Engraftment of Human Stem Cell-Derived Otic Progenitors in the Damaged Cochlea

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Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity

Neomycin ototoxicity and electrode insertion trauma both involve activation of the mitogen activated protein kinase (MAPK)/c-Jun-N-terminal kinase (JNK) cell death signal cascade. This article discusses mechanisms of cell death on a cell biology level (e.g. necrosis and apoptosis) and proposes the blocking of JNK signaling as a therapeutic approach for preventing the development of a permanent hearing loss that can be initiated by either neomycin ototoxicity or electrode insertion trauma. Blocking of JNK molecules incorporates the use of a peptide inhibitor (i.e. D-JNKI-1), which is specific for all three isoforms of JNK and has been demonstrated to prevent loss of hearing following either electrode insertion trauma or loss of both hearing and hair cells following exposure to an ototoxic level of neomycin. We present previously unpublished results that control for the effect of perfusate washout of aminoglycoside antibiotic by perfusion of the scala tympani with an inactive form of D-JNKI-1 peptide, i.e. JNKI-1(mut) peptide, which was not presented in the original J. Neurosci. article that tested locally delivered D-JNKI-1 peptide against both noise- and neomycin-induced hearing loss (i.e. Wang, J., Van De Water, T.R., Bonny, C., de Ribaupierre, F., Puel, J.L., Zine, A. 2003a. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J. Neurosci. 23, 8596-8607). D-JNKI-1 is a cell permeable peptide that blocks JNK signaling at the level of the three JNK molecular isoforms, which when blocked prevents the increases in hearing thresholds and the loss of auditory hair cells. This unique therapeutic approach may have clinical application for preventing: (1) hearing loss caused by neomycin ototoxicity; and (2) the progressive component of electrode insertion trauma-induced hearing loss.     

Antibacterial, antioxidant and cytotoxic activities of extracts of Conyza canadensis (L.) Cronquist growing in Tunisia

Antibacterial antioxidant and cytotoxic activities of petroleum ether, ethyl acetate and methanol extracts of Conyza Canadensis (L.) Cronquist were investigated. Antibacterial activity was evaluated using the agar diffusion and microwell dilution assays against four strains of bacteria. Antioxidant activity was measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and the cytotoxic activity was tested against Hep-2 cells (laryngeal carcinoma cell line) using methylene blue assays. Among tested extracts, the methanolic extract exhibited important antibacterial activity. It also showed good antioxidant activity with 50% inhibition concentration (IC₅₀) of 120 μg/ml. Cytotoxicity of extracts was time depend, increasing with exposure time and concentration. At 72 h of incubation, the ethyl acetate and petroleum ether extracts demonstrated effective cytotoxic activity against Hep-2 cells with IC₅₀ values of 45 and 50 μg/ml, respectively.     

Chemical composition and antimicrobial activity of extracts from Gliocladium sp. growing wild in Tunisia

The chemical composition of chloroformic, ethyl acetate, butanolic, and methanolic extracts isolated from the fungus Gliocladium sp. using different solvents of increasing polarity was analyzed by GC-FID and GC-MS. Furthermore, the antimicrobial activity of extracts was tested against five Gram-positive and Gram-negative bacteria and four pathogenic fungi. The tested extracts exhibited an interesting antibacterial activity against all bacteria tested, even against Gram-negative bacteria presenting frequently a higher resistance and against all fungi except Candida albicans.     

Modelling the spatial distribution of five natural hazards in the context of the WHO/EMRO Atlas of Disaster Risk as a step towards the reduction of the health impact related to disasters

Background  

Reducing the potential for large scale loss of life, large numbers of casualties, and widespread displacement of populations that can result from natural disasters is a difficult challenge for the individuals, communities and governments that need to respond to such events.     

Study of Swallowing Sound at the Esophagogastric Junction Before and After Fundoplication

Introduction  Swallowing sounds can be heard in the lower esophagus by xiphoid auscultation. We hypothesize that the xiphoid sound analysis could provide information concerning the integrity of the esophagogastric junction (EGJ), i.e., superposition of the lower esophageal sphincter (LES) and the diaphragm to assess clinical diagnosis of gastroesophageal reflux disease (GERD) and results of Nissen fundoplication (NF). The aim was to evaluate the changes in sound parameters using our acoustic technique after reorganization of the EGJ after NF. Methods  For 21 patients with GERD and hiatus hernia, two microphones were placed below the cricoid and on the xiphoid cartilages. The frequency and duration of xiphoid sounds, esophageal transit time were calculated. We defined the xiphoid sound as composed of vibration groups separated by periods >100 ms. The number of vibration groups, number of vibrations per group, and interval between groups were also calculated. Results  The xiphoid sound frequency was increased after NF, and the esophageal transit time and xiphoid sound duration were significantly decreased. A significant correlation was found between xiphoid sound duration and LES–diaphragm displacement. The number of vibration groups and interval between groups were reduced after NF. Conclusion  The acoustic technique for swallowing revealed the effects of NF upon the dynamic profile of the EGJ. The organization of vibration groups at the EGJ suggested that the passage of the bolus was modified by hiatus hernia, i.e., dissociation between the LES and the diaphragm and regularized by NF. Concomitant acoustic and radiologic study should contribute to better understanding of sound related to EGJ structure and boli.     

Culture conditions have an impact on the maturation of traceable,transplantable mouse embryonic stem cell‐derived otic progenitor cells

The generation of replacement inner ear hair cells (HCs) remains a challenge and stem cell therapy holds the potential for developing therapeutic solutions to hearing and balance disorders. Recent developments have made significant strides in producing mouse otic progenitors using cell culture techniques to initiate HC differentiation. However, no consensus has been reached as to efficiency and therefore current methods remain unsatisfactory. In order to address these issues, we compare the generation of otic and HC progenitors from embryonic stem (ES) cells in two cell culture systems: suspension vs. adherent conditions. In the present study, an ES cell line derived from an Atoh1‐green fluorescent protein (GFP) transgenic mouse was used to track the generation of otic progenitors, initial HCs and to compare these two differentiation systems. We used a two‐step short‐term differentiation method involving an induction period of 5 days during which ES cells were cultured in the presence of Wnt/transforming growth factor TGF‐β inhibitors and insulin‐like growth factor IGF‐1 to suppress mesoderm and reinforce presumptive ectoderm and otic lineages. The generated embryoid bodies were then differentiated in medium containing basic fibroblast growth factor (bFGF) for an additional 5 days using either suspension or adherent culture methods. Upon completion of differentiation, quantitative polymerase chain reaction analysis and immunostaining monitored the expression of otic/HC progenitor lineage markers. The results indicate that cells differentiated in suspension cultures produced cells expressing otic progenitor/HC markers at a higher efficiency compared with the production of these cell types within adherent cultures. Furthermore, we demonstrated that a fraction of these cells can incorporate into ototoxin‐injured mouse postnatal cochlea explants and express MYO7A after transplantation. Copyright © 2016 John Wiley & Sons, Ltd.