Meta-analysis of Cytochrome P4501A1 MspI Gene Polymorphism and Childhood Acute Leukemia

Objective To investigate the relationship between cytochrome P4501A1 （CYPIA1） Msp I gene polymorphism and childhood acute leukemia （AL）. Methods Relevant literature was extensively searched and screened by Pubmed and Wanfang Database, Chinese Science Journal Database and Chinese Journal Net. Various data consolidation, combined OR values and their 95% CI were tested by RevMan 4.2; Funnel plots were used for the bias analysis. Results Six related literatures were found to meet the requirements. According to heterogeneity results, there was no significant difference in homozygous types（P〉0.05）, while there was significant difference in two others types （P all〈0.05）. For wild CYPIAIMspl homozygous for the reference group, Combined OR of heterozygous mutation, homozygous, heterozygous ＋ homozygous mutation in AL and control groups were 1.18, 0.96, and 1.10 respectively. Subgroup analysis： Z values of CYP1A1Mspl homozygous, heterozygous ＋ homozygous in the acute lymphoblastic leukemia （ALL） and the control group were 0.10 and 0.76 respectively, Z values in non-acute lymphoblastic leukemia and control group were 0.74 and 0.75. Conclusion There is no correlation between CYP1A1Mspl gene polymorphism and the susceptibility of childhood AL.

The benzo(a) pyrene-induced mRNA expression of aromatic hydrocarbon receptor and cytochrome P4501A1 genes in rat liver

Objective To study the benzo(a)pyrene(B[a]P)-induced mRNA expression of aromatic hydrocarbon receptor(AHR)and cytochrome P4501A1(CYP1A1)genes in rat liver.Methods Rats were injected intraperitoneally with 5,10 and 15mg/kg of B[a]P.The total RNAs were extracted from rat livers by RNA purification kit,and the mRNA expression of AHR and CYP1A1 genes was determined by reverse transcription polymerase chain reaction(RT-PCR).β-actin was used as the internal control.The mRNA expression of both AHR and CYP1A1 genes was measured at indicated time points(24,48 and 72h)after B[a]P treatment at three different concentrations(5,10 and 15mg/kg).Results The mRNA expression of AHR gene increased in a time-dependent manner at the concentration of 10mg/kg but not at 5 and 15mg/kg of B[a]P.The mRNA expression of CYP1A1 gene differed significantly at 48h and 24h in rat livers treated with 10 and 15mg/kg dosage of B[a]P.The mRNA expression of AHR and CYP1A1 genes increased with B[a]P treatment in a concentration-dependent manner.The time-dependent increase in mRNA expression was shown by AHR but not by CYP1A1 gene with B[a]P(10mg/kg)treatment.Conclusion This study demonstrates that toxic B[a]P increases the mRNA expression of both AHR and CYP1A1 genes in vivo,suggesting that B[a]P may play a role in cancer genesis by this way.

Sensing cytochrome P4501A1 activity by a resorufin-based isoform-specific fluorescent probe

Cytochrome P4501 A1(CYP1A1),a heme-containing monooxygenase,is of particular importance for human health because of its vital roles in the metabolic activation of pro-carcinogenic compounds to the carcinogens.Deciphering the relevance of CYP1A1 to human diseases and screening of CYP1A1 modulators require reliable tool(s)for probing this key enzyme in complex biological matrices.Herein,a practical and ultrasensitive fluorescence-based assay for real-time sensing CYP1A1 activities in biological systems has been developed,via designing an isoform-specific fluorogenic sensor for CYP1A1(CHPO).The newly developed fluorogenic substrate for CYP1A1 has been carefully investigated in terms of specificity,sensitivity,precision,quantitative linear range and the anti-interference ability.The excellent selectivity,strong anti-interference ability and fast response kinetics,making the practicability of CHPObased CYP1A1 activity assay is better than that of most reported CYP1A1 activity assays.Furthermore,CHPO has been successfully used for imaging CYP1A1 activities in living cells and human tissues,as well as for high-throughput screening of CYP1A1 inhibitors using tissue preparations as enzyme sources.Collectively,this study provided a practical fluorogenic sensor for real-time sensing CYP1A1 in complex biological systems,which would strongly facilitate the investigations on the relevance of CYP1A1 to human diseases and promote high-throughput screening of CYP1A1 modulators for biomedical applications.

单细胞RNA测序揭露人FOXP3^+调节性T细胞稳定性的关键调控分子

T淋巴细胞的异质性和可塑性对于决定免疫应答至关重要.FOXP3的稳定表达通常是调节性T(Treg)细胞的分子特征,现已有研究报道在炎症条件下Treg表现出了异质性.然而,炎症与Treg细胞抑制活性之间的相互作用仍然难以捉摸.本文利用单细胞RNA测序研究了Treg细胞对促炎性细胞因子IL-6的响应.研究者观察到在IL-6刺激后Treg细胞分为两个亚群.TIGIT阴性的Treg细胞丢失了FOXP3基因的表达,获得了类似效应性T细胞的表型,而TIGIT阳性的Treg细胞则保留了较强的免疫抑制功能.本文还通过单细胞转录组分析揭示了IL-6刺激下Treg细胞的状态变化,以及CYP1A1作为Treg细胞抑制功能和稳定性的关键调控基因.CYP1A1缺陷型Treg细胞在IL-6刺激后出现类似Th17细胞的表型.本研究发现暗示CYP1A1作为Treg细胞的一个崭新的调节分子,具有潜在的生物治疗应用潜力.