中晚期非小细胞肺癌患者外周血淋巴细胞亚群特点分析

目的 分析中晚期非小细胞肺癌(NSCLC)患者外周血淋巴细胞亚群的分布特点及临床意义。方法 选择2022年1月至2023年4月收治的中晚期NSCLC患者93例,采用流式细胞术检测患者外周血总T、CD4⁺T、CD8⁺T、总B和NK细胞的比例及绝对值,分析其分布特征。结果 58.06%的患者外周血淋巴细胞比例降低,35.48%的患者外周血淋巴细胞绝对值降低。流式分析显示,外周血T(84.95%)、B(76.34%)和NK(92.47%)细胞分布比例多处于正常范围,CD4⁺/CD8⁺比例异常占60.22%。外周血T(60.22%)、CD4⁺T(58.06%)和CD8⁺T细胞(64.52%)绝对值以降低为主,B细胞绝对值降低者占44.09%,NK细胞绝对值降低者占32.26%。腺癌患者外周血总T细胞比例显著低于鳞癌患者水平(P=0.047)。腺癌患者外周血NK细胞比例和绝对值均显著低于鳞癌患者水平(P值分别为0.0025、0.02)。其余指标在不同病理类型之间的分...     

卡瑞利珠单抗联合含铂双药方案治疗非小细胞肺癌的临床研究

目的 分析卡瑞利珠单抗联合含铂双药方案一线治疗非小细胞肺癌(NSCLC)的临床疗效。方法 收集濮阳市安阳地区医院2020年1月至2022年12月行含铂双药方案治疗的82例驱动基因阴性晚期NSCLC患者临床资料,其中行卡瑞利珠单抗联合含铂双药一线治疗的有38例(观察组),仅行含铂双药一线治疗的有44例(对照组)。记录两组临床疗效[客观有效率(ORR)、疾病控制率(DCR)],比较两组治疗前及治疗4个周期后T淋巴细胞亚群(CD4⁺、CD8⁺、CD4⁺/CD8⁺)变化,分析两组患者生存情况[包括无进展生存(PFS)及总生存(OS)],并评估治疗不良反应。结果 观察组ORR及DCR均显著高于对照组(P<0.05)。治疗4个周期后,两组外周血CD4⁺及CD4⁺/CD8⁺均较治疗前升高(P<0.05),且观察组治疗后高于对照组(P<0.05);两组外周血CD8⁺均较治疗前降低(P<0.05),且观察组...     

PD-1+T细胞亚群比例与irAE患者的血清IFN-γ水平的相关性研究

目的 分析使用免疫检查点抑制剂(ICI)治疗后出现免疫相关不良反应(irAE)的非小细胞肺癌(NSCLC)患者的外周血T淋巴细胞亚群水平及其与血清细胞因子的关系。方法 前瞻性纳入2022年4～10月于某院就诊的非小细胞肺癌患者47例,其中根据有无发生irAE分为irAE组(n=12)和对照组(n=35),采用流式细胞术检测患者外周血淋巴细胞亚群的比例,比较两组间淋巴细胞亚群比例的差异性,Pearson相关性分析细胞因子与淋巴细胞亚群水平的相关性。结果 与对照组相比,irAE组患者外周血TCR-αβ⁺PD1⁺CD4^-CD8^-T细胞水平升高,差异具有统计学意义(P=0.045),其他T淋巴细胞亚群无明显差异。Pearson相关性分析结果显示外周血TCR-αβ⁺PD1⁺CD4^-CD8^-T细胞与血清干扰素-γ(IFN-γ)呈正相关关系(r=0.448;P=0.019)。结论irAE患者外周血TCR-αβ⁺     

探究生殖道感染对女性患者外周血T细胞亚群及炎症因子水平的影响

目的:探究生殖道感染对女性患者外周血T细胞亚群及炎症因子水平的影响。方法:抽取2021年9月—2022年6月期间在我院妇科接受生殖道感染诊断的女性患者72例,作为观察组;同期收集来我院妇科接受生殖道健康检查的女性体检者72例,作为参照组。两组均抽取晨起空腹状态下外周静脉血液,检测并比较两组患者外周血T细胞亚群(CD3⁺细胞、CD4⁺细胞、CD8⁺细胞、CD4⁺/CD8⁺)、血清炎症因子(IL-6、IL-8、TNF-α、hs-CRP)。结果:观察组CD3⁺T细胞水平为(48.41±4.37)%、CD4⁺T细胞水平为(45.01±4.10)%、CD4⁺/CD8⁺比值水平为(1.32±0.33),均低于参照组的(57.68±5.11)%、(52.04±4.21)%、(1.89±0.42),P<0.05;观察组的CD8⁺T细胞水平为(32.47±4.03)%,高于参照组的...     

替雷利珠单抗联合XELOX方案治疗晚期胃癌的临床研究

目的 探讨替雷利珠单抗注射液联合XELOX方案治疗晚期胃癌的临床疗效。方法 选取2021年1月—2023年1月泾县医院收治的60例晚期胃癌患者,采用随机数字表法将纳入患者分为对照组和治疗组,每组30例。对照组采用XELOX方案：第1天静脉滴注注射用奥沙利铂130 mg/m²,同时口服卡培他滨片1 000 mg/m²,2次/d,连续治疗14 d,并以3周为1个疗程。治疗组在对照组基础上静脉滴注替雷利珠单抗注射液200 mg/次,3周用药1次,3周为1个疗程。两组患者均连续治疗3个疗程。比较两组近期临床疗效、免疫功能指标和血清肿瘤标志物。结果 治疗组的总有效率高于对照组的总有效率(P<0.05)。治疗后,对照组CD3⁺T细胞、CD4⁺T细胞和CD4⁺T/CD8⁺T比值均显著降低,治疗组CD3⁺T细胞、CD4⁺T细胞和CD4⁺T/CD8⁺T比值均显著升高(P<0....     

参苓白术散联合靶向治疗对晚期非小细胞肺癌患者毒副反应及T细胞亚群、VEGF的影响研究

目的 探究参苓白术散联合靶向治疗对晚期非小细胞肺癌(NSCLC)患者毒副反应及T细胞亚群、血管内皮生长因子(VEGF)的影响。方法 60例晚期NSCLC患者,采用随机数字表法分为对照组与实验组,每组30例。对照组患者接受盐酸安罗替尼胶囊治疗,实验组患者在对照组上加用参苓白术散治疗。比较两组患者T细胞亚群变化情况、VEGF水平、毒副反应发生情况。结果 治疗前,两组患者的CD3⁺、CD4⁺、CD4⁺/CD8⁺水平比较,差异无统计学意义(P>0.05);治疗后,两组患者的CD3⁺、CD4⁺、CD4⁺/CD8⁺水平均明显高于本组治疗前,实验组患者的CD3⁺(67.25±6.48)%、CD4⁺(38.81±4.22)%、CD4⁺/CD8⁺(1.62±0.07)均明显高于对照组的(60.13±6.02)%、(35.04±3.15)%...     

对低ALT水平慢性乙型肝炎人群的HBcrAg及CD4+CD25+调节性T细胞的相关性分析

目的 探讨低ALT水平的慢性乙型肝炎患者外周血中乙型肝炎病毒核心相关抗原(HBcrAg)表达水平及与CD4⁺CD25⁺调节性T细胞之间的相关性，分析二者表达与疾病进展之间的关联性。方法 收集我院收治的81例未接受抗病毒治疗的低ALT水平的慢性乙型肝炎患者，ELISA检测其血清中HBcrAg表达，流式细胞术检测CD4⁺、CD4⁺CD25⁺、CD8⁺T数量及比值。Spearman法对二者相关性进行分析。结果 在HBeAg(+)与HBeAg(-)组，CD4⁺占淋巴细胞总数之比、ALT、AST、HBsAg、HBV DNA有明显差异。HBeAg(+)的10⁴ IU/mL6 IU/mL组中，HBcrAg与ALT呈正相关(r=0.800),与CD4⁺CD25⁺/CD4⁺呈负相关(r=-0.400),CD4<...     

康莱特联合洛铂治疗NSCLC伴恶性胸腔积液的疗效及对VEGF和MMP-9及T淋巴细胞水平的影响

目的：探讨康莱特联合洛铂治疗非小细胞肺癌(NSCLC)伴恶性胸腔积液的疗效及对血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)和T淋巴细胞水平的影响。方法：选择2020年7月—2021年12月收治的80例NSCLC伴恶性胸腔积液患者,按随机数字表法分为对照组和观察组,每组40例。对照组采用洛铂治疗,观察组用康莱特联合洛铂治疗。比较两组疗效、血管新生指标含量、T淋巴细胞水平[CD3⁺,CD4⁺,CD8⁺,CD4⁺/CD8⁺]及毒副反应。结果：观察组治疗4个疗程的总缓解率高于对照组(P<0.05)。治疗4个疗程后,两组胸腔积液VEGF,MMP-9水平低于治疗前,且观察组低于对照组(P<0.05);两组CD3⁺,CD4⁺,CD4⁺/CD8⁺低于治疗前,但观察组高于对照组;两组CD8⁺高于治疗前,但观察组低于对照组(P<0.05)。两组毒副反应发...     

膀胱肿瘤微环境细胞亚群分布及与复发的关系

目的：探讨浅表性膀胱癌肿瘤微环境肿瘤浸润细胞亚群分布及与肿瘤术后复发的相关性。方法：回顾性分析2018年1月-2021年12月78例获得随访的行经尿道膀胱肿瘤电切术的浅表性膀胱癌患者的临床资料,免疫组化法检测石蜡标本中肿瘤浸润细胞亚群的分布情况,并分析各细胞亚群之间的相关性及其与肿瘤术后复发的相关性。结果：CD3⁺T淋巴细胞是浅表性膀胱癌肿瘤微环境主要浸润的免疫细胞,CD20⁺B淋巴细胞、FOXP3⁺调节性T细胞(FOXP3⁺Treg细胞)、中性粒细胞弹性蛋白酶(NE)⁺中性粒细胞、CD8⁺T淋巴细胞浸润较多,而CD56⁺自然杀伤(NK)细胞浸润最少。CD3⁺T淋巴细胞、CD8⁺T淋巴细胞、CD20⁺ B淋巴细胞和FOXP3⁺ Treg细胞4种免疫细胞亚群两两之间都存在显著的正相关(P<0.01)。FOXP3⁺Treg细...     

卡瑞利珠单抗联合化疗对中晚期NSCLC患者细胞免疫、血管生成因子的影响

目的 探讨卡瑞利珠单抗联合化疗对中晚期非小细胞肺癌(NSCLC)患者细胞免疫、血管生成因子的影响。方法 选取2020年5月—2023年5月在郑州大学第二附属医院进行治疗的中晚期NSCLC患者86例,按随机对照原则分为对照组(43例,接受化疗治疗)、研究组(43例,接受化疗+卡瑞利珠单抗治疗),共治疗3个周期。对比两组临床疗效、肿瘤标志物水平[细胞角蛋白19的可溶性片段(Cyfra21-1)、糖类抗原125(CA125)、癌胚抗原(CEA)]、血管生成因子水平[血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)]、免疫功能[CD4⁺、CD3⁺、CD4⁺/CD8⁺、CD8⁺]以及不良反应发生率。结果 治疗后,研究组客观缓解率(ORR)、疾病控制率(DCR)均比对照组高(P<0.05);相比对照组,研究组治疗后血清Cyfra21-1、CA125、CEA、VEGF、bFGF水平均显著降低(P<0.05);相比对照组,研究组治疗后CD4⁺、...     

Impact of OATP transporters on pharmacokinetics

Membrane transporters are now recognized as important determinants of the transmembrane passage of drugs. Organic anion transporting polypeptides (OATP) form a family of influx transporters expressed in various tissues important for pharmacokinetics. Of the 11 human OATP transporters, OATP1B1, OATP1B3 and OATP2B1 are expressed on the sinusoidal membrane of hepatocytes and can facilitate the liver uptake of their substrate drugs. OATP1A2 is expressed on the luminal membrane of small intestinal enterocytes and at the blood-brain barrier, potentially mediating drug transport at these sites. Several clinically used drugs have been identified as substrates of OATP transporters (e.g. many statins are substrates of OATP1B1). Some drugs may inhibit OATP transporters (e.g. cyclosporine) causing pharmacokinetic drug–drug interactions. Moreover, genetic variability in genes encoding OATP transporters can result in marked inter-individual differences in pharmacokinetics. For example, a single nucleotide polymorphism (c.521T > C, p.Val174Ala) in the SLCO1B1 gene encoding OATP1B1 decreases the ability of OATP1B1 to transport active simvastatin acid from portal circulation into the liver, resulting in markedly increased plasma concentrations of simvastatin acid and an enhanced risk of simvastatin-induced myopathy. SLCO1B1 polymorphism also affects the pharmacokinetics of many other, but not all (fluvastatin), statins and that of the antidiabetic drug repaglinide, the antihistamine fexofenadine and the endothelin A receptor antagonist atrasentan. This review compiles the current knowledge about the expression and function of human OATP transporters, their substrate and inhibitor specificities, as well as pharmacogenetics.     

Ape1/Ref-1 Stimulates GDNF/GFR��1-mediated Downstream Signaling and Neuroblastoma Proliferation

We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor α1 (GFRα1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRα1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFRα1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFRα1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFRα1-specific RNA experiments demonstrated that the downregulation of GFRα1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLCγ-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFRα signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.     

Anthracycline resistance mediated by reductive metabolism in cancer cells: The role of aldo-keto reductase 1C3

Pharmacokinetic drug resistance is a serious obstacle that emerges during cancer chemotherapy. In this study, we investigated the possible role of aldo-keto reductase 1C3 (AKR1C3) in the resistance of cancer cells to anthracyclines. First, the reducing activity of AKR1C3 toward anthracyclines was tested using incubations with a purified recombinant enzyme. Furthermore, the intracellular reduction of daunorubicin and idarubicin was examined by employing the transfection of A549, HeLa, MCF7 and HCT 116 cancer cells with an AKR1C3 encoding vector. To investigate the participation of AKR1C3 in anthracycline resistance, we conducted MTT cytotoxicity assays with these cells, and observed that AKR1C3 significantly contributes to the resistance of cancer cells to daunorubicin and idarubicin, whereas this resistance was reversible by the simultaneous administration of 2′-hydroxyflavanone, a specific AKR1C3 inhibitor. In the final part of our work, we tracked the changes in AKR1C3 expression after anthracycline exposure. Interestingly, a reciprocal correlation between the extent of induction and endogenous levels of AKR1C3 was recorded in particular cell lines. Therefore, we suggest that the induction of AKR1C3 following exposure to daunorubicin and idarubicin, which seems to be dependent on endogenous AKR1C3 expression, eventually might potentiate an intrinsic resistance given by the normal expression of AKR1C3. In conclusion, our data suggest a substantial impact of AKR1C3 on the metabolism of daunorubicin and idarubicin, which affects their pharmacokinetic and pharmacodynamic behavior. In addition, we demonstrate that the reduction of daunorubicin and idarubicin, which is catalyzed by AKR1C3, contributes to the resistance of cancer cells to anthracycline treatment.     

The effect of antifungal combination on transcripts of a subset of drug-resistance genes in clinical isolates of Candida species induced biofilms

Biofilm formation is often associated with increased Candida resistance toward antifungal agents. Therefore, the current study aimed to assess the incidence of biofilm formation among Candida isolates and to investigate the effect of high doses of fluconazole {FLC}, voriconazole {VOC} and amphotericin B {AMB}, singly and in combination on mature biofilms. Moreover, it aimed to assess the expression of selected genes (CDR1, KRE1 and SKN1) responsible for Candida biofilm resistance. The study included 49 patients; samples were collected from the King Khalid Hospital, Riyadh, Saudi Arabia. Isolates were prepared for biofilm formation and quantification using 0.4% (w/v) crystal violet. Minimum Inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) were conducted by the broth microdilution method. Biofilm eradication was evaluated using counting, XTT stain intensity and observed under the inverted microscope. Selected genes were evaluated in Candida biofilms under the effect of antifungal exposure using QPCR. The major isolates were Candida albicans (65.3%) followed by Candida tropicalis and Candida glabrata. 77.6% of the strains were biofilm formers. AMB showed susceptibility in 87.8% of isolates, followed by VOC (77.6%) and FLC (67.3%). MIC50 and MIC90 were (0.03, 0.125), (0.5, 8), (2, >128) μg/ml for AMB, VOC and FLC, respectively. 34.7% and 18.4% of the isolates were antagonistic to AMB/FLC and AMB/VOC, respectively. Mature biofilms of ten selected isolates were found resistant to FLC (1000 μg/ml). VOR and AMB concentration required to inhibit biofilm formation was 16–250 fold higher than the MIC for planktonic cells. Isolates showed significant reduction with antifungal combination when compared with the untreated controls (p value ⩽ 0.01), or using fluconazole alone (p value ⩽ 0.05). High doses of the antifungals were employed to assess the effect on the persisters’ selected gene expression. Marked over expression of SKN1 and to a lesser extent KRE1 was noticed among the mature biofilms treated with AMB alone or in combination after 1 h of exposure, and SKN1 expression was even more sharply induced after 24 h. No statistically significant over expression of CDR1 was observed in biofilms after exposure to high doses of FLC, VOC or any of the combinations used.     

Involvement of intestinal calcium transporter 1 and metallothionein in cadmium accumulation in the liver and kidney of mice fed a low-calcium diet

Essential metals can affect the metabolism of nonessential metals. Calcium (Ca) is an essential mineral that is commonly lacking in the diet. When we fed 5-week-old male mice for 4 weeks on a purified diet containing 0.005% Ca (CaDF mice), the Ca concentration in the plasma, liver and kidneys did not decreased. Cd accumulation increased in the liver and kidneys of CaDF mice given 1mg/kg Cd orally each day for 5 days, but not in those given intraperitoneal injections of Cd or Cd-metallothionein (Cd-MT). The zinc (Zn) concentration increased significantly in the intestinal cytosol and plasma during the time the mice were fed the low-Ca diet, and expression of both MT-1 and ZnT-1 sharply increased with a similar time course. Intestinal mRNA expression of CaT1, a Ca transporter, was more than 10 times higher in CaDF mice than in controls, although expression of other transporters, including DMT1, decreased in CaDF mice. These results suggest that CaT1 may stimulate the intestinal absorption of Cd and Zn, and some Cd may be distributed to the kidneys along with MT induced by Zn.     

腺苷受体A1亚型对视网膜色素上皮细胞 免疫调节功能的影响

目的 研究视网膜色素上皮细胞（RPE）主要是通过何种亚型的腺苷受体（ARs）来结合腺苷,及其对 RPE 功能的影响。方法 体外培养人 ARPE-19 细胞系,定量 PCR 检测 4 种腺苷受体（ARA1、ARA2A、ARA2B、ARA3）基 因的表达;提取细胞膜蛋白,Western blot 检测 4 种腺苷受体在 RPE 细胞膜上的存在。体外培养 ARPE-19 细胞至 80% 融合后随机分为 A~E 组。其中,A 组为无干预对照组,B～E 组分别给予 ARA1 拮抗剂 DPCPX（50 nmol/L）、 ARA2A 拮抗剂 SCH58261（100 nmol/L）、ARA2B 拮抗剂 MRS1754（100 nmol/L）及 ARA3 拮抗剂 MRS1220（5 μmol/L） 干预。利用 H3-腺苷进行放射性配体结合实验,计算各组细胞对腺苷的最大结合容量（Bmax）。以肿瘤坏死因子 α （TNF-α）10 μg/L 及 γ 干扰素（IFN-γ）1 000 U/mL 联合干预体外培养的 ARPE-19 细胞,给予或不予 ARA1 激动剂 （CCPA）,酶联免疫吸附试验（ELISA）测定培养上清中白细胞介素（IL）-6、IL-10、转化生长因子 β（TGF-β）、单核细胞 趋化因子（MCP）-1、趋化因子 C-X-C 配体 10（CXCL10,IP-10）的含量。结果 在 ARPE-19 细胞中即可检测到 4 种 腺苷受体基因的表达,也可探测到其分子在细胞膜上的存在。A~E 组 ARPE-19 细胞结合腺苷的 Bmax （单位：fmol）分 别为 2.04±0.31、0.44±0.06、1.82±0.28、2.01±0.42 及 2.06±0.44,其中 B 组较其他各组 Bmax均降低（P＜0.01）。以 TNF- α 及 IFN-γ 激活 ARPE-19 细胞,与对照 RPE 组比较,CCPA 干预 RPE 组 IL-6、MCP-1 及 IP-10 的含量降低、IL-10 的含量增加（P＜0.01）。2 组 TGF-β 的含量差异无统计学意义。结论 ARA1 对 ARPE-19 细胞结合腺苷的能力具 有重要的调控作用,ARA1 受体介导的信号可抑制 ARPE-19 细胞分泌促炎因子及驱化因子,具有潜在的免疫抑制 作用。     

A novel in vitro pancreatic carcinogenesis model

Environmental factors (e.g., BaP) have been pointed out as one of the etiologies of pancreatic cancer. However, very limited experimental assays are available to identify pancreatic specific environmental mutagens or susceptibility genes. In this study, we have developed a simple in vitro cell culture model system that can be used to study the molecular and biochemical aspects of carcinogenesis in a near-normal immortalized pancreatic ductal epithelial cell lines. In order to demonstrate that xenobiotic stress response is intact in these cells, we employed standard molecular biology techniques. For examples, luciferase reporter and/or real-time quantitative PCR assays were used to determine stress-induced CYP1A1 and CYP1B1 gene expression. Western blotting and immunocytochemistry assays were used to demonstrate that TCDD or BaP could activate AhR signaling. For exploring the carcinogenesis mechanism, we incubated cells with [³H]BaP and determined BaP-DNA binding activity by measuring its radioactivity. BaP-DNA adduct formation was further confirmed by [³²P]-postlabeling assay. Finally, we demonstrated the effects of endogenous AhR or BRCA1 in BaP-DNA adduct accumulation in our cell system. As results, no apparent BaP-DNA adduct accumulation by [³²P]-postlabeling assay was found in either control-siRNA or AhR-siRNA pretreated cells. On the other hand, a significant increase of BaP-DNA adduct accumulation was found in BRCA1 knockdown cells. In conclusion, we suggest that this in vitro model may provide the feasibility for future studies on the molecular basis of pancreatic ductal cell carcinogenesis caused by dietary mutagens.     

Compartmentalization of endocannabinoids into lipid rafts in a microglial cell line devoid of caveolin-1

BACKGROUND AND PURPOSE

N-acyl ethanolamines (NAEs) and 2-arachidonoyl glycerol (2-AG) are endogenous cannabinoids and along with related lipids are synthesized on demand from membrane phospholipids. Here, we have studied the compartmentalization of NAEs and 2-AG into lipid raft fractions isolated from the caveolin-1-lacking microglial cell line BV-2, following vehicle or cannabidiol (CBD) treatment. Results were compared with those from the caveolin-1-positive F-11 cell line.

EXPERIMENTAL APPROACH

BV-2 cells were incubated with CBD or vehicle. Cells were fractionated using a detergent-free continuous OptiPrep density gradient. Lipids in fractions were quantified using HPLC/MS/MS. Proteins were measured using Western blot.

KEY RESULTS

BV-2 cells were devoid of caveolin-1. Lipid rafts were isolated from BV-2 cells as confirmed by co-localization with flotillin-1 and sphingomyelin. Small amounts of cannabinoid CB₁ receptors were found in lipid raft fractions. After incubation with CBD, levels and distribution in lipid rafts of 2-AG, N-arachidonoyl ethanolamine (AEA), and N-oleoyl ethanolamine (OEA) were not changed. Conversely, the levels of the saturated N-stearoyl ethanolamine (SEA) and N-palmitoyl ethanolamine (PEA) were elevated in lipid raft fractions. In whole cells with growth medium, CBD treatment increased AEA and OEA time-dependently, while levels of 2-AG, PEA and SEA did not change.

CONCLUSIONS AND IMPLICATIONS

Whereas levels of 2-AG were not affected by CBD treatment, the distribution and levels of NAEs showed significant changes. Among the NAEs, the degree of acyl chain saturation predicted the compartmentalization after CBD treatment suggesting a shift in cell signalling activity.

LINKED ARTICLES

This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7