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

連結網址：https://pubmed.ncbi.nlm.nih.gov/36845415/

Abstract

Introduction: Primary dysmenorrhea (PDM), the most prevalent gynecological problem among women of reproductive age, presents as a regular pattern of cyclic menstrual pain. The presence or absence of central sensitization (i.e., pain hypersensitivity) in cases of PDM is a contentious issue. Among Caucasians, the presence of dysmenorrhea is associated with pain hypersensitivity throughout the menstrual cycle, indicating pain amplification mediated by the central nervous system. We previously reported on the absence of central sensitization to thermal pain among Asian PDM females. In this study, functional magnetic resonance imaging was used to reveal mechanisms underlying pain processing with the aim of explaining the absence of central sensitization in this population.

Methods: Brain responses to noxious heat applied to the left inner forearm of 31 Asian PDM females and 32 controls during their menstrual and periovulatory phases were analyzed.

Results and discussion: Among PDM females experiencing acute menstrual pain, we observed a blunted evoked response and de-coupling of the default mode network from the noxious heat stimulus. The fact that a similar response was not observed in the non-painful periovulatory phase indicates an adaptive mechanism aimed at reducing the impact of menstrual pain on the brain with an inhibitory effect on central sensitization. Here we propose that adaptive pain responses in the default mode network may contribute to the absence of central sensitization among Asian PDM females. Variations in clinical manifestations among different PDM populations can be attributed to differences in central pain processing.

林峻宇助理教授研究團隊發表研究成果於Brief Bioinform.

連結網址：https://pubmed.ncbi.nlm.nih.gov/36719112/

Abstract

Recently, extracting inherent biological system information (e.g. cellular networks) from genome-wide expression profiles for developing personalized diagnostic and therapeutic strategies has become increasingly important. However, accurately constructing single-sample networks (SINs) to capture individual characteristics and heterogeneity in disease remains challenging. Here, we propose a sample-specific-weighted correlation network (SWEET) method to model SINs by integrating the genome-wide sample-to-sample correlation (i.e. sample weights) with the differential network between perturbed and aggregate networks. For a group of samples, the genome-wide sample weights can be assessed without prior knowledge of intrinsic subpopulations to address the network edge number bias caused by sample size differences. Compared with the state-of-the-art SIN inference methods, the SWEET SINs in 16 cancers more likely fit the scale-free property, display higher overlap with the human interactomes and perform better in identifying three types of cancer-related genes. Moreover, integrating SWEET SINs with a network proximity measure facilitates characterizing individual features and therapy in diseases, such as somatic mutation, mut-driver and essential genes. Biological experiments further validated two candidate repurposable drugs, albendazole for head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAD) and encorafenib for HNSCC. By applying SWEET, we also identified two possible LUAD subtypes that exhibit distinct clinical features and molecular mechanisms. Overall, the SWEET method complements current SIN inference and analysis methods and presents a view of biological systems at the network level to offer numerous clues for further investigation and clinical translation in network medicine and precision medicine.

廖光文教授研究團隊發表研究成果於 J Exp Clin Cancer Res

連結網址：https://jeccr.biomedcentral.com/articles/10.1186/s13046-023-02601-8

Abstract

Background

The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed.

Methods

The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells’ membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies.

Results

The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment.

Conclusions

Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.

王雲銘教授研究團隊發表研究成果於 Chemical Engineering Journal

連結網址：https://www.sciencedirect.com/science/article/pii/S1385894723001754#f0040

Abstract

Early surveillance of oral cancer demands utmost concern owing to its alarming prevalence in the modern world. An efficient electrochemical impedimetric immunosensor is fabricated based on bimetallic amino-functionalized FeCo metal–organic frameworks uniformly grown on porous nickel foam solid supports (FeCo-MOF/NF) as a transducer for the detection of oral squamous cell carcinoma (OSCC). Herein, the interleukin-1 receptor antagonist (IL-1RA) antibody is used as a biorecognition element for the first time in the determination of oral cancer in real human blood samples using electrochemical impedance spectroscopy (EIS). Furthermore, the presence of specific functional groups ensures selectivity and rapid sensitivity against the target analyte IL-1RA when compared to the other biomarkers including interleukin-6 (IL-6), interleukin-8 (IL-8), CYFRA 21-1, and so on. The immunosensor shows a wide linear dynamic detection range of IL-1RA (10 fg/mL to 10 ng/mL) with a limit of detection (LOD) of 7.30 fg/mL in buffer and 7.22 fg/mL in serum conditions and a limit of quantification (LOQ) of 22.14 fg/mL in PBS and 21.88 fg/mL in serum. For a real-life demonstration, IL-1RA in human samples is detected by the immunosensor for the first time and compared with the gold standard method. The immunosensor also displays an excellent correlation with the standard detection of IL-1RA in human samples. Altogether, this work demonstrates that the electrochemical immunosensor has a high clinical significance by being a promising alternative to conventional approaches.

張家靖教授研究團隊發表研究成果於 Int. J. Mol. Sci.

連結網址：https://www.mdpi.com/1422-0067/24/2/1348

Abstract

Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances

in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.