津白_3侏儒小鼠垂体前叶生长激素细胞的免疫细胞化学研究

津白_３侏儒小鼠（ｄＷ~ｔ）是１９８２年从津白_３纯系小鼠（ＴＡ_３）中发现,进而培育成侏的变种。本实验应用免疫细胞化学技术,对ｄｗ￣ｔ小鼠垂体前叶生长激素（ＧＨ）细胞进行观察,并根据体视学原理进行定量分析,以探讨ｄｗ~ｔ小鼠是否存在垂体发育缺陷。实验结果显示,ｄｗ~ｔ小鼠ＧＨ细胞的体积密度（Ｖｖ）和数密度（Ｎｖ）值均低于正常对照组,Ｐ＜０．０１～０．００１。表明ｄｗ~ｔ小鼠由于垂体前叶ＧＨ细胞数量减少,导致ＧＨ分泌不足,从而形成侏儒。     

Blockage of MDM2-mediated p53 ubiquitination by yuanhuacine restrains the carcinogenesis of prostate carcinoma cells by suppressing LncRNA LINC00665

Prostate cancer (PCa) is a challenging issue for men's health worldwide due to its uncontrolled proliferation and high metastatic potential. Increasing evidence has supported plant extracts and natural plant derivatives as promising antitumor therapy with less toxic side effects. Yuanhuacine is an active component isolated from Daphne genkwa and can effectively suppress the tumorigenesis of several cancers. However, its role in PCa remains unclear. In this study, yuanhuacine dose-dependently inhibited the proliferation and induced apoptosis of PCa cells. Moreover, yuanhuacine also restrained the invasion and migration of PCa cells. Mechanically, yuanhuacine decreased the ubiquitination and degradation of p53 protein, and ultimately increased p53 levels, which was regulated by inhibiting the phosphorylation and total protein levels of mouse double minute 2 (MDM2). Moreover, elevation of MDM2 reversed the suppressive efficacy of yuanhuacine in PCa cell viability, invasion, and migration. The network pharmacologic and bioinformatics analysis confirmed that MDM2 might be a common target of D. genkwa and LINC00665. Furthermore, yuanhuacine inhibited LINC00665 expression. Upregulation of LINC00665 reversed yuanhuacine-mediated inhibition in MDM2 protein expression and suppressed p53 levels by enhancing its ubiquitination in yuanhuacine-treated cells. Importantly, the inhibitory effects of yuanhuacine on cell viability and metastatic potential were offset after LINC00665 elevation. Together, the current findings highlight that yuanhuacine may possess tumor-suppressive efficacy by inhibiting LINC00665-mediated MDM2/p53 ubiquitination signaling. Therefore, this study indicates that yuanhuacine may be a promising candidate for the treatment of PCa.     

Functional Promoter -94 ins/del ATTG Polymorphism in NFKB1 Gene Is Associated with Bladder Cancer Risk in a Chinese Population

Background

A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer.

Materials and methods

TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.

Results

Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR)  = 1.92, 95% confidence interval (CI)  = 1.42–2.59]. The increased risk was more prominent among subjects over 65 years old (OR  = 2.37, 95% CI  = 1.52–3.70), male subjects (OR  = 1.97, 95% CI = 1.40–2.79) and subjects with self-reported family history of cancer (OR  = 3.59, 95% CI  = 1.19–10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR  = 2.07, 95% CI  = 1.51–2.85), grade 1 bladder cancer (OR  = 2.40, 95% CI  = 1.68–3.43), single tumor bladder cancer (OR  = 2.04, 95% CI  = 1.48–2.82) and smaller tumor size bladder cancer (OR  = 2.10, 95% CI  = 1.51–2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele.

Conclusions

In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.     

Ginsenoside Rg1 attenuates concanavalin A-induced hepatitis in mice through inhibition of cytokine secretion and lymphocyte infiltration

The effect of ginsenoside Rg1 (Rg1) on hepatic damage caused by concanavalin A (Con A) has not been fully elucidated. This study was designed to evaluate the protective effect of Rg1 on Con A-induced hepatitis in mice and explore the potential mechanisms of this effect. C57BL/6 mice were divided randomly into the following four experimental groups: phosphate-buffered saline group, Rg1 group, Con A group, Con A + Rg1 group. Mice received Rg1 (20 mg/kg) 3 h before intravenous administration of Con A (15 mg/kg). Levels of alanine transaminase, aspartate transaminase and cytokine production were measured, the amount of phosphorylated IκBα and p65 were tested, the numbers of CD4⁺ and CD8⁺ T lymphocytes infiltrated in the blood, spleen and liver were calculated, intercellular adhesion molecule-1 (ICAM-1) and interferon-inducible chemokine-10 (CXCL-10) levels were measured and histological examination of the livers was conducted. Pretreatment with Rg1 markedly reduced the elevated levels of serum aminotransferase, ameliorated liver damage and suppressed proinflammatory cytokines secretion via inhibition NF-κB activity following Con A injection of mice. Furthermore, Rg1 administration reduced ICAM-1 and CXCL-10 mRNA expression in the liver as well as the number of CD4⁺ and CD8⁺ T lymphocytes infiltrating in the liver. Rg1 reduced the incidence of liver damage through inhibition of the proinflammatory response and suppressed the recruitment of CD4⁺ and CD8⁺ T lymphocytes to the liver. These data indicate that Rg1 represents a novel agent for the treatment of T lymphocyte-dependent liver injury.     

MicroRNA-572 Improves Early Post-Operative Cognitive Dysfunction by Down-Regulating Neural Cell Adhesion Molecule 1

Post-operative cognitive dysfunction (POCD) is a commonly-seen postoperative complication in elderly patients. However, the underlying mechanisms of POCD remain unclear. miRNAs, which are reported to be involved in the pathogenesis of the nervous system diseases, may also affect POCD. In this study, miRNA microarray technology was used to analyze the circulating miRNA expression profile of POCD patients. Among the altered miRNAs, miR-572 had the greatest decrease, which was also verified in vivo in rat POCD model. Further analysis found that miR-572 could regulate the expression of NCAM1 in the hippocampal neurons and interfering miR-572 expression could facilitate the restoration of cognitive function in vivo. Moreover, clinical correlation analysis found that the miR-572 expression was associated with the incidence of POCD. Collectively, miR-572 is involved in the development and restoration of POCD and it may serve as a biological marker for early diagnosis of POCD.     

Effect of thrombolysis on myocardial injury: recombinant tissue plasminogen activator vs. alfimeprase

Plasmin-dependent thrombolytic agents are potentially prothrombotic and proinflammatory. Alfimeprase, a zinc-containing metalloproteinase, degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This study examines the hypothesis that thrombolysis in the absence of plasmin generation results in improved myocardial salvage on reperfusion. The thrombolytic effects of recombinant tissue plasminogen activator [rt-PA; 0.022 mg/kg, 1/10 of which was administered as a loading dose; the rest (9/10) was infused over 60 min by intracoronary (ic) administration] or alfimeprase (0.5 mg/kg over 1 min ic) were evaluated in a canine model of arterial thrombosis involving electrolytic injury of the left circumflex (LCX) coronary artery. Both agents induced thrombolysis, with onset of reperfusion being more rapid after alfimeprase compared with rt-PA (1.5 +/- 0.6 vs. 10.1 +/- 2.1 min). In the absence of adjunctive therapy, time to reocclusion after alfimeprase was 3.2 +/- 0.5 min compared with 77.5 +/- 31.9 min with rt-PA. The glycoprotein IIb/IIIa platelet receptor antagonist CRL-42796 prolonged reperfusion time after thrombolysis with alfimeprase or rt-PA. The effect of each lytic agent on myocardial infarct size was examined in a separate group of dogs subjected to 60 min of LCX coronary artery ligation and 4 h of reperfusion. Myocardial infarct size, expressed as percentage of the risk region, was larger (32.16 +/- 3.95%) after rt-PA compared with alfimeprase (19.85 +/- 3.61%) or that of the saline control group (18.46 +/- 3.34%). rt-PA in contrast to alfimeprase, a direct-acting fibrinolytic agent, is associated with an increase in myocyte reperfusion injury.     

Complete Genome Sequence of Porcine Reproductive and Respiratory Syndrome Virus Strain ZCYZ Isolated from Hybrid Wild Boars

A serologic investigation of porcine reproductive and respiratory syndrome virus (PRRSV) in hybrid wild boar herds was conducted during 2008–2009. PRRSV isolates with novel genetic markers were recovered. Experimental infection of pigs indicated that hybrid wild boars are involved in the epidemiology of PRRSV.     

Spatiotemporal variability of tree growth and its association with climate over Northwest China

Understanding spatiotemporal tree growth variability and its associations with climate can provide key insights into forest dynamics in the context of global climate change. Here, we conduct a comprehensive investigation on 64 ring-width chronologies across the entire Northwest (NW) China to understand the regional patterns of tree growth and climate–growth relationships. Using rotated principal component analysis and hierarchical clustering analysis, we found that tree growth was mainly determined by the climate and could be classified into nine groups. Most of the tree-ring chronologies in NW China showed high correlations with moisture conditions in the current and previous growing seasons. After removing age-related growth trends, inter-annual tree growth patterns are supposed to be mainly determined by climate and climate–growth relationships. Since climate–growth relationships for most tree-ring chronologies in this arid region are similar, patterns of tree growth are mainly determined by climate variability. Within each group, the strength of the common signal increases under extreme climate conditions. Thus, climate plays a more important role in determining tree growth in extreme climate conditions relative to the non-climate factors, leading to more coherent growth patterns.     

Difference in tree growth responses to climate at the upper treeline: Qilian Juniper in the Anyemaqen Mountains

Three ring-width chronologies were developed from Qilian Juniper (Sabina przewalskii Kom.) at the upper treeline along a west-east gradient in the Anyemaqen Mountains.Most chronological statistics,except for mean sensitivity (MS),decreased from west to east.The first principal component (PC1) Ioadings indicated that stands in a similar climate condition were most important to the variability of radial growth.PC2 Ioadings decreased from west to east,suggesting the difference of tree-growth between eastern and western Anyemaqen Mountains.Correlations between standard chronologies and climatic factors revealed different climatic influences on radial growth along a west-east gradient in the study area.Temperature of warm season (July-August) was important to the radial growth at the upper treeline in the whole study area.Precipitation of current May was an important limiting factor of tree growth only in the western (drier) upper treeline,whereas precipitation of current September limited tree growth in the eastern (wetter) upper treeline.Response function analysis results showed that there were regional differences between tree growth and climatic factors in various sampling sites of the whole study area.Temperature and precipitation were the important factors influencing tree growth in western (drier) upper treeline.However,tree growth was greatly limited by temperature at the upper treeline in the middle area,and was more limited by precipitation than temperature in the eastern (wetter) upper treeline.