期刊文献+
共找到178篇文章
< 1 2 9 >
每页显示 20 50 100
大麻素1型受体参与疼痛调节机制的研究进展 被引量:1
1
作者 周婷 李文娟 +2 位作者 刘荣鑫 张杰 薛建军 《临床麻醉学杂志》 CAS CSCD 北大核心 2024年第6期648-651,共4页
大麻素1型受体(CB1R)是近年来研究较为广泛的内源性大麻素受体之一,在中枢和外周神经系统均有表达。CB1R位于突触前膜,通过逆行抑制性突触传递调节神经递质的释放,是治疗疼痛的有效靶点。激活CB1R对伤害性、病理性和炎性疼痛均具有镇痛... 大麻素1型受体(CB1R)是近年来研究较为广泛的内源性大麻素受体之一,在中枢和外周神经系统均有表达。CB1R位于突触前膜,通过逆行抑制性突触传递调节神经递质的释放,是治疗疼痛的有效靶点。激活CB1R对伤害性、病理性和炎性疼痛均具有镇痛效应,拮抗CB1R可引起疼痛敏化。本文通过对CB1R结构功能、信号转导、镇痛机制方面进行综述,为进一步了解疼痛的病理生理学机制及探索更优疼痛治疗方法提供参考。 展开更多
关键词 大麻素1型受体 疼痛 镇痛机制 内源性大麻素
下载PDF
Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma 被引量:3
2
作者 Yan-Yu Wang Xu Yang +12 位作者 Yun-Chao Wang Jun-Yu Long Hui-Shan Sun Yi-Ran Li Zi-Yu Xun Nan Zhang Jing-Nan Xue Cong Ning Jun-Wei Zhang Cheng-Pei Zhu Long-Hao Zhang Xiao-Bo Yang Hai-Tao Zhao 《World Journal of Gastroenterology》 SCIE CAS 2023年第10期1614-1626,共13页
BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibito... BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC. 展开更多
关键词 Lenvatinib Programmed death receptor-1 inhibitor IMMUNOTHERAPY Hepatocellular carcinoma Transarterial chemoembolization Combination therapy
下载PDF
Role of Cannabinoid CB1 Receptor in Object Recognition Memory Impairment in Chronically Rapid Eye Movement Sleep-deprived Rats
3
作者 Kaveh Shahveisi Seyedeh Marziyeh Hadi +1 位作者 Hamed Ghazvini Mehdi Khodamoradi 《Chinese Medical Sciences Journal》 CAS CSCD 2023年第1期29-37,共9页
Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals ... Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique.The CB1R antagonist rimonabant(1 or 3 mg/kg,i.p.)was administered either at one hour prior to the sample phase for acquisition,or immediately after the sample phase for consolidation,or at one hour before the test phase for retrieval of NOR memory.For the reconsolidation task,rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition,consolidation,and retrieval,but it did not affect the reconsolidation of NOR memory.Rimonabant administration did not affect acquisition,consolidation,and reconsolidation;however,it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings,along with our previous report,would seem to suggest that RSD may affect different phases of recognition memory based on its duration.Importantly,it seems that the CB1R may,at least in part,be involved in the adverse effects of chronic RSD on the retrieval,but not in the acquisition,consolidation,and reconsolidation,of NOR memory. 展开更多
关键词 REM sleep deprivation novel object recognition memory cannabinoid CB1 receptor RIMONABANT
下载PDF
Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway
4
作者 Chenxi Zhao Tiangang Zhou +9 位作者 Ming Li Jie Liu Xiaoqing Zhao Yilin Pang Xinjie Liu Jiawei Zhang Lei Ma Wenxiang Li Xue Yao Shiqing Feng 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期434-439,共6页
Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we... Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury. 展开更多
关键词 ARGATROBAN ASTROGLIOSIS JAK/STAT signaling pathway protease-activated receptor-1 spinal cord injury THROMBIN vimentin
下载PDF
Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK 被引量:5
5
作者 Ya-Jing Feng Yong-Yu Li +2 位作者 Xu-Hong Lin Kun Li Ming-Hua Cao 《World Journal of Gastroenterology》 SCIE CAS 2016年第43期9515-9524,共10页
AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid(CB) receptors, WIN55-212-2(WIN55), in mice with experimental colitis, so as to supply experimental evidence for ... AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid(CB) receptors, WIN55-212-2(WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals' water supply with 4% dextran sulfate sodium(DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha(TNF-α) and interleukin-6(IL-6), and the myeloperoxidase(MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase(p38MAPK) and its phosphorylated form(p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580(SB), an inhibitor of p38, was investigated in parallel experiments, andthe data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38 MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38 MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38 MAPK signaling pathway and the endogenous CB system. 展开更多
关键词 Inflammatory bowel disease Endogenous cannabinoid system P38MAPK Experimental colitis CLAUDIN-1
下载PDF
Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway 被引量:1
6
作者 Cintia Folgueira Silvia Barja-Fernandez +13 位作者 Laura Prado Omar Al-Massadi Cecilia Castelao Veronica Pena-Leon Patricia Gonzalez-Saenz Javier Baltar Ivan Baamonde Rosaura Leis Carlos Dieguez Uberto Pagotto Felipe F Casanueva Sulay A Tovar Ruben Nogueiras Luisa M Seoane 《World Journal of Gastroenterology》 SCIE CAS 2017年第35期6403-6411,共9页
AIM To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular m TOR pathway in the stomach.METHODS Sprague Dawley rats were treated with vehicle, rimonabant, rapa... AIM To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular m TOR pathway in the stomach.METHODS Sprague Dawley rats were treated with vehicle, rimonabant, rapamycin or rapamycin+rimonabant. Gastric tissue obtained from the animals was used for biochemical assays: Nucb2 m RNA measurement by real time PCR, gastric Nucb2/nesfatin protein content by western blot, and gastric explants to obtain gastric secretomes. Nucb2/nesfatin levels were measured in gastric secretomes and plasma using enzyme-linked immunosorbent assay. RESULTS The inhibition of cannabinoid receptor 1(CB1) by the peripheral injection of an inverse agonist, namely rimonabant, decreases food intake and increases the gastric secretion and circulating levels of Nucb2/nesfatin-1. In addition, rimonabant treatment activates m TOR pathway in the stomach as showed by the increase in pm TOR/m TOR expression in gastric tissue obtained from rimonabant treated animals. These effects were confirmed by the use of a CB1 antagonist, AM281. When the intracellular pathway m TOR/S6 k was inactivated by chronic treatment with rapamycin, rimonabant treatment was no longer able to stimulate the gastric secretion of Nucb2/nesfatin-1.CONCLUSION The peripheral cannabinoid system regulates food intake through a mechanism that implies gastric production and release of Nucb2/Nesfatin-1, which is mediated by the m TOR/S6 k pathway. 展开更多
关键词 NUCB2/nesfatin-1 STOMACH Food INTAKE cannabinoid receptor 1 mTOR
下载PDF
Gasdermin D-mediated hepatocyte pyroptosis expands inflammatory responses that aggravate acute liver failure by upregulating monocyte chemotactic protein 1/CC chemokine receptor-2 to recruit macrophages 被引量:15
7
作者 Hong Li Xue-Ke Zhao +9 位作者 Yi-Ju Cheng Quan Zhang Jun Wu Shuang Lu Wei Zhang Yang Liu Ming-Yu Zhou Ya Wang Jing Yang Ming-Liang Cheng 《World Journal of Gastroenterology》 SCIE CAS 2019年第44期6527-6540,共14页
BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its me... BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF. 展开更多
关键词 Gasdermin D HEPATOCYTE PYROPTOSIS Acute liver failure MONOCYTE chemotactic PROTEIN 1/CC chemokine receptor-2
下载PDF
Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1 in Human Meningiomas 被引量:2
8
作者 易伟 陈坚 +1 位作者 Filimon H. Golwa 薛德麟 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第1期75-77,共3页
The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features an... The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor. 展开更多
关键词 MENINGIOMAS basic fibroblast growth factor fibroblast growth factor receptor-1 microvascular density IMMUNOHISTOCHEMISTRY
下载PDF
Sleeve gastrectomy prevents lipoprotein receptor-1 expression in aortas of obese rats 被引量:1
9
作者 Jie Bai Yong Wang Yuan Liu Dong-Hua Geng Jin-Gang Liu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第32期3739-3744,共6页
AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomi... AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomized into three groups: normal chow (control), high fat diet (HD) and high fat diet with sleeve gastrectomy (SG). After surgery, the HD and SG groups were fed a high fat diet. Animals were sacrificed and plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) levels were determined. LOX-1 protein and LOX-1 mRNA expression was also measured. Aortas were stained with Nile red to visualize adipose tissue. RESULT: Body weights were higher in the HD group compared to the other groups. HDL levels in control,HD, and SG groups were 32.9 ± 6.2 mg/dL, 43.4 ± 4.0 mg/dL and 37.5 ± 4.3 mg/dL, respectively. LDL levels in control, HD, and SG groups were 31.8 ± 4.5 mg/dL, 53.3 ± 5.1 mg/dL and 40.5 ± 3.7 mg/dL, respectively. LOX-1 protein and LOX-1 mRNA expression was greater in the HD group versus the other groups. Staining for adipose tissue in aortas was greater in the HD group in comparison to the other groups. Thus, a high fat diet elevates LOX-1 protein and mRNA expression in aorta. CONCLUSION: Sleeve gastrectomy decreases plasma LDL levels, and downregulates LOX-1 protein and mRNA expression. 展开更多
关键词 Sleeve gastrectomy Morbid obesity High fat diet AORTA Lipoprotein receptor-1 expression
下载PDF
Significance of 125I radioactive seed implantation on growth differentiation factor and programmed death receptor-1 during treatment of oral cancer 被引量:4
10
作者 Gang Xue Yao Feng Jia-Bin Li 《World Journal of Clinical Cases》 SCIE 2020年第5期874-886,共13页
BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and... BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment. 展开更多
关键词 125I radioactive seeds Oral cancer Growth differentiation factor 11 Programmed death receptor-1 Prognosis RECURRENCE
下载PDF
Expression of triggering receptor-1 in myeloid cells of mice with acute lung injury 被引量:1
11
作者 Ning Liu Qin Gu Yi-shan Zheng 《World Journal of Emergency Medicine》 SCIE CAS 2010年第2期144-148,共5页
BACKGROUND: Myeloid cell (TREM-1) is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury (ALl) by intraperitoneal injection of lipo... BACKGROUND: Myeloid cell (TREM-1) is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury (ALl) by intraperitoneal injection of lipopolysaccharide (LPS) was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS: Thirty BALB/C mice were randomly divided into a normal control group (n=6) and an ALl group (n=24). The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS: The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA (P=0.14); the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score (r=0.795, P=0.001 :r=0.499, P=0.034), but not with the expression of TREM-1 mRNA (P=0.176).CONCLUSION: The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation. 展开更多
关键词 Acute lung injury Triggering receptor-1 Myeloid cell EXPRESSION Tumor necrosisfactor Pathological scoring
下载PDF
LOTUS, a potent blocker of Nogo receptor-1 causing inhibition of axonal growth 被引量:1
12
作者 Yuji Kurihara Kohtaro Takei 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第1期46-48,共3页
Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system (CNS). Nogo proteins, myelin-as- sociated glycoprotein (MAG), oligodendrocyte myelin gl... Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system (CNS). Nogo proteins, myelin-as- sociated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and B lymphocyte stimulator (BLyS), are 4 inhibitors that commonly interact with the neuronal receptor, Nogo receptor-1 (NgR1), lead- ing to inhibition of axonal growth. Here, we demon- strate that lateral olfactory tract usher substance (LOTUS) binds to NgR1 and blocks the binding of all four ligands to NgR1, resulting in the suppression of axonal growth inhibition induced by these NgR1 li- gands. LOTUS allows neurons to overcome NgRl-me- diated axonal growth inhibition, raising the possibility that LOTUS may be useful in future therapeutic ap- proaches as an endogenous potent inhibitor of NgR1 for promoting neuronal regeneration. 展开更多
关键词 OMgp MAG a potent blocker of Nogo receptor-1 causing inhibition of axonal growth LOTUS
下载PDF
Pharmacological characterizationof synthetic cannabinoid MAM-2201:radioligand binding and abuse-related effects
13
作者 William E FANTEGROSSI Aaron JANOWSKY +8 位作者 Amy J ESHLEMAN Lauren N RUSSELL Saki FUKUDA Jyoti GOGOI Cassandra PRIOLEAU Ambuja S BALE Srihari R TELLA Merle G PAULE Takato HIRANITA 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2017年第10期1016-1017,共2页
OBJECTIVE Over 30% of all new psychoactive substances identified by the UN Office on Drugs and Crime in 2016 were synthetic cannabinoids.The recent emergence of MAM-2201 on the illicit market is troubling because this... OBJECTIVE Over 30% of all new psychoactive substances identified by the UN Office on Drugs and Crime in 2016 were synthetic cannabinoids.The recent emergence of MAM-2201 on the illicit market is troubling because this drug has no precedent in either the scientific or patent literature,and appears to be a novel compound developed specifically as a "graymarket" drug of abuse bystructurally combining the known synthetic cannabinoids JWH-122 and AM-2201.There is currently no published information regarding the pharmacology of MAM-2201.METHODS The present studies characterized cannabinoid-like effects of MAM-2201 in vitro(interactions with cannabinoid type 1 receptors[CB1 Rs]) and in vivo(in mice and rats).RESULTS In a radioligand binding assay using [3 H]CP55,940 in HEK cell membranes transfected with the CB1 R,MAM-2201(K i=5.4 nmol·L^(-1)),had higher binding affinity than WIN 55,212-2(K i=80 nmol·L^(-1)),and D9-THC(K i=8.3 nmol·L^(-1)).The E max values for MAM-2201 and WIN 55,212-2 in an assay of agonist inhibition of forskolin-stimulated c AMP were 85%(EC50=0.45 nmol·L^(-1)) and 95%,respectively,as compared with the D9-THC E max of 74%.In mice,MAM-2201(0.003-1.0 mg·kg^(-1),IP) produced dose-dependent cannabimimetic effects which were both more potent and more effective than those of D9-THC.MAM-2201 and D9-THC dose-dependently produced hypothermia:ED50=0.287 and 25.4 mg·kg^(-1),analgesia:ED50=0.125 and 29.4 mg·kg^(-1),and catalepsy:ED50=0.301 and18.9 mg·kg^(-1) in adult male CD1 mice.Importantly,MAM-2201 also elicited convulsant effects at a dose of 1.0 mg·kg^(-1) in 8/8 murine subjects.In rats,MAM-2201 produced dose-dependent D9-THC-like interoceptive effects in subjects trained to discriminate 3.0 mg·kg^(-1)(IP) D9-THC from saline.CONCLUSION MAM-2201 binds CB1 Rs with high affinity and agonist efficacy,and functions as a potent cannabinoid agonist in vivo across several complementary measures of cannabinoid activity in two rodent species. 展开更多
关键词 cannabinoid CB1 receptor behavior abuse liability
下载PDF
CB1R拮抗剂对MPTP诱导PD小鼠运动行为影响 被引量:1
14
作者 张腾元 商晓钰 +1 位作者 谢俊霞 徐华敏 《青岛大学学报(医学版)》 CAS 2023年第3期357-360,共4页
目的研究大麻素受体1(CB1R)拮抗剂NESS 0327对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠运动行为的影响。方法将24只8周龄C57BL/6J雄性小鼠随机分为对照组、MPTP组和MPTP+NESS 0327组。对照组和MPTP组小鼠均双侧黑... 目的研究大麻素受体1(CB1R)拮抗剂NESS 0327对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠运动行为的影响。方法将24只8周龄C57BL/6J雄性小鼠随机分为对照组、MPTP组和MPTP+NESS 0327组。对照组和MPTP组小鼠均双侧黑质致密部(SNpc)微量注射二甲基亚砜(DMSO)和Tween-80混合溶液,分别腹腔注射生理盐水和MPTP;MPTP+NESS 0327组小鼠则双侧SNpc微量注射NESS 0327,腹腔注射MPTP。小鼠连续5 d给药后进行旷场实验和爬杆实验检测小鼠运动能力的改变。结果旷场实验结果显示,3组小鼠总移动距离比较差异具有统计学意义(F=8.279,P<0.01),其中MPTP组小鼠总移动距离较对照组小鼠显著减少(q=5.705,P<0.01),MPTP+NESS 0327组小鼠总移动距离较MPTP组小鼠显著增加(q=3.504,P<0.05)。爬杆实验结果显示,3组小鼠下杆时间比较差异具有统计学意义(F=12.110,P<0.01),其中MPTP组小鼠下杆时间较对照组小鼠显著增加(q=6.790,P<0.01),MPTP+NESS 0327组小鼠的下杆时间较MPTP组小鼠显著减少(q=4.713,P<0.01)。结论SNpc给予CB1R拮抗剂NESS 0327可改善MPTP诱导的PD小鼠运动功能障碍。 展开更多
关键词 大麻素受体拮抗剂 帕金森病 1-甲基-4-苯基-1 2 3 6-四氢吡啶 密部 运动活动 小鼠
下载PDF
Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression
15
作者 Gonglin Hou Mingming Tang 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第13期1010-1016,共7页
There is evidence that the expression of members of the fibroblast growth factor (FGF) protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined w... There is evidence that the expression of members of the fibroblast growth factor (FGF) protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 (FGF2) and fibroblast growth factor receptor-1 (FGFR1) protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression. 展开更多
关键词 DEPRESSION HIPPOCAMPUS fibroblast growth factor-2 fibroblast growth factor receptor-1 neural regeneration
下载PDF
Novel Method for Synthesis of Diarylpyrazole Derivatives as Cannabinoid CB_1 Receptor Antagonists
16
作者 WU Ying-qiu ZHENG Guo-jun +2 位作者 WANG Ya-ping WANG Xiang-jing XIANG Wen-sheng 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2011年第1期66-69,共4页
A novel and efficient method was developed for the synthesis of diarylpyrazole derivatives as cannabinoid CB1 receptor antagonist via four step reactions. The key step was the synthesis of a diarylpyrazole skeleton, w... A novel and efficient method was developed for the synthesis of diarylpyrazole derivatives as cannabinoid CB1 receptor antagonist via four step reactions. The key step was the synthesis of a diarylpyrazole skeleton, which involved initial condensation of the sodium salt of compound 12 with diazonium compounds, and further cyclization by heating at reflux in acetic acid. Eight diarylpyrazole derivatives and nine new synthesized compounds were characterized by 1H NMR, IR, MS, and elemental analysis. The reaction conditions were mild and the overall yields of the target compounds ranged from 26% to 44%. 展开更多
关键词 cannabinoid CB1 receptor antagonist Diarylpyrazole derivative SR141716
下载PDF
Metabolic and inflammatory functions of cannabinoid receptor type 1 are differentially modulated by adiponectin
17
作者 Qiong Wei Jong Han Lee +4 位作者 Chia-Shan Wu Qun S Zang Shaodong Guo Hui-Chen Lu Yuxiang Sun 《World Journal of Diabetes》 SCIE 2021年第10期1750-1764,共15页
BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the ... BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the mediators of CB1 actions are not well defined.AIM To investigate whether the beneficial effects of CB1 inhibition are,at least in part,mediated by adiponectin.METHODS We compared metabolic and inflammatory phenotypes of wild-type(WT)mice,CB1-null(CB1^(-/-))and CB1/adiponectin double-knockout(DKO)mice.We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test,and inflammation using flow cytometry analysis of macrophages.RESULTS CB1^(-/-)mice exhibited significantly reduced body weight and fat mass when compared to WT mice.While no significance was found in total daily food intake and locomotor activity,CB1^(-/-)mice showed increased energy expenditure,enhanced thermogenesis in brown adipose tissue(BAT),and improved insulin sensitivity compared to WT mice.DKO showed no difference in body weight,adiposity,nor insulin sensitivity;only showed a modestly elevated thermogenesis in BAT compared to CB1^(-/-)mice.The metabolic phenotype of DKO is largely similar to CB1^(-/-)mice,suggesting that adiponectin is not a key mediator of the metabolic effects of CB1.Interestingly,CB1^(-/-)mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice;in contrast,DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^(-/-)mice,suggesting that adiponectin is an important mediator of the inflammatory effect of CB1.CONCLUSION Our findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms:CB1 regulates energy metabolism in an adiponectin-independent manner,and inflammation in an adiponectin-dependent manner.The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be taken into consideration in CB1 antagonist utilization. 展开更多
关键词 cannabinoid type 1 receptor ADIPONECTIN THERMOGENESIS MACROPHAGES Inflammation Insulin resistance
下载PDF
Distribution and Possible Function of Cannabinoid Receptor Subtype 1 in the Human Prostate
18
作者 Manabu Kamiyama Mizuya Fukasawa +5 位作者 Yoshio Takihana Norifumi Sawada Hiroshi Nakagomi Mitsuharu Yoshiyama Isao Araki Masayuki Takeda 《Open Journal of Urology》 2013年第2期102-109,共8页
Background: Cannabinoid receptor subtype 1 (CB1) has a relationship to the proliferation of various cells including malignant tumoral cells. We investigated and compared the expression of CB1 in benign and malignant h... Background: Cannabinoid receptor subtype 1 (CB1) has a relationship to the proliferation of various cells including malignant tumoral cells. We investigated and compared the expression of CB1 in benign and malignant human prostate tissues and in benign and malignant human prostate cell lines, as well as its function for the proliferation of human prostate cancer cells. Methods: Real-time quantitative PCR was performed to compare its expressions in human prostate tissues (normal, benign hyperplasia, and cancer) and prostate cell lines (3 normal and 3 malignant). For localization of CB1, immunofluorescent staining with rabbit anti-CB1 polyclonal antibodies and tetramethyl isothiocyanate (TRITC)-labeled swine anti-rabbit immunoglobulin (DAKO) were used under fluorescence microscope. To further analyze whether cell death was induced by anandamide (non-selective agonist for CB1/CB2) via a receptor dependent mechanism, the viability of DU145 cells, which is known as androgen-insensitive prostate cancer cell, was measured using MTT assay. Results: CB1mRNA was found to be expressed in the all 3 human prostate tissues, however, CB1 protein was expressed in BPH and low grade malignant PC tissues, but not in high grade malignant PC tissues. CB1 as for cell lines, the expression of CB1 was low in malignant cell lines except for DU145. Anandamide elicited cell death, which was significantly inhibited by AM251 (selective antagonist for CB1), indicating that cell death induced by anandamide in DU145 cells was mediated by CB1. Anandamide time-dependently elicits up-regulation of CB1 in DU145 cells. Conclusions: CB1 may be an inhibitory regulator of androgen-insensitive human prostate cancer epithelial cell growth. 展开更多
关键词 PROSTATE CANCER PROSTATE Cell cannabinoid RECEPTOR CB1
下载PDF
缴获电子烟油样品中75种合成大麻素的^(1)H qNMR定量分析研究 被引量:3
19
作者 刘翠梅 贾薇 +1 位作者 宋春辉 花镇东 《分析测试学报》 CAS CSCD 北大核心 2023年第5期605-613,共9页
通过考察75种合成大麻素(SCRAs)的关键定量参数,首次建立了可用于电子烟油样品中75种SCRAs定量分析的核磁共振氢谱定量分析方法(^(1)H qNMR)。以1,3,5-三甲氧基苯为内标,将烟油样品经氘代甲醇稀释后直接进行分析。方法的定量下限为0.03%... 通过考察75种合成大麻素(SCRAs)的关键定量参数,首次建立了可用于电子烟油样品中75种SCRAs定量分析的核磁共振氢谱定量分析方法(^(1)H qNMR)。以1,3,5-三甲氧基苯为内标,将烟油样品经氘代甲醇稀释后直接进行分析。方法的定量下限为0.03%(质量分数),日内相对标准偏差(RSD)小于0.90%,日间RSD小于1.5%,基质加标回收率为93.3%~100%。采用1H qNMR法对19份缴获烟油样品中的4种合成大麻素3,3-二甲基-2-[1-(5-氟戊基)吲唑-3-甲酰氨基]丁酸甲酯(5F-ADB)、2-[1-(5-氟戊基)-1H-吲哚-3-甲酰氨基]-3,3-二甲基丁酸甲酯(5F-MDMB-PICA)、2-[1-(4-氟丁基)-1H-吲唑-3-甲酰氨基]-3,3-二甲基丁酸甲酯(4FMDMB-BUTINACA)、N-(1-氨基-3,3-二甲基-1-氧代丁-2-基)-1-丁基-1H-吲唑-3-甲酰胺(ADB-BUTINACA)进行定量分析,得到其含量范围为0.072%~2.056%。19份烟油样品的^(1)H qNMR定量结果与高效液相色谱法定量结果无显著性差异。该研究所建立的电子烟油中SCRAs的定量分析^(1)H qNMR法无需标准物质,操作简单,定量结果准确,解决了缺乏标准物质时复杂基质中SCRAs定量分析的难题。目前国内外尚未有采用^(1)H qNMR对电子烟油中75种SCRAs定量分析的报道。该研究进一步拓宽了^(1)H qNMR技术在禁毒领域的应用范围,为复杂基质中毒品和新精神活性物质的定量分析提供了新的思路。 展开更多
关键词 电子烟油 新精神活性物质(NPS) 合成大麻素 核磁共振氢谱定量分析
下载PDF
Expression of DRD1 mRNA after Spinal Cord Injury Induced Spasticity in Rats
20
作者 Ying CHEN Xiang ZHANG +1 位作者 Xin MENG Liqun REN 《Medicinal Plant》 CAS 2023年第3期54-56,共3页
[Objectives]To investigate the spasticity of rat tail and the expression of dopamine receptor-1(DRD1)mRNA in the spinal cord after spinal cord injury(SCI)induced tail spasticity in rats.[Methods]Adult male Wistar rats... [Objectives]To investigate the spasticity of rat tail and the expression of dopamine receptor-1(DRD1)mRNA in the spinal cord after spinal cord injury(SCI)induced tail spasticity in rats.[Methods]Adult male Wistar rats were randomly divided into Sham group and SCI group.The second sacral spinal cord(S2)segment of SCI rats was completely transected.60 d after operation,the rat tail spasticity was scored,and then the spinal cord tissues below the level of S2 spinal cord transection were taken.The expression of DRD1 mRNA in the sacrococcygeal spinal cord was detected by qPCR.In addition,3 normal rats were used for DAR/neuronal nuclei(NeuN)and DRD1/choline acetyltransferase(ChAT)immunofluorescence staining to study the distribution of DRD1 in spinal cord and the properties of DRD1 positive cells.[Results]60 d after operation in SCI group,the tail spasticity of rats developed fully,and the symptoms of spasticity were typical.qPCR results showed that the expression of DRD1 mRNA in SCI group was significantly lower than that in Sham group(P<0.05).DRD1 was widely distributed in the dorsal horn,intermediate zone and ventral horn at the sacrococcygeal end of the rat spinal cord.[Conclusions]The decrease of DRD1 mRNA expression after SCI may be related to the occurrence and development of spasticity. 展开更多
关键词 Spinal cord injury SPASTICITY Dopamine receptor-1 Immunofluorescence staining qPCR
下载PDF
上一页 1 2 9 下一页 到第
使用帮助 返回顶部