Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia cells.

Farnesyltransferase inhibitors (FTIs) are currently under investigation for leukemia treatment. We evaluated the FTI manumycin A (manumycin) in two myeloid leukemia cell lines (U937 and HL-60). Manumycin induced nitric oxide production and apoptosis of the leukemia cells. Nitric oxide or other reactive oxygen species may induce oxidative DNA damage, and the number of apurinic sites increased after manumycin treatment, which was reversed by concurrent treatment with N-acetyl-L-cysteine. Since repair of DNA damage is important to cell survival, we hypothesized that methoxyamine, an inhibitor of base-excision repair, would enhance the antineoplastic effect of manumycin. The combination of manumycin and methoxyamine resulted in enhanced apoptosis by six criteria increased annexin V binding, release of mitochondrial cytochrome c into the cytosol, activation of caspase-9, activation of caspase-3, specific cleavage of poly-adenosyl ribose polymerase, and increase in the sub-G1 cell cycle fraction. The drug combination enhanced inhibition on the soft agar clonogenic assay and on the formazan dye cell viability assay. The effects of manumycin or manumycin plus methoxyamine on apoptosis were blocked by N-acetyl-L-cysteine, and partially by nitric oxide synthase inhibitors or scavenger of peroxide. We conclude that methoxyamine enhances manumycin-induced apoptosis in myeloid leukemia cells.     

The association of XRCC1 haplotypes and chromosomal damage levels in peripheral blood lymphocyte among coke-oven workers.

Theoretically, a haplotype has a higher level of heterozygosity than individual single nucleotide polymorphism (SNP) and the association study based on the haplotype may have an increased power for detecting disease associations compared with SNP-based analysis. In this study, we investigated the effects of four haplotype-tagging SNPs (htSNP) and the inferred haplotype pairs of the X-ray cross-complementing group 1 (XRCC1) gene on chromosome damage detected by the cytokinesis-block micronucleus assay. The study included 141 coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 66 nonexposed controls. The frequencies of total MN and MNed cells were borderline associated with the Arg(194)Trp polymorphism (P = 0.053 and P = 0.050, respectively) but not associated with the Arg(280)His, Arg(399)Gln and Gln(632)Gln polymorphisms among coke-oven workers. Five haplotypes, including CGGG, TGGG, CAGG, CGAG, and CGGA, were inferred based on the four htSNPs of XRCC1 gene. The haplotype CGGG was associated with the decreased frequencies of total MN and MNed cells, and the haplotypes TGGG and CGAG were associated with the increased frequencies of total MN and MNed cells with adjustment for covariates among coke-oven workers. This study showed that the haplotypes derived from htSNPs in the XRCC1 gene were more likely than single SNPs to correlate with the polycyclic aromatic hydrocarbon-induced chromosome damage among coke-oven workers.     

黄芪注射液对刀豆蛋白诱导的小鼠肝脏损伤的保护作用

目的：观察免疫损伤模型组与实验组小鼠外周血中T细胞亚群的变化情况，探讨黄芪注射液对小鼠肝脏损伤的保护作用。方法实验组小鼠每天腹腔注射黄芪注射液400μl，正常组与模型组小鼠每天给予等剂量的生理盐水。第7天在给药1小时后，模型组与实验组小鼠分别经尾静脉注射刀豆蛋白，正常组小鼠则给予等剂量的生理盐水。8小时后检测各组动物外周血中CD4^＋T、CD8^＋T细胞以及CD4^＋／CD25^＋T细胞所占比例，检测血浆转氨酶水平，制备肝脏病理标本，进行HE染色。结果尾静脉注射8小时后，实验组小鼠外周血的CD4^＋所占T细胞比例较模型组有所升高（P〈0．05），但仍低于正常组水平（P〉0．05）：而CD8^＋T细胞的比例则无明显变化（P〉0．05）。实验组ALT、AST水平明显低于模型组（P〈0．05）。实验组汇管区淋巴细胞浸润明显减少。结论黄芪注射液对刀豆蛋白诱导的小鼠肝损伤有确切的保护作用。     

闭角型青光眼患者红细胞免疫功能与EPO和ET-1的相关性

目的：探讨闭角型青光眼患者红细胞免疫功能与血清促红细胞生成素(EPO)和血浆内皮素-1(ET-1)的相关性。

方法：选取2017-06/10期间我院收治的闭角型青光眼患者30例(病例组)与眼部正常者30例(对照组)为研究对象。测定并比较两组受试者红细胞免疫功能、血清EPO和血浆ET-1浓度,分析之间的相关性。

结果：病例组受试者红细胞C3b受体花环率明显低于对照组(10.81%±2.01% vs 18.06%±3.44%),红细胞免疫复合物花环率明显高于对照组(17.21±3.49% vs 11.74±2.14%),血清EPO浓度明显高于对照组(26.10±5.22 mU/mL vs 22.68±4.06mU/mL),血浆ET-1浓度明显高于对照组(70.85±7.16ng/L vs 58.43±5.09ng/L)。闭角型青光眼患者红细胞C3b受体花环率与血清EPO浓度呈显著正相关(r=0.271,P<0.05),与血浆ET-1浓度无明显相关性。

结论：闭角型青光眼患者红细胞免疫功能与血清EPO浓度呈正相关。     

O-GlcNAc修饰在糖尿病心肌病中的作用及机制研究进展

<正>糖尿病是一种慢性代谢性紊乱疾病。据统计,我国2021年糖尿病患者数量已高达1.41亿[1]。糖尿病引发的心血管意外已成为患者死亡的主要原因,且死亡率明显高于非糖尿病患者[2]。糖尿病心肌病(diabetic cardiomyopathy, DCM)是一种因长期高血糖引起的心脏结构和功能异常的疾病,与多种信号通路有关。     

一种小鼠肠道纤维化模型建造的方法及评价

目的 探究一种使用酒精建造C57BL/6小鼠肠道纤维化模型的方法。方法 将6周龄C57BL/6小鼠根据不同酒精浓度分为正常对照组、50%乙醇组、三硝基苯磺酸(TNBS)/30%乙醇组、TNBS/50%乙醇组,采用灌肠液灌肠方式造模,每周灌肠1次,持续5周,第6周处死后取结直肠。整个实验期间观察小鼠生存状态、体重变化及生存率,每天进行小鼠疾病活跃指数(DAI)评价。固定包埋后,采用苏木精-伊红染色检测肠道黏膜以及腺体结构完整性;马森三色染色法检测小鼠肠道胶原沉积情况;免疫组织化学染色检测纤维化蛋白α-平滑肌肌动蛋白(α-SMA)的表达量。结果 与正常对照组比较,50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的黏膜破损、腺体丢失比例、纤维化蛋白α-SMA表达明显高于正常对照组,并且50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的DAI评分更高、胶原沉积更多,且TNBS/50%乙醇组高于TNBS/30%乙醇组,50%乙醇组与TNBS/30%乙醇组相近。结论 与正常组比较,50%乙醇组小鼠各时间点DAI评分均明显增高,整体纤维化程度与TNBS/30%乙醇组类似,单纯使用乙醇可以建造小鼠肠道的纤维化模型。     

Role of phloretin as a sensitizer to TRAIL-induced apoptosis in colon cancer

Phloretin is one of the apple polyphenols with anticancer activities. Since tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves important roles in inducing apoptosis, the present study examined the effect of phloretin on TRAIL-induced apoptosis in colon cancer cells. Treatment with both phloretin and TRAIL markedly suppressed the survival of cancer cells from several colon cancer cell lines compared with that of cells treated with either TRAIL or phloretin. Additionally, decreased numbers of colonies were observed following addition of phloretin and TRAIL. Furthermore, TRAIL- and phloretin-treated HT-29-Luc cells exhibited decreased luciferase activity. Increased apoptosis was observed in phloretin- and TRAIL-treated HT-29-Luc colon cancer cells, accompanying elevated levels of cleaved poly(ADP-ribose) polymerase, and caspase-3, −8 and −9. The expression levels of MCL1 apoptosis regulator BCL2 family member (Mcl-1) were decreased following addition of phloretin in colon cancer cells. In addition, overexpression of Mcl-1 in phloretin- and TRAIL-treated HT-29-Luc cells resulted in increased cell survival. Treatment of HT-29-Luc cells with a combination of cycloheximide (CHX) and phloretin led to a more prominent decrease in Mcl-1 expression compared with that in cells treated with CHX alone, while Mcl-1 expression was recovered by treatment with MG132. Binding of ubiquitin with Mcl-1 was verified using immunoprecipitation. Intraperitoneal injection of both TRAIL and phloretin into tumor xenografts was associated with a decreased tumor volume compared with that following injection with either TRAIL or phloretin. Overall, the present results suggest a synergistic effect of phloretin on TRAIL-induced apoptosis in colon cancer cells.     

不同程度近视患者行SMILE术后的有效光学区及角膜高阶像差比较

目的：比较低、中、高度近视患者行飞秒激光小切口基质透镜取出术(SMILE)后的有效光学区和角膜高阶像差。

方法：收集2019-02/2021-02在我院行SMILE手术的患者134例,均取右眼入组,按等效球镜度(SE)分为低度近视组SE>-3.00 D,中度近视组-6.00 D结果：SMILE术后1 mo,三组术后有效光学区均小于预设光学区,随着屈光度数增加,有效光学区越小(P<0.05); 术后1 mo角膜总高阶像差、球差、彗差均高于术前,除低近视度组球差术前与术后1 mo无差异(P>0.05),其余组别均有差异(P<0.05); 角膜总高阶像差、球差和彗差随着屈光度数增加而增加,三组角膜总高阶像差和球差有差异(均P<0.05),高度近视组与中度近视组、低度近视组彗差结果均有差异(P<0.05),中度近视组与低度近视组彗差结果无差异(P>0.05)。

结论：随着手术矫正的屈光度数增加,术后有效光学区减少越多,角膜高阶像差增加越明显; SMILE术后1 mo角膜高阶像差较术前增加。