Rosmarinic acid (RA), a main phenolic compound contained in rosemary which is used as tea, oil, medicine and so on, has been known to present anti-inflammatory, anti-oxidant and anti-cancer effects. ...Histone deacetylases (HDACs) are enzymes that play important roles in gene expression by removing the acetyl group from histone. The aberrant expression of HDAC in human tumors is related with the onset of human cancer. Especially, HDAC2, which belongs to HDAC class I composed of HDAC 1, 2, 3 and 8, has been reported to be highly expressed in prostate cancer (PCa) where it downregulates the expression of p53, resulting in an inhibition of apoptosis. The purpose of this study is to investigate the effect of RA in comparison with suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor used as an anti-cancer agent, on survival and apoptosis of PCa cell lines, PC-3 and DU145, and the expression of HDAC. RA decreased the cell proliferation in cell viability assay, and inhibited the colony formation and tumor spheroid formation. Additionally, RA induced early- and late-stage apoptosis of PC-3 and DU145 cells in Annexin V assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. In western blot analysis, RA inhibited the expression of HDAC2, as SAHA did. Proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E1 were downregulated by RA, whereas p21 was upregulated. In addition, RA modulated the protein expression of intrinsic mitochondrial apoptotic pathway-related genes, such as Bax, Bcl-2, caspase-3 and poly (ADP-ribose) polymerase 1 (
) (cleaved) via the upregulation of p53 derived from HDAC2 downregulation, leading to the increased apoptosis of PC-3 and DU145 cells. Taken together, treatment of RA to PCa cell lines inhibits the cell survival and induces cell apoptosis, and it can be used as a novel therapeutic agent toward PCa.
We developed an automatic method for staging periodontitis on dental panoramic radiographs using the deep learning hybrid method. A novel hybrid framework was proposed to automatically detect and ...classify the periodontal bone loss of each individual tooth. The framework is a hybrid of deep learning architecture for detection and conventional CAD processing for classification. Deep learning was used to detect the radiographic bone level (or the CEJ level) as a simple structure for the whole jaw on panoramic radiographs. Next, the percentage rate analysis of the radiographic bone loss combined the tooth long-axis with the periodontal bone and CEJ levels. Using the percentage rate, we could automatically classify the periodontal bone loss. This classification was used for periodontitis staging according to the new criteria proposed at the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. The Pearson correlation coefficient of the automatic method with the diagnoses by radiologists was 0.73 overall for the whole jaw (p < 0.01), and the intraclass correlation value 0.91 overall for the whole jaw (p < 0.01). The novel hybrid framework that combined deep learning architecture and the conventional CAD approach demonstrated high accuracy and excellent reliability in the automatic diagnosis of periodontal bone loss and staging of periodontitis.
Toll‐like receptors (TLRs) are usually expressed on immune cells such as macrophages, dendritic cells, mast cells, as well as on eosinophils and some epithelial cells. They play a central role in the ...recognition of harmful molecules that belong to invading microorganisms or internal damaged tissues, which lead to inflammation. Among the hallmarks of cancer, there is immune evasion and inflammation. Summing this with the discovery that a majority of cancers also seem to express TLRs, made researchers realize these receptors might also be linked with cancer progression. This review will cover some of the effects of TLR engagement in cancer cells that might induce the promotion or inhibition of cancer with mechanisms involved. The differences of TLR expression in cancer progression and its possible relation with patient prognosis, TLR genetic disorders found in cancer, and new strategies to cancer therapy will be discussed to target TLRs in cancer cells.
(a) Various cancer cells express TLR receptors. (b) TLR expression has also been related to cancer survival. (c) Promising various TLR‐targeted therapies that are still being furthered studied.
Insomnia is the most common sleep disorder with significant psychiatric/physical comorbidities in the general population. The aim of this study is to investigate whether socioeconomic and demographic ...factors are associated with gender differences in insomnia and subtypes in Korean population.
The present study used data from the nationwide, cross-sectional study on sleep among all Koreans aged 19 to 69 years. The Insomnia Severity Index (ISI) was used to classify insomnia symptoms and their subtypes (cutoff value: 9.5). The Pittsburgh Sleep Quality Index (PSQI), Goldberg Anxiety Scale (GAS) and Patient Health Questionnaire-9 (PHQ-9) were used to measure sleep quality, anxiety and depression.
A total of 2695 participants completed the survey. The overall prevalence of insomnia symptoms was 10.7%, including difficulty in initiating sleep (DIS) (6.8%), difficulty in maintaining sleep (DMS) (6.5%) and early morning awakening (EMA) (6.5%), and these symptoms were more prevalent in women than in men. Multivariate analysis showed that female gender, shorter sleep time and psychiatric complications were found to be independent predictors for insomnia symptoms and subtypes. After adjusting for covariates among these factors, female gender remained a significant risk factor for insomnia symptoms and their subtypes. As for men, low income was related to insomnia.
Approximately one-tenth of the sample from the Korean general population had insomnia symptoms. The prevalence of insomnia symptom and the subtypes were more prevalent in women than men. Gender is an independent factor for insomnia symptoms.
Gallic acid (GA) is known to possess diverse biological activities, including anticancer. Histone deacetylase (HDACs) are controlled by tumor suppressor gene transcription and are overexpressed in ...various tumors, resulting in tumor development, progression and poor prognosis. This study aims to demonstrate the effect of GA on inhibition of prostate cancer (PCa) progression by modulating the expression of HDAC1 and 2 in PCa cells. To prove our research rationale, we used diverse experimental methods. GA decreased the cell viability of only PCa cell lines and not normal cells (contrary to another HDAC inhibitor, suberoylanilide hydroxamic acid) and also inhibited colony and tumor spheroid formation. Exposure to GA decreased the mitochondrial membrane potential (ΔΨm), increased the number of apoptotic cells and induced DNA fragmentation. Western blot analysis revealed down-regulated expression of HDAC1 and 2, leading to up-regulation of acetyl-p53 expression at the protein level, subsequent to down-regulating the expression of cell-cycle-related genes, i.e., proliferating cell nuclear antigen (PCNA), Cyclin D1 and E1, up-regulating the expression of cell cycle arrest gene p21 and regulating the expression of apoptosis intrinsic pathway-related genes, such as Bax, Bcl-2, cleaved Caspase-3 and poly (ADP-ribose) polymerase 1 in both PCa cell lines. Furthermore, oral administration of GA for 8 weeks on PC-3 cells-derived tumor xenograft mice model decreases the tumor size, damages the tumor structure and down-regulates the expression of HDAC1 and 2 and PCNA in tumor mass, as confirmed by histological analysis. These results indicated that GA may hinder the PCa progression by inhibiting HDAC1 and 2 expression, thereby demonstrating the potential of GA to be used as HDACs inhibitor and anti-PCa therapeutics.
Mitochondrial membrane potential (MMP, ΔΨm) by JC-1 staining shows that suberoylanilide hydroxamic acid (SAHA) and gallic acid (GA) significantly decrease the red fluorescence-stained cells and increase the green fluorescence-stained cells when compared to negative control, indicating that treatment of SAHA and GA causes MMP depletion. Display omitted
Iridoids are glycosides found in plants, having inherent roles in defending them against infection by viruses and microorganisms, and in the rapid repair of damaged areas. The emerging roles of ...iridoid glycosides on pharmacological properties have aroused the curiosity of many researchers, and studies undertaken indicate that iridoid glycosides exert inhibitory effects in numerous cancers. This review focuses on the roles and the potential mechanism of iridoid glycosides at each stage of cancer development such as proliferation, epithelial mesenchymal transition (EMT), migration, invasion and angiogenesis. Overall, the reviewed literature indicates that iridoid glycosides inhibit cancer growth by inducing cell cycle arrest or by regulating apoptosis-related signaling pathways. In addition, iridoid glycosides suppress the expression and activity of matrix metalloproteinases (MMPs), resulting in reduced cancer cell migration and invasiveness. The antiangiogenic mechanism of iridoid glycosides was found to be closely related to the transcriptional regulation of pro-angiogenic factors, i.e., vascular endothelial growth factors (VEGFs) and cluster of differentiation 31 (CD31). Taken together, these results indicate the therapeutic potential of iridoid glycosides to alleviate or prevent rapid cancer progression and metastasis.
Fludioxonil (Flu) is a phenylpyrrole fungicide and is currently used in over 900 agricultural products globally. Flu possesses endocrine‐disrupting chemical‐like properties and has been shown to ...mediate various physiological and pathological changes, such as apoptosis and differentiation, in diverse cell lines. However, the effects of Flu on cardiomyocytes have not been studied so far. The present study investigated the effects of Flu on mitochondria in AC16 human cardiomyocytes and H9c2 rat cardiomyoblasts. Flu decreased cell viability in a water‐soluble tetrazolium assay and mediated morphological changes suggestive of apoptosis in AC16 and H9c2 cells. We confirmed that annexin V positive cells were increased by Flu through annexin V/propidium iodide staining. This suggests that the decrease in cell viability due to Flu may be associated with increased apoptotic changes. Flu consistently increased the expression of pro‐apoptotic markers such as Bcl‐2‐associated X protein (Bax) and cleaved‐caspase 3. Further, Flu reduced the oxygen consumption rate (OCR) in AC16 and H9c2 cells, which is associated with decreased mitochondrial membrane potential (MMP) as observed through JC‐1 staining. In addition, Flu augmented the production of mitochondrial reactive oxygen species, which can trigger oxidative stress in cardiomyocytes. Taken together, these results indicate that Flu induces mitochondrial dysregulation in cardiomyocytes via the downregulation of the OCR and MMP and upregulation of the oxidative stress, consequently resulting in the apoptosis of cardiomyocytes. This study provides evidence of the risk of Flu toxicity on cardiomyocytes leading to the development of cardiovascular diseases and suggests that the use of Flu in agriculture should be done with caution and awareness of the probable health consequences of exposure to Flu.
BACKGROUND:Percutaneous endoscopic lumbar discectomy (PELD) has remarkably evolved with successful results. Although PELD has gained popularity for the treatment of herniated disc (HD), the risk of ...surgical failure may be a major obstacle to performing PELD. We analyzed unsuccessful cases requiring reoperation.
OBJECTIVE:To find common causes of surgical failure and elucidate the limitations of the conventional PELD technique.
METHODS:A retrospective review was performed on all patients who had undergone PELD between January 2001 and December 2012. Unsuccessful PELD was defined as a case requiring reoperation within 6 weeks after primary surgery. Chart review was done, and preoperative, intraoperative, and postoperative radiographic reviews were performed. All unsuccessful PELD cases were classified according to the type of HD, location of herniation, extruded disc migration, working channel position, and intraoperative and postoperative findings.
RESULTS:In 12 years, 10 228 patients had undergone PELD; 436 (4.3%) cases were unsuccessful. The causes were incomplete removal of HDs in 283 patients (2.8%), recurrence in 78 (0.8%), persistent pain even after complete HD removal in 41 (0.4%), and approach-related pain in 21 (0.2%). Incomplete removal of the HD was caused by inappropriate positioning (95 cases; 33.6%) of the working channel and occurred in central HDs (91 cases; 32.2%), migrated HDs (70 cases; 24.7%), and axillary type HDs (63 cases; 22.3%).
CONCLUSION:Proper surgical indications and good working channel position are important for successful PELD. PELD techniques should be specifically designed to remove the disc fragments in various types of HD.
ABBREVIATIONS:HD, herniated discPELD, percutaneous endoscopic lumbar discectomy
Tumors are composed of subpopulations of cancer cells with functionally distinct features. Intratumoral heterogeneity limits the therapeutic effectiveness of cancer drugs. To address this issue, it ...is important to understand the regulatory mechanisms driving a subclonal variety within a therapy-resistant tumor. We identified tumor subclones of HN9 head and neck cancer cells showing distinct responses to radiation with different levels of p62 expression. Genetically identical grounds but epigenetic heterogeneity of the p62 promoter regions revealed that radioresistant HN9-R clones displayed low p62 expression via the creation of repressive chromatin architecture, in which cooperation between DNMT1 (DNA methyltransferases 1) and HDAC1 (histone deacetylases 1) resulted in DNA methylation and repressive H3K9me3 and H3K27me3 marks in the p62 promoter. Combined inhibition of DNMT1 and HDAC1 by genetic depletion or inhibitors enhanced the suppressive effects on proliferative capacity and in vivo tumorigenesis following irradiation. Importantly, ectopically p62-overexpressed HN9-R clones increased the induction of senescence along with p62-dependent autophagy activation. These results demonstrate the heterogeneous expression of p62 as the key component of clonal variation within a tumor against irradiation. Understanding the epigenetic diversity of p62 heterogeneity among subclones allows for improved identification of the functional state of subclones and provides a novel treatment option to resolve resistance to current therapies.
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