Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

Xenopus: An alternative model system for identifying muco-active agents

The airway epithelium in human plays a central role as the first line of defense against environmental contaminants. Most respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, and respiratory infections, disturb normal muco-ciliary functions by stimulating the hypersecretion of mucus. Several muco-active agents have been used to treat hypersecretion symptoms in patients. Current muco-active reagents control mucus secretion by modulating either airway inflammation, cholinergic parasympathetic nerve activities or by reducing the viscosity by cleaving crosslinking in mucin and digesting DNAs in mucus. However, none of the current medication regulates mucus secretion by directly targeting airway goblet cells. The major hurdle for screening potential muco-active agents that directly affect the goblet cells, is the unavailability of in vivo model systems suitable for high-throughput screening. In this study, we developed a high-throughput in vivo model system for identifying muco-active reagents using Xenopus laevis embryos. We tested mucus secretion under various conditions and developed a screening strategy to identify potential muco-regulators. Using this novel screening technique, we identified narasin as a potential muco-regulator. Narasin treatment of developing Xenopus embryos significantly reduced mucus secretion. Furthermore, the human lung epithelial cell line, Calu-3, responded similarly to narasin treatment, validating our technique for discovering muco-active reagent

Extracellular matrixes and neuroinflammation

The extracellular matrix is a critical component of every human tissue. ECM not only functions as a structural component but also regulates a variety of cellular processes such as cell migration, differentiation, proliferation, and cell death. In addition, current studies suggest that ECM is critical for the pathophysiology of various human diseases. ECM is composed of diverse components including several proteins and polysaccharide chains such as chondroitin sulfate, heparan sulfate, and hyaluronic acid. Each component of ECM exerts its own functions in cellular and pathophysiological processes. One of the interesting recent findings is that ECM is involved in inflammatory responses in various human tissues. In this review, we summarized the known functions of ECM in neuroinflammation after acute injury and chronic inflammatory diseases of the central nerve systems

Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells

Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse beta-cell lines, human islets and CB1R-null (CB1R(-/-)) mice, we have now investigated the role of CB1Rs in modulating beta-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse beta-cell lines and human islets. In addition, silencing CB1R in mouse cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in cells lacking insulin receptor. Furthermore, CB1R(-/-) mice had increased pro-insulin, GCK and GLUT2 expression in cells. Our results suggest that CB1R signalling in pancreatic islets may be harnessed to improve beta-cell glucose responsiveness and preserve their function. Thus, our findings further support that blocking peripheral CB1Rs would be beneficial to beta-cell function in type 2 diabetes

Temporary bilateral sensorineural hearing loss following cardiopulmonary bypass -A case report-

Sudden sensorineural hearing loss has been reported to occur following anesthesia and various non-otologic surgeries, mostly after procedures involving cardiopulmonary bypass. Unilateral sensorineural hearing loss resulting from microembolism is an infrequent complication of cardiopulmonary bypass surgery that has long been acknowledged. Moreover, there are few reports on the occurrence of bilateral sensorineural hearing loss without other neurologic deficits and its etiology has also not been determined. We describe here a rare case of bilateral hearing loss without other neurologic deficits in an otherwise healthy 27-year-old woman who underwent cardiopulmonary bypass surgery for repair of severe mitral valve stenosis. The patient suffered from profound sensorineural hearing loss in both ears that was recognized immediately upon extubation, and audiometry tests confirmed the diagnosis. Without any treatment, her hearing recovered almost completely by the time of her discharge one week after surgery

The prophylactic use of recombinant factor VIIa in a patient with DeBakey type III aortic dissection -A case report-

Little is known about the prophylactic use of recombinant factor VIIa (rFVIIa) in patients undergoing surgery for a bleeding aorta employing cardiopulmonary bypass. We report the successful use of rFVIIa in a patient undergoing hypothermic circulatory arrest and prolonged cardiopulmonary bypass for repair of a DeBakey type III aortic dissection

Anesthetic considerations of percutaneous transcatheter aortic valve implantation: first attempt in Korea -A report of 2 cases-

Conventional aortic valve replacement for severe aortic stenosis is associated with a high operative mortality in the elderly patients with significant comorbidities, including severe respiratory dysfunction, renal insufficiency, and compromised cardiac function. Human transcatheter aortic valve implantation was first reported in 2002 and has become a valid alternative in selected high-risk patients in Europe and North America. This article describes the first attempt of transfemoral transcatheter aortic valve implantation in Korea. The procedure was applied in two consecutive patients with severe aortic stenosis. Despite several intra-operative complications during procedure, the post-operative outcomes were good for both patients. At post-operative 30 days there was satisfactory prosthetic valve function and hemodynamic stability

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Developing an alternative model system of muco-ciliary epithelium and the study of the ERAD function on chondrogenesis

Department of Biological SciencesXenopus laevis is a well-known model animal to study developmental biology. Hundreds of eggs can be easily obtained from a single female by ovulation using human chorionic gonadotrophin (HCG) hormone, and developing embryos can be synchronized by in vitro fertilization. Also, Xenopus laevis egg is relatively larger than other model animals such as drosophila, zebrafish, and mouse. Furthermore, gene expression can be simply manipulated by performing mRNA or morpholino microinjection. Recently, CRISPR/Cas9 -mediated mutagenesis has been widely used to generate an F0 mutant using Xenopus embryos. Moreover, the developmental process is relatively faster compared with other animal models such as mouse or rats. Due to these advantages, I preferentially used Xenopus laevis as a model animal to conduct my graduate research project. My graduate research has two main ideas. First, my research focuses on studying the pathophysiology of the muco-ciliary epithelium. Secondly, I researched craniofacial cartilage development. In muco-ciliary epithelium research, I revealed proteomes of ciliary subdomains, especially transition zone and ciliary axoneme. Also, I developed a high-throughput screening system to discover muco-active reagents. In craniofacial cartilage research, I demonstrated that the ERAD complex is critical for chondrogenesis and is one of the significant causes of osteoarthritis.clos