IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab.

Background And Aims: Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1β has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1β, in the treatment of patients with AH.

Porcine Monocyte DNA Traps Formed during Infection with Pathogenic Strains.

() is an enteric pathogen of several mammalian species including man, frequently involving nosocomial resurgence, following oral administration of broad-spectrum antibiotics, but also with human-to-human infection occurring, and neonatal pigs with zoonotic transmission. To date, the immune response to . has mostly focused on neutrophils and cytokine/chemokines, particularly in human infection.

Revisiting Persistent Infection and the Carrier State: What Do We Know?

One characteristic of the few serovars that produce typhoid-like infections is that disease-free persistent infection can occur for months or years in a small number of individuals post-convalescence. The bacteria continue to be shed intermittently which is a key component of the epidemiology of these infections. Persistent chronic infection occurs despite high levels of circulating specific IgG.

Immune Modulation and the Development of Fowl Typhoid: A Model of Human Disease?

serovar Gallinarum (. Gallinarum) is the cause of typhoid in chickens but the immune factors that may facilitate the development of typhoid have not been fully elucidated. We show that, in contrast to non-typhoid .

Design, synthesis, and biological evaluation of novel arylcarboxamide derivatives as anti-tubercular agents.

Our group has previously reported several indolecarboxamides exhibiting potent antitubercular activity. Herein, we rationally designed several arylcarboxamides based on our previously reported homology model and the recently published crystal structure of the mycobacterial membrane protein large 3 (MmpL3). Many analogues showed considerable anti-TB activity against drug-sensitive (DS) () strain.

Diagnosis of sub-clinical coccidiosis in fast growing broiler chickens by MicroRNA profiling.

Coccidiosis in broiler chickens, caused by infection with Eimeria spp. remains one of the most economically important production diseases. Development of a genetic biomarker panel of sub-clinical infection would be an important biological tool for the management of broiler flocks.

Immune evasion by Salmonella: exploiting the VPAC1/VIP axis in human monocytes.

Immune evasion is a critical survival mechanism for bacterial colonization of deeper tissues and may lead to life-threatening conditions such as endotoxaemia and sepsis. Understanding these immune evasion pathways would be an important step for the development of novel anti-microbial therapeutics. Here, we report a hitherto unknown mechanism by which Salmonella exploits an anti-inflammatory pathway in human immune cells to obtain survival advantage.

Immunomodulation by vasoactive intestinal peptide is associated with increased survival and growth of Salmonella Typhimurium in mice.

Studies have shown that administration of vasoactive intestinal peptide (VIP) in mice rescues them from lethal endotoxaemia and that this is correlated with decreased concentration of inflammatory cytokines. VIP has, therefore, been proposed as a novel anti-inflammatory which could be used in the treatment of Gram negative sepsis. However, the effect of VIP has not been reported in mice infected with viable Gram negative bacteria.

Differential immune response to Eimeria maxima infection in fast- and slow-growing broiler genotypes.

Very little has been reported comparing resistance to coccidiosis in fast or slow growing broilers, the latter of which are becoming more prevalent in the broiler industry. We examined mRNA expression in the intestines of fast and slow growing broilers following Eimeria infection. We show that by day 13 post-infection (d pi) with 2500 or 7000 oocysts of Eimeria maxima, slower-growing (Ranger Classic) broilers significantly (P < 0.

Differential gene response to coccidiosis in modern fast growing and slow growing broiler genotypes.

We analysed intestinal tissues from groups of fast growing (Ross 308) broilers with natural or experimental coccidiosis, by genomic microarray. We identified genes that were differentially expressed (DE) in all groups and analysed expression of a panel of these, by qPCR, in Ross 308 and slow growing (Ranger classic) broilers, infected with 2500 or 7000 oocysts of Eimeria maxima for 6 or 13 days post-infection (dpi). Four genes (ADD3, MLLT10, NAV2 and PLXNA2) were upregulated (P <0.

Subgram-Scale Synthesis of Biomass Waste-Derived Fluorescent Carbon Dots in Subcritical Water for Bioimaging, Sensing, and Solid-State Patterning.

Fluorescent carbon dots (FCDs) have received considerable attention because of the great potential for a wide range of applications, from bioimaging to optoelectronic devices. In this work, we reported the synthesis of nitrogen-doped FCDs with an average size of 2 nm in a subcritical water apparatus by using biomass waste (i.e.

Kinase Targets for Mycolic Acid Biosynthesis in Mycobacterium tuberculosis.

Background: Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents.

Differential Immune Phenotypes in Human Monocytes Induced by Non-Host-Adapted Salmonella enterica Serovar Choleraesuis and Host-Adapted . Typhimurium.

We studied the effects of two serovar Typhimurium (host-adapted) strains (14028 and 4/74) and three Choleraesuis (non-host-adapted) strains (A50, A45, and B195) in human monocytes between 2 and 24 h postinfection (p.i.) to investigate whether differences in immune response may explain the much higher prevalence of sepsis in individuals infected with Choleraesuis.

Model of Persistent Salmonella Infection: Salmonella enterica Serovar Pullorum Modulates the Immune Response of the Chicken from a Th17-Type Response towards a Th2-Type Response.

infection affects a wide range of animals and humans, and a small number of serovars cause typhoid-like infections, one characteristic of which is persistent infection in convalescents. Avian-specific serovar Pullorum produces systemic disease in young chickens, which is followed by a carrier state in convalescent birds, leading to infection of the ovary at sexual maturity and vertical transmission. However, the immunological basis of persistent infection remains unclear.

Dysregulation of JAK/STAT genes by vasoactive intestinal peptide (VIP) in Salmonella-infected monocytes may inhibit its therapeutic potential in human sepsis.

Murine/LPS models of Gram negative sepsis indicate that vasoactive intestinal peptide (VIP) has therapeutic potential. We investigated the unknown effect of VIP on JAK/STAT proteins and genes in human monocytes infected with Salmonella Typhimurium 14028. S.

Molecular approaches to the diagnosis and monitoring of production diseases in pigs.

Production disease in pigs is caused by a variety of different pathogens, mainly enteric and respiratory and can result in significant economic loss. Other factors such as stress, poor husbandry and nutrition can also contribute to an animal's susceptibility to disease. Molecular biomarkers of production disease could be of immense value by improving diagnosis and risk analysis to determine best practice with an impact on increased economic output and animal welfare.

Improving the dissolution properties of curcumin using dense gas antisolvent technology.

The dissolution properties of curcumin are notoriously poor and hinder its bioavailability. To improve its dissolution properties, curcumin has been formulated with methyl-β-cyclodextrin and polyvinylpyrrolidone by the atomized rapid injection solvent extraction (ARISE) system. The compounds were co-precipitated from organic solutions using carbon dioxide at 30°C and 95bar as the antisolvent.

IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose-dependently activated via IL-36β and induces CD4+ lymphocyte proliferation.

We show that IL-36R is expressed by T (CD4+ and CD8+) and B (CD19+) lymphocytes in human blood and also by CD4+ T lymphocytes in the intestinal lamina propria. IL-36R protein was mostly stored in the cytoplasm of CD4 lymphocytes and B cells, during steady state conditions and the greatest expression of IL-36R mRNA was measured in CD4+ (T helper) lymphocytes. IL-36 β, which functions via IL-36R induced rapid and significant (P<0.

Oral vaccination with a rough attenuated mutant of S. Infantis increases post-wean weight gain and prevents clinical signs of salmonellosis in S. Typhimurium challenged pigs.

We show that oral inoculation of 14 day old conventional piglets with a rough attenuated Salmonella enterica serovar Infantis 1326/28Ф(r) (serogroup C1), 24h prior to oral challenge with S. enterica serovar Typhimurium 4/74 (serogroup B), resulted in significant weight gain (~10%) measured at 14 days post-weaning (38 days of age). Two days after challenge the S.

Vasoactive intestinal peptide (VIP) differentially affects inflammatory immune responses in human monocytes infected with viable Salmonella or stimulated with LPS.

We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10(-7)M) increased monocyte viability by 24% and 9% when cultured for 24h with 4/74 or Salmonella LPS (100ng/ml), respectively. Significantly increased (P<0.

IL-36α induces maturation of Th1-inducing human MDDC and synergises with IFN-γ to induce high surface expression of CD14 and CD11c.

We show that IL-36α induced maturation of human MDDCs and stimulated differentiation of IFN-γ producing (Type 1) CD3+ lymphocytes but was not as effective as IL-36β in doing so. For the first time, we also show that IL-36α induced expression of CD14 by MDDCs and this was highly potentiated by co-cultured with IFN-γ. In contrast, lipopolysaccharide (LPS) did not increase CD14 expression by MDDCs, suggesting that if MDDCs represent a physiologically relevant population in vivo, they need to be stimulated by relevant inflammatory cytokines prior to CD14 expression and detection of LPS, expressed by Gram negative bacteria.

Formation of nanocarrier systems by dense gas processing.

Nanocarrier systems, such as liposomes, polymersomes, and micelles, find applications in the delivery of a wide range of compounds, including targeted delivery of pharmaceuticals. Nanocarrier systems have the ability to increase the bioavailability, reduce toxicity, and avoid undesirable interactions of active pharmaceutical ingredients. In this work, a novel dense gas technique known as depressurization of an expanded solution into aqueous media (DESAM) was used to produce different types of nanocarrier systems.

A critical review of the arsenic uptake mechanisms and phytoremediation potential of Pteris vittata.

The discovery of the arsenic hyperaccumulator, Pteris vittata (Chinese brake fern), has contributed to the promotion of its application as a means of phytoremediation for arsenic removal from contaminated soils and water. Understanding the mechanisms involved in arsenic tolerance and accumulation of this plant provides valuable tools to improve the phytoremediation efficiency. In this review, the current knowledge about the physiological and molecular mechanisms of arsenic tolerance and accumulation in P.

Migrating lymph dendritic cells contain intracellular CD40 that is mobilized to the immunological synapse during interactions with antigen-specific T lymphocytes.

Steady state migrating rat lymph dendritic cells (LDC) are semimature, expressing high levels of surface MHC class II, but low levels of surface costimulatory molecules. In this study, we show that surface CD40 is not detectable, but LDC contain intracellular CD40. Multiple isoforms of CD40 were detected, including the type 1 isoform required for signal transduction.

VIP as a potential therapeutic agent in gram negative sepsis.

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use.