The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames ...(SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation-all likely contributing to the clinical manifestations of SARS-CoV infection.
Interleukin (IL)-33 promotes T helper (Th)2 immunity and systemic inflammation. The role of IL-33 in asthma has been widely investigated. IL-33 has also been suggested to play an important role in ...the pathogenesis of chronic obstructive pulmonary disease (COPD). This study investigated the clinical significance and usefulness of plasma IL-33 level in patients with COPD.
A total of 307 patients with stable COPD from 15 centers, who were in the Korean Obstructive Lung Disease cohort, were enrolled in this study. Plasma IL-33 levels were measured by enzyme-linked immunosorbent assay. We analyzed the association between IL-33 level and other clinical characteristics related to COPD. We also examined the features of patients with COPD who exhibited high IL-33 levels.
IL-33 levels varied, but were very low in most patients. Eosinophil count was significantly correlated with a plasma IL-33 level. In addition, old age and current smoking were related to a low IL-33 level. Significantly more patients with a higher IL-33 level had chronic bronchitis compared with those with a low IL-33 level.
Plasma IL-33 level in patients with stable COPD was related to eosinophil count and chronic bronchitis phenotype. Further studies are needed to identify the precise mechanisms of IL-33/ST2 pathway in patients with COPD.
Agrobacterium tumefaciens is a plant pathogenic bacterium that causes neoplastic growths, called 'crown gall', via the transfer and integration of transferred DNA (T-DNA) from the bacterium into the ...plant genome. We characterized an acetosyringone (AS)-induced tumour-inducing (Ti) plasmid gene, tzs (trans-zeatin synthesizing), that is responsible for the synthesis of the plant hormone cytokinin in nopaline-type A. tumefaciens strains. The loss of Tzs protein expression and trans-zeatin secretions by the tzs frameshift (tzs-fs) mutant is associated with reduced tumorigenesis efficiency on white radish stems and reduced transformation efficiencies on Arabidopsis roots. Complementation of the tzs-fs mutant with a wild-type tzs gene restored wild-type levels of trans-zeatin secretions and transformation efficiencies. Exogenous application of cytokinin during infection increased the transient transformation efficiency of Arabidopsis roots infected by strains lacking Tzs, which suggests that the lower transformation efficiency resulted from the lack of Agrobacterium-produced cytokinin. Interestingly, although the tzs-fs mutant displayed reduced tumorigenesis efficiency on several tested plants, the loss of Tzs enhanced tumorigenesis efficiencies on green pepper and cowpea. These data strongly suggest that Tzs, by synthesizing trans-zeatin at early stage(s) of the infection process, modulates plant transformation efficiency by A. tumefaciens.
The ability of a GA discharge to produce hydrogen peroxide (H2O2), a potent oxidizer, was investigated to evaluate the optimum operational condition of the GA discharge for bacterial inactivation. ...The concentration of H2O2 was measured in liquid phase, and its effective residual time was evaluated in a 200-W GA discharge system at different air and water flow rates. The concentration of H2O2 was the highest at the least water flow rate. In addition, a 5-log reduction in the colony forming unit (cfu) number of E. coli was observed at a H2O2 concentration of 100mg/L in water.
Natural course of early COPD Rhee, Chin Kook; Kim, Kyungjoo; Yoon, Hyoung Kyu ...
International journal of chronic obstructive pulmonary disease,
01/2017, Letnik:
12
Journal Article
Recenzirano
Odprti dostop
Few studies have examined the natural course of early COPD. The aim of this study was to observe the natural course of early COPD patients. We also aimed to analyze medical utilization and costs for ...early COPD during a 6-year period.
Patients with early COPD were selected from Korean National Health and Nutrition Examination Survey (KNHANES) data. We linked the KNHANES data of patients with early COPD to National Health Insurance data.
A total of 2,397 patients were enrolled between 2007 and 2012. The mean forced expiratory volume in 1 second (FEV
) was 78.6%, and the EuroQol five dimensions questionnaire (EQ-5D) index value was 0.9. In total, 110 patients utilized health care for COPD in 2007, and this number increased to 179 in 2012. The total mean number of days used per person increased from 4.9 in 2007 to 7.8 in 2012. The total medical cost per person also increased from 248.8 US dollar (USD) in 2007 to 780.6 USD in 2013. A multiple linear regression revealed that age, lower body mass index, lower FEV
(%), and lower EQ-5D score were significantly associated with medical costs.
Even in early COPD patients, some of them eventually progressed and utilized health care for COPD.
Food samples are collected nationwide from January 2016 to February 2017 and their contents of artificial radionuclides are measured to address the growing concerns regarding the radioactive ...contamination of food products in Korea. Specifically, 900 food samples are collected for this study and their contents of representative artificial radionuclides 134Cs, 137Cs, 239,240Pu, and 90Sr are analyzed. The analysis shows that the activity concentrations of 137Cs in fish range from minimum detectable activity (MDA) to 340 mBq/kg of fresh weight. The concentration factor (CF) determined for 137Cs as a measure of its bioavailability is calculated to be ca. 74 and found to be very similar to that (100) recommended by the International Atomic Energy Agency. With an MDA of <0.221 mBq/kg, the results reveal that 239,240Pu values in fish are below the MDA. The activity concentrations of 137Cs and 90Sr are lower than the MDA in both shellfish and seaweed, while the activity concentrations of 239,240Pu in shellfish range from 0.26 to 2.18 mBq/kg, and for seaweed samples range from 2.07 to 3.38 mBq/kg. The atom ratios of 240Pu/239Pu in shellfish caught at the Korean coast vary from 0.209 to 0.237, with a mean of 0.227. The higher 240Pu/239Pu atom ratio determined in shellfish is thought to be caused by the plutonium transported from the Pacific Proving Grounds rather than other sources such as the Fukushima nuclear power plant accident. The activity concentrations of 137Cs in mushrooms are found to vary from 1.0 to 21.4 Bq/kg, with the highest concentrations observed in the Oak (shiitake) and Sarcodon asparatus. 134Cs is detected in three mushroom specimens collected from Jeju Island and about 3–3.6% of 137Cs present in the wild mushrooms native to the Jeju Island are introduced as a result of the Fukushima nuclear plant accident. The annual effective doses of 137Cs received through consumption of mushrooms and fish are 2.0 × 10−4 mSv yr−1 and 3.9 × 10−5 mSv yr−1, and those values are negligible compared to the annual effective doses limit of 1 mSv yr−1.
•Man-made radionuclides in food stuffs in Korea were investigated.•The activity concentrations of 137Cs detected in this study were not different from those measured prior to the Fukushima NPP accident.•The activity concentrations of 239,240Pu in shellfish ranged from 0.26 to 2.18 mBq/kg and in seaweed ranged from 2.07 to 3.38 mBq/kg.•The activity concentrations of 137Cs detected in mushroom samples (1.0–21.4 Bq/kg) are considerably high.•The total annual effective dose of 137Cs received is negligible.
Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune ...responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration.
Cytochalasin B (CB) is a cell-permeable mycotoxin. It inhibits cytoplasmic division by blocking the formation of contractile microfilaments, it inhibits cell movement and induces nuclear extrusion. ...In the present study, we investigated the anticancer activity of CB in HeLa human cervical carcinoma cells. CB showed significant cytotoxicity, with an IC50 of 7.9 µM, in a WST-8 assay and significantly inhibited cell proliferation. Furthermore, results from Annexin V-FITC/propidium iodide double-staining indicated that CB induced early apoptosis of HeLa cells in a time-dependent manner. The cells exhibited apoptotic morphology, including cell shrinkage and nuclear condensation. CB induced cell cycle arrest at the S phase. We also observed inhibition of DNA replication in a 3H-thymidine incorporation assay. Furthermore, CB induced a time-dependent increase in reactive oxygen species and a decrease in mitochondrial membrane potential. Western blot analysis showed an increase in levels of mitochondrial factors Bax and Bcl-2, which was followed by activation of caspase-9 and -3. These results suggested that CB induced apoptosis via a mitochondrial-dependent pathway in HeLa cells.
Abstract Purpose Pneumocystis carinii pneumonia (PCP) is an opportunistic infection associated with morbidity and mortality in solid-organ transplant recipients. We retrospectively assessed the ...characteristics and outcomes of liver transplant (OLT) recipients with PCP compared with those of patients with severe non- P carinii pneumonia (non-PCP) who required intensive care with mechanical ventilation. Methods During the 2-year period between January 2008 and December 2009, 43 adult OLT recipients had severe pneumonia requiring mechanical ventilation; of these, 8 (19%) had PCP. During this period, routine antibiotic prophylaxis was administered for the first 6 months after OLT. Results The median period from OLT to development of PCP was 9.5 months (range, 1–67); the 1-year incidence was 0.9%. The 6 and 6 to 12-month incidences of non-PCP were 4.2% and 0.3%, respectively, and those of PCP were 0.3% and 0.6%, respectively. Four of 8 patients (50%) in the PCP group had a recent history of a rejection episode. PCP was associated with a higher incidence of prior antirejection treatment. There were no significant differences between PCP and non-PCP groups in age, gender, preoperative Model for End-stage Liver Disease score, primary diagnosis, graft type, and total number of rejection episodes. Conclusions These results indicate that the risk of PCP in OLT recipients is closely related to strong immunosuppressive treatment for acute cellular rejection episodes, suggesting the importance of PCP prophylaxis in these patients. Because most patients developed PCP at around 1 year, it may be advisable to prolong routine post-OLT PCP prophylaxis for 12 months, especially among patients receiving antirejection treatment.
PDF
