Physicochemical, morphological and cellular uptake properties of lutein nanodispersions prepared by using surfactants with different stabilizing mechanisms

In this study, we prepared a series of lutein nanodispersions via the solvent displacement method, by using surfactants with different stabilizing mechanisms. The surfactants used include Tween 80 (steric stabilization), sodium dodecyl sulfate (SDS; electrostatic stabilization), sodium caseinate (electrosteric stabilization) and SDS–Tween 80 (electrostatic–steric stabilization). We then characterized the resulting lutein nanodispersions in terms of their particle size, particle size distribution, zeta potential, lutein content, flow behavior, apparent viscosity, transmittance, color, morphological properties and their effects on cell viability and cellular uptake. The type of surfactant used significantly (p < 0.05) affected the physical properties of the nanodispersions, but the chemical properties (lutein content) remained unaffected. Transmission electron microscopy (TEM) images obtained from this study demonstrated that the solvent displacement method was capable of producing lutein nanodispersions containing spherical particles with sizes ranging from 66.20–125.25 nm, depending on the type of surfactant used. SDS and SDS–Tween 80 surfactants negatively affected the viability of the HT-29 cells used in this study. Thus, for the cellular uptake determination, only Tween 80 and sodium caseinate surfactants were used. The cellular uptake of the lutein nanodispersion stabilized by sodium caseinate was higher than that which was stabilized by Tween 80. All things considered, the type of surfactant with different stabilizing mechanisms did produce lutein nanodispersions with different characteristics. These findings would aid in future selection of surfactants in order to produce nanodispersions with desirable properties

The importance of Au⋯π(aryl) interactions in the formation of spherical aggregates in binuclear phosphane gold(I) complexes of a bipodal thiocarbamate dianion: a combined crystallographic and computational study, and anti-microbial activity

Binuclear phosphane gold(I) complexes of a bipodal thiocarbamate dianion, (R3PAu)2L, R = Et (1), Ph (2) and Cy (3), where LH2 is {1,4-[MeOC([double bond, length as m-dash]S)N(H)]2C6H4}, have been synthesised, and characterised spectroscopically (NMR and IR) and by X-ray crystallography. The gold atoms are linearly coordinated within a P-,S-donor set, and are oriented toward the central ring to form intramolecular Au⋯π(aryl) interactions, rather than the intramolecular Au⋯O interactions normally observed in mononuclear analogues. This phenomenon has been investigated by theory (LC-ωPBE-XDM) for 1 which revealed that the geometry optimised species with two Au⋯π(aryl) interactions is more stable by at least 12 kcal mol−1 compared to conformations having one or more Au⋯O interactions instead. The disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods were used to observe the inhibitory effect of complexes 1–3. The disk diffusion results demonstrated that 1 exhibited a broad spectrum of anti-bacterial activity toward 24 strains of Gram-positive and Gram-negative bacteria. By contrast, the anti-bacterial activity of 2 and 3 was limited to Gram-positive bacteria. Further evaluation showed that 1 exhibited marked bactericidal activity against B. cereus, B. subtilis, E. faecalis, L. monocytogenes, S. aureus, S. saprophyticus and methicillin resistant S. aureus cf. standard antibiotics tetracycline and chloramphenicol

Interaction of gene polymorphisms in the risk of coronary artery disease and random amplified polymorphic DNA analysis of coronary artery disease

Genetic variants of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), and cholesteryl ester transfer protein (CETP), influence homocysteine,nitric oxide synthesis, and high-density lipoprotein cholesterol (HDL-C) metabolism,respectively and might increase the risk of coronary artery disease (CAD). It is becoming increasingly proven that polymorphisms in multiple genes are involved in the pathogenesis of CAD. Therefore, this study was conducted to investigate the association and interaction of MTHFR C677T, eNOS G894T, eNOS 4a4b and CETP TaqIB polymorphisms with the risk of CAD in multi-ethnics Malaysian population and the usefulness of random amplified polymorphic DNA (RAPD) analysis in discriminating CAD patients. A total of 344 subjects including angiographically confirmed 243 CAD patients and 101 control subjects were genotyped. The presence of MTHFR 677T allele was significantly associated with the increased risk of CAD and it was associated with higher total cholesterol and low-density lipoprotein cholesterol levels in the Chinese group. The presence of eNOS 4a allele was significantly associated with the increased risk of CAD in Malay and Indian groups. The CETP B2B2 genotype was significantly associated with higher HDL-C and associated with decreased risk of CAD in the Malay group. Moreover, the concomitant presence of MTHFR 677T and CETP B1 alleles was significantly increased the risk of CAD in Malay group and Chinese group but not Indian. At the same time, the concomitant presence of both CETP B1 and eNOS 4a alleles was significantly increased the risk of CAD in Malay group and Indian group but not Chinese. The RAPD analysis show that, under certain conditions, genetic polymorphisms in genomic DNA of CAD patients could be detected by using RAPD analysis and enable the discrimination of the CAD patients from the controls. In conclusion, this study shows that gene polymorphisms differ in both distributions and association with CAD among different ethnic groups in Malaysia. Moreover, this study has identified a novel ethnic-specific gene-gene interactions, suggested that the role of gene-gene interaction in the pathogenesis of CAD might be ethnic specific. The detected polymorphisms by the arbitrary primers OPO 02 and OPO 10 enable the discrimination of the CAD patients from the controls. These findings can be further analysed for biomarker development

Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity

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Distribution of pericellular matrix molecules in the temporomandibular joint and their chondroprotective effects against inflammation

10.1038/ijos.2016.57INTERNATIONAL JOURNAL OF ORAL SCIENCE9143-5

Viral proteases activate the CARD8 inflammasome in the human cardiovascular system

Nucleotide-binding oligomerization domain (NBD), leucine-rich repeat (LRR) containing protein family (NLRs) are intracellular pattern recognition receptors that mediate innate immunity against infections. The endothelium is the first line of defense against blood-borne pathogens, but it is unclear which NLRs control endothelial cell (EC) intrinsic immunity. Here, we demonstrate that human ECs simultaneously activate NLRP1 and CARD8 inflammasomes in response to DPP8/9 inhibitor Val-boro-Pro (VbP). Enterovirus Coxsackie virus B3 (CVB3)-the most common cause of viral myocarditis-predominantly activates CARD8 in ECs in a manner that requires viral 2A and 3C protease cleavage at CARD8 p.G38 and proteasome function. Genetic deletion of CARD8 in ECs and human embryonic stem cell-derived cardiomyocytes (HCMs) attenuates CVB3-induced pyroptosis, inflammation, and viral propagation. Furthermore, using a stratified endothelial-cardiomyocyte co-culture system, we demonstrate that deleting CARD8 in ECs reduces CVB3 infection of the underlying cardiomyocytes. Our study uncovers the unique role of CARD8 inflammasome in endothelium-intrinsic anti-viral immunity.Nanyang Technological UniversityNational Research Foundation (NRF)Published versionThis work is supported by NRF-NRFF2017-05 from the National Research Foundation and MOH-000439 from the National Medical Research Council/Ministry of Health awarded to L. Ho, and NRF-NRFF11-2019-0006 from the National Research Foundation and Nanyang Assistant Professorship (Nanyang Technological University) awarded to F. Zhong

BCG-Induced Trained Immunity in Healthy Individuals: The Effect of Plasma Muramyl Dipeptide Concentrations

BCG vaccination protects not only against tuberculosis but also against heterologous infections. This effect differs between individuals, yet the factors responsible for this variation are unknown. BCG-induced nonspecific protection is, at least partially, mediated by innate immune reprogramming (trained immunity), which can be induced by the muramyl dipeptide (MDP) component of peptidoglycans. We aimed to study whether differential release of MDP in healthy individuals may explain variability of their response to BCG vaccination. Circulating MDP concentrations were increased up to three months after BCG vaccination. MDP concentrations at baseline, but not their increase postvaccination, positively correlated with the induction of trained immunity and not with mycobacteria-induced T-cell responses. Interestingly, MDP concentrations correlated with inflammatory markers in the circulation. In conclusion, circulating MDP concentrations are associated with the strength of trained immunity responses and thus influence the biological effects of BCG vaccination. This study increases our understanding about the role of MDP in BCG-induced trained immunity, which might help to optimize vaccine efficacy and explore novel applications of BCG vaccination

Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity

The human microbiota provides tonic signals that calibrate the host immune response1,2, but their identity is unknown. Bacterial peptidoglycan (PGN) subunits are likely candidates since they are well-known immunity-enhancing adjuvants, released by most bacteria during growth, and have been found in the blood of healthy people3-7. We developed a monoclonal antibody (mAb), 2E7, that targets muramyl-L-alanyl-D-isoglutamine (MDP), a conserved and minimal immunostimulatory structure of PGN. Using 2E7-based assays, we detected PGN ubiquitously in human blood at a broad range of concentrations that is relatively stable in each individual. We also detected PGN in the serum of several warm-blooded animals. However, PGN is barely detectable in the serum of germ-free mice, indicating that its origin is the host microbiota. Neutralization of circulating PGN via intraperitoneal administration of 2E7 suppressed the development of autoimmune arthritis and experimental autoimmune encephalomyelitis in mice. Arthritic NOD2-/- mice lacking the MDP sensor did not respond to 2E7, indicating that 2E7 dampens inflammation by blocking nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-mediated pathways. We propose that circulating PGN acts as a natural immune potentiator that tunes the host immune response; altering its level is a promising therapeutic strategy for immune-mediated diseases.National Medical Research Council (NMRC)This work was supported by National Medical Research Council grant no. BMRC/ BnB/0001b/2012 awarded to Y.W., L.C., and N.P