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Elizabeth Messineo, Alonda Pollins, Wesley Thayer
Polyethylene glycol (PEG) is a cell membrane fusogen (de StGroth et al., 1980; Hoehn et al., 1978 [2]; Pontecorvo et al., 1975 [3]). In clinical application PEG allows some axonal fusion in peripheral nerve repairs, resulting in retention of some mobility and sensation during the regeneration process and reducing muscular atrophy. Several manuscripts exist concerning in vivo models of PEG fusion, while there is a distinct lack of in vitro studies. This study optimizes an experimental in vitro PEG fusion procedure in B35 rat neuroblastoma cells, through alteration of PEG and dimethyl sulfoxide (DMSO) concentrations and utilizes flow cytometry for assessment...
February 5, 2019: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Gokhan Arslan, Bahattin Avci, Süleyman Emre Kocacan, Emil Rzayev, Mustafa Ayyildiz, Erdal Agar
Limited information exists on the link between purinergic class P2X7 receptors (P2X7Rs) and calcium ion channels in epilepsy; no data has been reported regarding the interaction between P2X7Rs and T-type calcium ion channels in epilepsy. Thus, this study is an evaluation of the role that T-type calcium ion channels play in the effect of P2X7Rs on penicillin-induced epileptiform activity. In the first set of experiments, P2X7R agonist BzATP (at 25-, 50-, 100- and 200-μg doses), P2X7R antagonist A-438079 (at 5-, 10-, 20- and 40-μg doses) and T-type calcium ion channel antagonist NNC-550396, were administered for electrophysiological analyses 30 min after penicillin injection (2...
January 26, 2019: Neuropharmacology
Peter Illes, Patrizia Rubini, Lumei Huang, Yong Tang
Alzheimer's disease (AD) is a neurodegenerative illness with genetic risk as an etiological factor in a subset of cases. In AD with autosomal dominant inheritance, the extracellular β-amyloid (Aβ) aggregates and intracellular neurofibrillary tangles which consist of hyperphosphorylated tau, appear to be involved in the neuronal damage; however, other forms of AD may have a polygenetic causality. Microglial cells orchestrate pathophysiological events responsible for neuronal damage in AD. They surround Aβ aggregates and the stimulation of microglial P2X7 receptors (P2X7Rs) by high local concentrations of ATP which originates from damaged CNS cells, results in degeneration of nearby neurons...
January 28, 2019: Expert Opinion on Therapeutic Targets
Giorgia Scarpellino, Tullio Genova, Luca Munaron
BACKGROUND: Purinergic signalling is involved in several physiological and pathophysiological processes. P2X7 receptor (P2X7R) is a calcium-permeable ion channel that is gaining interest as a potential therapeutic target for the treatment of different diseases including inflammation, pain, psychiatric disorders and cancer. P2X7R is ubiquitously expressed and sensitive to high ATP levels, usually found in tumor microenvironment. P2X7R regulates several cell functions, from migration to cell death, but its selective contribution to tumor progression remains controversial...
January 16, 2019: Recent Patents on Anti-cancer Drug Discovery
Yinling Chen, Yuanyuan Tang, Xuhui Tong, Jianfeng Wu, Yan Li, Shuying Dong
To investigate the protective effects of P2X7 receptor (P2X7R) inhibitor against cerebral ischemia/reperfusion (I/R) injury in rats and the possible mechanisms.
 Methods: The neurological deficit of rats was evaluated by Longa score. The infarct volume was examined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression levels of extracellular signal-regulated kinase (ERK), phosphorylation extracellular signal-regulated kinas p-ERK), connexin 43 (Cx43), Bax, Bcl-2 and cleaved caspase-3 were detected by Western blot...
November 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Elodie Martin, Majid Amar, Carine Dalle, Ihsen Youssef, Céline Boucher, Caroline Le Duigou, Matthias Brückner, Annick Prigent, Véronique Sazdovitch, Annett Halle, Jean M Kanellopoulos, Bertrand Fontaine, Benoît Delatour, Cécile Delarasse
No abstract text is available yet for this article.
January 2019: Molecular Psychiatry
Xin-Yue Xu, Xiao-Tao He, Jia Wang, Xuan Li, Yu Xia, Yi-Zhou Tan, Fa-Ming Chen
Accumulating evidence indicates that the pluripotency of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions; however, the underlying mechanisms remain largely unexplored. In this study, we hypothesize that the P2X7 receptor (P2X7R) is a key molecule linked to inflammation-associated impairment of PDLSCs. We first investigated P2X7R expression in PDLSCs under normal and inflammatory conditions and then determined the effect of a P2X7R agonist (BzATP) or antagonist (BBG) on PDLSC osteogenesis under various conditions...
January 8, 2019: Cell Death & Disease
Sarah Falk, Camilla Kristine Appel, Heidi Bahrt Bennedbæk, Tamara Al-Dihaissy, Anke Unger, Klaus Dinkel, Anne-Marie Heegaard
The functional role of P2X7 receptor (P2X7R) inhibition in cancer-induced bone pain has been highly contradictory. Whereas knockout studies have suggested pro-nociceptive effects, pharmacological studies suggest anti-nociceptive or no effect. The discrepancy is likely linked to the highly polymorphic nature of the P2X7R and the related functional differences in different tissue and conditions. In this study we tested the analgesic potential of AFC5261, a selective P2X7R antagonist, in a rat model of cancer-induced bone pain to evaluate if the opposing pro- and anti-nociceptive effects could be a consequence of long vs...
December 21, 2018: European Journal of Pharmacology
Wei Wang, Xiongxiong Zhong, Yongyong Li, Ruixian Guo, Sujuan Du, Lili Wen, Yanlu Ying, Tao Yang, Xu-Hong Wei
Chronic postsurgical pain (CPSP) remains a medical problem. Whether the descending modulation of nociceptive transmission from the rostral ventromedial medulla (RVM) plays a role in CPSP induced by skin/muscle incision and retraction (SMIR) in the thigh is still unknown. In the present study, we found that SMIR surgery, which induced either bilateral or unilateral mechanical allodynia, activated microglia, and upregulated interleukin-1β (IL-1β), an important cytokine, and 8-hydroxyguanine (8-OHG), an oxidative stress marker in the RVM...
December 20, 2018: Journal of Neurochemistry
Wen-Yuan Zhang, Yu-Jin Guo, Wen-Xiu Han, Meng-Qi Yang, Lu-Ping Wen, Ke-Yi Wang, Pei Jiang
Increasing evidence suggests that inflammation is related to the pathophysiology of depression. Curcumin (CUR), which is a natural component extracted from the rhizome of Curcuma longa, seems to be efficacious in depression treatment. Hence, the present study aims to explore whether the anti-depressive effect of curcumin is connected to its anti-inflammatory features. Twenty-one SD rats were randomly divided into three groups, namely, control, CUMS (chronic unpredictable mild stress), and CUMS + CUR. After stress exposure for four weeks, the CUMS group showed depressive-like behaviors, and the curcumin treatment successfully corrected the depressive-like behaviors in stressed rats...
December 10, 2018: International Immunopharmacology
K Barth, R Bläsche, A Neißer, S Bramke, J A Frank, M Kasper
Correction to: Histochem Cell Biol (2016).
December 11, 2018: Histochemistry and Cell Biology
Zahra Naseri, Reza Kazemi Oskuee, Mahmoud Reza Jaafari, Mehdi Forouzandeh Moghadam
Background: Exosomes, widely recognized natural nanovesicles, represent one of the recently discovered modes of intercellular communication due to their ability to transmit crucial cellular information that can be engineered to have robust delivery and targeting capacity. MiR-142-3p, one of the upregulated microRNAs (miRNAs) in many types of breast cancer, activates the canonical Wnt signaling pathway and transactivates the miR-150 expression, and results in the hyperproliferation of cancer cells in vitro and mammary glands in vivo...
2018: International Journal of Nanomedicine
Chao Wang, Xiao-Xia Hou, Hong-Liang Rui, Li-Jing Li, Jing Zhao, Min Yang, Li-Jun Sun, Hong-Rui Dong, Hong Cheng, Yi-Pu Chen
Background/Aims: It is known that chronic low-grade inflammation contributes to the initiation and development of both diabetes and diabetic nephropathy (DN), so we designed this study to investigate the role of P2X7R and NLRP3 inflammasome in DN pathogenesis and the antagonistic effects of artificially cultivated Ophiocordyceps sinensis (ACOS). Methods: A rat model of DN caused by high-fat-diet feeding and low-dose streptozotocin injection and a mouse podocyte injury model induced by high-glucose (HG) stimulation were established, and the intervention effects of ACOS on them were observed...
2018: Journal of Diabetes Research
P A F Pacheco, R M S Galvão, A F M Faria, N L Von Ranke, M S Rangel, T M Ribeiro, M L Bello, C R Rodrigues, V F Ferreira, D R da Rocha, R X Faria
Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1β cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake...
November 27, 2018: Bioorganic & Medicinal Chemistry
Xia Li, Quan Jin, Yu Zhang, Yan-Ling Wu, Cheng-Min Jin, Ben-Wen Cui, Ying Li, Ming-Ji Jin, Yue Shang, Min Jiang, Hong-Xu Yang, Mei Wu, Jian Liu, Li-Hua Lian, Ji-Xing Nan
Pleurotus citrinopileatus (golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatus aqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol feeding murine models were established by intragastrically administering ethanol or feeding ethanol-containing Lieber-DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatus decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG) and hepatic TG levels...
November 29, 2018: Journal of Agricultural and Food Chemistry
Wen-Jun Su, Ting Zhang, Chun-Lei Jiang, Wei Wang
Backgrounds: Abundant reports indicate that neuroinflammatory signaling contributes to behavioral complications associated with depression and may be related to treatment response. The glial cells, especially microglia and astrocytes in brain regions of hippocampus and medial prefrontal cortex (mPFC), are major components of CNS innate immunity. Moreover, purinergic receptor P2X, ligand-gated ion channel 7 (P2X7R) was recently reckoned as a pivotal regulator in central immune system. Besides, it was pointed out that clemastine, a first-generation histamine receptor H1 (HRH1) antagonist with considerable safety profile and pharmacological effect, may suppress immune activation through modulating P2X7R...
2018: Frontiers in Cellular Neuroscience
Mingzhang Gao, Min Wang, Barbara E Glick-Wilson, Jill A Meyer, Jonathan S Peters, Paul R Territo, Mark A Green, Gary D Hutchins, Hamideh Zarrinmayeh, Qi-Huang Zheng
The overexpression of P2X7R is associated with neuroinflammation and plays an important role in various neurodegenerative diseases. The [18 F]fluoropropyl derivative of GSK1482160, [18 F]IUR-1602, has been first prepared and examined as a new potential P2X7R radioligand. The reference standard IUR-1602 was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoropropylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 13% in three steps. The target tracer [18 F]IUR-1602 was synthesized from desmethyl-GSK1482160 with 3-[18 F]fluoropropyl tosylate, prepared from propane-1,3-diyl bis(4-methylbenzenesulfonate) and K[18 F]F/Kryptofix2...
November 16, 2018: Applied Radiation and Isotopes
Laura Janks, Cristian V R Sharma, Terrance M Egan
BACKGROUND: The ATP-gated ionotropic P2X7 receptor (P2X7R) has the unusual ability to function as a small cation channel and a trigger for permeabilization of plasmalemmal membranes. In murine microglia, P2X7R-mediated permeabilization is fundamental to microglial activation, proliferation, and IL-1β release. However, the role of the P2X7R in primary adult human microglia is poorly understood. METHODS: We used patch-clamp electrophysiology to record ATP-gated current in cultured primary human microglia; confocal microscopy to measure membrane blebbing; fluorescence microscopy to demonstrate membrane permeabilization, caspase-1 activation, phosphatidylserine translocation, and phagocytosis; and kit-based assays to measure cytokine levels...
November 21, 2018: Journal of Neuroinflammation
Yuchun Zuo, Jikai Wang, Fan Liao, Xiaoxin Yan, Jianming Li, Lei Huang, Fei Liu
Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular disease that usually has a poor prognosis. Heat shock proteins (HSPs) have been implicated in the mechanisms of SAH-associated damage, including increased inflammation and reduced neurogenesis. The aim of this study was to investigate the effects of HSP90 inhibition on inflammation and neurogenesis in a mouse model of experimental SAH induced by endovascular surgery. Western blotting showed HSP90 levels to be decreased, while neurogenesis, evaluated by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry, was decreased in the hippocampuses of SAH mice...
2018: Frontiers in Molecular Neuroscience
Brendan Le Daré, Tatiana Victoni, Aude Bodin, Manuel Vlach, Elise Vene, Pascal Loyer, Vincent Lagente, Thomas Gicquel
Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome, and are involved in many ethanol-related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis and certain cancers)...
November 17, 2018: Fundamental & Clinical Pharmacology
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