[The expression and clinical significance of neutrophil myeloperoxidase in patients with myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis].

Objective: To investigate the expression and clinical significance of neutrophil myeloperoxidase (MPO) in patients with MPO-antibody associated vasculitis (AAV). Methods: Thirty-six newly diagnosed MPO-AAV patients who were hospitalized in the First Affiliated Hospital, Anhui Medical University from July 2018 to June 2021 were enrolled,and 36 age and sex matched healthy subjects were selected as controls. Neutrophil MPO level was detected by flow cytometry (FCM) and MPO mRNA was tested by real time quantitative polymerase chain reaction (RT-qPCR) in all subjects. Serum complement fragment C5 (C5a) and MPO in both groups and serum MPO-anti-antineutrophilic cytoplasmic antibody(ANCA) in MPO-AAV group were measured by enzyme linked immunosorbent assay (ELISA), while the disease activity was evaluated by Birmingham vasculitis activity score-V3 (BVAS-V3). Results: Compared with the heathy control group, the expression of MPO mRNA in neutrophils, serum MPO and complement C5a in MPO-AAV group were significantly higher[MPO mRNA:30.2±11.5 vs. 1.9±0.6, P<0.001;MPO:(112.0±68.7) IU/L vs. (87.4±22.9) IU/L, P=0.01; C5a:(187.3±90.3) ng/ml vs. (107.3±31.1) ng/ml, P<0.001; respectively], while the mean fluorescence intensity (MFI) of MPO in neutrophils were significantly lower [ 1 343.3±723.4 vs. 2 868.0±1 136.5, P<0.001]. In MPO-AAV group, the expression of neutrophil MPO mRNA was positively correlated with serum MPO-ANCA and MPO levels (r=0.537, P=0.001 and r=0.358, P=0.032; respectively). Multiple regression analysis suggested that neutrophil MPO mRNA expression was positively correlated with serum MPO-ANCA level (ß=0.695, P=0.006); neutrophil MPO level was negatively correlated with serum MPO-ANCA, MPO and complement C5a levels (r=-0.335, P=0.046; r=-0.372, P=0.026; r=-0.577, P<0.001; respectively). Further, neutrophil MPO level was negatively correlated with serum complement C5a level (ß=-0.374, P=0.043). BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils, serum MPO-ANCA, MPO and complement C5a (r=0.598, P<0.001; r=0.599, P<0.001; r=0.537, P=0.001; r=0.415, P=0.012; respectively) and negatively correlated with MPO level in neutrophils (r=-0.342, P=0.041). In multiple regression analysis it suggested that BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils (ß=0.511, P=0.002). Conclusion: In MPO-AAV patients, MPO synthesis and release in neutrophils are both significantly increased, which might be influenced by serum MPO-ANCA and C5a, respectively. Furthermore, MPO synthesis activity in neutrophils is an independent factor related to disease activity.

Identifying significant pathways of hepatitis B virus-related hepatocellular carcinoma based on crosstalk and network pathways.

This study aims to identify significant pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) based on the pathway network strategy. We proposed a pathway network where a protein-protein interaction (PPI) network was integrated with the crosstalk of pathways. Pathway data were first obtained from background PPI network, Reactome pathway database, and common genes between mRNA differentially expressed genes (DEGs), and miRNA target genes of HBV-related HCC. Pathway interactions were subsequently randomly extracted based on gene-gene interactions, and a weight value was assigned to each crosstalk using the Spearman correlation coefficient. Finally, pathways and crosstalk were visualized via Cytoscape to construct the final pathway network. A total of 9 common genes were identified between 396 mRNA DEGs and 400 miRNA target genes, and 17 pathways were identified based on background pathways and common genes. In addition, we constructed a pathway network that included 136 interactions and 17 pathways. The weight value of netrin-1 signaling and regulation of Frizzled proteins (FZD) by ubiquitination was the largest, at 0.228. In conclusion, we identified 17 significant pathways that might act as potential biomarkers of HBV-related HCC. This information may offer some insight into treatment and detection of HBV-related HCC.

Proteomics identification of PGAM1 as a potential therapeutic target for urothelial bladder cancer.

Urothelial bladder cancer (UBC) is a major global health problem. There have been no major advances for the treatment of UBC in the last 30 years. In this study, we attempted to discover novel candidate therapeutic biomarkers for UBC. We utilized a two-dimensional polyacrylamide gel electrophoresis (2-DE) and ESI-Q-TOF MS/MS-based proteomic method to compare and identify differentially expressed proteins in UBC and adjacent normal tissues. Thirty five differentially expressed proteins (over 2-fold, p<0.05) were identified. Further cluster analysis revealed these proteins were mainly involved in metabolism, apoptosis regulation, calcium ion binding and so on. Among them, phosphoglycerate mutase 1 (PGAM1), significantly up-regulated in UBC, was selected for detailed analysis. Immunohistochemical data showed that increased expression of PGAM1 was correlated with the severity of histological grade. Knockdown of PGAM1 expression by RNAi contributed to a marked antitumor activity in vivo. Moreover, we found, upon attenuation of PGAM1, its substrate 3-PG (3-phosphoglycerate) was up-regulated and product 2-PG (2-phosphoglycerate) was down-regulated, which consequently inhibited aerobic glycolysis and oxidative pentose phosphate pathway (PPP) that are essential to cancer cell proliferation. Our finding showed that PGAM1 might serve as a promising therapeutic target for UBC.

Massive apoptosis of thymocytes in T-cell-deficient Id1 transgenic mice.

Id1 is an inhibitor of a group of basic helix-loop-helix transcription factors, collectively called E proteins, which includes E12, E47, E2-2, and HEB. We have generated transgenic mice in which Id1 is specifically expressed in T cells. The total number of thymocytes in these mice is less than 4% of that in wild-type mice. The majority of the transgenic thymocytes are CD4 and CD8 double negative and bear the cell surface markers of multipotent progenitor cells. A small number of thymocytes, however, differentiate into CD4 or CD8 single-positive T cells, which also display different characteristics from their wild-type counterparts. More importantly, apoptotic cells constitute about 50% of the total thymocytes. These apoptotic thymocytes have rearranged their T-cell receptor genes, suggesting that they are differentiating T cells. This finding has raised the possibility that the T-cell deficiency in Id1 transgenic mice is the result of a massive apoptosis of differentiating T cells triggered by Id1 expression as opposed to a developmental block at the earliest progenitor stage. The progenitor cells accumulated in the transgenic mice might have survived because they are not susceptible to the apoptotic signals. Despite the massive cell death of the thymocytes at young ages, Id1 transgenic mice frequently develop T-cell lymphoma later in their life span, and lymphomagenesis appears to occur at different stages of T-cell development. Taken together, our data suggest that E proteins, being the targets of Id1, are essential regulators for normal T-cell differentiation and tumor suppression.

Coexistent atypical polypoid adenomyoma and endometrial adenocarcinoma.

Atypical polypoid adenomyoma (APA) is a rare entity that is believed to follow a benign course. We report a case of APA with coexistent endometrial adenocarcinoma. The example raises the possibility that APA may progress to endometrial adenocarcinoma in some cases.

Serum albumin adducts in the molecular epidemiology of aflatoxin carcinogenesis: correlation with aflatoxin B1 intake and urinary excretion of aflatoxin M1.

Aflatoxin-serum albumin adducts in the blood of 42 residents of Guangxi Province, People's Republic of China, were determined and compared with intake of aflatoxin B1 (AFB1) and excretion of aflatoxin M1 (AFM1) in urine. Blood specimens were obtained during the same period that urine was collected and that diet was sampled. Serum albumin was isolated from blood by affinity chromatography on Reactive Blue 2-Sepharose and subjected to enzymatic proteolysis using Pronase. Immunoreactive products were purified by immunoaffinity chromatography and quantified by competitive radioimmunoassay. A highly significant correlation (r = 0.60, P less than 0.00003) of adduct level with AFM1 excretion was observed. An equally highly significant correlation of adduct level with intake (r = 0.69, P less than 0.000001) was also observed. From the slope of the regression line for adduct level as a function of intake, it was calculated that 1.4-2.3% of ingested AFB1 becomes covalently bound to serum albumin, a value very similar to that observed when rats are administered AFB1.