Differential intracellular fate of Burkholderia pseudomallei 844 and Burkholderia thailandensis UE5 in human monocyte-derived dendritic cells and macrophages

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia pseudomallei </it>(<it>Bp</it>) is a category B biothreat organism that causes a potentially fatal disease in humans and animals, namely melioidosis. <it>Burkholderia thailandensis </it>(<it>Bt</it>) is another naturally occurring species that is very closely related to <it>Bp</it>. However, despite this closely related genotype, <it>Bt </it>is considered avirulent as it does not cause the disease. In the present study, we compared the growth kinetics of <it>B. pseudomallei </it>strain 844 (<it>Bp</it>-844) in human monocyte-derived dendritic cells (MoDCs) and macrophages (Mφs), as well as its ability to stimulate host cell responses with those of <it>B. thailandensis </it>strain UE5 (<it>Bt</it>-UE5).</p> <p>Results</p> <p>Primary human MoDCs and Mφs were infected with <it>Bp</it>-844 and its intracellular growth kinetics and ability to induce host cell responses were evaluated. The results were compared with those obtained using the <it>Bt</it>-UE5. In human MoDCs, both bacteria were similar in respect to their ability to survive and replicate intracellularly, induce upregulation of costimulatory molecules and cytokines and bias T helper cell differentiation toward a Th1 phenotype. By contrast, the two bacteria exhibited different growth kinetics in human Mφs, where the intracellular growth of <it>Bt</it>-UE5, but not <it>Bp</it>-844, was significantly suppressed. Moreover, the ability of Mφs to kill <it>Bp</it>-844 was markedly enhanced following stimulation with IFN-γ.</p> <p>Conclusion</p> <p>The data presented showed that while both strains were similar in their ability to survive and replicate in human MoDCs, only <it>Bp</it>-844 could readily replicate in human Mφs. Both bacteria induced similar host cellular responses, particularly with regard to their ability to bias T cell differentiation toward a Th1 phenotype.</p

Influence of Carbon Black/Silica Hybrid Ratio on Properties of Passenger Car Tire Sidewall

Influence of carbon black (CB)/precipitated silica (SiO2) hybrid ratio on properties of a passenger car tire (PCT) sidewall based on natural rubber (NR) and butadiene rubber (BR) blend was investigated. Rubbers filled with various hybrid filler ratios at a constant loading of 50 phr were prepared and tested. The filler reinforcement efficiency in association with crucial properties of the tire sidewall were of interest. Results show the enhanced rubber–filler interaction with increasing SiO2 fraction leading to the improvement in many vulcanizate properties including hardness, tensile strength, tear strength and fatigue resistance, at the expense of cure efficiency and hysteretic behaviors (i.e., reduced heat build-up resistance and increased dynamic set). The results also suggest the improvement in tire sidewall performance of the NR/BR vulcanizates reinforced with CB/SiO2 hybrid filler, compared to that of the CB-filled vulcanizate

Effects of Blend Ratio and SBR Type on Properties of Carbon Black-Filled and Silica-Filled SBR/BR Tire Tread Compounds

This work aimed at investigating the effects of blend ratio between styrene butadiene rubber (SBR) and butadiene rubber (BR) and SBR type (E-SBR and S-SBR) on properties of SBR/BR tire tread compounds. Influences of these parameters on properties of the tread compounds reinforced by 80 parts per hundred rubber (phr) of carbon black (CB) and silica were also compared. Results reveal that hardness, strengths, and wet grip efficiency were impaired whereas rolling resistance was improved with increasing BR proportion. Surprisingly, the presence of BR imparted poorer abrasion resistance in most systems, except for the CB-filled E-SBR system in which an enhanced abrasion resistance was observed. Obviously, S-SBR gave superior properties (tire performance) compared to E-SBR, particularly obvious in the silica-filled system. Compared with CB, silica gave comparable strengths, better wet grip efficiency, and lower rolling resistance. Carbon black, however, offered greater abrasion resistance than silica

Sulfated galactans from red seaweed Gracilaria fisheri target epidermal growth factor receptor (EGFR) and inhibit cholangiocarcinoma cells (CCA) proliferation

Cholangiocarcinoma (CCA) is increasing in incidence worldwide and is resistant to chemotherapeutic agents, making treatment of CCA a major challenge. Previous studies reported that natural sulfated polysaccharides (SPs) disrupted growth factor receptor activation in cancer cells. The present study, therefore, aimed at investigating the anti-proliferation effect of sulfated galactans (SG) isolated from the red seaweed Gracilaria fisheri (G. fisheri) on CCA cell lines. Direct binding activity of SG to CCA cells, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were determined. The effect of SG on proliferation of CCA cells was investigated. Cell cycle analyses and expression of signaling molecules associated with proliferation were also determined. The results demonstrated that SG bound directly to EGFR. SG inhibited proliferation of various CCA cell lines by inhibiting EGFR and extracellular signal-regulated kinases (ERK) phosphorylation, and inhibited EGF-induced increased cell proliferation. Cell cycle analyses showed that SG induced cell cycle arrest at the G0/G1 phase, down-regulated cell cycle genes and proteins (cyclin-D, cyclin-E, Cdk-4, Cdk-2), and up-regulated the tumor suppressor protein P53 and the cyclin-dependent kinase inhibitor P21. Taken together, these data demonstrate that SG from G. fisheri inhibited proliferation of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on EGFR activation and EGFR/ERK signaling pathway. SG presents a potential EGFR targeted molecule, which may be further clinically developed in a combination therapy for CCA treatment

Salivary Secretory Immunoglobulin a secretion increases after 4-weeks ingestion of chlorella-derived multicomponent supplement in humans: a randomized cross over study

<p>Abstract</p> <p>Background</p> <p>Chlorella, a unicellular green alga that grows in fresh water, contains high levels of proteins, vitamins, minerals, and dietary fibers. Some studies have reported favorable immune function-related effects on biological secretions such as blood and breast milk in humans who have ingested a chlorella-derived multicomponent supplement. However, the effects of chlorella-derived supplement on mucosal immune functions remain unclear. The purpose of this study was to investigate whether chlorella ingestion increases the salivary secretory immunoglobulin A (SIgA) secretion in humans using a blind, randomized, crossover study design.</p> <p>Methods</p> <p>Fifteen men took 30 placebo and 30 chlorella tablets per day for 4 weeks separated by a 12-week washout period. Before and after each trial, saliva samples were collected from a sterile cotton ball that was chewed after overnight fasting. Salivary SIgA concentrations were measured using ELISA.</p> <p>Results</p> <p>Compliance rates for placebo and chlorella ingestions were 97.0 ± 1.0% and 95.3 ± 1.6%, respectively. No difference was observed in salivary SIgA concentrations before and after placebo ingestion (<it>P </it>= 0.38). However, salivary SIgA concentrations were significantly elevated after chlorella ingestion compared to baseline (<it>P </it>< 0.01). No trial × period interaction was identified for the saliva flow rates. Although the SIgA secretion rate was not affected by placebo ingestion (<it>P </it>= 0.36), it significantly increased after 4-week chlorella ingestion than before intake (<it>P </it>< 0.01).</p> <p>Conclusions</p> <p>These results suggest 4-week ingestion of a chlorella-derived multicomponent supplement increases salivary SIgA secretion and possibly improves mucosal immune function in humans.</p

Academic-industry partnerships in addressing nutrition--[infection-immunity-inflammation] interactions.

The interaction between nutrition and infection is a key determinant of human health. Traditionally the interaction has centered on the role of nutrients in defining host defenses and the impact of infection in defining nutritional needs and status. Over the past decades the interaction has expanded its scope to encompass the role of specific nutrients in defining acquired immune function, in the modulation of inflammatory processes and on the virulence of the infectious agent itself. More recently the role of micronutrients and fatty acids on the response of cells and tissues to hypoxic and toxic damage has been recognized suggesting a fourth dimension to the interaction. The list of nutrients affecting infection, immunity, inflammation and cell injury has expanded from traditional protein-energy supply to several vitamins, multiple minerals and more recently specific lipid components of the diet. The promise of nutrition in the defense against infection, inflammation and tissue injury has spawned a thriving pharma-nutritional supplement industry and the development of novel foods that require appropriate evaluation of efficacy, safety and effectiveness relative to costs. Academics need to aware of the ethics and the pitfalls in the interaction with industry; conversely industry has to define its role in the process of bringing new knowledge to useful products. The process needs to be interactive, transparent and clearly place public interest above all other considerations