JWH-122 Consumption Adverse Effects: A Case of Hallucinogen Persisting Perception Disorder Five-Year Follow-Up

Synthetic cannabinoid receptor agonists are a heterogeneous group of psychotropic drugs functionally related to Δ9-tetrahydrocannabinol. These substances, marketed as cannabis substitutes, have been associated with numerous cases of severe intoxication and death across the world. In our article, we describe a case of hallucinogen persisting perception disorder developing in a natural cannabis user after consumption of JWH-122, a naphthoylindole largely used since 2010. Clinical symptomatology persisted for about four years and was alleviated through treatment with clonazepam. Considering that natural cannabis consumption can induce the development of a hallucinogen persisting perception disorder, it is not excluded that, in our patient, symptoms lasted a long time due to cannabis consumption. This article describes the clinical evolution from onset to resolution of all symptoms.     

Description of a 111-kb pathogenicity island (PAI) encoding various virulence features in the enterohemorrhagic E. coli (EHEC) strain RW1374 (O103:H2) and detection of a similar PAI in other EHEC strains of serotype 0103:H2

Human infections with enterohemorrhagic E. coli (EHEC) strains of serotype O103:H2 are of increasing importance in Germany. As bovines are the principal EHEC reservoir behind the occurrence of human infections, we analyzed a pathogenicity island (PAI I(RW1374)) of bovine O103:H2 strain RW1374 to identify putative virulence features. This PAI I(RW1374) harbors a functional 34-kb locus of enterocyte effacement (LEE) core region and has a total length of 111 kb. About 43 kb upstream of the LEE core a gene cassette consisting of efa1/lifA gene and flanking IS elements suggests another putative transposon within the PAI(IRW1374). In addition, the ent gene, encoding a Shigella ShET-2 enterotoxin homologue, is present about 57 kb upstream of the LEE core. This PAI is therefore a complex assembly of various virulence determinants including the efa1/lifA and the ent gene resembling O157:H7 PAI OI-122/SpLE3 as well as the LEE core region. An integrase gene on the very left end of PAI I(Rw1374) is disrupted by an IS629 homologue. In an attempt to mobilize the LEE core we performed conjugation, transformation and transduction experiments. We were, however, unable to mobilize the whole or even single regions of PAI I(RW1374). Comparative studies with other strains of serotype O103:H2 isolated from humans, bovines and food showed that they all harbored a similar phe V-inserted PAI including the virulence genes ent and lifA/efa1 as well as the large virulence-associated plasmid encoding the EHEC hemolysin. This combination of several virulence factors confirms the complex virulence of O103:H2 EHEC and may at least partly explain the high virulence of this EHEC serotype in humans.     

Claudin‐1, miR‐122 and apolipoprotein E transductions improve the permissivity of SNU‐182, SNU‐398 and SNU‐449 hepatoma cells to hepatitis C virus

Hepatitis C virus (HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU‐182, SNU‐398 and SNU‐449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin‐1 (CLDN1) expression limited the viral entry process in SNU‐182 and SNU‐398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR‐122 partly restored the replication of a JFH1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU‐182 and SNU‐398 cells but not in SNU‐449 cells. Nevertheless, the supplementation of SNU‐182, SNU‐398 and SNU‐449 cells with CLDN1, miR‐122 and ApoE was not sufficient to render these cells as permissive as HuH‐7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR‐122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection.     

大鼠颅脑损伤后脑组织miR-122-5p含量变化及其对神经功能的影响

目的 探讨大鼠颅脑损伤后脑组织miR-122-5p含量变化及其对神经功能的影响。方法 将40只成年SD大鼠随机分为假手术组,TBI模型组,乱序miRNA组,miR-122-5p模拟物组。采用Feeney法制备TBI大鼠模型;乱序miRNA组造模24 h后,立体定向注射乱序miRNA 5 μl（20 μmol/L）;miR-122-5p模拟物组造模24 h后,立体定向注射miR-122-5p模拟物组5 μl（20 μmol/L）。qRT-PCR法检测大鼠脑组织miR-122-5p的表达变化;免疫印迹法法检测p53蛋白表达水平;水迷宫法检测学习记忆功能;TUNEL法检测脑组织细胞凋亡情况;流式细胞术检测脑细胞线粒体膜电位的变化。结果 与假手术组大鼠比较,模型组和乱序miRNA组大鼠脑组织miR-122-5p表达明显减少,p53蛋白显著上调,脑组织细胞凋亡数明显增多,线粒体膜电位下降显著,水迷宫测试大鼠寻找隐形平台时间显著延长;与模型组大鼠比较,miR-122-5p模拟物组大鼠miR-122-5p表达明显增加,并伴随p53蛋白低表达,细胞凋亡水平下降,神经功能障碍得到明显逆转。结论 颅脑损伤后miR-122-5p的表达下调可能导致p53蛋白的表达升高,促进神经细胞凋亡。     

SP1被鉴定为miR-122-5p的一个转录因子

目的:miR-122-5p跟精子发生相关,本研究主要是探究miR-122-5p在睾丸内的转录因子. 方法:采用生物信息学方法预测到miR-122-5p启动子的可能转录因子为SP1和GATA4,然后分别构建双荧光素酶pGL3-miR-122-5p promoter载体、pcDNA3.1(+)-SP1表达载体和pcDNA3...     

应用实时荧光定量PCR检测血清miR-122和miR-22及其在慢性乙型肝炎患者中的表达

目的 建立血清中microRNA(miRNA)的实时荧光定量PCR(qRT-PCR)的检测方法,对慢性乙型肝炎患者血清中miR-122和miR-22的表达水平进行检测和分析,探讨其在慢性乙型肝炎患者血清中表达的意义。 方法 茎环引物用于成熟型miRNA反转录,以建立SYBR Green Ⅰ PCR筛选和定量检测miRNA的方法。同时,采用10倍梯度稀释的miR-122标准品cDNA(1~10⁹拷贝/微升)评价其敏感度;采用熔解曲线评价其检测miRNA的特异性;通过对2×10⁵、2×10⁶、2×10⁷拷贝/微升的miR-122标准品cDNA分别进行批内20次重复实验,以其循环阈值(Ct)的变异系数(CV)评价其精密度。采用建立的qRT-PCR技术检测慢性乙型肝炎患者及正常人血清中miR-122和miR-22的表达水平。 结果 建立了茎环引物的RT-PCR法检测血清中的miRNA,该方法的线性范围宽,敏感度高,重复性好,方法简便。在慢性乙型肝炎患者组中血清miR-122和miR-22的相对表达量分别为17.88和5.35;与正常对照组中血清miR-122和miR-22的相对表达量(分别为1.80和1.67)比较,差异有统计学意义(P均=0.000)。 结论 建立了茎环引物RT-PCR实时荧光定量PCR方法检测血清中的miR-122和miR-22,血清miR-122和miR-22在慢性乙型肝炎患者的血清中表达显著升高。     

miR-122-5p通过靶向CREB1抑制食管癌细胞及移植瘤的生长

背景与目的:miR-122在多种肿瘤中表达异常,参与肿瘤细胞增殖、凋亡等,而cAMP反应元件结合蛋白1(cAMP response element-binding protein 1,CREB1)参与食管癌发展过程,研究miR-122-5p通过靶向CREB1对食管癌细胞及移植瘤生长的作用及机制.方法:选取2017年11...     

类风湿性关节炎患者CD8~+ CD122~+调节性T淋巴细胞和白细胞介素-10的水平变化及意义

目的探讨类风湿性关节炎(RA)患者外周血中CD8+CD122+调节性T淋巴细胞(Tregs)及细胞因子白细胞介素-10(IL-10)的水平变化及其临床意义。方法收集62例RA患者与26例健康体检者,采用流式细胞仪测定研究对象外周血中的CD8+CD122+Tregs水平,双抗夹心酶联免疫吸附试验测定血清中IL-10浓度。结果RA活动期和稳定期患者外周血中的CD8+CD122+Tregs和IL-10的含量明显低于健康对照组,差异有统计学意义(P<0.05)。RA活动期患者上述指标含量均显著低于稳定期患者,差异均有统计学意义(P<0.05)。同时,RA患者血清中的IL-10的浓度与外周血中的CD8+CD122+Tregs细胞水平情况呈正相关(rs=0.297,P<0.05)。结论 RA患者外周血中具有免疫负调控功能的CD8+CD122+Tregs和IL-10水平较低,可能与类风湿性关节炎的发生相关。     

MicroRNA-122表达与大鼠慢性肝损伤的相关性

目的观察microRNA-122（miR-122）在大鼠慢性肝损伤早期和晚期的表达及其与大鼠肝损伤的关系。方法用40％CCl4经皮下注射2周和6周后分别建立大鼠早期慢性肝损伤模型（早期病变组,n=10）和晚期慢性肝损伤模型（晚期病变组,n=10）,另设正常组（n=10）作为对照。提取肝组织总RNA,将总RNA逆转录为cDNA,采用TaqMan探针法进行Real—time PCR检测,观察miR-122的表达变化。结果成功建立大鼠慢性肝损伤早期和晚期病变模型;早期病变组和晚期病变组miR-122表达分别下降至正常组的27．0％和5．6％。结论miR-122在慢性肝损伤早、晚期呈进行性下降,与肝损伤存在密切关系。