IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice

BACKGROUND@#High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. @*METHODS@#To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. @*RESULTS@#At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. @*CONCLUSION@#IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice

BACKGROUND@#High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. @*METHODS@#To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. @*RESULTS@#At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. @*CONCLUSION@#IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

Differential expression of microRNAs in the saliva of patients with aggressive periodontitis: a pilot study of potential biomarkers for aggressive periodontitis

Purpose@#The aim of this study was to compare microRNA (miRNA) gene expression in saliva using miRNA polymerase chain reaction (PCR) arrays in healthy and aggressive periodontitis (AP) patients. @*Methods@#PCR arrays of 84 miRNAs related to the human inflammatory response and autoimmunity from the saliva samples of 4 patients with AP and 4 healthy controls were performed. The functions and diseases related to the miRNAs were obtained using TAM 2.0. Experimentally validated targets of differentially expressed miRNAs were obtained from mirTarBase. Gene ontology terms and pathways were analyzed using ConsensusPathDB. @*Results@#Four downregulated miRNAs (hsa-let-7a-5p, hsa-let-7f-5p, hsa-miR-181b-5p, and hsa-miR-23b-3p) were identified in patients with AP. These miRNAs are associated with cell death and innate immunity, and they target genes associated with osteoclast development and function. @*Conclusions@#This study is the first analysis of miRNAs in the saliva of patients with AP.Identifying discriminatory human salivary miRNA biomarkers reflective of periodontal disease in a non-invasive screening assay is crucial for the development of salivary diagnostics. These data provide a first step towards the discovery of key salivary miRNA biomarkers for AP.

Differential expression of microRNAs in the saliva of patients with aggressive periodontitis: a pilot study of potential biomarkers for aggressive periodontitis

Purpose@#The aim of this study was to compare microRNA (miRNA) gene expression in saliva using miRNA polymerase chain reaction (PCR) arrays in healthy and aggressive periodontitis (AP) patients. @*Methods@#PCR arrays of 84 miRNAs related to the human inflammatory response and autoimmunity from the saliva samples of 4 patients with AP and 4 healthy controls were performed. The functions and diseases related to the miRNAs were obtained using TAM 2.0. Experimentally validated targets of differentially expressed miRNAs were obtained from mirTarBase. Gene ontology terms and pathways were analyzed using ConsensusPathDB. @*Results@#Four downregulated miRNAs (hsa-let-7a-5p, hsa-let-7f-5p, hsa-miR-181b-5p, and hsa-miR-23b-3p) were identified in patients with AP. These miRNAs are associated with cell death and innate immunity, and they target genes associated with osteoclast development and function. @*Conclusions@#This study is the first analysis of miRNAs in the saliva of patients with AP.Identifying discriminatory human salivary miRNA biomarkers reflective of periodontal disease in a non-invasive screening assay is crucial for the development of salivary diagnostics. These data provide a first step towards the discovery of key salivary miRNA biomarkers for AP.

Identification of Biomarkers for Breast Cancer Using Databases

Breast cancer is one of the major causes of cancer death in women. Many studies have sought to identify specific molecules involved in breast cancer and understand their characteristics. Many biomarkers which are easily measurable, dependable, and inexpensive, with a high sensitivity and specificity have been identified. The rapidly increasing technology development and availability of epigenetic informations play critical roles in cancer. The accumulated data have been collected, stored, and analyzed in various types of databases. It is important to acknowledge useful and available data and retrieve them from databases. Nowadays, many researches utilize the databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Surveillance, Epidemiology and End Results (SEER), and Embase, to find useful informations on biomarkers for breast cancer. This review summarizes the current databases which have been utilized for identification of biomarkers for breast cancer. The information provided by this review would be beneficial to seeking appropriate strategies for diagnosis and treatment of breast cancer.

Rabbit gastric ulcer models: comparison and evaluation of acetic acid-induced ulcer and mucosectomy-induced ulcer / 한국실험동물학회지

In this study, we examined rabbit gastric ulcer models that can serve as more clinically relevant models. Two types of ulcer model were studied: acetic acid-induced ulcers (AAU) and mucosal resection-induced ulcers (MRU). For AAU, rabbit gastric mucosa was exposed by median laparotomy and treated with bottled acetic acid. MRU was examined as a model for endoscopic mucosal resection (EMR). Normal saline was injected into the submucosal layer and the swollen mucosa was resected with scissors. Endoscopic mucosal resection (EMR) is frequently performed for treatment of early gastric cancers. This procedure inevitably leads to ulcers and bleeding. Bleeding control is the major concern in endoscopic mucosectomy, and some endoscopic hemostatic agents are currently under clinical and preclinical studies. MRU was developed as a model for these induced ulcers and the evaluation of the healing process. The clinical relevancy of those models was compared with that of rat models. Progressive healing was observed for 7 days based on histology. Rabbit models demonstrate round, deep ulcers with clear margins and well-defined healing stages that were difficult to define in rat models.

Combined Treatment with Anticancer Vaccine Using Genetically Modified Endothelial Cells and Imatinib in Bladder Cancer

PURPOSE: We sought to maximize the antitumor effect of an anticancer vaccine based on genetically modified endothelial cells by combining it with the platelet-derived growth factor receptor inhibitor imatinib. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were infected with 10 MOI of Ad-CMV-mGMCSF to make anticancer vaccines. One million mouse bladder cancer cells (MBT-2) were subcutaneously inoculated in C3H mice. The experimental groups included the following: Group 1 (phosphate-buffered saline), Group 2 (anticancer vaccine and GM-CSF), Group 3 (imatinib), and Group 4 (anticancer vaccine, GM-CSF, and imatinib). Tumor growth and body weight were measured weekly. At 4 weeks, the tumors were immunostained with anti-CD31, and microvessel density (MVD) was measured. To evaluate the immunological mechanism of each treatment, flow cytometry analysis of activated CD4 and CD8 cells was performed. RESULTS: At 4 weeks, the mean body weight of each group, excluding the extracted tumor weight, was not significantly different. Since week 3, the mean tumor volume in Group 4 was the smallest among the treatment groups (p<0.05), and a synergistic suppressive effect on tumor volume was observed in Group 4. The MVD in Group 4 was the most suppressed among the treatment groups (p<0.05), and a synergistic anti-angiogenic effect was observed. Flow cytometry analysis revealed that activated CD4+ and CD8+ cells increased in Group 2 and decreased in Group 3 compared with the other groups. CONCLUSIONS: The combination of genetically modified endothelial cell vaccines and imatinib showed a synergistic antiangiogenic effect in bladder cancer.