The involvement of AMPK/GSK3-beta signals in the control of metastasis and proliferation in hepato-carcinoma cells treated with anthocyanins extracted from Korea wild berry Meoru

BACKGROUND: Activation of the Wnt pathway is known to promote tumorigenesis and tumor metastasis, and targeting Wnt pathway inhibition has emerged as an attractive approach for controlling tumor invasion and metastasis. The major pathway for inhibiting Wnt is through the degradation of β-catenin by the GSK3-beta/CK1/Axin/APC complex. It was found that Hep3B hepato-carcinoma cells respond to anthocyanins through GSK3-beta-induced suppression of beta-catenin; however, they cannot dephosphorylate GSK3-beta without AMPK activation. METHODS: We tested the effects of anthocyanins on proliferation and apoptosis by MTT and Annexin V-PI staining in vitro. Mouse xenograft models of hepato-carcinomas were established by inoculation with Hep3B cells, and mice were injected with 50 mg/kg/ml of anthocyanins. In addition, protein levels of p-GSK3-beta, beta-catenin, p-AMPK, MMP-9, VEGF, and Ang-1 were also analyzed using western blot. RESULTS: Anthocyanins decrease phospho-GSK3-beta and beta-catenin expression in an in vivo tumor xenograft model, increase AMPK activity in this model, and inhibit cell migration and invasion, possibly by inhibiting MMP-2 (in vitro) and the panendothelial marker, CD31 (in vivo). To elucidate the role of the GSK3-beta/beta-catenin pathway in cancer control, we conditionally inactivated this pathway, using activated AMPK for inhibition. Further, we showed that AMPK siRNA treatment abrogated the ability of anthocyanins to control cell proliferation and metastatic potential, and Compound C, an AMPK inhibitor, could not restore GSK3-beta regulation, as exhibited by anthocyanins in Hep3B cells. CONCLUSION: These observations imply that the AMPK-mediated GSK3-beta/beta-catenin circuit plays crucial roles in inhibiting cancer cell proliferation and metastasis in anthocyanin-treated hepato-carcinoma cells of Meoru origin

Simultaneous Total Occlusion of Multiple Distal Coronary Arteries in Acute Myocardial Infarction

Simultaneous multiple coronary artery thrombosis is a rare finding in ST segment elevation myocardial infarction (STEMI). We report a case of myocardial infarction with multiple ST segment elevation on the electrocardiography and total occlusions of the distal left anterior descending artery (dLAD), as well as of the second and third obtuse marginal artery on emergency coronary angiography. Thrombus aspiration was performed at dLAD and systemic glycoprotein IIb/IIIa inhibitor was used successfully. In patients with STEMI, multiple coronary thromboses are unusual and associated with patient fatality. However, assertive thrombus aspiration and antiplatelet therapy could be effective in STEMI patients with multiple distal coronary artery occlusions

Preparation of nanoscale inorganic CsPbIxBr3-x perovskite photosensitizers on the surface of mesoporous TiO2 film for solid-state sensitized solar cells

Metal chalcogenide quantum dot (QD)-like all-inorganic nanoscale perovskite photosensitizers of CsPbIxBr3-x were prepared on the surface of mesoscopic TiO2 film by a direct two-step spin-coating of lead and cesium halide precursors for application into solid-state dye-sensitized solar cells (DSSCs), as confirmed by impedance frequency response analysis. A few nanometer-sized hemisphere-shaped dots of CsPbIxBr3-x perovskites were deposited and distributed separately onto TiO2, which were checked by scanning and transmission electron microscopic (SEM and TEM) techniques. The as-deposited CsPbIxBr3-x perovskites were stable only in the case of including about 20% or more bromide in the composition of halides. When the bromide content increased in the ratio of halides of CsPbIxBr3-x, gradual decrease in lattice spacing and blue-shift of emission peaks were observed in X-ray diffraction (XRD) and photoluminescence (PL) measurements, respectively. These well-defined nano-particulate CsPbIxBr3-x perovskites were incorporated into solid-state DSSCs and tested as a new type of photosensitizers. The initial power conversion efficiency (PCE) of ca. 1.0–3.5% based on relatively thin mesoporous TiO2 film (~1 μm) looks promising with many parameters remaining for possibly more optimization. The best result, 3.79%, was obtained from CsPbI2.2Br0.80 25 days after initial measurement. These CsPbIxBr3-x-sensitized cells displayed a stable record of PCE over ~2 month and no hysteresis behavior in current-voltage traces

Association of high estimated glomerular filtration rate with risk of atrial fibrillation: a nationwide cohort study

AimWhile the relationship between impaired kidney function and atrial fibrillation (AF) is well established, there is limited research exploring the association between elevated estimated glomerular filtration rate (eGFR) and AF development. This study aimed to examine the association between higher-than-normal eGFR and AF risk using a nationwide longitudinal study of the general population in Korea.Materials and methodsThis study utilized the National Health Insurance Service cohort database of Korea, analyzing data from 2,645,042 participants aged 20–79 years who underwent health examinations between 2010 and 2011. Participants with a history of end-stage renal disease, renal transplantation, and AF prior to the index date were excluded. Renal function was assessed using eGFR levels, calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Baseline characteristics were gathered through questionnaires, while comorbidities and AF occurrence outcomes were identified and validated using diagnostic codes and medication histories. The study employed Kaplan–Meier survival curves and Cox proportional hazard models to evaluate the association between eGFR and AF occurrence.ResultsThe mean age of subjects was 48.82 ± 10.08 years. Over a median follow-up of 9.58 years, 27,469 (1.04%) AF cases were identified. The risk for AF increased in the higher-than-normal decile, as demonstrated by Kaplan–Meier survival curves (p < 0.001). The eGFR <30 mL/min/1.73 m2 group was associated with an increased risk of AF [hazard ratio (HR): 1.22, 95% confidence interval (CI) (1.01, 1.46), p = 0.039], while the eGFR >120 mL/min/1.73 m2 group was associated with a decreased risk of AF [HR: 0.88, 95% CI (0.78, 0.98), p = 0.045]. Compared to the 5th decile, the 1st [HR: 1.08, 95% CI (1.03, 1.13), p = 0.010] eGFR decile was significantly associated with an increased risk of AF, while the 10th [HR: 0.77, 95% CI (0.70, 0.85), p < 0.001] eGFR decile was significantly associated with a reduced risk of AF.ConclusionThe study revealed that individuals with eGFR>120 mL/min/1.73 m2 or those falling within eGFR 10th decile (>113.41 mL/min/1.73 m2) demonstrated an inverse association linked to a reduced risk of AF. Our study suggests that general population with higher-than-normal eGFR levels may have a lower risk of developing AF

The role of S100A4 for bone metastasis in prostate cancer cells

Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells. Methods In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT characteristics, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells. Results The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT traits of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT characteristics in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government MSIT (NRF-2020R1A2C2010082 and NRF-2018R1A5A2024418) to H.-H. Kim and by the National Research Foundation of Korea grant (NRF-2019R1A2C4070083) to H.J. Kim. The funding body has no role in the design of the study; collection, analysis, and interpretation of data; and in writing the manuscript

Impact of Chronic Cough on Health-Related Quality of Life in the Korean Adult General Population: The Korean National Health and Nutrition Examination Survey 2010–2016

PurposeChronic cough is a prevalent condition in the community and may pose considerable impairment to quality of life (QoL). However, its disease burden remains largely undefined in the general population. The present study investigated the relationship between chronic cough and health-related QoL in a Korean nationwide population database, with an emphasis on clinical conditions which may confound the impact of cough.MethodsThis study analyzed cross-sectional datasets of adults (aged ≥ 40 years) in the Korean National Health and Nutrition Examination Survey 2010–2016. Health-related QoL was assessed using the 3-level EuroQoL 5-dimension component (EQ-5D-3L) index score. The presence of chronic cough and other conditions were defined using structured questionnaires.ResultsThe prevalence of chronic cough was 3.48% ± 0.17% among adults aged ≥ 40 years. The overall EQ-5D-3L index score was significantly lower in subjects with than without chronic cough (0.79 ± 0.01 vs. 0.86 ± 0.00, P < 0.001). In subgroup analyses by age and sex, chronic cough had a notably large impact on QoL in women aged ≥ 65 years (vs. those without chronic cough: 0.55 ± 0.04 vs. 0.70 ± 0.01, P < 0.001), although the mean difference in the scores exceeded the minimally important difference score of 0.05 in all subgroups. In multivariate analyses, chronic cough was significantly associated with QoL, independent of confounders including depression, arthritis, asthma, and chronic obstructive pulmonary disease. In dimension analyses, chronic cough was more associated with anxiety/depression, pain/discomfort, and usual activities than with self-care or mobility in the EQ-5D.ConclusionsThe present study demonstrated significant associations between chronic cough and health-related QoL in a nationwide large general adult population aged ≥ 40 years, which were independent of clinical confounders. The impact of chronic cough was greater in women aged ≥ 65 years. These findings indicate a considerable burden of chronic cough in the general population and warrant further investigations to assess the disease burden of chronic cough in a global scale