Virulence genes of Parkinson's disease and autophagy / 中华老年医学杂志

Parkinson's disease(PD)is a common neurodegenerative disease mainly affecting old persons.The pathogenesis of PD is still unclear, although it has been studied for many years.Recently, more and more evidences show that the dysfunction of autophagy plays a pivotal role in the pathogenesis of PD.Substantial progress in the genetic research of PD has showed that several pathogenic genes were identified correlated with autophagy, in particular, playing an important role in sporadic cases of PD.Here, we will discuss pathogenic genes-correlated dysfunctional autophagy-lysosomes system, so as to specify the pathogenesis of PD and provide a clue for its treatment.

Idiopathic hypereosinophilic syndrome with gastrointestinal manifestations:A report of 9 cases and literature review / 吉林大学学报(医学版)

Objective:To investigate the clinical characteristics of idiopathic hypereosinophilic syndrome (IHES) with gastrointestinal manifestations,and to improve the level of diagnosis and treatment of IHES. Methods:The clinical materials, process of diagnosis and treatment and prognosis of 9 patients diagnosed as IHES with gastrointestinal manifestations were retrospectively analyzed. Results:The average age of 9 patients was (22.66± 12.86)years old,and the ratio of male and female was about 1.25∶ 1. The main clinical manifestations included abdominal pain,diarrhea and abdominal distension.The eosinophil percentages in peripheral blood and bone marrow of the patients were (42.66 ± 19.88 )% and (39.33 + 15.99 )%, respectively.The ascites exudate cytology examination showed eosinophil infiltrated.The results of gastroscope or colonoscope showed mucosal hyperemia and edema,scattered bleeding spots, and dark red granular hyperplasia; the colon was affected frecuently.The histological biopsy confirmed that the mucosal was infiltrated by eosinophils.The abdominal CT of 6 patients showed that the walls of stomach or bowel were thickened.The abdominal symptoms disappeared,and the ascites was absorpted in 9 patients after the treatment of glucocorticoid.After 2 years of follow up,2 patients had relapse, others had no recurrence.Conclusion:Performing the routine diagnosis and treatment of gastrointestinal diseases, the clinicians should consider the possibility of IHES in order to avoid the misdiagnosis and delayed treatment. When IHES is diagnosed,steroid treatment should be performed in preference.

Bone marrow mononuclear cell transplant therapy in mice with CCl4-induced acute liver failure.

BACKGROUND/AIMS: Stem cell transplantation has theoretical potential for the treatment of certain liver diseases. However, the use of bone marrow mononuclear cells as a therapy for liver disease has received little attention. The present study was to examine whether bone marrow mononuclear cells might be useful in the management of acute liver failure in an animal model. MATERIALS AND METHOTS: Bone marrow mononuclear cells were harvested from BALB/c mice and then labeled with the fluorescent dye PKH26. The labeled cells were subsequently infused into the tail veins of mice in which hepatic injury had been induced by CCl4 toxicity. After transplantation, the labeled cells in the liver were studied by fluorescent microscopy, and the levels of proliferating cell nuclear antigen and albumin were quantified in bone marrow mononuclear cell-treated and untreated groups. Serum aminotransferase activity was also monitored at various time points post-liver injury. RESULTS: Transplanted bone marrow mononuclear cells labeled with PKH26 were found to populate the damaged liver around the portal and centrolobular regions, and they appeared to differentiate into albumin-producing hepatocyte-like cells. Animals that received bone marrow mononuclear cells also showed a trend toward improved liver enzymes as well enhanced survival rates, relative to controls. CONCLUSIONS: These findings suggest that systemically delivered bone marrow mononuclear cells may relocate to and be retained by the injured liver; transplantation of bone marrow mononuclear cells showed an overall beneficial effect in a murine model of acute liver failure.

Effect of ß -catenin siRNA on proliferation and apoptosis of hepatoma cell line SMMC-7721 and HepG-2.

BACKGROUND/AIMS: The aim of this study was to investigate the effect of expression of siRNA ß- catenin silent gene on cell cycle and apoptosis of different hepatoma cells. METHODOLOGY: The effect of the ß-catenin-siRNA recombinant plasmid on the growth of different hepatoma cells was observed by MTT assays; and the effect of the recombinant plasmid on proliferation and apoptosis of different hepatoma cells was detected through flow cytometry. RESULTS: Transfection of the ß-catenin-siRNA recombinant plasmid into hepatoma cells significantly inhibited ß-catenin expression at protein and mRNA levels (p<0.05) as shown by western blotting and RT-PCR, respectively. The MTT assay showed that ß-catenin-siRNA can significantly inhibit growth of hepatoma cells. The results of flow cytometry showed that the growth of different hepatoma cells was blocked at G0/G1 phase and compared with the control group there was a significant difference (p<0.05). Flow cytometry also showed that apoptosis of different hepatoma cells, compared with the control group, was significantly different (p<0.05). CONCLUSIONS: Inhibition of ß-catenin in hepatoma cells can inhibit growth and promote apoptosis, and there was difference in the effect on proliferation and apoptosis between different hepatoma cells.

Construction, expression and characterization of a dual cancer-specific fusion protein targeting carcinoembryonic antigen in intestinal carcinomas.

The abundantly expressed carcinoembryonic antigen (CEA) on several cancer types is an attractive target for antibody-directed therapy. However, CEA is also present in some normal tissues. Here, we produced a dual functioning protein, designated as CAtin that exhibits both specific binding and killing functions, by fusing a tumor-specific apoptosis-inducing molecular Apoptin to C-terminus of an anti-CEA single-chain disulfide-stabilized Fv antibody (scdsFv). The CAtin proteins were expressed in Escherichia coli (E. coli), refolded and purified on an immobilized Ni2+ affinity chromatography column. SDS-PAGE and Western blotting revealed that the recombinant protein was well-expressed and the yield was approximately 250mg/L. We demonstrated by flow cytometry and immunofluorescence assays that CAtin could bind specifically to human colon carcinoma cells (LoVo), but almost not to human uterine cervix (Hela). The results suggest that CAtin is active and specific toward CEA-positive cells and may potentially be used in CEA-targeted cancer therapy.

Study on transplantation of induced bone marrow mesenchymal stem cells via various route for the treatment of chronic liver injury / 中华消化杂志

Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via various route for treatment of chronic liver injury.Methods MSCs were isolated and expanded by density gradient centrifugation combined with adherent culture.MSCs were induced to differentiate into hepatocyte-like cells in vitro.The markers of hepatocyte lineage were examined by RT-PCR and immunocytochemistry.The changes of ultramicrostructure of MSCs were observed by transmission electron microscope.One hundred and fourteen Wistar rats were treated with mixture of 40%CCl4 and peanut oil to establish chronic liver injury model and another 6 rats were served as control.Twelve rats in model group were died within 8 weeks,and the rest rats were divided into portal vein,spleen and tail vein transplantation groups.The rats were transplanted with DAPI-labelled MSCs which were induced for 14 days.The distribution of the DAPI-labelled cells were observed by fluorescence microscopy.The liver function and pathology were examined.Results AFP mRNA expression were detected at 7th and 14th day after induction,expressions of ALB mRNA,CK18 and hepatocyte antigen were found at 14th and 2lth day.The ultrastructure examination revealed that MSCs were enlarged with a lot of endoplasmic reticulum,mitochondrion,lysosome and glycogen granule.DAPI labelled cells were found in the spleen and liver transplantion groups.The pathological changes of liver were alleviated in all treated groups,especially in intraspleenic transplantion group(P＜0.05).Conclusions Induced bone marrow MSCs can ameliorate liver function of chronic hepatic injury after transplantation.The intraspleenic transplantation is better than others.