Profiling the metabolic disorder and detection of colorectal cancer based on targeted amino acids metabolomics.

BACKGROUND: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics. METHODS: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed. RESULTS: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis. CONCLUSION: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.

The effects of Salvia przewalskii total phenolic acid extract on immune complex glomerulonephritis.

CONTEXT: Salvia przewalskii Maxim. (Lamiaceae) is a Chinese herbal medicine that has long been used for the treatment of cardiovascular disease. OBJECTIVE: The study investigated the therapeutic efficacy of S. przewalskii total phenolic acid extract (SPE) on immune complex glomerulonephritis (ICG) in rats. MATERIALS AND METHODS: Sixty-two Wistar rats were randomized into six groups. ICG was induced in all groups except normal control group. SPE was administered intragastrically at 24 h intervals for 40 consecutive days. Urine protein (UP), total serum protein (TSP), serum albumin (SA), serum cholesterol (SC) and serum urea nitrogen (SUN) were measured one day before, on day 20 and 40 after SPE administration. On day 40 after SPE administration, the kidneys were removed and prepared into pathologic sections. In addition, kidney wet mass was measured for calculating the kidney wet mass coefficient (KWMC). RESULTS: UP excretion was reduced significantly on day 20 after SPE administration in all three SPE groups as compared with that in medium group, and this effect was observable continuously until 40 days after SPE administration. Compared with medium group, TSP and SA were increased in all three SPE groups after 40 days treatment, while SC and SUN were decreased. KWMC was decreased significantly in 100 mg/kg SPE group after 40 days treatment compared with that in medium group. Histopathologic analyses showed that renal inflammatory infiltration and kidney intumesce were alleviated in all three SPE groups. CONCLUSIONS: SPE may be a potential therapeutic drug for glomerulonephritis.

Decreased expression of TIPE2 contributes to the hyperreactivity of monocyte to Toll-like receptor ligands in primary biliary cirrhosis.

BACKGROUND AND AIM: Previous studies have shown differential TIPE2 expression in several autoimmune diseases. However, the expression levels of TIPE2 in primary biliary cirrhosis (PBC) remained unclear. The purposes of this study were to evaluate TIPE2 expression levels in patients with PBC and further investigate its role in PBC pathogenesis. METHODS: A total of 40 PBC patients and 44 healthy controls were included in the present study. Quantitative reverse-transcription polymerase chain reaction and western blotting were used to determine the differences in mRNA and protein expression levels of TIPE2. The correlations of TIPE2 expression levels and clinical characteristics, inflammatory cytokines, and ursodeoxycholic acid treatment were also assessed. Besides, the influence of TIPE2 on the reactivity of monocyte to Toll-like receptor ligands was further analyzed. RESULTS: The expression levels of TIPE2 were significantly decreased in PBC patients compared with normal controls (P < 0.01). The expression levels of TIPE2 were negatively correlated with alanine aminotransferase (r = -0.40, P = 0.01), alkaline phosphatase (r = -0.36, P = 0.02), gamma glutamyl transpeptidase (r = -0.53, P < 0.01), tumor necrosis factor (TNF)-α (r = -0.332, P = 0.03), interleukin (IL)-1ß (r = -0.386, P = 0.01), and IL-8 (r = -0.366, P = 0.02) levels in sera from PBC patients. TIPE2 expression level could be significantly increased after ursodeoxycholic acid treatment (P < 0.01). The production of TNF-α, IL-1ß, and IL-8 by monocytes from PBC patients after stimulation with lipopolysaccharide and lipoteichoic acid was significantly increased when TIPE2 was knocked down. Furthermore, TIPE2 knockdown could promote activation of nuclear factor-κB pathways through increasing phosphorylation and degradation of IκB in peripheral blood monocytes from PBC patients. CONCLUSION: The present study reported that insufficient expression of TIPE2 might be involved in the hyperreactivity of monocyte to Toll-like receptor ligands in PBC.

APOC3 induces endothelial dysfunction through TNF-α and JAM-1.

BACKGROUND: The fatality rate for cardiovascular disease (CVD) has increased in recent years and higher levels of triglyceride have been shown to be an independent risk factor for atherosclerotic CVD. Dysfunction of endothelial cells (ECs) is also a key factor of CVD. APOC3 is an important molecule in lipid metabolism that is closely associated with hyperlipidemia and an increased risk of developing CVD. But the direct effects of APOC3 on ECs were still unknown. This study was aimed at determining the effects of APOC3 on inflammation, chemotaxis and exudation in ECs. METHODS: ELISA, qRT-PCR, immunofluorescence, flow cytometry and transwell assays were used to investigate the effects of APOC3 on human umbilical vein endothelial cells (HUVECs). SiRNA-induced TNF-α and JAM-1 silencing were used to observe how APOC3 influenced the inflammatory process in the ECs. RESULTS: Our results showed that APOC3 was closely associated with the inflammatory process in ECs, and that this process was characterized by the increased expression of TNF-α. Inflammatory processes further disrupted the tight junctions (TJs) between HUVECs by causing increased expression of JAM-1. JAM-1 was involved in maintaining the integrity of TJs, and it promoted the assembly of platelets and the exudation of leukocytes. Changes in its expression promoted chemotaxis and the exudation of ECs, which contributed to atherosclerosis. While the integrity of the TJs was disrupted, the adhesion of THP-1 cells to HUVECs was also increased by APOC3. CONCLUSIONS: In this study, we describe the mechanism by which APOC3 causes inflammation, chemotaxis and the exudation of ECs, and we suggest that controlling the inflammatory reactions that are caused by APOC3 may be a new method to treat CVD.

Human Epididymis Protein 4: A Novel Biomarker for Lupus Nephritis and Chronic Kidney Disease in Systemic Lupus Erythematosus.

BACKGROUND: Human epididymis protein 4 (HE4) is an available tumor biomarker for detecting ovarian cancer. However, it is unknown if serum HE4 could be a novel biomarker for diagnosis of lupus nephritis (LN) and chronic kidney disease (CKD) in patients with systemic lupus erythematosus (SLE). METHODS: This study enrolled 209 SLE patients, 75 patients with renal dysfunction without SLE and 32 healthy subjects. HE4 concentrations were analyzed by ELISA (enzyme-linked immunosorbent assay; Fujirebio Diagnostics, Sweden). The receiver operating characteristic (ROC) curves were constructed to assess diagnostic accuracy of HE4 for LN or CKD in SLE. RESULTS: Serum HE4 level was significantly higher in SLE patients than that in healthy controls (P < 0.001), especially for those with LN or CKD. It was also higher in patients with renal dysfunction without SLE than healthy controls (P < 0.001), while there was no significant difference between these patients and those with SLE with CKD (P = 0.73). Multivariate analysis showed significant association between increased HE4 and LN or CKD after controlling for confounders. ROC curves showed the cutoff values were 150.1 pM (sensitivity, 76.8%; specificity, 91.1%) for the diagnosis of LN in SLE and 233.9 pM (sensitivity, 92.9%; specificity, 93.5%) for CKD in SLE. CONCLUSIONS: Increased serum HE4 level is closely associated with the development of LN or CKD in SLE patients. Furthermore, it can be used as a novel and useful biomarker for diagnosis of LN or CKD.

Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients.

OBJECTIVE: Although there have been extensive investigations on neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) in many diseases, their roles in systemic lupus erythematosus (SLE) remain unclear. The purpose of the present study was to evaluate NLR, PLR, and MPV levels in adult SLE patients and explore their clinical significance. METHODS: A retrospective study involving 154 adult SLE patients and 151 healthy controls was performed. All clinical characteristics of the SLE patients were extracted from their medical records. NLR, PLR, and MPV levels between SLE patients and healthy controls were compared, and correlations between these indexes and clinical characteristics were analyzed. RESULTS: Increased NLR, PLR, and MPV were observed in SLE patients. NLR was positively correlated with C-reaction protein (r = 0.509, p < 0.01), erythrocyte sedimentation rate (r = 0.610, p < 0.01), and SLE Disease Activity Index (SLEDAI) scores (r = 0.471, p < 0.01). PLR was positively correlated with SLEDAI scores (r = 0.44, p < 0.01). SLE patients with nephritis had higher NLR and PLR levels than those without nephritis (p < 0.01, p = 0.03). In addition, an NLR level of 2.065 was determined as predictive cut-off value of SLE (sensitivity 74.7%, specificity 77.5%, AUC = 0.828). Multiple regression analysis suggested that NLR was independently associated with SLE disease activity. CONCLUSIONS: NLR and PLR could reflect inflammatory response and disease activity in SLE patients.

Epidemiology of primary Sjögren's syndrome: a systematic review and meta-analysis.

OBJECTIVE: Epidemiological studies of primary Sjögren's syndrome (pSS) are crucial for describing the burden to society and the public medical system and for shedding light on aetiology. Previous reports of the epidemiology of pSS show variable outcomes. We conducted a systematic review of the epidemiology of pSS to assess the prevalence rates (PRs) and incidence rates (IRs), and to investigate possible geographic variations in pSS. METHODS: A systematic literature search of PubMed and Embase (updated to 22 October 2013) was performed to identify all published reports on the epidemiology of pSS. The incidence and prevalence rates of pSS were summarised with IRs or PRs and 95% CIs. RESULTS: The literature search yielded 1880 related citations. Only 21 fulfilled the inclusion criteria. According to a random-effects model, the pooled IR for pSS was 6.92 (95% CI 4.98 to 8.86) per 100 000 person-years. The overall PR was 60.82 (95% CI 43.69 to 77.94) cases per 100 000 inhabitants with a slightly lower estimate of Baodong Qin is BDQ, Jiaqi Wang is JQW, Zaixing Yang is ZXY, Renqian Zhong is RQZ. 43.03 (25.74 to 60.31) cases per 100 000 inhabitants when only considering population-based studies. The female/male ratio in incidence data was 9.15 (95% CI 3.35 to 13.18). The female/male ratio in prevalence data was 10.72 (95% CI 7.35 to 15.62). The overall age of pSS patients was 56.16 years (95% CI 52.54 to 59.78). CONCLUSIONS: Incidence and prevalence rates of pSS vary widely around the world. The results help us better understand the global epidemiology of pSS. Large population-based studies combining meticulous case-finding and case-ascertainment strategies are needed.

Adjuvant therapy in the treatment of gallbladder cancer: a meta-analysis.

BACKGROUND: The benefit of adjuvant therapy (AT) for gallbladder cancer (GBC) is unclear as evidenced by conflicting results from nonrandomized studies. Here we aimed to perform a meta-analysis to determine the impact of AT on overall survival (OS). METHODS: We used data from MEDLINE, EMBASE and the Cochrane Collaboration Library and published between October 1967 and October 2014. Studies that evaluated AT compared with curative-intent surgery alone for resected GBC were included. Subgroup analyses of benefit based on node status, margins status, and American Joint Committee on Cancer (AJCC) staging were prespecified. Data were weighted and pooled using random-effect modeling. RESULTS: Ten retrospective studies involving 3,191 patients were analyzed. There was a nonsignificant improvement in OS with AT compared with surgery alone (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.56-1.03). A significant improvement was observed in OS with chemotherapy (CT) compared with surgery alone (HR, 0.42; 95% CI, 0.22-0.80) by sensitivity analysis. The greatest benefit for AT was also observed in those with R1 disease (HR, 0.33; 95% CI, 0.19-0.59), LN-positive disease (HR, 0.71; 95% CI, 0.63-0.81), and AJCC staging meeting or exceeding tumor Stage II (HR, 0.45; 95% CI, 0.26-0.79), but not in those with LN-negative or R0 disease. CONCLUSION: Our results strongly support the use of CT as an AT in GBC. Moreover, patients with node positivity, margin positivity, or non-stage I disease are more likely to benefit from AT.

Hematocrit Level could Reflect Inflammatory Response and Disease Activity in Patients with Systemic Lupus Erythematosus.

BACKGROUND: The previous study has reported the association of hematocrit (HCT) with inflammation in several diseases. But the role of HCT in systemic lupus erythematosus (SLE) remained unclear. We tried to evaluate the clinical significance of HCT levels in patients with SLE. METHODS: A retrospective study including 127 adult SLE patients and 146 normal healthy controls was performed. HCT levels between SLE patients and normal healthy controls were compared, and correlations between HCT and clinical characteristics were evaluated. RESULTS: HCT levels in SLE patients were significantly decreased as compared with the normal healthy controls and negatively correlated with C-reactive protein (CRP) (r = -0.336, p < 0.01), erythrocyte sedimentation rate (ESR) (r = -0.332, p < 0.01), and SLEDAI scores (r = -0.376, p < 0.01). HCT levels were also significantly lower in SLE patients with decreased C3 and C4 as compared with those in SLE patients with normal C3 and C4, indicating that HCT was positively correlated with C3 and C4 levels (r = 0.272, p < 0.01; r = 0.273, p < 0.01). HCT was decreased in SLE patients with the presence of anti-Sm and anti-RNP antibodies as compared with those without these auto-antibodies (p = 0.013, p < 0.01). After adjusting RBC count and hemoglobin level, multiple linear regression analysis showed that HCT was independently associated with disease activity in SLE patients. In addition, HCT levels were elevated after treatment. CONCLUSIONS: HCT is correlated with CRP, ESR, and SLEDAI, suggesting that HCT could reflect inflammatory response and disease activity in SLE patients.

Neutrophil- and platelet-to-lymphocyte ratios are correlated with disease activity in rheumatoid arthritis.

BACKGROUND: Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are reported to be increased in various inflammation-related diseases, but their clinical significance in rheumatoid arthritis (RA) remains unclear. The aim of the present study was to explore whether NLR and PLR were candidate indices for RA disease-activity assessment. METHODS: The medical records of 128 RA patients and 78 healthy individuals were retrospectively reviewed. Correlations of NLR and PLR with the disease activity of RA were evaluated. RESULTS: NLR and PLR were increased significantly in RA patients. NLR was significantly positively correlated with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and Disease-Activity Score including 28 joints (DAS28) in RA patients, while PLR was positively correlated with CRP and DAS28, but not with ESR. CONCLUSIONS: Both NLR and PLR values may prove to be potential indices for RA disease-activity assessment.

Primary Sjogren's syndrome and malignancy risk: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between primary Sjögren's syndrome (pSS) and the risks of malignancy including overall malignancy and site-specific malignancies through a systematic review and meta-analysis. METHODS: We searched Pubmed before January 2013, with a restriction to English language publications. Studies were included if they met the following criteria: (1) a cohort or observational study; (2) pSS as one of the exposure interests; (3) cancer as an outcome of interest; (4) relative risk (RR) or standardised incidence rate (SIR) with 95% CIs. We used a random or fixed effects model to calculate the pooled RR according to the heterogeneity test. RESULTS: Fourteen studies involving more than 14 523 patients with pSS were included. Compared with the general population, patients with pSS had significantly increased risks of overall cancer (pooled RR 1.53; 95% CI 1.17 to 1.88), non-Hodgkin lymphoma (NHL) (pooled RR 13.76; 95% CI 8.53 to 18.99) and thyroid cancer (pooled RR 2.58; 95% CI 1.14 to 4.03). A significant association was found in various subgroup meta-analyses for NHL but, for overall malignancy, a significant association was only found in some groups. Additionally, the number of studies exploring the association of pSS with the risk of solid malignancies was so small that we could not carry out subgroup meta-analyses. CONCLUSIONS: This meta-analysis indicates that pSS is significantly associated with increased risks of overall malignancy, NHL and thyroid cancer. However, it is not yet known whether the apparent increased risk of overall malignancy in patients with pSS is due to the relatively high prevalence of NHL in that group.

Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis.

OBJECTIVES: Elevated expression of Siglec-1 on circulating monocytes has been reported in some inflammatory and autoimmune diseases, but its expression and role in RA has not been elucidated. The aims of this study were to determine the expression of Siglec-1 in peripheral blood and to explore its role in mononuclear cell reactivity to autoantigen in RA. METHODS: Siglec-1 protein and mRNA levels in 42 RA patients, 39 OA patients, 28 SLE patients and 42 normal controls were determined by flow cytometry and quantitative RT-PCR, respectively. In addition, 10 patients with active RA received DMARDs for 12 weeks and the frequencies of Siglec-1-positive cells and the 28-joint DAS (DAS28) were assessed before and after therapy. Furthermore, TNF-α, IFN-γ and type II collagen were used to up-regulate Siglec-1. Peripheral blood mononuclear cells (PBMCs) from different groups were stimulated with mitogens or antigens and cell proliferation and cytokine production were determined. RESULTS: The protein and mRNA levels of Siglec-1 on PBMCs and monocytes in RA patients were significantly higher than those in OA patients and healthy controls. Moreover, the expression of Siglec-1 protein on PBMCs was positively correlated with DAS28, ESR, high-sensitivity CRP and IgM-RF, but not with anti-CCP antibody. Interestingly, Siglec-1 expression was decreased in parallel with the decrease in the DAS28 after 12 weeks of anti-rheumatic treatment. Furthermore, TNF-α, IFN-γ and type II collagen can up-regulate Siglec-1 in PBMCs. Elevated PBMC proliferation and proinflammatory cytokine production to collagen stimulation in RA patients decreased when Siglec-1 was inhibited by anti-Siglec-1 antibodies. CONCLUSION: Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for monitoring disease activity in RA. Siglec-1 may also play a proinflammatory role in stimulating lymphocyte proliferation and activation in RA.

A meta-analysis of the association of IL-6 -174 G/C and -572 G/C polymorphisms with systemic lupus erythematosus risk.

The results from previous studies on association of IL-6 -174 G/C and -572 G/C polymorphisms with the risk of systemic lupus erythematosus (SLE) remained inconsistent. Therefore, a meta-analysis was performed to assess the association between these two polymorphisms and SLE susceptibility. A literature-based search was conducted to identify all relevant studies. Pooled data were estimated by fixed- and random-effects models when appropriate. Nine publications were included in the meta-analysis, seven for -174 G/C polymorphism and three for -572 G/C polymorphism. The results indicated that IL-6 -174 G/C polymorphism was significantly associated with SLE risk for recessive model and allele analysis in overall populations (OR 1.64, 95 % CI 1.10-2.45, P = 0.016; and 1.34, 1.05-1.72, P = 0.019, respectively, for recessive model and allele analysis) or in Caucasians (OR 1.37, 95 % CI 1.04-1.82, P = 0.027; and 1.27, 1.04-1.54, P = 0.018, respectively, for recessive model and allele analysis). Also, significant association between IL-6 -572 G/C polymorphism and SLE was found under recessive model (OR 1.49, 95 % CI 1.10-2.01, P = 0.009), but not under dominant model and allele analysis (OR 1.05, 95 % CI 0.77-1.43, P = 0.750; and 1.21, 1.00-1.48, P = 0.054, respectively, for dominant model and allele analysis). Additionally, our meta-analysis showed that IL-6 -174 G/C polymorphism was significantly associated with discoid skin lesions (P < 0.05). The present study indicates that IL-6 -174 G/C and -572 G/C polymorphisms could be candidates for susceptibility to SLE. Furthermore, a large number of studies should be performed to explore the association of IL-6 polymorphisms with the risk and clinical characteristics of SLE patients in different ethnics.

Primary biliary cirrhosis and cancer risk: a systematic review and meta-analysis.

UNLABELLED: Several studies have indicated that primary biliary cirrhosis (PBC) may be associated with increased risk of some cancers, but the results are controversial. We conducted a systematic review of studies to examine the association of PBC with cancer risk by meta-analysis. We searched the PubMed and EMBASE databases for English-language studies published before November 2011. Studies were included if they reported relative risk estimates with 95% confidence intervals (CIs) or related data for the association between PBC and cancer risk. Approximately 16,300 PBC patients from several countries were included in this analysis. Of the 3510 titles identified, 16 publications involving 17 studies meeting the inclusion criteria were included in the meta-analysis. Compared with the general population, PBC patients had a significantly higher risk of overall cancer (pooled rate ratio [RR], 1.55; 95% CI, 1.28-1.83) and hepatocellular carcinoma (HCC) (pooled RR, 18.80; 95% CI, 10.81-26.79). For stomach and pancreas cancers, the results of one study that only examined male patients with PBC indicated that PBC patients had increased risk of stomach cancer and pancreatic cancer, whereas the results of other studies of mixed-sex patients showed no significant association. Therefore, despite inconsistent results, the meta-analysis could not be conducted for assessing the association. PBC was not significantly associated with increased risk of other cancers. CONCLUSION: The present systematic review and meta-analysis demonstrate that PBC is closely associated with a greater risk of overall cancer and HCC, but not with other cancers. The data regarding the association between PBC and risks of several cancers need to be further confirmed in future studies.

Increased IL-23 and IL-17 expression by peripheral blood cells of patients with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a typical autoimmune disease for which the pathogenesis remains unclear. IL-23 and IL-17 are pro-inflammatory cytokines of the "IL-23/IL-17 axis," which may play a key role in the pathogenesis of autoimmune diseases. In this study, we investigated the expression of IL-23 and IL-17 in the peripheral blood of patients with PBC and its clinical significance. We used quantitative PCR to determine mRNA expressions of IL-23, IL-23 receptor, and IL-17 in peripheral blood mononuclear cells (PBMC) from PBC patients. ELISA's were used to determine patients' serum levels of IL-23 and IL-17. IL-23- and IL-17-producing cells in liver biopsis were also analyzed. Compared to a healthy control group, the mRNA expression levels of IL-23 p19, its corresponding receptor, IL-23R, and IL-17 in PBMC's from PBC patients were significantly increased, and these levels were correlated with PBC disease stages. PBC patients' serum levels of IL-23 and IL-17 were higher than those in a post-hepatic cirrhosis group and a healthy group, and were significantly higher in the early PBC disease stages than in the advanced PBC stages. There were significantly more IL23+ and IL-17+ mononuclear cells in portal areas of liver tissues in advanced stages of this disease than in the early stages. The serum levels of IL-23 and IL-17 in PBC patients were positively correlated with serum GGT levels. Thus, IL-23 and IL-17 may play an important role in the pathogenesis of PBC by promoting inflammation. Because the IL-23 and IL-17 levels in the peripheral blood of PBC patients were increased and were correlated with clinical stages, they may be indices that could be used to clinically monitor PBC.

Hepatitis C virus genotype diversity in Shanghai, China.

We studied 67 hepatitis C virus (HCV) isolates from 64 hospitalized patients in Shanghai, China. Genotype 1 was prevalent, and genotypes 2, 3, 6 were found for the first time in Shanghai. A rare mixed infection with three subtypes (1a, 1b, 2a) was found. The complete genome sequence of a subtype 3b isolate was determined and analyzed.

Analysis of altered microRNA expression profiles in peripheral blood mononuclear cells from patients with primary biliary cirrhosis.

BACKGROUND AND AIM: MicroRNA, as an important regulator of gene expression, has been found to be associated with several diseases. MicroRNA expression profiles have been identified in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the expression profile in peripheral blood mononuclear cells (PBMCs) from primary biliary cirrhosis (PBC) patients and the role of microRNA in PBC remained unclear. The present study aimed to explore abnormal microRNA regulation in PBC. METHODS: MicroRNA array was performed in PBMCs obtained from PBC patients versus healthy controls. Then, six of the 17 differentially expressed microRNAs were confirmed using quantitative real-time polymerase chain reaction. Based on bioinformatics analysis, we identified the potential biological processes and significant signaling pathways affected by these microRNAs, and generated the microRNA-gene network. RESULTS: According to microRNA array, a total of 17 microRNAs were found to be differentially expressed. Six microRNAs have been validated using quantitative real-time polymerase chain reaction, and the results were consistent with microRNA array analysis. The bioinformatics analysis showed that the potential target genes of these microRNAs were involved in cell proliferation, cell differentiation, apoptosis, and signal transduction. Similarly, these microRNAs also affected endocytosis, mitogen-activated protein kinase signaling pathway, transforming growth factor-ß signaling pathway, Wnt signaling pathway, calcium signaling pathway, etc. CONCLUSION: In the present study, 17 microRNAs were identified to be differentially expressed in PBMCs from PBC patients. Functional bioinformatics analysis demonstrated that prediction genes targeted by these microRNAs were involved in multiple biological processes and signaling pathways. The present study offers intriguing new perspectives on the involvement of microRNA in PBC, but the precise mechanisms need to be validated further.

Value of baseline platelet count for prediction of complications in primary biliary cirrhosis patients treated with ursodeoxycholic acid.

BACKGROUND: Decreased platelet count has been observed in various liver diseases, but its significance in primary biliary cirrhosis (PBC) remains unknown. The present study aimed to evaluate the predictive value of the platelet count at diagnosis for PBC-related complications in patients newly diagnosed with PBC and treated with ursodeoxycholic acid (UDCA). METHODS: Ninety-six PBC patients without complications treated with UDCA immediately after diagnosis were retrospectively reviewed. All hematologic and chemical parameters, Mayo risk score and PBC-related complications including upper gastrointestinal hemorrhage, presence of ascites, serum bilirubin concentration > 102.6 µmol/L and onset of hepatic encephalopathy were extracted. The associations between these parameters at diagnosis and complications were determined and the prognostic value of the platelet count was evaluated by receiver operating characteristics (ROC) analysis, Kaplan-Meier method and Cox proportional hazard model with the hazard ratio (HR) and 95% confidence interval (CI) calculated. RESULTS: Patients with PBC-related complications had significantly decreased platelet count and serum bilirubin concentration, prolonged prothrombin time, and increased Mayo risk score compared to those without complications. A platelet count of ≤ 132.5 × 10(9)/L was associated with the occurrence of complications, with an area under the ROC curve of 0.74 (95% CI: 0.64-0.85). The association remained even after adjustment for Mayo risk score (HR: 2.85; 95% CI: 1.46-5.54; p < 0.01), as shown in the Cox proportional hazard model. CONCLUSIONS: Decreased platelet count is a predictive factor for PBC-related complications. A cut-off value of ≤ 132.5 × 10(9)/L is recommended for the baseline platelet count to predict complications in patients newly diagnosed with PBC and treated with UDCA.

Meta-analysis of the association between the IL-12B +1188 A/C polymorphism and cancer risk.

BACKGROUND: Because of inconsistent results from previous studies on the association of IL-12B +1188 A/C polymorphism with cancer risk, a meta-analysis was performed to assess the association. MATERIALS AND METHODS: A literature search was performed to identify all relevant studies to May 31, 2012, with a restriction to English and Chinese publications. Pooled data were estimated using a random-effects model. RESULTS: 17 publications were included in the meta-analysis. The results indicated that the polymorphism was significantly associated with a decreased risk for overall cancer (odds ratio (OR), 95% confidence interval (CI): 0.86, 0.76-0.97, p = 0.007; 0.80, 0.68-0.95, p = 0.012; and 0.88, 0.78-0.99, p = 0.032, respectively for dominant model, recessive model, and allele analysis) or nasopharyngeal cancer and hepatocellular carcinoma. This association was also found in Asians (OR, 95% CI: 0.89, 0.80-0.99, p = 0.031; 0.82, 0.68-0.98, p = 0.027; and 0.89, 0.80-1.00, p = 0.047, respectively for dominant model, recessive model, and allele analysis), but not in Europeans and Americans. CONCLUSION: The present study indicates that the IL-12B +1188 A/C polymorphism could play a protective role in the development of cancer. More investigations involving various cancer types among various populations are needed.

[Abnormal expression of miR-let-7b in primary biliary cirrhosis and its clinical significance].

OBJECTIVE: To evaluate the expression of microRNA (miR)-let-7b in peripheral blood cells of patients with primary biliary cirrhosis (PBC) and investigate its relationship to clinical disease parameters. METHODS: Peripheral blood and serum samples were obtained for study from 60 PBC patients and 60 healthy controls. Peripheral blood cells were extracted and subjected to real-time PCR to measure miR-let-7b expression. Serum levels of interleukin (IL)-18, total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured by standard biochemical assays. The relationship between miR-let-7b expression and disease parameters was assessed by Spearman's rank correlation test. RESULTS: PBC patients showed significantly lower expression of miR-let-7b in peripheral blood cells than healthy controls (P less than 0.001); moreover, the miR-let-7b expression level decreased in parallel to increases in disease severity (stage I > II / III > IV). In PBC patients, the miR-let-7b expression was significantly correlated with Mayo risk scores (r = -0.4930, P less than 0.001), IL-18 (r = -0.4643, P less than 0.001) and ALP (r = -4119, P less than 0.001), but not with TBIL or GGT. CONCLUSION: Decreased expression of miR-let-7b may be associated with development and progression of PBC, and this miRNA may represent a novel target of improved diagnostic and preventive strategies for PBC.