Attenuation of allograft rejection by intragraft inhibition of class II transcativator in high responder rat liver transplantation

Major histocompatibility complex‐II (MHC‐II) plays an important role in graft rejection and class II transactivator (CIITA) is the key regulator for MHC‐II expression. The aim of this study was to determine the efficacy of intragraft inhibition of CIITA in attenuating liver transplant rejection. Three plasmids containing small hairpin RNA (shRNA) against rat CIITA (pCIITA‐shRNA) and one control plasmid of pHK‐shRNA were constructed. In vitro dendritic cell (DC) transfection and liver transfection via portal vein in donor rats (n = 8) by shRNA plasmids were performed to confirm the inhibitory effect of pCIITA‐shRNA on CIITA expression. It showed that expressions of CIITA and MHC‐II were significantly inhibited by pCIITA‐shRNA in both DC in vitro and liver of donor rats in vivo (p < 0.05 vs. control pHK‐shRNA treatment). pCIITA1‐shRNA was proved to be the best inhibitor among three pCIITA‐shRNAs and then used in high‐responder rat liver transplantation model (DA donors‐to‐Lewis recipients). Transplant groups (n = 16/group) include untreated recipients transplanted with donor liver graft pretreated with either saline, or pHK‐shRNA, or pCIITA1‐shRNA. Cyclosporine‐treated (10 mg/kg, im, day 0–7) recipients transplanted with unmodified liver grafts were used as no rejection control. The results showed that the recipient rats survived significantly longer in pCIITA1‐shRNA‐treated group with markedly attenuated liver graft rejection (p < 0.05 vs. saline and pHK‐shRNA‐treated groups). Furthermore, significantly decreased intragraft expressions of CIITA, MHC‐II, IL‐2, and IFN‐γ were found in pCIITA1‐shRNA‐treated group (p < 0.05 vs. saline and pHK‐shRNA‐treated groups). This study suggests that intragraft inhibition of CIITA could be a novel strategy for attenuating graft rejection in liver transplantation. © 2014 Wiley Periodicals, Inc. Microsurgery 35:52–59, 2015.     

Current status of randomized controlled trials for laparoscopic gastric surgery for gastric cancer in China

China alone accounts for nearly 42% of all new gastric cancer cases worldwide, and gastric cancer is the third leading cause of cancer deaths in China nowadays. Without mass screening programs, unfortunately over 80% of all Chinese patients have been diagnosed as advanced diseases. As in other Asian countries, especially Japan and Korea, laparoscopic gastrectomy for the treatment of gastric cancer has gained increasingly popularity in China during the past decade. Whether laparoscopic surgery can be safely and effectively performed in the treatment of gastric cancer remains controversial, particularly with regard to curative intent in advanced diseases. Given the high incidence of these cancers, and their advanced stage at diagnosis, China has a significant interest in determining the safety and effectiveness of laparoscopic gastrectomy. A well‐designed randomized controlled trial (RCT) is considered the only feasible way to provide conclusive evidence. To date, China has not played a significant role in terms of conducting RCT concerning laparoscopic surgery for gastric cancer. However, an effort has been made by the Chinese researchers, with the great help from our colleagues in neighboring countries such as Korea and Japan, through the establishment of the Chinese Laparoscopic Gastrointestinal Surgery Study Group. In this review, we present the current status of RCT for laparoscopic gastric surgery for gastric cancer in China, including published and ongoing registered RCT.     

Multiple Genes of the Renin-Angiotensin System Are Novel Targets of Wnt/β-Catenin Signaling

Activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because of compensatory upregulation of renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary to achieve greater efficacy. By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and β-catenin induced the binding of LEF-1 to these sites in kidney tubular cells. Overexpression of either β-catenin or different Wnt ligands induced the expression of all RAS genes. Conversely, a small-molecule β-catenin inhibitor ICG-001 abolished RAS induction. In a mouse model of nephropathy induced by adriamycin, either transient therapy or late administration of ICG-001 abolished established proteinuria and kidney lesions. ICG-001 inhibited renal expression of multiple RAS genes in vivo and abolished the expression of other Wnt/β-catenin target genes. Moreover, ICG-001 therapy restored expression of nephrin, podocin, and Wilms’ tumor 1, attenuated interstitial myofibroblast activation, repressed matrix expression, and inhibited renal inflammation and fibrosis. Collectively, these studies identify all RAS genes as novel downstream targets of Wnt/β-catenin. Our results indicate that blockade of Wnt/β-catenin signaling can simultaneously repress multiple RAS genes, thereby leading to the reversal of established proteinuria and kidney injury.     

Evaluation of Intraductal Ultrasonography,Endoscopic Brush Cytology and K-ras,P53 Gene Mutation in the Early Diagnosis of Malignant Bile Duct Stricture

Background:In qualitative diagnosis of bile duct stenosis,single diagnostic measure is difficult to make a correct diagnosis,to combine several diagnostic techniques may be helpful to make an accurate ...     

Proteomic analysis of exosomes derived from human lymphoma cells

Background

Exosomes secreted by tumor cells contain specific antigens that may have immunotherapeutic purposes. The aim of this study was to characterize the proteomic content of lymphoma cell-derived exosomes (LCEXs).

Methods

In this study, exosomes derived from Raji cells (EXO_Raji) were purified and proteins of EXO_Raji were separated by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein bands were identified by mass spectrometry. The protein components of EXO_Raji were analyzed using shotgun technology, and the function proteins of EXO_Raji were defined and described using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results

A total of 197 proteins were identified in EXO_Raji; 139 proteins were also identified in Raji cells, showing an overlap of 70.56% of the total proteins in EXO_Raji. Interestingly, the remaining 58 proteins were unique to EXO_Raji. The GO database and KEGG were used to define and describe the function of proteins. The data showed that some important proteins involved in antigen procession and presentation as well as cell migration and adhesion were also identified in EXO_Raji, such as MHC-I and II, HSC70, HSP90, and ICMA-1.

Conclusions

LCEXs express a discrete set of proteins involved in antigen presentation and cell migration and adhesion, suggesting that LCEXs play an important role in the regulation of immunity and interaction between lymphoma cells and their microenvironment. LCEXs harbor most of the proteins of lymphoma cells and could be one of the sources of lymphoma-associated antigens for immunotherapeutic purposes.     

生长激素在神经系统疾病治疗中的作用

生长激素的生理作用主要是促进物质代谢与生长发育。研究表明,生长激素对机体各器官和各组织均有影响,在神经系统疾病的神经再生和神经保护过程中,生长激素也起到了一定的作用。本文总结生长激素治疗常见神经系统疾时所起的作用以及可能的机制。