Inhibition of Hypoxic Pulmonary Vasoconstriction of Rats by Carbon Monoxide

Hypoxic pulmonary vasoconstriction (HPV), a unique response of pulmonary circulation, is critical to prevent hypoxemia under local hypoventilation. Hypoxic inhibition of K+ channel is known as an important O2-sensing mechanism in HPV. Carbon monoxide (CO) is suggested as a positive regulator of Ca2+-activated K+ channel (BKCa), a stimulator of guanylate cyclase, and an O2-mimetic agent in heme moiety-dependent O2 sensing mechanisms. Here we compared the effects of CO on the HPV (Po2, 3%) in isolated pulmonary artery (HPVPA) and in blood-perfused/ventilated lungs (HPVlung) of rats. A pretreatment with CO (3%) abolished the HPVPA in a reversible manner. The inhibition of HPVPA was completely reversed by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. In contrast, the HPVlung was only partly decreased by CO. Moreover, the partial inhibition of HPVlung by CO was affected neither by the pretreatment with ODQ nor by NO synthase inhibitor (L-NAME). The CO-induced inhibitions of HPVPA and HPVlung were commonly unaffected by tetraethylammonium (TEA, 2 mM), a blocker of BKCa. As a whole, CO inhibits HPVPA via activating guanylate cyclase. The inconsistent effects of ODQ on HPVPA and HPVlung suggest that ODQ may lose its sGC inhibitory action when applied to the blood-containing perfusate

S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model

Inflammation, insoluble protein deposition and neuronal cell loss are important features in the Alzheimer's disease (AD) brain. To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APPV717I-CT100 transgenic mice, an animal model of AD, and isolated the S100a9 gene, which encodes an inflammation-associated calcium binding protein. In another AD animal model, Tg2576 mouse brain, and in human AD brain, induction of S100a9 was confirmed. The endogenous expression of S100a9 was induced by treatment with Aβ or CT peptides in a microglia cell line, BV2 cells. In these cells, silencing study of S100a9 showed that the induction of S100a9 increased the intracellular calcium level and up-regulated the inflammatory cytokines (IL-1β and TNFα) and iNOS. S100a9 lentiviral short hairpin RNA (sh-S100a9) was injected into the hippocampus region of the brains of 13-month-old Tg2576 mice. At two months after injection, we found that knockdown of S100a9 expression had improved the cognition decline of Tg2576 mice in the water maze task, and had reduced amyloid plaque burden. These results suggest that S100a9 induced by Aβ or CT contributes to cause inflammation, which then affects the neuropathology including amyloid plaques burden and impairs cognitive function. Thus, the inhibition of S100a9 is a possible target for AD therapy

Repression of FLOWERING LOCUS T Chromatin by Functionally Redundant Histone H3 Lysine 4 Demethylases in Arabidopsis

FLOWERING LOCUS T (FT) plays a key role as a mobile floral induction signal that initiates the floral transition. Therefore, precise control of FT expression is critical for the reproductive success of flowering plants. Coexistence of bivalent histone H3 lysine 27 trimethylation (H3K27me3) and H3K4me3 marks at the FT locus and the role of H3K27me3 as a strong FT repression mechanism in Arabidopsis have been reported. However, the role of an active mark, H3K4me3, in FT regulation has not been addressed, nor have the components affecting this mark been identified. Mutations in Arabidopsis thaliana Jumonji4 (AtJmj4) and EARLY FLOWERING6 (ELF6), two Arabidopsis genes encoding Jumonji (Jmj) family proteins, caused FT-dependent, additive early flowering correlated with increased expression of FT mRNA and increased H3K4me3 levels within FT chromatin. Purified recombinant AtJmj4 protein possesses specific demethylase activity for mono-, di-, and trimethylated H3K4. Tagged AtJmj4 and ELF6 proteins associate directly with the FT transcription initiation region, a region where the H3K4me3 levels were increased most significantly in the mutants. Thus, our study demonstrates the roles of AtJmj4 and ELF6 as H3K4 demethylases directly repressing FT chromatin and preventing precocious flowering in Arabidopsis

Analysis of differentially expressed long non-coding RNAs in LPS-induced human HMC3 microglial cells

Abstract Background Long non-coding RNAs (lncRNAs) are emerging as key modulators of inflammatory gene expression, but their roles in neuroinflammation are poorly understood. Here, we identified the inflammation-related lncRNAs and correlated mRNAs of the lipopolysaccharide (LPS)-treated human microglial cell line HMC3. We explored their potential roles and interactions using bioinformatics tools such as gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), and weighted gene co-expression network analysis (WGCNA). Results We identified 5 differentially expressed (DE) lncRNAs, 4 of which (AC083837.1, IRF1-AS1, LINC02605, and MIR3142HG) are novel for microglia. The DElncRNAs with their correlated DEmRNAs (99 total) fell into two network modules that both were enriched with inflammation-related RNAs. However, treatment with the anti-inflammatory agent JQ1, an inhibitor of the bromodomain and extra-terminal (BET) protein BRD4, neutralized the LPS effect in only one module, showing little or even enhancing effect on the other. Conclusions These results provide insight into, and a resource for studying, the regulation of microglia-mediated neuroinflammation and its potential therapy by small-molecule BET inhibitors

Ubiquitous-Severance Hospital Project: Implementation and Results

OBJECTIVES: The purpose of this study was to review an implementation of u-Severance information system with focus on electronic hospital records (EHR) and to suggest future improvements. METHODS: Clinical Data Repository (CDR) of u-Severance involved implementing electronic medical records (EMR) as the basis of EHR and the management of individual health records. EHR were implemented with service enhancements extending to the clinical decision support system (CDSS) and expanding the knowledge base for research with a repository for clinical data and medical care information. RESULTS: The EMR system of Yonsei University Health Systems (YUHS) consists of HP integrity superdome servers using MS SQL as a database management system and MS Windows as its operating system. CONCLUSIONS: YUHS is a high-performing medical institution with regards to efficient management and customer satisfaction; however, after 5 years of implementation of u-Severance system, several limitations with regards to expandability and security have been identifiedope

Occupational Rhinitis Induced by Capsaicin

Capsaicin is the spice component of red pepper. It can be easily inhaled, inducing a reproducible cough and provokes a secretory response from the human nasal mucosa. To date, there has been no report of occupational rhinitis (OR) caused by capsaicin. We report the case of a 44-year-old female mill worker who developed occupational rhinitis after 4 years of exposure to capsaicin. She developed nasal congestion, rhinorrhea, and itchy nose, which were all aggravated upon exposure at the workplace. The patient had negative responses to all common inhalant allergens, including capsaicin, by skin prick tests. The nasal provocation test with capsaicin showed that the nasal symptom score and eosinophil count increased 10 minutes after the provocation and decreased after 1 to 3 hours; no significant response was noted to house dust mite allergen. The patient's work-related rhinitis improved 1 month after she relocated and started pharmacological treatment. To our knowledge, this is the first case of OR caused by capsaicin exposure in the workplace. We provide evidence suggesting that OR may be mediated by a non-immunological mechanism

Association between use of hydrochlorothiazide and nonmelanoma skin cancer: Common data model cohort study in Asian population

Although hydrochlorothiazide (HCTZ) has been suggested to increase skin cancer risk in white Westerners, there is scant evidence for the same in Asians. We analyzed the association between the use of hydrochlorothiazide and non-melanoma in the Asian population using the common data model. METHODS: A retrospective multicenter observational study was conducted using a distributed research network to analyze the effect of HCTZ on skin cancer from 2004 to 2018. We performed Cox regression to evaluate the effects by comparing the use of HCTZ with other antihypertensive drugs. All analyses were re-evaluated using matched data using the propensity score matching (PSM). Then, the overall effects were evaluated by combining results with the meta-analysis. RESULTS: Positive associations were observed in the use of HCTZ with high cumulative dose for non-melanoma skin cancer (NMSC) in univariate analysis prior to the use of PSM. Some negative associations were observed in the use of low and medium cumulative doses. CONCLUSION: Although many findings in our study were inconclusive, there was a non-significant association of a dose-response pattern with estimates increasing in cumulative dose of HCTZ. In particular, a trend with a non-significant positive association was observed with the high cumulative dose of HCTZ

LOWER EXTREMITY KINEMATICS OF SKI MOTION ON HILLS

This research study aimed to collect thre- dimensional joint angles of the lower extremity during a basic ski motion in order to provide more quantitative teaching guide-lines for ski instructors. Eleven infrared cameras were placed to cover the capture volume of three different stopping movements (e.g. “Pflug Fahren”) on hills. Six ski instructors participated in the test. Three trials of each stop were selected for comparison. Based on the results, skiers tended to use the edge of the ski and maintain a wider “V” shape at the shortest stop distance (e.g. 2m) compared to the other stops. Also, each skier had to invert the foot with a less flexed and more abducted knee and hip position as the stopping distance was decreased. This information will be useful for the development of more objective teaching guide-lines for beginner skiers