BackgroundMetabolome analysis including amino acid profile is under investigation as an approach in cancer screening. The present study aims to analyze plasma free amino acid (PFAA) profiles in cancer patients and investigate their potential as biomarkers of malignancy.MethodsPlasma samples from 56 gastric cancer patients, 28 breast cancer patients, 33 thyroid cancer patients, and 137 age-matched healthy controls were collected in the study. PFAA levels were measured and their perioperative alterations were analyzed. Biological effects of ten cancer-related amino acids were further validated in gastric and breast cancer cells.ResultsWe found that PFAA profiles of cancer patients differed significantly from those of healthy controls. Decreased concentrations of PFAAs were associated with lymph node metastases in gastric cancer. Levels of PFAAs such as aspartate and alanine increased after tumor resection. PFAA levels correlated with clinical tumor markers in gastric cancer patients and pathological immunohistochemistry markers in breast cancer patients. Specifically, alanine, arginine, aspartate and cysteine had proliferative effects on breast cancer cells. Proliferation of gastric cancer cells was promoted by cysteine, but inhibited by alanine and glutamic acid. Furthermore, alanine treatment decreased total and stable fraction of gastric cancer cells, and alanine and glutamic acid induced apoptosis of gastric cancer cells.ConclusionsPFAA patterns in cancer patients are altered perioperatively. Tumor-related amino acids identified by dynamic study of PFAA patterns may have the potential to be developed as novel biomarkers for diagnosis and prognosis of cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0408-1) contains supplementary material, which is available to authorized users.
Bifidobacterium Catenulatum ZYB0401 in combination with Lactobacillus Fermentum ZYL0401 could be useful in restoring intestinal microflora and in preventing liver injury in hepatic I/R of rats.
The amino acid metabolism in patients with hepatitis B virus (HBV) infection is significantly changed. In this study, we analyzed the relationship between the amino acid profiles and varying clinical stages of HBV infection, and investigated their significance. The plasma amino acid concentrations in 115 patients with HBV infection and 32 healthy donors were detected and analyzed, and the main indicators of liver function were measured. Correlation analysis was performed between the amino acid profiles (Fischer's ratio, branched-chain amino acid to tyrosine ratio [BTR]) and the key indicators of liver function in patients with HBV infection. Fisher's ratio and the BTR of patients with HBV infection was found to differ from that of the healthy controls, and was also found to significantly correlate with the stage of HBV infection. Changes in the BTR were closely related to the level of key indicators of liver function, and a significant relationship was detected between the Fischer's ratio and the BTR (r=0.928, p<0.001). These results suggest that Fischer's ratio and the BTR can indirectly reflect the degree of liver cell injury. Determining and tracking the plasma amino acid profiles could, therefore, be used for the diagnosis, treatment selection, and prognosis of patients with varying stages of HBV infection.
Chronic infection with hepatotropic viruses is the main cause of chronic liver disease and cirrhosis worldwide. Toll-like receptor 3 (TLR3) and Toll-like receptor 7 (TLR7) are pathogen-recognition receptors that are expressed on innate immune cells. They recognize viral RNA, which induces their activation, with a subsequent increase in type I interferon transcription. Hepatitis C virus (HCV) infection inhibits the expression of TLR3 and TLR7; however, the mechanism by which this occurs is unclear. MicroRNAs (miRNAs) are small RNAs that posttranscriptionally regulate gene expression. Their aberrant expression is commonly correlated with disease status, as is the case with HCV infection. Here, we found that miR-758 levels were increased in patients with HCV infection and were correlated with TLR3 and TLR7 expression levels in the patients with HCV infection, and bioinformatics analysis predicted that TLR3 and TLR7 are targets of miR-758. Therefore, we postulate that HCV may increase the level of miR-758, which inhibits the expression of TLR3 and TLR7, resulting in a loss of antiviral effect. In order to test our hypothesis, we constructed an HCV core protein expression plasmid and used it to transfect liver cells. The results showed that HCV infection increased miR-758 levels and decreased TLR3/TLR7 expression. Furthermore, using RT-PCR and luciferase reporter analysis, we found that miR-758 targets TLR3 and TLR7, with a subsequent decrease in IFNα and IFNβ production. In conclusion, our results highlight the upregulation of miR-758 expression by HCV as a novel mechanism contributing to downregulation of TLR3 and TLR7 in patients with HCV infection.
Objective To clarify the value of endotoxin concentrations in expressed prostatic secretions (EPS) in the diagnosis and classi®cation of chronic prostatitis. Patients, subjects and methods The study included 88 consecutive patients with chronic prostatitis and 15 controls with no urological disease. The diagnosis and classi®cation were based on a history, symptoms, a digital rectal examination of the prostate, and a white blood cell count in the EPS. Endotoxin concentrations in the EPS or urine were measured using a colorimetric assay and standard microbiological methods used to identify bacterial growth. Results In men with chronic prostatitis caused by Gramnegative or combined Gram-negative and -positive bacteria, the endotoxin levels in urine collected immediately after prostatic massage were signi®cantly greater (P<0.01) than in a midstream urine sample, and the concentration in the EPS was signi®cantly higher (P<0.05) than that in the control group. The same was true of patients with chronic prostatitis and Gram-positive bacteria isolated from the EPS or urine after massage. In patients with chronic pelvic pain syndrome (grade IIIA) the endotoxin level in the urine after massage was also signi®cantly higher (P<0.05) than that of the midstream sample, but there was no signi®cant difference between the concentration in these samples in patients with grade IIIB, and no signi®cant difference between the endotoxin concentration of the EPS in patients with grade IIIB and that in controls. Conclusion Endotoxin concentrations are increased in the EPS or urine (after prostatic massage) of men with bacterial chronic prostatitis or chronic pelvic pain syndrome grade IIIA. The current routine examinations (including bacterial culture and routine examination of EPS or urine) before diagnosis and classi®cation of chronic prostatitis are insuf®cient to describe the cause and pathogenesis of this condition. The endotoxin concentration of the EPS or urine after massage may provide a supplementary tool to identify the cause of chronic prostatitis.
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