Exploring the Antimycobacterial Potential of Podocarpusflavone A from : In Vitro and In Vivo Insights.

: Tuberculosis (TB) is one of the leading infectious causes of death worldwide, highlighting the importance of identifying new anti-TB agents. In previous research, our team identified antimycobacterial activity in leaf extract; therefore, this study aims to conduct further exploration of its potential. : Classical chromatography was applied for fractionation and spectrometric techniques were utilized for chemical characterization.

A Murine Model of Infection Reproducing Necrotic Lung Pathology Reveals Considerable Heterogeneity in Virulence of Clinical Isolates.

Among non-tuberculous mycobacteria, is one of the most pathogenic, able to cause pulmonary disease indistinguishable from tuberculosis in immunocompetent susceptible adults. The lack of animal models that reproduce human-like lung disease, associated with the necrotic lung pathology, impairs studies of virulence and pathogenicity. In this study, we examined the ability of the C57BL/6 mice, intratracheally infected with highly virulent strains, to produce a chronic infection and necrotic lung pathology.

Natural products from and their antimycobacterial and anti-inflammatory activity.

Tuberculosis (TB) remains a worldwide public health threat because of the emergence of resistant strains and subsequent inappropriate response to current therapy. We have been studying the plants' antimycobacterial and anti-inflammatory potential. Dichloromethane fraction (DCM) from Cham.

Harmful Effects of Granulocytic Myeloid-Derived Suppressor Cells on Tuberculosis Caused by Hypervirulent Mycobacteria.

Background: The role of myeloid-derived suppressor cells (MDSCs) in patients with severe tuberculosis who suffer from uncontrolled pulmonary inflammation caused by hypervirulent mycobacterial infection remains unclear.

Methods: This issue was addressed using C57BL/6 mice infected with highly virulent Mycobacterium bovis strain MP287/03.

Results: CD11b+GR1int population increased in the bone marrow, blood and lungs during advanced disease.

Identification of the Apa protein secreted by Mycobacterium avium subsp. paratuberculosis as a novel fecal biomarker for Johne's disease in cattle.

Paratuberculosis (PTB) or Johne's disease is a chronic intestinal infection of ruminants, caused by Mycobacterium avium subsp. paratuberculosis. The shedding of mycobacteria in the feces starts at the initial stages and increases with disease progression, suggesting that antigens secreted by mycobacteria could be excreted in the feces.

Correction: Hypervirulent Mycobacterium tuberculosis strain triggers necrotic lung pathology associated with enhanced recruitment of neutrophils in resistant C57BL/6 mice.

[This corrects the article DOI: 10.1371/journal.pone.

Hypervirulent Mycobacterium tuberculosis strain triggers necrotic lung pathology associated with enhanced recruitment of neutrophils in resistant C57BL/6 mice.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) that in most cases induces irreversible necrosis of lung tissue as a result of excessive inflammatory reactions. The murine model of TB in resistant C57BL/6 mice infected with reference Mtb strains is widely used in TB studies; however, these mice do not show a necrotic pathology, which restricts their use in studies of irreversible tissue damage. Recently, we demonstrated that necrotic lung lesions could be induced in the C57BL/6 mice by highly virulent Mtb strains belonging to the modern Beijing sublineage.

Nitric Oxide Production Inhibition and Anti-Mycobacterial Activity of Extracts and Halogenated Sesquiterpenes from the Brazilian Red Alga Laurencia Dendroidea J. Agardh.

Background: Red algae of the genus Laurencia J. V. Lamouroux are a rich source of secondary metabolites with important pharmacological activities such as anti-tumoral, anti-inflammatory, anti-fungal, anti-viral, anti-leishmanial, anti-helminthic, anti-malarial, anti-trypanosomal, anti-microbial as well as anti-bacterial against Mycobacterium tuberculosis.

Innate immunity in tuberculosis: how the sensing of mycobacteria and tissue damage modulates macrophage death.

The success of Mycobacterium tuberculosis as a human pathogen has been attributed to the ability of the bacillus to proliferate inside macrophages and to induce cell death. This review describes how the sensors of the innate immune system modulate the cell death pathways in infected macrophages and, consequently, the pathogenesis of tuberculosis.

Antimycobacterial and anti-inflammatory activities of substituted chalcones focusing on an anti-tuberculosis dual treatment approach.

Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions.

Antimycobacterial and nitric oxide production inhibitory activities of Ocotea notata from Brazilian restinga.

The genus Ocotea (Lauraceae) is distributed mainly in tropical and subtropical regions. Some species of this genus as O. puberula and O.

Pulmonary infection with hypervirulent Mycobacteria reveals a crucial role for the P2X7 receptor in aggressive forms of tuberculosis.

The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell death. To investigate whether the innate immune response to damage signals could contribute to the development of pulmonary necrotic lesions in severe forms of tuberculosis, disease progression was examined in C57BL/6 and P2X7R-/- mice that were intratracheally infected with highly virulent mycobacterial strains (Mycobacterium tuberculosis strain 1471 of the Beijing genotype family and Mycobacterium bovis strain MP287/03). The low-dose infection of C57BL/6 mice with bacteria of these strains caused the rapid development of extensive granulomatous pneumonia with necrotic areas, intense bacillus dissemination and anticipated animal death.

Mycobacterium tuberculosis strains of the modern sublineage of the Beijing family are more likely to display increased virulence than strains of the ancient sublineage.

Strains of the Beijing genotype family of Mycobacterium tuberculosis are a cause of particular concern because of their increasing dissemination in the world and their association with drug resistance. Phylogenetically, this family includes distinct ancient and modern sublineages. The modern strains, contrary to the ancestral counterparts, demonstrated increasing prevalence in many world regions that suggest an enhanced bacterial pathogenicity.

Sesquiterpenes from the Brazilian red alga Laurencia dendroidea J. Agardh.

Two new chamigrane sesquiterpenes 1-2 and three known compounds 3-5 were isolated from a lipophilic extract of the red alga Laurencia dendroidea collected from the Southeastern Brazilian coast. Dendroidone (1) and dendroidiol (2) were isolated from samples collected at Biscaia Inlet, Angra dos Reis, Rio de Janeiro and at Manguinhos Beach, Serra, Espírito Santo, respectively. Debromoelatol (3), obtusane (4) and (1S*,2S*,3S*,5S*,8S*,9S*)-2,3,5,9-tetramethyltricyclo[6.

Bothropic antivenom based on monoclonal antibodies, is it possible?

Neutralizing monoclonal antibodies against three major toxic components of Bothrops atrox venom were produced and tested. The mAbs against phospholipase A2, hemorrhagic metalloprotease, and thrombin-like enzymes were produced in large amounts and purified with caprylic acid followed by ammonium sulfate precipitation. Purified mAbs were analyzed by SDS-PAGE and their ability to neutralize the respective toxins was tested.

Pathogenic Mycobacterium bovis strains differ in their ability to modulate the proinflammatory activation phenotype of macrophages.

Background: Tuberculosis, caused by Mycobacterium tuberculosis or Mycobacterium bovis, remains one of the leading infectious diseases worldwide. The ability of mycobacteria to rapidly grow in host macrophages is a factor contributing to enhanced virulence of the bacteria and disease progression. Bactericidal functions of phagocytes are strictly dependent on activation status of these cells, regulated by the infecting agent and cytokines.

Apa antigen of Mycobacterium avium subsp. paratuberculosis as a target for species-specific immunodetection of the bacteria in infected tissues of cattle with paratuberculosis.

Comparative genomics of Mycobacterium spp. have revealed conservative genes and respective proteins differently expressed in mycobacteria that could be used as targets for the species-specific immunodiagnostics. The alanine and proline-rich antigen Apa is a mycobacterial protein that present significant variability in primary sequence length and composition between members of M.

Difference in virulence of Mycobacterium avium isolates sharing indistinguishable DNA fingerprint determined in murine model of lung infection.

Background: Opportunistic Mycobacterium avium typically causes disease in immunocompromised patients and in some groups of apparently healthy individuals. The high virulence of some bacterial lineages increases the disease risk. High-resolution molecular genotyping studies of M.

Antimycobacterial activity and alkaloid prospection of Psychotria species (Rubiaceae) from the Brazilian Atlantic Rainforest.

Ten Psychotria species were collected in two fragments of Atlantic Forest in Rio de Janeiro: Psychotria pubigera (P1A and B), P. ruelliifolia (P2), P. suterela (P3), P.

Sub-lethal heat shock induces plasma membrane translocation of 70-kDa heat shock protein in viable, but not in apoptotic, U-937 leukaemia cells.

Heat shock protein 70 kDa, Hsp70, is an important intracellular factor that protects cells from stress. Unusual plasma membrane expression of Hsp70, observed in some cancer cells, contributes to the cell's recognition and elimination by the immune system. Induction of apoptosis in cancer cells was demonstrated to increase Hsp70 translocation to the surface membrane, enhancing immunogenic effects through the stimulation of dendritic cells.

Mycobacteria directly induce cytoskeletal rearrangements for macrophage spreading and polarization through TLR2-dependent PI3K signaling.

Macrophage migration and adhesion are important for the control of mycobacterial infection and are critically dependent on the reorganization of the cytoskeleton. Mycobacteria elicit rapid morphological changes, such as cell spreading, a process relevant to in vivo changes of macrophage shape during extravasation and migration. In this study, we investigated the BCG mycobacteria-induced signaling events leading to macrophage cytoskeletal rearrangements employing specific pharmacological inhibitors to suppress distinct kinase pathways known to be elicited by infection.

Activation of phosphatidylinositol 3-kinase and c-Jun-N-terminal kinase cascades enhances NF-kappaB-dependent gene transcription in BCG-stimulated macrophages through promotion of p65/p300 binding.

The proinflammatory response of infected macrophages is an important early host defense mechanism against mycobacterial infection. Mycobacteria have been demonstrated to induce proinflammatory gene transcription through the Toll-like receptors, (TLR)2 and TLR 4, which initiate signaling cascades leading to nuclear factor (NF)-kappaB activation. The main transduction pathway responsible for NF-kappaB activation has been established and involves the MyD88, interleukin-1 receptor-associated kinase, tumor necrosis factor receptor-associated factor-6, NF-kappaB-inducing kinase, and inhibitor of kappaB kinase complex.

Transfection of NS0 myeloma fusion partner cells with HSP70 gene results in higher hybridoma yield by improving cellular resistance to apoptosis.

Mouse myeloma NS0 cells widely used in hybridoma technology lack the expression of a major stress protein Hsp70 which is the principal component of the basic cellular defense mechanism. These cells rapidly undergo apoptosis at the late-stationary phase of batch culture following nutrient exhaustion. Since Hsp70 was recently demonstrated to protect cells against numerous apoptotic stimuli, the aim of the present study was to examine the protective potential of the protein expression in engineered myeloma NS0 cells and in resulting hybridomas.