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Campylobacter jejuni is the leading cause of bacterial-derived gastroenteritis worldwide and can lead to several post-infectious inflammatory disorders. Despite the prevalence and health impacts of the bacterium, interactions between the host innate immune system and C. jejuni remain poorly understood. To expand on earlier work demonstrating that neutrophils traffic to the site of infection in an animal model of campylobacteriosis, we identified significant increases in several predominantly neutrophil-derived proteins in the feces of C. jejuni-infected patients, including lipocalin-2, myeloperoxidase, and neutrophil elastase. Selleck PD98059 In addition to demonstrating that these proteins significantly inhibited C. jejuni growth, we determined they are released during formation of C. jejuni-induced neutrophil extracellular traps (NETs). Using quantitative and qualitative methods, we found that purified human neutrophils are activated by C. jejuni and exhibit signatures of NET generation, including presence of protein arginine deiminase-4, histone citrullination, myeloperoxidase, neutrophil elastase release, and DNA extrusion. Production of NETs correlated with C. jejuni phagocytosis/endocytosis and invasion of neutrophils, suggesting that host- and bacterial-mediated activities are responsible for NET induction. Further, NET-like structures were observed within intestinal tissue of C. jejuni infected ferrets. Lastly, induction of NETs significantly increased human colonocyte cytotoxicity, indicating that NET formation during C. jejuni infection may contribute to observed tissue pathology. These findings provide further understanding of C. jejuni-neutrophil interactions and inflammatory responses during campylobacteriosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The efficient backbone-directed self-assembly of cyclic metalla[3]catenanes by the combination of tetrachloroperylenediimide (TCPDI)-based dinuclear rhodium(III) clips and 4,4'-diazopyridine or 4,4'-dipyridylethylene ligands is realized in a single-step strategy. The topology and coordination geometry of the cyclic metalla[3]catenanes are characterized by NMR spectroscopy, ESI-TOF-MS spectrometry, UV-vis-NIR spectroscopy and X-ray diffraction studies. The most remarkable feature of the formed cyclic metalla[3]catenane is that it contains π-aggregates (ca. 2.6 nm) incorporating six TCPDIs. Further studies revealed that cyclic metalla[3]catenanes can be converted reversibly to their corresponding sodium adducts and precursor building blocks, respectively. This strategy opens the possibility of generating unique supramolecular structures from discrete functional π-aggregates with precise arrangements. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Globus is a non-painful sensation of a tightness or a lump/foreign body in the throat that is not associated with dysphagia and may actually improve during meals. While several otorhinolaryngologic, thyroid, and esophageal disorders have been linked to globus, cause-and-effect relationships are difficult to establish. Consequently, though part of the evaluation, objective otorhinolaryngologic and esophageal testing is often negative. The presence of alarm symptoms, particularly pain, weight loss, dysphagia, or odynophagia is indications for objective testing. A diagnosis of idiopathic globus requires exclusion of pharyngeal, laryngeal, and esophageal disorders with laryngoscopy, endoscopy, high-resolution manometry, barium radiography, and/or ambulatory reflux monitoring. A trial of acid-suppressive therapy may be reasonable in the absence of alarm symptoms, especially if concurrent reflux symptoms are identified. Ablation of heterotopic gastric mucosa in the proximal esophagus has been reported to improve globus symptoms. Beyond these specific approaches, further management of idiopathic globus consists of reassurance, neuromodulators, and complementary approaches. Globus has a benign course with no long-term consequences, and the overall prognosis is good as the magnitude of symptoms may decline over time. © 2020 John Wiley & Sons Ltd.In this study, an adjustable pH-responsive drug delivery system using mesoporous silica nanoparticles (MSNs) as the host materials and the modified polypeptides as the nanovalves is reported. Since the polypeptide can self-assemble via electrostatic interaction at pH 7.4 and be disassembled by pH changes, the modified poly(l-lysine) and poly(l-glutamate) are utilized for pore blocking and opening in the study. Poly(l-lysine)-MSN (PLL-MSN) and poly(l-glutamate)-MSN (PLG-MSN) are synthesized via the ring opening polymerization of N-carboxyanhydrides onto the surface of mesoporous silica nanoparticles. The successful modification of the polypeptide on MSN is proved by Zeta potential change, X-ray photoelectron spectroscopy (XPS), solid state NMR, and MALDI-TOF MS. In vitro simulated dye release studies show that PLL-MSN and PLG-MSN can successfully load the dye molecules. The release study shows that the controlled release can be constructed at different pH by adjusting the ratio of PLL-MSN to PLG-MSN. Cellular uptake study indicates that the drug is detected in both cytoplasm and nucleus, especially in the nucleus. In vitro cytotoxicity assay indicates that DOX loaded mixture nanoparticles (ratio of PLL-MSN to PLG-MSN is 11) can be triggered for drug release in HeLa cells, resulting in 88% of cell killing. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Interventions and small molecules, which promote formation of reactive oxygen species (ROS), have repeatedly been shown to increase stress resistance and lifespan of different model organisms. These phenotypes occur only in response to low concentrations of ROS, while higher concentrations exert opposing effects. This non-linear or hormetic dose-response relationship has been termed mitohormesis, since ROS are mainly generated within the mitochondrial compartment. A report by Matsumura et al in this issue of EMBO Reports now demonstrates that an endogenously formed metabolite, namely N-acetyl-L-tyrosine (NAT), is instrumental in promoting cellular and organismal resilience by inducing mitohormetic mechanisms, likely in an evolutionarily conserved manner [1]. © 2020 The Authors.
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