The anti-cholestatic effects of Coptis chinensis Franch. alone and combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley: dual effects on fecal metabolism and microbial diversity.

Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms. Methods: Rats with α-naphthylisothiocyanate (ANIT, 50 mg/kg)-induced cholestasis were administered low (0.3 g/kg) and high (0.6 g/kg) doses of CF, as well as CF combined with TR at doses of 0.6 g/kg and 0.9 g/kg, respectively. The anti-cholestatic effects of these treatments were assessed by determining their anti-inflammatory, hypolipidemic, and anti-oxidative stress properties. Additionally, fecal metabolomics and fecal microorganisms were analyzed. Results: Low dose CF had a more potent hypolipidemic effect than high dose CF, whereas high dose CF had more potent anti-inflammatory and anti-oxidative stress effects. Combination with TR enhanced the hypolipidemic effect, but antagonized the anti-inflammatory effect, of CF. Analyses of fecal metabolomics and fecal microorganisms showed differences in the regulation of lipid- and amino acid metabolism-related pathways, including pathways of linoleic acid, tyrosine, and arachidonic acid metabolism, and amino acid biosynthesis between different doses of CF as well as between different doses of CF in combination with TR. These differences may contribute to differences in the anti-cholestatic effects of these preparations. Conclusion: CF dose influences its anti-cholestatic efficacy. The combination with TR had synergistic or antagonistic effects on the properties of CF, perhaps by altering fecal metabolism and fecal microbial homeostasis.

Resveratrol Delays Diabetic Cardiomyopathy Fibrosis by Regulating Mitochondrial Autophagy.

Objective: To explore whether resveratrol can postpone the fibrosis associated with diabetic cardiomyopathy (DCM) by modulating the mitochondrial autophagy response through the AMPK/SIRT1-mediated IRE1α/PINK signaling pathway. Methods: A DCM mouse model was established using a high-sugar high-fat diet and streptozotocin. Resveratrol was administered to a subset of the DCM mouse models for comparison. Echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy were employed to evaluate the cardiac status, myocardial fibrosis, myocardial cell apoptosis, and morphological changes of myocardial cells and their internal mitochondria in each group of mice. Western blot staining was performed on myocardial tissues to assess the protein expression levels of p-AMPK, SIRT1, SIRT3, p22, GP91, p-IRE1α, XBP1s PINK, Parkin, LC3I, and Beclin. Mouse myocardial cells were cultured in vitro and intervened with a high-sugar high-fat diet, resveratrol, and GSK690693 (an AMPK inhibitor) to observe the protein expression levels of p-AMPK, p22, XBP1s, and PINK in mouse myocardial cells in each group. Results: Results from echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy showed that resveratrol administration alleviated cardiac damage, myocardial fibrosis, myocardial cell apoptosis, and mitochondrial autophagy in DCM mice. Resveratrol administration promoted the expression of phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1), and sirtuin 3 (SIRT3) in the myocardial tissue of mice, while lowering the elevated protein expression levels of p22 subunit (p22), guanine nucleotide-binding protein q polypeptide 1 (GP91), phosphorylated inositol-requiring enzyme 1 alpha (p-IRE1α), X-box binding protein 1 spliced form (XBP1s), PTEN-induced putative kinase 1 (PINK), Parkin, microtubule-associated proteins light chain 3 isoform I (LC3I), and Beclin (Bcl-2 interacting protein) caused by DCM. GSK690693 (an AMPK inhibitor) suppressed the expression of p-AMPK, SIRT1, and SIRT3 and enhanced the protein expression of p22, XBP1s, and PINK. Conclusion: Resveratrol postpones dilated cardiomyopathy fibrosis by regulating the mitochondrial autophagy response through the AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1)-mediated inositol-requiring enzyme 1 alpha (IRE1α)/PTEN-induced putative kinase 1 (PINK) signaling pathway.

Mediation analysis of urinary metals and stroke risk by inflammatory markers.

BACKGROUND: The association between metals and stroke has been reported, but the mediating role of inflammation between metals and stroke remains unclear. METHODS: We included 9326 adults from the National Health and Nutrition Examination Survey in this study. Through least absolute selection and shrinkage operator (LASSO) regression, weighted quantile sum (WQS) regression, logistic regression, linear regression, restricted cubic spline analysis, and mediation analysis, we explored the association between metals and stroke, as well as the association between metals and inflammatory indicators, and further evaluated the mediating effect of inflammatory indicators on the association between selected metals and stroke risk. RESULTS: The results of the present study suggested positive associations between mixed metals, cadmium and uranium and stroke risk. There is a positive correlation and dose‒response relationship between cadmium and C-reactive protein (CRP). Moreover, CRP mediates 10.1% of the association between cadmium and stroke. CONCLUSIONS: At the epidemiological level, CRP mediates the association between cadmium and stroke risk, suggesting that inflammation may be a potential mechanism for metal-induced stroke.

Ice Control during Cryopreservation of Heart Valves and Maintenance of Post-Warming Cell Viability.

Heart valve cryopreservation was employed as a model for the development of complex tissue preservation methods based upon vitrification and nanowarming. Porcine heart valves were loaded with cryoprotectant formulations step wise and vitrified in 1−30 mL cryoprotectant formulations ± Fe nanoparticles ± 0.6 M disaccharides, cooled to −100 °C, and stored at −135 °C. Nanowarming was performed in a single ~100 s step by inductive heating within a magnetic field. Controls consisted of fresh and convection-warmed vitrified heart valves without nanoparticles. After washing, cell viability was assessed by metabolic assay. The nanowarmed leaflets were well preserved, with a viability similar to untreated fresh leaflets over several days post warming. The convection-warmed leaflet viability was not significantly different than that of the nanowarmed leaflets immediately after rewarming; however, a significantly higher nanowarmed leaflet viability (p < 0.05) was observed over time in vitro. In contrast, the associated artery and fibrous cardiac muscle were at best 75% viable, and viability decreased over time in vitro. Supplementation of lower concentration cryoprotectant formulations with disaccharides promoted viability. Thicker tissues benefited from longer-duration cryoprotectant loading steps. The best outcomes included a post-warming incubation step with α-tocopherol and an apoptosis inhibitor, Q-VD-OPH. This work demonstrates progress in the control of ice formation and cytotoxicity hurdles for the preservation of complex tissues.

Phosphonate coating of commercial iron oxide nanoparticles for nanowarming cryopreserved samples.

New preservation technologies may allow for organ banking similar to blood and biomaterial banking approaches. Using cryoprotective agents (CPAs), aqueous solutions with organic components such as DMSO, propylene glycol, and added salts and sugars, organs can be used to vitrify and store organs at -140 °C. When needed, these organs can be rewarmed in a rapid and uniform manner if CPAs are supplemented with iron oxide nanoparticles (IONPs) in an applied radiofrequency field. Speed and uniformity of warming are both IONP concentration and CPA suspension dependent. Here we present a coating method of small molecule phosphonate linker (PLink) and biocompatible polymer (i.e. polyethylene glycol PEG) that tunes stability and increases the maximum allowable concentration of IONPs in CPA suspension. PLink contains a phosphonate 'anchor' for high irreversible binding to iron oxide and a carboxylic acid 'handle' for ligand attachment. PLink-PEG removes and replaces the initial coating layer of commercially available IONPs (EMG1200 (hydrophobic) and EMG308 (hydrophilic) Ferrotec, Inc., increasing colloidal stability and decreasing aggregation in both water and CPAs, (verified with dynamic light scattering) from minutes (uncoated) to up to 6 days. Heating properties of EMG1200, specific absorption rate (SAR), measured using an applied field of 360 kHz and 20 kA m-1, increased from 20 to 180 W per g Fe with increasing PLink-PEG5000. PEG replacing the initially hydrophobic coating decreased aggregation in water and CPA, consistent with earlier studies on heating performance. Furthermore, although the size is minimized at 0.20 mol PEG per g Fe, heating is not maximized until concentrations above 0.43 mol PEG per g Fe on EMG1200. SAR on hydrophilic EMG308 was preserved at 400 W per g Fe regardless of the amount of PLink added to the core. Herein concentrations of IONP in VS55 (common CPA) significantly above our previous capabilities, sIONP at 10 mg Fe per mL, was reached, 25 mg Fe per mL of 308-PEG5000 and 60 mg Fe per mL of 1200-PEG5000, approaching stock EMG308 in water, 60 mg Fe per mL. Furthermore, at these concentrations cryopreserved Human dermal fibroblast cells were successfully nanowarmed (at applied fields described above), with higher viability as compared to convective rewarming in a water bath and heating rate close to 200 °C min-1, 2.5 times faster than our current system. Using PLink as the coating method allowed for higher concentrations of IONPs to be successfully suspended in CPA without affecting the heating ability. Additionally, the model ligand, PEG, allowed for increased stability over time in nanowarming experiments.

[Spatial variability of nutrients and heavy metals in paddy field soils based on GIS and Geostatistics.] / 基于GISå’Œåœ°ç»Ÿè®¡å­¦çš„ç¨»ç”°åœŸå£¤å »åˆ†ä¸Žé‡é‡‘å±žç©ºé—´å˜å¼‚.

Based on a grid (25 m X 25 m) equidistant sampling, the spatial variability of pH, organic matter, total nitrogen, available phosphorus, CEC and three typical heavy metal elements Cd, As and Pb in soil tillage layer (0-20 cm) were analyzed by using GIS and Geostatistics in the paddy field of 3.56 hm2 in Beishan Town, Changsha County, Hunan Province. The results showed that soil pH value and Pb content showed weak variation, and other indexes showed moderate variation. The order of variation was following available phosphorus ＞ Cd ＞ total nitrogen ＞ organic matter ＞ CEC ＞ As ＞ Pb ＞ pH. Results of the semi-variance test showed that the best fitting model of the semi-variance function of organic matter, available phosphorus and As was exponential, and the best semi-variance function of pH, total nitrogen, CEC, Cd, Pb was spherical. All the indicators had a strong spatial correlation except for CEC, which showed moderate spatial correlation. Kriging interpolation analysis showed that pH, total nitrogen, CEC, Pb were plaque distribution, while organic matter, available phosphorus, Cd and As were block and banded distribution. Vegetation, topography and human activities were the main factors driving the variation of soil nutrients and heavy metals in the study area. The correlation between soil nutrients and heavy metals content was significant, among which pH and organic matter, Cd and Pb reached a very significant correlation level.

A novel combination of astilbin and low-dose methotrexate respectively targeting A2AAR and its ligand adenosine for the treatment of collagen-induced arthritis.

Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment with frequently serious adverse effects. Therefore, combination of low-dose MTX with other drugs is often used in clinic. In this study, we investigated the improvement of astilbin and low-dose MTX combination on collagen-induced arthritis in DBA/1J mice. Results showed that the clinic score, incidence rate, paw swelling, pathological changes of joints and rheumatoid factors were more alleviated in combination therapy than MTX or astilbin alone group. Elevated antibodies (IgG, IgG1, IgG2a, IgM and anti-collagen IgG) and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, IFN-γ and IL-17A) in serum were significantly inhibited, while anti-inflammatory cytokine, IL-10, was enhanced by combination therapy. Further studies indicated that combination therapy significantly decreased Th1 and Th17 cell differentiation and increased Treg cell differentiation. Mechanisms analysis demonstrated combination therapy greatly inhibited Con A-activated MAPK and inflammatory transcriptional signals. Moreover, MTX activated adenosine release and astilbin specifically up-regulated A2A adenosine receptor (A2AAR) expression simultaneously, which most probably contributed to the synergistic efficacy of combination therapy. ZM241385, a specific antagonist of A2AAR, greatly blocked the effects of combination therapy on T cell functions and downstream pathways. All these findings suggest that astilbin is a valuable candidate for low-dose MTX combined therapy in RA via increasing A2AAR/adenosine system and decreasing ERK/NFκB/STATs signals.

Ultrathin Coating of Confined Pt Nanocatalysts by Atomic Layer Deposition for Enhanced Catalytic Performance in Hydrogenation Reactions.

Metal-support interfaces play a prominent role in heterogeneous catalysis. However, tailoring the metal-support interfaces to realize full utilization remains a major challenge. In this work, we propose a graceful strategy to maximize the metal-oxide interfaces by coating confined nanoparticles with an ultrathin oxide layer. This is achieved by sequential deposition of ultrathin Al2 O3 coats, Pt, and a thick Al2 O3 layer on carbon nanocoils templates by atomic layer deposition (ALD), followed by removal of the templates. Compared with the Pt catalysts confined in Al2 O3 nanotubes without the ultrathin coats, the ultrathin coated samples have larger Pt-Al2 O3 interfaces. The maximized interfaces significantly improve the activity and the protecting Al2 O3 nanotubes retain the stability for hydrogenation reactions of 4-nitrophenol. We believe that applying ALD ultrathin coats on confined catalysts is a promising way to achieve enhanced performance for other catalysts.

Microwave absorption properties of carbon nanocoils coated with highly controlled magnetic materials by atomic layer deposition.

In this work, atomic layer deposition is applied to coat carbon nanocoils with magnetic Fe(3)O(4) or Ni. The coatings have a uniform and highly controlled thickness. The coated nanocoils with coaxial multilayer nanostructures exhibit remarkably improved microwave absorption properties compared to the pristine carbon nanocoils. The enhanced absorption ability arises from the efficient complementarity between complex permittivity and permeability, chiral morphology, and multilayer structure of the products. This method can be extended to exploit other composite materials benefiting from its convenient control of the impedance matching and combination of dielectric-magnetic multiple loss mechanisms for microwave absorption applications.

Effects of icariside II on improving erectile function in rats with streptozotocin-induced diabetes.

Icariin and icariside II (ICA II), 2 active components isolated from herba epimedii, have a closely structural relationship. There is evidence that icariin may be useful in the treatment of erectile dysfunction (ED); however, the study on the therapeutic efficacy of ICA II on ED is currently scant. We investigated the effects of ICA II on improving erectile function of rats with streptozocin-induced diabetes. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into normal control and diabetic groups. Diabetes was induced by a one-time intraperitoneal injection of streptozocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 4 groups including a saline-treated placebo arm and 3 ICA II-treated models (1, 5, and 10 mg/kg/d). After 3 months, penile hemodynamics was measured by cavernous nerve electrostimulation (CNE) with real time intracorporal pressure assessment. Penises were harvested with subsequent histological examination (picrosirius red stain, Hart elastin stain, and immunohistochemical stain) and Western blots to explore the expression of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and transforming growth factor ß1 (TGFß1)/Smad2 signaling pathways. Diabetes significantly attenuated erectile responses to CNE. Diabetic rats had decreased corpus cavernosum smooth muscle/collagen ratio and endothelial cell content relative to the control group. The ratio of collagen I to III was significantly lower in the corpora of diabetic rats; furthermore, cavernous elastic fibers were fragmented in the diabetic animals. Neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase, and vascular endothelial growth factor were expressed at lower levels in the diabetic group; ICA II-treated diabetic rats had higher expression in the penis relative to placebo-treated diabetic animals. Both the TGFß1/Smad2/connective tissue growth factor (CTGF) signaling pathway and apoptosis were down-regulated in the penis from ICA II-treated rats. ICA II treatment attenuates diabetes-related impairment of penile hemodynamics, likely by increasing smooth muscle, endothelial function, and nNOS expression. ICA II could alter corpus cavernosum fibrous-muscular pathological structure in diabetic rats, which could be regulated by the TGFß1/Smad2/CTGF and NO-cGMP signaling pathways.

The TGF-ß1/Smad/CTGF pathway and corpus cavernosum fibrous-muscular alterations in rats with streptozotocin-induced diabetes.

Diabetes-associated erectile dysfunction is associated with increased extracellular matrix deposition and reduced smooth muscle content in the corpus cavernosum. The mechanisms of these processes are not well understood. In this study, we investigated fibromuscular changes in the corpus cavernosum of rats with streptozotocin-induced diabetes to determine the mechanisms underlying pathologic changes in penile structure and function. Forty 8-week-old Sprague-Dawley rats were randomly distributed into control and diabetic groups. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin 60 mg/kg. Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real-time intracorporal pressure assessment. The penis was harvested for histologic examination (Masson trichrome stain, picrosirius red stain, Hart elastin stain, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and immunohistochemistry) and Western blot. Diabetes significantly attenuated erectile response to cavernous nerve electrostimulation. Diabetic animals exhibited a decreased smooth muscle/collagen ratio in the corpus cavernosum. The ratio of collagen I to II fibers was significantly lower in the corpora of diabetic rats compared with controls. Cavernous elastic fibers were fragmented in diabetic rats. There was up-regulation of the transforming growth factor ß1/Smad/connective tissue growth factor signaling pathway in diabetic rats. Phospho-Smad2 expression was higher in smooth muscle cells and fibroblasts of diabetic rats, as was the apoptotic index. The up-regulation of the transforming growth factor ß1/Smad/connective tissue growth factor signaling pathway might play an important role in diabetes-induced fibrous-muscular structural changes and deterioration of erectile function.