Human Neutrophil Defensins and Their Effect on Epithelial Cells

Background: The aims of the present study include: 1) to localize human neutrophil defensin‐1 (HNP‐1) through HNP‐3 in gingiva and in neutrophil extract‐treated epithelial cell monolayers; 2) to determine the effects of HNP‐1 on the epithelial cell viability, attachment, and spreading; and 3) to analyze the effect of HNP‐1 on the bacterial adherence to epithelial cells. Methods: For localization of HNP‐1 through HNP‐3 in gingival tissue and in preincubated cell monolayers, immunohistochemical and immunocytochemical methods were used. Viability and proliferation of epithelial cells were determined with commercial kits after incubating the keratinocytes with different HNP‐1 concentrations (low, 1 to 5 μg/mL; moderate, 10 μg/mL; high, 20 to 50 μg/mL). Attachment and spreading of keratinocytes on fibronectin‐coated surfaces in the presence of HNP‐1 were evaluated under microscope. Attachment of Fusobacterium nucleatum ATCC25586 and Prevotella intermedia ATCC25611 on keratinocytes preincubated with HNP‐1 were determined with a standard antibiotic test. Results: HNP‐1 through HNP‐3 localized in the junctional epithelium of clinically healthy gingiva and in the pocket epithelium of gingiva with periodontitis. When keratinocyte monolayers were incubated with neutrophil extracts, HNP‐1 through HNP‐3 were bound to the periphery of the growing cell colonies. In low HNP‐1 concentrations, the keratinocyte proliferation enhanced. Moderate and high concentrations of HNP‐1 increased the cellular death significantly. HNP‐1 increased the attachment and spreading of keratinocytes on fibronectin‐coated surfaces and bacterial attachment to keratinocytes in a concentration‐dependent manner. Conclusion: HNP‐1 plays a role in the integrity of keratinocytes by stimulating their proliferation, attachment, and spreading, whereas higher doses increase the bacterial attachment and keratinocyte death.     

抗甲胎蛋白单链抗体与阿霉素联合对人肝癌细胞Huh7增殖的抑制作用

探讨抗人甲胎蛋白(AFP)单链抗体和阿霉素(DOX)单用或联用对人肝癌细胞Huh7细胞增殖的抑制作用。采用MTT法检测抗AFP单链抗体、阿霉素单用及联合作用对Huh7细胞增殖的影响;采用Annexin V/PI荧光双染法检测抗AFP单链抗体、阿霉素单用及联合作用对Huh7细胞凋亡的影响;采用PI单染法检测抗AFP单链抗体、阿霉素单用及联合作用对Huh7细胞周期分布的影响。结果表明,抗AFP单链抗体、阿霉素单药组与联用组均能有效抑制Huh7细胞增殖,呈剂量依赖性,且两药联用具有协同效应;抗AFP单链抗体、阿霉素单用及联用均可诱导细胞凋亡且抗AFP单链抗体(40 μg/mL)与阿霉素(0.25 μg/mL)联合组凋亡率明显高于单独给药组,具有统计学意义(P<0.05);抗AFP单链抗体(40 μg/mL)单独作用后,Huh7的细胞周期阻滞于G₀/G₁期,阿霉素(0.25 μg/mL)单独作用Huh7的细胞周期阻滞于S期,而当两种药物联用时,Huh7的细胞周期被阻滞于G₂/M期,抑制细胞增殖。     

Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR null mutants,yet alpha7 nAChR agonists do not improve probabilistic learning

Cognitive impairments, e.g., reward learning, are present in various psychiatric disorders and warrant treatment. Improving reward-related learning could synergistically enhance psychosocial treatments and cognition generally. A critical first step is to understand the mechanisms underlying reward learning. The dopamine system has been implicated in such learning, but less known is how indirect activation of this system may affect reward learning. We determined the role of alpha7 nicotinic acetylcholine receptors (nAChR) on a probabilistic reversal learning task (PRLT) in mice that includes reward and punishment. Male alpha7 knockout (KO), heterozygous (HT), and wildtype (WT) littermate mice (n?=?84) were treated with vehicle, 0.03, or 0.3?mg/kg nicotine. Two cohorts of C57BL/6NJ male mice were treated with various alpha7 nAChR ligands, including the full agonists PNU282877 and AR-R-17779, the positive allosteric modulator CCMI, the partial agonist SSR180711, and the antagonist methyllycaconitine. All mice were then tested in the PRLT. Nicotine (0.3?mg/kg) significantly improved initial reward learning in alpha7 WT and HT mice but did not improve learning in KO mice, suggesting an involvement of the alpha7 nAChR in the pro-learning effects of nicotine. Neither alpha7 nAChR treatments (PNU282987, AR-R-17779, CCMI, SSR180711, nor methyllycaconitine) affected mouse PRLT performance however. Nicotine improved reward learning via a mechanism that may include alpha7 nAChRs. This improvement unlikely relied solely on alpha7 nAChRs however, since no alpha7 nAChR ligand improved reward learning in normal mice. Future assessments of the effects of other nAChR subtypes on reward learning are needed.     

四川省三个核设施地区水源水总α、总β放射性水平调查

目的 调查四川省三个核设施地区水源水总α、总β放射性水平,为本省核设施地区水源水放射性水平提供基线数据库。方法 根据国家标准《生活饮用水标准检验方法放射性指标》（GB/T 5750.13-2006）的方法要求,调查四川省三个核设施地区水源水总α、总β放射性水平。结果 三个核设施地区水源水总α比活度范围为（0.016~0.188）Bq/L;总β比活度范围为（0.028~0.229）Bq/L,处于全国平均中下水平,属于正常的本底水平。结论 三个核设施地区水源水总α、总β放射性水平均低于《生活饮用水卫生标准》（GB 5749-2006）中的国家标准限值。     

核磁共振结合血清甲胎蛋白、肌酸激酶水平诊断凶险型前置胎盘合并胎盘植入的价值

目的对核磁共振(MRI)结合血清甲胎蛋白(AFP)、肌酸激酶(CK)表达诊断凶险型前置胎盘合并胎盘植入的价值进行探讨。方法选取2015年1月-2016年10月收治的90例凶险型前置胎盘患者,根据手术和术后病理结果分为凶险型前置胎盘合并胎盘植入组(简称植入组,53例)和凶险型前置胎盘非胎盘植入组(简称非植入组,37例),比较两组患者静脉血中AFP、CK的水平,并将所有患者的MRI结果、血清学检查结果及两者联合检查结果与病理结果进行比较。结果植入组血清AFP和CK表达水平显著高于非植入组(P<0.05)。MRI、血清学检查及二者联用的诊断灵敏度(71.74%vs.67.92%)、漏诊率(28.3%vs.32.13%)、阴性预测值(63.34%vs.63.0%)和符合率(71.12%vs.72.25%)之间比较,差异具有统计学意义(P<0.05),联合诊断的灵敏度(90.56%)、阴性预测值(86.84%)和符合率(90.00%)均显著高于单独的MRI或血清学检查(P<0.05),漏诊率(9.43%)低于单独的MRI或血清学检查(P<0.05)。结论 MRI联合血清AFP、CK表达检测能提高诊断的灵敏度和诊断符合率,优于单项检测,具有一定的诊断价值。     

血清肿瘤标志物联合检测在原发性肝癌诊断中的价值研究

目的:探讨细胞周期素A2(CCNA2)与甲胎蛋白(AFP)、癌胚抗原(CEA)、癌抗原199(CA199)及癌抗原724(CA724)的联合检测在原发性肝癌临床诊断中的价值,以期筛选出理想的肿瘤标志物组合,提高肝癌诊断的准确率。方法:选取2020年10月—2021年3月天津市第三中心医院收治的原发性肝癌患者68例为研究对象,作为原发性肝癌组;另选择同期收治的80例肝病患者作为肝良性疾病组,80例健康体检者作为健康对照组。采集各研究对象清晨空腹静脉血5 mL,采用addicare1100酶免仪利用酶联免疫吸附法(ELISA)检测血清CCNA2,采用罗氏e801全自动电化学发光仪及其配套试剂检测血清AFP、CEA、CA199和CA724。评估上述指标单项及联合检测在早期PLC诊断的应用价值。结果:健康对照组血清肿瘤标志物均显著低于肝良性疾病组与原发性肝癌组,差异有统计学意义(P＜0.05)。68例原发性肝癌患者中,对AFP、CEA、CA199、CA724和CCNA2等血清肿瘤标志物水平予以检测,联合检测的特异性和准确性均显著高于各指标的单项检测结果,差异有统计学意义(P＜0.05)。结论: CCNA2作为一种新型的肿瘤标志物,对肝癌的诊断具有一定的价值。CA199、CEA、AFP、CA724、CCNA2联合检测能显著提升原发性肝癌的诊断阳性率,对尽早诊断原发性肝癌具有重要意义。     

Lenstar LS900测量仪与 iTrace视觉功能分析仪测量白内障患者术前Kappa角与Alpha角一致性研究

目的　比较Lenstar LS900测量仪与iTrace视觉功能分析仪测量年龄相关性白内障患者术前Kappa角与Alpha角的一致性。方法　收集2017年12月至2018年6月在中国医科大学附属第四医院眼科就诊的年龄相关性白内障患者55例（59眼）,术前分别应用Lenstar LS900测量仪和iTrace视觉功能分析仪测量以瞳孔为中心的视轴偏心距（Kappa角）和以虹膜为中心的视轴偏心距（Alpha角）。先收集在角膜顶点平面分解的X轴和Y轴坐标,再通过三角函数计算偏心距,最后分别比较X轴、Y轴、瞳孔直径、角膜水平直径、视轴偏心距。两种仪器所测数据的比较采用配对t检验,一致性比较采用Bland-Altman分析。结果　Lenstar LS900测量的Kappa角为（0.270±0.128）mm,Alpha角为（0.349±0.128）mm,瞳孔直径为（4.101±0.773）mm,角膜水平直径（白到白,WTW）为（10.848±0.467）mm,X轴Kappa角为（0.016±0.225）mm,Y轴Kappa角为（0.105±0.185）mm,X轴Alpha角为（0.010±0.353）mm,Y轴Alpha角为（0.042±0.195）mm。iTrace视觉功能分析仪测量的Kappa角为（0.296±0.131）mm,Alpha角为（0.338±0.121）mm,瞳孔直径为（4.103±0.797）mm,角膜水平直径（白到白,WTW）为（10.837±0.475）mm,X轴Kappa角为（0.022±0.233）mm,Y轴Kappa角为（0.091±0.172）mm,X轴Alpha角为（0.006±0.345）mm,Y轴Alpha角为（0.029±0.112）mm。两种仪器测量各项数据比较,差异均无统计学意义（均为P>0.05）。Bland-Altman分析显示,两种仪器的检测结果具有较好的一致性。结论　Lenstar LS900与iTrace两种仪器测量年龄相关性白内障患者术前的Kappa角和Alpha角的一致性良好,能够为屈光性人工晶状体的选择提供一定的参考依据。     

The clinical efficacy of cosmeceutical application of liquid crystalline nanostructured dispersions of alpha lipoic acid as anti-wrinkle

Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3). In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2 and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method. Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature, rheological measurements and in vitro drug release studies. Results suggested that by increasing P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo controlled clinical study was conducted, aiming to evaluate the efficacy as an anti-wrinkle agent and volunteer’s satisfaction upon application of topical 30% P407 gel loaded with ALA cubosomes. Results indicated reduction in facial lines, almost complete resolution of fine lines in the periorbital region and upper lip area and overall improvement in skin color and texture in most volunteers. There were no instances of irritation, peeling or other apparent adverse side effects.