Th17 Cells as Potential Probiotic Therapeutic Targets in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways. In recent years, it was shown that T helper 17 (Th17) cells are involved in the pathogenesis of IBD, which makes them an attractive therapeutic target. Th17 cells preferentially produce interleukin (IL)-17A–F as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD was demonstrated. Probiotics are live microorganisms that when orally ingested in adequate amounts, confer a health benefit to the host by modulating the enteric flora or by stimulating the local immune system. Several studies indicated the effectiveness of probiotics in preventing and treating IBD (ulcerative colitis, and Crohn’s disease). Furthermore, there is mounting evidence of probiotics selectively targeting the Th17 lineage in the prevention and management of inflammatory and autoimmune diseases such as IBD. This review highlights critical roles of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as a novel therapeutic approach for IBD through manipulation of Th17 cells. The potential molecular mechanisms by which probiotics modulate Th17 cells differentiation and production are also discussed.     

Apigenin-7-Glycoside Prevents LPS-Induced Acute Lung Injury via Downregulation of Oxidative Enzyme Expression and Protein Activation through Inhibition of MAPK Phosphorylation

Apigenin-7-glycoside (AP7Glu) with multiple biological activities is a flavonoid that is currently prescribed to treat inflammatory diseases such as upper respiratory infections. Recently, several studies have shown that its anti-inflammatory activities have been strongly linked to the inhibition of secretion of pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOs) and cyclooxygenase-2 (COX-2) induced through phosphorylation nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) pathways. Additionally, inflammation, which can decrease the activities of antioxidative enzymes (AOEs) is also observed in these studies. At the same time, flavonoids are reported to promote the activities of heme oxygenase-1 (HO-1) decreased by LPS. The purpose of this study was to assess these theories in a series of experiments on the suppressive effects of AP7Glu based on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and acute lung injury in mice in vivo. After six hours of lipopolysaccharide (LPS) stimulation, pulmonary pathological, myeloperoxidase (MPO) activity, total polymorphonuclear leukocytes (PMN) cells, cytokines in bronchoalveolar lavage fluid (BALF) and AOEs, are all affected and changed. Meanwhile, our data revealed that AP7Glu not only did significantly inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti-inflammatory effect through the MAPK and inhibitor NF-κB (IκB) pathways.     

Anti-influenza Drug Discovery: Identification of an Orally Bioavailable Quinoline Derivative through Activity- and Property-Guided Lead Optimization

From a high-throughput screening (HTS) hit with inhibitory activity against virus-induced cytophathic in the low micromolar range, we have developed a potent anti-influenza lead through careful optimization without compromising the drug-like properties of the compound. An orally bioavailable compound was identified as a lead agent with nanomolar activity against influenza, representing a 140-fold improvement over the initial hit.     

Thermal degradation analysis of the isocyanate polyhedral oligomeric silsequioxanes (POSS)/sulfone epoxy nanocomposite

The sulfone epoxy (SEP)/polyhedral oligomeric silsesquioxane (POSS) nanocomposite contains bulky POSS side chains was studied in this research. Its glass transition temperature (T_g) decreases with the bulky POSS content, indicating that the bulky POSS side chains could not only generate the oligomers but also interrupt the network architectures of SEP. Homogeneous and uniform dispersion of POSS in SEP matrix can be obtained through the carbamate/oxazolidon covalent linkage, which is evidenced by scanning electron microscopy. The increasing concentration of POSS into SEP exhibits an increase of char yield in the nanocomposites, indicating that the POSS segments provide the antithermal‐oxidation effect for SEP/POSS, thereby inhibiting thermal degradation under open air at high temperatures. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Roles of Nitric Oxide and Asymmetric Dimethylarginine in Pregnancy and Fetal Programming

Nitric oxide (NO) regulates placental blood flow and actively participates in trophoblast invasion and placental development. Asymmetric dimethylarginine (ADMA) can inhibit NO synthase, which generates NO. ADMA has been associated with uterine artery flow disturbances such as preeclampsia. Substantial experimental evidence has reliably supported the hypothesis that an adverse in utero environment plays a role in postnatal physiological and pathophysiological programming. Growing evidence suggests that the placental nitrergic system is involved in epigenetic fetal programming. In this review, we discuss the roles of NO and ADMA in normal and compromised pregnancies as well as the link between placental insufficiency and epigenetic fetal programming.     

Coarse-grained modeling of model poly(urethane urea)s: Microstructure and interface aspects

Poly(urethane urea) elastomers are versatile and can be tailored to exhibit a broad range of mechanical response under high strain rate deformation. In this work, we utilize coarse-grained molecular dynamics simulations to elucidate the molecular mechanisms, particularly the effects of hard segment content, intermolecular interaction, and rigidity of the interface between the hard and soft segments on local morphology and rate-dependent stress-strain behavior in the ballistic regime. Simulation results qualitatively agree with available experimental data, where analysis of hard segment orientation during tensile and compression deformation and dynamic strain rate sensitivity was also performed. Further study of the intermolecular interaction on the stress-strain behavior reveals that it has a strong effect on strain hardening, particularly for a rigid interface, once the hard segment content reaches the percolation threshold. Simulation results also show that interface intermolecular interaction could become more dominant over interface rigidity in the initial stress-strain response, particularly below percolation.     

Mechanistic Insights and Photodegradation of Heterostructure Graphene Oxide/Titanium Dioxide

Topics in Catalysis - In this study, the electrospinning method was used to prepare graphene oxide/titanium dioxide (GO/TiO2) nanofibers with different contents of GO as photocatalysts used to...     

Moisture sorption on the wetting behavior of poly(p-phenylene terephthalamide) fibers in water and epoxy resin

The moisture sorption of poly(p-phenylene terephthalamide) (PPTA) fibers and the effects of moisture on the wetting behavior of these fibers in water and in an epoxy resin were studied. The moisture regains in the Kevlar 149 fibers followed a third order polynomial dependency on increasing relative humidity at 23°C. When preconditioned at 0% relative humidity (R.H.), water wettability of Kevlar 49 fibers was superior to that of Kevlar 149 fibers. Resin wettability of the dried Kevlar 49 fibers, on the other hand, was lower than that of Kevlar 149 fibers. Wettability in water and resin of these two fiber types was affected differently by moisture. Exposure to 97% R.H. moisture level significantly lowered water wettability of Kevlar 49 fibers but did not affect the wettability of Kevlar 149 fibers in water. Resin wettability of Kevlar 49 fibers was improved upon exposure to moisture, but the opposite was observed on Kevlar 149 fibers.     

Influence of dietary long-chain PUFA on premature baboon lung FA and dipalmitoyl PC composition

One of the major survival challenges of premature birth is production of lung surfactant. The lipid component of surfactant, dipalmitoyl PC (DPPC), increases in concentration in the period before normal term birth via a net shift in FA composition away from unsaturates. We investigated the influence of dietary DHA and arachidonic acid (AA) on lung FA composition and DPPC concentration in term and preterm baboons. Pregnant animals/neonates were randomized to one of four groups: breast-fed (B), term formula-fed (T⁻), preterm formulafed (P⁻), and preterm fed formula supplemented with DHA-AA (P⁺). Breast milk contained 0.68%wt DHA and the P⁺ group formula contained 0.61%wt DHA. In the preterm groups (P⁻ and P⁺), pregnant females received a course of antenatal corticosteroids. At the adjusted age of 4 wk, neonate lung tissue was harvested, and FA composition and DPPC were analyzed. Palmitate was ∼28%wt of lung total FA and no significant differences were found among the four treatment groups. In contrast, DPPC in the B group lung tissue was significantly greater than DPPC in the unsupplemented groups, but not compared with the P⁺ group. The B and P⁺ groups were not significantly different in DHA and AA, but were different compared with the unsupplemented (T, P⁻) groups. These results indicate that LCP supplementation increases lung DHA and AA, without compromising overall lung 16∶0 or DPPC. The shift in FA composition toward greater unsaturation in the groups consuming LCP supported improved surfactant lipid concentration in preterm neonate lungs.     

Shrinkage and warpage prediction of injection‐molded thin‐wall parts using artificial neural networks

This study demonstrates the successful use of back‐propagation artificial neural networks (BPANNs) in predicting the shrinkage and warpage of injection‐molded thin‐wall parts. The effects of structural parameters of a BPANN on the predictionaccuracy and the capability of a BPANN in determining the optimal process condition are also discussed. The training and testing data are obtained experimentally based on a Taguchi L₂₇ (3¹³) test schedule. The results show that the trained BPANN can successfully predict the shrinkage and warpage of injection‐molded thin‐wall parts. Comparing the prediction accuracies of the trained BPANN and C‐Mold software, it is noted that the trained BPANN predicts more accurately. In terms of determining the optimal process condition for minimizing the shrinkage and warpage of injected thin‐wall parts, the trained BPANN is also shown to give a better optimal process condition than Taguchi's method. Polym. Eng. Sci. 44:2029–2040, 2004. © 2004 Society of Plastics Engineers.