Profile of new vascular damage biomarkers in middle-aged men with arterial hypertension

PurposeNormal endothelial function is important for the homeostasis of the cardiovascular (CV) system. The aim of the present study was to determine the profile of key parameters of endothelial dysfunction in middle-aged men that play a significant role in the functioning of endothelial vessels, which seems to be crucial for the early diagnosis of cardiovascular disorders.Materials and methodsThe study included 53 men, 20 with hypertension (HTN), 18 with HTN and related diseases, 15 healthy controls Apart from general testing (BMI, biochemical analysis, SBP, DBP), we used the Griess reaction to assess the total amount of nitric oxide (NO), and used ELISA to verify the concentrations of malondialdehyde (MDA), nitrotyrosine (NT), asymmetric dimethylarginine (ADMA), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), and myeloperoxidase (MPO). Furthermore, we assessed the concentration of circulating free DNA (cfDNA) using the fluorescence method.ResultsThe values of MDA, ADMA, cfDNA, and MPO observed in samples from men with HTN were determined to be higher compared to those from men without HTN. In the group of men with HTN and other concomitant cardiovascular disorders, we observed low concentrations of NO, MDA, and ADMA with high concentrations of cfDNA.ConclusionsThe results obtained for parameters selected for the study, should be considered by cardiologists as a prompt to include in the diagnostic profile the assessment of NO and cfDNA concentrations for risk evaluation and/or diagnosis of endothelial dysfunction in patients suffering from HTN or related complications.     

运用MRI评估超顺磁性氧化铁纳米粒在肝硬化肝癌组织中分布变化的实验研究

目的研究超顺磁性氧化铁纳米粒(SPIO)作为MRI对比剂在肝硬化肝癌组织中分布变化情况,探讨其用于分子靶向成像的可行性。方法 SPF级雄性SD大鼠35只,体质量(200±20)g,鼠龄3个月。按完全随机分组的方法分成实验组25只和对照组10只,实验组予质量浓度0.1mg/mL的二乙基亚硝胺(DENA)溶液自由饮用,对照组饮用灭菌0.9%氯化钠溶液。于给药后20周先进行MRI平扫,再注入SPIO后1、24、48、72、96h分别行MRI增强扫描,每一时段5只。同理,空白对照组每一时段取2只。分析MRI图像,取血液标本进行肝功能测定,取肝脏标本进行苏木精-伊红和普鲁士蓝染色病理学检查。结果实验组大鼠肝功能指标丙氨酸氨基转移酶及天冬氨酸转氨酶[分别为(130.43±8.83)、(415.00±55.44)U/L]较对照组[分别为(39.57±7.25)、(132.93±39.03)U/L]显著升高(P<0.001)。正常肝组织及肝硬化组织,注入SPIO后1 h,各序列上肝脏组织信号明显下降,24 h肝脏组织信号强度下降百分比(PSIL)达到最大,48、72、96 h后均下降,各时段PSIL差异有统计学意义(P<0.001);而20周肝癌组织,注入SPIO各时段其信号无明显变化(P>0.05)。普鲁士蓝染色显示,正常肝组织及肝硬化组织蓝染的Kupffer细胞数在24 h达到最多,后逐步减少;部分高分化肝癌组织散在少许蓝染的Kupffer细胞,低分化肝癌组织内无蓝染细胞。不同肝脏组织SPIO增强后MRI各序列信号变化与组织中蓝染的Kupffer细胞数呈线性相关趋势,具有显著统计学意义(r正常=0.927,r肝硬化=0.912,P<0.01)。结论通过MRI扫描动态观察SPIO分布变化情况,不仅可用于肝脏恶性病变的检出,而且具有将SPIO作为MRI对比剂用于分子靶向成像的潜能。     

Antibacterial action of nitric oxide-releasing hyperbranched polymers against ex vivo dental biofilms

ObjectivesThis study investigates the antibiofilm action of nitric oxide (NO)-releasing hyperbranched polymers against ex vivo multispecies periodontal biofilms.MethodsThe antibiofilm efficacy of NO-releasing hyperbranched polymers was evaluated as a function of NO-release properties, polymer concentrations, and oxygen levels in the exposure media. 16s rRNA sequencing technique was employed to evaluate the impact of NO-releasing hyperbranched polymers on the microbial composition of the biofilms.ResultsThe addition of NO release significantly improved the antibiofilm action of the hyperbranched polymers, with NO-releasing hyperbranched polyamidoamines of largest NO payloads being more effective than hyperbranched polykanamycins. Furthermore, the NO-releasing hyperbranched polymers reduced the biofilm metabolic activity in a dose-dependent manner, killing biofilm-detached bacteria under both aerobic and anaerobic conditions, with greater antimicrobial efficacy observed under aerobic conditions.SignificanceThese results demonstrate for the first time the potential therapeutic utility of NO-releasing hyperbranched polymers for treating multispecies dental biofilms.     

热灌注化疗对口腔颌面部恶性肿瘤患者NO及T淋巴细胞的影响

目的: 探讨热灌注化疗对口腔颌面部恶性肿瘤患者NO及T淋巴细胞的影响。方法: 选取汉堡大学休伯特斯·沃尔德癌症中心2017年12月—2019年12月收治的口腔颌面部恶性肿瘤患者60例,按照随机数字表法分为热化疗组(30例)与常规化疗组(30例),常规化疗组患者给予单纯静脉化疗,热化疗组患者在静脉化疗的基础上给予热化疗。比较2组患者的治疗效果、NO及T淋巴细胞数量、生存质量以及毒副反应之间的差异。采用SPSS 22.0软件包进行数据统计。结果: 热化疗组的治疗有效率及疾病控制率显著高于常规化疗组。治疗后,热化疗组患者NO含量显著高于常规化疗组,CD4⁺、CD4⁺/CD8⁺显著高于常规化疗组,热化疗组患者体力功能、情感功能、社会功能等功能性指标及综合生存质量评分显著高于常规化疗组,疲劳、疼痛、便秘等症状性指标显著低于常规化疗组,差异均具有统计学意义(P<0.05)。2组患者的毒副作用比较差异无统计学意义(P>0.05)。结论: 热化疗可显著提高口腔颌面部恶性肿瘤患者的治疗效果及NO含量,改善患者的免疫功能,提高生存质量,且安全性较高。     

育龄女性MTHFR、MTRR基因多态性分布以及与血清叶酸和同型半胱氨酸水平的相关性研究

目的探讨叶酸代谢关键酶基因5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C和甲硫氨酸合成酶还原酶(MTRR)A66G多态性在育龄女性中的分布特征,并分析不同遗传特征对外周血叶酸和同型半胱氨酸(Hcy)水平的影响。方法选取2018年3月至2020年1月在上海计生所医院妇科就诊的汉族育龄女性2 651例,根据知情同意原则,采集口腔黏膜上皮脱落细胞,抽提基因组DNA,使用荧光定量PCR方法检测MTHFR C677T、A1298C和MTRR A66G基因多态性,采用化学发光法检测外周血叶酸水平,循环酶法检测血清Hcy水平。结果 (1)MTHFR C677TCC、CT、TT的基因型频率分别为33.2%、47.9%、18.9%,C、T等位基因频率分别为57.1%、42.9%;MTHFR A1298C AA、AC、CC的基因型频率分别为66.6%、30.5%、2.9%,A、C等位基因频率分别为81.8%、18.2%;MTRR A66G AA、AG、GG的基因型频率分别为56.4%、36.9%、6.8%,A、G等位基因频率分别为74.8%、25.2%。(2)MTHFR C677T和A1298C两位点连锁有7种组合,频率最高的是CT/AA(31.9%),没有CT/CC和TT/CC组合。两位点间存在完全连锁不平衡(D′=0.984,R2=0.161)。(3)MTHFR C677T不同基因型的叶酸和Hcy水平差异有统计学意义(P<0.05)。TT基因型的叶酸水平低于CC基因型,TT基因型的Hcy水平高于CC基因型。经单因素Logistic回归分析发现,MTHFR C677T TT基因型发生高Hcy血症的危险性是CC基因型的9.97倍(95%CI:3.81~26.05)。MTHFR A1298C和MTRR A66G不同基因型与血清叶酸及Hcy水平差异无统计学意义(P>0.05)。(4)经单因素回归分析,Hcy水平与叶酸水平呈负相关(R2=0.061,P<0.05),叶酸水平可解释Hcy水平个体差异的6.1%。结论获取了上海市汉族育龄女性MTHFR和MTRR基因多态性的群体遗传学特征,血清Hcy水平与MTHFR C677T基因多态性以及血清叶酸水平有关。筛查MTHFR和MTRR基因多态性并监测Hcy水平对围生期保健有重要的指导意义。     

Anti-inflammatory effects of peptides from a marine algicolous fungus Acremonium sp. NTU492 in BV-2 microglial cells

Located in tropical and subtropical region, Taiwan is an island with high algal species diversity. In this study, a number of fungal strains were isolated from marine macroalgae collected from northeastern intertidal zone of Taiwan. Preliminary anti-inflammatory screening has shown that the methanolic extracts of solid fermented products of the red alga Mastophora rosea-derived fungal strain Acremonium sp. NTU492 exhibited significant bioactivity. In an attempt to disclose the active principles from this fungal strain, a series of separation and purification was thus undertaken, which has led to the isolation and characterization of seven compounds including four new peptides, namely acrepeptins A–D (1–4), along with previously reported destruxin B (5), guangomide A (6), and guangomide B (7). Their structures were elucidated by spectroscopic analysis and compared with literatures. Of these, acrepeptins A (1) and C (3) showed markedly inhibitory activities on nitric oxide production in lipopolysaccharide-activated microglial BV-2 cells with IC₅₀ values of 12.0 ± 2.3 and 10.6 ± 4.0 μM, respectively. Furthermore, acrepeptins A (1) and C (3) significantly attenuated the expression of inducible nitric oxide synthase in a concentration-dependent manner (5–40 μM).     

2型糖尿病合并血管并发症患者一氧化氮和内皮素水平评价

目的：探讨合并血管并发症的2型糖尿病患者血清一氧化氮（ nitric oxide,NO）和内皮素（ endothelin,ET）水平的变化,并分析各危险因素与两者之间的关系。方法入选2型糖尿病患者98例,根据分组条件分为糖尿病合并血管并发症组（ A组,49例）和糖尿病无血管并发症组（ B组,49例）,同期选择年龄、体质指数相匹配的健康对照44例（ C组）。所有受试者记录身高、体质量、血压、病程,抽血检测空腹血糖（ fasting blood-glucose,FBG）、糖化血红蛋白（hemoglobin A1c,HbA1c）、血脂各项指标,以及血清NO和ET-1水平。结果与C组比较,A组及B组的NO水平均显著降低[（43．87±12．05）和（53．29±11．75）μmol／L vs （66．08±16．48）μmol／L,P＜0．01],而ET-1水平显著升高[（100．25±20．34）和（77．55±14．84）ng／L vs （53．62±8．40）ng／L,P＜0．01]。 A组NO水平显著低于B组[（43．87±12．05） vs （53．29±11．75）μmol／L,P＜0．01],而 ET-1水平显著高于B组[（100．25±20．34） vs （77．55±14．84）ng／L ,P＜0．01]。在糖尿病两组之间,收缩压、舒张压、HbA1c及病程,A组明显高于B组（P＜0．01）。相关分析显示,舒张压、收缩压、空腹血糖、HbA1c与NO之间存在负相关;HDL-C与NO之间存在正相关。HDL-C与ET-1存在负相关;收缩压、LDL-C、血尿酸、空腹血糖、HbA1c与ET-1之间存在正相关。结论糖尿病患者血清NO和ET水平明显异常,存在血管内皮功能损伤;有血管并发症者损伤更严重,且与血糖、血压、血脂的控制水平具有相关性。