The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, ...the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice. Treatment with SYN1143 or SGX523 inhibited HGF-induced c-Met phosphorylation in MC3T3-E1 and C3H10T1/2 cells. Cell proliferation of MC3T3-E1 or C3H10T1/2 was not significantly affected by the concentrations of these inhibitors. Co-treatment with chemical inhibitor of c-Met and osteogenic inducing media enhanced osteoblast-specific genes expression and calcium nodule formation accompanied by increased Runx2 expression via c-Met receptor-dependent but Erk-Smad signaling independent pathway. Notably, the administration of these c-Met inhibitors significantly repaired critical-sized calvarial bone defects. Collectively, our results suggest that chemical inhibitors of c-Met receptor tyrosine kinase might be used as novel therapeutics to induce bone regeneration.
The present study aimed towards adsorptive removal of the toxic azo dye onto biochar derived from Eucheuma spinosum biomass. Characterization of the produced biochar was performed using X-ray ...diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET). Eucheuma spinosum biochar (ES-BC) produced at 600 °C revealed a maximum adsorption capacity of 331.97 mg/g towards reactive red 120 dye. The adsorption data fitted best to the pseudo-second order kinetics (R2 > 0.99) and Langmuir isotherm (R2 > 0.98) models. These adsorption models signified the chemisorption mechanism with monolayer coverage of the adsorbent surface with dye molecules. Furthermore, the adsorption process was mainly governed by electrostatic interaction, ion exchange, metal complexation, and hydrogen bonding as supported by the solution pH, FTIR, XPS, and XRD investigation. Nevertheless, alone adsorption technology could not offer a complete solution for eliminating the noxious dyes. Therefore, the bioelectrochemical system (BES) equipped with previously isolated marine Shewanella marisflavi BBL25 was intended for the complete remediation of azo dye. The BES II demonstrated highest dye decolorization (97.06%) within 48 h at biocathode where the reductive cleavage of the azo bond occurred. Cyclic voltammetry (CV) studies of the BES revealed perfect redox reactions taking place where the redox mediators shuttled the electrons to the dye molecule to accelerate the dye decolorization. Besides, the GC-MS analysis revealed biotransformation of the dye into less toxic metabolites as tested using a phyto and cytogenotoxicity.
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•Macroalgae derived biochar showed excellent performance for azo dye adsorption.•Pseudo-second order and Langmuir isotherm were the best suited adsorption model.•Shewanella marisflavi BBL25 attained >97% dye decolorization at biocathode.•Cyclic voltammetry revealed direct and mediator driven electron transfer mechanism.•This study provides a suitable and sustainable approach for remediation of azo dyes.
There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ...ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1β, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis.
This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012 Korea National Health and Nutrition ...Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged ...and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
Low-level somatic mutations have been shown to be the major genetic etiology of intractable epilepsy. The extents thereof, however, have yet to be systematically and accurately explored in a large ...cohort of resected epilepsy brain tissues. Moreover, clinically useful and precise analysis tools for detecting low-level somatic mutations from unmatched formalin-fixed paraffin-embedded (FFPE) brain samples, the most clinically relevant samples, are still lacking. In total, 446 tissues samples from 232 intractable epilepsy patients with various brain pathologies were analyzed using deep sequencing (average read depth, 1112x) of known epilepsy-related genes (up to 28 genes) followed by confirmatory site-specific amplicon sequencing. Pathogenic mutations were discovered in 31.9% (74 of 232) of the resected epilepsy brain tissues and were recurrently found in only eight major focal epilepsy genes, including
AKT3, DEPDC5, MTOR, PIK3CA, TSC1, TSC2, SCL35A2
, and
BRAF
. Somatic mutations, two-hit mutations, and germline mutations accounted for 22.0% (51), 0.9% (2), and 9.1% (21) of the patients with intractable epilepsy, respectively. The majority of pathogenic somatic mutations (62.3%, 33 of 53) had a low variant allelic frequency of less than 5%. The use of deep sequencing replicates in the eight major focal epilepsy genes robustly increased PPVs to 50–100% and sensitivities to 71–100%. In an independent FCDII cohort of only unmatched FFPE brain tissues, deep sequencing replicates in the eight major focal epilepsy genes identified pathogenic somatic mutations in 33.3% (5 of 15) of FCDII individuals (similar to the genetic detecting rate in the entire FCDII cohort) without any false-positive calls. Deep sequencing replicates of major focal epilepsy genes in unmatched FFPE brain tissues can be used to accurately and efficiently detect low-level somatic mutations, thereby improving overall patient care by enriching genetic counseling and informing treatment decisions.
Objectives We analyzed the relation between platelet aggregation measured by light transmittance aggregometry (LTA) and platelet reactivity index (PRI) measured by vasodilator-stimulated ...phosphoprotein phosphorylation (VASP-P) assay. Background It has been suggested that LTA and VASP-P assay correlate differently according to the level of P2Y12 receptor blockade by thienopyridines. Methods We simultaneously measured platelet function by LTA and VASP-P assay in 466 East Asians undergoing elective percutaneous coronary intervention after a 600-mg clopidogrel loading. High on-clopidogrel platelet reactivity (HPR) was defined by published consensus criteria. Results The degree of correlation between LTA and the VASP-P assay was different according to PRI levels. The correlation was lower in patients with poor responsiveness (PRI >60%) (n = 216) (0.035 ≤ r2 ≤ 0.047), which was greater in responsive patients (PRI ≤60%) (n = 250) (0.315 ≤ r2 ≤ 0.526). Despite a 600-mg loading, East Asians had a high prevalence of HPR (40.1%-63.5%), and the prevalence of HPR also differed between LTA and VASP-P assay. A PRI cutoff of >58% (area under curve, 0.829; 95% confidence intervals, 0.792-0.862; P < .001) corresponded to the published HPR cutoff by 5-μM adenosine diphosphate–induced maximal platelet aggregation >46%. Conclusions This is the largest study correlating platelet reactivity measured by LTA and VASP-P assay in a percutaneous coronary intervention–treated cohort. The correlation is dependent on the level of responsiveness. Future investigations are needed to better define the optimal cutoffs of HPR measured by LTA and VASP-P assay for personalized antiplatelet therapy.
AbstractContextFew randomized controlled trials of advance care planning (ACP) with a decision aid (DA) show an effect on patient preferences for end-of-life (EOL) care over time, especially in ...racial/ethnic settings outside the U.S. ObjectivesThe objective of this study was to examine the effect of a decision aid consisting of a video and an ACP booklet for EOL care preferences among patients with advanced cancer. MethodsUsing a computer-generated sequence, we randomly assigned (1:1) patients with advanced cancer to a group that received a video and workbook that both discussed either ACP (intervention group) or cancer pain control (control group). At baseline, immediately after intervention, and at 7 weeks, we evaluated the subjects' preferences. The primary outcome was preference for EOL care (active treatment, life-prolonging treatment, or hospice care) on the assumption of a fatal disease diagnosis and the expectation of death 1) within 1 year, 2) within several months, and 3) within a few weeks. We used Bonferroni correction methods for multiple comparisons with an adjusted P level of 0.005. ResultsFrom August 2017 to February 2018, we screened 287 eligible patients, of whom 204 were enrolled to the intervention (104 patients) or the control (100 patients). At postintervention, the intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within 1 year ( P < 0.005). Assuming a life expectancy of several months, the change in preferences was significant for active treatment and hospice care ( P < 0.005) but not for life-prolonging treatment. The intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within a few weeks ( P < 0.005). From baseline to 7 weeks, the decrease in preference in the intervention group was not significant for active treatment, life-prolonging treatment, and hospice care in the intervention group in the subset expecting to die within 1 year, compared with the control group. Assuming a life expectancy of several months and a few weeks, the change in preferences was not significant for active treatment and for life-prolonging treatment but was significantly greater for hospice care in the intervention group ( P < 0.005). ConclusionACP interventions that included a video and an accompanying book improved preferences for EOL care.
Little information exists on the prevalence of metabolic syndrome (MetS) in Korea since 2007. We aimed to provide up-to-date estimates of the prevalence of MetS and its trend in the general adult ...population in Korea.
We compared the prevalence and pattern of MetS among participants in the Korean National Health and Nutrition Examination Surveys (KNHANES) IV (2007–2009), V (2010–2012), and VI (2013–2015), aged ≥19 years. Data from the 2005 census of the Korean population were presented according to age standardization.
The overall age-standardized prevalence of MetS in 2013–2015 was 20.3% (95% confidence interval CI, 19.6%–21%). Since 2007, the overall prevalence of MetS has remained stable, whereas the prevalences among men and women, respectively, have increased and decreased slightly. By contrast, the prevalence of MetS among men aged 19–49 years has shown an increasing tendency since 2007. Moreover, nearly 40% of women aged ≥60 years had MetS in 2013–2015. Among the five components of MetS, only elevated fasting glucose level has shown an increasing trend since 2007 in both men and women. As the family income and educational level decreased, the prevalence of MetS increased.
The overall prevalence of MetS has remained stable since 2007. However, the prevalence of MetS was higher in middle-aged men and women aged ≥60 years. Considering the close association between MetS and socioeconomic status, age- and sex-specific strategies should be developed at the national level for the treatment and prevention of MetS in Korea.
•The prevalence of metabolic syndrome (MetS) in Korea has remained stable since 2007.•The prevalence of MetS was higher in middle-aged men and women aged≥60 years.•As the family income and educational level decreased, the prevalence of MetS increased.
Background. There have been few reports on the causes and treatment outcomes for nosocomial spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis. Methods. We performed a ...retrospective cohort study to compare the microbiological and clinical characteristics in nosocomial versus community-acquired SBP. All patients with SBP, for whom culture was proven to be positive for SBP at Samsung Medical Center (Seoul, Republic of Korea) from 1 January 2000 through 31 June 2007, were included. Medical records and laboratory data were reviewed. Nosocomial SBP was defined as SBP diagnosed after 72 h of hospitalization. Results. A total of 236 patients with SBP were enrolled (mean age ±SD age, 56.6±10.7 years); 166 patients were women, and 70 were men. Nosocomial and community-acquired SBP occurred in 126 and 110 patients, respectively. Escherichia coli accounted for 102 (43.2%) of 236 isolates, Klebsiella species accounted for 33 isolates (14.0%), and Streptococcus species accounted for 23 isolates (9.8%). The overall 30-day mortality rate for nosocomial SBP was higher than that for community-acquired SBP (58.7% vs. 37.3%; P=.001). Nosocomial isolates of gram-negative organisms were significantly more resistant to third-generation cephalosporins (41% vs. 10.0%; P<.001) and quinolones (50.0% vs. 30.9%; P=.003), compared with community-acquired isolates. Multivariate analysis revealed that nosocomial infection, concomitant hepatocellular carcinoma, presentation with acute renal failure or shock, and resistance to third-generation cephalosporins were significant risk factors for 30-day mortality associated with SBP. Conclusions. Nosocomial SBP has a poorer outcome than community-acquired SBP. The resistance to third-generation cephalosporins for gram-negative organisms, which are more common in nosocomial cases of SBP than in community-acquired cases of SBP, adversely affects the outcome of SBP in patients with liver cirrhosis.
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