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Early-life adversity (ELA) is linked with the increased risk for inflammatory and metabolic diseases in later life, but the mechanisms remain poorly understood. Intestinal epithelial glucose transporters sodium-glucose-linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) are the major route for intestinal glucose uptake but have also received increased attention as modulators of inflammatory and metabolic diseases. Here, we tested the hypothesis that early weaning (EW) in pigs, an established model of ELA, alters the development of epithelial glucose transporters and coincides with elevated markers of metabolic inflammation. The jejunum and ileum of 90-day-old pigs previously exposed to EW (16 days wean age), exhibited reduced SGLT1 activity (by ∼ 30%, P < 0.05) than late weaned (LW, 28 days wean age) controls. In contrast, GLUT2-mediated glucose transport was increased (P = 0.003) in EW pigs than in LW pigs. Reciprocal changes in SGLT1- and GLUT2-mediated transport coincided with transporter protein expression in the intestinal brush-border membranes (BBMs) that were observed at 90 days and 150 days of age. Ileal SGLT1-mediated glucose transport and BBM expression were inhibited by the β-adrenergic receptor (βAR) blocker propranolol in EW and LW pigs. In contrast, propranolol enhanced ileal GLUT2-mediated glucose transport (P = 0.015) and brush-border membrane vesicle (BBMV) abundance (P = 0.035) in LW pigs, but not in EW pigs. Early-weaned pigs exhibited chronically elevated blood glucose and C-reactive protein (CRP) levels, and adipocyte hypertrophy and upregulated adipogenesis-related gene expression in visceral adipose tissue. Altered development of intestinal glucose transporters by EW could underlie the increased risk for later life inflammatory and metabolic diseases. NEW & NOTEWORTHY These studies reveal that early-life adversity in the form of early weaning in pigs causes a developmental shift in intestinal glucose transport from SGLT1 toward GLUT2-mediated transport. Early weaning also induced markers of metabolic inflammation including persistent elevations in blood glucose and the inflammatory marker CRP, along with increased visceral adiposity. Altered intestinal glucose transport might contribute to increased risk for inflammatory and metabolic diseases associated with early-life adversity.

With its initial outbreak in China, the virus was referred as "coronavirus". WHO has named it "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). It has been described as the successor to SARS-CoV-1which is a positive-sense single-stranded RNA virus. The virus spreads mainly between people who are in close contact (less than two metres or six feet) through small droplets produced during coughing, sneezing, or talking. Infected people exhale the contaminated droplets which are then inhaled into the lungs, or settle on other non- infected people's faces his/her mucosae (mouth and nose) or conjunctiva (eyes) get exposed to potentially infective respiratory droplets to cause new infection. It mainly enters human cells by binding to the receptor angiotensin converting enzyme 2 (ACE2). Research works are in progress to find potential targets to control the pandemic. To control and treat the virus various targets are under study and these targets range from modulating host cell receptor for the virus entry to generate an effective adaptive immune response.

The innate immune response is a vital part of the body's antiviral defense system. The innate immune response is initiated by various receptor interactions, including danger associated molecular patterns (DAMPs). The S100A9 is a member of the DAMPs protein family and, is released by activated phagocytic cells such as neutrophils, monocytes, macrophages or endothelial cells, and S100A9 induces its effect through TLR4/MyD88 pathway. Bovine viral diarrhea virus (BVDV) is one of the major devastating disease in the cattle industry worldwide. It shows its effect through immunosuppression and develops persistent infection in calves born from infected cows. The current study revealed that BVDV potentially induced immunosuppression by the interaction of BVDV Npro protein with cellular S100A9 protein. The Inhibition of S100A9 protein expression by small interfering RNA (siRNA) enhanced the virus replication in infected cells. Overexpression of bovine S100A9 enhanced the ncpBVDV2a 1373 mediated Type-I interferon production. A co-immunoprecipitation experiment demonstrated a strong interaction between ncp BVDV2a 1373 Npro protein and cellular S100A9 protein. This suggested that BVDV Npro reduced the S100A9 protein availability/activity in infected cells, resulting in reduced Type-I interferon production. A further study of S100A9-BVDV interaction will be need for better understanding of BVDV pathophysiology., Highlights • The bovine viral diarrhea virus (BVDV) nonstructural protein, Npro, is responsible for immunosuppression. • The mechanism of Npro immune immunosuppression is not well characterized. • S100A9, a cell protein that contains danger associated molecular patterns (DAMP), is important in innate immunity. • S100A9 protein and Npro protein associate while overexpression of S100A9 enhanced Type-I interferon production. • Inhibition of S100A9 by siRNA aided BVDV replication. Npro interacting with S100A9 may result in immunosuppression.

Targeting dendritic cells (DCs), either ex vivo (Ex. Sipuleucel-T) or in vivo, for stimulating cellular immunity has been a leading approach for cancer vaccines. We have rationally engineered a nanoparticle (NP)-based delivery system for vaccines (InAc-NPs) using inulin acetate (InAc) as the polymer to target DCs. The material and the antigen-encapsulated InAc-NPs (∼190 nm in diameter) were characterized for their physicochemical properties. As a potent vaccine adjuvant, InAc-NPs activated TLR4 on multiple immune cells, including DCs and primary swine and human cells, to secrete various cytokines as detected by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. In addition, InAc-NPs promoted the maturation of DCs as observed by a decreased phagocytic ability and enhanced capability to activate various maturation markers (MHC-I, MHC-II, CD40, and CD80) quantified using flow cytometry. In mice, the InAc-NPs produced strong serum antibody titers (total IgG, IgG1, and IgG2a) against the encapsulated antigen (ovalbumin) similar to complete Freund's adjuvant. Additionally, as a dose-sparing delivery system, antigen delivered through InAc-NPs generated higher antibody titers (IgG1, 1.57 times; IgG-total, 1.66 times; and IgG2a, 29.8 times) even at 100 times less antigen dose. High amounts of cytokines representing both humoral (IL4 and IL10) and cell-mediated (IL2 and IFN-γ) immunities were secreted from splenocytes of mice immunized with InAc-NPs. Importantly, InAc-NPs provided complete protection in 100% of the vaccinated mice from metastasis of intravenously injected melanoma cells (B16-F10) to lungs. In addition, the InAc-NPs were cleared from the injection site within 30 h of injection (in vivo imaging) and displayed no toxicity at the injection site (histology). The current study demonstrates that the multifunctional InAc-based nanovaccine delivery system has potential applications in cancer immunotherapy and delivering vaccines against various infectious diseases.

Autophagy is a cellular process that maintains cellular homeostasis by the proteolytic recycling of cytoplasm. Autophagy occurs at basal levels in almost all cells. It is upregulated in cellular stress including starvation, oxidative stress or during infection. Several viruses including flavivirus have developed strategies to subvert or use autophagy for their efficient replication. Bovine viral diarrhea virus (BVDV) is a member of the Flaviviridae family and the pestivirus virus group. BVDV is responsible for significant economic loss in cattle industry worldwide. A unique characteristic of BVDV is the well-characterized genetic changes that can result in two different phenotypes (biotypes) in cell culture: cytopathic (cp) or non-cytopathic (ncp) effects. The ncp viruses are the most prevalent and important for clinical disease. This study was carried out to determine the effect of different BVDV phenotypes using the virus pair, cp TGAC and ncp TGAN in autophagy induction, as well as to investigate the role of autophagy in BVDV induced cytopathic effect.showed that both biotypes (cp and ncp) of BVDV induced autophagy in immortal Madin-Darby bovine kidney (MDBK) cell line as well as primary bovine turbinate (Bt) cells following infection. There was no significant difference between cp or ncp strains of BVDV in autophagosome formation (p0.05) in either MDBK or Bt cells. The autophagy inhibiting drug, 3-methyladenine (3MA) significantly reduced autophagy (p0.05) as well as viral replication. While autophagy inducing drug rapamycin significantly enhanced autophagy as well as viral replication. The co-localization study using, BVDV NS5A, Erns and E1 proteins with autophagy marker, light chain-3 (LC3) revealed that BVDV replication was associated with autophagosomes. This study revealed that both cp and ncp strains of BVDV induced autophagy at similar level and used autophagy machinery for their replication.

Bovine viral diarrhea virus (BVDV) infection causes immune dysfunction. The current study investigated the effect of cytopathic (cp) or noncytopathic (ncp) strains of BVDV on immunomodulation by the levels of total serum immunoglobulin G (IgG), the IgG1, IgG2, BVDV neutralizing antibodies and total white blood cell (WBC) count. Twenty (20) BVDV seronegative dairy calves (5–6 months old) were divided in two groups of ten. The animals were infected with either a cp or ncp virus isolated from the same animal (ncp BVDV1b-TGAN or cp BVDV1b-TGAC). One group of 10 was infected with ncp TGAN while the other group of 10 was infected with cp TGAC. Calves infected with cp BVDV had a significant decrease in total IgG as well as IgG1 concentration at 7 days post infection (DPI) that recovered by 21 DPI (total IgG) and 35 DPI (IgG1), respectively. There was no effect of ncp BVDV infection on total IgG concentration in the first 7 days of infection (DOI); however, IgG1 concentration was significantly reduced and IgG2 concentration was significantly increased at 7 DOI. At 35 DPI, ncp TGAN-infected calves had significantly higher total IgG, IgG1 as well as IgG2 compared to cp TGAC-infected calves. Ncp BVDV induced higher BVDV homologous and heterologous neutralizing antibodies compared to the cp BVDV strain. Calves infected with ncp BVDV had significantly reduced WBC counts at 7 DPI that recovered by 14 DPI. Overall, these findings indicate that humoral immunosuppression occurs early following BVDV infection with the largest effect on IgG1 levels.

Background Psychological stress and heightened mast cell (MC) activation are linked with important immunologic disorders, including allergy, anaphylaxis, asthma, and functional bowel diseases, but the mechanisms remain poorly defined. We have previously demonstrated that activation of the corticotropin-releasing factor (CRF) system potentiates MC degranulation responses during IgE-mediated anaphylaxis and psychological stress through corticotropin-releasing factor receptor subtype 1 (CRF1) expressed on MCs. Objective In this study we investigated the role of corticotropin-releasing factor receptor subtype 2 (CRF2) as a modulator of stress-induced MC degranulation and associated disease pathophysiology. Methods In vitro MC degranulation assays were performed with bone marrow–derived mast cells (BMMCs) derived from wild-type (WT) and CRF2-deficient (CRF2−/−) mice and RBL-2H3 MCs transfected with CRF2-overexpressing plasmid or CRF2 small interfering RNA. In vivo MC responses and associated pathophysiology in IgE-mediated passive systemic anaphylaxis and acute psychological restraint stress were measured in WT, CRF2−/−, and MC-deficient KitW-sh/W-sh knock-in mice. Results Compared with WT mice, CRF2−/− mice exhibited greater serum histamine levels and exacerbated IgE-mediated anaphylaxis and colonic permeability. In addition, CRF2−/− mice exhibited increased serum histamine levels and colonic permeability after acute restraint stress. Experiments with BMMCs and RBL-2H3 MCs demonstrated that CRF2 expressed on MCs suppresses store-operated Ca2+ entry signaling and MC degranulation induced by diverse MC stimuli. Experiments with MC-deficient KitW-sh/W-sh mice systemically engrafted with WT and CRF2−/− BMMCs demonstrated the functional importance of MC CRF2 in modulating stress-induced pathophysiology. Conclusions MC CRF2 is a negative global modulator of stimuli-induced MC degranulation and limits the severity of IgE-mediated anaphylaxis and stress-related disease pathogenesis.

Vaccine adjuvants are an essential part of modern vaccine design, especially against intracellular pathogens such as M. tuberculosis, malarial parasite, HIV, influenza virus and Ebola. The present work offers a unique approach to designing novel vaccine adjuvants by identifying polymers that mimic "pathogen associated molecular patterns" (PAMPS) and engineering an immune-active particulate vaccine delivery system that uses the polymer. By using this strategy, we report the discovery of the first plant polymer based toll-like receptor-4 (TLR-4) agonist, inulin acetate (InAc). InAc was synthesised from the plant polysaccharide inulin. Inulin acetate as a polymer and particles prepared using InAc were characterised using various physicochemical techniques. The TLR-4 agonistic activity of InAc was established in multiple immune, microglial, dendritic, peripheral blood mononuclear (human and swine) and genetically modified epithelial cells (HEK293) that exclusively express TLR-4 on their surface. InAc activated all the above-mentioned cells to release proliferative cytokines; however, InAc failed to activate when the were cells either pre-incubated with a TLR-4 specific antagonist or isolated from mice deficient in adapter proteins involved in TLR signalling (Mal/MyD88). Antigen encapsulated microparticles prepared with TLR-4 agonist InAc mimicked pathogens to offer improved antigen delivery to dendritic cells compared to soluble antigen (47 times) or antigen encapsulated poly(lactic-co-glycolic acid) (PLGA) particles (1.57 times). In conclusion, InAc represents a novel polymer-based modern vaccine adjuvant targeting specific signalling pathways of the innate immune system, which could be formulated into a platform vaccine delivery system against cancer and viral diseases.

Bovine viral diarrhea virus (BVDV) is an important viral disease of cattle that causes immune dysfunction. Macrophages are the key cells for the initiation of the innate immunity and play an important role in viral pathogenesis. In this in vitro study, we studied the effect of the supernatant of BVDV-infected macrophage on immune dysfunction. We infected bovine monocyte-derived macrophages (MDM) with high or low virulence strains of BVDV. The supernatant recovered from BVDV-infected MDM was used to examine the functional activity and surface marker expression of normal macrophages as well as lymphocyte apoptosis. Supernatants from the highly virulent 1373-infected MDM reduced phagocytosis, bactericidal activity and downregulated MHC II and CD14 expression of macrophages. Supernatants from 1373-infected MDM induced apoptosis in MDBK cells, lymphocytes or BL-3 cells. By protein electrophoresis, several protein bands were unique for high-virulence, 1373-infected MDM supernatant. There was no significant difference in the apoptosis-related cytokine mRNA (IL-1beta, IL-6 and TNF-a) of infected MDM. These data suggest that BVDV has an indirect negative effect on macrophage functions that is strain-specific. Further studies are required to determine the identity and mechanism of action of these virulence factors present in the supernatant of the infected macrophages.

Of all the stressors a pig encounters in production, early weaning is the most stressful. Under current early weaning practices, the young pig is exposed to multiple concurrent stressors including maternal and littermate separation, transportation, changes in social hierarchy, and a change in environment and food source. Moreover, the stress of weaning causes significant intestinal barrier loss and inflammation during critical stages of postnatal gut development. The immediate, negative impacts of early weaning on gut health and performance are well-known, but the long-term consequences are poorly understand. However, recent evidence from field investigations and basic science research have demonstrated that early weaning has negative consequences on performance and health from wean-to-finish. A fundamental understanding of the biological mechanisms by which current early weaning practices alter gut develop and predispose pigs to performance inefficiencies and disease throughout the production lifespan is lacking. This represents a significant gap in knowledge for the U.S. swine industry, as biological targets for interventions and management are currently lacking. This presentation will provide an overview of postnatal gut development in the pig and how early life stressors, such as early weaning, alter the normal development of critical gut health parameters, including intestinal epithelial barrier function, nutrient transport and immune function, and the link to performance and disease resistance throughout the production lifespan.

Early weaning (EW) has negative impacts on performance and health that persist from wean-to-finish. The mechanisms linking EW and lifetime performance reductions are poorly understood. The objective of this study was to investigate whether EW influences the long-term development of intestinal epithelial nutrient transporter function and expression and the potential mechanisms. Yorkshire gilts were split-weaned from their sows at 15 d (EW) or 28 d of age (Late Weaning; LW) and transferred to an on-site nursery room. All pigs received the same diets in a standard phase feeding program and were euthanized at 75 d of age. Mid-jejunum and distal ileum were mounted on Ussing chambers to evaluate Na+-dependent glucose and amino acid (AA) transporter function, measured as nutrient-induced changes in short circuit current (Isc). EW gilts exhibited reduced capacity for electrogenic transport of glucose (by ~30%; P < 0.05) and glutamate, glutamine, and alanine by (~ 30–35%; P < 0.05), compared with LW pigs. In contrast, jejunal and ileal lysine transporter function was upregulated (by 110% and 25%, respectively; P < 0.05) in EW pigs. Epithelial expression for glucose transporter (SGLT1) was reduced (P < 0.05) while glucose/fructose transporter (GLUT2), fructose transporter (GLUT5) and lysine transporters (B0AT1, CAT1, and ATB0, +) were enhanced in the EW jejunum. No differences observed in villus morphology between EW and LW pigs. Pretreatment of ileal mucosa on Ussing chambers with the Na+ channel blocker (Tetrodotoxin) or the β-adrenergic receptor blocker (Propranolol) augmented glucose, lysine and alanine transporter function in EW but not LW pigs. Together, these data show that EW in gilts induces lasting and divergent alterations in intestinal nutrient transporter function and expression which is mediated in part by the enteric nervous system and β-adrenergic receptor pathways. These new findings may explain why EW pigs exhibit lasting deleterious impacts on performance. Further mechanism-based investigations could reveal new targets for optimizing performance in EW pigs throughout the production lifespan.

Bovine viral diarrhea virus (BVDV) has long been associated with a wide variety of clinical syndromes and immune dysregulation, many which result in secondary bacterial infections. Current understanding of immune cell interactions that result in activation and tolerance are explored in light of BVDV infection including: depletion of lymphocytes, effects on neutrophils, natural killer cells, and the role of receptors and cytokines. In addition, we review some new information on the effect of BVDV on immune development in the fetal liver, the role of resident macrophages, and greater implications for persistent infection.

Purpose Two distinguishable subclades of H5N1 (classic and variant strains) are cocirculating among the poultry populations in Egypt despite the intensive vaccination programs. A study to investigate the genetic relationship between avian influenza virus (AIV) isolates from backyard chickens in Sharkia (2009–2011), subclades, and commercially available vaccines was carried out. Methods Forty-eight suspected AIV infected birds were clinically examined and used for virus isolation followed by reverse transcription-polymerase chain reaction. Four H5N1 virus isolates were sequenced and analyzed. The intravenous pathogenicity index (IVPI) of three AIV isolates was determined. Results Thirty-four hemagglutinating viral agents (30 AIV subtype H5N1 and 4 Newcastle disease virus) were detected. Both the nucleotide and amino acid sequence identities of four H5N1 virus isolates (SHZA-0412/2009, SHZA-0801/2010, SHMK-1903/2010, and SHAH-1403/2011) were high—98.4–99.7% and 100%, respectively—indicative of their genetic homogeneity. The hemagglutinin cleavage site characterization revealed the presence of multiple basic amino acids (–PQRERRRKKR/GL–) of the highly pathogenic phenotype. These results were supported by IVPI in chickens of 2.69–2.90. The similarity of our isolates with H5N1 AIV vaccine strains (93.9–95.1%) was higher than that with H5N2 strains (77.8–91.9%). The divergence of four sequences with classic and variant lineages is 2–2.7% and 2.3–3%, respectively, with two amino acid substitutions (A249P and N251Y). Conclusion Genetic characterization and IVPI data of backyard H5N1 isolates are indicative of a highly pathogenic avian influenza virus with hemagglutinin cleavage site constancy and two amino acids substitutions with Egyptian classic and variant lineages, suggesting a beginning of antigenic drift.

Bovine viral diarrhea virus (BVDV) is a positive single stranded RNA virus belonging to the Pestivirus genus of the Flaviviridae family. BVDV has a wide host range that includes most ruminants. Noncytopathic (ncp) BVDV may establish lifelong persistent infections in calves following infection of the fetus between 40 and 120 days of gestation. Cytopathic (cp) BVDV strains arise from ncp strains via mutations. The most common cp mutations are insertions of RNA derived from either host or a duplication of viral sequences into the region of the genome coding for the NS2/3 protein. Superinfection of a persistently infected animal with a cp virus can give rise to mucosal disease, a condition that is invariably fatal. A herd of 136 bred 3-year old cows was studied. These cows gave birth to 41 PI animals of which 23 succumbed to mucosal disease. In this study, we characterized the ncp and cp viruses isolated from 13 of these animals. All viruses belonged to the BVDV type 2a genotype and were highly similar. All the cp viruses contained an insertion in the NS2/3 coding region consisting of the sequences derived from the transcript encoding a DnaJ protein named Jiv90. Comparison of the inserted DnaJ regions along with the flanking viral sequences in the insertion 3' end of the 13 cp isolates revealed sequence identities ranging from 96% to 99% with common borders. This suggested that one animal likely developed a cp virus that then progressively spread to the other 12 animals. Interestingly, when the inserted mammalian gene replicated within viral genome, it showed conservation of the same conserved motifs between the different species, which may indicate a role for these motifs in the insertion function within the virus genome. This is the first characterization of multiple cp bovine viral diarrhea virus isolates that spread in a herd under natural conditions.

The purified Immunoglobulin G (IgG) is effectively used in passive immunization. There are various methods to isolate the IgG from serum, with its own advantages and disadvantages. In the current study, a comparative efficacy of the affinity chromatography...

Early life adversity (ELA) is a risk factor for later life emergence of functional and inflammatory GI disorders in people and animals. In this study, we compared the early GI immune responses in male piglets exposed to early weaning (EW) at 16–18 d of age, a form of ELA we’ve previously shown result in altered GI developmental and health trajectories similar to ELA in humans, with that of late weaned piglets (LW: 28 d of wean age). RNA transcriptome analysis of ileal mucosa at 24h post-weaning revealed that EW pigs exhibited a greater number of differentially expressed genes (765 vs 110 genes, for EW and LW piglets, respectively), characterized by a large number of upregulated genes associated with immune cell trafficking and inflammation. Mast cells (MC), stress-sensitive innate immune cells which orchestrate the immune response, were acutely activated in EW and LW pigs but in a differential manner. Compared with LW piglets, EW piglets exhibited higher levels of serum histamine which coincided with a downregulation in the gene expression of histamine degrading enzymes, DAO and HNMT in intestinal mucosa. Mast cell tryptase (MCT7) and chymase (CMA1) gene expression were upregulated in ileal and colonic mucosa (within 3h post-weaning) in both EW and LW piglets; however, this response was greater in LW pigs. Together, these data show that weaning stress in piglets induces rapid GI MC activation which precedes immune cell recruitment and intestinal inflammation and that postnatal age has a significant influence on the level and nature of this response. Further investigation of how EW and LW piglets differentially regulate early GI immune responses is expected to provide new insight into the mechanisms of GI and immune disorders associated with ELA.

The essential oil obtained from rhizomes of Hedychium coronarium Koenig and Hedychium spicatum Buch-Ham. growing wildly in Kumaun region of central Himalaya were analysed by GC and GC-MS. Forty six compounds representing 98.7 % of H. coronarium oil were identified. The main components identified were linalool (29.3 %), limonene (20.3 %), trans-meta-mentha,2,8diene (12.9 %), γ-terpinene (8.9 %) and 10-epi-γ-eudismol (3.8 %).Thirty six compounds accounting 87.4 % of H. spicatum oil were identified.The major constituents were 1,8-cineole (17.6 %), α-eudesmol (17 %), 10-epi-γ-eudismol (9.7%), δ-cadinene (7.5 %), cubenol (6.9 %), germacrene D-4–01 (6.8 %) and γ-cadinene (5.4 %). H. coronarium oil was rich in monoterpene hydrocarbons while H. spicatum oil was rich in suquiterpene alcohols. Both the oils showed antibacterial activity against five pathogenic bacteria, viz. Escherichia coli, Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruoginosa and Proteus vulgaris.

Continuous inflammation in the colon often leads to chronic diseases such as inflammatory bowel disease (IBD) and colorectal cancer. Recent evidence strongly suggests the role of Toll-Like Receptors 2 and 4 in the etiology of aforementioned diseases. Therefore, pharmacological inhibition of TLR-2/TLR-4 has been a new promising strategy for preventing inflammation in IBD and colorectal cancer. In the current study, we have developed a novel polymer-drug complex (Ora-Curcumin) as a TLR-2/TLR-4 antagonist to modulate the gut innate immune system. Ora-Curcumin is a molecular complex of curcumin with a hydrophilic polymer Eudrgit® S100 prepared by nano-precipitation. Ora-curcumin is more water soluble (~1000 times) and stable than curcumin in aqueous buffers. It is water soluble only at pHs above 6.8. Therefore, once consumed orally, it is expected to be soluble and functionally available only at the luminal side of the colon where the pH reaches 6.8. In addition, Ora-Curcumin was potent TLR-4 antagonist that significantly inhibited the release of IL-8 and TNF-a from TLR-4 expressing human kidney epithelial cells (HEK293TLR4YFP-MD2) and mouse dendritic cells, respectively, in response to TLR stimulation with Monophosphoryl Lipid A (MPLA) or dead E. coli. The in-vivo potential of Ora-Curcumin in modulation of acute inflammation and intestinal microbiome is currently in progress. To this end, we have developed a unique polymer based water soluble TLR-2/TLR-4 antagonist which also provides enhanced local delivery to colon to prevent or treat IBD and colorectal cancer. As an anti-bacterial and by altering host immune system to control inflammation, Ora-Curcumin is also expected to modulate colon microbiome and improve GI health.

Background Dendritic cells (DC) are important antigen presentation cells that monitor, process, and present antigen to T cells. Viruses that infect DC can have a devastating impact on the immune system. In this study, the ability of bovine viral diarrhea virus (BVDV) to replicate and produce infectious virus in monocyte-derived dendritic cells (Mo-DC) and monocytes was studied. The study also examined the effect of BVDV infection on Mo-DC expression of cell surface markers, including MHCI, MHCII, and CD86, which are critical for DC function in immune response. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from bovine blood through gradient centrifugation. The adherent monocytes were isolated from PBMCs and differentiated into Mo-DC using bovine recombinant interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GMCSF). To determine the effect of BVDV on Mo-DC, four strains of BVDV were used including the severe acute non-cytopathic (ncp) BVDV2a-1373; moderate acute ncp BVDV2a 28508-5; and a homologous virus pair [i.e., cytopathic (cp) BVDV1b TGAC and ncp BVDV1b TGAN]. The Cooper strain of bovine herpesvirus 1 (BHV1) was used as the control virus. Mo-DC were infected with one of the BVDV strains or BHV-1 and were subsequently examined for virus replication, virus production, and the effect on MHCI, MHCII, and CD86 expression. Results The ability of monocytes to produce infectious virus reduced as monocytes differentiated to Mo-DC, and was completely lost at 120 hours of maturation. Interestingly, viral RNA increased throughout the course of infection in Mo-DC, and the viral non-structural (NS5A) and envelope (E2) proteins were expressed. The ncp strains of BVDV down-regulated while cp strain up-regulated the expression of the MHCI, MHCII, and CD86 on Mo-DC. Conclusions The study revealed that the ability of Mo-DC to produce infectious virus was reduced with its differentiation from monocytes to Mo-DC. The inability to produce infectious virus may be due to a hindrance of virus packaging or release mechanisms. Additionally, the study demonstrated that ncp BVDV down-regulated and cp BVDV up-regulated the expression of Mo-DC cell surface markers MHCI, MHCII, and CD86, which are important in the mounting of immune responses.

Out of 150 small ruminants examined from villages near Pantnagar and organized farms, among them 144 animals were found positive for mixed parasitic infection, including Haemonchus sp, Paramphistomum sp, Trichuris sp. and Moniezia sp. Overall prevalence was found 96.00% in which animals from villages has more prevalence (96.15%) than organized farm (96.00%) but organized farms has more prevalence of Haemonchus sp (95.00%) than animals of villages (76.92%), overall Paramphistomum sp was found 36.00% while Trichuris sp and Moniezia sp revealed 14.00% and 12.00% prevalence, respectively. [Vet World 2009; 2(7.000): 265-266]