The effect of IGF-1 on symptoms of sleep deprivation in a rat model of inflammatory heart disease and metabolic syndrome

Sleep deprivation (SD) has become a worldwide public health concern due to the many negative health consequences associated with suboptimal sleep. SD has been linked to a catabolic hormone signature, heart disease, hypertension, diabetes, and an increase in morbidity and mortality. Herein, we investigated the effects and mechanism of SD on cardiac and metabolic health and evaluated the impact of exogenously supplied IGF-1 on these symptoms. In the present study, we show that 5 days of acute SD negatively impacted all of the various indicators of cardiac and metabolic health. All symptoms of SD were ameliorated by daily administration of IGF-1, however. IGF-1 administration also reduced the phosphorylation of Akt and expression of Bax, a promoter of apoptosis. Conversely, the expression of Bcl-2, an inhibitor of apoptosis, was elevated by IGF-1, and all IGF-1 effects were suppressed by the PI3K/Akt inhibitor LY294002, reaffirming the importance of the PI3K/Akt pathway in the maintenance of cardiac and metabolic health.     

Modulation of peanut-induced allergic immune responses by oral lactic acid bacteria-based vaccines in mice

Peanut allergy (PNA) has becoming a non-negligible health concern worldwide. Thus far, allergen-specific immunotherapy aimed at inducing mucosal tolerance has widely been regarded as a major management strategy for PNA. The safety profiles and the intrinsic probiotic properties of lactic acid bacteria (LAB) render them attractive delivery vehicles for mucosal vaccines. In the present study, we exploited genetically modified Lactococcus lactis to produce peanut allergen Ara h 2 via different protein-targeting systems and their immunomodulatory potency for allergic immune responses in mice were investigated. By comparison with the strain expressing the cytoplasmic form of Ara h 2 (LL1), the strains expressing the secreted and anchored forms of Ara h 2 (LL2 and LL3) were more potent in redirecting a Th2-polarized to a non-allergic Th1 immune responses. Induction of SIgA and regulatory T cells were also observed at the local levels by orally administration of recombinant L. lactis. Our results indicate that allergen-producing L. lactis strains modulated allergic immune responses and may be developed as promising mucosal vaccines for managing allergic diseases.     

Complete mitochondrial genome of black porgy Acanthopagrus schlegelii (Perciformes, Sparidae)

Black porgy, Acanthopagrus schlegelii, is a marine protandrous hermaphrodite and belongs to one of the most important species commercialized for food in various areas of Asia. In this study, the complete mitochondrial genome of A. schlegelii has been determined. The mitogenome was 16,649 bp in length and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 non-coding regions. It shared 90.2%, 82.3%, and 82.1% mitogenome sequence with Acanthopagrus latus, Parargyrops edita, and Pagrus major, respectively.     

Evidence for diffuse central retinal edema in vivo in diabetic male Sprague Dawley rats

Background

Investigations into the mechanism of diffuse retinal edema in diabetic subjects have been limited by a lack of animal models and techniques that co-localized retinal thickness and hydration in vivo. In this study we test the hypothesis that a previously reported supernormal central retinal thickness on MRI measured in experimental diabetic retinopathy in vivo represents a persistent and diffuse edema.

Methodology/Principal Findings

In diabetic and age-matched control rats, and in rats experiencing dilutional hyponatremia (as a positive edema control), whole central retinal thickness, intraretinal water content and apparent diffusion coefficients (ADC, ‘water mobility’) were measured in vivo using quantitative MRI methods. Glycated hemoglobin and retinal thickness ex vivo (histology) were also measured in control and diabetic groups. In the dilutional hyponatremia model, central retinal thickness and water content were supernormal by quantitative MRI, and intraretinal water mobility profiles changed in a manner consistent with intracellular edema. Groups of diabetic (2, 3, 4, 6, and 9 mo of diabetes), and age-matched controls were then investigated with MRI and all diabetic rats showed supernormal whole central retinal thickness. In a separate study in 4 mo diabetic rats (and controls), MRI retinal thickness and water content metrics were significantly greater than normal, and ADC was subnormal in the outer retina; the increase in retinal thickness was not detected histologically on sections of fixed and dehydrated retinas from these rats.

Conclusions/Significance

Diabetic male Sprague Dawley rats demonstrate a persistent and diffuse retinal edema in vivo, providing, for the first time, an important model for investigating its pathogenesis and treatment. These studies also validate MRI as a powerful approach for investigating mechanisms of diabetic retinal edema in future experimental and clinical investigations.     

Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network

The arachidonic acid (AA) metabolic network produces key inflammatory mediators which have been considered as hallmark contributors in various inflammatory related diseases. Enzymes in this network, such as 5-lipoxygenase (5-LOX), cyclooxygenase (COX), leukotriene A(4) hydrolase (LTA4H) and prostaglandin E synthase (PGES), have been used as targets for anti-inflammatory drug discovery. Multi-target drugs and drug combinations have also been developed for this network. However, how the inhibitors alter the dynamics of metabolite production and which combinatorial target intervention solutions are better needs further exploration. We did a system based intervention analysis on the AA metabolic network. Using an LC-MS/MS method, we quantitatively studied the eicosanoid metabolites responses of AA metabolic network during stimulation of Sprague Dawley rat blood samples with the calcium ionophore. Our results indicate that inhibiting the upstream rather than the downstream target of 5-LOX pathway will simultaneously alter the AA metabolism to the COX pathway (and vice versa). Therefore, single-target inhibitors cannot control all the inflammatory mediators at the same time. We also suggest that in the case of multiple-target anti-inflammatory solutions, the combination of inhibitors of the downstream enzymes may have stronger inhibition efficiency and cause less side-effects compared to the other solutions. One therapeutic strategy, LTA4H/COX inhibition solution, was found promising for the intervention of inflammatory mediator biosynthesis and at the same time stimulating the production of anti-inflammatory agents.     

粗茎鳞毛蕨应用的研究

为开发利用粗茎鳞毛蕨(Dryopteris crassirhizoma Nakai)的药用和观赏价值、提高其质量和产量,对其进行了人工有性繁殖和复壮研究.在大批量人工有性育苗的基础上,予以分组复壮、对照栽培.筛选出了经济简便的技术路线,观察了形态发育与栽培条件的相关性.     

Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors

The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer’s disease.

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Spectroscopic studies on the interaction of chromium (VI) and chromium (III) with keyhole limpet hemocyanin

The interactions of keyhole limpet hemocyanin (KLH) with chromium nitrate, potassium dichromate, and chromate were investigated using fluorescence, UV–vis absorption and circular dichroism (CD) spectroscopy under simulated physiological conditions. The experimental results showed that the different forms of chromium could quench the intrinsic fluorescence of KLH following a static quenching mechanism rather than by dynamic collision, which indicated that a Cr–KLH complex was formed. The Stern–Volmer quenching constants for the interaction indicated that the binding reaction of KLH with Cr(VI) was stronger the binding of KLH with Cr(III). The thermodynamic values for binding of Cr(VI) to KLH are ΔH > 0 and ΔS > 0. By contrast, the values for the interaction of Cr(III) with KLH are ΔH < 0 and ΔS < 0. The results of synchronous fluorescence, UV–vis absorption and CD spectroscopy showed that the α‐helical secondary structure and conformation of KLH were altered by different forms of chromium. Copyright © 2016 John Wiley & Sons, Ltd.     

Enhanced Anti-Inflammatory Efficacy Through Targeting to Macrophages: Synthesis and <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation of Folate-Glycine-Celecoxib

As an effective COX-2 inhibitor, celecoxib is widely used in anti-inflammation therapy. However, it may cause cardiovascular risks and renal adverse effects. In the present study, we aimed to construct a celecoxib prodrug with enhanced anti-inflammatory efficacy and reduced adverse effects using folate in order to target activated macrophages. Folate-glycine-celecoxib was synthesized and identified by ¹H-NMR, MS, and FTIR analyses. The cytotoxicity of folate-glycine-celecoxib was tested on murine macrophage cells (RAW264.7) using thiazolyl blue tetrazolium bromide. Cellular uptake studies were employed to determine targeting ability toward folate receptors via flow cytometry and confocal microscopy. Anti-inflammatory efficacy of folate-glycine-celecoxib was investigated by measuring the concentration of LPS-induced nitric oxide (NO). Folate-glycine-celecoxib exhibited lower cytotoxicity than conventional celecoxib, and this conjugate could be targetedly transported into RAW264.7 cells through binding with folate receptors on cell surface. Through targeting to RAW264.7 cells, folate-glycine-celecoxib exhibited better effects than equimolar celecoxib in NO inhibition, suggesting greater anti-inflammatory activity. These findings demonstrated that the prodrug folate-glycine-celecoxib had potential to treat inflammatory disease with low cytotoxicity and high targeting ability.     

Calibration of pneumotachographs using a calibrated syringe.

Pneumotachograph require frequent calibration. Constant-flow methods allow polynomial calibration curves to be derived but are time consuming. The iterative syringe stroke technique is moderately efficient but results in discontinuous conductance arrays. This study investigated the derivation of first-, second-, and third-order polynomial calibration curves from 6 to 50 strokes of a calibration syringe. We used multiple linear regression to derive first-, second-, and third-order polynomial coefficients from two sets of 6-50 syringe strokes. In part A, peak flows did not exceed the specified linear range of the pneumotachograph, whereas flows in part B peaked at 160% of the maximum linear range. Conductance arrays were derived from the same data sets by using a published algorithm. Volume errors of the calibration strokes and of separate sets of 70 validation strokes (part A) and 140 validation strokes (part B) were calculated by using the polynomials and conductance arrays. Second- and third-order polynomials derived from 10 calibration strokes achieved volume variability equal to or better than conductance arrays derived from 50 strokes. We found that evaluation of conductance arrays using the calibration syringe strokes yields falsely low volume variances. We conclude that accurate polynomial curves can be derived from as few as 10 syringe strokes, and the new polynomial calibration method is substantially more time efficient than previously published conductance methods.