Coinfection with porcine circovirus type 2 and Streptococcus suis serotype 2 enhances pathogenicity by dysregulation of the immune responses in piglets.

Porcine circovirus type 2 (PCV-2) and Streptococcus suis (S. suis) are common pathogens in pigs. Both pathogens are associated with the porcine respiratory disease complex. Clinically, coinfection of PCV-2 and S. suis are often detected in pigs with respiratory symptoms, while interactions between the two pathogens during coinfection and the coinfection pathogenesis are poorly understood. In this study, a piglet model coinfected with PCV-2 and Streptococcus suis serotype 2 (SS2) was established; coinfection of piglets increased the contents of SS2 in blood, and piglets showed more severe pneumonia, myocarditis and arthritis. Peripheral blood mononuclear cells (PBMCs) were collected and coinfected piglets showed high expression levels of inflammatory cytokines and TLR2, TLR4, while levels of CD4, CD8 and MHC II were reduced. In addition, in order to further explore the mechanisms of coinfection induced cytokine overexpression, an in vitro model of coinfection with PCV-2 and SS2 was established using cells of the porcine monocytic line 3D4/21. Similar to the in vivo results,coinfected cells exhibited increased expression of the cytokines IL-6, IL-8, TNF-α and the receptors TLR2, TLR4, while they showed a lower expression of MHC II than cells infected with SS2 alone. Furthermore, in coinfected 3D4/21 cells, both MAPK and NF-κB signaling pathways were activated, and the increased expression of IL-8 was related to TLR4. In general, coinfection with PCV-2 and SS2 exacerbated the inflammatory response and probably impaired macrophage antigen presentation, resulting in immune dysregulation and increasing the severity of host infection.

A small non-coding RNA facilitates Brucella melitensis intracellular survival by regulating the expression of virulence factor.

Brucella species are the causative agents of brucellosis, a worldwide zoonotic disease that affects a broad range of mammals and causes great economic losses. Small regulatory RNAs (sRNAs) are post-transcriptional regulatory molecules that participate in the stress adaptation and pathogenesis of Brucella. In this study, we characterized the role of a novel sRNA, BSR1141, in the intracellular survival and virulence of Brucella melitensis. The results show that BSR1141 was highly induced during host infections and under in vitro stress situations that simulated the conditions encountered within host phagocytes. In addition, a BSR1141 mutant showed reduced survival both under in vitro stress conditions and in mice, confirming the role of BSR1141 in Brucella intracellular survival. Bioinformatic and experimental approaches revealed that BSR1141 affects the expression of many target genes, including the Brucella virulence component virB2. These data indicate that BSR1141 could influence the expression of virB2, which is important for B. melitensis pathogenesis and intracellular survival. This work provides new insight into the mechanism of adaptation to environmental stress and into the pathogenesis of intracellular pathogens.

GP73 regulates Hepatic Steatosis by enhancing SCAP-SREBPs interaction.

Elevated Golgi phosphoprotein 2 (GP73, also known as GOLPH2 or GOLM1) expression in serum and liver, which can be induced by viral infection and cytokine treatments, is intimately connected with liver disease, including acute hepatitis, cirrhosis and hepatocellular carcinoma (HCC). However, its pathogenic roles in hepatic diseases have never been clarified in detail. Here, we showed that the upregulated GP73 is indispensable for SREBPs activation and lipogenesis. Notably, GP73 overexpression enhanced SCAP-SREBPs binding and its Golgi trafficking even under cholesterol sufficiency. Consistent with these functional findings, GP73 blockage could alleviate tunicamycin-induced liver steatosis by reducing SREBPs activation. A significant positive correlation of GP73 with genes in lipid metabolism pathway was also identified in liver cancer based on data from The Cancer Genome Atlas (TCGA) dataset. Our findings revealed previously unrecognized role of GP73 in lipid metabolism.

Serum Golgi protein 73 is a prognostic biomarker of liver transplantation patients.

BACKGROUND: The death after liver transplantation (LT) was most commonly caused by HCC recurrence. Golgi protein 73 (GP73), a type II Golgi membrane protein, has been proved to be a better serum marker for HCC. OBJECTIVE: This study aims to clarify the relationship between serum GP73 levels and tumor recurrence as well as survival of HCC patients after LT. METHODS: Between November 2003 and July 2008, serum samples from 60 liver transplantation patients and 72 healthy individuals were collected. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Patient survival was analyzed using log-rank test along with Kaplan-Meier method. Receiver operating characteristic (ROC) curve was utilized to analyze the diagnostic value of serum GP73 levels. Cox regression was utilized to analyze prognostic factors with multiple variables. RESULTS: Serum GP73 concentrations in HCC patients were much higher than that in healthy controls (P<0.001). Patients with lower serum GP73 levels at LT-6Month had better overall survival and recurrence-free survival than those with higher serum GP73 levels. ROC analyzing results showed that higher serum GP73 levels at 6 month post-LT could significantly predict mortality (P=0.020) as well as HCC recurrence (P=0.001) after liver transplantation. Multivariate analysis revealed that serum GP73 levels at LT-6Month was an independent predictor of good prognosis (P=0.002). CONCLUSION: Serum GP73 levels could be used to predict tumor recurrence and survival in HCC sufferers after LT.

Metabonomics reveals plasma metabolic changes and inflammatory marker in polycystic ovary syndrome patients.

Polycystic ovary syndrome (PCOS) is a common, clinically heterogeneous endocrine disorder affecting women of reproductive age, associated with endocrinopathy and metabolic abnormalities. Although some metabolic parameters have been investigated, very little information has been reported on the changes of small metabolites in biofluids. The aim of this study was to establish the metabolic profile of PCOS and compare it with that of controls. In this cross-sectional study of 34 women with PCOS and 36 controls, contents of small metabolites and lipids in plasma samples were measured using nuclear magnetic resonance (NMR)-based techniques and analyzed using multivariate statistical methods. Significant decrease (P < 0.05) in the levels of amino acids (leucine, isoleucine, methionine, glutamine, and arginine), citrate, choline, and glycerophosphocholine/phosphocholine (GPC/PC), and increase (P < 0.05) in the levels of lactate, dimethylamine (DMA), creatine, and N-acetyl glycoproteins were observed in PCOS patients compared with the controls. Subgroups of patients with obesity, metabolic syndrome, or hyperandrogenism exhibited greater metabolic deviations than their corresponding subgroups without these factors. PCOS patients have perturbations in amino acid metabolism, the tricarboxylic acid (TCA) cycle, and gut microflora, as well as mild disturbances in glucose and lipid metabolism. The elevated level of N-acetyl glycoproteins demonstrates the existence of low-grade chronic inflammation in PCOS patients.

Novel plasmid and its variant harboring both a bla(NDM-1) gene and type IV secretion system in clinical isolates of Acinetobacter lwoffii.

The spread of the bla(NDM-1) gene is gaining worldwide attentions. This gene is usually carried by large plasmids and has been discovered in diverse bacteria since it was originally found in Klebsiella pneumoniae. Here we report the complete sequences of a bla(NDM-1)-bearing plasmid, pNDM-BJ01, and its variant, pNDM-BJ02, isolated from clinical Acinetobacter lwoffii strains. The plasmid pNDM-BJ01 is 47.3 kb in size and cannot be classified into any known plasmid incompatibility group, thus representing a novel plasmid with an unknown maintenance mechanism. This plasmid contains both a bla(NDM-1) gene and a type IV secretion system (T4SS) gene cluster. The T4SS is assigned to the P-type T4SS group, which usually encode a short, rigid pilus, and the bla(NDM-1) gene is located within a composite transposon flanked by two insertion elements of ISAba125. Plasmid pNDM-BJ02 is nearly identical to pNDM-BJ01 except that one copy of the ISAba125 element is missing, and it is therefore regarded as a variant of pNDM-BJ01. Sequence alignment indicated that this bla(NDM-1)-containing composite transposon, which can also be captured by other mobile elements, was probably a product of multiple recombination events and can move as a whole by transposition.

[Evaluation on HIV antibody testing strategy currently used in China].

OBJECTIVE: To evaluate the yield of HIV antibody testing strategy currently used on different populations, in China. METHODS: (1) The following samples were collected and tested according to the currently used HIV antibody testing strategy in China. 103 133 samples from the general populations (outpatients, new recruits and blood donors), 1276 people under high risk (spouses of the HIV infected individuals, intravenous drug users) and 2323 biochemical or immunological abnormal samples. (2) Retrospective analysis was done on data from the HIV testing among outpatients in General Hospital of People's Armed Police Forces, from Jan., 2002 to Dec., 2008 and in three provincial central HIV test and confirmatory laboratories. RESULTS: (1) The yields of HIV antibody screening were significantly different in different populations. The probability of screening reactive to be true positive was 50% in high risk population, significantly higher than in the general population. The probability of screening reactive to be true positive was 19.58% in the confirmatory laboratory mainly towards the general population, but significantly lower than results from the confirmatory laboratories done on the high risk population. (2) From 2002 to 2008, in the General Hospital of People's Armed Police Forces, the probability of screening reactive to be true positive in the clinical HIV test was increasing from 3.7% to 16.0%, where as the efficiency of the repeat screening testing decreased from 92.6% to 61.5%. CONCLUSION: The predictive value of HIV antibody screening reactive was significantly greater in high risk population than in general population. The precision of HIV antibody initial screening was substantially increased with the improvement of HIV antibody test kits and of quality control in the HIV test laboratories in recent years. It is suggested that different HIV test strategies to be implemented in different populations.