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991.
Sascha Münster‐Müller Isabelle Matzenbach Thomas Knepper Ralf Zimmermann Michael Pütz 《Drug testing and analysis》2020,12(1):119-126
Vaping of synthetic cannabinoids via e‐cigarettes is growing in popularity. In the present study, we tentatively identified 12 by‐products found in a pure sample of the synthetic cannabinoid Cumyl‐5F‐PINACA (1‐(5‐fluoropentyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H‐indazole‐3‐carboxamide), a prevalent new psychoactive substance (NPS) in e‐liquids, via high‐resolution mass spectrometry fragmentation experiments (HRMS/MS). Furthermore, we developed a procedure to reproducibly extract this synthetic cannabinoid and related by‐products from an e‐liquid matrix via chloroform and water. The extracts were submitted to flash chromatography (F‐LC) to isolate the by‐products from the main component. The chromatographic impurity signature was subsequently assessed by ultra‐high‐performance liquid chromatography coupled to mass spectrometry (UHPLC–MS) and evaluated by automated integration. The complete sample preparation sequence (F‐LC + UHPLC–MS) was validated by comparing the semi‐quantitative signal integrals of the chromatographic impurity signatures of five self‐made e‐liquids with varying concentrations of Cumyl‐5F‐PINACA [0.1, 0.2, 0.5, 0.7 and 1.0% (w/w)], giving an average relative standard deviation of 6.2% for triplicate measurements of preparations of the same concentration and 10.5% between the measurements of the five preparations with different concentrations. Lastly, the chromatographic signatures of 14 e‐liquid samples containing Cumyl‐5F‐PINACA from police seizures and Internet test purchases were evaluated via hierarchical cluster analysis for potential links. For the e‐liquid samples originating from test purchases, it was found that the date of purchase, the identity of the online shop, and the brand name are the critical factors for clustering of samples. 相似文献
992.
目的探讨糖尿乐胶囊联合地特胰岛素注射液治疗2型糖尿病的临床疗效。方法选取2018年5月-2019年5月在大连市第五人民医院治疗的2型糖尿病患者86例,根据用药的差别分为对照组(43例)和治疗组(43例)。对照组皮下注射地特胰岛素注射液,0.1~0.2 U/kg/次,1次/d;治疗组在对照组基础上口服糖尿乐胶囊,1.2 g/次,3次/d。两组患者均治疗4周。观察两组患者临床疗效,同时比较治疗前后两组患者血糖相关指标、血清学指标、血糖波动情况和氧化应激指标。结果治疗后,对照组和治疗组临床有效率分别为81.40%和97.67%,两组比较差异有统计学意义(P<0.05)。经治疗,两组患者空腹血糖(FBG)、糖化血红蛋白(Hb A1c)、餐后2 h血糖(2 h PG)、胰岛素(FINS)、超敏C反应蛋白(hs-CRP)、γ-谷氨酰转移酶(γ-GT)、人颗粒蛋白前体(PGRN)、瘦素(LP)、血糖标准差(SDBG)、平均血糖波动幅度(MAGE)、24 h血糖波动次数(NGE)、24h血糖平均绝对差(MODD)和丙二醛(MDA)水平均显著下降(P<0.05),而脂联素(APN)、分泌型卷曲相关蛋白5(SFRP5)、谷胱甘肽过氧化物酶(GSH-PX)和超氧化物歧化酶(SOD)水平均显著升高(P<0.05),且治疗组这些指标较对照组改善更明显(P<0.05)。结论地特胰岛素注射液联合糖尿乐胶囊治疗2型糖尿病能够明显效控制血糖,促进机体氧化应激状态的改善。 相似文献
993.
目的 探究七氟醚对急性心肌缺血再灌注(AIRI)模型的老龄大鼠血清5-羟色胺(5-HT)、白介素(IL)-1α、IL-1β和海马组织超氧化物歧化酶(SOD)、丙二醛(MDA)的影响。方法 选取SPF级健康雄性老龄大鼠40只,随机分为5组,建立AIRI模型,模型组给予氧气吸入,七氟醚组分别吸入1%、2%、3%及4%的七氟醚,采用免疫组织化学法检测大鼠心脏组织5-HT、IL-1α、IL-1β的蛋白表达量;ELISA法检测血清5-HT、IL-1α、IL-1β浓度;采用黄嘌呤氧化酶法测定海马组织SOD的活性,硫代巴比妥酸显色法测定海马组织MDA活性;实时荧光定量PCR(RT-qPCR)法检测血清5-HT、IL-1α、IL-1β和海马组织SOD、MDA中mRNA的表达量。结果 与模型组比较,七氟醚2%、3%、4%浓度组心脏组织、血清中5-HT、IL-1α、IL-1β蛋白水平、血清中5-HT、IL-1α、IL-1β mRNA水平显著降低(P<0.05);七氟醚2%、3%、4%浓度组海马组织MDA蛋白及mRNA水平显著降低,SOD蛋白及mRNA水平显著升高(P<0.05)。结论 2%~4%的七氟醚能够显著降低AIRI模型老龄大鼠心脏、血清5-HT、IL-1α、IL-1β表达水平,降低海马组织MDA水平,提高SOD活性。 相似文献
994.
The novel 1,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine framework, a structurally rigidified variant of the 1‐phenylbenzazepine template, was synthesized via direct arylation as a key reaction. Evaluation of the binding affinities of the rigidified compounds across a battery of serotonin, dopamine, and adrenergic receptors indicates that this scaffold unexpectedly has minimal affinity for D1 and other dopamine receptors and is selective for the 5‐HT6 receptor. The affinity of these systems at the 5‐HT6 receptor is significantly influenced by electronic and hydrophobic interactions as well as the enhanced rigidity of the ligands. Molecular docking studies indicate that the reduced D1 receptor affinity of the rigidified compounds may be due in part to weaker H‐bonding interactions between the oxygenated moieties on the compounds and specific receptor residues. Key receptor–ligand H‐bonding interactions, salt bridges, and π–π interactions appear to be responsible for the 5‐HT6 receptor affinity of the compounds. Compounds 10 (6,7‐dimethoxy‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) and 12 (6,7‐dimethoxy‐2‐methyl‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) have been identified as structurally novel, high affinity (Ki = 5 nM), selective 5‐HT6 receptor ligands. 相似文献
995.
Long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is reported to be linked to inflammation and cell apoptosis. However its role in sepsis induced kidney injury remains unclear. This study aims to explore the possible mechanism of CRNDE in kidney injury induced by sepsis. In vivo urine-derived sepsis (US) rat model and in vitro LPS-induced HK-2 and HEK293 cells were established. Kidney function was measured in rats from different groups. Relative levels of tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) in kidney tissue were detected via Enzyme-linked immune sorbent assay (ELISA). Then we up- or down-regulated CRNDE and miRNA-181a-5p expression in the cells. The biological influence of CRNDE and miR-181a-5p on cells was studied using CCK-8 assay and Annexin V assay. Interaction between CRNDE and miR-181a-5p was determined by bioinformatics analysis, RT-PCR, and dual luciferase reporter assay. Peroxisome proliferator-activated receptor-α (PPARα) and cell apoptosis related molecules were detected by western blot. We demonstrated that CRNDE was markedly down-regulated while miR-181a-5p was significantly up-regulated in sepsis models. CRNDE interacted with miR-181a-5p, and negatively regulated its expression level. CRNDE knockdown in rats increased the urea nitrogen and serum creatinine in plasma. Knockdown of CRNDE or transfection of miR-181a-5p significantly inhibited proliferation and promoted apoptosis of HK-2 and HEK293 cells, while overexpression of CRNDE and transfection of miR-181a-5p inhibitors had opposite effects. For mechanism, miR-181a-5p directly targeted the 3′ untranslated region of PPARα, and depressed its protein level, and PPARα was regulated indirectly by CRNDE. We concluded that CRNDE protected renal cell from sepsis-induced injury via miR-181a-5p/PPARα pathway. 相似文献
996.
997.
BackgroundChemokine-like factor 1 (CKLF1) is a chemokine increased significantly in ischemic brain poststroke. It shows chemotaxis effects on various immune cells, but the mechanisms of CKLF1 migrating neutrophils are poorly understood. Recent studies have provided evidence that CC chemokine receptor 5 (CCR5), a receptor of CKLF1, is involved in ischemic stroke.PurposesTo investigate the effects of HIF-1α guided AAV in ischemic brain, investigating the outcome of stroke, and examining the involvement of CKLF1/CCR5 axis in recruitment of neutrophils.ResultsHIF-1α guided AAV knocked down CKLF1 in ischemic area and alleviated brain damage of rats. CKLF1 migrated neutrophils through CCR5, worsening inflammatory responses. Akt/GSK-3β pathway may involve in CKLF1/CCR5 axis guided neutrophils chemotaxis.ConclusionsCKLF1/CCR5 axis is involved in neutrophils migration of rats with transient cerebral ischemia. CKLF1/CCR5 axis may be a useful target for stroke therapy. 相似文献
998.
ObjectiveInflammation and oxidative stress are the major mechanisms implicated in lipopolysaccharide (LPS)-induced AKI. Spina Gleditsiae is a traditional Chinese anti-inflammatory medicine, from which a large number of flavonoids, such as 5-O-methyldihydroquercetin (GS1) and cilicicone B (GS2), were isolated in the present study. Here, we examined the reno-protective effects and potential underlying mechanisms of GS1 and GS2 in mice with LPS-induced AKI.MethodsWe analyzed renal function; the serum metabolic profile, inflammatory cytokine levels, peripheral white blood cell count, renal cell apoptosis, renal oxidant and antioxidant levels, and renal expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), TIR-domain-containing adapter-inducing interferon-β (TRIF), nuclear factor-ĸB (NF-ĸB), interferon regulatory factor 3 (IRF3), NOD-, LRR- and pyrin domain-containing 3 (NLRP3, inflammasome), cleaved caspase-1, and interleukin 1 receptor type I (IL-1R1) in mice with LPS-induced AKI.ResultsGS1 and GS2 improved renal function and significantly reduced the levels of inflammatory cytokines and oxidative stress markers. In addition, PCA score scatter plots suggest that the GS1 and GS2 groups were clustered with the control group, indicating that these compounds contributed to the recovery of mice with AKI toward the normal condition. Moreover, GS1 and GS2 inhibited the expression of TLR4, MyD88, TRIF, p-NF-ĸB, p-IRF3, NLRP3, cleaved caspase-1, and IL-1R1.ConclusionThe reno-protective effects of GS1 and GS2 are mediated via the MyD88/TRIF and NLRP3 pathways to reduce inflammation and oxidative stress through TLR4 signaling. 相似文献
999.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Neuroinflammation induced by microglia plays an important role in the pathogenesis of PD. Long noncoding RNA GAS5 was showed to have significant effects on regulating inflammatory response. Here, we aim to investigate the effects of GAS5 on the inflammatory response of PD, and the underlying mechanism. An in vivo model of PD was established in C57BL/6 mice by rotenone and an in vitro cell model was conducted on microglia by lipopolysaccharide (LPS). Our results indicated that GAS5 was upregulated in tissues in a mice model of PD and microglia activated by LPS. Gain- and loss- of functional experiments demonstrated that GAS5 promoted the inflammation of microglia in vitro. Besides, the knockdown of GAS5 repressed the PD progression in vivo. Mechanistically, GAS5 positively regulated the NLRP3 expression via competitively sponging miR-223-3p. Overall, our finding illuminates that GAS5 accelerates PD progression through targeting miR-223-3p/NLRP3 axis. 相似文献
1000.
目的在人前列腺癌细胞系中分选CK5^+CK8^+细胞,了解其分子生物学特性。方法流式细胞术在人前列腺癌细胞系PC3和LNCaP中分选CK5^+CK8^+细胞,用实时荧光定量聚合酶链反应(RT-PCR)和蛋白质印迹法方法检测LNCaP细胞分选的CK5^+CK8^+细胞CK5、CK8、雄激素受体(AR)和前列腺特异抗原(PSA)的表达,细胞迁移实验检测CK5^+CK8^+细胞迁移能力,琼脂糖凝胶克隆形成实验检测CK5^+CK8^+细胞成瘤能力。采用t检验进行统计学分析。结果采用流式细胞术可以在PC3中分选出(21.3±4.6)%的CK5^+CK8^+细胞,在LNCaP中分选出(1.2±0.4)%的CK5^+CK8^+细胞。与非CK5^+CK8^+细胞相比,LNCaP中分选的CK5^+CK8^+细胞CK5 mRNA表达差异有统计学意义(t=10.435,P<0.001),CK8 mRNA表达差异无统计学意义(t=1.974,P=0.121),AR和PSA mRNA表达差异有统计学意义(t=4.317,3.232;P=0.016,0.037)。蛋白质印迹法检测得到类似结果。细胞培养7 d后,CK5^+CK8^+细胞和非CK5^+CK8^+细胞均可以在Transwell小室迁移生长,迁移细胞数分别为(60±7)个和(32±5)个,2者比较差异有统计学意义(t=6.031,P=0.004)。细胞培养14 d后,CK5^+CK8^+细胞和非CK5^+CK8^+细胞均可以在软琼脂糖凝胶中克隆性生长,阳性克隆数分别为(71±5)个和(27±3)个,差异有统计学意义(t=13.009,P<0.001)。结论人前列腺癌细胞系LNCaP和PC3都可以分选出CK5^+CK8^+细胞,LNCaP中CK5^+CK8^+细胞AR和PSA均有一定程度表达,迁移和成瘤能力增强。 相似文献