Objective: To explore the anti-nociceptive effect of patchouli alcohol(PA), the essential oil isolated from Pogostemon cablin(Blanco) Bent, and determine the mechanism in molecular levels. Methods: The acetic acid-ind...Objective: To explore the anti-nociceptive effect of patchouli alcohol(PA), the essential oil isolated from Pogostemon cablin(Blanco) Bent, and determine the mechanism in molecular levels. Methods: The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to con?rm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor(MOR). Cyclooxygenase 2(COX2)and MOR of mouse brain were expressed for determination of PA’s target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. Results: PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution(P<0.01) and allodynia after intra-plantar formalin(P<0.01) in mice. PA also up-regulated COX2 mRNA and protein(P<0.05) with a down-regulation of MOR(P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level(P<0.05) induced by PA may play an important role in its anti-nociceptive effect.PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Conclusions: Both COX2 and MOR are involved in the mechanism of PA’s anti-nociceptive effect,and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA’s effect on MOR.展开更多
To investigate lymphangiogenesis in tumor tissues and 5' Nase, Flt 4, Flk 1 expressions Methods 5' Nase and Aplase expressions and the morphology of lymphatics in gastric carcinoma tissues were observed...To investigate lymphangiogenesis in tumor tissues and 5' Nase, Flt 4, Flk 1 expressions Methods 5' Nase and Aplase expressions and the morphology of lymphatics in gastric carcinoma tissues were observed with enzyme histochemistry Flt 4 and Flk 1 expression in gastric carcinoma and sarcoma tissues was studied by immunohistochemistry CNE 2z cells were implanted into the subdermal layer of nude mice and hyaluronic acid was injected at the same sites After 4 or 5 weeks, nasopharyngeal carcinoma (NPC) xenograft tissues were cut for immunohistochemistry and enzyme histochemistry, and lymphangiogenesis, 5' Nase, Alpase, Flt 4 and Flk 1 expression in NPC tissues was studied Hyaluronic acid contents in sera of the patients with NPC and mice with NPC xenografts were measured by radioimmunoassay Results There were a lot of lymphatics and solid strip like tissues in gastric carcinoma and NPC xenograft treated with hyaluronic acid The total number of lymphatics (26 9±14 2/HP) increased significantly in gastric carcinoma tissues Flt 4 and Flk 1 positive expression was found in gastric carcinoma, sarcoma tissues and NPC xenograft Most of the vessels with positive Flt 4 were lymphatics Flk 1 expression was only found in the walls of blood vessels Hyaluronic acid content (363 52±98 15?ng/ml) in sera of patients with NPC was higher than that of the patients with chronic nasopharyngeal imflammation (306 29±27 15?ng/ml), with a significant difference ( P =0 039) The hyaluronic acid content in sera of nude mice with NPC (2120 59±490 22?ng/ml) was markedly higher than that in normal mice (1588 99±502 12?ng/ml), with a significant difference between them ( P =0 007) Conclusion There are a lot of lymph capillaries with positive 5' Nase in gastric carcinoma and NPC xenograft treated with hyaluronic acid Flt 4 positive expression is shown in gastric carcinoma, sarcoma tissues and NPC xenografts The results suggest there is lymphangiogenesis in these malignant tumor tissues Hyaluronic acid contents in sera of patients with NPC and nude mice with NPC increase, which may promote the formation of lymphatics展开更多
目的通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中铁死亡相关基因的表达及其与程序性死亡受体配体-1(programmed death ligand-1,PD-L1)和免疫细胞的关系,为D...目的通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中铁死亡相关基因的表达及其与程序性死亡受体配体-1(programmed death ligand-1,PD-L1)和免疫细胞的关系,为DLBCL的治疗提供新的靶标。方法通过TCGA数据库查找获得22个铁死亡相关基因。从TCGA数据库获取48例DLBCL(DLBCL组)及54例反应性淋巴结增生患者(对照组)淋巴结标本的铁死亡相关基因以及PD-L1的表达数据。使用Wilcoxon秩和检验进行组间差异性表达分析。基因表达相关性分析采用Spearman相关性分析。采用R软件包pheatmap分析DLBCL中铁死亡相关基因表达与免疫细胞的相关性。采用R软件GSVA包分析铁死亡相关基因表达与磷脂酰肌醇-3-激酶-蛋白激酶B-哺乳动物雷帕霉素靶蛋白(phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin,PI3K-Akt-mTOR)信号通路的相关性。结果DLBCL中周期素依赖性激酶抑制因子1A(cyclin dependent kinase inhibitor 1A,CDKN1A)、70 kDa热休克蛋白5(heat shock 70 kDa protein 5,HSPA5)、内质膜蛋白复合体亚基2(endoplasmic membrane protein complex subunit 2,EMC2)、溶质载体家族7成员11(solute carrier family 7,member 11,SLC7A11)、金属硫蛋白1G(metallothionein 1G,MT1G)、热休克蛋白B1(heat shock protein B1,HSPB1)、谷胱甘肽过氧化酶4(glutathione peroxidase4,GPX4)、范可尼贫血互补群D2(Fanconi anemia complementary group D2,FANCD2)、柠檬酸合成酶(citrate synthase,CS)、CDGSH铁硫结构域1(CDGSH iron sulfur domain 1,CISD1)、法尼基二磷酸法尼基转移酶1(farnesyl diphosphate farnesyltransferase 1,FDFT1)、SLC1A5、转铁蛋白受体(transferrin receptor,TFRC)、核糖体蛋白L8(ribosomal protein L8,RPL8)、核受体共激活因子4(nuclear receptor coativator 4,NCOA4)、二肽基肽酶Ⅳ(dipeptidyl peptidaseⅣ,DPP4)和花生四烯酸15脂氧合酶(arachidonate-15-lipoxygenase,ALOX15)基因表达均上调(均P<0.05)。免疫细胞相关分析显示,铁死亡相关基因可激活体内巨噬细胞M1(P<0.05)。DLBCL中长链脂酰辅酶A合成酶4(acyl-CoA synthetase long chain family member 4,ACSL4)、CDKN1A、DPP4、EMC2、谷氨酰胺酶2(glutaminase 2,GLS2)、HSPA5、溶血卵磷脂酰基转移酶3(lysophosphatidylcholine acyltransferase 3,LPCAT3)、MT1G、NCOA4、红细胞衍生核因子2样蛋白2(nuclear factor erythroid 2-like-2,NFE2L2)、精脒/精胺N1-乙酰基转移酶1(spermidine/spermine N1-acetyltransferase 1,SAT1)、SLC7A11和TFRC这些铁死亡相关基因的表达均与PD-L1表达呈正相关(均r>0.4,均P<0.05)。铁死亡相关基因LPCAT3、NCOA4和TFRC的表达均与PI3K-AktmTOR通路呈正相关(均r>0.4,均P<0.05)。结论多数铁死亡相关基因在DLBCL组织中高表达,且与PD-L1、免疫浸润及PI3K-Akt-mTOR通路有关。展开更多
基金Supported by the National Natural Science Foundation of China(No.81374006 and No.81073092)the Special Foundation for New Drug Innovation of Tsinghua University(No.20142000077),China
文摘Objective: To explore the anti-nociceptive effect of patchouli alcohol(PA), the essential oil isolated from Pogostemon cablin(Blanco) Bent, and determine the mechanism in molecular levels. Methods: The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to con?rm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor(MOR). Cyclooxygenase 2(COX2)and MOR of mouse brain were expressed for determination of PA’s target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. Results: PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution(P<0.01) and allodynia after intra-plantar formalin(P<0.01) in mice. PA also up-regulated COX2 mRNA and protein(P<0.05) with a down-regulation of MOR(P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level(P<0.05) induced by PA may play an important role in its anti-nociceptive effect.PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Conclusions: Both COX2 and MOR are involved in the mechanism of PA’s anti-nociceptive effect,and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA’s effect on MOR.
基金hisstudywassupportedbygrantsfromtheBureauofPublicHealth Guangdong China !(No 1997337)
文摘To investigate lymphangiogenesis in tumor tissues and 5' Nase, Flt 4, Flk 1 expressions Methods 5' Nase and Aplase expressions and the morphology of lymphatics in gastric carcinoma tissues were observed with enzyme histochemistry Flt 4 and Flk 1 expression in gastric carcinoma and sarcoma tissues was studied by immunohistochemistry CNE 2z cells were implanted into the subdermal layer of nude mice and hyaluronic acid was injected at the same sites After 4 or 5 weeks, nasopharyngeal carcinoma (NPC) xenograft tissues were cut for immunohistochemistry and enzyme histochemistry, and lymphangiogenesis, 5' Nase, Alpase, Flt 4 and Flk 1 expression in NPC tissues was studied Hyaluronic acid contents in sera of the patients with NPC and mice with NPC xenografts were measured by radioimmunoassay Results There were a lot of lymphatics and solid strip like tissues in gastric carcinoma and NPC xenograft treated with hyaluronic acid The total number of lymphatics (26 9±14 2/HP) increased significantly in gastric carcinoma tissues Flt 4 and Flk 1 positive expression was found in gastric carcinoma, sarcoma tissues and NPC xenograft Most of the vessels with positive Flt 4 were lymphatics Flk 1 expression was only found in the walls of blood vessels Hyaluronic acid content (363 52±98 15?ng/ml) in sera of patients with NPC was higher than that of the patients with chronic nasopharyngeal imflammation (306 29±27 15?ng/ml), with a significant difference ( P =0 039) The hyaluronic acid content in sera of nude mice with NPC (2120 59±490 22?ng/ml) was markedly higher than that in normal mice (1588 99±502 12?ng/ml), with a significant difference between them ( P =0 007) Conclusion There are a lot of lymph capillaries with positive 5' Nase in gastric carcinoma and NPC xenograft treated with hyaluronic acid Flt 4 positive expression is shown in gastric carcinoma, sarcoma tissues and NPC xenografts The results suggest there is lymphangiogenesis in these malignant tumor tissues Hyaluronic acid contents in sera of patients with NPC and nude mice with NPC increase, which may promote the formation of lymphatics
