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Intestinal barrier dysfunction and intestinal inflammation interact in the progression of Crohn's disease (CD). A recent study indicated that Epac‐2 protected the intestinal barrier and had anti‐inflammatory effects. The present study examined the function of Epac‐2 in CD‐like colitis. Interleukin‐10 gene knockout (Il‐10 −/−) mice exhibit significant spontaneous enteritis and were used as the CD model. These mice were treated with Epac‐2 agonists (Me‐cAMP) or Epac‐2 antagonists (HJC‐0350) or were fed normally (control), and colitis and intestinal barrier structure and function were compared. A Caco‐2 and RAW 264.7 cell co‐culture system were used to analyse the effects of Epac‐2 on the cross‐talk between intestinal epithelial cells and inflammatory cells. Epac‐2 activation significantly ameliorated colitis in mice, which was indicated by reductions in the colitis inflammation score, the expression of inflammatory factors and intestinal permeability. Epac‐2 activation also decreased Caco‐2 cell permeability in an LPS‐induced cell co‐culture system. Epac‐2 activation significantly suppressed nuclear factor (NF)‐κB/mitogen‐activated protein kinase (MAPK) signalling in vivo and in vitro. Epac‐2 may be a therapeutic target for CD based on its anti‐inflammatory functions and protective effects on the intestinal barrier.

Rampant use of tetracycline in animal feed is a threat to food security, the environment, and human health because of the risk of drug residues. Therefore, it is necessary to establish a sensitive, efficient, and reliable method for qualitative and quantitative detection of tetracycline. In this paper, we synthesized fluorescent carbon dots (FCDs) by thermal cracking of crab shell waste, and obtained a fluorescence quantum yield of 30%. Characterization of the FCDs by transmission electron microscopy, Fourier-transform infrared spectroscopy, ultraviolet visible absorption spectroscopy, and photoluminescence spectroscopy showed that they were fluorescent and evenly distributed with an average size of approximately 10 nm. We designed a sensitive probe for detecting tetracycline using the fluorescence intensity change of the FCDs. This method is sensitive, inexpensive, and environmentally friendly. The concentration of tetracycline was examined by comparing the fluorescence intensities of the FCDs before and after tetracycline addition. The limit of detection for tetracycline was 0.005 mg/L (signal-to-noise ratio = 3), which is promising for method development.

Destabilization of balanced immune cell numbers and frequencies is a common feature of viral infections. This occurs due to, and further enhances, viral immune evasion and survival. Since the discovery of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which manifests in coronavirus disease 2019 (COVID-19), a great number of studies have described the association between this virus and pathologically increased or decreased immune cell counts. In this review, we consider the absolute and relative changes to innate and adaptive immune cell numbers, in COVID-19. In severe disease particularly, neutrophils are increased, which can lead to inflammation and tissue damage. Dysregulation of other granulocytes, basophils and eosinophils represents an unusual COVID-19 phenomenon. Contrastingly, the impact on the different types of monocytes leans more strongly to an altered phenotype, e.g. HLA-DR expression, rather than numerical changes. However, it is the adaptive immune response that bears the most profound impact of SARS-CoV-2 infection. T cell lymphopenia correlates with increased risk of intensive care unit admission and death; therefore, this parameter is particularly important for clinical decision-making. Mild and severe diseases differ in the rate of immune cell counts returning to normal levels post disease. Tracking the recovery trajectories of various immune cell counts may also have implications for long-term COVID-19 monitoring. This review represents a snapshot of our current knowledge, showing that much has been achieved in a short period of time. Alterations in counts of distinct immune cells represent an accessible metric to inform patient care decisions or predict disease outcomes.

Diuron, a commonly used herbicide and antifouling biocide, has been frequently detected in seawater. The effects of diuron on fish behaviour are currently poorly understood. Herein, the marine medaka (Oryzias melastigma) was continuously exposed to environmentally realistic levels of diuron from the fertilised egg stage to the adult stage. Behavioural evaluation of adult marine medaka indicated that exposure to diuron increased anxiety in the light-dark test and increased predator avoidance. In addition, diuron exposure significantly reduced aggression, social interaction, shoaling, and learning and memory ability. However, only negligible variations in foraging behaviour and in behaviour in the novel tank test were observed. Marine medaka chronically exposed to diuron also showed decreased levels of dopamine in the brain, and changes were observed in the transcription of genes related to dopamine synthesis, degradation and receptors. Exposure to 5000 ng/L diuron caused significant downregulation of the expression of the genes of tyrosine hydroxylase and monoamine oxidase and significantly upregulated the expression of the genes of the D5 dopaminergic receptor. The relative expression of the D4 dopaminergic receptor was significantly upregulated in the 50, 500 and 5000 ng/L diuron-treated groups. These findings highlight the significant neurotoxic effects of diuron and the extent to which this may involve the dopaminergic system of the brain. More broadly, this study reveals the ecological risk associated with environmentally realistic levels of diuron in marine animals.

OBJECTIVESRottlerin, a pan PDE inhibitor, has a variety of pharmacological activities, including enhancing barrier function and mediating anti-inflammatory activity by changing the distribution of occludin and ZO-1. Nevertheless, the function of rottlerin on Crohn disease (CD) keep unknown. Our aim of the study is to investigate the role of rottlerin on CD-like colitis and its mechanism.METHODSWild-type mice which were 8-10 weeks old were randomly divided into three treatment groups: (i) the normal feeding, no administration (control) group, (ii) the group administered 3% dextran sodium sulfate (DSS) alone, and (iii) the group administered rottlerin (100 mg/kg) and 3% DSS. In this study, the effect of rottlerin on the function and structure of the intestinal barrier was investigated, and the possible mechanism was discussed. We performed signaling pathway analysis and flow cytometry to identify the detailed mechanisms by which rottlerin (10 μg/mL) treatment inhibits cell growth arrest and the attenuation of TJ proteins in LPS-treated FHs 74 int cells.RESULTSRottlerin treatment significantly ameliorated colitis induced by DSS in WT mice, which was manifested by a decrease in inflammation score, the attenuation of inflammatory factors and the inhibition of destruction on intestinal barrier structure. Rottlerin enhanced the levels of occludin and ZO-1, and improved the function of intestinal barrier, which may have been why rottlerin ameliorated colitis in WT mice. The anti-inflammatory effect of rottlerin may be partly due to the activation of Epac-2/Rap-1 signaling.CONCLUSIONSRottlerin may treat CD in humans via enhancing TJ proteins expression and improving the function of intestinal barrier.

Dehydration of D-xylose to yield furfural was carried out using bimetallic salts of a heteropolyacid as the catalyst at 160–220 °C in the DMSO/H2O mixtures. The effect of Sn/Cs molar ratio of the bimetallic salts of 12-tungstophosphoric acid (PW) obtained by ultrasound-assisted coprecipitation on dehydration of D-xylose was investigated. The resultant catalysts were characterized by X-ray diffraction, N2 adsorption, field emission scanning electron microscopy and energy dispersive X-ray (EDX). It was found that the Sn-Cs codoped PW catalysts retained the Keggin crystal structure of PW. Sn0.625Cs0.5PW was the most active catalyst in the dehydration of D-xylose into furfural. The maximum D-xylose conversion (close to 100 wt %) and furfural yield (63 wt %) were achieved at 200 °C for 3 h in DMSO/H2O mixtures. It was found that 16.7 wt % Sn0.625Cs0.5PW on a chitosan-derived support displayed similar catalytic activity to that of Sn0.625Cs0.5PW and good stability after recycling six times.

Objectives Some evidence suggests that type II diabetes mellitus (T2DM) and osteoarthritis (OA) usually occur together clinically, and the symptoms are more obvious compared with non-diabetic patients with OA. We aimed to explore the effects in cartilage degradation, damage, and aging after T2DM combined with OA. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the young-control group (YCG, n = 10), old-control group (OCG, n = 10), and old T2DM-induced OA group (OTOG, n = 10) after the pre-experiment. T2DM model was established using a high-fat diet and streptozotocin. In vivo, all rats were evaluated by behavior, histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). In vitro, chondrocytes of 17-day-old SD rats were cultured to obtain the passage 1 (P1) and passage 5 (P5) chondrocytes. The effects of different concentrations glucose on chondrocyte senescence were evaluated by chondrocyte staining, immunofluorescence, western blotting, and ROS analysis. Results The results of histology (hematoxylin-eosin staining, safranin O-fast green staining, alizarin red S staining, and Mankin score), immunohistochemistry (COL-II, MMP-13, and p21), ELISA (IL-6 and IL-8), western blotting (COL-II, MMP-13, p21, p53, and p16), immunofluorescence, and ROS analysis indicated that the degeneration and aging in the articular cartilage of OTOG were more serious than other groups. Moreover, high concentration glucose can accelerated the degradation and aging degree of cartilage. The changes in P5 are more obvious than in P1 cells. Conclusion T2DM-induced OA can aggravate the aging of articular cartilage in aging individuals. High concentration glucose can cause a certain degree of damage, degradation, and aging of chondrocytes.

λ-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, antitumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE2 signal pathway. BA pretreatment significantly reduced the inflammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE2 in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE2 signaling pathway activation.

The purpose of this work was to study the anatomic and metabolic changes that occur with tumor progression, regression and recurrence in a switchable MYC-driven murine breast cancer model. Serial 1H MRI and hyperpolarized [1-13C]pyruvate metabolic imaging were used to investigate the changes in tumor volume and glycolytic metabolism over time during the multistage tumorigenesis. We show that acute de-induction of MYC expression in established tumors results in rapid tumor regression and significantly reduced glycolytic metabolism as measured by pyruvate-to-lactate conversion. Moreover, cancer recurrences occurring at the tumor sites independently of MYC expression were observed to accompany markedly increased lactate production.

e24168Background: The PI3K/mTOR pathway is a relevant therapeutic target yet real-time monitoring of pathway inhibition is challenging. Metabolic MR imaging using hyperpolarized 13C-pyruvate provid...

Purpose The purpose of this study was to investigate 13C hyperpolarization of α-ketobutyrate (αKB), an endogenous molecular analog of pyruvate, and its in vivo enzymatic conversion via lactate dehydrogenase (LDH) using localized MR spectroscopy. Methods Hyperpolarized (HP) 13C MR experiments were conducted using [13C]αKB with rats in vivo and with isolated LDH enzyme in vitro, along with comparative experiments using [13C]pyruvate. Based on differences in the kinetics of its reaction with individual LDH isoforms, HP [13C]αKB was investigated as a novel MR probe, with added specificity for activity of LDHB-expressed H (“heart”-type) subunits of LDH (e.g., constituents of LDH-1 isoform). Results Comparable T1 and polarization values to pyruvate were attained (T1 = 52 s at 3 tesla [T], polarization = 10%, at C1). MR experiments showed rapid enzymatic conversion with substantially increased specificity. Formation of product HP [13C]α-hydroxybutyrate (αHB) from αKB in vivo was increased 2.7-fold in cardiac slabs relative to liver and kidney slabs. In vitro studies resulted in 5.0-fold higher product production from αKB with bovine heart LDH-1, as compared with pyruvate. Conclusions HP [13C]αKB may be a useful MR probe of cardiac metabolism and other applications where the role of H subunits of LDH is significant (e.g., renal cortex and brain). Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.