Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action. CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies.
Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis.
In this study, TiO2 nanofibers with a high aspect ratio and a large specific surface area were synthesized using the electrospinning technique, and the effect of calcination temperature on their crystal structure, diameter, specific surface area and photocatalytic activity was systematically investigated. The electrospun, as-prepared PVP/TTIP nanofibers were several tens of micrometers in length with a diameter of 74 nm. TiO2 nanofibers with an average diameter of 50 nm were prepared after calcination at various temperatures. The calcination temperature significantly influenced the photocatalytic and material properties of TiO2 including grain size and specific surface area. When compared to other nanostructured TiO2 materials, such as commercial TiO2 nanoparticles (P25, Degussa), the TiO2 nanofibers exhibited greater photocatalytic activity for the degradation of acetaldehyde and ammonia.
This cross-sectional, observational study aimed to integrate the analyses of relationships of physical activity, depression, and sleep with cognitive function in community-dwelling older adults using a single model. To this end, physical activity, sleep, depression, and cognitive function in 864 community-dwelling older adults from the Suwon Geriatric Mental Health Center were assessed using the International Physical Activity Questionnaire, Montgomery-Asberg Depression Rating Scale, Pittsburgh Sleep Quality Index, and Mini-Mental State Examination for Dementia Screening, respectively. Their sociodemographic characteristics were also recorded. After adjusting for confounders, multiple linear regression analysis was performed to investigate the effects of physical activity, sleep, and depression on cognitive function. Models 4, 5, 7, and 14 of PROCESS were applied to verify the mediating and moderating effects of all variables. Physical activity had a direct effect on cognitive function (effect = 0.97, p < 0.01) and indirect effect (effect = 0.36; confidence interval: 0.18, 0.57) through depression. Moreover, mediated moderation effects of sleep were confirmed in the pathways where physical activity affects cognitive function through depression (F-coeff = 13.37, p < 0.001). Furthermore, these relationships differed with age. Thus, the associations among physical activity, depression, and sleep are important in interventions for the cognitive function of community-dwelling older adults. Such interventions should focus on different factors depending on age.
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