Hemoglobin-Induced Nitric Oxide Synthase Overexpression and Nitric Oxide Production Contribute to Blood–Brain Barrier Disruption in the Rat

Hemoglobin (Hb) released from extravasated erythrocytes may have a critical role in the process of blood–brain barrier (BBB) disruption and subsequent edema formation after intracerebral hemorrhage (ICH). Excessive nitric oxide (NO) production synthesized by nitric oxide synthase (NOS) has been well documented to contribute to BBB disruption. However, considerably less attention has been focused on the role of NO in Hb-induced BBB disruption. This study was designed to examine the hypothesis that Hb-induced NOS overexpression and excessive NO production may contribute to the changes of tight junction (TJ) proteins and subsequent BBB dysfunction. Hemoglobin was infused with stereotactic guidance into the right caudate nucleus of male Sprague Dawley rats. Then, we investigated the effect of Hb on the BBB permeability, changes of TJ proteins (claudin-5, occludin, zonula occludens-1 (ZO-1), and junctional adhesion molecule-1 (JAM-1)), iron deposition, expression of inducible NOS (iNOS) and endothelial NOS (eNOS), as well as NO production. Hb injection caused a significant increase in BBB permeability. Significant reduction of claudin-5, ZO-1, and JAM-1 was observed after Hb injection as evidenced by PCR and immunofluorescence. After a decrease at early stage, occludin showed a fivefold increase in mRNA level at 7 days. Significant iron deposition was detectable from 48 h to 7 days in a time-dependent manner. The iNOS and eNOS levels dramatically increased after Hb injection concomitantly with large quantities of NO released. Furthermore, enhanced iNOS or eNOS immunoreactivity was co-localized with diffused or diminished claudin-5 staining. We concluded that overexpressed NOS and excessive NO production induced by Hb may contribute to BBB disruption, which may provide an important potential therapeutic target in the treatment of ICH.     

Use of pyrazoles as ligands greatly enhances the catalytic activity of titanium iso-propoxide for the ring-opening polymerization of l-lactide: a cooperation effect

Using TiOⁱPr₄ with a pyrazole ligand for one-pot LA polymerization improved catalytic activity compared with using TiOⁱPr₄ only. At 60 °C, TiOⁱPr₄ with ^furPz exhibited a higher catalytic activity (approximately 3-fold) than TiOⁱPr₄. At room temperature, TiOⁱPr₄ with ^BuPz exhibited a higher catalytic activity (approximately 17-fold) than TiOⁱPr₄. High molecular mass PLA (M_nGPC = 51 100, and Đ = 1.10) could be produced by using TiOⁱPr₄ with ^furPz in melt polymerization ([TiOⁱPr₄] : [^furPz] = 1000 : 1 : 1 at 100 °C, 240 min). The crystal structure of ^MePz₂Ti₂OⁱPr₇ revealed the cooperative activation between two Ti atoms during LA polymerization.

Using TiOⁱPr₄ with a pyrazole ligand for one-pot LA polymerization improved catalytic activity compared with using TiOⁱPr₄ only.     

The structural composition of components contributes to the superiority of the geoherb Alisma orientale for “diuresis and diffusing dampness”

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale. The effects of “diuresis and diffusing dampness” using salt-made Alisma orientale from seven different origins were investigated through pharmacodynamic experiments in vivo and in vitro. The results indicated that salt-made Alisma orientale from different origins had diuretic efficacy; this was demonstrated by the significant increase in the volume of rat urine, the concentration of Na⁺, K⁺, and Cl⁻ in the urine, and the significant decrease in the levels of AQP-2 in rat renal medulla and HK-2 cells. It was also revealed that the diuretic effect of salt-made Alisma orientale from Fujian Province is stronger than those from other provinces. Moreover, the main components and their proportions in the salt-made Alisma orientale samples were further analyzed via principal component analysis. The results showed that alisol A 24-acetate, alisol B, and 23-acetyl alisol B are the main components of salt-made Alisma orientale, and the optimal structural ratio of alisol A 24-acetate, alisol B, and 23-acetyl alisol B was found to be 5.38 : 14.34 : 11.31 via optimizing the ratios of the three main components. It is worth noting that the optimal ratio of the three main components after optimization is the closest to the ratio of the three main components in salt-made Alisma orientale from Fujian Province. This paper reveals the “mystery” of the content ratio of the main active components and its effect on the efficacy, and showed that the proportional relationship between the content of multiple components is the key to their interactions. Therefore, this method of evaluating the quality of salt-made Alisma orientale is obviously reliable, and this study lays the foundations for quality evaluation of salt-made Alisma orientale and other herb slices.

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale.     

Histone demethylase JHDM2A regulates H3K9 dimethylation in response to arsenic-induced DNA damage and repair in normal human liver cells

Long-term arsenic exposure is a worldwide public health problem that causes serious harm to human health. The liver is the main target organ of arsenic toxicity; arsenic induces disruption of the DNA damage repair pathway, but its mechanisms remain unclear. In recent years, studies have found that epigenetic mechanisms play an important role in arsenic-induced lesions. In this study, we conducted experiments in vitro using normal human liver cells (L-02) to explore the mechanism by which the histone demethylase JHDM2A regulates H3K9 dimethylation (me2) in response to arsenic-induced DNA damage. Our results indicated that arsenic exposure upregulated the expression of JHDM2A, downregulated global H3K9me2 modification levels, increased the H3K9me2 levels at the promoters of base excision repair (BER) genes (N-methylpurine-DNA glycosylase [MPG], XRCC1 and poly(ADP-ribose)polymerase 1) and inhibited their expression levels, causing DNA damage in cells. In addition, we studied the effects of overexpression and inhibition of JHDM2A and found that JHDM2A can participate in the molecular mechanism of arsenic-induced DNA damage via the BER pathway, which may not be involved in the BER process because H3K9me2 levels at the promoter region of the BER genes were unchanged following JHDM2A interference. These results suggest a potential mechanism by which JHDM2A can regulate the MPG and XRCC1 genes in the process of responding to DNA damage induced by arsenic exposure and can participate in the process of DNA damage repair, which provides a scientific basis for understanding the epigenetic mechanisms and treatments for endemic arsenic poisoning.     

Formation of Protein Corona on Nanoparticle Affects Different Complement Activation Pathways Mediated by C1q

Pharmaceutical Research - The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its...     

原发性肺黏膜相关淋巴组织淋巴瘤的18F-FDG PET/CT影像学表现

目的 分析原发性肺黏膜相关淋巴组织（MALT）淋巴瘤的18F-FDG PET/CT影像学表现,提高对原发性肺MALT淋巴瘤的认识及诊断能力。 方法 回顾性分析2006年11月至2017年4月经病理确诊的9例原发性肺MALT淋巴瘤患者（男性6例、女性3例,中位年龄59岁）的临床资料及18F-FDG PET/CT显像资料,记录病灶的部位、数量、密度、大小、形态及最大标准化摄取值（SUV_max）,以及纵隔及肺门淋巴结等情况;分析影像信息并同时进行相关文献复习。 结果 9例原发性肺MALT淋巴瘤患者18F-FDG PET/CT表现分为3型:实变型4例、肿块型3例、弥漫肺炎型2例。实变型表现为大小、受累范围不等的实变影;肿块型表现为单发或多发、边缘毛糙的实性肿块影;弥漫肺炎型表现为肺叶内或双肺弥漫的斑片、团块样软组织密度影。在9例患者中可见支气管充气征8例（部分伴有支气管扩张）、三角型灌注征3例、病灶向中心聚拢4例、钙化2例、胸腔积液2例、肺门及纵隔淋巴结肿大2例。所有病灶18F-FDG 代谢不均匀增高,中位SUV_max为6.0（2.6~8.3）;2例弥漫肺炎型纵隔及肺门淋巴结18F-FDG摄取异常增高,SUV_max分别为13.0、4.7。 结论 原发性肺MALT淋巴瘤的18F-FDG PET/CT表现常为斑片状致密影,多见实变影,内部常见支气管充气征,18F-FDG轻度摄取,结合相对缓慢的病程,可考虑为原发性肺MALT淋巴瘤。     

分化型甲状腺癌术后首次血清刺激性Tg水平对远处转移的预测价值

目的 探讨分化型甲状腺癌（DTC）患者术后首次血清预先刺激性甲状腺球蛋白（ps-Tg）水平对远处转移的预测价值。 方法 收集2016年8月至2017年8月首次行131I治疗的113例DTC患者的临床资料,其中男性32例、女性81例,年龄15~68（44.85±12.01）岁。将患者分为无远处转移（M0）组和远处转移（M1）组。所有患者在未服或停服左旋甲状腺素4周后,行甲状腺功能与抗体水平等检测,行131I治疗后全身显像（Rx-WBS）和局部SPECT/CT断层融合显像。采用χ2检验、独立样本t检验和Mann-Whitney秩和检验对比2组患者的基本资料;采用Mann-Whitney秩和检验比较2组之间ps-Tg水平的差异;非参数法建立ps-Tg水平的受试者工作特征（ROC）曲线,获得最佳诊断界值点（DCP）。 结果 M0组（85例）与M1组（28例）的病理类型、颈部淋巴转移情况及131I治疗剂量均存在差异,且差异有统计学意义（χ2=12.588、12.588、12.581,P=0.003、0.003、0.002）;而性别、年龄、肿瘤分期、手术至首次检测ps-Tg的时间、促甲状腺激素和甲状腺球蛋白抗体水平的差异均无统计学意义。2组患者ps-Tg水平的M（P25~P75）分别为1.95（0.70~6.98） ng/mL和95.05（6.98~278.47） ng/mL,且差异有统计学意义（U=417.5,P=0.000）。ps-Tg水平ROC曲线下面积为0.825（95%CI:0.713~0.936）,灵敏度、特异度和准确率分别为71.4%、91.8% 和86.7%,DCP为28.80 ng/mL。 结论 DTC术后首次血清ps-Tg水平对预测DTC远处转移有重要价值。     

维持性血液透析终末期肾病患者肠道菌群特点探讨

 目的 探讨维持性血液透析终末期肾病(end stage renal disease,ESRD)患者肠道菌群的特点。方法 收集维持性血液透析的稳定ESRD患者和健康对照组受试者各22例粪便样本,提取样本DNA,进行16S rRNA基因测序,对肠道菌群的分布情况进行分析。结果 (1)维持性血液透析ESRD组观察到的各样品微生物物种量、物种多样性较健康对照组低,物种多样性在18～44岁组有统计学差异;(2)两组在纲、目、科、属、种分类水平上分别发现2、4、9、29、28个相对丰度有统计学差异的物种(P<0.05); 其中Negatibicutes纲、粪球菌属-3相对丰度维持性血液透析ESRD组低于健康对照组,而丹毒丝纲、目、科、属、种水平相对丰度维持性血液透析ESRD组高于健康对照组;(3)通过KEGG代谢途径的差异分析,推测两组间有3个存在统计学差异的代谢途径(P<0.05),其中与碳水化合物代谢途径相关基因在健康对照组粪便样品中显著富集,而与细胞运动性及药物耐药途径相关基因在维持性血液透析ESRD组粪便样品中显著富集。结论 维持性血液透析ESRD组患者肠道微生物群落多样性降低,与健康对照组比较在微生物群落相对丰度、KEGG功能预测相关基因代谢途径上存在差异。