摘要:
Excitatory toxicity is still a hot topic in the study of ischemic stroke, and related research has focused mainly on neurons. Adenosine is an important neuromodulator that is known as a “biosignature” in the central nervous system (CNS). The protective effect of exogenous adenosine on neurons has been confirmed, but its mechanism remains elusive. In this study, astrocytes were pretreated with adenosine, and the effects of an A2a receptor (A2aR) inhibitor (SCH58261) and A2b receptor (A2bR) inhibitor (PSB1115) on excitatory glutamate were investigated. An oxygenglucose deprivation/reoxygenation (OGD/R) and glutamate model was generated invitro. Post-model assessment includedexpression levels of glutamate transporters (glt-1), gap junction protein (Cx43) and glutamate receptor (AMPAR), Na+-K+-ATPase activity, and diffusion distance of dyes. Glutamate and glutamine contents were determined at different time points. The results showed that (1) adenosine could improve the function of Na+-K+-ATPase, upregulate the expression of glt-1, and enhance the synthesis of glutamine in astrocytes. This effect was associated with A2aR activation but not with A2bR activation. (2) Adenosine could inhibit the expression of gap junction protein (Cx43) and reduce glutamate diffusion. Inhibition of A2aR attenuated adenosine inhibition of gap junction intercellular communication (GJIC) in the OGD/R model, while it enhanced adenosine inhibition of GJIC in the glutamate model, depending on the glutamate concentration. (3) Adenosine could cause AMPAR gradually entered the nucleus from the cytoplasm, thereby reducing the expression of AMPAR on the cell membrane. Taken together, the results indicate that adenosine plays a role of anti-excitatory toxicity effect in protection against neuronal death and the functional recovery of ischemic stroke mainly by targeting astrocytes, which are closely related to A2aR. The present study provided a scientific basis for adenosine prevention and ischemic stroke treatment, thereby providing a new approach for alleviating ischemic stroke.
摘要:
BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is a major complication of liver resection or transplantation. However, the mechanism underlying hepatic I/R injury remains obscure. The aim of the present study was to investigate the role of Chemokine-like factor 1 (CKLF1) in hepatic I/R injury. METHODS: Rats were subjected to 70% hepatic ischemia for 90min, followed by 6, 12, 24, 48 and 96h of reperfusion. The expression of CKLF1 was measured by real-time PCR and western blot. The effect of C19, an antagonism peptide of CKLF1, on hepatic I/R injury was investigated. RESULTS: After subjected to 70% hepatic ischemia and reperfusion, the ALT and AST were increased. H&E results showed serious liver damage. The mRNA and protein levels of CKLF1 expression were upregulated during hepatic I/R. Immunohistochemistry staining results showed that neutrophil infiltration was increased in the ischemia lobe. MPO activity was significantly higher post reperfusion. TNF-α and IL-1β were upregulated during hepatic I/R. C19 administration significantly reduced the level of ALT and AST, decreased the necrosis area of liver tissue. Furthermore, C19 treatment inhibited neutrophil infiltration and reduced MPO activity. Meanwhile, C19 decreased the expression of TNF-α and IL-1β. The phosphorylation of P38, JNK were inhibited by C19 treatment. CONCLUSION: CKLF1 was upregulated during hepatic I/R. Inhibiting CKLF1 by C19, an antagonism peptide of CKLF1, could alleviate hepatic I/R injury, reduce neutrophil infiltration, decrease inflammatory response. The protective effect of C19 may related to MAPK signaling pathway.
摘要:
Aims & ScopeThe International Journal of Speech Technology is a research journal that focuses on speech technology and its applications. It promotes research and description on all aspects of speech input and output, including theory, experiment, testing, base technology, applications. The journal is an international forum for the dissemination of research related to the applications of speech technology as well as to the technology itself as it relates to real-world applications. Articles describing original work in all aspects of speech technology are included. Sample topics include but are not limited to the following: • applications employing digitized speech, synthesized speech or automatic speech recognition • technological issues of speech input or output • human factors, intelligent interfaces, robust applications • integration of aspects of artificial intelligence and natural language processing• international and local language implementations of speech synthesis and recognition • development of new algorithms• interface description techniques, tools and languages • testing of intelligibility, naturalness and accuracy • computational issues in speech technology • software development tools • the use of speech in multimedia This is the only journal which presents papers on both the base technology and theory as well as all varieties of applications. It encompasses all aspects of the three major technologies: text-to-speech synthesis, automatic speech recognition and stored (digitized) speech.Coverage in the Journals@Ovid database begins with the November 1999 issue.
摘要:
Cinnamomum camphora Chvar. Borneol (CCCB) and Cinnamomum camphora Chvar. Cineol (CCCC) are two different chemical types of C. camphora. The clinical application of these chemical types of CC shows big differences, but sometimes they are confused because of the similarity of morphological features. To identify the two types of CC and to analyze the differences of compositions, their morphological characteristics were investigated by microscopic techniques and the chemical components were determined by GC-MS analysis and GC internal standard method. Distinguishing features of morphological characteristics were the shape, petiol, gland, and smell. Microscopic study of the transverse sections of leaves showed 13 - 15 columns xylem vessel in the leaves of CCCB, 11 - 13 columns xylem vessel, and more obvious and thicker cell walls of fiber cells in the leaves of CCCC. From this research, GC-MS analysis of essential oil of the leaves could provide mainly differential characteristics to distinguish between CCCB and CCCC. The total of 33 compounds were identified in the essential oil of CCCB leaves and the main component was d-borneol (55.11%), while d-borneol in CCCC leaves was not the main component and the amount of d-borneol might be related to the microstructure of gland. L(-)-camphor and d-borneol were quantitatively analyzed by GC with FID detector, using methyl salicylate as the internal standard. Each gram of the total essential oil contains 0.68 g of d-borneol in CCCB, and each gram of the total essential oil contains 0.150 and 0.015 g of L(-)-camphor in CCCB and CCCC, respectively, from Hunan province. Other habitats showed the same trend. This research was aimed to establish a method based on the microscopic, GC-MS, and GC techniques to identify and quantify CCCB and CCCC compositions, for providing scientific data to ensure with accuracy the origin of CCCB and CCCC plant material.
摘要:
OBJECTIVE: To investigate efficacy of Lidan Tang (LDT) on gallstone induced by high fat diet in mice, and to study its underlying mechanism. METHODS: Mice were fed with high fat diet every day and treated with LDT (9.01 times of human clinic dosage). Mice were randomly divided into 6 groups as control group, gallstone model group (high-fat diet), positive control ursodeoxycholic acid (UDCA) group (80 mg.kg(-1).d(-1) i.g.), LDT low dose group (6 kg/d, i.g.), LDT middle dose group (12 kg/d, i.g.), and LDT high dose group (24 kg/d, i. g.). The whole experiment was lasted for 4 weeks. The levels of ALT, AST, LDH, CHO, HDL-C and LDL-C in serum were measured, the pathological sections were observed by hematoxylin-eosin staining, the activities of antioxidant enzymes were measured by kits, and the proteins related to oxidative stress and lipid transport were detected by Western blot analysis. RESULTS: LDT could significantly reduce the contents of ALT and AST in serum and improve the pathological tissue of liver. LDT could significantly reduce the content of MDA and LPO, and increase the level of GSH and GSH-PX in liver tissue. The data of Western blot showed that LDT had antioxidant effect promoting Keap1/Nrf2 pathway and regulated the process of lipid transport, which was statistically significant. In addition, LDT treatment inhibited the expression of ATP-binding cassette transports ABCG5/8 in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. CONCLUSION: LDT has protective effect on gallstones induced by high fat diet in mice, which might be based on the protective effect on liver, including enhancing the antioxidant capacity of liver and reducing the production of lipid peroxides. (C) 2020 JTCM. All rights reserved.
作者机构:
湖南中医药大学药学院,湖南 长沙 410208;中国医学科学院药物研究所神经科学中心,天然药物活性物质与功能国家重点实验室,北京 100050;[张钊; 楚世峰] State Key Lab of Bioaclive Substances and Functions of Natural Medicine, Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China;[彭也; 陈乃宏] College of Pharmacy, Ниnaп University of Chinese Medicine, Changsha, 410208, China, State Key Lab of Bioaclive Substances and Functions of Natural Medicine, Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China
摘要:
Ginseng has been traditionally used to treat diabetes mellitus (DM) in China. Ginsenoside Rg1 is a major active ingredient in processed ginseng, which elicits proven biological and pharmacological effects. Although a correlation between nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and predisposition to type 1 diabetes mellitus (T1DM) has been identified, the mechanism underlying the potential function and activation of NLRP3 inflammasome in DM have not been elucidated to date. The present study aimed to elucidate the effects and underlying mechanism of Rg1 on streptozotocin (STZ)-induced T1DM in mice through short or long-term observation. Concurrently, we intended to explore the relationships between inflammasome, pyroptosis and oxidative stress and the role of NLRP3 and Keap1/Nrf2/HO-1 pathways in the development and progression of DM. Using ELISA and Western blot analysis, we found that Rg1 attenuated abnormally elevated blood glucose, reduced inflammatory factors IL-1beta and IL-18 in the blood, decreased ALT and AST levels, promoted insulin secretion, and weakened the function of NLRP3 in mouse liver and pancreas. In addition, Rg1 protected against STZ-induced reactive oxygen species-mediated inflammation by upregulating Nrf2/ARE pathway, which further activated antioxidant enzymes. Interestingly, Rg1 also regulated H3K9 methylation in liver and pancreas, as detected by immunohistochemistry. In summary, these data provide new understanding about the mechanism of Rg1 action, suggesting that it is a potential drug applied for preventing the occurrence and development of T1DM.
作者机构:
[Wang, Zhen-Zhen; Lou, Yu-Xia; Jin, Can; Chen, Nai-Hong; Xia, Cong-Yuan; Chu, Shi-Feng] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China.;[Wang, Zhen-Zhen; Lou, Yu-Xia; Jin, Can; Chen, Nai-Hong; Xia, Cong-Yuan; Chu, Shi-Feng] Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, Beijing 100050, Peoples R China.;[Wang, Zhen-Zhen] Yantai Univ, Key Lab Mol Pharmacol & Drug Evaluat, Minist Educ, Yantai 264005, Peoples R China.;[Ren, Si-Yu; Chen, Nai-Hong; Wang, Hui-Qin] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Ren, Si-Yu; Chen, Nai-Hong; Wang, Hui-Qin] Hunan Engn Technol Ctr Standardizat & Funct Chine, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Chen, Nai-Hong] C;Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, Beijing 100050, Peoples R China.
摘要:
Our previous studies have shown that ginsenoside Rg1 (Rg1) exerts antidepressant-like effects in animal models of depression, accompanied by an improvement of astrocytic gap junction functions. However, whether connexin 43 (Cx43), the major connexin forming gap junctions between astrocytes, is the key regulator of Rg1-induced antidepressant-like effects is still unknown. In this study, we examine in vitro and in vivo the involvement of Cx43 in the antidepressant effects of Rg1. Corticosterone was used to establish an in vitro rat model of depression. Treatment with Rg1 1 h prior to corticosterone significantly improved the cell viability of astrocytes, which was significantly inhibited by carbenoxolone, a widely used gap junction inhibitor. Moreover, Rg1 treatment significantly ameliorated antidepressant-sensitive behaviours induced by infusion of carbenoxolone or Gap26, a selective inhibitor of Cx43, into the prefrontal cortex of the animals. Rg1 treatment increased the expression of Cx43 compared with Gap26 group. According to these results, the antidepressant-like effects of Rg1 were mainly mediated by Cx43-formed gap junctions.
作者机构:
[Un M.-Y.] Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[王真真] Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China;[王惠芹; 陈乃宏] Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China, Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China
作者机构:
[Chen Nai-Hong; Feng Ju-Ling] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.;[Wang Zhen-Zhen; Chen Nai-Hong] Peking Union Med Coll, Neurosci Ctr, Inst Mat Med, Beijing 100050, Peoples R China.;[Wang Zhen-Zhen; Chen Nai-Hong] Chinese Acad Med Sci, Beijing 100050, Peoples R China.;[Feng Ju-Ling] Univ South China, Hengyang Med Coll, Res Lab Translat Med, Hengyang 421001, Peoples R China.;[Zhao Lei] Univ South China, Affiliated Hosp 1, Dept Gastrointestinal Surg, Hengyang 421001, Peoples R China.
通讯机构:
[Chen Nai-Hong] H;[Chen Nai-Hong] P;Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.;Peking Union Med Coll, Neurosci Ctr, Inst Mat Med, Beijing 100050, Peoples R China.
摘要:
Ginseng has been used as a well-known traditional Chinese medicine since ancient times. Ginsenosides as its main active constituents possess a broad scope of pharmacological properties including stimulating immune function, enhancing cardiovascular health, increasing resistance to stress, improving memory and learning, developing social functioning and mental health in normal persons, and chemotherapy. Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides from Panax ginseng. When applied to cancer treatment, Rh2 not only exhibits the anti-proliferation, anti-invasion, anti-metastasis, induction of cell cycle arrest, promotion of differentiation, and reversal of multi-drug resistance activities against multiple tumor cells, but also alleviates the side effects after chemotherapy or radiotherapy. In the past decades, nearly 200 studies on Rh2 in the treatment of cancer have been published, however no specific reviews have been conducted by now. So the purpose of this review is to provide a systematic summary and analysis of the anticancer effects and the potential mechanisms of Rh2 extracted from Ginseng then give a future prospects about it. In the end of this paper the metabolism and derivatives of Rh2 also have been documented. (C) 2020 Elsevier Masson SAS. All rights reserved.