一类带有脉冲出生和垂直传染的时滞SEIS传染病模型

建立并分析了一个带有脉冲出生、垂直传染和时滞的SEIS传染病模型.利用频闪映射得到了无病周期解的存在性,并得到了两个临界值R~*和R_*,当R~*<1时,无病周期解全局吸引,疾病消失;当R_*>1时,疾病持续.     

Rice bran enzymatic extract restores endothelial function and vascular contractility in obese rats by reducing vascular inflammation and oxidative stress

BackgroundRice bran enzymatic extract (RBEE) used in this study has shown beneficial activities against dyslipidemia, hyperinsulinemia and hypertension. Our aim was to investigate the effects of a diet supplemented with RBEE in vascular impairment developed in obese Zucker rats and to evaluate the main mechanisms mediating this action.Methods and resultsObese Zucker rats were fed a 1% and 5% RBEE-supplemented diet (O1% and O5%). Obese and their lean littermates fed a standard diet were used as controls (OC and LC, respectively). Vascular function was evaluated in aortic rings in organ baths. The role of nitric oxide (NO) was investigated by using NO synthase (NOS) inhibitors. Aortic expression of endothelial NOS (eNOS), inducible NOS (iNOS), tumor necrosis factor (TNF)-α and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and superoxide production in arterial wall were determined. Endothelial dysfunction and vascular hyperreactivity to phenylephrine in obese rats were ameliorated by RBEE treatment, particularly with 1% RBEE. Up-regulation of eNOS protein expression in RBEE-treated aortas should contribute to this activity. RBEE attenuated vascular inflammation by reducing aortic iNOS and TNF-α expression. Aortas from RBEE-treated groups showed a significant decrease of superoxide production and down-regulation of NADPH oxidase subunits.ConclusionRBEE treatment restored endothelial function and vascular contractility in obese Zucker rats through a reduction of vascular inflammation and oxidative stress. These results show the nutraceutical potential of RBEE to prevent obesity-related vascular complications.     

Chlorogenic acid,a dietary polyphenol,protects acetaminophen-induced liver injury and its mechanism

Chlorogenic acid (CGA) is one of the most abundant dietary polyphenols, possessing well-known antioxidant capacity. The present study is designed to observe the protection provided by CGA against acetaminophen (AP)-induced liver injury in mice in vivo and the underlying mechanisms engaged in this process. Serum transaminases analysis and liver histological evaluation demonstrated the protection of CGA against AP-induced liver injury. CGA treatment decreased the increased number of liver apoptotic cells induced by AP in a dose-dependent manner. CGA also inhibited AP-induced cleaved activation of caspase-3, 7. Moreover, CGA reversed AP-decreased liver reduced glutathione (GSH) levels, glutamate-cysteine ligase (GCL) and glutathione reductase activity. Further results showed that CGA increased mRNA and protein expression of the catalytic subunit of GCL (GCLC), thioredoxin (Trx) 1/2 and thioredoxin reductase (TrxR) 1. Furthermore, CGA abrogated AP-induced phospholyated activation of ERK1/2, c-Jun N-terminal kinase (JNK), p38 kinases and molecular signals upstream. The results of this study demonstrate that CGA counteracts AP-induced liver injury at various levels by preventing apoptosis and oxidative stress damage, and more specifically, both the GSH and Trx antioxidant systems and the mitogen-activated protein kinase (MAPK) signaling cascade appear to be engaged in this protective mechanism.     

20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol,a metabolite of ginseng,inhibits colon cancer growth by targeting TRPC channel-mediated calcium influx

Abnormal regulation of Ca²⁺ mediates tumorigenesis and Ca²⁺ channels are reportedly deregulated in cancers, indicating that regulating Ca²⁺ signaling in cancer cells is considered as a promising strategy to treat cancer. However, little is known regarding the mechanism by which Ca²⁺ affects cancer cell death. Here, we show that 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol (20-GPPD), a metabolite of ginseng saponin, causes apoptosis of colon cancer cells through the induction of cytoplasmic Ca²⁺. 20-GPPD decreased cell viability, increased annexin V-positive early apoptosis and induced sub-G1 accumulation and nuclear condensation of CT-26 murine colon cancer cells. Although 20-GPPD-induced activation of AMP-activated protein kinase (AMPK) played a key role in the apoptotic death of CT-26 cells, LKB1, a well-known upstream kinase of AMPK, was not involved in this activation. To identify the upstream target of 20-GPPD for activating AMPK, we examined the effect of Ca²⁺ on apoptosis of CT-26 cells. A calcium chelator recovered 20-GPPD-induced AMPK phosphorylation and CT-26 cell death. Confocal microscopy showed that 20-GPPD increased Ca²⁺ entry into CT-26 cells, whereas a transient receptor potential canonical (TRPC) blocker suppressed Ca²⁺ entry. When cells were treated with a TRPC blocker plus an endoplasmic reticulum (ER) calcium blocker, 20-GPPD-induced calcium influx was completely inhibited, suggesting that the ER calcium store, as well as TRPC, was involved. In vivo mouse CT-26 allografts showed that 20-GPPD significantly suppressed tumor growth, volume and weight in a dose-dependent manner. Collectively, 20-GPPD exerts potent anticarcinogenic effects on colon carcinogenesis by increasing Ca²⁺ influx, mainly through TRPC channels, and by targeting AMPK.     

One-step electrochemically co-assembled redox-active [Ru(bpy)(2)(tatp)](2+)-BSA-SWCNTs hybrid film for non-redox protein biosensors

A redox-active [Ru(bpy)(2)(tatp)](2+)-BSA-SWCNTs (bpy=2,2'-bipyridine, tatp=1,4,8,9-tetra-aza-triphenylene, BSA=bovine serum albumin, SWCNTs=single-walled carbon nanotubes) hybrid film is fabricated on an indium-tin oxide (ITO) electrode via one-step electrochemical co-assembly approach. BSA is inherently dispersive and therefore served as the linking mediator of SWCNTs, which facilitate the redox reactions of [Ru(bpy)(2)(tatp)](2+) employed as a reporter of BSA. The evidences from differential pulse voltammetry, cyclic voltammetry, scanning electron microscope, emission spectroscopy and fluorescence microscope reveal that the [Ru(bpy)(2)(tatp)](2+)-BSA-SWCNTs hybrid can be electrochemically co-assembled on the ITO electrode, showing two pairs of well-defined Ru(II)-based redox waves. Furthermore, the electrochemical co-assembly of the [Ru(bpy)(2)(tatp)](2+)-BSA-SWCNTs hybrid is found to be strongly dependent on the simultaneous presence of BSA and SWCNTs, indicating a good linear response to BSA in the range from 6 to 50mgL(-1). The results from this study provide an electrochemical co-assembly method for the development of non-redox protein biosensors.     

Meeting report of the European mouse complex genetics network SYSGENET

The second scientific meeting of the European systems genetics network for the study of complex genetic human disease using genetic reference populations (SYSGENET) took place at the Center for Cooperative Research in Biosciences in Bilbao, Spain, December 10–12, 2012. SYSGENET is funded by the European Cooperation in the Field of Scientific and Technological Research (COST) and represents a network of scientists in Europe that use mouse genetic reference populations (GRPs) to identify complex genetic factors influencing disease phenotypes (Schughart, Mamm Genome 21:331–336, 2010). About 50 researchers working in the field of systems genetics attended the meeting, which consisted of 27 oral presentations, a poster session, and a management committee meeting. Participants exchanged results, set up future collaborations, and shared phenotyping and data analysis methodologies. This meeting was particularly instrumental for conveying the current status of the US, Israeli, and Australian Collaborative Cross (CC) mouse GRP. The CC is an open source project initiated nearly a decade ago by members of the Complex Trait Consortium to aid the mapping of multigenetic traits (Threadgill, Mamm Genome 13:175–178, 2002). In addition, representatives of the International Mouse Phenotyping Consortium were invited to exchange ongoing activities between the knockout and complex genetics communities and to discuss and explore potential fields for future interactions.     

Caffeine-containing energy drink improves sprint performance during an international rugby sevens competition

The aim of this study was to determine the effects of a caffeine-containing energy drink on physical performance during a rugby sevens competition. A second purpose was to investigate the post-competition urinary caffeine concentration derived from the energy drink intake. On two non-consecutive days of a friendly tournament, 16 women from the Spanish National rugby sevens Team (mean age and body mass = 23 ± 2 years and 66 ± 7 kg) ingested 3 mg of caffeine per kg of body mass in the form of an energy drink (Fure^®, ProEnergetics) or the same drink without caffeine (placebo). After 60 min for caffeine absorption, participants performed a 15-s maximal jump test, a 6 × 30 m sprint test, and then played three rugby sevens games against another national team. Individual running pace and instantaneous speed during the games were assessed using global positioning satellite (GPS) devices. Urine samples were obtained pre and post-competition. In comparison to the placebo, the ingestion of the energy drink increased muscle power output during the jump series (23.5 ± 10.1 vs. 25.6 ± 11.8 kW, P = 0.05), running pace during the games (87.5 ± 8.3 vs. 95.4 ± 12.7 m/min, P < 0.05), and pace at sprint velocity (4.6 ± 3.3 vs. 6.1 ± 3.4 m/min, P < 0.05). However, the energy drink did not affect maximal running speed during the repeated sprint test (25.0 ± 1.5 vs. 25.0 ± 1.7 km/h). The ingestion of the energy drink resulted in a higher post-competition urine caffeine concentration than the placebo (3.3 ± 0.7 vs. 0.2 ± 0.1 μg/mL; P < 0.05). In summary, 3 mg/kg of caffeine in the form of a commercially available energy drink considerably enhanced physical performance during a women’s rugby sevens competition.     

Vehiculization determines the endocytic internalization mechanism of Zn(II)-phthalocyanine

It is generally accepted that compounds of nanomolecular size penetrate into cells by different endocytic processes. The vehiculization strategy of a compound is a factor that could determine its uptake mechanism. Understanding the influence of the vehicle in the precise mechanism of drug penetration into cells makes possible to improve or modify the therapeutic effects. In this study, using human A-549 cells, we have characterized the possible internalization mechanism of the photosensitizer Zn(II)-phthalocyanine (ZnPc), either dissolved in dimethylformamide (ZnPc–DMF) or included in liposomes of dipalmitoyl-phosphatidyl-choline. Specific inhibitors involved in the main endocytic pathways were used. Co-incubation of cells with ZnPc–liposomes and dynasore (dinamin-mediated endocytosis inhibitor) resulted in a significant decrease of photodamage, whereas other inhibitors did not alter the photodynamic effect of ZnPc. On the contrary, cells treated with ZnPc–DMF in the presence of dynasore, genistein (caveolin-mediated endocytosis inhibitor) or cytochalasin D (macropinocytosis and caveolin-mediated endocytosis inhibitor) showed a significant decrease in ZnPc uptake and photodynamic damage. These results suggest that ZnPc–DMF penetrates into cells mainly by caveolin-mediated endocytosis, whereas ZnPc–liposomes are internalized into cells preferentially by clathrin-mediated endocytosis. We conclude that using different drug vehiculization systems, it is possible to modify the internalization mechanism of a therapeutic compound, which could be of great interest in clinical research.