食管鳞癌组织中CDC2、CLDN5蛋白表达及其临床病理意义的研究

目的探讨CDC2及CLDN5在食管鳞癌中表达及其临床病理特征的关系。方法应用免疫组化Elivision法检测90例食管鳞癌组织、28例正常食管黏膜组织及16例重度不典型增生组织中CDC2和CLDN5的蛋白表达情况。结果在食管鳞癌和正常食管黏膜组织中CDC2和CI。DN5的阳性表达率分别为88．89％（80／90）、85．56％（77／90）和48．86％（12／28）、25．00％（7／28）,两者差异有统计学意义（P〈O．05）。CDC2蛋白表达在低分化食管鳞癌中明显高于高分化食管鳞癌;临床分期Ⅲ＋Ⅳ期组的CDC2蛋白的表达显著高于I期、Ⅱ期组（P〈O．05）。CDC2和CLDN5在食管鳞癌中表达呈正相关（r=0．537,P〈o．05）。结论CDC2和CLDN5在食管鳞癌的发生、发展过程中可能发挥重要作用,可能作为食管癌临床早期诊断的重要指标。     

小鼠血管内膜增生模型的建立

该文主要介绍一种可以在小鼠中有效地诱导血管内膜增生的方法。该方法使用硅胶管嵌套小鼠股动脉,造成股动脉血管内膜增生。病理切片观察表明,实验组小鼠股动脉与假手术组相比出现了内膜层和中膜层不规则增厚,管腔狭窄,细胞排列紊乱,内膜炎症细胞浸润等。免疫组织化学染色显示内膜增生部分是由于血管平滑肌细胞（VsMCs）增生和基质积聚所致。该模型的建立对动脉粥样硬化病理机制研究和治疗药物的研发具有重要意义。     

Stem Cell Transplantation Increases Antioxidant Effects in Diabetic Mice

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, blood glucose levels and insulin, and increased plasma adiponectin levels. The upregulation of HO-1 was associated with significantly (p<0.05) increased levels of peNOS and pAKT, but decreased levels of iNOS in the kidneys of db/db mice. Plasma creatinine levels also decreased (p<0.05), and the expression of type IV collagen was improved. Thus IBM-BMT+TT unregulated the expression of HO-1, peNOS and pAKT, while decreasing iNOS levels in the kidney of db/db mice. This was associated with an improvement in renal function.     

Very-Long-Chain Fatty Acids Are Involved in Polar Auxin Transport and Developmental Patterning in Arabidopsis

Very-long-chain fatty acids (VLCFAs) are essential for many aspects of plant development and necessary for the synthesis of seed storage triacylglycerols, epicuticular waxes, and sphingolipids. Identification of the acetyl-CoA carboxylase PASTICCINO3 and the 3-hydroxy acyl-CoA dehydratase PASTICCINO2 revealed that VLCFAs are important for cell proliferation and tissue patterning. Here, we show that the immunophilin PASTICCINO1 (PAS1) is also required for VLCFA synthesis. Impairment of PAS1 function results in reduction of VLCFA levels that particularly affects the composition of sphingolipids, known to be important for cell polarity in animals. Moreover, PAS1 associates with several enzymes of the VLCFA elongase complex in the endoplasmic reticulum. The pas1 mutants are deficient in lateral root formation and are characterized by an abnormal patterning of the embryo apex, which leads to defective cotyledon organogenesis. Our data indicate that in both tissues, defective organogenesis is associated with the mistargeting of the auxin efflux carrier PIN FORMED1 in specific cells, resulting in local alteration of polar auxin distribution. Furthermore, we show that exogenous VLCFAs rescue lateral root organogenesis and polar auxin distribution, indicating their direct involvement in these processes. Based on these data, we propose that PAS1 acts as a molecular scaffold for the fatty acid elongase complex in the endoplasmic reticulum and that the resulting VLCFAs are required for polar auxin transport and tissue patterning during plant development.     

Community-based knowledge transfer and exchange: Helping community-based organizations link research to action

Background

Community-based organizations (CBOs) are important stakeholders in health systems and are increasingly called upon to use research evidence to inform their advocacy, program planning, and service delivery efforts. CBOs increasingly turn to community-based research (CBR) given its participatory focus and emphasis on linking research to action. In order to further facilitate the use of research evidence by CBOs, we have developed a strategy for community-based knowledge transfer and exchange (KTE) that helps CBOs more effectively link research evidence to action. We developed the strategy by: outlining the primary characteristics of CBOs and why they are important stakeholders in health systems; describing the concepts and methods for CBR and for KTE; comparing the efforts of CBR to link research evidence to action to those discussed in the KTE literature; and using the comparison to develop a framework for community-based KTE that builds on both the strengths of CBR and existing KTE frameworks.

Discussion

We find that CBR is particularly effective at fostering a climate for using research evidence and producing research evidence relevant to CBOs through community participation. However, CBOs are not always as engaged in activities to link research evidence to action on a larger scale or to evaluate these efforts. Therefore, our strategy for community-based KTE focuses on: an expanded model of 'linkage and exchange' (i.e., producers and users of researchers engaging in a process of asking and answering questions together); a greater emphasis on both producing and disseminating systematic reviews that address topics of interest to CBOs; developing a large-scale evidence service consisting of both 'push' efforts and efforts to facilitate 'pull' that highlight actionable messages from community relevant systematic reviews in a user-friendly way; and rigorous evaluations of efforts for linking research evidence to action.

Summary

Through this type of strategy, use of research evidence for CBO advocacy, program planning, and service delivery efforts can be better facilitated and continually refined through ongoing evaluations of its impact.

     

Structure of the ribosome associating GTPase HflX

The HflX‐family is a widely distributed but poorly characterized family of translation factor‐related guanosine triphosphatases (GTPases) that interact with the large ribosomal subunit. This study describes the crystal structure of HflX from Sulfolobus solfataricus solved to 2.0‐Å resolution in apo‐ and GDP‐bound forms. The enzyme displays a two‐domain architecture with a novel “HflX domain” at the N‐terminus, and a classical G‐domain at the C‐terminus. The HflX domain is composed of a four‐stranded parallel β‐sheet flanked by two α‐helices on either side, and an anti‐parallel coiled coil of two long α‐helices that lead to the G‐domain. The cleft between the two domains accommodates the nucleotide binding site as well as the switch II region, which mediates interactions between the two domains. Conformational changes of the switch regions are therefore anticipated to reposition the HflX‐domain upon GTP‐binding. Slow GTPase activity has been confirmed, with an HflX domain deletion mutant exhibiting a 24‐fold enhanced turnover rate, suggesting a regulatory role for the HflX domain. The conserved positively charged surface patches of the HflX‐domain may mediate interaction with the large ribosomal subunit. The present study provides a structural basis to uncover the functional role of this GTPases family whose function is largely unknown. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

Bisphenol A: developmental toxicity from early prenatal exposure

Bisphenol A (BPA) exposure has been documented in pregnant women, but consequences for development are not yet widely studied in human populations. This review presents research on the consequences for offspring of BPA exposure during pregnancy. Extensive work in laboratory rodents has evaluated survival and growth of the conceptus, interference with embryonic programs of development, morphological sex differentiation, sex differentiation of the brain and behavior, immune responsiveness, and mechanism of action. Sensitive measures include RAR, aryl hydrocarbon receptor, and Hox A10 gene expression, anogenital distance, sex differentiation of affective and exploratory behavior, and immune hyperresponsiveness. Many BPA effects are reported at low doses (10–50 µg/kg d range) by the oral route of administration. At high doses (>500,000 µg/kg d) fetal viability is compromised. Much of the work has centered around the implications of the estrogenic actions of this agent. Some work related to thyroid mechanism of action has also been explored. BPA research has actively integrated current knowledge of developmental biology, concepts of endocrine disruption, and toxicological research to provide a basis for human health risk assessment. Birth Defects Res (Part B) 89:441–466, 2010. © 2010 Wiley‐Liss, Inc.     

N-Acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious rats

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection ofKlebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetyl-cysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-, IL-1, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-, IL-1, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-, IL-1, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.     

Early Changes of β-Catenins and Menins in Spinal Cord Dorsal Horn after Peripheral Nerve Injury

Injury to the peripheral nervous system can lead to spontaneous pain, hyperalgesia and allodynia. Previous studies have shown sprouting of Aβ-fibres into lamina II of the spinal cord dorsal horn after nerve injury and the formation of new synapses by these sprouts. β-Catenin and menin as synaptogenic factors are critically involved in synapse formation. However, the roles of β-catenin and menin in neuropathic pain are still unclear. Using Western blot analysis we investigated the changes of β-catenin and menin in the spinal dorsal horn after unilateral spared nerve injury (SNI). We demonstrated an increase in both β-catenin and menin protein levels in the ipsilateral spinal dorsal horn at days 1 and 3 following spared nerve injury (P < 0.05). These increases were associated with changes in paw withdrawal threshold to mechanical stimuli and weight bearing deficit suggestive of pain behavior and spontaneous ongoing pain respectively. However, the injury-associated increases in β-catenins and menins levels returned to control levels at day 14. In conclusion, these results indicate that peripheral nerve injury induces upregulation of β-catenins and menins in the dorsal horn of the spinal cord, which may contribute to the development of chronic neuropathic pain. Antagonists of these molecules may serve as new therapeutic agents.     

Systems genetics analyses predict a transcription role for P2P-R: Molecular confirmation that P2P-R is a transcriptional co-repressor

Background  

The 250 kDa P2P-R protein (also known as PACT and Rbbp6) was cloned over a decade ago and was found to bind both the p53 and Rb1 tumor suppressor proteins. In addition, P2P-R has been associated with multiple biological functions, such as mitosis, mRNA processing, translation and ubiquitination. In the current studies, the online GeneNetwork system was employed to further probe P2P-R biological functions. Molecular studies were then performed to confirm the GeneNetwork evaluations.