Proteomic and biochemical analyses reveal the activation of unfolded protein response, ERK-1/2 and ribosomal protein S6 signaling in experimental autoimmune myocarditis rat model

<p>Abstract</p> <p>Background</p> <p>To investigate the molecular and cellular pathogenesis underlying myocarditis, we used an experimental autoimmune myocarditis (EAM)-induced heart failure rat model that represents T cell mediated postinflammatory heart disorders.</p> <p>Results</p> <p>By performing unbiased 2-dimensional electrophoresis of protein extracts from control rat heart tissues and EAM rat heart tissues, followed by nano-HPLC-ESI-QIT-MS, 67 proteins were identified from 71 spots that exhibited significantly altered expression levels. The majority of up-regulated proteins were confidently associated with unfolded protein responses (UPR), while the majority of down-regulated proteins were involved with the generation of precursor metabolites and energy metabolism in mitochondria. Although there was no difference in AKT signaling between EAM rat heart tissues and control rat heart tissues, the amounts and activities of extracellular signal-regulated kinase (ERK)-1/2 and ribosomal protein S6 (rpS6) were significantly increased. By comparing our data with the previously reported myocardial proteome of the Coxsackie viruses of group B (CVB)-mediated myocarditis model, we found that UPR-related proteins were commonly up-regulated in two murine myocarditis models. Even though only two out of 29 down-regulated proteins in EAM rat heart tissues were also dysregulated in CVB-infected rat heart tissues, other proteins known to be involved with the generation of precursor metabolites and energy metabolism in mitochondria were also dysregulated in CVB-mediated myocarditis rat heart tissues, suggesting that impairment of mitochondrial functions may be a common underlying mechanism of the two murine myocarditis models.</p> <p>Conclusions</p> <p>UPR, ERK-1/2 and S6RP signaling were activated in both EAM- and CVB-induced myocarditis murine models. Thus, the conserved components of signaling pathways in two murine models of acute myocarditis could be targets for developing new therapeutic drugs or methods aimed at treating enigmatic myocarditis.</p

Dual Therapy with Cidofovir and Mirtazapine for Progressive Multifocal Leukoencephalopathy in a Sarcoidosis Patient

Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease caused by JC virus (JCV) reactivation in immunocompromised patients. The disease course of PML is often progressive, fatal and at present, there are few reports on successful treatment outcomes. Case Report: A 45-year-old man with systemic sarcoidosis presented with rapidly progressive dementia and right hemiparesis. The patient was diagnosed with PML as confirmed via brain biopsy and JCV PCR. With a combination treatment of cidofovir and mirtazapine, there was significant improvement of neurological symptoms without measurable functional deficit. Conclusion: This case suggests that dual therapy with cidofovir and mirtazapine might be an effective treatment option in PML patients with sarcoidosis

Basic Fibroblast Growth Factor Activates MEK/ERK Cell Signaling Pathway and Stimulates the Proliferation of Chicken Primordial Germ Cells

BACKGROUND: Long-term maintenance of avian primordial germ cells (PGCs) in vitro has tremendous potential because it can be used to deepen our understanding of the biology of PGCs. A transgenic bioreactor based on the unique migration of PGCs toward the recipients' sex cord via the bloodstream and thereby creating a germline chimeric bird has many potential applications. However, the growth factors and the signaling pathway essential for inducing proliferation of chicken PGCs are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Therefore, we conducted this study to investigate the effects of various combinations of growth factors on the survival and proliferation of PGCs under feeder-free conditions. We observed proliferation of PGCs in media containing bFGF. Subsequent characterization confirmed that the cultured PGCs maintained expression of PGC-specific markers, telomerase activity, normal migrational activity, and germline transmission. We also found that bFGF activates the mitogen-activated protein kinase kinase/extracellular-signal regulated kinase (MEK/ERK) signaling. Also, the expression of 133 transcripts was reversibly altered by bFGF withdrawal. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that chicken PGCs can be maintained in vitro without any differentiation or dedifferentiation in feeder free culture conditions, and subsequent analysis revealed that bFGF is one of the key factors that enable proliferation of chicken PGCs via MEK/ERK signaling regulating downstream genes that may be important for PGC proliferation and survival

Assessment of Allergic Rhinitis Websites in Korea

Objectives. The internet has become an important source of medical information and a great amount of information related to allergic rhinitis (AR) is available on the internet. However, the quality of this information is still a matter of debate. Therefore, this study was conducted to assess the AR-related information on Korean websites. Methods. The key word "allergic rhinitis" was entered into 4 popular search engines, and this led to identifying 40 websites. After being categorized according to authorship, the informational value of these websites was evaluated using 4 different assessment tools such as the Journal of the American Medical Association (JAMA) benchmarks, the DISCERN questionnaire, the Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 Update and the Health On the Net (HON) code. Results. The 40 websites containing AR-related information were categorized according to their authorship as Western physician: 20, Oriental physician: 14, commercial: 1, and others: 5. The mean citation frequencies of the JAMA benchmarks and the ARIA 2008 Update concepts was 1.23 out of 4 and 4.33 out of 8, respectively, while the mean DISCERN score was 1.92 out of 5. When the websites were evaluated based on the type of authorship, the mean citation frequencies of the AMA 2008 Update concepts were Western physician: 5.35, Oriental physician: 2.64. Additionally, three websites authored by Western physicians and 13 authored by Oriental physicians contained unreliable information. Among these 16 websites, only 3 websites met the requirements for the HON code "Justification". Conclusion. AR-related information available on Korean websites is of variable quality and not all of the information provided is justifiable. Thus, performing surveillance of the medical information on these websites is necessary. Furthermore, common criteria that can be used to evaluate the websites created by both Western and Oriental physicians are also needed.Bousquet J, 2008, ALLERGY, V63, P8*HLTH NET FDN, 2006, HLTH NET COD COND VESILVA LVE, 2005, BRAZILIAN J OTHORHIN, V71, P590Park HW, 2004, J KOREAN MED SCI, V19, P364Winker MA, 2000, JAMA-J AM MED ASSOC, V283, P1600Charnock D, 1999, J EPIDEMIOL COMMUN H, V53, P105Silberg WM, 1997, JAMA-J AM MED ASSOC, V277, P1244

The Effect of 1,8-Cineole Inhalation on Preoperative Anxiety: A Randomized Clinical Trial

The aim of this study was to investigate the effect of inhalation of eucalyptus oil and its constituents on anxiety in patients before selective nerve root block (SNRB). This study was a randomized controlled trial carried out in 62 patients before SNRB. The patients were randomized to inhale limonene, 1,8-cineole, or eucalyptus oil, each at concentrations of 1% vol/vol in almond oil or almond oil (control). Anxiety-visual analog scale (A-VAS), state-trait anxiety inventory (STAI), profile of mood states (POMS), pain-visual analog scale (P-VAS), blood pressure, and pulse rate were measured before and after inhalation prior to SNRB. Measures of anxiety, including A-VAS (P<0.001), STAI (P=0.005), and POMS (P<0.001), were significantly lower in 1,8-cineole than in the control group and significantly greater in 1,8-cineole than in the eucalyptus group in A-VAS. P-VAS was significantly lower after than before inhalation of limonene, 1,8-cineole, and eucalyptus, despite having no significant difference in the four groups compared with control group. 1,8-Cineole, a major constituent of eucalyptus, was effective in decreasing anxiety before SNRB. The present findings suggest that inhalation of 1,8-cineole may be used to relieve anxiety before, during, and after various operations, in addition to SNRB

Reliable Multivalued Conductance States in TaOx, Memristors through Oxygen Plasma-Assisted Electrode Deposition with in Situ-Biased Conductance State Transmission Electron Microscopy Analysis

Transition metal oxide-based memristors have widely been proposed for applications toward artificial synapses. In general, memristors have two or more electrically switchable stable resistance states that device researchers see as an analogue to the ion channels found in biological synapses. The mechanism behind resistive switching in metal oxides has been divided into electrochemical metallization models and valence change models. The stability of the resistance states in the memristor vary widely depending on: oxide material, electrode material, deposition conditions, film thickness, and programming conditions. So far, it has been extremely challenging to obtain reliable memristors with more than two stable multivalued states along with endurances greater than similar to 1000 cycles for each of those states. Using an oxygen plasma-assisted sputter deposition method of noble metal electrodes, we found that the metal-oxide interface could be deposited with substantially lower interface roughness observable at the nanometer scale. This markedly improved device reliability and function, allowing for a demonstration of memristors with four completely distinct levels from similar to 6 x 10(-6) to similar to 4 x 10(-8) S that were tested up to 10(4) cycles per level. Furthermore through a unique in situ transmission electron microscopy study, we were able to verify a redox reaction-type model to be dominant in our samples, leading to the higher degree of electrical state controllability. For solid-state synapse applications, the improvements to electrical properties will lead to simple device structures, with an overall power and area reduction of at least 1000 times when compared to SRAM.11Ysciescopu

Dokaz protutijela protiv velikog metilja Fasciola hepatica u goveda na otoku Ulleung, Koreja.

We performed a cross-sectional study to estimate the seroprevalence of Fasciola hepatica in herds of cattle on Ulleung island, Korea. Blood samples were collected from randomly selected cattle and the sera were separated and analysed with an ELISA to detect antibodies against F. hepatica. The positive samples were classified as mildly, moderately or strongly positive. Out of 405 cattle sera assessed, 38 (9.4%) were seropositive for antibodies against F. hepatica. From these, 2.5% each were moderately or strongly positive and 4.4% were mildly positive. A significantly higher seroprevalence (P<0.05) was observed in young animals (<2 y old, 15.3%) compared to adults (≥2 y old, 5.4%), while no significant difference in seropositivity was found between male and female animals. This is the the first report of F. hepatica seroprevalence in cattle herds in Korea. These findings may be used to establish a base-line of information for future investigations focused on the significance of F. hepatica in Korea.Provedeno je presječno istraživanje radi procjene seroprevalencije invadiranosti velikim metiljem Fasciola hepatica u stadima goveda na otoku Ulleung u Koreji. Uzorci krvi bili su uzeti od nasumce odabranih goveda, a odvojeni uzorci seruma bili su pretraženi imunoenzimnim testom na prisutnost protutijela specifičnih za velikog metilja. Pozitivni uzorci bili su svrstani u skupine: slabo, umjereno i jako pozitivni. Od 405 pretraženih uzoraka seruma, 38 (9,4%) je bilo pozitivnih na protutijela specifična za metilj F. hepatica. Od toga je 2,5% uzoraka bilo umjereno ili jako pozitivno, a 4,4% slabo pozitivno. Značajno veća seroprevalencija (P<0,05) ustanovljena je u mladih životinja (u dobi manjoj od dvije godine, 15,3%) u usporedbi s odraslima (≥2 godine, 5,4%), dok nije ustanovljena značajna razlika u seropozitivnosti između mužjaka i ženki. Ovo je prvo izvješće o seroprevalenciji velikog metilja u stadima goveda u Koreji. Nalazi mogu biti od koristi za buduća istraživanja o značenju velikog metilja F. hepatica u Koreji