Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes

MUC1 mucin is known to serve as a target molecule in the killing of breast cancer cells by cytotoxic T-lymphocytes (CTLs). We searched for a possible mechanism allowing tumour cells to escape from autologous CTLs. When the killing of breast cancer cells by autologous lymphocytes was examined in 26 patients with breast cancer, significant tumour cell lysis was observed in 8 patients, whereas virtually no autologous tumour cell lysis was detected in as many as 18 patients. In the patients who showed negligible tumour cell lysis, the autologous tumour cells expressed MUC1-related antigenic epitopes much more weakly than the tumour cells in the patients who exhibited strong cytotoxicity (significant statistically at P< 0.0005-0.0045), suggesting that the unresponsiveness of cancer cells to CTLs observed in these patients was mainly due to loss of MUC1 expression or modulation of its antigenicity. A breast cancer cell line, NZK-1, established from one of the cytotoxicity-negative patients, did not express MUC1 and was resistant to killing by CTLs, while control breast cancer cell lines expressing MUC-1 were readily killed by CTLs. Transfection of NZK-1 cells with MUC1 cDNA induced significant lysis by autologous T-lymphocytes. These results supported the importance of MUC1 mucin in autologous anti-tumour immunity, but suggested that the major escape mechanism of tumour cells from autologous T-lymphocytes is the loss and/or modulation of MUC1 antigenicity on tumour cells, which would limit the effectiveness of possible immunotherapy designed to target the MUC1 mucin.     

2-苯氧茚酮类乙酰胆碱酯酶抑制剂的3D-QSAR研究

目的研究2-苯氧茚酮类乙酰胆碱酯酶抑制剂的三维定量构效关系。方法采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA)对结构与活性的关系进行研究。结果CoMFA模型表明立体场和静电场对活性的贡献分别为0.805和0.195;CoMSIA模型阐明疏水场和氢键场对活性也有一定的影响。结论两种3D-QSAR模型都显示出相当高的预测能力,CoMFA和CoMSIA的交叉验证值q2分别为0.881和0.918,通过对两种3D-QSAR模型等势图的分析,可为开展进一步的药物设计和结构优化提供理论指导和依据。     

HPLC-ELSD法同时测定注射用双黄连中4种糖类成分

目的建立测定注射用双黄连（冻干）中果糖、葡萄糖、蔗糖和肌醇含量的HPLC-ELSD方法。方法采用Alltech GRACE prevail carbohydrate ES色谱柱;漂移管温度：100℃;载气（N2）流速：2.0L·min-1;流动相：乙腈-水（7525）;流速：1.0mL·min-1;柱温：30℃。结果果糖、葡萄糖、蔗糖和肌醇进样量分别在0.530~3.975μg（r=0.9996）、0.626~4.695μg（r=0.9999）、0.722~5.415μg（r=0.9997）、0.208~1.560μg（r=0.9995）范围内,质量对数与峰面积对数呈良好的线性关系;平均加样回收率分别为100.1%、97.1%、98.5%、96.1%,RSD分别为2.8%、3.0%、3.4%、3.7%。结论该方法可同时测定注射用双黄连（冻干）中4种糖类成分的含量,分离度好,快速、简便,重现性好,可用于双黄连注射剂中糖类成分的含量测定。     

新型含异噁唑的甘草次酸酰胺类衍生物的合成研究

目的合成甘草次酸酰胺的异噁唑衍生物,寻找活性好的抗炎药物。方法以甘草次酸为原料,与3-取代苯基-5-异唑甲胺进行偶联,合成了6个新型甘草次酸酰胺类衍生物,采用IR、1H-NMR、13C-NMR、MS等方法确定其化学结构。以二甲苯引起的小鼠耳肿模型和醋酸引起的小鼠腹膜炎模型评价了抗炎活性。结果IR、1H-NMR、13C-NMR、MS等数据表明这些化学结构正确。其中,化合物具有明显的抗炎活性。结论合成的系列新化合物结构正确,发现了一个抗炎活性较强的化合物。     

Consumption of a Low Carbohydrate Diet in Overweight or Obese Pregnant Women Is Associated with Longer Gestation of Pregnancy

Studies of obstetric outcomes in women consuming low-carbohydrate diets have reported conflicting results. Most studies have defined low-carbohydrate diets by the percentage that carbohydrates contribute to overall energy intake, rather than by an absolute amount in grams per day (g/d). We hypothesised that a low absolute carbohydrate diet affects obstetric outcomes differently than a low percentage carbohydrate diet. Dietary data were collected from overweight or obese women in the Study of Probiotic IN Gestational diabetes at 16- and 28-weeks’ gestation. Obstetric outcomes were compared between women whose carbohydrate intake was in the lowest quintile vs quintiles 2–5. Mean gestation was increased in women whose absolute carbohydrate intake was in the lowest quintile at 16 and at both 16- and 28-weeks’ gestation compared with all other women (16: 39.7 vs. 39.1 weeks, p = 0.008; 16 and 28: 39.8 vs. 39.1, p = 0.005). In linear regression analysis, a low absolute carbohydrate intake at 16 and at 28 weeks’ gestation was associated with increased gestation at delivery (16: p = 0.04, adjusted R² = 0.15, 28: p = 0.04, adjusted R² = 0.17). The coefficient of beta at 16 weeks’ gestation was 0.50 (95% CI 0.03–0.98) and at 28 weeks’ gestation was 0.51 (95%CI 0.03–0.99) meaning that consumption of a low absolute carbohydrate diet accounted for an extra 3.5 days in gestational age. This finding was not seen in women whose percentage carbohydrate intake was in the lowest quintile. Low-carbohydrate consumption in pregnancy is associated with increased gestational age at delivery.     

利福霉素类衍生物的研究进展

本文回顾了利福霉素的发现及发展过程,介绍了此类药物的构效关系,并对其结构上C-3,C-4,C-11,C-25等部位的改造及目前研究较热的几种新的利福霉素类药物,如利福美坦、FCE-22250、利福拉齐,KRM-1657等的研究状况进行了综述和展望.     

苯丙烯酰胺类化合物的合成及抗肿瘤活性研究

目的设计并合成一系列苯丙烯酰胺衍生物并考察其抗肿瘤活性。方法以4-氨甲基苯甲酸为原料合成一系列苯甲酰胺类组蛋白去乙酰化酶抑制剂。目标化合物经过1H-NMR、MS鉴定,且采用MTT法对其抗肿瘤活性进行了初步评价。结果与结论设计并合成了8个新化合物,其中3个化合物显示出良好的抗肿瘤活性,为进一步对抗肿瘤药物的结构优化奠定了一定的基础。     

Prebiotics and the Human Gut Microbiota: From Breakdown Mechanisms to the Impact on Metabolic Health

The colon harbours a dynamic and complex community of microorganisms, collectively known as the gut microbiota, which constitutes the densest microbial ecosystem in the human body. These commensal gut microbes play a key role in human health and diseases, revealing the strong potential of fine-tuning the gut microbiota to confer health benefits. In this context, dietary strategies targeting gut microbes to modulate the composition and metabolic function of microbial communities are of increasing interest. One such dietary strategy is the use of prebiotics, which are defined as substrates that are selectively utilised by host microorganisms to confer a health benefit. A better understanding of the metabolic pathways involved in the breakdown of prebiotics is essential to improve these nutritional strategies. In this review, we will present the concept of prebiotics, and focus on the main sources and nature of these components, which are mainly non-digestible polysaccharides. We will review the breakdown mechanisms of complex carbohydrates by the intestinal microbiota and present short-chain fatty acids (SCFAs) as key molecules mediating the dialogue between the intestinal microbiota and the host. Finally, we will review human studies exploring the potential of prebiotics in metabolic diseases, revealing the personalised responses to prebiotic ingestion. In conclusion, we hope that this review will be of interest to identify mechanistic factors for the optimization of prebiotic-based strategies.     

CEA,CA72-4在结直肠癌中的临床应用探讨

目的 探讨血清肿瘤标志物癌胚抗原(CEA),糖类抗原CA72-4在结直肠癌诊断、术后效果监测、预后判断的应用价值.方法 应用电化学发光分析法测定血清中CEA,CA72-4,共测定35例健康成人及91例病理确诊结直肠癌患者,并检测32例术后患者的血清水平.结果 对照组CEA为2.1±1.4 ng/mL,CA72-4为4.8±2.1 u/mL.结直肠癌患者Dukes B、C、D期CEA,CA72-4均较对照组有明显增高,差异有统计学意义(P＜0.05),并且血清水平随临床分期的严重程度而增高.32例术前患者血清CEA为27.9±22.1 ng/mL,CA72-4为9.4±6.3 u/mL,术后CEA,CA72-4血清水平分别为2.5±1.7 ng/mL,4.5±3.4 u/mL,检测结果较术前明显下降,差异有统计学意义(P＜0.05).两者的联合检测可提高诊断的敏感性及有效性,但是特异性有所降低.结论 CEA,CA72-4对结直肠癌诊断、术后效果监测、预后判断有意义,但是血清肿瘤标记物诊断敏感性不理想,有必要进行新的肿瘤标记物研究.     

Effect of Different Carbohydrate Intakes within 24 Hours after Glycogen Depletion on Muscle Glycogen Recovery in Japanese Endurance Athletes

Daily muscle glycogen recovery after training is important for athletes. Few studies have reported a continuous change in muscle glycogen for 24 h. We aimed to investigate the changes in carbohydrate intake amount on muscle glycogen recovery for 24 h after exercise using ¹³C-magnetic resonance spectroscopy (¹³C-MRS). In this randomized crossover study, eight male participants underwent prolonged high-intensity exercise, and then consumed one of the three carbohydrate meals (5 g/kg body mass (BM)/d, 7 g/kg BM/d, or 10 g/kg BM/d). Glycogen content of thigh muscle was measured using ¹³C-MRS before, immediately after, and 4 h, 12 h and 24 h after exercise. Muscle glycogen concentration decreased to 29.9 ± 15.9% by exercise. Muscle glycogen recovery 4–12 h after exercise for the 5 g/kg group was significantly lower compared to those for 7 g/kg and 10 g/kg groups (p < 0.05). Muscle glycogen concentration after 24 h recovered to the pre-exercise levels for 7 g/kg and 10 g/kg groups; however, there was a significant difference for the 5 g/kg group (p < 0.05). These results suggest that carbohydrate intake of 5 g/kg BM/d is insufficient for Japanese athletes to recover muscle glycogen stores 24 h after completing a long-term high-intensity exercise.