Biomedical Journal最新文献

{"title":"Hepatocellular carcinoma systemic treatment 2024 update: from early to advanced stage.","authors":"Wei Teng, Tai-Chi Wu, Shi-Ming Lin","doi":"10.1016/j.bj.2024.100815","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100815","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) ranks the sixth most common malignancy but the third leading cause of cancer-related mortality in the world. Significant breakthroughs have been made in systemic treatment for HCC over the past two decades, which have improved treatment outcomes. In addition to multiple tyrosine kinase inhibitors (mTKIs), immune checkpoint inhibitors (ICIs) and antiangiogenic drugs are increasingly being applied. The combination of ICI and antiangiogenic or dual ICIs has become the new standard of care due to remarkable response rates. However, currently available systemic regimens are primarily reserved for certain patients in the intermediate and advanced stages who will not benefit from locoregional treatments. Evidence supporting the use of systemic treatment as neoadjuvant or adjuvant therapies in patients with early-stage HCC, especially the high risk of recurrence after curative treatments, remains limited. This review identified recent developments in systemic therapy, including mTKIs and ICIs, considering results on first- and second-line treatment, role of neoadjuvant and adjuvant settings, and combination with loco-regional therapy. Various ongoing clinical trials regarding the role of systemic therapies and potential novel targets in patients with early-, intermediate-, and advanced-stage HCC were also summarized and revealed that systemic therapy is no longer limited to advanced-stage HCC. Moreover, the introduction of T-cell redirecting strategies, including bispecific antibodies and chimeric antigen receptor T cells, has revolutionized the treatment landscape for HCC. Future research should focus on an in-depth exploration of the mechanisms governing the establishment of tumor barriers.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100815"},"PeriodicalIF":4.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Bioenergetics Deficiency in cisd-1 Mutants is Linked to AMPK-Mediated Lipid Metabolism.","authors":"Kuei-Ching Hsiung, Hsiang-Yu Tang, Mei-Ling Cheng, Li-Man Hung, Bertrand Chin-Ming Tan, Szecheng J Lo","doi":"10.1016/j.bj.2024.100806","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100806","url":null,"abstract":"<p><strong>Background: </strong>CISD-1 is a mitochondrial iron-sulfate [2Fe-2S] protein known to be associated with various human diseases, including cancer and diabetes. Previously, we demonstrated that CISD-1 deficiency in worms lowers glucose and ATP levels. In this study, we further explored how worms compensate for lower ATP levels by analyzing changes in cytoplasmic and mitochondrial iron content, AMPK activities, and total lipid profiles.</p><p><strong>Materials and methods: </strong>Expression levels of CISD-1 and CISD-1::GFP fusion proteins in wild-type worms (N2), cisd-1-deletion mutants (tm4993 and syb923) and GFP insertion transgenic worms (PHX953 and SJL40) were examined by western blot. Fluorescence microscopy analyzed CISD-1::GFP pattern in PHX953 embryos and adults, and lipid droplet sizes in N2, cisd-1, aak-2 and aak-2;cisd-1 worms. Total and mitochondrial iron content, electron transport complex profiles, and AMPK activity were investigated in tm4993 and syb923 mutants. mRNA levels of mitochondrial β-oxidation genes, acs-2, cpt-5, and ech-1, were quantified by RT-qPCR in various genetic worm strains. Lipidomic analyses were performed in N2 and cisd-1(tm4993) worms.</p><p><strong>Results: </strong>Defects in cisd-1 lead to an imbalance in iron transport and cause proton leak, resulting in lower ATP production by interrupting the mitochondrial electron transport chain. We identified a signaling pathway that links ATP deficiency-induced AMPK (AMP activated protein kinase) activation to the expression of genes that facilitate lipolysis via β-oxidation.</p><p><strong>Conclusion: </strong>Our data provide a functional coordination between CISD-1 and AMPK constitutes a mitochondrial bioenergetics quality control mechanism that provides compensatory energy resources.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100806"},"PeriodicalIF":4.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of purinoreceptors in the release of extracellular vesicles and consequences on immune response and cancer progression.","authors":"Thomat Duret, Mohammed Elmallah, Jérôme Rollin, Philippe Gatault, Lin-Hua Jiang, Sébastien Roger","doi":"10.1016/j.bj.2024.100805","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100805","url":null,"abstract":"<p><p>Cell-to-cell communication is a major process for accommodating cell functioning to changes in the environments and to preserve tissue and organism homeostasis. It is achieved by different mechanisms characterized by the origin of the message, the molecular nature of the messenger, its speed of action and its reach. Purinergic signalling is a powerful mechanism initiated by extracellular nucleotides, such as ATP, acting on plasma membrane purinoreceptors. Purinergic signalling is tightly controlled in time and space by the action of ectonucleotidases. Recent studies have highlighted the critical role of purinergic signalling in controlling the generation, release and fate of extracellular vesicles and, in this way, mediating long-distance responses. Most of these discoveries have been made in immune and cancer cells. This review is aimed at establishing the current knowledge on the way which purinoreceptors control extracellular vesicle-mediated communications and consequences for recipient cells.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100805"},"PeriodicalIF":4.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Excess Charge Mitigation in Electromagnetic Hygiene: An Integrative review.","authors":"Isaac A Jamieson, J Nigel B Bell, Paul Holdstock","doi":"10.1016/j.bj.2024.100801","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100801","url":null,"abstract":"<p><p>The electromagnetic characteristics of many environments have changed significantly in recent decades. This is in large part due to the increased presence of equipment that emits electromagnetic radiation and materials that may often readily gain excess charge. The presence of excess charge can often increase risk of infection from pathogens, and likelihood of individuals experiencing compromised performance, respiratory problems and other adverse health issues from increased uptake of particulate matter. It is proposed that adopting improved electromagnetic hygiene measures, including optimized humidity levels, to reduce the presence of inappropriate levels of electric charge can help reduce the likelihood of ill health, infection and poor performance arising from contaminant inhalation and deposition, plus reduce the likelihood of medical devices and other electronic devices getting damaged and/or having their data compromised. It is suggested that such measures should be more widely adopted within clinical practice guidelines and water, sanitation and hygiene programs.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100801"},"PeriodicalIF":4.1,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divine life force: The fragile power of blood","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2024.100804","DOIUrl":"10.1016/j.bj.2024.100804","url":null,"abstract":"<div><div>Issue 47–6 of the <em>Biomedical Journal</em> explores the delicate boundaries of human blood. It examines the relationship between anemia and the gut microbiome, as well as the modified activation patterns in compensatory blood oxygenation observed in COVID-19, and lastly a series of experiments investigates the effects of SARS-CoV-2 variant spike proteins on the biology and morphology of red blood cells. Additionally, a fungus endemic to Taiwan shows potential as a treatment for pulmonary fibrosis, while relevant co-infections in schistosomiasis appear to be benefitting from altered receptor signaling in macrophages. A genomic study identifies an important locus in Taiwanese patients with Tourette syndrome, and a retrospective evaluation is conducted on the incidental detection of common bile duct dilatation in pediatric patients.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 6","pages":"Article 100804"},"PeriodicalIF":4.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning Significantly Boosts CRT Response Prediction Using Synthetic Longitudinal Strain Data: Training on Synthetic Data and Testing on Real Patients.","authors":"Ying-Feng Chang, Kun-Chi Yen, Chun-Li Wang, Sin-You Chen, Jenhui Chen, Pao-Hsien Chu, Chao-Sung Lai","doi":"10.1016/j.bj.2024.100803","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100803","url":null,"abstract":"<p><strong>Background: </strong>Recently, as a relatively novel technology, artificial intelligence (especially in the deep learning fields) has received more and more attention from researchers and has successfully been applied to many biomedical domains. Nonetheless, just a few research works use deep learning skills to predict the cardiac resynchronization therapy (CRT)-response of heart failure patients.</p><p><strong>Objective: </strong>We try to use the deep learning-based technique to construct a model which is used to predict the CRT response of patients with high prediction accuracy, precision, and sensitivity.</p><p><strong>Methods: </strong>Using two-dimensional echocardiographic strain traces from 131 patients, we pre-processed the data and synthesized 2,000 model inputs through the synthetic minority oversampling technique (SMOTE). These inputs trained and optimized deep neural networks (DNN) and one-dimensional convolution neural networks (1D-CNN). Visualization of prediction results was performed using t-distributed stochastic neighbor embedding (t-SNE), and model performance was evaluated using accuracy, precision, sensitivity, F1 score, and specificity. Variable importance was assessed using Shapley additive explanations (SHAP) analysis.</p><p><strong>Results: </strong>Both the optimal DNN and 1D-CNN models demonstrated exceptional predictive performance, with prediction accuracy, precision, and sensitivity all around 90%. Furthermore, the area under the receiver operating characteristic curve (AUROC) of the optimal 1D-CNN and DNN models achieved 0.8734 and 0.9217, respectively. Crucially, the most significant input variables for both models align well with clinical experience, further corroborating their robustness and applicability in real-world settings.</p><p><strong>Conclusions: </strong>We believe that both the DL models could be an auxiliary to help in treatment response prediction for doctors because of the excellent prediction performance and the convenience of obtaining input data to predict the CRT response of patients clinically.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100803"},"PeriodicalIF":4.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements, Challenges, and Future Prospects in Clinical Hyperpolarized Magnetic Resonance Imaging: A Comprehensive Review.","authors":"Ching-Yi Hsieh, Ying-Chieh Lai, Kuan-Ying Lu, Gigin Lin","doi":"10.1016/j.bj.2024.100802","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100802","url":null,"abstract":"<p><p>Hyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2-13C]pyruvate and [1-13C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100802"},"PeriodicalIF":4.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Communicating across distances – Biological functions of extracellular vesicles","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2024.100792","DOIUrl":"10.1016/j.bj.2024.100792","url":null,"abstract":"<div><div>This issue of the <em>Biomedical Journal</em> features a special section on extracellular vesicles (EVs), covering their role in neurological diseases, viral infections, trogocytosis, allogeneic organ rejection and tolerance, as well as EV biodistribution. Two articles explore the mechanisms of Parkinson's disease, focusing on white matter and exosomes. This journal issue also examines polyomavirus-induced damage in renal transplant grafts, proposes a miRNA signature as a diagnostic biomarker for Kawasaki disease, discusses neural gating and associated brain wave alterations, and further clarifies the relationship between gut microbiota and immune checkpoint inhibitors. Additionally, the importance of therapeutic drug monitoring is reaffirmed.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 5","pages":"Article 100792"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ratio of Remaining to Expected Small Bowel Length Predicts Enteral Autonomy in Pediatric Patients with Short Bowel Syndrome.","authors":"Chia-Wei Chang, Pai-Jui Yeh, Hung-Hsian Lai, Mi-Chi Chen, Yung-Ching Ming, Jing-Yao Lai, Ming-Wei Lai","doi":"10.1016/j.bj.2024.100791","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100791","url":null,"abstract":"<p><strong>Background: </strong>Pediatric patients with short bowel syndrome (SBS) often require long-term parenteral nutrition and intravenous fluid support (PN) until enteral autonomy (EA). However, long-term PN accounts for many complications. We aimed to investigate the outcome and predictors of EA in these patients.</p><p><strong>Material and methods: </strong>This retrospective observational study was conducted in Children's Medical Center, Chang Gung Memorial Hospital, a tertiary hospital in Northern Taiwan. Twenty-four patients afflicted with short bowel syndrome between 2002 and 2021 were included. Demographics, operation results, follow-up status, complications, and outcomes were reviewed.</p><p><strong>Results: </strong>Among the 24 patients, 14 were males (58%). The median age at bowel resection was 3 days (IQR, 1.3 to 28.8 days). The most common etiologies were total/subtotal intestinal aganglionosis (TIA) (N=6) and malrotation with midgut volvulus (N=6). The median length of the residual small intestine was 25cm (IQR, 7.8 to 71.3cm). Ten (41.7%) had preserved ileocecal valve, and 14 (58.3%) had colon-in-continuity. Intestinal failure-associated liver disease (IFALD) occurred in 14 patients (58.3%), but none had advanced disease. Seven (29.2%) patients achieved enteral autonomy after 10.1±7.3 months. Five patients (21%) expired due to sepsis. Logistic regression and Kaplan-Meier analysis showed the predictors of enteral autonomy were remaining-to-expected small bowel length ratio > 25% and the absence of IFALD.</p><p><strong>Conclusions: </strong>In this pediatric short bowel syndrome study, enteral autonomy was achieved in 29% after a mean PN duration of 10 months. The remaining-to-expected small bowel length ratio at bowel resection was the most critical predictor of enteral autonomy.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100791"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytidine Deaminase Enhances Liver Cancer Invasion by Modulating Epithelial-Mesenchymal Transition via NFκB Signaling.","authors":"Chia-Jung Liao, Yang-Hsiang Lin, Huei-Tzu Chien, Yi-Wen Wang, Tzu-Kang Lin, Chau-Ting Yeh, Kwang-Huei Lin","doi":"10.1016/j.bj.2024.100789","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100789","url":null,"abstract":"<p><strong>Background: </strong>Cancer metastasis is the leading cause of cancer-related deaths, underscoring the importance of understanding its underlying mechanisms. Hepatocellular carcinoma (HCC), a highly malignant type of cancer, was selected as our research model.</p><p><strong>Material and methods: </strong>We aimed to develop high-metastatic cell lines using in vitro and in vivo selection strategies and identify critical metastasis-related genes through microarray analyses by comparing them with parental cells.</p><p><strong>Results: </strong>Our results showed that the high-metastatic cell lines exhibited significantly stronger invasion abilities than parental cells. Microarray analyses identified cytidine deaminase (CDA), a gene associated with systemic chemotherapy resistance, as one of the overexpressed genes in the high-metastatic cells. Data analysis from The Cancer Genome Atlas Program revealed that while CDA is downregulated in HCC, patients with high CDA expression tend to have poorer prognoses. Cell models confirmed that CDA overexpression enhances cell migration and invasion, whereas CDA knockdown inhibits these abilities. Investigating the key molecules involved in the epithelial-mesenchymal transition (EMT), we found that CDA overexpression increases the expression of fascin, N-cadherin, β-catenin, and snail while decreasing E-cadherin expression. Conversely, CDA knockdown produced opposite results. Additionally, we discovered that CDA regulates NF-κB signaling, which controls the expression of N-cadherin, thereby promoting the invasion capability of HCC cells.</p><p><strong>Conclusions: </strong>We isolated highly metastatic cells and identified potential HCC metastasis-related genes. CDA promotes cell invasion by regulating EMT through the NF-κB pathway. Future studies are warranted to explore the potential of CDA as a biomarker for prognosis and therapeutic decision-making.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100789"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}