Category Archives: 研究發表

Artificial intelligence-driven pan-cancer analysis reveals miRNA signatures for cancer stage prediction

何信瑩教授研究團隊發表研究成果於Human Genetics and Genomics Advances

連結網址:https://pubmed.ncbi.nlm.nih.gov/37124139/

Abstract

The ability to detect cancer at an early stage in patients who would benefit from effective therapy is a key factor in increasing survivability. This work proposes an evolutionary supervised learning method called CancerSig to identify cancer stage-specific microRNA (miRNA) signatures for early cancer predictions. CancerSig established a compact panel of miRNA signatures as potential markers from 4,667 patients with 15 different types of cancers for the cancer stage prediction, and achieved a mean performance: 10-fold cross-validation accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of 84.27% ± 6.31%, 0.81 ± 0.12, 0.80 ± 0.10, and 0.80 ± 0.06, respectively. The pan-cancer analysis of miRNA signatures suggested that three miRNAs, hsa-let-7i-3p, hsa-miR-362-3p, and hsa-miR-3651, contributed significantly toward stage prediction across 8 cancers, and each of the 67 miRNAs of the panel was a biomarker of stage prediction in more than one cancer. CancerSig may serve as the basis for cancer screening and therapeutic selection.

Data-Driven Two-Stage Framework for Identification and Characterization of Different Antibiotic-Resistant Escherichia coli Isolates Based on Mass Spectrometry Data

李宗夷教授研究團隊發表研究成果於Microbiology Spectrum

連結網址:https://pubmed.ncbi.nlm.nih.gov/37042778/

Abstract

In clinical microbiology, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is frequently employed for rapid microbial identification. However, rapid identification of antimicrobial resistance (AMR) in Escherichia coli based on a large amount of MALDI-TOF MS data has not yet been reported. This may be because building a prediction model to cover all E. coli isolates would be challenging given the high diversity of the E. coli population. This study aimed to develop a MALDI-TOF MS-based, data-driven, two-stage framework for characterizing different AMRs in E. coli. Specifically, amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM) were used. In the first stage, we split the data into two groups based on informative peaks according to the importance of the random forest. In the second stage, prediction models were constructed using four different machine learning algorithms-logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). The findings demonstrate that XGBoost outperformed the other four machine learning models. The values of the area under the receiver operating characteristic curve were 0.62, 0.72, 0.87, 0.72, and 0.72 for AMC, CAZ, CIP, CRO, and CXM, respectively. This implies that a data-driven, two-stage framework could improve accuracy by approximately 2.8%. As a result, we developed AMR prediction models for E. coli using a data-driven two-stage framework, which is promising for assisting physicians in making decisions. Further, the analysis of informative peaks in future studies could potentially reveal new insights. IMPORTANCE Based on a large amount of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) clinical data, comprising 37,918 Escherichia coli isolates, a data-driven two-stage framework was established to evaluate the antimicrobial resistance of E. coli. Five antibiotics, including amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM), were considered for the two-stage model training, and the values of the area under the receiver operating characteristic curve (AUC) were 0.62 for AMC, 0.72 for CAZ, 0.87 for CIP, 0.72 for CRO, and 0.72 for CXM. Further investigations revealed that the informative peak m/z 9714 appeared with some important peaks at m/z 6809, m/z 7650, m/z 10534, and m/z 11783 for CIP and at m/z 6809, m/z 10475, and m/z 8447 for CAZ, CRO, and CXM. This framework has the potential to improve the accuracy by approximately 2.8%, indicating a promising potential for further research.

Ferroptosis Signature Shapes the Immune Profiles to Enhance the Response to Immune Checkpoint Inhibitors in Head and Neck Cancer

楊慕華教授與林峻宇助理教授團隊共同發表研究成果於Advanced Science

連結網址:https://pubmed.ncbi.nlm.nih.gov/37026630/

Abstract

As a type of immunogenic cell death, ferroptosis participates in the creation of immunoactive tumor microenvironments. However, knowledge of spatial location of tumor cells with ferroptosis signature in tumor environments and the role of ferroptotic stress in inducing the expression of immune-related molecules in cancer cells is limited. Here the spatial association of the transcriptomic signatures is demonstrated for ferroptosis and inflammation/immune activation located in the invasive front of head and neck squamous cell carcinoma (HNSCC). The association between ferroptosis signature and inflammation/immune activation is more prominent in HPV-negative HNSCC compared to HPV-positive ones. Ferroptotic stress induces PD-L1 expression through reactive oxygen species (ROS)-elicited NF-κB signaling pathway and calcium influx. Priming murine HNSCC with the ferroptosis inducer sensitizes tumors to anti-PD-L1 antibody treatment. A positive correlation between the ferroptosis signature and the active immune cell profile is shown in the HNSCC samples. This study reveals a subgroup of ferroptotic HNSCC with immune-active signatures and indicates the potential of priming HNSCC with ferroptosis inducers to increase the antitumor efficacy of immune checkpoint inhibitors.

Menstrual cycle-modulated intrinsic connectivity enhances olfactory performance during periovulatory period

謝仁俊教授研究團隊發表研究成果於Rhinology

連結網址:https://pubmed.ncbi.nlm.nih.gov/37000430/

Abstract

Background: Olfactory capacity increases during the period of ovulation, perhaps as an adjunct to mate selection; however, researchers have yet to elucidate the neural underpinning of menstrual cycle-dependent variations in olfactory performance.

Methodology: A cohort of healthy volunteers (n = 88, grand cohort) underwent testing for gonadal hormone levels and resting-state functional magnetic resonance imaging with a focus on intrinsic functional connectivity (FC) in the olfactory network based on a priori seeds (piriform cortex and orbitofrontal cortex) during the periovulatory (POV) and menstrual (MEN) phases. A subcohort (n = 20, olfaction cohort) returned to the lab to undergo testing of olfactory performance during the POV and MEN phases of a subsequent menstrual cycle.

Results: Olfactory performance and FC were both stronger in the periovulatory phase than in the menstrual phase. Enhanced FC was observed in the network targeting the cerebellum in both the grand and olfaction cohorts, while enhanced FC was observed in the middle temporal gyrus, lingual gyrus, dorsal medial prefrontal cortex, and postcentral gyrus in the grand cohort. Periovulatory progesterone levels in the grand cohort were positively correlated with FC in the network targeting the insula and paracentral lobule.

Conclusion: Our analysis revealed that superior olfactory function in the periovulatory period is associated with enhanced intrinsic connectivity in the olfactory network. These findings can be appreciated in the context of evolutionary biology.

Osimertinib Induces the Opposite Effect of Proliferation and Migration in the Drug Resistance of EGFR-T790M Non-small Cell Lung Cancer Cells

趙瑞益教授研究團隊發表研究成果於Anti-Cancer Agents in Medicinal Chemistry

連結網址:https://www.eurekaselect.com/article/129735

Abstract

Background: Lung cancer has become one of the leading causes of cancer incidence and mortality worldwide. Non-small cell lung carcinoma (NSCLC) is the most common type among all lung cancer cases. NSCLC patients contained high levels of activating epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion, L858R and T790M. Osimertinib, a third-generation of EGFR tyrosine kinase inhibitor (EGFR-TKI), has therapeutic efficacy on the EGFR-T790M mutation of NSCLC patients; however, treatment of osimertinib still can induce drug resistance in lung cancer patients. Therefore, investigation of the drug resistance mechanisms of osimertinib will provide novel strategies for lung cancer therapy.

Methods: The H1975OR osimertinib-resistant cell line was established by prolonged exposure with osimertinib derived from the H1975 cells. The cell proliferation ability was evaluated by the cell viability and cell growth assays. The cell migration ability was determined by the Boyden chamber assays. The differential gene expression profile was analyzed by genome-wide RNA sequencing. The protein expression and location were analyzed by western blot and confocal microscopy.

Results: In this study, we established the osimertinib-resistant H1975 (T790M/L858R) cancer cells, named the H1975OR cell line. The cell growth ability was decreased in the H1975OR cells by comparison with the H1975 parental cells. Conversely, the cell migration ability was elevated in the H1975OR cells. We found the differential gene expression profile of cell proliferation and migration pathways between the H1975OR and H1975 parental cells. Interestingly, the protein levels of phospho-EGFR, PD-L1, E-cadherin and β-catenin were decreased, but the survivin and N-cadherin proteins were increased in the H1975OR drug-resistant cells.

Conclusion: Osimertinib induces the opposite effect of proliferation and migration in the drug resistance of EGFRT790M lung cancer cells. We suggest that differential gene and protein expressions in the cell proliferation and migration pathways may mediate the drug resistance of osimertinib in lung cancer cells. Understanding the molecular drugresistant mechanisms of proliferation and migration pathways of osimertinib may provide novel targets and strategies for the clinical treatment of EGFR-TKIs in lung cancer patients.

Preventing ischemia-reperfusion injury by acousto-mechanical local oxygen delivery

何奕儒助理教授研究團隊發表研究成果於Journal of Controlled Release

連結網址:https://www.sciencedirect.com/science/article/pii/S0168365923001852?via%3Dihub

Abstract

Ischemia-reperfusion (I/R) injury is a pathological process that causes vascular damage and dysfunction which increases recurrence and/or mortality in myocardial infarction, ischemic stroke, and organ transplantation. We hypothesized that ultrasound-stimulated oxygen-loaded microbubble (O2-MB) cavitation would enhance mechanical force on endothelium and simultaneously release oxygen locally at the targeted vessels. This cooperation between biomechanical and biochemical stimuli might modulate endothelial metabolism, providing a potential clinical approach to the prevention of I/R injury. Murine hindlimb and cardiac I/R models were used to demonstrate the feasibility of injury prevention by O2-MB cavitation. Increased mechanical force on endothelium induced eNOS-activated vasodilation and angiogenesis to prevent re-occlusion at the I/R vessels. Local oxygen therapy increased endothelial oxygenation that inhibited HIF-1α expression, increased ATP generation, and activated cyclin D1 for cell repair. Moreover, a decrease in interstitial H2O2 level reduced the expression of caspase3, NFκB, TNFα, and IL6, thus ameliorating inflammatory responses. O2-MB cavitation showed efficacy in maintaining cardiac function and preventing myocardial fibrosis after I/R. Finally, we present a potential pathway for the modulation of endothelial metabolism by O2-MB cavitation in relation to I/R injury, wound healing, and vascular bioeffects.

Erinacine S from Hericium erinaceus mycelium promotes neuronal regeneration by inducing neurosteroids accumulation

黃兆祺教授研究團隊發表研究成果於Journal of Food and Drug Analysis

連結網址:https://www.jfda-online.com/journal/vol31/iss1/3/

Abstract

Erinacines derived from Hericium erinaceus have been shown to possess various health benefits including neuroprotective effect against neurodegenerative diseases, yet the underlying mechanism remains unknown. Here we found that erinacine S enhances neurite outgrowth in a cell autonomous fashion. It promotes post-injury axon regeneration of PNS neurons and enhances regeneration on inhibitory substrates of CNS neurons. Using RNA-seq and bioinformatic analyses, erinacine S was found to cause the accumulation of neurosteroids in neurons. ELISA and neurosteroidogenesis inhibitor assays were performed to validate this effect. This research uncovers a previously unknown effect of erinacine S on raising the level of neurosteroids.

Enhanced intrinsic functional connectivity in the visual system of visual artist: Implications for creativity

謝仁俊教授研究團隊發表研究成果於Frontiers in Neuroscience

連結網址:https://www.frontiersin.org/articles/10.3389/fnins.2023.1114771/full

 

Introduction: This study sought to elucidate the cognitive traits of visual artists (VAs) from the perspective of visual creativity and the visual system (i.e., the most fundamental neural correlate).

 

Methods: We examined the local and long-distance intrinsic functional connectivity (FC) of the visual system to unravel changes in brain traits among VAs. Twenty-seven university students majoring in visual arts and 27 non-artist controls were enrolled.

 

Results: VAs presented enhanced local FC in the right superior parietal lobule, right precuneus, left inferior temporal gyrus (ITG), left superior parietal lobule, left angular gyrus, and left middle occipital gyrus. VAs also presented enhanced FC with the ITG that targeted the visual area (occipital gyrus and cuneus), which appears to be associated with visual creativity.

 

Discussion: The visual creativity of VAs was correlated with strength of intrinsic functional connectivity in the visual system. Learning-induced neuroplasticity as a trait change observed in VAs can be attributed to the macroscopic consolidation of consociated neural circuits that are engaged over long-term training in the visual arts and aesthetic experience. The consolidated network can be regarded as virtuoso-specific neural fingerprint.

Role of the stress-responsive two-component system CpxAR in regulating fimbriae expression in Klebsiella pneumoniae CG43

彭慧玲教授研究團隊發表研究成果於J Microbiol Immunol Infect.

連結網址:https://pubmed.ncbi.nlm.nih.gov/36898943/

Abstract

Background: CpxAR is a two-component system that allows bacteria to reorganize
envelope structures in response to extracellular stimuli. CpxAR negatively affects type 1 fimbriae expression in Klebsiella pneumoniae CG43, a hypervirulent strain. The involvement of CpxAR in the regulation of type 3 fimbriae expression was investigated.
Methods: cpxAR, cpxA, and cpxR gene-specific deletion mutants were generated. The deletion effects on the expression of type 1 and type 3 fimbriae were analyzed via measuring the promoter activity, mannose sensitive yeast agglutination activity, biofilm formation, and the production of the major pilins FimA and MrkA respectively. RNA sequencing analysis of CG43S3, DcpxAR, DcpxR and Dfur was employed to study the regulatory mechanism influencing the expression of type 3 fimbriae.
Results: Deletion of cpxAR increased type 1 and type 3 fimbrial expression. Comparative transcriptomic analysis showed that the expression of oxidative stress-responsive enzymes, type 1 and type 3 fimbriae, and iron acquisition and homeostasis control systems were differentially affected by cpxAR or cpxR deletion. Subsequent analysis revealed that the small RNA RyhB negatively affects the expression of type 3 fimbriae, while CpxAR positively controls ryhB expression. Finally, the site-directed mutation of the predicted interacting sequences of RyhB with the mRNA of MrkA attenuated the RyhB repression of type 3 fimbriae.

A genome-wide association study (GWAS) of the personality constructs in CPAI-2 in Taiwanese Hakka populations

林勇欣副教授研究團隊發表研究成果於PLOS ONE

連結網址:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281903

Abstract

Here in this study we adopted genome-wide association studies (GWAS) to investigate the genetic components of the personality constructs in the Chinese Personality Assessment Inventory 2 (CPAI-2) in Taiwanese Hakka populations, who are likely the descendants of a recent admixture between a group of Chinese immigrants with high emigration intention and a group of the Taiwanese aboriginal population generally without it. A total of 279 qualified participants were examined and genotyped by an Illumina array with 547,644 SNPs to perform the GWAS. Although our sample size is small and that unavoidably limits our statistical power (Type 2 error but not Type 1 error), we still found three genomic regions showing strong association with Enterprise, Diversity, and Logical vs. Affective Orientation, respectively. Multiple genes around the identified regions were reported to be nervous system related, which suggests that genetic variants underlying the certain personalities should indeed exist in the nearby areas. It is likely that the recent immigration and admixture history of the Taiwanese Hakka people created strong linkage disequilibrium between the emigration intention-related genetic variants and their neighboring genetic markers, so that we could identify them despite with only limited statistical power.

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