Objective-The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I. Methods and Results-Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I N ), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I Glyc in vitro ), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I Glyc in vivo ), discoidal reconstituted high-density lipoproteins (

The female vaginal environment contains diverse microorganisms, and their interactions play significant roles in health and disease. Lactobacillus species are the predominant vaginal microorganisms in healthy women and relevant as a barrier to defense against pathogens, including Candida albicans. The yeast-to-hyphae transition is believed to be a determinant of C. albicans pathogenesis. In this study, we investigated the effects of vaginal isolates of L. crispatus (seven strains), L. gasseri (six strains), and L. jensenii (five strains) on growth, hyphal formation and virulence-related genes expression of C. albicans ATCC 10231. We found that the L. crispatus showed the most significant antimicrobial activities in microplate-based liquid medium assay (P < 0.05). All seven cell-free supernatants (CFS) from L. crispatus strains reduced the growth of C. albicans by >60%. The effects might be due to their productions of some secretory antimicrobial compounds in addition to H2O2 and organic acids. Furthermore, each of the CFS of Lactobacillus strains was found to significantly suppress the yeast-to-hyphae transition of C. albicans under hyphae-inducing conditions (RPMI 1640 medium supplemented with 10% fetal bovine serum). The hyphae inhibition rates of C. albicans treated by CFS from L. crispatus, L. gasseri, and L. jensenii were 88.3 ± 3.02%, 84.9 ± 6.0%, and 81.9 ± 6.2%, respectively. Moreover, the expression of hyphae-specific genes (ALS3, HWP1, ECE1, EAP1, and SAP5) and transcriptional regulatory genes (EFG1, TEC1, and NRG1) were analyzed using quantitative real-time PCR. The results demonstrated that L. crispatus CFS significantly down-regulated the expression of hyphae-specific genes ALS3 (0.140-fold)), HWP1 (0.075-fold), and ECE1 (0.045-fold), while up-regulated the expression of the negative transcriptional regulator gene NRG1 with 1.911-fold. The antimicrobial compounds from L. crispatus B145 against Candida growth were heat stable and protease resistance, but those against hyphal formation were partially sensitive to the same treatments. Our novel findings suggest that L. crispatus, a dominant Lactobacillus species associated with a healthy vagina, could strongly inhibit C. albicans growth and hyphal formation. L. crispatus might repress the expression of hyphae-specific genes (ALS3, HWP1, and ECE1) in a NRG1-dependent manner. Besides, L. crispatus B145 is highly worthwhile for probiotic investigation.

Objective-To determine if niacin can confer cardiovascular benefit by inhibiting vascular inflammation and improving endothelial function independent of changes in plasma lipid and lipoprotein levels. Methods and Results-New Zealand white rabbits received normal chow or chow supplemented with 0.6% or 1.2%(wt/wt) niacin. This regimen had no effect on plasma cholesterol, triglyceride, or high-density lipoprotein levels. Acute vascular inflammation and endothelial dysfunction were induced in the animals with a periarterial carotid collar. At the 24-hour postcollar implantation, the endothelial expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1 was markedly decreased in the niacin-supplemented animals compared with controls. Niacin also inhibited intima-media neutrophil recruitment and myeloperoxidase accumulation, enhanced endothelial-dependent vasorelaxation and cyclic guanosine monophosphate production, increased vascular reduced glutathione content, and protected against hypochlorous acid-induced endothelial dysfunction and tumor necrosis factor ␣-induced vascular inflammation. Conclusion-Previous human intervention studies have demonstrated that niacin inhibits coronary artery disease. Thisbenefit is thought to be because of its ability to reduce low-density lipoprotein and plasma triglyceride levels and increase high-density lipoprotein levels. The present study showed that niacin inhibits vascular inflammation and protects against endothelial dysfunction independent of these changes in plasma lipid levels. Key Words: niacin Ⅲ inflammation Ⅲ endothelial dysfunction N iacin (nicotinic acid) has been used for more than 30 years to treat plasma lipid disorders and to prevent atherosclerotic cardiovascular disease. 1 At pharmacological doses, niacin reduces low-density lipoprotein cholesterol, plasma triglyceride, nonesterified fatty acid, and lipoprotein(a) levels. Niacin also increases the concentration of high-density lipoproteins (HDLs). 2 Human intervention studies have indicated that treatment with niacin, either alone or in combination with other lipid-lowering agents, can slow or reverse the progression of atherosclerosis and reduce cardiovascular event rates and total mortality in patients with hypercholesterolemia and established atherosclerotic cardiovascular disease. 2 In combination therapy with statins, niacin reduces cardiovascular events 3 and slows coronary atherosclerosis progression. 4 It also reduces coronary stenosis progression in patients with metabolic syndrome. 5 It has always been assumed that these beneficial effects are the result of the lipid-modifying effects of niacin.However, recent data have indicated that niacin also decreases C-reactive protein levels, 6 improves endothelial dysfunction, 7,8 increases the endothelial and leukocyte oxidation-reduction (redox) state in vitro, 9 inhibits cytokine-induced monocyte adhesion to human endothelial cells, 9,10 improves plaque stability, and reduces thrombosis. 11 It...

Objectives— The apolipoprotein (apo)A-I mimetic peptide 5A is highly specific for ATP-binding cassette transporter (ABC)A1-mediated cholesterol efflux. We investigated whether the 5A peptide shares other beneficial features of apoA-I, such as protection against inflammation and oxidation. Methods— New Zealand white rabbits received an infusion of apoA-I, reconstituted high-density lipoprotein (HDL) containing apoA-I ([A-I]rHDL), or the 5A peptide complexed with phospholipids (1-palmitoyl-2-linoleoyl phosphatidylcholine [PLPC]), before inserting a collar around the carotid artery. Human coronary artery endothelial cells (HCAECs) were incubated with (A-I)rHDL or 5A/PLPC before stimulation with tumor necrosis factor α. Results— ApoA-I, (A-I)rHDL, and 5A/PLPC reduced the collar-mediated increase in (1) endothelial expression of cell adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1; (2) production, as well as the expression of the Nox4 catalytic subunits of the NADPH oxidase; and (3) infiltration of circulating neutrophils into the carotid intima–media. In HCAECs, both 5A/PLPC and (A-I)rHDL inhibited tumor necrosis factor-α–induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, as well as the nuclear factor κB signaling cascade and production. The effects of the 5A/PLPC complex were no longer apparent in HCAECs knocked down for ABCA1. Conclusion— Like apoA-I, the 5A peptide inhibits acute inflammation and oxidative stress in rabbit carotids and HCAECs. In vitro, the 5A peptide exerts these beneficial effects through interaction with ABCA1.

A novel lanthanide-organic framework (Eu-HODA), consisting of 2,2',3,3'-oxidiphthalic acids as efficient sensitizing units, is assembled and characterized. Eu-HODA features rare chiral helical channels despite the achiral nature of HODA. It is found that this MOF shows a unique luminescent response to methanol, in contrast to n-propanol and ethanol. Eu-HODA reveals a turn-off luminescence switching initiated by acetone molecules with an EC of 0.03 vol %, which is below the occupational exposure limit of acetone stipulated by the American Conference of Governmental Industrial Hygienists. Furthermore, it also exhibits high sensitivity (Stern-Volmer constant K = 2.09 × 10 L/mol) and low detection limit (6.4 ppb) for Fe ions in pure water because of the existence of uncoordinated carboxyl groups within open frameworks. Eu-HODA-based test paper provides a simple and reliable detection method for Fe in practical applications.

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1β were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

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