Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on ...histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 μM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1β, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase iNOS), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 μM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human β-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.
Recurrence and chemoresistance in colorectal cancer remain important issues for patients treated with conventional therapeutics. Metformin and phenformin, previously used in the treatment of ...diabetes, have been shown to have anticancer effects in various cancers, including breast, lung and prostate cancers. However, their molecular mechanisms are still unclear. In this study, we examined the effects of these drugs in chemoresistant rectal cancer cell lines. We found that SW837 and SW1463 rectal cancer cells were more resistant to ionizing radiation and 5‐fluorouracil than HCT116 and LS513 colon cancer cells. In addition, metformin and phenformin increased the sensitivity of these cell lines by inhibiting cell proliferation, suppressing clonogenic ability and increasing apoptotic cell death in rectal cancer cells. Signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling pathways were more activated in rectal cancer cells, and inhibition of signal transducer and activator of transcription 3 expression using an inhibitor or siRNA sensitized rectal cancer cells to chemoresistant by inhibition of the expression of antiapoptotic proteins, such as X‐linked inhibitor of apoptosis, survivin and cellular inhibitor of apoptosis protein 1. Moreover, metformin and phenformin inhibited cell migration and invasion by suppression of transforming growth factor β receptor 2‐mediated Snail and Twist expression in rectal cancer cells. Therefore, metformin and phenformin may represent a novel strategy for the treatment of chemoresistant rectal cancer by targeting signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling.
Metformin and phenformin decreased the expression of pro‐apoptotic proteins by inhibiting STAT3 phosphorylation at Ser‐727 and suppressed invasion and migration by inhibiting TGFBR2‐mediated signaling
Keratin (KRT) 19 is a poor prognostic marker for hepatocellular carcinoma (HCC); however, regulatory mechanisms underlying its expression remain unclear. We have previously reported the presence of ...fibrous tumor stroma in KRT19-positive HCC, suggesting that cross-talk between cancer-associated fibroblasts (CAF) and tumor epithelial cells could regulate KRT19 expression. This was investigated in this study using an
model of paracrine interaction between HCC cell lines (HepG2, SNU423) and hepatic stellate cells (HSC), a major source of hepatic myofibroblasts. HSCs upregulated transcription and translation of KRT19 in HCC cells via paracrine interactions. Mechanistically, hepatocyte growth factor (HGF) from HSCs activated c-MET and the MEK-ERK1/2 pathway, which upregulated KRT19 expression in HCC cells. Furthermore, AP1 (JUN/FOSL1) and SP1, downstream transcriptional activators of ERK1/2, activated KRT19 expression in HCC cells. In clinical specimens of human HCC (
= 339), HGF and KRT19 protein expression correlated with CAF levels. In addition, HGF or MET protein expression was associated with FOSL1 and KRT19 expression and was found to be a poor prognostic factor. Analysis of data from The Cancer Genome Atlas also revealed KRT19 expression was closely associated with CAF and MET-mediated signaling activities. These results provide insights into the molecular background of KRT19-positive HCC that display an aggressive phenotype.
These findings reveal KRT19 expression in hepatocellular carcinoma is regulated by cross-talk between cancer-associated fibroblasts and HCC cells, illuminating new therapeutic targets for this aggressive disease.
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Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) ...are introduced for transforming accumulated glucose (in cancer cells) to hydroxyl radicals for starvation/chemodynamic therapy. Cu may also suppress cancer cell growth via cuproptosis‐mediated cell death. Berberine hydrochloride (BER) is engaged as a chemotherapeutic agent in the hydrogel reactor for combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, Cu is participated as a gel crosslinker by coordinating with catechol groups in hyaluronic acid‐dopamine (HD) polymer. Controlling viscoelasticity of hydrogel reactor can extend the retention time following local injection and provide sustained drug release patterns. Low biodegradation rate of designed HD/BER/GOx/Cu hydrogel can reduce dosing frequency in local cancer therapy and avoid invasiveness‐related inconveniences. Especially, it is anticipated that HD/BER/GOx/Cu hydrogel system can be applied for reducing size of breast cancer prior to surgery as well as tumor growth suppression in clinical application.
Cuproptosis‐inducible hydrogel reactor system equipped with chemo/starvation/chemodynamic modalities is designed for localized breast cancer therapy. Local injection of crosslinked hyaluronic acid hydrogel system to breast cancer region efficiently suppressed the growth of primary tumor and its recurrence by multiple therapeutic mechanisms (e.g., cuproptosis, glucose deprivation, ROS generation, and antiproliferation).
Next-Generation Sequencing (NGS) is now widely used in biomedical research for various applications. Processing of NGS data requires multiple programs and customization of the processing pipelines ...according to the data platforms. However, rapid progress of the NGS applications and processing methods urgently require prompt update of the pipelines. Recent clinical applications of NGS technology such as cell-free DNA, cancer panel, or exosomal RNA sequencing data also require appropriate customization of the processing pipelines. Here, we developed SEQprocess, a highly extendable framework that can provide standard as well as customized pipelines for NGS data processing.
SEQprocess was implemented in an R package with fully modularized steps for data processing that can be easily customized. Currently, six pre-customized pipelines are provided that can be easily executed by non-experts such as biomedical scientists, including the National Cancer Institute's (NCI) Genomic Data Commons (GDC) pipelines as well as the popularly used pipelines for variant calling (e.g., GATK) and estimation of allele frequency, RNA abundance (e.g., TopHat2/Cufflink), or DNA copy numbers (e.g., Sequenza). In addition, optimized pipelines for the clinical sequencing from cell-free DNA or miR-Seq are also provided. The processed data were transformed into R package-compatible data type 'ExpressionSet' or 'SummarizedExperiment', which could facilitate subsequent data analysis within R environment. Finally, an automated report summarizing the processing steps are also provided to ensure reproducibility of the NGS data analysis.
SEQprocess provides a highly extendable and R compatible framework that can manage customized and reproducible pipelines for handling multiple legacy NGS processing tools.
The number of adult learners who participate in online learning has rapidly grown in the last two decades due to online learning's many advantages. In spite of the growth, the high dropout rate in ...online learning has been of concern to many higher education institutions and organizations. The purpose of this study was to determine whether persistent learners and dropouts are different in individual characteristics (i.e., age, gender, and educational level), external factors (i.e., family and organizational supports), and internal factors (i.e., satisfaction and relevance as sub-dimensions of motivation). Quantitative data were collected from 147 learners who had dropped out of or finished one of the online courses offered from a large Midwestern university. Dropouts and persistent learners showed statistical differences in perceptions of family and organizational support, and satisfaction and relevance. It was also shown that the theoretical framework, which includes family support, organizational support, satisfaction, and relevance in addition to individual characteristics, is able to predict learners' decision to drop out or persist. Organizational support and relevance were shown to be particularly predictive. The results imply that lower dropout rates can be achieved if online program developers or instructors find ways to enhance the relevance of the course. It also implies that adult learners need to be supported by their organizations in order for them to finish online courses that they register for.
Particulate matter (PM) is a significant environmental pollutant that promotes respiratory diseases, including lung injury and inflammation, by inducing oxidative stress.
(black soybean) is ...traditionally used to prevent chronic respiratory disease via inducing antioxidant and anti-inflammatory effects. To investigate the effects of
SC65 fermented GR (GR-SC65) and
ON81A (GR-ON81A) against PM-induced oxidative stress and cell death in A549 cells, we performed the 2-7-dichlorodihydrofluorescein diacetate and cell counting kit-8 assays, as well as Hoechst 33342 and propidium iodide staining and western blotting. GR-SC65 showed the highest total polyphenolic contents and 1,1-diphenyl-2-picrylidrazil radical scavenging activity among lactic acid bacteria-fermented GRs (
< 0.001 vs. GR). Four soy peptides, β-conglycinin breakdowns (INAENNQRNF, ISSEDKPFN, LAFPGSAQAVEK, and LAFPGSAKDIEN), were detected in GR-SC65, but not in GR. In GR-SC65, PM-induced A549 cell death was less than that observed in GR-ON81A and GR (
< 0.001 vs. PM-treated group). GR-SC65 significantly decreased intracellular reactive oxidative species (ROS) when compared with PM (***
< 0.001 vs. PM). GR-SC65 decreased the levels of BAX, active caspase-9, -3, and poly ADP-ribose polymerase (PARP) proteins (
< 0.01,
< 0.001 vs. PM), while increasing the level of BCL-2 protein, a mitochondrial anti-apoptotic protein (
< 0.001 vs. PM). Our findings indicate that GR-SC65 inhibited PM-induced cell death by suppressing the levels of ROS, active caspase-9 and -3, and PARP proteins, while enhancing the level of BCL-2 protein in type II alveolar epithelial A549 cells. Therefore, GR-SC65 might be a potential therapeutic and preventive agent against PM-induced lung injury.
To investigate the relationship between Temporomandibular disorder (TMD) and associated comorbidities in groups matched according to age and sex.
Using data from the cross-sectional fifth Korea ...National Health and Nutrition Examination Survey (KNHANES). Of the 25,534 eligible KNHANES, 17,762 adults aged ≥19 years who responded to survey questionnaire on TMD and comorbidities. Subjects were classified into eight groups according to age and sex. Logistic regression analyses were performed to evaluate the association between TMD and comorbidities according to age and sex.
Of the enrolled participants, 2,107 (11.86%) complained of ≥1 TMD symptoms. In all groups, odds ratios (ORs) for prevalence of TMD were >1 in those with tinnitus. Rhinitis was closely associated with TMD in 6 groups. ORs for TMD with comorbidities according to age and sex were as follows: hypertension, men aged 50-64 years (OR 0.62; CI 0.41-0.94); ischemic heart disease, men aged 35-49 years (4.38; 1.54-12.47); osteoarthritis, women aged 50-64 years (1.38; 1.03-1.86); diabetes mellitus, men aged 35-49 years (0.21; 0.05-0.88); depression, men aged 50-64 years (1.68; 1.00-2.83), women aged 35-49 years (1.39; 1.05-1.85) and women aged 65-80 years (2.01; 1.46-2.77); migraine, men aged 50-64 years (1.60; 1.14-2.25), women aged d35-49 years (1.44; 1.14-1.81) and women aged 35-49 years (1.43; 1.07-1.90); cold hypersensitivity in the hands and feet, men aged 19-34 years (1.64; 1.05-2.58), men aged 35-49 years (1.68; 1.04-2.70), men aged 65-80 years (1.74; 1.09-2.75) and women aged 35-49 years (1.45; 1.15-1.84); olfaction disorder, men aged 50-64 years (2.49; 1.39-4.43); voice disorder, men aged 50-64 years (2.25; 1.28-3.96) and women aged 65-80 years (1.69; 1.09-2.63).
This study confirmed that the types and effects of comorbidities related to prevalence of TMD may differ according to the patient's age and sex and this result will increase the predictability of the onset of TMD.
The aim of this study was to develop a self-diagnostic scale that could distinguish smartphone addicts based on the Korean self-diagnostic program for Internet addiction (K-scale) and the ...smartphone's own features. In addition, the reliability and validity of the smartphone addiction scale (SAS) was demonstrated.
A total of 197 participants were selected from Nov. 2011 to Jan. 2012 to accomplish a set of questionnaires, including SAS, K-scale, modified Kimberly Young Internet addiction test (Y-scale), visual analogue scale (VAS), and substance dependence and abuse diagnosis of DSM-IV. There were 64 males and 133 females, with ages ranging from 18 to 53 years (M = 26.06; SD = 5.96). Factor analysis, internal-consistency test, t-test, ANOVA, and correlation analysis were conducted to verify the reliability and validity of SAS.
Based on the factor analysis results, the subscale "disturbance of reality testing" was removed, and six factors were left. The internal consistency and concurrent validity of SAS were verified (Cronbach's alpha = 0.967). SAS and its subscales were significantly correlated with K-scale and Y-scale. The VAS of each factor also showed a significant correlation with each subscale. In addition, differences were found in the job (p<0.05), education (p<0.05), and self-reported smartphone addiction scores (p<0.001) in SAS.
This study developed the first scale of the smartphone addiction aspect of the diagnostic manual. This scale was proven to be relatively reliable and valid.
In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of ...the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.
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