人新饱食分子蛋白1在妊娠期代谢异常中的研究进展

人新饱食分子蛋白1(Nesfatin-1)是一种分泌性肽,与抑食功能有关,但其作用机制尚未完全阐明。国内外学者研究发现,Nesfatin-1不仅影响抑食功能,还参与能量代谢。目前,Nesfatin-1在2型糖尿病、代谢综合征、妊娠期糖尿病及摄食行为中的研究较多,而在妊娠期代谢异常等方面涉及甚少。该文就Nesfatin-1在妊娠期代谢异常的研究进展作一综述。     

妊娠期糖尿病孕妇血糖和体重控制情况研究

目的探讨系统化血糖及体重控制对妊娠期糖尿病孕妇妊娠结局的影响。方法选择2018年1月-2019年1月中山大学附属第三医院粤东医院收治的100例妊娠期糖尿病孕妇作为研究对象,按护理方式的不同分为观察组和对照组各50例。对照组接受常规治疗及饮食指导干预,观察组在对照组基础上进行系统化血糖和体重控制干预。比较两组孕妇餐前空腹血糖、体重控制情况及母婴并发症发生情况。结果观察组孕妇的血糖及体重控制情况优于对照组,且观察组孕妇及围生儿并发症的发生率低于对照组,差异均有统计学意义(P<0.05)。结论接受系统化血糖及体重控制的妊娠期糖尿病孕妇取得的效果较好,其血糖和体重指数控制较好,母婴并发症少,具有临床推广价值。     

虾青素对过氧化氢诱导胎盘滋养细胞HTR-8/SVneo的影响

目的观察虾青素通过烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶/活性氧(ROS)信号通路对过氧化氢(H2O2)诱导人胎盘滋养细胞HTR-8/SVneo的影响。方法实验分为空白组、模型组和实验组,每组8个复孔;实验组HTR-8/SVneo细胞预先以10 nmol·L^-1虾青素处理24 h,之后实验组和模型组细胞均以250μmol·L-1H2O2作用24 h;空白组未进行任何药物干预。以噻唑蓝(MTT)法检测各组HTR-8/SVneo细胞增殖情况,以DCF-DA荧光染色检测各组HTR-8/SVneo细胞内ROS水平,检测各组HTR-8/SVneo细胞培养上清中乳酸(LDH)及氧化应激指标含量,以蛋白质印迹法检测各组细胞NADPH氧化酶4(NOX4)、p22phox蛋白表达情况。结果干预后24 h,空白组、模型组及实验组HTR-8/SVneo细胞内ROS荧光强度值分别为2.76±0.43,34.15±2.34,15.61±1.85,LDH分别为(756.24±31.05),(1785.46±34.69),(1235.26±26.75)U·L^-1,超氧化物歧化酶(SOD)分别为(23.56±2.24),(10.04±2.02),(15.16±3.08)U·mg^-1,丙二醛(MDA)分别为(0.46±0.14),(0.96±0.21),(0.68±0.13)U·mg^-1,Nox4蛋白相对表达量分别为0.32±0.04,0.89±0.06,0.64±0.03,p22phox蛋白相对表达量分别为0.15±0.03,0.75±0.04,0.49±0.02,模型组分别与空白组和实验组比较,差异均有统计学意义(均P<0.05)。结论虾青素对H2O2诱导人胎盘滋养细胞HTR-8/SVneo氧化应激损伤具有保护作用,可能与干扰NADPH氧化酶/ROS信号通路活性有关。     

强化血糖控制对胰腺癌合并糖尿病患者术后血糖变异性的影响

目的 探讨强化血糖控制对胰腺癌合并糖尿病患者术后血糖变异性的影响。方法 选取2019年1月-2020年1月我院普通外科研究所收治的90例胰腺癌行胰十二指肠切除术后患者为研究对象，随机分为对照组和试验组各45例,对照组给予常规模式护理，试验组在对照组基础上给予强化血糖控制干预，比较两组患者初始血糖值、平均血糖值、血糖标准差及血糖变异系数。结果 两组初始血糖值相比较，差异无统计学意义（P＞0.05）。与对照组相比较，强化血糖控制后平均血糖值[(8.03±1.12)vs(8.80±1.58)]、血糖标准差[(1.730.93)vs(2.16±0.71)]、血糖变异系数[(20.72±10.04)vs(24.88±7.63)]均降低，试验组患者血糖控制水平明显优于对照组（P<0.05）。结论 强化血糖控制能有效改善胰腺癌合并糖尿病患者术后血糖水平，保障患者安全，改善预后，促进康复。     

Deficient glucose uptake is linked to impaired Glut1 expression upon CD3/CD28 stimulation in memory T cells from pleural effusions secondary to lung cancer

Glucose and nutrient uptake is essential in supporting T cell activation and is increased upon CD3/CD28 stimulation. As T cells from pleural effusions secondary to lung cancer show impaired function, we hypothesized that these cells might have altered expression of nutrient transporters. Here, we analysed by flow cytometry the expression of the transferrin receptor CD71, amino acid transporter CD98 and glucose transporter Glut1 and glucose uptake in pleural effusion‐derived T cells from lung cancer patients, after stimulation via CD3/CD28 under normoxia or hypoxia (2% O₂). We compared the response of T cells from pleural effusions secondary to lung cancer with that of T cells from nonmalignant effusions. In memory T cells from both groups, anti‐CD3/CD28‐stimulation under normoxia upregulated CD98 and CD71 expression (measured as median fluorescence intensity, MFI) in comparison with anti‐CD3‐stimulation. Costimulation under hypoxia tended to increase CD98 expression compared to CD3‐stimulation in memory T cells from both groups. Remarkably, in the cancer group, memory T cells stimulated via CD3/CD28 under hypoxia failed to increase CD71 and Glut1 expression levels compared to the cells receiving anti‐CD3 stimulation, a phenomenon that contrasted with the behaviour of memory T cells from nonmalignant effusions. Consequently, glucose uptake by memory T cells from the cancer group was not increased after CD3/CD28 stimulation under hypoxia, implying that their glycolytic metabolism is defective. As this process is required for inducing an antitumoural response, our study suggests that memory T cells are rendered dysfunctional and are unable to eliminate lung tumour cells.     

In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

Studies on the L-2-hydroxy-acid oxidase 2 catalyzed metabolism of S-mandelic acid and its analogues

Mandelic acid (MA) is generally used as a biomarker of the exposure of styrene, which is classified as a class of hazardous environmental pollutants, and also used as an important chiral intermediate in pharmaceutical industry. The previous studies have found the excretion of phenylglyoxylic acid (PGA) in human and rat, a metabolite of MA, was mainly from S-MA rather than R-MA. The metabolic mechanism, however, is not clear. In order to explore the possible metabolic mechanism, the enzyme types involved in the stereoselectivity metabolism of MA were firstly studied, and then human and rat long-chain 2-hydroxy-acid oxidase 2 (HAO2) were recombinantly expressed to study the metabolic profiles of S-MA and its analogues. The results indicated that HAO2 might catalyze the stereoselectivity metabolism of S-MA in rats. Human HAO2 (hHAO2) and rat HAO2 (rHAO2) isozymes β₁ and β₂ were successfully cloned and expressed with high purity and good enzyme activities. The enzyme kinetic profiles of these enzymes were different for S-MA and analogues. The order of catalytic efficiency for hHAO2 and rHAO2, however, was reverse. It might be relevance to the difference in active amino acid residues and loop 4 in human and rat L-2-hydroxy acid oxidase isozyme B crystal structures.