tbuckley/cabot-search huggingface dataset:
Recapitulating the Cancer‐Immunity Cycle on a Chip
Authors: Yujin Lee, Jaehong Min, Solbin Kim, Wooju Park, Jihoon Ko, Noo Li Jeon
Journal: Advanced Healthcare Materials (2024)

The cancer-immunity cycle is a fundamental framework for understanding how the immune system interacts with cancer cells, balancing T cell recognition and elimination of tumors while avoiding autoimmune reactions. Despite advancements in immunotherapy, there remains a critical need to dissect each phase of the cycle, particularly the interactions among the tumor, vasculature, and immune system within the tumor microenvironment (TME). Innovative platforms such as organ-on-a-chip, organoids, and bioprinting within microphysiological systems (MPS) are increasingly utilized to enhance the understanding of these interactions. These systems meticulously replicate crucial aspects of the TME and immune responses, providing robust platforms to study cancer progression, immune evasion, and therapeutic interventions with greater physiological relevance. This review explores the latest advancements in MPS technologies for modeling various stages of the cancer-immune cycle, critically evaluating their applications and limitations in advancing the understanding of cancer-immune dynamics and guiding the development of next-generation immunotherapeutic strategies.
An Oxidative Stress Nano‐Amplifier for Improved Tumor Elimination and Combined Immunotherapy
Authors: Wei Zhang, Yijun Ran, Mi Yang, Yaqin Hu, Zhigang Wang, Yang Cao, Haitao Ran
Journal: Advanced Healthcare Materials (2024)

Abstract Amplifying oxidative stress to disrupt intracellular redox homeostasis can accelerate tumor cell death. In this work, an oxidative stress amplifier (PP@T) is prepared for enhanced tumor oxidation therapy to reduce tumor growth and metastases. The nano‐amplifier has been successfully constructed by embedding MTH1 inhibitor (TH588) in the PDA‐coated porphyrin metal–organic framework PCN‐224. The controllable‐released TH588 is demonstrated from pores can hinder MTH1‐mediated damage‐repairing process by preventing the hydrolysis of 8‐oxo‐dG, thereby amplifying oxidative stress and exacerbating the oxidative DNA damage induced by the sonodynamic therapy of PP@T under ultrasound irradiation. Furthermore, PP@T can effectively induce immunogenic cell death to trigger systemic anti‐tumor immune response. When administered in combination with immune checkpoint blockade, PP@T not only impedes the progression of the primary tumor but also achieves obvious antimetastasis in breast cancer murine models, including orthotopic and artificial whole‐body metastasis models. Furthermore, the nanoplatform also provides photoacoustic imaging for in vivo treatment guidance. In conclusion, by amplifying oxidative stress and reactive oxygen species sensitized immunotherapy, this image‐guided nanosystem shows potential for highly specific, effective combined therapy against tumor cells with negligible side‐effects to normal cells which will provide a new insight for precise tumor treatment.
An atlas of genetic effects on cellular composition of the tumor microenvironment
Authors: Yimin Cai, Zequn Lu, Can Chen, Ying Zhu, Zhirui Chen, Zuyou Wu, Jingyi Peng, Xuanyu Zhu, Ziying Liu, Bin Li, Ming Zhang, Jinyu Huang, Yanmin Li, Yizhuo Liu, Qianying Ma, Chunyi He, Shuoni Chen, Wen Tian, Linyun Fan, Caibo Ning, Hui Geng, Bin Xu, Haijie Li, Xu Zhu, Jun Fang, Xiaoyang Wang, Shaokai Zhang, Meng Jin, Chaoqun Huang, Xiaojun Yang, Jianbo Tian, Xiaoping Miao
Journal: Nature Immunology (2024)
Epigenetic therapy potentiates transposable element transcription to create tumor-enriched antigens in glioblastoma cells
Authors: H. Josh Jang, Nakul M. Shah, Ju Heon Maeng, Yonghao Liang, Noah L. Basri, Jiaxin Ge, Xuan Qu, Tatenda Mahlokozera, Shin-Cheng Tzeng, Russell B. Williams, Michael J. Moore, Devi Annamalai, Justin Y. Chen, Hyung Joo Lee, Patrick A. DeSouza, Daofeng Li, Xiaoyun Xing, Albert H. Kim, Ting Wang
Journal: Nature Genetics (2024)
Pulmonary Vein Isolation vs Sham Intervention in Symptomatic Atrial Fibrillation
Authors: Rajdip Dulai, Neil Sulke, Nick Freemantle, Pier D. Lambiase, David Farwell, Neil T. Srinivasan, Stuart Tan, Nikhil Patel, Adam Graham, Rick A. Veasey
Journal: JAMA (2024)

There are concerns that pulmonary vein isolation for atrial fibrillation may have a profound placebo effect, but no double-blind randomized clinical trials have been conducted.
Withdrawal notice to &lt;Corrigendum to “Comparison of baseline patient characteristics in Italian oncology drug monitoring registries and clinical trials: a real-world cross-sectional study” [The Lancet Regional Health – Europe 41 (2024) 100912]&gt;
Authors: Maria Lucia Iacovino, Simone Celant, Luca Tomassini, Laura Arenare, Andrea Caglio, Andrea Canciello, Flavio Salerno, Pier Paolo Olimpieri, Susanna Di Segni, Antonella Sferrazza, Maria Carmela Piccirillo, Giordano Domenico Beretta, Carmine Pinto, Livio Blasi, Saverio Cinieri, Luigi Cavanna, Massimo Di Maio, Pierluigi Russo, Francesco Perrone
Journal: The Lancet Regional Health - Europe (2024)

[This retracts the article DOI: 10.1016/j.lanepe.2024.100973.].
Restrictive or Liberal Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: 6-Month Mortality in the MINT Trial
Authors: Tabassome Simon, Brandon M. Herbert, Maria Mori Brooks, Shaun G. Goodman, John H. Alexander, Philippe Gabriel Steg, Renato D. Lopes, Shahab Ghafghazi, Claire Bouleti, Howard A. Cooper, Eric L. McCamant, Kevin R. Bainey, Herbert D. Aronow, J. Dawn Abbott, Caroline Alsweiler, Marnie Bertolet, Dean A. Fergusson, Andrew M. Goldsweig, Paul C. Hébert, Jeffrey L. Carson
Journal: Circulation (2024)
Decorating Delivery Vehicles Using Hyaluronic Acid Oligosaccharides Enables Active Targeting Toward Cancer and Minimizes Adverse Effect of Chemotherapeutics
Authors: Weibin Jia, Runrun Li, Fengjuan Zou, Min Li, Hongjuan Weng, Qianqian Shen, Guozhen Qi, Ruipiao Zhou, Yikang Shi, Guofeng Gu, Fengshan Wang, Zonggang Chen
Journal: Advanced Healthcare Materials (2024)

Abstract The major drawback of conventional chemotherapeutic treatment is the non‐specificity or inability to ascertain and target cancerous cells directly. In this study, an active targeting strategy that is poised to carry the anticancer agents to the desired sites for therapeutic action while avoiding toxicity to normal organs is provided. The active targeting of delivery vehicles is achieved by ligand‐receptor interactions, in particular the specific binding between hyaluronic acid oligosaccharides (oHAs) and CD44 receptors. This study first prepares oHAs by the size‐exclusion chromatography and utilizes them to decorate chitosan (CTS) as basic materials (oHAs‐CTS) for drug delivery, then fabricates oHAs‐CTS into micro/nanoscale carriers to encapsulate agents for cancer chemotherapy. The oHAs‐CTS micro/nanocarriers exhibit high drug encapsulation efficiency (58–87%), and the drug releases present a sustained behavior. Notably, oHAs‐CTS delivery vehicles display an enhanced active targeting toward cancers and alleviate the cytotoxic effects on normal cells. Additionally, in vivo results show that drug‐laden oHAs‐CTS nanocarriers demonstrate a significant inhibitory effect on 4 T1 tumors without any toxicity to the major organs. Taken together, the findings highlight the potential of oHAs‐CTS micro/nanospheres as delivery vehicles with enhanced active targeted capability toward cancers and minimized adverse effects of chemotherapeutic agents for cancer treatment.
What We Have Learned About Reducing Low-Density Lipoprotein Cholesterol and Coronary Plaques
Authors: Steven E. Nissen
Journal: JAMA Cardiology (2024)

Flavio G. Biccirè, MD; Ryota Kakizaki, MD, PhD; Konstantinos C. Koskinas, MD, MSc; Yasushi Ueki, MD, PhD; Jonas Häner, MD; Hiroki Shibutani, MD, PhD; Jacob Lønborg, MD; Ernest Spitzer, MD; Juan F. Iglesias, MD; Tatsuhiko Otsuka, MD; George C. M. Siontis, MD, PhD; Stefan Stortecky, MD; Christoph Kaiser, MD; Maria Ambühl, MSc; Laura Morf, MSc; Anna S. Ondracek, MD; Robert-Jan van Geuns, MD, PhD; David Spirk, MD; Joost Daemen, MD, PhD; François Mach, MD; Stephan Windecker, MD; Thomas Engstrøm, MD, PhD; Irene Lang, MD; Sylvain Losdat, PhD; Lorenz Räber, MD, PhD
Asthma development is associated with low mucosal <scp>IL</scp>‐10 during viral infections in early life
Authors: Mathias Elsner Melgaard, Signe Kjeldgaard Jensen, Anders Eliasen, Casper‐Emil Tingskov Pedersen, Jonathan Thorsen, Marianne Mikkelsen, Nilofar Vahman, Ann‐Marie Malby Schoos, James Gern, Susanne Brix, Jakob Stokholm, Bo Lund Chawes, Klaus Bønnelykke
Journal: Allergy (2024)

Abstract Background Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting. Objectives To investigate in situ virus‐specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma. Methods We included 493 episodes of acute respiratory illnesses in 277 children aged 0–3 years from the COPSAC 2010 mother–child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high‐sensitivity MesoScale Discovery kits and compared between children with and without viral PCR‐identification in nasopharyngeal samples. Finally, we investigated whether the virus‐specific immune response was associated with asthma by age 6 years. Results Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN‐ɣ, TNF‐α, CCL4, CXCL10 and IL‐10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR &lt;0.05). Children developing asthma had decreased levels of IL‐10 (FDR &lt;0.05) during viral episodes compared to children not developing asthma. Conclusion We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL‐10) immune mediator level. This provides insight into the interplay between early‐life viral infections, airway immunity and asthma development.
An Ultrasensitive Molecularly Imprinted Point‐Of‐Care Electrochemical Sensor for Detection of Glial Fibrillary Acidic Protein
Authors: Yixuan Li, Liuxiong Luo, Lenart Senicar, Rica Asrosa, Burcu Kizilates, Kaizhong Xing, Elias Torres, Lizhou Xu, Danyang Li, Neil Graham, Amanda Heslegrave, Henrik Zetterberg, David J. Sharp, Bing Li
Journal: Advanced Healthcare Materials (2024)

Abstract Accurate assessment of neurological disease through monitoring of biomarkers has been made possible using the antibody‐based assays. But these assays suffer from expensive development of antibody probes, reliance on complicated equipments, and high maintenance costs. Here, using the novel reduced graphene oxide/polydopamine‐molecularly imprinted polymer (rGO/PDA‐MIP) as the probe layer, a robust electrochemical sensing platform is demonstrated for the ultrasensitive detection of glial fibrillary acidic protein (GFAP), a biomarker for a range of neurological diseases. A miniaturized integrated circuit readout system is developed to interface with the electrochemical sensor, which empowers it with the potential to be used as a point‐of‐care (POC) diagnostic tool in primary clinical settings. This innovative platform demonstrated good sensitivity, selectivity, and stability, with imprinting factor evaluated as 2.8. A record low limit‐of‐detection (LoD) is down to 754.5 ag mL −1 , with a wide dynamic range from 1 to 10 6 fg mL −1 . The sensing platform is validated through the analysis of GFAP in clinical plasma samples, yielding a recovery rate range of 81.6–108.8% compared to Single Molecule Array (Simoa). This cost‐effective and user‐friendly sensing platform holds the potential to be deployed in primary and resource‐limited clinical settings for the assessment of neurological diseases.
Transition Metal Complexes as Therapeutics: A New Frontier in Combatting Neurodegenerative Disorders through Protein Aggregation Modulation
Authors: Govinda R. Navale, Imtiaz Ahmed, Mi Hee Lim, Kaushik Ghosh
Journal: Advanced Healthcare Materials (2024)

Neurodegenerative disorders (NDDs) are a class of debilitating diseases that progressively impair the protein structure and result in neurological dysfunction in the nervous system. Among these disorders, Alzheimer's disease (AD), prion diseases such as Creutzfeldt-Jakob disease (CJD), and Parkinson's disease (PD) are caused by protein misfolding and aggregation at the cellular level. In recent years, transition metal complexes have gained significant attention for their potential applications in diagnosing, imaging, and curing these NDDs. These complexes have intriguing possibilities as therapeutics due to their diverse ligand systems and chemical properties and can interact with biological systems with minimal detrimental effects. This review focuses on the recent progress in transition metal therapeutics as a new era of hope in the battle against AD, CJD, and PD by modulating protein aggregation in vitro and in vivo. It may shed revolutionary insights into unlocking new opportunities for researchers to develop metal-based drugs to combat NDDs.
Star wars against leukemia: attacking the clones
Authors: Monika M. Toma, Tomasz Skorski
Journal: Leukemia (2024)

Abstract Leukemia, although most likely starts as a monoclonal genetic/epigenetic anomaly, is a polyclonal disease at manifestation. This polyclonal nature results from ongoing evolutionary changes in the genome/epigenome of leukemia cells to promote their survival and proliferation advantages. We discuss here how genetic and/or epigenetic aberrations alter intracellular microenvironment in individual leukemia clones and how extracellular microenvironment selects the best fitted clones. This dynamic polyclonal composition of leukemia makes designing an effective therapy a challenging task especially because individual leukemia clones often display substantial differences in response to treatment. Here, we discuss novel therapeutic approach employing single cell multiomics to identify and eradicate all individual clones in a patient.
Temporary mechanical circulatory support in infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials with 6-month follow-up
Authors: Holger Thiele, Jacob E Møller, Jose P S Henriques, Margriet Bogerd, Melchior Seyfarth, Daniel Burkhoff, Petr Ostadal, Richard Rokyta, Jan Belohlavek, Steffen Massberg, Marcus Flather, Matthias Hochadel, Steffen Schneider, Steffen Desch, Anne Freund, Hans Eiskjær, Norman Mangner, Janine Pöss, Amin Polzin, P Christian Schulze, Carsten Skurk, Uwe Zeymer, Christian Hassager, Daniel Burkhoff, Howard Cohen, Corinna Brunckhorst, William W. O'Neill, Holger Thiele Thiele, Peter Sick, Enno Boudriot, Klaus-Werner Diederich, Rainer Hambrecht, Josef Niebauer, Gerhard Schuler, Melchior Seyfarth, Dirk Sibbing, Iris Bauer, Georg Fröhlich, Lorenz Bott-Flügel, Robert Byrne, Josef Dirschinger, Adnan Kastrati, Albert Schömig, Dagmar M. Ouweneel, Erlend Eriksen, Krischan D. Sjauw, Ivo M. van Dongen, Alexander Hirsch, Erik J.S Packer, M. Marie Vis, Joanna J. Wykrzykowska, Karel T. Koch, Jan Baan, Robbert J De Winter, Jan J. Piek, Wim K Lagrand, Bas A.J.M de Mol, Jan G.P. Tijssen, José P.S. Henriques, Jacob E. Møller, Thomas Engstrøm, Lisette Okkels Jensen, Hans Eiskjær, Norman Mangner, Amin Polzin, P. Christian Schulze, Carsten Skurk, Peter Nordbeck, Peter Clemmensen, Vasileios Panoulas, Sebastian Zimmer, Andreas Schäfer, Nikos Werner, Martin Frydland, Lene Holmvang, Jesper Kjærgaard, Rikke Sørensen, Jacob Lønborg, Matias Greve, Evald H. Christiansen, Axel Linke, Felix J. Woitek, Ralf Westenfeld, Sven Moebius-Winkler, Kristian Wachtell, Hanne Berg Ravn, Jens Flensted Lassen, Søren Boesgaard, Oke Gerke, Christian Hassager, Korbinian Lackermair, Stefan Brunner, Mathias Orban, Sven Peterss, Martin Orban, Hans D. Theiss, Bruno C. Huber, Gerd Juchem, Frank Born, Anne-Laure Boulesteix, Axel Bauer, Maximilian Pichlmaier, Jörg Hausleiter, Steffen Massberg, Christian Hagl, Sabina P.W. Guenther, Petr Ostadal, Richard Rokyta, Jiri Karasek, Andreas Kruger, Dagmar Vondrakova, Marek Janotka, Jan Naar, Jana Smalcova, Marketa Hubatova, Milan Hromadk, Stefan Volovar, Miroslava Seyfrydova, Jiri Jarkovsky, Michal Svoboda, Ales Linhart, Jan Belohlavek, Amerjeet S. Banning, Manel Sabaté, Martin Orban, Jay Gracey, Teresa López-Sobrino, Steffen Massberg, Adnan Kastrati, Kris Bogaerts, Tom Adriaenssens, Colin Berry, Andrejs Erglis, Steven Haine, Truls Myrmel, Sameer Patel, Irene Buera, Alessandro Sionis, Victoria Vilalta, Hakeem Yusuff, Christiaan Vrints, David Adlam, Marcus Flather, Anthony H. Gershlick, Holger Thiele, Uwe Zeymer, Ibrahim Akin, Michael Behnes, Tienush Rassaf, Amir-Abbas Mahabadi, Ralf Lehmann, Ingo Eitel, Tobias Graf, Tim Seidler, Andreas Schuster, Carsten Skurk, Daniel Duerschmied, Peter Clemmensen, Marcus Hennersdorf, Stephan Fichtlscherer, Ingo Voigt, Melchior Seyfarth, Stefan John, Sebastian Ewen, Axel Linke, Eike Tigges, Peter Steffen Nordbeck, Leonhard Bruch, Christian Jung, Jutta Franz, Philipp Lauten, Tomaz Goslar, Hans-Josef Feistritzer, Janine Pöss, Eva Kirchhof, Taoufik Ouarrak, Steffen Schneider, Steffen Desch, Anne Freund
Journal: The Lancet (2024)
Promoters constrain evolution of expression levels of essential genes in <i>Escherichia coli</i>
Authors: Saburo Tsuru, Naoki Hatanaka, Chikara Furusawa
Journal: Molecular Biology and Evolution (2024)

Variability in expression levels in response to random genomic mutations varies among genes, influencing both the facilitation and constraint of phenotypic evolution in organisms. Despite its importance, both the underlying mechanisms and evolutionary origins of this variability remain largely unknown due to the mixed contributions of cis- and trans-acting elements. To address this issue, we focused on the mutational variability of cis-acting elements, that is, promoter regions, in Escherichia coli. Random mutations were introduced into the natural and synthetic promoters to generate mutant promoter libraries. By comparing the variance in promoter activity of these mutant libraries, we found no significant difference in mutational variability in promoter activity between promoter groups, suggesting the absence of a signature of natural selection for mutational robustness. In contrast, the promoters controlling essential genes exhibited a remarkable bias in mutational variability, with mutants displaying higher activities than the wild types being relatively rare compared to those with lower activities. Our evolutionary simulation on a rugged fitness landscape provided a rationale for this vulnerability. These findings suggest that past selection created nonuniform mutational variability in promoters biased toward lower activities of random mutants, which now constrains the future evolution of downstream essential genes toward higher expression levels.
Decellularized Biohybrid Nerve Promotes Motor Axon Projections
Authors: Abijeet Singh Mehta, Sophia L. Zhang, Xinran Xie, Shreyaa Khanna, Joshua Tropp, Xudong Ji, Rachel E. Daso, Colin K. Franz, Sumannas W. Jordan, Jonathan Rivnay
Journal: Advanced Healthcare Materials (2024)

Abstract Developing nerve grafts with intact mesostructures, superior conductivity, minimal immunogenicity, and improved tissue integration is essential for the treatment and restoration of neurological dysfunctions. A key factor is promoting directed axon growth into the grafts. To achieve this, biohybrid nerves are developed using decellularized rat sciatic nerve modified by in situ polymerization of poly(3,4‐ethylenedioxythiophene) (PEDOT). Nine biohybrid nerves are compared with varying polymerization conditions and cycles, selecting the best candidate through material characterization. These results show that a 1:1 ratio of FeCl 3 oxidant to ethylenedioxythiophene (EDOT) monomer, cycled twice, provides superior conductivity (&gt;0.2 mS cm −1 ), mechanical alignment, intact mesostructures, and high compatibility with cells and blood. To test the biohybrid nerve's effectiveness in promoting motor axon growth, human Spinal Cord Spheroids (hSCSs) derived from HUES 3 Hb9:GFP cells are used, with motor axons labeled with green fluorescent protein (GFP). Seeding hSCS onto one end of the conduit allows motor axon outgrowth into the biohybrid nerve. The construct effectively promotes directed motor axon growth, which improves significantly after seeding the grafts with Schwann cells. This study presents a promising approach for reconstructing axonal tracts in humans.
Targeting RAC1 reactivates pyroptosis to reverse paclitaxel resistance in ovarian cancer by suppressing P21‐activated kinase 4
Authors: Jiangchun Wu, Yong Wu, Tianyi Zhao, Xiangwei Wang, Qinhao Guo, Simin Wang, Siyu Chen, Xingzhu Ju, Jin Li, Xiaohua Wu, Zhong Zheng
Journal: MedComm (2024)

Pyroptosis may play an important role in the resistance of ovarian cancer (OC) to chemotherapy. However, the mechanism by which pyroptosis modulation can attenuate chemotherapy resistance has not been comprehensively studied in OC. Here, we demonstrated that RAS-associated C3 botulinum toxin substrate 1 (RAC1) is highly expressed in OC and is negatively correlated with patient outcomes. Through cell function tests and in vivo tumor formation tests, we found that RAC1 can promote tumor growth by mediating paclitaxel (PTX) resistance. RAC1 can mediate OC progression by inhibiting pyroptosis, as evidenced by high-throughput automated confocal imaging, the release of lactate dehydrogenase (LDH), the expression of the inflammatory cytokines IL-1β/IL-18 and the nucleotide oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Mechanically, RNA-seq, gene set enrichment analysis (GSEA), coimmunoprecipitation (Co-IP), mass spectrometry (MS), and ubiquitination tests further confirmed that RAC1 inhibits caspase-1/gasdermin D (GSDMD)-mediated canonical pyroptosis through the P21-activated kinase 4 (PAK4)/mitogen-activated protein kinase (MAPK) pathway, thereby promoting PTX resistance in OC cells. Finally, the whole molecular pathway was verified by the results of in vivo drug combination tests, clinical specimen detection and the prognosis. In summary, our results suggest that the combination of RAC1 inhibitors with PTX can reverse PTX resistance by inducing pyroptosis through the PAK4/MAPK pathway.
Universal CRISPR‐Cas12a and Toehold RNA Cascade Reaction on Paper Substrate for Visual <i>Salmonella</i> Genome Detection (Adv. Healthcare Mater. 22/2024)
Authors: Mahera J. Kachwala, Farishta Hamdard, Damla Cicek, Hilal Dagci, Christopher W. Smith, Nabeel Kalla, Mehmet V. Yigit
Journal: Advanced Healthcare Materials (2024)
Bilaterally Aligned Electroosmotic Flow Generated by Porous Microneedle Device for Dual‐Mode Delivery (Adv. Healthcare Mater. 22/2024)
Authors: Gaobo Wang, Kosuke Kato, Sae Ichinose, Daisuke Inoue, Airi Kobayashi, Hitoshi Terui, Soichiro Tottori, Makoto Kanzaki, Matsuhiko Nishizawa
Journal: Advanced Healthcare Materials (2024)