Baicalin ameliorates the gut barrier function and intestinal microbiota of broiler chickens.

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus, Lachnoclostridium, Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified_f__Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

Immunosuppressive Ability of Trichinella spiralis Adults Can Ameliorate Type 2 Inflammation in a Murine Allergy Model.

BACKGROUND: There is an increase in the global incidence of allergies. The hygiene hypothesis and the old friend hypothesis reveal that helminths are associated with the prevalence of allergic diseases. The therapeutic potential of Trichinella spiralis is recognized; however, the stage at which it exerts its immunomodulatory effect is unclear. METHODS: We evaluated the differentiation of bone marrow-derived macrophages stimulated with T spiralis excretory-secretory products. Based on an ovalbumin-induced murine model, T spiralis was introduced during 3 allergy phases. Cytokine levels and immune cell subsets in the lung, spleen, and peritoneal cavity were assessed. RESULTS: We found that T spiralis infection reduced lung inflammation, increased anti-inflammatory cytokines, and decreased Th2 cytokines and alarms. Recruitment of eosinophils, CD11b+ dendritic cells, and interstitial macrophages to the lung was significantly suppressed, whereas Treg cells and alternatively activated macrophages increased in T spiralis infection groups vs the ovalbumin group. Notably, when T spiralis was infected prior to ovalbumin challenge, intestinal adults promoted proportions of CD103+ dendritic cells and alveolar macrophages. CONCLUSIONS: T spiralis strongly suppressed type 2 inflammation, and adults maintained lung immune homeostasis.

Molecular Simulation Study on the Interaction between Porcine CR1-like and C3b.

The molecular basis of porcine red blood cell immune adhesion function stems from the complement receptor type 1-like (CR1-like) on its cell membrane. The ligand for CR1-like is C3b, which is produced by the cleavage of complement C3; however, the molecular mechanism of the immune adhesion of porcine erythrocytes is still unclear. Here, homology modeling was used to construct three-dimensional models of C3b and two fragments of CR1-like. An interaction model of C3b-CR1-like was constructed by molecular docking, and molecular structure optimization was achieved using molecular dynamics simulation. A simulated alanine mutation scan revealed that the amino acids Tyr761, Arg763, Phe765, Thr789, and Val873 of CR1-like SCR 12-14 and the amino acid residues Tyr1210, Asn1244, Val1249, Thr1253, Tyr1267, Val1322, and Val1339 of CR1-like SCR 19-21 are key residues involved in the interaction of porcine C3b with CR1-like. This study investigated the interaction between porcine CR1-like and C3b using molecular simulation to clarify the molecular mechanism of the immune adhesion of porcine erythrocytes.

Baicalin ameliorates high fat diet-induced nonalcoholic fatty liver disease in mice via adenosine monophosphate-activated protein kinase-mediated regulation of SREBP1/Nrf2/NF-κB signaling pathways.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease around the world, imposing severe threats on human health. Unfortunately, no clinically approved drugs are available for use as yet. Baicalin (BA) is reported to have hepatoprotective effects, and it is not clear whether BA can treat NAFLD and how. Here, a high-fat diet (HFD)-induced NAFLD mouse model was established to explore the protective roles and mechanisms of BA against HFD-induced NAFLD. Physiochemical results showed that BA exhibited significantly protective effects against HFD-induced NAFLD in mice. Liver transcriptomic analysis revealed that BA attenuated HFD-induced NAFLD via activating AMPK pathway, which was confirmed by the AMPK inhibitor Compound C. Additionally, the expression changes of AMPK downstream genes demonstrated that BA exerted ameliorative effects against NAFLD through AMPK-mediated inhibition of SREBP1 and NF-κB pathways, and activation of Nrf2 pathway. Taken together, our study reveals the protective roles of BA against HFD-caused NAFLD through AMPK-mediated modulation of SREBP1/Nrf2/NF-κB pathways, suggesting that BA has potential drug development implications. Most importantly, our study creates a paradigm through the combination of molecular biology and bioinformatics for further studies of action mechanisms of biomolecules combating diseases.

Curcumol inhibits EMCV replication by activating CH25H and inhibiting the formation of ROs.

BACKGROUND: Zedoary turmeric oil extracted from the roots of curcuma (Curcuma aeruginosa Roxb.) is used for the treatment of myocarditis in China. EMCV infection causes abortion in pregnant sows and myocarditis in piglets. Our previous studies demonstrated that curcumol significantly increased the expression of IFN-ß in EMCV infected HEK-293T cells. The present results showed that curcumol inhibits EMCV replication by interfering the host cell cholesterol homeostasis and reducing ROs production through activation of the JAK/STAT signaling pathway. METHOD: This study was designed to explore whether curcumol can inhibit the replication of encephalomyocarditis viruses (EMCV) in cell culture. The expression level of JAK1, IRF9, STAT2, P-STAT2, CH25H, PI4KA and OSBP in EMCV-infected HEK-293T cells treated with curcumol, ribavirin or hydroxypropyl-ß-CD (HPCD) were determined by Western blotting (WB). The cholesterol level in EMCV infected HEK-293T cells treated with curcumol and HPCD were detected using Amplex™ Red Cholesterol Assay Kit. The antiviral effects of curcumol and HPCD on EMCV were also quantitatively detected by real-time fluorescence quantitative PCR (q-PCR). The amount and morphology of ROs were observed by transmission electron microscopy (TEM). RESULTS: The results demonstrated that curcumol significantly (P < 0.05) increased the expression of JAK1, IRF9, P-STAT2 and CH25H proteins, while that of STAT2, PI4KA and OSBP were remained unchanged. Compared with virus group (0.134 µg.µg-1 proteins), the total cholesterol level was significantly (P < 0.05) reduced by curcumol (0.108 µg.µg-1 proteins) and HPCD (0.089 µg.µg-1 proteins). Compared with virus group (88237 copies), curcumol (41802 copies) and HPCD (53 copies) significantly (P < 0.05) reduced EMCV load. Curcumol significantly reduced the production of ROs in EMCV-infected HEK-293T cells and activated CH25H through the JAK/STAT signaling pathway. CONCLUSION: Curcumol inhibited EMCV replication by affecting the cholesterol homeostasis and the production of ROs in HEK-293T cell.

Study on the mechanism of scutellarin's protective effect against ZEA-induced mouse ovarian granulosa cells injury.

Zearalenone (ZEA), a mycotoxin produced by Fusarium, can cause reproductive disorders by targeting ovarian granulosa cells (GCs). We previous showed that scutellarin (Scu) rescues ZEA-induced GCs damage in mice. In this study, we employed iTRAQ-based proteomics to investigate the mechanism underlying the restorative effects of Scu in this model. Compared to the model group, we identified 415 differentially expressed proteins (DEPs) in both the control and Scu-treated groups, and found that these were enriched mainly in the biosynthesis and metabolism, drug metabolism, and pentose phosphate pathway. Moreover, the MAPK and heat shock protein-necroptosis pathway were implicated in regulating ZEA toxicity and the protective effect of Scu. Receptor-interacting serine threonine-protein kinase 1 (RIPK1) showed the highest fold-change in expression in the Scu-treated group. Small-interfering RNA-mediated RIPK1 knockdown further promoted the increase in cleaved-caspase-3 expression induced by ZEA, but not in the cells treated with Scu. These data indicated the involvement of multiple targets and pathways in the protective effect of Scu against ZEA-induced damage. Our findings also indicated that RIPK1 may be involved in the inhibition of GCs apoptosis induced by ZEA.

Measurement of Post-Exercise Response of Local Arterial Parameters Using an Adjustable Microfluidic Tactile Sensor.

In this work, we demonstrate an adjustable microfluidic tactile sensor for measurement of post-exercise response of local arterial parameters. The sensor entailed a polydimethylsiloxane (PDMS) microstructure embedded with a 5×1 resistive transducer array. The pulse signal in an artery deflected the microstructure and registered as a resistance change by the transducer aligned at the artery. PDMS layers of different thicknesses were added to adjust the microstructure thickness for achieving good sensor-artery conformity at the radial artery (RA) and the carotid artery (CA). Pulse signals of nine (n=9) young healthy male subjects were measured at-rest and at different times post-exercise, and a medical instrument was used to simultaneously measure their blood pressure and heart rate. Vibration-model-based analysis was conducted on a measured pulse signal to estimate local arterial parameters: elasticity, viscosity, and radius. The arterial elasticity and viscosity increased, and the arterial radius decreased at the two arteries 1min post-exercise, relative to at-rest. The changes in pulse pressure (PP) and mean blood pressure (MAP) between at-rest and 1min post-exercise were not correlated with that of heart rate and arterial parameters. After the large 1min post-exercise response, the arterial parameters and PP all went back to their at-rest values over time post-exercise.Clinical Relevance- The study results show the potential application of an affordable, user-friendly device for a more comprehensive arterial health assessment.

The Fabrication of Amino Acid Incorporated Nanoflowers with Intrinsic Peroxidase-like Activity and Its Application for Efficiently Determining Glutathione with TMB Radical Cation as Indicator.

The assessment of glutathione (GSH) levels is associated with early diagnostics and pathological analysis for various disorders. Among all kinds of techniques for detecting GSH, the colorimetric assay relying on the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by many nanomaterials with peroxidase-like activity attracts increasing attention owing to its outstanding merits, such as high sensitivity and high selectivity. However, the aggregation between the nanomaterials severely hinders the entrance of TMB into the "active site" of these peroxidase mimics. To address this problem, the D-amino acid incorporated nanoflowers possessing peroxidase-like activity with a diameter of 10-15 µm, TMB and H2O2 were employed to establish the detection system for determining the level of glutathione. The larger diameter size of the hybrid nanoflowers substantially averts the aggregation between them. The results confirm that the hybrid nanoflowers detection system presents a low limit of detection, wide linear range, perfect selectivity, good storage stability and desired operational stability for the detection of GSH relying on the intrinsic peroxidase-like activity and favorable mechanical stability of the hybrid nanoflowers, indicating that the hybrid nanoflowers detection system has tremendous application potential in clinical diagnosis and treatment.

Understanding the Role of Longitudinal Arterial Wall Motion in Blood Circulation from the Perspective of a Piano String.

This work is aimed to establish engineering theories of the coupled longitudinal and radial motion of the arterial wall. By treating the arterial wall as a piano string in the longitudinal direction and as a viscoelastic material in the circumferential direction, and considering pulsatile pressure and wall shear stress from axial blood flow in an artery, the fully-formed governing equations of the coupled motion of the arterial wall are obtained and are related to the engineering theories of axial blood flow for a unified engineering understanding of blood circulation in the cardiovascular (CV) system. The longitudinal wall motion and the radial wall motion are essentially a longitudinal elastic wave and a transverse elastic wave, respectively, traveling along the arterial tree, with their own propagation velocities dictated by the physical properties and geometrical parameters of the arterial wall. The longitudinal initial tension is essential for generating a transverse elastic wave in the arterial wall to accompany the pulsatile pressure wave in axial blood flow. Under aging and subclinical atherosclerosis, propagation of the two elastic waves and coupling of the two elastic waves weakens and consequently might undermine blood circulation.

Post-exercise Response of Arterial Parameters for Arterial Health Assessment Using a Microfluidic Tactile Sensor and Vibration-Model-Based Analysis: A Proof-of-Concept Study.

OBJECTIVE: Arterial stiffness and endothelial function are two established surrogate markers of subclinical atherosclerosis and are quantified by three arterial parameters: elasticity, viscosity and radius of the arterial wall. Yet, the current methods for their assessment are unsuitable for routine use. Post-exercise response of the cardiovascular (CV) system serves as a more sensitive detection of subclinical arterial abnormalities that are not apparent at-rest. The objective of this study is to propose a novel method that can measure post-exercise response of arterial parameters and is also suitable for routine use. APPROACH: A microfluidic tactile sensor with a location-insensitive configuration was used for arterial pulse signal measurements on six asymptomatic male subjects, offering measurement reliability, ease use by a layperson, and affordability. By treating the arterial pulse signal as a vibration signal of the arterial wall, vibration-model-based analysis of only one measured pulse signal with no calibration was conducted for simultaneous estimation of three arterial parameters. Exercise-intensity-normalized percent changes in arterial parameters were utilized to remove the influence of variation in exercise intensity on post-exercise response, and then their measured values were compared for difference in post-exercise response between the subjects. MAIN RESULTS: One subject who was obese, on subject who had insomnia, and the oldest subject in the study demonstrated differences in post-exercise response at the radial artery (RA), as compared with the three subjects free of those three factors. Despite a lack of statistical significance, the observed difference at the RA between subjects was supported by (i) their consistency with the related findings in the literature, and (ii) their consistency with the measured values at the carotid artery (CA) and superficial temporal artery (STA) and the anatomical difference between the three arteries. SIGNIFICANCE: The proposed method has the potential of offering an affordable and convenient diagnosis tool for routine arterial health assessment.

Model-based analysis of arterial pulse signals for tracking changes in arterial wall parameters: a pilot study.

Arterial wall parameters (i.e., radius and viscoelasticity) are prognostic markers for cardiovascular diseases (CVD), but their current monitoring systems are too complex for home use. Our objective was to investigate whether model-based analysis of arterial pulse signals allows tracking changes in arterial wall parameters using a microfluidic-based tactile sensor. The sensor was used to measure an arterial pulse signal. A data-processing algorithm was utilized to process the measured pulse signal to obtain the radius waveform and its first-order and second-order derivatives, and extract their key features. A dynamic system model of the arterial wall and a hemodynamic model of the blood flow were developed to interpret the extracted key features for estimating arterial wall parameters, with no need of calibration. Changes in arterial wall parameters were introduced to healthy subjects ([Formula: see text]) by moderate exercise. The estimated values were compared between pre-exercise and post-exercise for significant difference ([Formula: see text]). The estimated changes in the radius, elasticity and viscosity were consistent with the findings in the literature (between pre-exercise and 1 min post-exercise: - 11% ± 4%, 55% ± 38% and 28% ± 11% at the radial artery; - 7% ± 3%, 36% ± 28% and 16% ± 8% at the carotid artery). The model-based analysis allows tracking changes in arterial wall parameters using a microfluidic-based tactile sensor. This study shows the potential of developing a solution to at-home monitoring of the cardiovascular system for early detection, timely intervention and treatment assessment of CVD.

Correlation between stress drop and applied strain as a biomarker for tumor detection.

This is the first study to measure the viscoelastic behavior of tumor tissues using stepwise compression-relaxation testing, and investigate the measured (Δσ-ε) relation between stress drop (Δσ) and applied strain (ε) as a biomarker for tumor detection. Stepwise compression-relaxation testing was implemented via a 2D tactile sensor to measure stress drop at each applied strain of a sample. Pearson correlation analysis was conducted to quantify the measured Δσ-ε relation as slope of stress drop versus applied strain (m=Δσ/ε) and coefficient of determination (R2). The measured results on soft materials revealed no dependency of coefficient of determination on the testing parameters and dependency of slope on them. Three groups of tissues: five mouse breast tumor (BT) tissues ex vivo, two mouse pancreatic tumor (PT) tissues in vivo and six normal tissues, were measured by using different testing parameters. Coefficient of determination was found to show significant difference among the center, edge and outside sites of all the BT tissues, and no difference between the BT outside sites and the normal tissues. Coefficient of determination also revealed significant difference between before and after treatment of the PT tissues, and no difference between the PT tissues after treatment and the normal tissues. Moreover, coefficient of determination of the PT tissues before treatment was found to be significantly different from that of the BT center sites, but slope failed to capture their difference. Dummy tumors made of silicon rubbers were found to behave differently from the native tumors. By removing the need of fitting the time-dependent data with a viscoelastic model, this study offered a time-efficient solution to quantifying the viscosity for tumor detection.