Nanoparticles up-regulate tumor necrosis factor-alpha and CXCL8 via reactive oxygen species and mitogen-activated protein kinase activation.

Evaluating the toxicity of nanoparticles is an integral aspect of basic and applied sciences, because imaging applications using traditional organic fluorophores are limited by properties such as photobleaching, spectral overlaps, and operational difficulties. This study investigated the toxicity of nanoparticles and their biological mechanisms. We found that nanoparticles, quantum dots (QDs), considerably activated the production of tumor necrosis factor (TNF)-alpha and CXC-chemokine ligand (CXCL) 8 through reactive oxygen species (ROS)- and mitogen-activated protein kinases (MAPKs)-dependent mechanisms in human primary monocytes.

A protein-bound polysaccharide, PSK, enhances tumor suppression induced by docetaxel in a gastric cancer xenograft model.

Background: We have reported previously that docetaxel (TXT) induces apoptosis and nuclear factor-kappaB (NF-kappaB) activation, and that blockade of NF-kappaB activation augments TXT-induced apoptosis in human gastric cancer cells. In addition, we have also shown that a protein-bound polysaccharide PSK enhances TXT-induced apoptosis through NF-kappaB inhibition in human pancreatic cancer cells. Based on these observations, in the present study the possibility that PSK could enhance TXT-mediated tumor suppression was examined in vivo and in vitro.

Analysis of low molecular weight plasma proteins using ultrafiltration and large gel two-dimensional electrophoresis.

In this study, various solvent systems were applied to obtain a high and consistent recovery rate of low molecular weight plasma proteins (LMPP) from human plasma. A buffer system containing 7 M urea, 2 M thiourea, 25 mM NH(4)HCO(3) + 20% ACN (pH 8.2) produced the highest recovery rate of LMPP.

NADPH oxidase 2 interaction with TLR2 is required for efficient innate immune responses to mycobacteria via cathelicidin expression.

Gp91(phox)/NADPH oxidase (NOX) 2 is the main catalytic component of NOX, which mediates the phagocytic killing of ingested pathogens via the production of reactive oxygen species (ROS). However, Mycobacterium tuberculosis (Mtb) is relatively resistant to the microbicidal effects of ROS. Thus, the exact roles of NOX2 in the innate immune control against Mtb infection are not fully resolved.

Destruction of Bacillus licheniformis spores by microwave irradiation.

Aims: To investigate the sporicidal mechanisms of microwave irradiation on Bacillus licheniformis spores.

Methods And Results: We measured spore viability and the release of DNA and proteins, and performed transmission electron microscopy (TEM). A microwave oven (0.

Induction of cell death in human macrophages by a highly virulent Korean Isolate of Mycobacterium tuberculosis and the virulent strain H37Rv.

Recent studies have suggested that virulent strains of Mycobacterium tuberculosis induce apoptosis in macrophages less often than do attenuated strains. K-strain, which belongs to the Beijing family, is the most frequently isolated clinical strain of M. tuberculosis in Korea.

Pharmacological stimulation of NADH oxidation ameliorates obesity and related phenotypes in mice.

Objective: Nicotinamide adenine dinucleotides (NAD+ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD+-to-NADH ratio is implicated in metabolic syndrome. However, it is still unknown whether a modulating intracellular NAD+-to-NADH ratio is beneficial in treating metabolic syndrome. We tried to determine whether pharmacological stimulation of NADH oxidation provides therapeutic effects in rodent models of metabolic syndrome.

Innate immune responses to Mycobacterium ulcerans via toll-like receptors and dectin-1 in human keratinocytes.

Mycobacterium ulcerans (MU), an environmental pathogen, causes Buruli ulcer, a severe skin disease. We hypothesized that epidermal keratinocytes might not be a simple barrier, but play a role during MU infection through pattern-recognition receptors expressed in keratinocytes. We found that keratinocyte Toll-like receptors (TLRs) 2 and 4 and Dectin-1 actively participate in the innate immune response to MU, which includes the internalization of bacteria, the production of reactive oxygen species (ROS), and the expression of chemokines and LL-37.

Secretory phospholipase A2 plays an essential role in microglial inflammatory responses to Mycobacterium tuberculosis.

In previous studies, we have shown that reactive oxygen species (ROS)-mediated inflammatory signaling is essential for microglial proinflammatory responses to Mycobacterium tuberculosis (Mtb). To further investigate the molecular mechanisms governing these processes, we sought to describe the role of phospholipase A(2) (PLA(2)) in Mtb-induced ROS generation and inflammatory mediator release by microglia. Inhibition of secretory PLA(2) (sPLA(2)), but not cytosolic PLA(2) (cPLA(2)), profoundly abrogated Mtb-mediated ROS release, the generation of various inflammatory mediators (tumor necrosis factor, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-2 and -9), and the activation of nuclear factor (NF)-kappaB and MAPKs (ERK1/2, p38, and JNK/SAPK) by murine microglial BV-2 cells or primary mixed glial cells.

Transcriptional regulatory defects in the first intron of Bruton's tyrosine kinase.

Background: X-linked agammaglobulinemia (XLA), characterized by the early onset of recurrent bacterial infections, profound hypogammaglobulinemia, and a markedly diminished number of peripheral B lymphocytes, is caused by mutations in the Bruton's tyrosine kinase (BTK) gene. The >600 unique mutations identified to date include single base pair substitutions, small insertions or deletions, and gross deletions. A few cases, however, have been found to have no mutations in the coding region even with reduced BTK mRNA or protein expression.

Rhodium(I)-catalyzed one-pot synthesis of dialkyl ketones from methanol and alkenes through directed sp3 C-H bond activation of N-methylamine.

The hydroacylation of methanol with alkenes was developed using a catalytic system consisting of Rh(I), 2-amino-4-picoline and benzoic acid; the reaction is speculated to occur by the initial N-methylation of 2-amino-4-picoline with methanol, and the subsequent dehydrogenation of the resulting N-methylamine, followed by double chelation-assisted hydroimination of alkene with the imine to give dialkyl ketones after hydrolysis.

Role of apoptosis-regulating signal kinase 1 in innate immune responses by Mycobacterium bovis bacillus Calmette-Guérin.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces innate immune responses through Toll-like receptor (TLR) 2 and TLR4. We investigated the role of apoptosis-regulating signal kinase (ASK) 1 in reactive oxygen species (ROS)-mediated innate immune responses induced by BCG mycobacterial infection. In macrophages, M.

Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell death.

Microglial cells are activated during excitotoxin-induced neurodegeneration. However, the in vivo role of microglia activation in neurodegeneration has not yet been fully elucidated. To this end, we used Ikkbeta conditional knockout mice (LysM-Cre/Ikkbeta(F/F)) in which the Ikkbeta gene is specifically deleted in cells of myeloid lineage, including microglia, in the CNS.

A dual regulatory role of apurinic/apyrimidinic endonuclease 1/redox factor-1 in HMGB1-induced inflammatory responses.

Apurinic/apyrimidinic endonuclease 1/Redox factor-1 (APE1) is a multifunctional protein involved in reduction-oxidation regulation. High-mobility group box 1 (HMGB1) is released by necrotic cells and various inflammatory stimuli, acting as an inflammatory marker in sepsis and autoimmune diseases. Here, we report the dual regulatory role of APE1 in inflammatory signaling to extracellular HMGB1 or in the release of endogenous HMGB1 in human monocytes/macrophages.

Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions.

Strong evidence exists for interactions of zwitterionic phosphate and amine groups in sphingosine-1 phosphate (S1P) to conserved Arg and Glu residues present at the extracellular face of the third transmembrane domain of S1P receptors. The contribution of Arg(120) and Glu(121) for high-affinity ligand-receptor interactions is essential, because single-point R(120)A or E(121)A S1P(1) mutants neither bind S1P nor transduce S1P function. Because S1P receptors are therapeutically interesting, identifying potent selective agonists with different binding modes and in vivo efficacy is of pharmacological importance.

Roles of reactive oxygen species in CXCL8 and CCL2 expression in response to the 30-kDa antigen of Mycobacterium tuberculosis.

Background: The 30-kDa antigen (Ag) of Mycobacterium tuberculosis (M. tuberculosis) is a strong inducer of innate and adaptive immune responses in human tuberculosis. The generation of reactive oxygen species (ROS) plays an important role in inflammatory signaling as well as antimicrobial defense.

Highly fluorescent supramolecular gels with chirality transcription through hydrogen bonding.

A highly fluorescent organogel with transparency was formed through a hydrogen (H)-bonding interaction between a non-fluorescent and achiral 2-(3',5'-bis-trifluoromethyl-biphenyl-4-yl)-3-(4-pyridin-4-yl-phenyl)-acrylonitrile (CN-TFMBPPE) monomer and chiral sergeant l-tartaric acid (TA) (or d-TA), with gel formation being accompanied by a drastic fluorescence enhancement as well as chirality induction.

Ligand-binding pocket shape differences between sphingosine 1-phosphate (S1P) receptors S1P1 and S1P3 determine efficiency of chemical probe identification by ultrahigh-throughput screening.

We have studied the sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G-protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function.

The effects of high-power microwaves on the ultrastructure of Bacillus subtilis.

Aims: To investigate the microbicidal mechanisms of high-power microwave (2.0 kW) irradiation on Bacillus subtilis and to determine the effect of this procedure on the ultrastructure of the cell wall.

Methods And Results: We performed viability test, examined cells using transmission electron microscopy (TEM), and measured the release of intracellular proteins and nucleic acids.

Mycobacterium tuberculosis lipoprotein-induced association of TLR2 with protein kinase C zeta in lipid rafts contributes to reactive oxygen species-dependent inflammatory signalling in macrophages.

Membrane lipid rafts are enriched in cholesterol and play an important role as signalling platforms. However, the roles of lipid rafts and associated signalling molecules in the innate immune responses to mycobacteria remain unknown. Here we show that stimulation with Mycobacterium tuberculosis 19 kDa lipoprotein, a TLR2/1 agonist, results in translocation of TLR2 to lipid rafts, coalescence of lipid rafts and production of reactive oxygen species (ROS) that drive pro-inflammatory responses.

Mycobacterial interaction with innate receptors: TLRs, C-type lectins, and NLRs.

Purpose Of Review: The recent discovery of novel classes of receptors, including toll-like receptors and nucleotide-binding oligomerization domain (NOD)-like receptors is challenging the crucial role of the innate immune system in the recognition of Mycobacterium tuberculosis. The present review is to focus on the roles and mechanisms of specific pattern-recognition receptor-microbial interaction for the host defense against mycobacterial infections.

Recent Findings: Toll-like receptors, key players in innate immunity, are now known to be important for the initiation and coordination of host responses to Mycobacterium tuberculosis.

Diagnosis of pulmonary tuberculosis using MTB12 and 38-kDa antigens.

Background And Objective: Mycobacterium tuberculosis MTB12 protein plays an essential role in pro-inflammatory responses during the early stages of human pulmonary tuberculosis (TB), even though the T-cell immunoreactivity of MTB12 is weaker than that of the 30-kDa antigen (Ag). The objective of this study was to evaluate the humoral immune responses induced by MTB12 Ag during human TB.

Methods: Using an ELISA, anti-MTB12 IgG levels in the sera of TB patients and healthy controls were compared with those induced by the 30-kDa Ag and 38-kDa Ag, or both.

Identification of novel metronidazole-inducible genes in Mycobacterium smegmatis using a customized amplification library.

The incidence of antibiotic resistance in pathogenic bacteria is rising. Bacterial resistance may be a natural defense of organisms, or it may result from spontaneous mutations or the acquisition of exogenous resistance genes. We grew spontaneous metronidazole-resistant Mycobacterium smegmatis mutants on solid medium cultures and employed differential expression using a customized amplification library to analyze the global gene profiles of metronidazole-resistant mutants under hypoxic conditions.

Mycobacterium abscessus activates the macrophage innate immune response via a physical and functional interaction between TLR2 and dectin-1.

Mycobacterium abscessus (Mab) is an emerging and rapidly growing non-tuberculous mycobacterium (NTM). Compared with M. tuberculosis, which is responsible for tuberculosis, much less is known about NTM-induced innate immune mechanisms.