Leigh syndrome or subacute necrotizing encephalomyelopathy is a rare, rapidly progressive neurodegenerative disorder. In general, symptoms such as shortness of breath and decreased cardiac function usually occur within 1 year of life. It is a serious disease with a mortality rate of 75% in 2–3 years. The cause of Leigh syndrome is DNA mutation. Approximately 75% of patients have nuclear DNA mutations while 25% have mitochondrial DNA mutations. Clinical symptoms vary depending on the affected brain area. Neuroimaging plays an important role in diagnosing patients with Leigh syndrome. Late-onset Leigh syndrome is rarer and progresses more slowly compared to the classic form. Here, we report a case of late-onset Leigh's syndrome mimicking Wernicke's encephalopathy.

BACKGROUND: Sorbus rufopilosa, a tsema rowan, is a species of the small ornamental trees in the genus Sorbus and the family Rosaceae found in East Asia. The bioactivities of S. rufopilosa have not yet been fully determined. The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. METHODS: To examine the antioxidant activity of EESR, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay was performed. Inhibitory effect of EESR on cancer cell growth and proliferation was determined by water-soluble tetrazolium salt assay. To investigate the mechanism of EESR-mediated cytotoxicity, HT29 cells were treated with various concentrations of EESR and the induction of cell cycle arrest and apoptosis was analyzed by flow cytometry, 4,6-diamidino-2-phenylindole staining, and Western blot analysis. RESULTS: EESR showed significant antioxidant activity and inhibitory effect on HT29 cell growth in a dose-dependent manner. EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. EESR-induced apoptosis was associated with the upregulation of p53, a death receptor Fas, and a pro-apoptotic protein Bax and the activation of caspase 3, 8, and 9, resulting in the degradation of PARP. CONCLUSIONS: EESR possessing antioxidant activity efficiently inhibits proliferation of HT29 cells by inducing both cell cycle arrest and apoptosis. EESR may be a possible candidate for the anticancer drug development.
Adenocarcinoma* ; Apoptosis* ; Blotting, Western ; Caspase 3 ; CDC2 Protein Kinase ; Cell Cycle Checkpoints* ; Cell Cycle* ; Colon* ; Cyclin B ; Ethanol ; Far East ; Flow Cytometry ; HT29 Cells* ; Humans* ; Rosacea ; Rosaceae ; Sorbus* ; Trees ; Up-Regulation

OBJECTIVES: The objective of this study was to investigate the relationship between psychological distress and pain in cancer patients. METHODS: 249 patients with cancer who visited National Health Insurance Service Ilsan Hospital between April 2013 and March 2014 were evaluated with National Cancer Center Psychological Symptom Inventory(NCC-PSI) which consisted of Modified Distress Thermometer(MDT) and Modified Impact Thermometer(MIT). Each scale was divided into 3 subscales targeting separate symptoms: insomnia, anxiety, and depression. Psychological distress was defined as positive for those who scored above the cutoff values in at least one of all six subscales. The Numeric Rating Scale for Pain(NRS-Pain) was used to assess the subjective severity of pain. Logistic regression was performed to investigate the association between psychological distress and pain. RESULTS: Univariate logistic regression analysis showed that pain, gender, compliance, and two subscale scores of Hospital Anxiety and Depression Scale(HADS) were significantly associated with psychological distress. Multivariate logistic regression analysis showed that pain and HADS anxiety subscale score maintained a statistically significant association with psychological distress adjusted for variables including age, gender, years of education, Eastern Cooperative Oncology Group performance status, cancer stage, Charlson Comorbidity Index, compliance, and HADS depression subscale score. One point increase in pain was 1.31 times more likely to cause psychological distress. In secondary analysis, pain was significantly associated with all subscales of NCC-PSI, except MIT-anxiety subscale. CONCLUSIONS: This study suggests that NCC-PSI, a screening tool for psychological distress, reflects pain. We recommend that physicians who treat cancer patients consider the examination of psychological distress which provides comprehensive evaluation of various factors regarding quality of life.
Anxiety ; Comorbidity ; Compliance ; Depression ; Education ; Humans ; Logistic Models ; Mass Screening* ; National Health Programs ; Quality of Life ; Sleep Initiation and Maintenance Disorders

Cedrol, a sesquiterpene alcohol, isolated from Juniperus chinensis has been reported to inhibit minichromosome maintenance (MCM) proteins as cancer biomarkers in human lung cancer in vitro. In the present study, we investigated the anti-cancer activity of cedrol in vitro and in vivo using human colorectal cancer HT29 cells and a human colorectal tumor xenograft model. Cedrol inhibited MCM protein expression and cell growth in HT29 cells, which are associated with G1 arrest and the induction of apoptosis. We demonstrated that cedrol effectively reduced HT29 tumor growth without apparent weight loss in a human tumor xenograft model.Compared with vehicle- and adriamycin-treated tumor tissues, cedrol induced changes in the tumor tissue structure, resulting in a reduced cell density within the tumor parenchyma and reduced vascularization. Moreover, the expression of MCM7, an important subunit of MCM helicase, was significantly suppressed by cedrol in tumor tissue. Collectively, these results suggest that cedrol may act as a potential anti-cancer agent for colorectal cancer by inhibiting MCM protein expression and tumor growth.

BACKGROUND: Osmanthus matsumuranus, a species of Oleaceae, is found in East Asia and Southeast Asia. The bioactivities of O. matsumuranus have not yet been fully understood. Here, we studied on the molecular mechanisms underlying anti-cancer effect of ethanol extract of O. matsumuranus (EEOM). METHODS: Inhibitory effect of EEOM on cell growth and proliferation was determined by WST assay in various cancer cells. To investigate the mechanisms of EEOM-mediated cytotoxicity, HepG2 cells were treated with various concentration of EEOM and analyzed the cell cycle arrest and apoptosis induction by flow cytometry, Western blot analysis, 4,6-diamidino-2-phenylindole (DAPI) staining and DNA fragmentation. RESULTS: EEOM showed the cytotoxic activities in a dose-dependent manner in various cancer cell lines but not in normal cells, and HepG2 cells were most susceptible to EEOM-induced cytotoxicity. EEOM induced G2/M arrest in HepG2 cells associated with decreased expression of cyclin-dependent kinase 1 (CDK1), cyclin A and cylcin B, and increased expression of phospho-checkpoint kinase 2, p53 and CDK inhibitor p21. Immunofluorescence staining showed that EEOM-treated HepG2 increased doublet nuclei and condensed actin, resulting in cell rounding. Furthermore, EEOM-mediated apoptosis was determined by Annexin V staining, chromatin condensation and DNA fragmentation. EEOM caused upregulation of FAS and Bax, activation of caspase-3, -8, -9, and fragmentation of poly ADP ribose polymerase. CONCLUSIONS: These results suggest that EEOM efficiently inhibits proliferation of HepG2 cells by inducing both G2/M arrest and apoptosis via intrinsic and extrinsic pathways, and EEOM may be used as a cancer chemopreventive agent in the food or nutraceutical industry.
Actins ; Annexin A5 ; Apoptosis* ; Asia, Southeastern ; Blotting, Western ; Carcinoma, Hepatocellular* ; Caspase 3 ; CDC2 Protein Kinase ; Cell Cycle Checkpoints ; Cell Line ; Chromatin ; Cyclin A ; Dietary Supplements ; DNA Fragmentation ; Ethanol ; Far East ; Flow Cytometry ; Fluorescent Antibody Technique ; Hep G2 Cells* ; Humans* ; Oleaceae ; Phosphotransferases ; Poly(ADP-ribose) Polymerases ; Up-Regulation

Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma (PPAR-γ), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-γ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of PPAR-γ. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.
Down-Regulation* ; Epidermis ; Glycolipids ; Homeostasis ; Humans* ; JNK Mitogen-Activated Protein Kinases* ; Keratinocytes* ; Membrane Proteins ; Peroxidase ; Phosphorylation* ; Phosphotransferases ; PPAR gamma ; Protein Kinases ; RNA, Messenger ; Skin ; Transcription Factors ; Water

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by an inhaled inciting antigen that leads to the inflammation of the lung parenchyma and small airway with immunologic reactions. Over the last decades, the most effective therapeutic option for HP has been limited to antigen avoidance. The differential diagnosis of HP from other ILDs is the beginning of treatment as well as diagnosis. However, the presence of several overlapping clinical and radiologic features makes differentiating HP from other ILDs particularly challenging. In 2020, a multidisciplinary committee of experts from the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax suggested a new clinical practice guideline classifying HP into nonfibrotic and fibrotic phenotypes on the basis of chest high-resolution CT (HRCT) findings. Therefore, we introduced a new diagnostic algorithm based on chest HRCT in the clinical practice guideline for the diagnosis of HP.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by an inhaled inciting antigen that leads to the inflammation of the lung parenchyma and small airway with immunologic reactions. Over the last decades, the most effective therapeutic option for HP has been limited to antigen avoidance. The differential diagnosis of HP from other ILDs is the beginning of treatment as well as diagnosis. However, the presence of several overlapping clinical and radiologic features makes differentiating HP from other ILDs particularly challenging. In 2020, a multidisciplinary committee of experts from the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax suggested a new clinical practice guideline classifying HP into nonfibrotic and fibrotic phenotypes on the basis of chest high-resolution CT (HRCT) findings. Therefore, we introduced a new diagnostic algorithm based on chest HRCT in the clinical practice guideline for the diagnosis of HP.

Background: To propose a deep learning architecture for automatically detecting the complex structure of the aortic annulus plane using cardiac computed tomography (CT) for transcatheter aortic valve replacement (TAVR). Methods: This study retrospectively reviewed consecutive patients who underwent TAVR between January 2017 and July 2020 at a tertiary medical center. Annulus Detection Permuted AdaIN network (ADPANet) based on a three-dimensional (3D) U-net architecture was developed to detect and localize the aortic annulus plane using cardiac CT. Patients (N = 72) who underwent TAVR between January 2017 and July 2020 at a tertiary medical center were enrolled. Ground truth using a limited dataset was delineated manually by three cardiac radiologists. Training, tuning, and testing sets (70:10:20) were used to build the deep learning model. The performance of ADPANet for detecting the aortic annulus plane was analyzed using the root mean square error (RMSE) and dice similarity coefficient (DSC). Results: In this study, the total dataset consisted of 72 selected scans from patients who underwent TAVR. The RMSE and DSC values for the aortic annulus plane using ADPANet were 55.078 ± 35.794 and 0.496 ± 0.217, respectively. Conclusion Our deep learning framework was feasible to detect the 3D complex structure of the aortic annulus plane using cardiac CT for TAVR. The performance of our algorithms was higher than other convolutional neural networks.