Protective effects of lutein against vancomycin-induced acute renal injury in mice via upregulation of peroxisome proliferator-activated receptor gamma/nuclear factor erythroid 2-related factor 2 and inhibition nuclear factor-kappaB/caspase 3.

Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-ß-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.

Current Use of Cardiac Biomarkers in Various Heart Conditions.

Biomarkers are increasingly recognized to have significant clinical value in early identification and progression of various cardiovascular diseases. There are many heart conditions, such as congestive heart failure (CHF), ischemic heart diseases (IHD), and diabetic cardiomyopathy (DCM), and cardiac remodeling, in which the severity of the cardiac pathology can be mirrored through these cardiac biomarkers. From the emergency department (ED) evaluation of acute coronary syndromes (ACS) or suspected acute myocardial infarction (AMI) with cardiac marker Troponin to the diagnosis of chronic conditions like Heart Failure (HF) with natriuretic peptides, like B-type natriuretic peptide (BNP), N-terminal pro-B- type natriuretic peptide (Nt-proBNP) and mid regional pro-atrial natriuretic peptide (MR- proANP), their use is continuously increasing. Their clinical importance has led to the discovery of newer biomarkers, such as the soluble source of tumorigenicity 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), and various micro ribonucleic acids (miRNAs). Since cardiac pathophysiology involves a complex interplay between inflammatory, genetic, neurohormonal, and biochemical levels, these biomarkers could be enzymes, hormones, and biologic substances showing cardiac injury, stress, and malfunction. Therefore, multi-marker approaches with different combinations of novel cardiac biomarkers, and continual assessment of cardiac biomarkers are likely to improve cardiac risk prediction, stratification, and overall patient wellbeing. On the other hand, these biomarkers may reflect coexisting or isolated disease processes in different organ systems other than the cardiovascular system. Therefore, knowledge of cardiac biomarkers is imperative. In this article, we have reviewed the role of cardiac biomarkers and their use in the diagnosis and prognosis of various cardiovascular diseases from different investigations conducted in recent years.

Hepatitis B virus enhances interleukin-27 expression both in vivo and in vitro.

The immune system plays important roles in determining the outcomes of hepatitis B virus (HBV) infection. Interleukin-27 (IL-27) is a recently identified pro-inflammatory cytokine produced by macrophages, dendritic cells, and epithelial cells. To determine the correlation between HBV infection and IL-27 expression, we investigated the serum IL-27 levels in patients with HBV infection and in healthy individuals. Results showed that IL-27 was significantly elevated in patients as compared to healthy individuals (P<0.001). IL-27 was also detected at higher levels in patients with liver cirrhosis or hepatocellular carcinoma than those with acute hepatitis B or chronic hepatitis B (P<0.05). We also found that IL-27 expression was influenced by HBV e antigen. In addition, our in vitro studies demonstrated that IL-27 promoter activity, mRNA and protein expression were all stimulated in cells transfected with infectious HBV clone.

Increased level of IL-32 during human immunodeficiency virus infection suppresses HIV replication.

Interleukin-32 was recently identified as a pro-inflammatory cytokine produced by T-lymphocytes, natural killer cells, epithelial cells, and blood monocytes. IL-32 is induced by IFN-gamma in a time-dependent manner suggesting a role for IL-32 in innate and adaptive immune responses. In this study we present evidence that Human immunodeficiency virus promotes interleukin-32 production at both mRNA and protein levels. Our results showed that there is a 74% increase in the serum levels of IL-32 among HIV patients as compared to healthy individuals. There was a three-fold increase in the promoter activity of the IL-32 in the present infections HIV clone. This increase in IL-32 promoter activity was substantiated by increased IL-32 mRNA and protein levels. We have also demonstrated that IL-32 suppresses HIV replication. Our results show that HIV LTR activity was increased by more than six-folds when endogenous IL-32 was knocked down by IL-32-specific siRNA whereas it decreased by one-fold when IL-32 was over expressed in the cells. Similarly a more than two-fold increase and a 50% decrease in HIV p24 values were noted when IL-32 was knocked down and when IL-32 was over expressed in the cells, respectively. Our present work shows that raised IL-32 levels in HIV infection may in turn hamper HIV replication; one of the protective mechanisms of nature.

Single-chain intracellular antibodies inhibit influenza virus replication by disrupting interaction of proteins involved in viral replication and transcription.

Influenza A virus is responsible for influenza epidemics in avian and human populations and poses a great threat to human health. Many researches have been focused on the prevention and treatment of influenza A virus infection. The nucleoprotein (NP) of the virus is an important protein due to its ability to interact with a variety of viral and cellular factors and its role in the viral RNA synthesis. In this study, we have used the influenza A virus nucleoprotein as target for anti-viral therapy through a new approach. By screening a human single-chain intracellular antibody (intrabody) cDNA library using nucleoprotein as bait in a yeast antigen-antibody two-hybrid system, we have identified several intrabodies that specifically interact with the viral nucleoprotein. Interaction between nucleoprotein and anti-nucleoprotein intrabodies was further confirmed by mammalian two-hybrid analysis. Results showed that anti-nucleoprotein intrabodies changed their cellular distribution in association with the viral nucleoprotein. Further studies indicated that anti-nucleoprotein intrabodies abolished the accumulation of not only the complementary RNA and virion RNA but also messenger RNA of influenza virus. In addition, anti-nucleoprotein intrabodies significantly inhibited influenza A virus transcription and replication through blocking the interaction of nucleoprotein with the viral polymerase proteins, polymerase basic protein 1 and polymerase basic protein 2. Thus, this study not only provides a powerful tool for the study of viral protein's functions, but also opens a new potential avenue for the prevention and treatment of influenza virus infections.

Activation of interleukin-32 pro-inflammatory pathway in response to influenza A virus infection.

BACKGROUND: Interleukin (IL)-32 is a recently described pro-inflammatory cytokine that has been reported to be induced by bacteria treatment in culture cells. Little is known about IL-32 production by exogenous pathogens infection in human individuals. METHODS AND FINDINGS: In this study, we found that IL-32 level was increased by 58.2% in the serum samples from a cohort of 108 patients infected by influenza A virus comparing to that of 115 healthy individuals. Another pro-inflammatory factor cyclooxygenase (COX)-2-associated prostaglandin E2 was also upregulated by 2.7-fold. Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. Interestingly, we found that COX-2-associate PGE(2) production activated by influenza virus infection was significantly suppressed by over-expression of IL-32 but increased by IL-32-specific siRNA, suggesting there was a feedback mechanism between IL-32 and COX-2. CONCLUSIONS: IL-32 is induced by influenza A virus infection via COX-2 in the inflammatory cascade. Our results provide that IL-32 is a potential target for anti-inflammatory medicine screening.

Origin of highly pathogenic H5N1 avian influenza virus in China and genetic characterization of donor and recipient viruses.

Genetic analysis of all eight genes of two Nanchang avian influenza viruses, A/Duck/Nanchang/1681/92 (H3N8-1681) and A/Duck/Nanchang/1904/92 (H7N1-1904), isolated from Jiangxi province, China, in 1992, showed that six internal genes of H3N8-1681 virus and five internal (except NS gene) genes of H7N1-1904 virus were closely similar to A/Goose/Guangdong/1/96 (H5N1) virus, the first highly pathogenic avian influenza (HPAI) virus of subtype H5N1 isolated in Asia. The neuraminidase (NA) gene of Gs/Gd/1/96 had the highest genetic similarity with A/Duck/Hokkaido/55/96 (H1N1-55) virus. The haemagglutinin (HA) gene of Gs/Gd/1/96 virus might have originated as a result of mutation of H5 HA gene from A/Swan/Hokkaido/51/96 (H5N3-51)-like viruses. The PA gene of H5N3-51 virus had the highest similarity with Gs/Gd/1/96. This study explains the origin of first Asian HPAI H5N1 virus in Guangdong by the reassortment of Nanchang (close to Guangdong) and Hokkaido (Japan) (H1N1-55 and H5N3-51) viruses. Genetic characteristics of donor and recipient viruses were also studied.