Viruses are frequently found in the airway of patients with pneumonia requiring ICU admission and may cause severe forms of pneumonia. Patients with viral infection and bacterial infection had comparable mortality rates.
Here we identify a novel class of biological membrane ion channel blockers called single-walled carbon nanotubes (SWNTs). SWNTs with diameter distributions peaked at ϳ0.9 and 1.3 nm, C 60 fullerenes, multi wall nanotubes (MWNTs), and hyperfullerenes (nano-"onions") were synthesized by several techniques and applied to diverse channel types heterologously expressed in mammalian cells. External as-fabricated and purified SWNTs blocked K ؉ channel subunits in a dose-dependent manner. Blockage was dependent on the shape and dimensions of the nanoparticles used and did not require any electrochemical interaction. SWNTs were more effective than the spherical fullerenes and, for both, diameter was the determining factor. These findings postulate new uses for SWNTs in biological applications and provide unexpected insights into the current view of mechanisms governing the interaction of ion channels with blocking molecules.Because of the physiological role they play, ion channels exhibit unique structures, including the pore that provides the physical pathway for ion movements across the plasma membrane and several charged domains that attract and/or repel ions (1). These characteristics make ion channels easy targets for external agents such as natural toxins and synthetic drugs that react with them by establishing electrochemical interactions. Thus, blocking agents have been used not only as the basic components for commercial pesticides and potential therapeutic drugs but also to infer functional information (1).The identification of new classes of molecules to target ionchannels is of significant interest in biological research, and, therefore, we sought to explore the possibility of using novel materials such as selected single-walled carbon nanotubes (SWNTs), 1 as ion channel blockers. In recent years there have been several attempts to use nanotubes for biological purposes because of their unique mechanical, chemical, and electrical properties (2). For example, nanotubes have been successfully used for the helical crystallization of proteins (3) and the growth of embryonic rat brain neurons (4) and as potential biosensors and bioreactors (5, 6). Here we show that SWNTs of certain diameters can efficiently block K ϩ channels. MATERIALS AND METHODSNanotubes and Fullerene Synthesis-SWNTs, with a diameter distribution peaked in the 0.8 -0.9 nm range, were grown by chemical vapor deposition (CVD) in a horizontal tube reactor using a three-stage process. In the first stage, the catalyst/support system was obtained via wet mixing followed by combustive calcination. Magnesium nitrate hexahydrate, cobalt nitrate hexahydrate, ammonium heptamolybdate tetrahydrate, and citric acid (the latter to induce combustion) were mixed with enough distilled water to give a clear solution, which was heated to 550°C for 5-10 min in air. The resulting powder of general composition MgO (1-x-y) Co x Mo y (where nanoscale Co-Mo is the catalyst in a typical molybdenum/cobalt atomic ratio of 1:4, and MgO is the catalyst support) was taken out,...
PurposeThe aim of this study is to report on preliminary data regarding the prevalence of major eye diseases in Korea.MethodsWe obtained data from the Korea National Health and Nutrition Examination Survey, a nation-wide cross-sectional survey and examinations of the non-institutionalized civilian population in South Korea (n = 14,606), conducted from July 2008 to December 2009. Field survey teams included an ophthalmologist, nurses, and interviewers, traveled with a mobile examination unit and performed interviews and ophthalmologic examinations.ResultsThe prevalence of visual impairment, myopia, hyperopia and astigmatism in participants over 5 years of age was 0.4 ± 0.1%, 53.7 ± 0.6%, 10.7 ± 0.4%, and 58.0 ± 0.6%, respectively. The prevalence of strabismus and blepharoptosis in participants over 3 years of age was 1.5 ± 0.1% and 11.0 ± 0.8%, respectively. In participants over 40 years of age, the prevalence of cataract, pterygium, early and late age-related macular degeneration, diabetic retinopathy and glaucoma was 40.2 ± 1.3%, 8.9 ± 0.5%, 5.1 ± 0.3%, 0.5 ± 0.1%, 13.4 ± 1.5%, and 2.1 ± 0.2%, respectively.ConclusionsThis is the first nation-wide epidemiologic study conducted in South Korea for assessment of the prevalence of eye diseases by both the Korean Ophthalmologic Society and the Korea Center for Disease Control and Prevention. This study will provide preliminary information for use in further investigation, prevention, and management of eye diseases in Korea.
Although melatonin has a variety of biological actions such as antitumor, antiangiogenic, and antioxidant activities, the osteogenic mechanism of melatonin still remains unclear. Thus, in the present study, the molecular mechanism of melatonin was elucidated in the differentiation of mouse osteoblastic MC3T3-E1 cells. Melatonin enhanced osteoblastic differentiation and mineralization compared to untreated controls in preosteoblastic MC3T3-E1 cells. Also, melatonin increased wound healing and dose-dependently activated osteogenesis markers such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN), bone morphogenic protein (BMP)-2 and -4 in MC3T3-E1 cells. Of note, melatonin activated Wnt 5 α/β, β-catenin and the phosphorylation of c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a time-dependent manner while it attenuated phosphorylation of glycogen synthase kinase 3 beta (GSK-3β) in MC3T3-E1 cells. Consistently, confocal microscope observation revealed that BMP inhibitor Noggin blocked melatonin-induced nuclear localization of β-catenin. Furthermore, Western blotting showed that Noggin reversed activation of β-catenin and Wnt5 α/β and suppression of GSK-3β induced by melatonin in MC3T3-E1 cells, which was similarly induced by ERK inhibitor PD98059. Overall, these findings demonstrate that melatonin promotes osteoblastic differentiation and mineralization in MC3T3-E1 cells via the BMP/ERK/Wnt pathways.
Resistin secreted from macrophages may contribute to atherogenesis by virtue of its effects on vascular endothelial cells and smooth muscle cells in humans.
Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by genetic mutations that lead to the disruption of dystrophin in muscle fibers. There is no curative treatment for this devastating disease. Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) has emerged as a powerful tool for genetic manipulation and potential therapy. Here we demonstrate that CRIPSR-mediated genome editing efficiently excised a 23-kb genomic region on the X-chromosome covering the mutant exon 23 in a mouse model of DMD, and restored dystrophin expression and the dystrophin-glycoprotein complex at the sarcolemma of skeletal muscles in live mdx mice. Electroporation-mediated transfection of the Cas9/gRNA constructs in the skeletal muscles of mdx mice normalized the calcium sparks in response to osmotic shock. Adenovirus-mediated transduction of Cas9/gRNA greatly reduced the Evans blue dye uptake of skeletal muscles at rest and after downhill treadmill running. This study provides proof evidence for permanent gene correction in DMD.
Background and Purpose-MicroRNAs (miRNA) are single-stranded short RNA molecules that regulate gene expression by either degradation or translational repression of mRNA. Although miRNAs control a number of conditions and diseases, few neuroprotective miRNAs have been described. In this study, we investigated neuroprotective miRNAs induced early in ischemic preconditioning. Methods-Ischemic preconditioning or focal cerebral ischemia was induced in mice by transient occlusion of the middle cerebral artery for 15 or 120 minutes. We prepared RNA samples from the ischemic cortex at 3 or 24 hours after the onset of ischemia. Selective miRNAs then were synthesized and transfected into Neuro-2a cells before oxygen-glucose deprivation. Results-We detected a total of 360 miRNAs. Two miRNA families, miR-200 and miR-182, were selectively upregulated at 3 hours after ischemic preconditioning. Transfections of some of these were neuroprotective in in vitro ischemia. Among them, miR-200b, miR-200c, and miR-429 targeted prolyl hydroxylase 2 and had the best neuroprotective effect. Conclusion-Two miRNA families, miR-200 and miR-182, were upregulated early after ischemic preconditioning and the miR-200 family was neuroprotective mainly by downregulating prolyl hydroxylase 2 levels. These miRNAs may be useful in future research and therapeutic applications. (Stroke. 2010;41:1646-1651.)
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