with increased rates of mortality. Currently, therapies to treat AKI are not available, so identification of new targets which, upon diagnosis of AKI, can be modulated to ameliorate renal damage is essential. In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295, was designed, synthesized, and tested in vitro and in silico. In vivo testing of the CB2 agonist was performed using a mouse model of bilateral IRI, which is a common model to mimic human AKI...
November 29, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29174035/effects-of-standard-ethanolic-extract-from-erythrina-velutina-in-acute-cerebral-ischemia-in-mice
#2
Francisca Taciana Rodrigues de Sousa, Caren Nádia Soares de Sousa, Naiara Coelho Ximenes, Anália Barbosa Almeida, Lucas Moraes Cabral, Cláudio Felipe Vasconcelos Patrocínio, Aline Holanda Silva, Luzia Kalyne Almeida Moreira Leal, José Eduardo Ribeiro Honório Júnior, Danielle Macedo, Silvânia Maria Mendes Vasconcelos
The objective of this study was to verify a possible neuroprotective effect of the ethanolic extract of Erythrina velutina (EEEV). Male Swiss mice were submitted to transient cerebral ischemia by occlusion of both carotid arteries for 30 min and treated for 5 days with EEEV (200 or 400 mg/kg) or Memantine (MEM) 10 mg/kg, with initiation of treatment 2 or 24 h after Ischemia. On the 6th day after the induction of ischemia, the animals were submitted to evaluation of locomotor activity and memory and then sacrificed...
November 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29115616/metabolic-alterations-in-the-rat-cerebellum-following-acute-middle-cerebral-artery-occlusion-as-determined-by-1h-nmr-spectroscopy
#3
Zi-Long Hu, Huan-Huan Xia, Yun-Jun Yang, Hong Zheng, Liang-Cai Zhao, Yong-Chun Chen, Qi-Chuan Zhuge, Neng-Zhi Xia, Hong-Chang Gao, Wei-Jian Chen
Supratentorial focal ischemia may reduce cerebral blood volume and cerebellar glucose metabolic rate contralateral to the region of ischemia. The present study investigated the effects of middle cerebral artery occlusion (MCAO) on cerebral metabolism in the ischemic cerebral hemisphere and the non‑ischemic cerebellum in rats 1, 3, 9 and 24 h following ischemia using ex vivo proton nuclear magnetic resonance (1H NMR) spectroscopy. The results demonstrated that focal ischemia induced increases in the levels of lactate and alanine, and a decrease in succinate, as early as 1 h following ischemia in the left cerebral hemisphere and the right cerebellum...
October 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29089759/in-vitro-and-in-vivo-protein-release-and-anti-ischemia-reperfusion-injury-properties-of-bone-morphogenetic-protein-2-loaded-glycyrrhetinic-acid-poly-ethylene-glycol-b-poly-l-lysine-nanoparticles
#4
Fang Shan, YuJuan Liu, Haiying Jiang, Fei Tong
Here, we describe a bone morphogenetic protein-2 (BMP-2) nanocarrier based on glycyrrhetinic acid (GA)-poly(ethylene glycol) (PEG)-b-poly(l-lysine) (PLL). A protein nanocarrier was synthesized, characterized and evaluated as a BMP-2 delivery system. The designed nanocarrier was synthesized based on the ring-opening polymerization of amino acid N-carboxyanhydride. The final product was measured with (1)H nuclear magnetic resonance. GA-PEG-b-PLL nanocarrier could combine with BMP-2 through electrostatic interaction to form polyion complex (PIC) micelles...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29043002/humanin-analogue-s14g-humanin-has-neuroprotective-effects-against-oxygen-glucose-deprivation-reoxygenation-by-reactivating-jak2-stat3-signaling-through-the-pi3k-akt-pathway
#5
Guang-Sheng Gao, Yun Li, Heng Zhai, Jing-Wen Bi, Fu-Sen Zhang, Xiao-Ying Zhang, Shao-Hua Fan
Stroke, characterized by a disruption of blood supply to the brain, is a major cause of morbidity and mortality worldwide. Although humanin, a 24-amino acid polypeptide, has been identified to have multiple neuroprotective functions, the level of humanin in plasma has been demonstrated to decrease with age, which likely limits the effects against stroke injury. A potent humanin analogue, S14G-humanin (HNG), generated by replacement of Ser14 with glycine, has been demonstrated to have 1,000-fold stronger biological activity than humanin...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29035834/synergistic-effect-of-mild-hypothermia-and-the-notch-inhibitor-dapt-against-post-stroke-seizures
#6
Guo-Shuai Yang, Xiao-Yan Zhou, Xue-Fang An, Xuan-Jun Liu, Yan-Jun Zhang, Dan Yu
Seizure is a serious complication of stroke, indicating poor prognosis. Notch signaling is associated with neuronal activity. Inhibition of Notch signaling suppresses seizure activity induced by kainic acid. The present study investigated the effect of the Notch inhibitor, DAPT, alone or in combination with mild hypothermia, on post-stroke seizures. A global cerebral ischemia (GCI) model was performed in Sprague Dawley (SD) male rats. Seizure activity was evaluated by the frequency of seizure attacks, seizure severity scores, and seizure discharges...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29026150/essential-role-of-the-na-ca2-exchanger-ncx-in-glutamate-enhanced-cell-survival-in-cardiac-cells-exposed-to-hypoxia-reoxygenation
#7
Marta Maiolino, Pasqualina Castaldo, Vincenzo Lariccia, Silvia Piccirillo, Salvatore Amoroso, Simona Magi
Myocardial ischemia culminates in ATP production impairment, ionic derangement and cell death. The provision of metabolic substrates during reperfusion significantly increases heart tolerance to ischemia by improving mitochondrial performance. Under normoxia, glutamate contributes to myocardial energy balance as substrate for anaplerotic reactions, and we demonstrated that the Na(+)/Ca(2+) exchanger1 (NCX1) provides functional support for both glutamate uptake and use for ATP synthesis. Here we investigated the role of NCX1 in the potential of glutamate to improve energy metabolism and survival of cardiac cells subjected to hypoxia/reoxygenation (H/R)...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28985560/ferroptosis-a-regulated-cell-death-nexus-linking-metabolism-redox-biology-and-disease
#8
REVIEW
Brent R Stockwell, José Pedro Friedmann Angeli, Hülya Bayir, Ashley I Bush, Marcus Conrad, Scott J Dixon, Simone Fulda, Sergio Gascón, Stavroula K Hatzios, Valerian E Kagan, Kay Noel, Xuejun Jiang, Andreas Linkermann, Maureen E Murphy, Michael Overholtzer, Atsushi Oyagi, Gabriela C Pagnussat, Jason Park, Qitao Ran, Craig S Rosenfeld, Konstantin Salnikow, Daolin Tang, Frank M Torti, Suzy V Torti, Shinya Toyokuni, K A Woerpel, Donna D Zhang
Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28952876/structure-and-characterization-of-a-high-affinity-c5a-monoclonal-antibody-that-blocks-binding-to-c5ar1-and-c5ar2-receptors
#9
Caroline S Colley, Bojana Popovic, Sudharsan Sridharan, Judit E Debreczeni, David Hargeaves, Michael Fung, Ling-Ling An, Bryan Edwards, Joanne Arnold, Elizabeth England, Laura Eghobamien, Ulf Sivars, Liz Flavell, Jonathan Renshaw, Kate Wickson, Paul Warrener, Jingying Zha, Jessica Bonnell, Rob Woods, Trevor Wilkinson, Claire Dobson, Tristan J Vaughan
C5a is a potent anaphylatoxin that modulates inflammation through the C5aR1 and C5aR2 receptors. The molecular interactions between C5a-C5aR1 receptor are well defined, whereas C5a-C5aR2 receptor interactions are poorly understood. Here, we describe the generation of a human antibody, MEDI7814, that neutralizes C5a and C5adesArg binding to the C5aR1 and C5aR2 receptors, without affecting complement-mediated bacterial cell killing. Unlike other anti-C5a mAbs described, this antibody has been shown to inhibit the effects of C5a by blocking C5a binding to both C5aR1 and C5aR2 receptors...
September 27, 2017: MAbs
https://www.readbyqxmd.com/read/28917082/protective-effect-of-salusin-%C3%AE-and-salusin-%C3%AE-against-ethanol-induced-gastric-ulcer-in-rats
#10
Ayhan Tanyeli, Ersen Eraslan, Elif Polat, Tuğba Bal
BACKGROUND: Alcohol consumption has been found to be associated with gastric ulcers, including gastric mucosal lesions. Salusin-α and salusin-β are bioactive peptides having 28 and 20 amino acids, respectively. Salusin-α and salusin-β immunoreactivity has been detected in the stomach and in the intestines. It has been reported that the salusins regulate the cytokine levels and decrease the infarct area in the heart tissue after ischemia. In this study, we investigated the effects of the salusins in the gastric injury formed with ethanol...
November 27, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28889959/metabolic-profiles-revealed-anti-ischemia-reperfusion-injury-of-yangxinshi-tablet-in-rats
#11
Hai Zhang, Yahong Zhao, Zhengxiang Xia, Hongli Du, Yue Gao, Dan Xue, Zhenyu Zhu, Yifeng Chai
ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial ischemia-reperfusion (I/R) injury is a serious injury that is resulted from the recovery of blood supply after myocardial ischemia. Yangxinshi tablet is a compound Chinese herbal preparation and often used to alleviate the myocardial ischemia in clinical, but its protective mechanism of anti-myocardial ischemia reperfusion injury remains unclear. The objective of this study was to evaluate the anti-I/R injury effect of Yangxinshi tablet on a myocardial I/R rat model and to identify serum biomarker metabolites associated with I/R based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomic method, and explore the metabolic mechanism of anti-I/R injury of Yangxinshi tablet...
September 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28852376/bdnf-pro-peptide-a-novel-synaptic-modulator-generated-as-an-n-terminal-fragment-from-the-bdnf-precursor-by-proteolytic-processing
#12
REVIEW
Toshiyuki Mizui, Koji Ohira, Masami Kojima
Most growth factors are initially synthesized as precursors and it was cleaved into bioactive mature domain and pro-domain. However, compared with the expression and function of bioactive mature domain, the biological role of the pro-domain is poorly understood. Unexpectedly, we found that the pro-domain (or pro-peptide) of brain-derived neurotrophic factor (BDNF), which is well-known neurotrophic factor in brain, has a potential ability to facilitate hippocampal long-term depression. Furthermore, a BDNF polymorphism Val66Met, which substitute valine into methionine at 66 amino acid, impacted the biological activity of the BDNF pro-peptide...
July 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28840574/cardioprotection-by-minocycline-in-a-rabbit-model-of-ischemia-reperfusion-injury-detection-of-cell-death-by-in-vivo-111-in-gsao-spect
#13
Takayoshi Yamaki, Hans J de Haas, Nobuhiro Tahara, Artiom Petrov, Dilbahar Mohar, Nezam Haider, Jun Zhou, Atsuko Tahara, Yasuchika Takeishi, Hendrikus H Boersma, Tiziano Scarabelli, Annapoorna Kini, H William Strauss, Jagat Narula
BACKGROUND: Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion. METHODS: Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion...
August 24, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28822163/-mechanism-of-treatment-effect-of-huanglian-huangqin-herb-pairs-on-cerebral-ischemia-rats-based-on-metabolomic-approach
#14
Hui-Ting Cao, Hua-Xu Zhu, Qi-Chun Zhang, Li-Wei Guo
The metabolic effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats was studied by using metabolomic method. The rat model of ischemia reperfusion injury induced by introduction of transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Ultra high performance liquid chromatography-series four pole time of flight mass spectrometry method(UPLC-Q-TOF/MS), Markerlynx software, and principal component analysis and partial least-squares discriminant analysis were used to analyze the different endogenous metabolites among the urine samples of sham rats, cerebral ischemia model rats, Huanglian groups (HL), Huangqin groups (HQ) and Huanglian-Huangqin herb pairs groups (LQ) was achieved, combined with accurate information about the endogenous metabolites level and secondary fragment ions, retrieval and identification of possible biological markers, metabolic pathway which build in MetPA database...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28821850/comparative-metabonomics-of-wenxin-keli-and-verapamil-reveals-differential-roles-of-gluconeogenesis-and-fatty-acid-%C3%AE-oxidation-in-myocardial-injury-protection
#15
Miaomiao Jiang, Qiuying Wang, Jingrui Chen, Yanan Wang, Guanwei Fan, Yan Zhu
Metabonomics/metabolomics is a rapid technology for comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, the application of which has led to understanding pathophysiologic mechanisms of cardiometabolic diseases, defining predictive biomarkers for those diseases, and also assessing the efficacious effects of incident drugs. In this study, proton nuclear magnetic resonance (NMR)-based metabonomics was employed to identify the metabolic changes in rat plasma caused by myocardial ischemia-reperfusion injury (MIRI), and to compare the metabolic regulatory differences between traditional Chinese medicine Wenxin Keli (WXKL) and Western medicine verapamil...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821752/hybrid-nitric-oxide-donor-and-its-carrier-for-the-treatment-of-peripheral-arterial-diseases
#16
Duong Q Le, Aneetta E Kuriakose, Dat X Nguyen, Kytai T Nguyen, Suchismita Acharya
Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28803916/mitigating-ischemic-injury-of-stem-cell-derived-insulin-producing-cells-after-transplant
#17
Gaetano Faleo, Holger A Russ, Steven Wisel, Audrey V Parent, Vinh Nguyen, Gopika G Nair, Jonathan E Freise, Karina E Villanueva, Gregory L Szot, Matthias Hebrok, Qizhi Tang
The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28772228/carbon-dots-based-photoelectrochemical-sensors-for-ultrasensitive-detection-of-glutathione-and-its-applications-in-probing-of-myocardial-infarction
#18
Zhengping Li, Jun Zhang, Yunxiao Li, Shuang Zhao, Peixin Zhang, Yue Zhang, Jinshun Bi, Guohua Liu, Zhao Yue
In this work, photoelectrochemical (PEC) sensors based on carbon dots (CDs) were developed for ultrasensitive detection of glutathione (GSH) without additional catalysts. In this PEC sensing system, CDs exhibited both photoelectric and catalytic properties. Silver nanoparticles (AgNPs), graphene oxide (GO), and mesoporous silica (MS) were introduced in order to enhance the sensing properties of CDs for GSH. Among the different hybrid nanocomposites, CDs@MS based PEC sensors exhibited the best sensing properties: the sensitivity and limit of detection (LOD) for GSH were found to be 57...
July 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28700007/impact-of-dexmedetomidine-on-amino-acid-contents-and-the-cerebral-ultrastructure-of-rats-with-cerebral-ischemia-reperfusion-injury
#19
Sheng Lin, Guangli Zhou, Wei Shao, Zhijian Fu
Purpose: To investigate the effects of dexmedetomidine (DEX) on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury (I/R). Methods: Thirty-six, male, Wistar rats were randomly divided into three groups: the sham operation group (group C), the ischemia-reperfusion group (group I/R), and the DEX group (group D). The middle cerebral artery occlusion model was prepared by the modified Longa method. The time of ischemia was 180 min, and 120 min after reperfusion, the amount of glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain were measured, and the ultrastructure-level changes in the cerebral cortex were examined using electron microscopy...
June 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28699721/comparison-of-pre-and-post-ischemic-treatment-of-telmisartan-and-nimodipine-combination-in-experimentally-induced-cerebral-ischemia
#20
(no author information available yet)
Time dependent intervention plays a crucial role in preventing neurodegeneration after ischemic insult. The intensity of excitotoxicity is greater in the secondary reperfusion phase (2-4 h) compared to the primary occlusion phase (2 h), which could be attributed to secondary elevation of excitatory amino acids (EAA) in cerebral ischemia. In the present study, we tried to assess the neuroprotective effects of telmisartan and nimodipine (TM-NM) combination on the secondary reperfusion phase. The drug treatments were made immediately after reperfusion and their effects were compared with pre-treatment...
September 2016: Indian Journal of Experimental Biology
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