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Protective effect of oleic acid against very long-chain fatty acid-induced apoptosis in peroxisome-deficient CHO cells
Get PDFVery long-chain fatty acids (VLCFAs) are degraded exclusively in peroxisomes, as evidenced by the accumulation of VLCFAs in patients with certain peroxisomal disorders. Although accumulation of VLCFAs is considered to be associated with health issues, including neuronal degeneration, the mechanisms underlying VLCFAs-induced tissue degeneration remain unclear. Here, we report the toxic effect of VLCFA and protective effect of C18:1 FA in peroxisome-deficient CHO cells. We examined the cytotoxicity of saturated and monounsaturated VLCFAs with chain-length at C20-C26, and found that longer and saturated VLCFA showed potent cytotoxicity at lower accumulation levels. Furthermore, the extent of VLCFA-induced toxicity was found to be associated with a decrease in cellular C18:1 FA levels. Notably, supplementation with C18:1 FA effectively rescued the cells from VLCFA-induced apoptosis without reducing the cellular VLCFAs levels, implying that peroxisome-deficient cells can survive in the presence of accumulated VLCFA, as long as the cells keep sufficient levels of cellular C18:1 FA. These results suggest a therapeutic potential of C18:1 FA in peroxisome disease and may provide new insights into the pharmacological effect of Lorenzo's oil, a 4:1 mixture of C18:1 and C22:1 FA.journal articl
Identification of Low-Density Lipoprotein Receptor-Related Protein 1 as a CXCL14 Receptor Using Chemically Synthesized Tetrafunctional Probes
Get PDFCXCL14 is a primordial CXC-type chemokine that transports CpG oligodeoxynucleotides (ODN) into endosomes and lysosomes in dendritic cells, thereby leading to activation of the Toll-like receptor 9 (TLR9)-mediated innate immune system. However, the underlying molecular mechanism by which CXCL14-CpG ODN complex enter cells remains elusive. Herein, we describe the chemical synthesis of CXCL14-derived photoaffinity probes and their application to identification of target receptors for CXCL14 using quantitative proteomics. By utilizing native chemical ligation and maleimide-thiol coupling chemistry, we synthesized site-specifically modified CXCL14-based photoaffinity probes that contain photoreactive 2-aryl-5-carboxytetrazole (ACT) and a hydrazine labile cleavable linker. CXCL14-based probes were found to be capable of binding CpG ODN to immune cells, whose bioactivities were comparable to native CXCL14. Application of CXCL14-derived probes to quantitative proteomic experiments enabled identification of dozens of target receptor candidates for CXCL14 in mouse macrophage-derived RAW264.7 cells, and we discovered that low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for CXCL14 by competitive proteome profiling. We further showed that disruption of LRP1 affected incorporation of CXCL14-CpG ODN complex in the cells. Overall, this report highlights the power of synthetic CXCL14-derived photoaffinity probes combined with chemical proteomics to discover previously unidentified receptors for CXCL14, which could promote understanding of the molecular functions of CXCL14 and the elaborate machinery of innate immune systems.journal articl
Reducing echocardiographic examination time through routine use of fully automated software : a comparative study of measurement and report creation time
Get PDFBackground
Manual interpretation of echocardiographic data is time-consuming and operator-dependent. With the advent of artificial intelligence (AI), there is a growing interest in its potential to streamline echocardiographic interpretation and reduce variability. This study aimed to compare the time taken for measurements by AI to that by human experts after converting the acquired dynamic images into DICOM data.
Methods
Twenty-three consecutive patients were examined by a single operator, with varying image quality and different medical conditions. Echocardiographic parameters were independently evaluated by human expert using the manual method and the fully automated US2.ai software. The automated processes facilitated by the US2.ai software encompass real-time processing of 2D and Doppler data, measurement of clinically important variables (such as LV function and geometry), automated parameter assessment, and report generation with findings and comments aligned with guidelines. We assessed the duration required for echocardiographic measurements and report creation.
Results
The AI significantly reduced the measurement time compared to the manual method (159 ± 66 vs. 325 ± 94 s, p < 0.01). In the report creation step, AI was also significantly faster compared to the manual method (71 ± 39 vs. 429 ± 128 s, p < 0.01). The incorporation of AI into echocardiographic analysis led to a 70% reduction in measurement and report creation time compared to manual methods. In cases with fair or poor image quality, AI required more corrections and extended measurement time than in cases of good image quality. Report creation time was longer in cases with increased report complexity due to human confirmation of AI-generated findings.
Conclusions
This fully automated software has the potential to serve as an efficient tool for echocardiographic analysis, offering results that enhance clinical workflow by providing rapid, zero-click reports, thereby adding significant value.journal articl
Echocardiographic artificial intelligence for pulmonary hypertension classification
Get PDFObjective: The classification of pulmonary hypertension (PH) is crucial for determining the appropriate therapeutic strategy. We investigated whether machine learning (ML) algorithms may assist in echocardiographic PH prediction, where current guidelines recommend integrating several different parameters.
Methods: We obtained physical and echocardiographic data from 885 patients who underwent right heart catheterization (RHC). Patients were classified into three groups: non-PH, pre-capillary PH, and post-capillary PH, based on values obtained from RHC. Utilizing 24 parameters, we created predictive models employing four different classifiers and selected the one with the highest area under the curve (AUC). We then calculated the macro-average classification accuracy for PH on the derivation cohort (n=720) and prospective validation dataset (n=165), comparing the results with guideline-based echocardiographic assessment obtained from each cohort.
Results: Logistic regression with elastic net regularization had the highest classification accuracy, with AUCs of 0.789, 0.766, and 0.742 for normal, pre-capillary PH, and post-capillary PH, respectively. The ML model demonstrated significantly better predictive accuracy than the guideline-based echocardiographic assessment in the derivation cohort (59.4% vs. 51.6%, p<0.01). In the independent validation dataset, the ML model's accuracy was comparable to the guideline-based PH classification (59.4% vs. 57.8%, p=0.638).
Conclusions: This preliminary study suggests promising potential for our ML model in predicting echocardiographic PH. Further research and validation are needed to fully assess its clinical utility in PH diagnosis and treatment decision-making.journal articl
2023年度徳島大学全学FD推進プログラムの実施報告
Get PDF徳島大学では，2002年度から全学FD推進プログラムを通じて，FDの体系化，組織化，日常化を推進してきた。2023年度は，4年ぶりにワークショップ型のプログラムを対面で実施し，参加者同士の情報交換の機会を提供することができた。オンラインツールを活用した双方向FD「授業について考えるランチセミナー」では，2022年度に引き続き高知大学と共同でFDプログラムの開発・運営を行った。「大学教育カンファレンスin徳島」は対面会場での実施をメインとし，一部のプログラムをオンラインで配信するハイブリッド型で開催したことで，参加者同士の情報交換の機会を作ることができた上に，学外からの参加も多数あり，多様な参加ニーズに応えることができた。本年度実施した各プログラムの概要を記載し，アンケート結果等から窺える成果と今後の課題について考察する。Tokushima University has been promoting the systematization, organization, and routinization of faculty development (FD) through the university-wide FD promotion program since FY2002. In FY2023, workshop-style programs were held face-to-face for the first time in four years. Thereby, we were able to provide an opportunity for participants to exchange information with each other. Moreover, following the example from the preceding year, in 2023, the online interactive FD seminar “Lunch Seminar on Thinking about Classes” was developed and managed jointly with Kochi University. Moreover “University Education Conference” was held face-to-face, and some programs were delivered online, so we could create opportunities for participants to exchange information with each other. It is noteworthy that there were many participants from outside the university, and we were able to meet their diverse needs. An overview of each program conducted this year and discussions about future challenges based on the results of the questionnaire are described.departmental bulletin pape
Low prognostic nutrition index as a prognostic biomarker in elderly patients with early gastric cancer after gastrectomy
Get PDFPurpose Non-invasive biomarkers including systemic inflammatory or nutrition-based index including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) lymphocyte to monocyte ratio (LMR), and prognostic nutritional index (PNI) can be useful in determining treatment strategies for elderly patients with early gastric cancer (EGC). The aim of this study was to investigate the significance of these index for predicting the long-term survival of EGC patients aged 80 years over. Methods This study included 80 elderly EGC patients with pStageIA after gastrectomy. Optimal cutoff value for PNI, NLR, PLR and LMR were set by using receiver operating curve analysis. The long-term outcomes after gastrectomy were analyzed by univariate and multivariate Cox regression analyses. Results Cut-off value for PNI, NLR, PLR and LMR was set at 46.5, 2.8, 210 and 4.6, respectively. By univariate analyses, low PNI, high NLR, high PLR and low LMR were significantly associated with worse prognosis. By multivariate analysis, low PNI was confirmed as an independent prognostic factor after gastrectomy (HR 0.17 ; 95% CI 0.03–0.91 ; P = 0.04). 5-year overall survival rate of patients with low PNI (≤ 46.5) were 52.4%. Conclusion Low PNI might be useful biomarker to predict worse prognosis of elderly EGC patients after gastrectomy.journal articl