Sun-Long Cheng

Proteomics analysis of A375 human malignant melanoma cells in response to arbutin treatment

Although the toxicogenomics of A375 human malignant melanoma cells treated with arbutin have been elucidated using DNA microarray, the proteomics of the cellular response to this compound are still poorly understood. In this study, we performed proteomic analyses to investigate the anticancer effect of arbutin on the protein expression profile in A375 cells. After treatment with arbutin (8 microg/ml) for 24, 48 and 72 h, the proteomic profiles of control and arbutin-treated A375 cells were compared, and 26 differentially expressed proteins (7 upregulated and 19 downregulated proteins) were identified by MALDI-Q-TOF MS and MS/MS. Among these proteins, 13 isoforms of six identical proteins were observed. Bioinformatic tools were used to search for protein function and to predict protein interactions. The interaction network of 14 differentially expressed proteins was found to be correlated with the downstream regulation of p53 tumor suppressor and cell apoptosis. In addition, three upregulated proteins (14-3-3G, VDAC-1 and p53) and five downregulated proteins (ENPL, ENOA, IMDH2, PRDX1 and VIME) in arbutin-treated A375 cells were validated by RT-PCR analysis. These proteins were found to play important roles in the suppression of cancer development.

Urine interleukin‐1β in children with acute pyelonephritis and renal scarring

Aim:  Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin (IL)‐1β is an important inflammatory mediator that appears early during bacterial infection. This prospective study examined urine IL‐1β levels in children with acute pyelonephritis documented by 99mTc‐dimercaptosuccinic acid (DMSA) scan, and also evaluated whether this cytokine correlated with renal scarring.

Proteomics analysis of kojic acid treated A375 human malignant melanoma cells.

Although the toxicogenomics of kojic acid treated A375 human malignant melanoma cells has been elucidated, the proteomics of cellular response is still poorly understood. We performed proteomic analysis to investigate the anticancer effect of kojic acid on protein expression profile in A375 cells. A375 cells were treated with kojic acid at 8 microg/mL for 24, 48, and 72 h. With the use of 2-D PAGE and MALDI-Q-TOF MS and MS/MS analyses, proteomic profiles of A375 cells between control and kojic acid treatment were compared, and 30 differentially expressed proteins, containing 2 up-regulated proteins and 28 down-regulated proteins, were identified. Among these proteins, 17 isoforms of 5 identical proteins were observed and 11 chaperone proteins showed the high proportion of protein spots with 36.7% of total proteins. Bioinformatic tools were used to search for protein function and prediction of protein interaction. Sixteen differentially expressed proteins exhibited interaction network linked to the downstream regulations of p53 tumor suppressor and cell apoptosis, which may lead to suppress the melanogenesis and tumorigenesis of kojic acid treated A375 cells. In addition, GRP75, VIME and 2AAA were validated by Western blot analysis, whereas GRP75, 2AAA, HS90B, ENPL and KPYM were validated by RT-PCR. Therefore, these proteins play the important roles in cancer progression and may be potential biomarkers that are useful for diagnostic and therapeutic applications of malignant melanoma cancer.

Toxicogenomics of A375 human malignant melanoma cells

Toxicogenomics applications are increasingly applied to the evaluation of preclinical drug safety, and to explain toxicities associated with compounds at the mechanism level. In this review, we aim to describe the application of toxicogenomics tools for studying the genotoxic effect of active compounds on the gene-expression profile of A375 human malignant melanoma cells, through the other molecular functions of target genes, regulatory pathways and mechanisms of malignant melanomas. It also includes the current systems biology approaches, which are very useful for analyzing the biological system and understanding the entire mechanisms of malignant melanomas. We believe that this review would be very potent and useful for studying the toxicogenomics of A375 melanoma cells, and for further diagnostic and therapeutic applications.

Intrapleural Urokinase Treatment in Children with Complicated Parapneumonic Effusion

Intrapleural instillation of fibrinolytic agent such as urokinase has been shown to be effective as an adjunctive therapy for children with complicated parapneumonic effusion and empyema. In this study, we described our experience with the use of intrapleural urokinase in the management of complicated parapneumonic effusion in children. We collected 13 patients with a mean age of 50.8 months with parapneumonic pleural effusion or empyema; all were treated with intrapleural urokinase after poor response to appropriate antibiotics and simple tube drainage. We also reviewed another 13 patients with a mean age of 45.8 months from the clinical records of children hospitalized with the same conditions prior to urokinase introduction as a control group. The mean fluid drained during the first 24 hours and the first 72 hours after urokinase instillation were significantly greater than those during 24 hours before instillation, p=0.002 and p<0.001, respectively. The total volume of fluid drained was also greater in the urokinase group than that in the control group (p<0.001). The mean duration of chest tube drainage was significantly shorter in the urokinase group (8.7 +/- 2.8 days vs. 14.7 +/- 6.1 days, p<0.02). The mean length of hospitalization was also significantly shorter in the urokinase group (15.5 +/- 5.3 days vs. 24.4 +/- 6.9 days, p=0.002). All 13 patients were managed successfully with urokinase treatment without further surgical procedures. None of the patients experienced any side effect or adverse event after urokinase instillation. Two patients of the control group finally underwent surgical debridement. In conclusion, the use of intrapleural urokinase treatment in children with complicated parapneumonic effusion is an effective and safe therapy.

Down-regulation of granulocyte-macrophage colony-stimulating factor by 3C-like proteinase in transfected A549 human lung carcinoma cells

BackgroundSevere Acute Respiratory Syndrome (SARS) is a severe respiratory illness caused by a novel virus, the SARS coronavirus (SARS-CoV). 3C-like protease (3CLpro) of SARS-CoV plays a role in processing viral polypeptide precursors and is responsible of viral maturation. However, the function of 3CLpro in host cells remains unknown. This study investigated how the 3CLpro affected the secretion of cytokines in the gene-transfected cells.ResultsFrom immunofluorescence microscopy, the localization of c-myc tagged 3CLpro was detected both in the cytoplasm and nucleus of transfected A549 cells. Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly decreased in 3CLpro-transfected cells by both RT-PCR and ELISA, but without changes in other cytokines, i.e., IL-1β, IL-6, IL-8, IL12p40, TNF-α, and TGF-β. Furthermore, the protein levels of NF-kB decreased in 3CLpro-transfected A549 cells when compared to EGFP transfected cells.ConclusionsOur results suggest that the 3CLpro may suppress expression of GM-CSF in transfected A549 cells through down-regulation of NF-kB production.

Congenital mesoblastic nephroma presenting with massive hematuria and hemorrhagic shock: report of one case.

Congenital mesoblastic nephroma (CMN) is a rare benign tumor that occurs during the neonatal period and early infancy. The vast majority of these tumors present as asymptomatic palpable abdominal masses. We describe an unusual presentation of a CMN in a 10-month-old male infant who presented with massive hematuria and the development of hemorrhagic shock. Abdominal ultrasound showed a heterogeneous solid complex mass measuring 4.8 x 3.5 cm arising from the upper pole of the left kidney. The patient was resuscitated using intravenous fluids and blood transfusions because persistent massive bloody urine leading to progressive shock occurred the night of the admission day. Preoperative diagnosis was possible Wilms tumor of the left kidney. The histopathological findings were consistent with the character of a cellular variant of CMN. The patient was free of recurrence and metastasis at the 2-year follow-up examination. Our case report suggests that CMN is a rare benign renal tumor during infancy and may present with unusual massive hematuria and shock.