Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine.

Inactivated Foot-and-Mouth Disease (FMD) vaccine has proven to be effective in the control of the disease. However, its production has some disadvantages, including the costly biosafety facilities required for the production of huge amounts of growing live virus, the need of an exhaustive purification process to eliminate non-structural proteins of the virus in the final formulations in order to differentiate infected from vaccinated animals and variable local regulatory restrictions to produce and commercialize the vaccine. Thus, a novel vaccine against FMD that overcome these restrictions is desirable.

Mitochondrial genome architecture in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction, a decreased liver mitochondrial DNA (mtDNA) content, and impaired energy metabolism. To understand the clinical implications of mtDNA diversity in the biology of NAFLD, we applied deep-coverage whole sequencing of the liver mitochondrial genomes. We used a multistage study design, including a discovery phase, a phenotype-oriented study to assess the mutational burden in patients with steatohepatitis at different stages of liver fibrosis, and a replication study to validate findings in loci of interest.

Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) develops from a complex process, which includes changes in the liver methylome. Betaine plays a pivotal role in the regulation of methylogenesis. We performed a two-stage case-control study, which included patients with biopsy-proven NAFLD to explore circulating levels of betaine and its association with the histological spectrum.

Heat Shock Protein 27 is down-regulated in Ballooned Hepatocytes of Patients with Nonalcoholic Steatohepatitis (NASH).

Ballooning degeneration (BD) of hepatocytes is a distinguishing histological feature associated with the progression of nonalcoholic fatty liver disease (NAFLD). Under the assumption that NAFLD severity is associated with metabolic-stress we explored the hypothesis that heat shock 27 kDa protein 1 (HSP27), a protein chaperone involved in stress resistance and cytoskeletal-remodeling, might be deregulated in ballooned hepatocytes. We observed that fasting plasma glucose (fpG) (p = 0.

Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.

Background: Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown.

Objective: We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS.

Design: Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10).

Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease: The Role of DNA Hydroxymethylation and TET Proteins.

The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5-methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD)-associated molecular traits could be explained.

Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity.

Unlabelled: We explored the role of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C/T nonsynonymous (p.Glu167Lys) variant in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and disease severity. A total of 361 individuals (135 control subjects and 226 patients with histologically proven NAFLD) were included in a sample with 97% power for the additive genetic model.

Brucella abortus induces collagen deposition and MMP-9 down-modulation in hepatic stellate cells via TGF-β1 production.

In patients with active brucellosis, the liver is frequently affected by histopathologic lesions, such as granulomas, inflammatory infiltrations, and parenchymal necrosis. Herein, we examine some potential mechanisms of liver damage in brucellosis. We demonstrate that Brucella abortus infection inhibits matrix metalloproteinase-9 (MMP-9) secretion and induces collagen deposition and tissue inhibitor of matrix metalloproteinase-1 secretion induced by hepatic stellate cells (LX-2).

Brucella abortus induces TNF-α-dependent astroglial MMP-9 secretion through mitogen-activated protein kinases.

Background: Central nervous system (CNS) invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. We have recently demonstrated that B. abortus infects microglia and astrocytes, eliciting the production of a variety of pro-inflammatory cytokines which contribute to CNS damage.

Brucella abortus invasion of synoviocytes inhibits apoptosis and induces bone resorption through RANKL expression.

Arthritis is one of the most common complications of human active brucellosis, but its pathogenic mechanisms have not been completely elucidated. In this paper, we describe the role of synoviocytes in the pathogenesis of brucellar arthritis. Our results indicate that Brucella abortus infection inhibited synoviocyte apoptosis through the upregulation of antiapoptotic factors (cIAP-2, clusterin, livin, and P21/CIP/CDNK1A).

Induction of osteoclastogenesis in an in vitro model of Gaucher disease is mediated by T cells via TNF-α.

Gaucher disease is a lysosomal storage disorder caused by deficiency of glucocerebrosidase enzymatic activity leading to accumulation of its substrate glucocerebrosidase mainly in macrophages. Skeletal disorder of Gaucher disease is the major cause of morbidity and is highly refractory to enzyme replacement therapy. However, pathological mechanisms of bone alterations in Gaucher disease are still poorly understood.

Brucella abortus-infected macrophages modulate T lymphocytes to promote osteoclastogenesis via IL-17.

The pathogenic mechanisms of bone loss caused by Brucella species have not been completely deciphered. Although T lymphocytes (LTs) are considered important to control infection, the mechanism of Brucella-induced T-cell responses to immunopathological features is not known. We present in vitro and in vivo evidence showing that Brucella abortus-induced inflammatory response leads to the activation of LTs, which further promote osteoclastogenesis.

Brucella abortus invasion of osteoblasts inhibits bone formation.

Osteoarticular brucellosis is the most common presentation of the active disease in humans. Loss of bone is a serious complication of localized bacterial infection of bones or the adjacent tissue, and brucellosis proved not to be the exception. The skeleton is a dynamic organ system which is constantly remodeled.

Brucella abortus induces apoptosis of human T lymphocytes.

Immune evasion is essential for Brucella abortus to survive in the face of robust adaptive CD4+ T cell response. We have previously demonstrated that B. abortus can indirectly inhibit CD4+ T cells by down-regulating MHC-II expression and antigen presentation on macrophages.

Macrophage-elicited osteoclastogenesis in response to Brucella abortus infection requires TLR2/MyD88-dependent TNF-α production.

Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown. In this manuscript, we described an immune mechanism for inflammatory bone loss in response to infection by Brucella abortus. We established a requirement for MyD88 and TLR2 in TNF-α-elicited osteoclastogenesis in response to B.

Potential role of fibroblast-like synoviocytes in joint damage induced by Brucella abortus infection through production and induction of matrix metalloproteinases.

Arthritis is one of the most common complications of human brucellosis, but its pathogenic mechanisms have not been elucidated. Fibroblast-like synoviocytes (FLS) are known to be central mediators of joint damage in inflammatory arthritides through the production of matrix metalloproteinases (MMPs) that degrade collagen and of cytokines and chemokines that mediate the recruitment and activation of leukocytes. In this study we show that Brucella abortus infects and replicates in human FLS (SW982 cell line) in vitro and that infection results in the production of MMP-2 and proinflammatory mediators (interleukin-6 [IL-6], IL-8, monocyte chemotactic protein 1 [MCP-1], and granulocyte-macrophage colony-stimulating factor [GM-CSF]).

Granulocyte-macrophage colony-stimulating factor- and tumor necrosis factor alpha-mediated matrix metalloproteinase production by human osteoblasts and monocytes after infection with Brucella abortus.

Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown. Since matrix metalloproteinases (MMPs) are involved in joint and bone damage in inflammatory and infectious diseases, we investigated the production of MMPs by human osteoblasts and monocytes, either upon Brucella abortus infection or upon reciprocal stimulation with factors produced by each infected cell type. B.

Prepatellar bursitis due to Brucella abortus: case report and analysis of the local immune response.

A case of prepatellar bursitis in a man with chronic brucellosis is presented. Brucella abortus biotype 1 was isolated from the abundant yellowish fluid obtained from the bursa. Clinical and epidemiological data did not suggest a direct inoculation of the agent in the bursa.

Brucella-infected hepatocytes mediate potentially tissue-damaging immune responses.

Background & Aims: Hepatic involvement is frequent in human brucellosis. While different histopathological lesions have been reported in these patients, the underlying cellular and molecular mechanisms have not been addressed.

Methods: This study assessed whether Brucella abortus can infect a human hepatoma cell line and induce a proinflammatory response in these cells.