Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complicated inflammatory disease, and the underlying mechanism remains unclear. While some reactive oxygen/nitrogen species-related gene products are reported to participate in CRSwNP, a systemic and full analysis of oxidative-stress-associated genes in CRSwNP has not been extensively studied. Therefore, this study sought to catalog the gene-expression patterns related to oxidative stress and antioxidant defense in control and CRSwNP patients. In total, 25 control and 25 CRSwNP patients were recruited. The distribution and expression of 4-hydroxynonenal and 3-nitrotyrosine as markers of oxidative stress—which is represented by lipid peroxidation and the protein nitration of tyrosine residues in CRSwNP nasal polyps (NPs)—were more apparently increased than those found in the control nasal mucosae, as determined by immunohistochemistry (IHC). The expression of 84 oxidative-stress-related genes in nasal mucosae and NP tissues was analyzed via real-time PCR, which showed that 19 genes and 4 genes were significantly up- and downregulated, respectively; among them, inducible nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) were notably upregulated, whereas lactoperoxidase (LPO), myeloperoxidase (MPO), and superoxide dismutase 3 (SOD3) were highly downregulated. Changes in the mRNA and protein levels of these redox proteins were confirmed with a customized, real-time PCR array and RT-PCR analysis, as well as Western blotting and IHC assays. A receiver operating characteristic curve analysis further suggested that LPO, MPO, SOD3, HO-1, and iNOS are possible endotype predictors of CRSwNP development. Collectively, we present an oxidative-stress-related gene profile of CRSwNP NP tissues, providing evidence that the systemic changes in oxidative stress and the antioxidative defense system, including novel iNOS, heme peroxidases, and other genes, are closely linked to CRSwNP pathology, development, and progression.

Background: Traumatic brain injury (TBI) causes axon tearing and synapse degradation, resulting in multiple neurological dysfunctions and exacerbation of early neurodegeneration; the repair of axonal and synaptic structures is critical for restoring neuronal function. C-C Motif Chemokine Ligand 5 (CCL5) shows many neuroprotective activities. Method: A close-head weight-drop system was used to induce mild brain trauma in C57BL/6 (wild-type, WT) and CCL5 knockout (CCL5-KO) mice. The mNSS score, rotarod, beam walking, and sticker removal tests were used to assay neurological function after mTBI in different groups of mice. The restoration of motor and sensory functions was impaired in CCL5-KO mice after one month of injury, with swelling of axons and synapses from Golgi staining and reduced synaptic proteins-synaptophysin and PSD95. Administration of recombinant CCL5 (Pre-treatment: 300 pg/g once before injury; or post-treatment: 30 pg/g every 2 days, since 3 days after injury for 1 month) through intranasal delivery into mouse brain improved the motor and sensory neurological dysfunctions in CCL5-KO TBI mice. Results: Proteomic analysis using LC-MS/MS identified that the “Nervous system development and function”-related proteins, including axonogenesis, synaptogenesis, and myelination signaling pathways, were reduced in injured cortex of CCL5-KO mice; both pre-treatment and post-treatment with CCL5 augmented those pathways. Immunostaining and western blot analysis confirmed axonogenesis and synaptogenesis related Semaphorin, Ephrin, p70S6/mTOR signaling, and myelination-related Neuregulin/ErbB and FGF/FAK signaling pathways were up-regulated in the cortical tissue by CCL5 after brain injury. We also noticed cortex redevelopment after long-term administration of CCL5 after brain injury with increased Reelin positive Cajal-Rerzius Cells and CXCR4 expression. CCL5 enhanced the growth of cone filopodia in a primary neuron culture system; blocking CCL5’s receptor CCR5 by Maraviroc reduced the intensity of filopodia in growth cone and also CCL5 mediated mTOR and Rho signalling activation. Inhibiting mTOR and Rho signaling abolished CCL5 induced growth cone formation. Conclusions: CCL5 plays a critical role in starting the intrinsic neuronal regeneration system following TBI, which includes growth cone formation, axonogenesis and synaptogensis, remyelination, and the subsequent proper wiring of cortical circuits. Our study underscores the potential of CCL5 as a robust therapeutic stratagem in treating axonal injury and degeneration during the chronic phase after mild brain injury. Graphical

Objective: To investigate the efficacy of intratympanic steroid therapy in adults with sudden sensorineural hearing loss, and to analyse the factors associated with treatment outcome.Design: Retrospective study of patients undergoing intratympanic steroid injection for sudden sensorineural hearing loss between 1 January 2006 and 30 June 2007 at a teaching hospital in Taipei, Taiwan.Results: Patients who received intratympanic steroid therapy within seven days of disease onset achieved a significantly better response rate (76.1 per cent), compared with the delayed treatment group (50 per cent). The total response rate, after four steroid injections, was 68.9 per cent. Patients with low and mid-frequency hearing loss were more responsive to steroid treatment. Vertigo was a negative prognostic factor for recovery. There were no long-term sequelae of intratympanic steroid treatment.Conclusion: Intratympanic steroid injection may be a simple and effective treatment for patients with sudden sensorineural hearing loss.

Background: Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that a carotenoid, lycopene, can directly bind to PDGF and affect its related functions in VSMCs. In this study we examined the effect of the other naturally occurring carotenoid, lutein, on PDGF signaling and migration in VSMCs. Methods: Western blotting was performed to examine PDGF and H₂O₂ signaling. Flowcytometry was used to determine PDGF binding to VSMCs. Fluorescence microscopy was performed to examine intracellular ROS production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay. Results: Lutein reduced PDGF signaling, including phosphorylation of PDGFR-β and its downstream protein kinases/enzymes such as phospholipase C-γ, Akt, and mitogen-activated protein kinases (MAPKs). Although lutein possesses a similar structure to lycopene, it was striking that lutein inhibited PDGF signaling through a different way from lycopene in VSMCs. Unlike lycopene, lutein not only interacted with (bound to) PDGF but also interfered with cellular components. This was evidenced that preincubation of PDGF with lutein and treatment of VSMCs with lutein followed by removing of lutein compromised PDGF-induced signaling. Lutein reduced PDGF-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H₂O₂-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H₂O₂-induced PDGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that lutein functionally inhibited PDGF-induced VSMC migration, whereas its stereo-isomer zeaxanthin did not, revealing a special action of lutein on VSMCs. Conclusions: Our study reveals a differential action mechanism of lutein from other reported caroteinoids and suggests a possible beneficial effect of lutein but not zeaxanthin on prevention of vascular diseases.