tbuckley/cabot-search huggingface dataset:
MS-20 enhances the gut microbiota-associated antitumor effects of anti-PD1 antibody
Authors: Pei-Jung Lee, Chien-Min Hung, Ai-Jen Yang, Cheng-Yu Hou, Hung-Wen Chou, Yi-Chung Chang, Wen-Cheng Chu, Wen-Yen Huang, Wen-Chih Kuo, Chia-Chun Yang, Kuo-I Lin, Kuo-Hsuan Hung, Li-Chun Chang, Kang-Yun Lee, Han-Pin Kuo, Kung-Ming Lu, Hsin-Chih Lai, Ming-Liang Kuo, Wan-Jiun Chen
Journal: Gut Microbes (2024)

Cancer immunotherapy has been regarded as a promising strategy for cancer therapy by blocking immune checkpoints and evoking immunity to fight cancer, but its efficacy seems to be heterogeneous among patients. Manipulating the gut microbiota is a potential strategy for enhancing the efficacy of immunotherapy. Here, we report that MS-20, also known as "Symbiota®", a postbiotic that comprises abundant microbial metabolites generated from a soybean-based medium fermented with multiple strains of probiotics and yeast, inhibited colon and lung cancer growth in combination with an anti-programmed cell death 1 (PD1) antibody in xenograft mouse models. Mechanistically, MS-20 remodeled the immunological tumor microenvironment by increasing effector CD8+ T cells and downregulating PD1 expression, which were mediated by the gut microbiota. Fecal microbiota transplantation (FMT) from mice receiving MS-20 treatment to recipient mice increased CD8+ T-cell infiltration into the tumor microenvironment and significantly improved antitumor activity when combined with anti-PD1 therapy. Notably, the abundance of Ruminococcus bromii, which increased following MS-20 treatment, was positively associated with a reduced tumor burden and CD8+ T-cell infiltration in vivo. Furthermore, an ex vivo study revealed that MS-20 could alter the composition of the microbiota in cancer patients, resulting in distinct metabolic pathways associated with favorable responses to immunotherapy. Overall, MS-20 could act as a promising adjuvant agent for enhancing the efficacy of immune checkpoint-mediated antitumor therapy.
Serum bile acids profiles are altered without change of the gut microbiota composition following a seven-day prednisolone therapy in severe alcoholic hepatitis
Authors: Damien Esparteiro, Grégory Fouquet, Anoïsia Courtois, Guillaume Jedraszak, Léa Marticho, Mathilde Gourdel, Stéphanie Billon-Crossouard, Mikaël Croyal, Mickaël Naassila, Eric Nguyen-Khac, Ingrid Marcq
Journal: Gut Microbes (2024)

Severe Alcoholic Hepatitis (sAH) is an acute form of liver injury caused by chronic and heavy alcohol drinking. A one-month corticosteroids course is the only sAH reference treatment, and its interactions with the Gut Microbiota (GM), which is a key contributor to liver injury, remain unknown. To evaluate the evolution of the GM in sAH patients, we retrospectively investigated the composition of the GM of 27 sAH patients at the Amiens University Hospital before (D0) and after (D7) a 7-day corticotherapy course using fecal metagenomics sequencing. We also quantified fecal Short-Chain Fatty Acids (SCFA) and fecal and serum Bile Acids (BA), as well as serum Lipopolysaccharide-Binding Protein (LBP). Overall, the community and taxonomical analyses did not reveal any GM evolution between D0 and D7, nor did the SCFA profiles analysis. However, in serum but not fecal samples, the ratio of glyco-conjugated to tauro-conjugated BA was significantly reduced at D7, independently of the response to treatment, while two BA were enriched in non-responder patients. LBP concentration significantly diminished between D0 and D7, which may indicate an improvement of the gut barrier. The stability of the GM of sAH is interesting in the perspective of new treatments based on GM modulation.
Multifunctional Bioactive Nanozyme Systems for Enhanced Diabetic Wound Healing
Authors: Suyue Gao, Xuefeng He, Hengdeng Liu, Yiling Liu, Hanwen Wang, Ziheng Zhou, Lei Chen, Xiaoyuan Ji, Ronghua Yang, Julin Xie
Journal: Advanced Healthcare Materials (2024)

Abstract The protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO₂–Au–mSiO₂@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO₂ head and MnO₂ extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO₂–Au–mSiO₂@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS‐scavenging and growth factor‐releasing system, is developed. The HAMA‐mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti‐inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.
A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with pathogenic antibodies to mannose glycan
Authors: Joana Gaifem, Cláudia S. Rodrigues, Francesca Petralia, Inês Alves, Eduarda Leite-Gomes, Bruno Cavadas, Ana M. Dias, Catarina Moreira-Barbosa, Joana Revés, Renee M. Laird, Mislav Novokmet, Jerko Štambuk, Siniša Habazin, Berk Turhan, Zeynep H. Gümüş, Ryan Ungaro, Joana Torres, Gordan Lauc, Jean-Frederic Colombel, Chad K. Porter, Salomé S. Pinho
Journal: Nature Immunology (2024)

Abstract Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut. There is growing evidence in Crohn’s disease (CD) of the existence of a preclinical period characterized by immunological changes preceding symptom onset that starts years before diagnosis. Gaining insight into this preclinical phase will allow disease prediction and prevention. Analysis of preclinical serum samples, up to 6 years before IBD diagnosis (from the PREDICTS cohort), revealed the identification of a unique glycosylation signature on circulating antibodies (IgGs) characterized by lower galactosylation levels of the IgG fragment crystallizable (Fc) domain that remained stable until disease diagnosis. This specific IgG2 Fc glycan trait correlated with increased levels of antimicrobial antibodies, specifically anti- Saccharomyces cerevisiae (ASCA), pinpointing a glycome–ASCA hub detected in serum that predates by years the development of CD. Mechanistically, we demonstrated that this agalactosylated glycoform of ASCA IgG, detected in the preclinical phase, elicits a proinflammatory immune pathway through the activation and reprogramming of innate immune cells, such as dendritic cells and natural killer cells, via an FcγR-dependent mechanism, triggering NF-κB and CARD9 signaling and leading to inflammasome activation. This proinflammatory role of ASCA was demonstrated to be dependent on mannose glycan recognition and galactosylation levels in the IgG Fc domain. The pathogenic properties of (anti-mannose) ASCA IgG were validated in vivo. Adoptive transfer of antibodies to mannan (ASCA) to recipient wild-type mice resulted in increased susceptibility to intestinal inflammation that was recovered in recipient FcγR-deficient mice. Here we identify a glycosylation signature in circulating IgGs that precedes CD onset and pinpoint a specific glycome–ASCA pathway as a central player in the initiation of inflammation many years before CD diagnosis. This pathogenic glyco-hub may constitute a promising new serum biomarker for CD prediction and a potential target for disease prevention.
Ustekinumab for type 1 diabetes in adolescents: a multicenter, double-blind, randomized phase 2 trial
Authors: Danijela Tatovic, Ashish Marwaha, Peter Taylor, Stephanie J. Hanna, Kym Carter, W. Y. Cheung, Steve Luzio, Gareth Dunseath, Hayley A. Hutchings, Gail Holland, Steve Hiles, Greg Fegan, Evangelia Williams, Jennie H. M. Yang, Clara Domingo-Vila, Emily Pollock, Muntaha Wadud, Kirsten Ward-Hartstonge, Susie Marques-Jones, Jane Bowen-Morris, Rachel Stenson, Megan K. Levings, John W. Gregory, Timothy I. M. Tree, Colin Dayan, Evelien Gevers, Shankar Kanumakala, Sunil Nair, Chris Gardner, Michal Ajzensztejn, Christina Wei, Chris Mouditis, Fiona Campbell, James Greening, Emma Webb, Mimi Chen, Rakesh Amin, Billi White, Ambika Shetty, Chris Bidder, Nicholas Conway, Amalia Mayo, Eleni Christakou, Kamila Sychowska, Yasaman Shahrabi, Maximilian Robinson, Simi Ahmed, Jan Dutz, Laura Cook
Journal: Nature Medicine (2024)

Immunotherapy targeting the autoimmune process in type 1 diabetes (T1D) can delay the loss of β-cells but needs to have minimal adverse effects to be an adjunct to insulin in the management of T1D. Ustekinumab binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, targeting development of T helper 1 cells and T helper 17 cells (T
Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial
Authors: Kai-Feng Pan, Wen-Qing Li, Lian Zhang, Wei-Dong Liu, Jun-Ling Ma, Yang Zhang, Kurt Ulm, Jian-Xi Wang, Lei Zhang, Monther Bajbouj, Lan-Fu Zhang, Ming Li, Michael Vieth, Michael Quante, Le-Hua Wang, Stepan Suchanek, Raquel Mejías-Luque, Heng-Min Xu, Xiao-Han Fan, Xuan Han, Zong-Chao Liu, Tong Zhou, Wei-Xiang Guan, Roland M. Schmid, Markus Gerhard, Meinhard Classen, Wei-Cheng You
Journal: Nature Medicine (2024)
Non-canonical FLT3 alterations reveal novel germline FLT3 variants leading to somatic gene rescue mutations
Authors: Jaymeson Gordon, Carlos Bravo-Perez, Luca Guarnera, Serhan Unlu, Naomi Kawashima, Arooj Ahmed, Christopher Haddad, Yasuo Kubota, Ishani Nautiyal, Fauzia Ullah, Danai Dima, Nakisha D. Williams, Tariq Kewan, Waled Bahaj, Hetty E. Carraway, Chao-Yie Yang, Carmelo Gurnari, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Blood Cancer Journal (2024)
Patterns of Infliximab Biosimilar Uptake for Medicare, Medicaid, and Private Insurance from 2016 to 2022
Authors: Eric T. Roberts, Jing Li, Nick Bansback, Chien‐Wen Tseng, Steve Shiboski, Gabriela Schmajuk, Jinoos Yazdany
Journal: Arthritis & Rheumatology (2024)

Biosimilars have the potential to reduce spending on biologic drugs, yet uptake has been slower than anticipated. We investigated how successive introductions of infliximab biosimilars influenced their adoption by major US insurance providers.
Th2 Compensatory Effect Following Benralizumab Treatment for Eosinophilic Gastritis
Authors: Netali Ben-Baruch Morgenstern, Yrina Rochman, Julie M Caldwell, Margaret H Collins, Vincent A Mukkada, Philip E Putnam, Scott M Bolton, Kara L Kliewer, Marc E Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2024)
Measures of mental imagery in emotional disorders: A COSMIN systematic review of psychometric properties
Authors: Stephen A McIntyre, Jessica Richardson, Susan Carroll, Saava O'Kirwan, Chloe Williams, Victoria Pile
Journal: Clinical Psychology Review (2024)

Dysfunctional imagery processes characterise a range of emotional disorders. Valid, reliable, and responsive mental imagery measures may support the clinical assessment of imagery and advance research to develop theory and imagery-based interventions. We sought to review the psychometric properties of mental imagery measures relevant to emotional disorders.
RIPK3 causes mitochondrial dysfunction and albuminuria in diabetic podocytopathy through PGAM5-Drp1 signaling
Authors: Jeong Suk Kang, Nam-Jun Cho, Seong Woo Lee, Jeong Geon Lee, Ji-Hye Lee, Jawoon Yi, Min Sun Choi, Samel Park, Hyo-Wook Gil, Joon Cheol Oh, Seung Seob Son, Mi Ju Park, Jong-Seok Moon, Donghyeong Lee, So-Young Kim, Seung-Hoon Yang, Sang Soo Kim, Eun Soo Lee, Choon Hee Chung, Jihwan Park, Eun Young Lee
Journal: Metabolism (2024)
Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases
Authors: Kelsey R. van Straalen, Joseph Kirma, Christine M. Yee, Luke F. Bugada, Syed M. Rizvi, Fei Wen, Rachael Wasikowski, Jennifer Fox, Tran H. Do, Charles F. Schuler, Enze Xing, Amanda S. MacLeod, Paul W. Harms, Celine C. Berthier, J. Michelle Kahlenberg, Monica W.L. Leung, Lam C. Tsoi, Johann E. Gudjonsson
Journal: Journal of Allergy and Clinical Immunology (2024)
Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving
Authors: Hamidreza Moheimani, Samuel Stealey, Sydney Neal, Eya Ferchichi, Jialiang Zhang, Marcus Foston, Lori A. Setton, Guy M. Genin, Nathaniel Huebsch, Silviya P. Zustiak
Journal: Advanced Healthcare Materials (2024)

Abstract Alginate hydrogels are widely used as biomaterials for cell culture and tissue engineering due to their biocompatibility and tunable mechanical properties. Reducing alginate molecular weight is an effective strategy for modulating hydrogel viscoelasticity and stress relaxation behavior, which can significantly impact cell spreading and fate. However, current methods like gamma irradiation to produce low molecular weight alginates suffer from high cost and limited accessibility. Here, a facile and cost‐effective approach to reduce alginate molecular weight in a highly controlled manner using serial autoclaving is presented. Increasing the number of autoclave cycles results in proportional reductions in intrinsic viscosity, hydrodynamic radius, and molecular weight of the polymer while maintaining its chemical composition. Hydrogels fabricated from mixtures of the autoclaved alginates exhibit tunable mechanical properties, with inclusion of lower molecular weight alginate leading to softer gels with faster stress relaxation behaviors. The method is demonstrated by establishing how viscoelastic relaxation affects the spreading of encapsulated fibroblasts and glioblastoma cells. Results establish repetitive autoclaving as an easily accessible technique to generate alginates with a range of molecular weights and to control the viscoelastic properties of alginate hydrogels, and demonstrate utility across applications in mechanobiology, tissue engineering, and regenerative medicine.
Micro/Nanomotor‐Driven Intelligent Targeted Delivery Systems: Dynamics Sources and Frontier Applications
Authors: Yue Yu, Ling Liang, Ting Sun, Haiying Lu, Pushan Yang, Jinrong Li, Qinjiao Pang, Jia Zeng, Ping Shi, Jianshu Li, Yongping Lu
Journal: Advanced Healthcare Materials (2024)

Abstract Micro/nanomotors represent a promising class of drug delivery carriers capable of converting surrounding chemical or external energy into mechanical power, enabling autonomous movement. Their distinct autonomous propulsive force distinguishes them from other carriers, offering significant potential for enhancing drug penetration across cellular and tissue barriers. A comprehensive understanding of micro/nanomotor dynamics with various power sources is crucial to facilitate their transition from proof‐of‐concept to clinical application. In this review, micro/nanomotors are categorized into three classes based on their energy sources: endogenously stimulated, exogenously stimulated, and live cell‐driven. The review summarizes the mechanisms governing micro/nanomotor movements under these energy sources and explores factors influencing autonomous motion. Furthermore, it discusses methods for controlling micro/nanomotor movement, encompassing aspects related to their structure, composition, and environmental factors. The remarkable propulsive force exhibited by micro/nanomotors makes them valuable for significant biomedical applications, including tumor therapy, bio‐detection, bacterial infection therapy, inflammation therapy, gastrointestinal disease therapy, and environmental remediation. Finally, the review addresses the challenges and prospects for the application of micro/nanomotors. Overall, this review emphasizes the transformative potential of micro/nanomotors in overcoming biological barriers and enhancing therapeutic efficacy, highlighting their promising clinical applications across various biomedical fields.
Fibrinolytic Platelet Decoys Reduce Cancer Metastasis by Dissociating Circulating Tumor Cell Clusters
Authors: Brian Schnoor, Kenise Morris, Regina K. Kottana, Rebekah Muldoon, Jaeden Barron, Anne‐Laure Papa
Journal: Advanced Healthcare Materials (2024)

During metastasis, circulating tumor cells (CTCs) can travel in the bloodstream as individual cells or clusters, associated with fibrin and platelets. Clusters have a higher metastatic potential due to their increased ability to withstand shear stress and arrest in small vessels. Moreover, CTC-platelet interaction protects CTCs from shear stress and immune detection. The objective of this project is to develop a fibrinolytic platelet system to leverage platelet-CTC interactions and dissociate CTC clusters. For this approach, tissue plasminogen activator (tPA) is loaded onto two modified platelet systems: platelet Decoys and lyophilized platelets. The activities of the systems are characterized using a Förster Resonance Energy Transfer-based assay and an angiogenic assay. Furthermore, the ability of the system to dissociate cancer cell clusters in vitro is assessed using light transmission aggregometry. The data demonstrates that the fibrinolytic platelets can maintain tPA activity, interact with CTCs, and dissociate cancer cell clusters. Finally, fibrinolytic platelets are assessed in vivo, demonstrating a decreased tumor load and increased survival with tPA-Decoy treatment, which is selected as the optimal treatment based on favorable in vitro results and in vivo trials. Therefore, this fibrinolytic platelet approach is a promising method for leveraging platelet-CTC interactions to disperse CTC clusters and reduce metastasis.
Dried Blood Matrix as a New Material for the Detection of DNA Viruses
Authors: Jongwon Lim, Joanne Hwang, Hyegi Min, Matthew Wester, Chansong Kim, Enrique Valera, Hyun Joon Kong, Rashid Bashir
Journal: Advanced Healthcare Materials (2024)

Abstract The gold standard for diagnosing viruses such as the Hepatitis B Virus has remained largely unchanged, relying on conventional methods involving extraction, purification, and polymerase chain reaction (PCR). This approach is hindered by limited availability, as it is time‐consuming and requires highly trained personnel. Moreover, it suffers from low recovery rates of the nucleic acid molecules for samples with low copy numbers. To address the challenges of complex instrumentation and low recovery rate of DNA, a drying process coupled with thermal treatment of whole blood is employed, resulting in the creation of a dried blood matrix characterized by a porous structure with a high surface‐to‐volume ratio where it also inactivates the amplification inhibitors present in whole blood. Drawing on insights from Brunauer–Emmett–Teller (BET)‐ Barrett–Joyner–Halenda (BJH) analysis, scanning electron microscopy (SEM), and fluorescence recovery after photobleaching (FRAP), detection assay is devised for HBV, as a demonstration, from whole blood with high recovery of DNA and simplified instrumentation achieving a limit of detection (LOD) of 10 IU mL −1 . This assay can be completed in &lt;1.5 h using a simple heater, can be applied to other DNA viruses, and is expected to be suitable for point‐of‐care, especially in low‐resource settings.
CRISPR technology in human diseases
Authors: Qiang Feng, Qirong Li, Hengzong Zhou, Zhan Wang, Chao Lin, Ziping Jiang, Tianjia Liu, Dongxu Wang
Journal: MedComm (2024)

Abstract Gene editing is a growing gene engineering technique that allows accurate editing of a broad spectrum of gene‐regulated diseases to achieve curative treatment and also has the potential to be used as an adjunct to the conventional treatment of diseases. Gene editing technology, mainly based on clustered regularly interspaced palindromic repeats (CRISPR)–CRISPR‐associated protein systems, which is capable of generating genetic modifications in somatic cells, provides a promising new strategy for gene therapy for a wide range of human diseases. Currently, gene editing technology shows great application prospects in a variety of human diseases, not only in therapeutic potential but also in the construction of animal models of human diseases. This paper describes the application of gene editing technology in hematological diseases, solid tumors, immune disorders, ophthalmological diseases, and metabolic diseases; focuses on the therapeutic strategies of gene editing technology in sickle cell disease; provides an overview of the role of gene editing technology in the construction of animal models of human diseases; and discusses the limitations of gene editing technology in the treatment of diseases, which is intended to provide an important reference for the applications of gene editing technology in the human disease.
The rising SARS‐CoV‐2 JN.1 variant: evolution, infectivity, immune escape, and response strategies
Authors: Yishan Lu, Danyi Ao, Xuemei He, Xiawei Wei
Journal: MedComm (2024)

The JN.1 variant of COVID-19 has emerged as the dominant strain worldwide since the end of 2023. As a subclade of the BA.2.86 variant, JN.1 harbors a unique combination of mutations inherited from the BA.2.86 lineage, notably featuring the novel L455S mutation within its receptor-binding motif. This mutation has been linked to increased transmissibility and enhanced immune evasion capabilities. During the rise of JN.1, evidence of resistance to various monoclonal antibodies and reduced cross-neutralization effects of the XBB.1.5 vaccine have been observed. Although the public health threat posed by the JN.1 variant appears relatively low, concerns persist regarding its evolutionary trajectory under immune pressure. This review provides a comprehensive overview of the evolving JN.1 variant, highlighting the need for continuous monitoring and investigation of new variants that could lead to widespread infection. It assesses the efficacy of current vaccines and therapeutics against emerging variants, particularly focusing on immunocompromised populations. Additionally, this review summarizes potential vaccine advancements and clinical treatments for COVID-19, offering insights to optimize prevention and treatment strategies. This review thoroughly evaluates the JN.1 variant's impact on public health and its implications for future vaccine and therapeutic development, contributing to ongoing efforts to mitigate the risk of virus transmission and disease severity.