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1.
Biomed Pharmacother ; 117: 109052, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31176170

ABSTRACT

Mesenchymal stem cells (MSCs) pretreatment is an effective route for improving cell-based therapy of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that the application of human umbilical cord-MSCs (hUC-MSCs) pretreated with angiotensin-II (Ang-II) might be a potential therapeutic approach for severe acute pancreatitis (SAP). Therefore, the effect of Ang-II pretreated hUC-MSCs on SAP was investigated in vitro and in vivo. METHODS: In the present study, human umbilical cord-derived MSCs pretreated with or without Ang-II were delivered through the tail vein of rats 12 h after induction of SAP. Pancreatitis severity scores and serum lipase levels, as well as the levels of VEGF and VEGFR2 were evaluated. RESULTS: We found that the administration of Ang-II-MSCs significantly inhibited pancreatic injury, as reflected by reductions of pancreatitis severity scores, serum amylase and serum lipase levels. Furthermore, the reduced apoptotic rate and increased tube formation in human umbilical vein endothelial Cells (HUVEC) were found resulting from the administration of Ang-II-MSC-CM. Moreover, knockdown of VEGFR2 can block the effect of Ang-II-MSC-CM on preventing HUVEC from apoptosis, as well as the capacity of tube formation was also suppressed. In addition, the expression of increased Bcl-2 and alleviated caspase-3 were observed in HUVEC and HUVEC transfectants exposure to Ang-II-MSC-CM. CONCLUSION: Collectively, these results elucidated that the pretreatment of hUC-MSCs with Ang-II improved the outcome of MSC-based therapy for SAP via enhancing angiogenesis and ameliorating endothelial cell dysfunction in a VEGFR2 dependent manner.


Subject(s)
Angiotensin II/pharmacology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Pancreas/injuries , Pancreas/pathology , Pancreatitis/therapy , Umbilical Cord/cytology , Acute Disease , Animals , Apoptosis/drug effects , Culture Media, Conditioned/pharmacology , Disease Models, Animal , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Models, Biological , Neovascularization, Physiologic/drug effects , Pancreas/drug effects , Pancreatitis/pathology , Paracrine Communication/drug effects , Rats , Vascular Endothelial Growth Factor Receptor-2/metabolism
2.
World J Gastroenterol ; 24(9): 1022-1034, 2018 Mar 07.
Article in English | MEDLINE | ID: mdl-29531466

ABSTRACT

AIM: To evaluate the prognostic value of the number of retrieved lymph nodes (LNs) and other prognostic factors for patients with distal cholangiocarcinomas, and to determine the optimal retrieved LNs cut-off number. METHODS: The Surveillance, Epidemiology and End Results database was used to screen for patients with distal cholangiocarcinoma. Patients with different numbers of retrieved LNs were divided into three groups by the X-tile program. X-tile from Yale University is a useful tool for outcome-based cut-point optimization. The Kaplan-Meier method and Cox regression analysis were utilized for survival analysis. RESULTS: A total of 449 patients with distal cholangiocarcinoma met the inclusion criteria. The Kaplan-Meier survival analysis for all patients and for N1 patients revealed no significant differences among patients with different retrieved LN counts in terms of overall and cancer-specific survival. In patients with node-negative distal cholangiocarcinoma, patients with four to nine retrieved LNs had a significantly better overall (P = 0.026) and cancer-specific survival (P = 0.039) than others. In the subsequent multivariate analysis, the number of retrieved LNs was evaluated to be independently associated with survival. Additionally, patients with four to nine retrieved LNs had a significantly lower overall mortality risk [hazard ratio (HR) = 0.39; 95% confidence interval (CI): 0.20-0.74] and cancer cause-specific mortality risk (HR = 0.32; 95%CI: 0.15-0.66) than other patients. Additionally, stratified survival analyses showed persistently better overall and cancer-specific survival when retrieving four to nine LNs in patients with any T stage of tumor, a tumor between 20 and 50 mm in diameter, or a poorly differentiated or undifferentiated tumor, and in patients who were ≤ 70-years-old. CONCLUSION: The number of retrieved LNs was an important independent prognostic factor for patients with node-negative distal cholangiocarcinoma. Additionally, patients with four to nine retrieved LNs had better overall and cancer-specific survival rates than others, but the reason and mechanism were unclear. This conclusion should be validated in future studies.


Subject(s)
Bile Duct Neoplasms/pathology , Cholangiocarcinoma/secondary , Age Factors , Aged , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Chi-Square Distribution , Cholangiocarcinoma/mortality , Cholangiocarcinoma/surgery , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , Risk Factors , SEER Program , Time Factors , Treatment Outcome , Tumor Burden , United States/epidemiology
3.
Mol Med Rep ; 16(6): 8011-8018, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28983615

ABSTRACT

Budd­Chiari syndrome (BCS) is an uncommon disease characterized by the occlusion or obstruction of hepatic venous outflow. The mechanism of BCS is still unclear and there are no accurate and effective diagnostic or therapeutic tools. In the present study, blood samples from BCS patients and healthy controls were used for RNA­sequencing. The differentially expressed genes (DEGs) in BCS patients compared with healthy controls were identified. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and Protein­Protein Interaction (PPI) networks construction were performed for DEGs. A total of 405 DEGs including 317 upregulated and 88 downregulated DEGs were identified. The cytosol was the most significantly enriched GO term and the proteasome was also identified as significant enriched pathway. According to the PPI network of 30 DEGs (18 upregulated and 12 downregulated DEGs), synuclein α, tubulin ß­2A class IIa and zinc finger protein Gfi­1b (GFIIB) were the three most significant hub proteins. In conclusion, several DEGs including secreted protein acidic and cysteine rich, lipocalin­2, GFI1B and proteasome­associated DEGs may be associated with the pathological process of BCS. These results can provide novel clues for the pathogenesis and provide novel diagnostic and therapeutic strategies for BCS.


Subject(s)
Budd-Chiari Syndrome/genetics , Gene Expression Profiling , Gene Expression Regulation , Transcriptome , Adult , Aged , Budd-Chiari Syndrome/metabolism , Case-Control Studies , Computational Biology/methods , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Molecular Sequence Annotation , Protein Interaction Mapping , Protein Interaction Maps , Sequence Analysis, RNA
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(5): 1150-1, 2010 May.
Article in Chinese | MEDLINE | ID: mdl-20501418

ABSTRACT

OBJECTIVE: To analyze the pathological and clinical features of IgA nephropathy (IgAN) in west Guangdong province. METHODS: The pathological type and clinical features of 120 patients with IgAN were retrospectively analyzed. RESULTS: Mesangial proliferative glomerulonephritis and focal segmental glomerulosclerosis were the most frequent features of IgAN. IgM deposit could be found in half of the IgAN patients, especially in the IgAN patients with focal segmental glomerulosclerosis. CONCLUSION: The incidence of IgAN may vary between different regions. Clinically, misdiagnosis of other renal diseases as IgAN may often occur. The nature and severity of glomerular immunoglobulin deposition can be related to the pathogenesis and progression of IgAN.


Subject(s)
Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/pathology , Adult , China , Female , Glomerulonephritis, Membranoproliferative/pathology , Glomerulosclerosis, Focal Segmental/pathology , Humans , Male , Retrospective Studies , Young Adult
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