Advanced biologyPub Date : 2024-08-12DOI: 10.1002/adbi.202400034
Marilisa Cortesi, Dongli Liu, Elyse Powell, Ellen Barlow, Kristina Warton, Caroline E. Ford
{"title":"Accurate Identification of Cancer Cells in Complex Pre-Clinical Models Using a Deep-Learning Neural Network: A Transfection-Free Approach","authors":"Marilisa Cortesi, Dongli Liu, Elyse Powell, Ellen Barlow, Kristina Warton, Caroline E. Ford","doi":"10.1002/adbi.202400034","DOIUrl":"10.1002/adbi.202400034","url":null,"abstract":"<p>3D co-cultures are key tools for in vitro biomedical research as they recapitulate more closely the in vivo environment while allowing a tighter control on the culture's composition and experimental conditions. The limited technologies available for the analysis of these models, however, hamper their widespread application. The separation of the contribution of the different cell types, in particular, is a fundamental challenge. In this work, ORACLE (OvaRiAn Cancer ceLl rEcognition) is presented, a deep neural network trained to distinguish between ovarian cancer and healthy cells based on the shape of their nucleus. The extensive validation that are conducted includes multiple cell lines and patient-derived cultures to characterize the effect of all the major potential confounding factors. High accuracy and reliability are maintained throughout the analysis (F1<sub>score</sub>> 0.9 and Area under the ROC curve -ROC-AUC- score = 0.99) demonstrating ORACLE's effectiveness with this detection and classification task. ORACLE is freely available (https://github.com/MarilisaCortesi/ORACLE/tree/main) and can be used to recognize both ovarian cancer cell lines and primary patient-derived cells. This feature is unique to ORACLE and thus enables for the first time the analysis of in vitro co-cultures comprised solely of patient-derived cells.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-08-09DOI: 10.1002/adbi.202400134
Cécile Beust, Alberto Valdeolivas, Anthony Baptista, Galadriel Brière, Nicolas Lévy, Ozan Ozisik, Anaïs Baudot
{"title":"The Molecular Landscape of Premature Aging Diseases Defined by Multilayer Network Exploration","authors":"Cécile Beust, Alberto Valdeolivas, Anthony Baptista, Galadriel Brière, Nicolas Lévy, Ozan Ozisik, Anaïs Baudot","doi":"10.1002/adbi.202400134","DOIUrl":"10.1002/adbi.202400134","url":null,"abstract":"<p>Premature Aging (PA) diseases are rare genetic disorders that mimic some aspects of physiological aging at an early age. Various causative genes of PA diseases have been identified in recent years, providing insights into some dysfunctional cellular processes. However, the identification of PA genes also revealed significant genetic heterogeneity and highlighted the gaps in this understanding of PA-associated molecular mechanisms. Furthermore, many patients remain undiagnosed. Overall, the current lack of knowledge about PA diseases hinders the development of effective diagnosis and therapies and poses significant challenges to improving patient care.</p><p>Here, a network-based approach to systematically unravel the cellular functions disrupted in PA diseases is presented. Leveraging a network community identification algorithm, it is delved into a vast multilayer network of biological interactions to extract the communities of 67 PA diseases from their 132 associated genes. It is found that these communities can be grouped into six distinct clusters, each reflecting specific cellular functions: DNA repair, cell cycle, transcription regulation, inflammation, cell communication, and vesicle-mediated transport. That these clusters collectively represent the landscape of the molecular mechanisms that are perturbed in PA diseases, providing a framework for better understanding their pathogenesis is proposed. Intriguingly, most clusters also exhibited a significant enrichment in genes associated with physiological aging, suggesting a potential overlap between the molecular underpinnings of PA diseases and natural aging.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-08-09DOI: 10.1002/adbi.202300629
Khushbu Agrawal, Sunil Kumar
{"title":"Wavelet Collocation Method for HIV-1/HTLV-I Co-Infection Model Using Hermite Polynomial","authors":"Khushbu Agrawal, Sunil Kumar","doi":"10.1002/adbi.202300629","DOIUrl":"10.1002/adbi.202300629","url":null,"abstract":"<p>In this study, the dynamic behavior of fractional order co-infection model with human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) is analyzed using operational matrix of Hermite wavelet collocation method. Also, the uniqueness and existence of solutions are calculated based on the fixed point hypothesis. For the fractional order co-infection model, its positivity and boundedness are demonstrated. Furthermore, different types of Ulam-Hyres stability are also discussed. The numerical solution of the model are obtained by using the operational matrix of the Hermite wavelet approach. This scheme is used to solve the system of nonlinear equations that are very fruitful and easy to implement. Additionally, the stability analysis of the numerical scheme is explained. The mathematical model taken in this work incorporates the biological characteristics of both HIV-1 and HTLV-I. After that all the equilibrium points of the fractional order co-infection model are found and their existence conditions are explored with the help of the Caputo derivative. The global stability of all equilibrium points of this model are determined with the help of Lyapunov functions and the LaSalle invariance principle. Convergence analysis is also discussed. Hermite wavelet operational matrix methods are more accurate and convergent than other numerical methods. Lastly, variations in model dynamics are found when examining different fractional order values. These findings will be valuable to biologists in the treatment of HIV-1/HTLV-I.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 10","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-08-09DOI: 10.1002/adbi.202300511
Landys Lopez Quezada, Felix Mba Medie, Rebeccah J. Luu, Robert B. Gaibler, Elizabeth P. Gabriel, Logan D. Rubio, Thomas J. Mulhern, Elizabeth E. Marr, Jeffrey T. Borenstein, Christine R. Fisher, Ashley L. Gard
{"title":"Predicting Clinical Outcomes of SARS-CoV-2 Drug Efficacy with a High-Throughput Human Airway Microphysiological System","authors":"Landys Lopez Quezada, Felix Mba Medie, Rebeccah J. Luu, Robert B. Gaibler, Elizabeth P. Gabriel, Logan D. Rubio, Thomas J. Mulhern, Elizabeth E. Marr, Jeffrey T. Borenstein, Christine R. Fisher, Ashley L. Gard","doi":"10.1002/adbi.202300511","DOIUrl":"10.1002/adbi.202300511","url":null,"abstract":"<p>The average cost to bring a new drug from its initial discovery to a patient's bedside is estimated to surpass $2 billion and requires over a decade of research and development. There is a need for new drug screening technologies that can parse drug candidates with increased likelihood of clinical utility early in development in order to increase the cost-effectiveness of this pipeline. For example, during the COVID-19 pandemic, resources were rapidly mobilized to identify effective therapeutic treatments but many lead antiviral compounds failed to demonstrate efficacy when progressed to human trials. To address the lack of predictive preclinical drug screening tools, PREDICT96-ALI, a high-throughput (<i>n</i> = 96) microphysiological system (MPS) that recapitulates primary human tracheobronchial tissue,is adapted for the evaluation of differential antiviral efficacy of native SARS-CoV-2 variants of concern. Here, PREDICT96-ALI resolves both the differential viral kinetics between variants and the efficacy of antiviral compounds over a range of drug doses. PREDICT96-ALI is able to distinguish clinically efficacious antiviral therapies like remdesivir and nirmatrelvir from promising lead compounds that do not show clinical efficacy. Importantly, results from this proof-of-concept study track with known clinical outcomes, demonstrate the feasibility of this technology as a prognostic drug discovery tool.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202300511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-07-30DOI: 10.1002/adbi.202400099
Zhenyu Hu, Yongjie Luo, Wei Lin, Xiaolian Wu
{"title":"IRF4 Suppresses Osteogenic Differentiation of Periodontal Ligament Stem Cells by Activating IL-18 Signaling Pathway in Periodontitis","authors":"Zhenyu Hu, Yongjie Luo, Wei Lin, Xiaolian Wu","doi":"10.1002/adbi.202400099","DOIUrl":"10.1002/adbi.202400099","url":null,"abstract":"<p>The present study aims to investigate the role of interferon regulatory factor 4 (IRF4) in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and analyze the underlying signaling of these processes. In this study, IRF4 is upregulated in periodontitis periodontal ligament tissues, as compared to healthy periodontal ligament tissues. IRF4 knockdown increases cell proliferation, decreases levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-8, enhances osteogenic activity, and increases the expression of RUNX family transcription factor 2, Collagen I, and Osteocalcin in PDLSCs. The opposite results are observed in IRF4 overexpressed PDLSCs. Additionally, GSEA shows that IRF4 activates the interleukin-18 (IL-18) signaling pathway. The expressions of IL-18, B-cell translocation gene 2, interleukin-1beta, and caspase-3 are decreased by IRF4 knockdown, while increased by IRF4 overexpression. IL-18 overexpression eliminates the promoting effect of IRF4 knockdown on osteogenic differentiation of PDLSCs. In conclusion, IRF4 suppresses osteogenic differentiation of PDLSCs by activating the IL-18 signaling pathway.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-07-29DOI: 10.1002/adbi.202400213
Evelyn Echevarria-Cruz, David W McMillan, Kieran F Reid, Rodrigo J Valderrábano
{"title":"Spinal Cord Injury Associated Disease of the Skeleton, an Unresolved Problem with Need for Multimodal Interventions.","authors":"Evelyn Echevarria-Cruz, David W McMillan, Kieran F Reid, Rodrigo J Valderrábano","doi":"10.1002/adbi.202400213","DOIUrl":"https://doi.org/10.1002/adbi.202400213","url":null,"abstract":"<p><p>Spinal cord injury is associated with skeletal unloading, sedentary behavior, decreases in skeletal muscle mass, and exercise intolerance, which results in rapid and severe bone loss. To date, monotherapy with physical interventions such as weight-bearing in standing frames, computer-controlled electrically stimulated cycling and ambulation exercise, and low-intensity vibration are unsuccessful in maintaining bone density after SCI. Strategies to maintain bone density with commonly used osteoporosis medications also fail to provide a significant clinical benefit, potentially due to a unique pathology of bone deterioration in SCI. In this review, the available data is discussed on evaluating and monitoring bone loss, fracture, and physical and pharmacological therapeutic approaches to SCI-associated disease of the skeleton. The treatment of SCI-associated disease of the skeleton, the implications for clinical management, and areas of need are considered for future investigation.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400213"},"PeriodicalIF":3.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-07-29DOI: 10.1002/adbi.202400231
Kell Grandjean da Costa, Eduardo Bodnariuc Fontes, Alekya Menta, Arthur F Kramer, Roger A Fielding, Joe Verghese, Christopher Kowaleski, Nathan Ward, Kieran F Reid
{"title":"Prefrontal Cortex Oxygenation During Exercise in Older Adults with Motoric Cognitive Risk Syndrome.","authors":"Kell Grandjean da Costa, Eduardo Bodnariuc Fontes, Alekya Menta, Arthur F Kramer, Roger A Fielding, Joe Verghese, Christopher Kowaleski, Nathan Ward, Kieran F Reid","doi":"10.1002/adbi.202400231","DOIUrl":"https://doi.org/10.1002/adbi.202400231","url":null,"abstract":"<p><p>Motoric cognitive risk syndrome (MCR) is a pre-dementia syndrome characterized by subjective memory complaints and gait impairments that may be related to lower prefrontal cortex (PFC) function. Acute bouts of aerobic exercise are shown to improve PFC function, however, the acute effects of exercise on PFC oxygenation have not yet been examined in MCR. This study aims to characterize the PFC oxygenation responses during acute exercise in older adults with MCR. Nineteen older adults with MCR performed a submaximal cycling exercise protocol. Functional near-infrared spectroscopy (fNIRS) is used to measure concentrations of oxygenated (OxyHb) and deoxygenated (DeoxyHb) hemoglobin from the PFC. There is a trend for increased OxyHb concentrations and decreased DeooxyHb concentrations during exercise. Exercise also induced significant increases in ratings of perceived exertion (RPEs) and heart rate. A significant, positive correlation between PFC OxyHb and RPEs during the cycling exercise are also observed. The findings reveal that PFC oxygenation increases during exercise in an intensity-dependent manner and the subjective perception of exertion is associated with the magnitude of PFC oxygenation. These results suggest that moderate-intensity cycling exercise may have beneficial effects on increasing cerebral blood flow in the PFC of older adults with MCR.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400231"},"PeriodicalIF":3.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Progress in Generation of Inner Ear Organoid","authors":"Yanjun Zong, Xiaozhou Liu, Yaqi Zhang, Jiahui Zhao, Xinyu Shi, Zhengdong Zhao, Yu Sun","doi":"10.1002/adbi.202400223","DOIUrl":"10.1002/adbi.202400223","url":null,"abstract":"<p>Inner ear organoids play a crucial role in hearing research. In comparison to other animal models and 2D cell culture systems, inner ear organoids offer significant advantages for studying the mechanisms of inner ear development and exploring novel approaches to disease treatment. Inner ear organoids derived from human cells are more closely resemble normal human organs in development and function. The 3D culture system of the inner ear organoid enhances cell–cell interactions and mimics the internal environment. In this review, the progress and limitations of organoid culture methods derived from tissue-specific progenitors and pluripotent stem cells (PSCs) are summarized, which may offer new insights into generating organoids that closely resemble the inner ear in terms of morphology and function.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 10","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering of Erythrocytes as Drug Carriers for Therapeutic Applications.","authors":"Baoshuo Jia, Yujie Shi, Yuling Yan, Hui Shi, Jing Zheng, Jianbo Liu","doi":"10.1002/adbi.202400242","DOIUrl":"https://doi.org/10.1002/adbi.202400242","url":null,"abstract":"<p><p>Erythrocytes, also known as red blood cells (RBCs), have garnered considerable attention as potential carriers for drug delivery, owing to their inherent properties such as biocompatibility, biodegradability, and prolonged circulation half-life. This paper presents a comprehensive overview of the role of erythrocytes in drug delivery, elucidating recent advancements in delivering a diverse array of therapeutic agents, including small molecules, nucleic acids, antibodies, protein enzymes, and nanoparticles. Two primary strategies for encapsulating drugs within erythrocytes are systematically discussed: internal loading and surface loading. Each strategy offers distinct advantages in terms of drug stability and release kinetics. Notably, the utilization of erythrocyte membrane camouflaged nanocarriers holds promise for enhancing the biocompatibility of conventional nanoparticles and facilitating targeted drug delivery. Furthermore, the broad spectrum of biomedical applications of erythrocyte-based drug delivery systems are examined, ranging from cancer treatment to diabetes management, thrombosis prevention, and immunotherapy. This review provides a comprehensive evaluation of current technologies in erythrocyte-loaded drug delivery, highlighting the strengths, weaknesses, and future directions for advancing therapeutic interventions in various disease contexts.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400242"},"PeriodicalIF":3.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-07-22DOI: 10.1002/adbi.202400148
Lan Yao, Chengyuan Yang, J. Carolyn Graff, Guiying Wang, Gang Wang, Weikuan Gu
{"title":"From Reactive to Proactive – The Future Life Design to Promote Health and Extend the Human Lifespan","authors":"Lan Yao, Chengyuan Yang, J. Carolyn Graff, Guiying Wang, Gang Wang, Weikuan Gu","doi":"10.1002/adbi.202400148","DOIUrl":"10.1002/adbi.202400148","url":null,"abstract":"<p>Disease treatment and prevention have improved the human lifespan. Current studies on aging, such as the biological clock and senolytic drugs have focused on the medical treatments of various disorders and health maintenance. However, to efficiently extend the human lifespan to its theoretical maximum, medicine can take a further proactive approach and identify the inapparent disorders that affect the gestation, body growth, and reproductive stages of the so-called “healthy” population. The goal is to upgrade the standard health status to a new level by targeting the inapparent disorders. Thus, future research can shift from reaction, response, and prevention to proactive, quality promotion and vigor prolonging; from single disease-oriented to multiple dimension protocol for a healthy body; from treatment of symptom onset to keep away from disorders; and from the healthy aging management to a healthy promotion design beginning at the birth.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 10","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}