tbuckley/cabot-search huggingface dataset:
<scp>FoxO1</scp> Deficiency in M‐<scp>MDSCs</scp> Exacerbates B Cell Dysfunction in Systemic Lupus Erythematosus
Authors: Liping Tan, Wei Kong, Kangxing Zhou, Shuangan Wang, Jun Liang, Yayi Hou, Huan Dou
Journal: Arthritis & Rheumatology (2024)

Objective Myeloid‐derived suppressor cells (MDSCs) contribute to the pathogenesis of systemic lupus erythematosus (SLE), in part due to promoting the survival of plasma cells. Forkhead box protein O1 (FoxO1) expression in monocytic MDSCs (M‐MDSCs) exhibits a negative correlation with the SLE Disease Activity Index (SLEDAI) score. This study aimed to investigate the hypothesis that M‐MDSCs specific FoxO1 deficiency enhances aberrant B cell function in aggressive SLE. Methods We used GEO datasets and clinical cohorts to verify the FoxO1 expression and circulating M‐MDSCs clinical significance. Using Cre‐LoxP technology, we generated myeloid FoxO1 deficiency mice (m FoxO1 ‐/‐ ) to establish murine lupus‐prone models. The transcriptional stage was assessed by integrating ChIP‐seq with transcriptomic analysis, luciferase reporter assay and ChIP‐qPCR. Methylated RNA immunoprecipitation sequencing, RNA sequencing and CRISPR‐dCas9 were used to identify m 6 A modification. In vitro B cell co‐culture experiments, Capmatinib intragastric administration, m 6 A‐modulated MDSCs adoptive transfer, and SLE patient sample validation were performed to determine the role of FoxO1 on M‐MDSCs dysregulation during B cell autoreacted with SLE. Results We present evidence that low FoxO1 is predominantly expressed in M‐MDSCs in both SLE patients and lupus mice, and mice with myeloid FoxO1 deficiency (m FoxO1 ‐/‐ ) are more prone to B cell dysfunction. Mechanically, FoxO1 inhibits Met transcription by binding to the promoter region. M‐MDSCs FoxO1 deficiency blocks the Met/COX2/PGE2 secretion pathway, promoting B cell proliferation and hyperactivation. Met antagonist Capmatinib effectively mitigates lupus exacerbation. Furthermore, ALKBH5 targeting catalyzes m 6 A modification on FoxO1 mRNA in CDS and 3'‐UTR regions. Upregulation of FoxO1 mediated by ALKBH5 overexpression in M‐MDSCs improves lupus progression. Finally, these correlations were confirmed in untreated SLE patients. Conclusion Our findings indicate that effective inhibition of B cells mediated by ALKBH5/FoxO1/Met axis in M‐MDSCs could offer a novel therapeutic approach to manage SLE. image
Macropinocytosis-targeted peptide-docetaxel conjugate for bystander pancreatic cancer treatment
Authors: Young Seok Cho, Hanhee Cho, Ha Rin Kim, Seong Jin Park, Joo Hye Yeo, Yoon Gun Ko, Jinu Lee, Sang Yoon Kim, Kwangmeyung Kim, Youngro Byun
Journal: Journal of Controlled Release (2024)
Combination of multivalent DR5 receptor clustering agonists and histone deacetylase inhibitors for treatment of colon cancer
Authors: Jiahui Li, Jaden Arnold, Monika Sima, Hasan Al Faruque, Jacob Galang, Sophia Hu-Lieskovan, Jindřich Kopeček, Jiyuan Yang
Journal: Journal of Controlled Release (2024)
Anti-CTLA-4 antibody self-presented dendritic cell nanovesicles boost the immunotherapy of hepatocellular carcinoma after microwave ablation
Authors: Tan Li, Bo Li, Liteng Lin, Gengjia Chen, Xiaobin Wang, Ye Chen, Wensou Huang, Mingyue Cai, Xintao Shuai, Kangshun Zhu
Journal: Journal of Controlled Release (2024)
Leveraging machine learning to streamline the development of liposomal drug delivery systems
Authors: Remo Eugster, Markus Orsi, Giorgio Buttitta, Nicola Serafini, Mattia Tiboni, Luca Casettari, Jean-Louis Reymond, Simone Aleandri, Paola Luciani
Journal: Journal of Controlled Release (2024)

Drug delivery systems efficiently and safely administer therapeutic agents to specific body sites. Liposomes, spherical vesicles made of phospholipid bilayers, have become a powerful tool in this field, especially with the rise of microfluidic manufacturing during the COVID-19 pandemic. Despite its efficiency, microfluidic liposomal production poses challenges, often requiring laborious, optimization on a case-by-case basis. This is due to a lack of comprehensive understanding and robust methodologies, compounded by limited data on microfluidic production with varying lipids. Artificial intelligence offers promise in predicting lipid behaviour during microfluidic production, with the still unexploited potential of streamlining development. Herein we employ machine learning to predict critical quality attributes and process parameters for microfluidic-based liposome production. Validated models predict liposome formation, size, and production parameters, significantly advancing our understanding of lipid behaviour. Extensive model analysis enhanced interpretability and investigated underlying mechanisms, supporting the transition to microfluidic production. Unlocking the potential of machine learning in drug development can accelerate pharmaceutical innovation, making drug delivery systems more adaptable and accessible.
Tissue nano-transfection of antimicrobial genes drives bacterial biofilm killing in wounds and is potentially mediated by extracellular vesicles
Authors: Tatiana Z Cuellar-Gaviria, Maria Angelica Rincon-Benavides, Hatice Nur Halipci Topsakal, Ana Isabel Salazar-Puerta, Shara Jaramillo-Garrido, Mia Kordowski, Carlos A Vasquez-Martinez, Kim Truc Nguyen, Xilal Y Rima, Pranav S J B Rana, Orlando Combita-Heredia, Binbin Deng, Kavya Dathathreya, David W McComb, Eduardo Reategui, Daniel Wozniak, Natalia Higuita-Castro, Daniel Gallego-Perez
Journal: Journal of Controlled Release (2024)
Crucial role of biosensors in the detection of helminth biomarkers in public health programmes
Authors: Maria Cambra-Pellejà, Lisette van Lieshout, Luis Baptista-Pires, Miguel Vilaplana, José Muñoz, Javier Gandasegui, Claudio Parolo
Journal: The Lancet Microbe (2024)

Helminthiases are highly prevalent but neglected infections that affect more than 1·5 billion people worldwide. Considering the worldwide prevalence of helminthiases, WHO has declared them a public health concern since 2001, necessitating rigorous control and elimination efforts. However, only a few reliable point-of-care diagnostic tests are available for assessing the effectiveness of public health interventions targeting helminthiases, thus increasing the risk of suboptimal outcomes, misallocation of resources, and emergence of drug-resistant helminths. This Review provides an introduction on helminthiases and strategies to achieve control, elimination, interruption in transmission, and eradication of these infections. The Review then comprehensively details the existent biosensors that can be used to detect these infections in human samples, focusing on their target biomarkers, the bioreceptors used, and the sensing readouts. The Review concludes with an in-depth discussion on the persistent challenges related to helminthiases, aiming to encourage the development of much-needed diagnostics specific to these neglected infections.
A Case of Biologic-Resistant Hand Dermatitis Demonstrates Dual T2/T17 Transcriptomic Abnormalities and Responds to JAK Inhibition
Authors: Mark A Taylor, Michelle Yuan, Sijia Wang, Jeffrey P North, Jeffry B Cheng, Raymond J Cho
Journal: British Journal of Dermatology (2024)

Many patients do not respond to targeted pathway-specific biologic therapies but predicting such failure remains an outstanding challenge. Here, in a case of adult-onset hand dermatitis that did not respond to multiple targeted biologic therapies, we detected gene expression programs activated in both atopic dermatitis and psoriasis, via high-resolution genetic profiling. Broader, kinase-based immunosuppression elicited a near complete clinical response. Therefore, our data suggest that such cases harboring greater molecularly complexity might be identified prospectively, circumventing some failures of single pathway blockade.
Deep learning based highly accurate transplanted bioengineered corneal equivalent thickness measurement using optical coherence tomography
Authors: Daewoon Seong, Euimin Lee, Yoonseok Kim, Che Gyem Yae, JeongMun Choi, Hong Kyun Kim, Mansik Jeon, Jeehyun Kim
Journal: npj Digital Medicine (2024)

Corneal transplantation is the primary treatment for irreversible corneal diseases, but due to limited donor availability, bioengineered corneal equivalents are being developed as a solution, with biocompatibility, structural integrity, and physical function considered key factors. Since conventional evaluation methods may not fully capture the complex properties of the cornea, there is a need for advanced imaging and assessment techniques. In this study, we proposed a deep learning-based automatic segmentation method for transplanted bioengineered corneal equivalents using optical coherence tomography to achieve a highly accurate evaluation of graft integrity and biocompatibility. Our method provides quantitative individual thickness values, detailed maps, and volume measurements of the bioengineered corneal equivalents, and has been validated through 14 days of monitoring. Based on the results, it is expected to have high clinical utility as a quantitative assessment method for human keratoplasties, including automatic opacity area segmentation and implanted graft part extraction, beyond animal studies.
Impact of postpartum physical activity on maternal depression and anxiety: a systematic review and meta-analysis
Authors: Andy Deprato, Stephanie-May Ruchat, Muhammad Usman Ali, Chenxi Cai, Milena Forte, Madelaine Gierc, Sarah Meyer, Talia Noel Sjwed, Safi Shirazi, Brittany A Matenchuk, Paris A T Jones, Allison Sivak, Margie H Davenport
Journal: British Journal of Sports Medicine (2024)

Objective To examine the influence of postpartum exercise on maternal depression and anxiety. Design Systematic review with random effects meta-analysis and meta-regression. Data sources Online databases up to 12 January 2024, reference lists, recommended studies and hand searches. Eligibility criteria Randomised controlled trials (RCTs) and non-randomised interventions of any publication date or language were included if they contained information on the Population (postpartum people), Intervention (subjective or objective measures of frequency, intensity, duration, volume, type, or mode of delivery of exercise), Comparator (no exercise or different exercise measures), and Outcome (postpartum depression, anxiety prevalence, and/or symptom severity). Results A total of 35 studies (n=4072) were included. Moderate certainty evidence from RCTs showed that exercise-only interventions reduced the severity of postpartum depressive symptoms (19 RCTs, n=1778, SMD: −0.52, 95% CI −0.80 to –0.24, I 2 =86%, moderate effect size) and anxiety symptoms (2 RCTs, n=513, SMD: −0.25, 95% CI −0.43 to −0.08, I 2 =0%, small effect size), and the odds of postpartum depression by 45% (4 RCTs, n=303 OR 0.55, 95% CI 0.32 to 0.95, I 2 =0%) compared with no exercise. No included studies assessed the impact of postpartum exercise on the odds of postpartum anxiety. To achieve at least a moderate reduction in the severity of postpartum depressive symptoms, postpartum individuals needed to accumulate at least 350 MET-min/week of exercise (eg, 80 min of moderate intensity exercise such as brisk walking, water aerobics, stationary cycling or resistance training). Conclusions Postpartum exercise reduced the severity of depressive and anxiety symptoms and the odds of postpartum depression.
Rapid and Efficient Immune Response Induced by a Designed Modular Cholera Toxin B Subunit (CTB)-based Self-assembling Nanoparticle
Authors: Chao Pan, Shujuan Yu, Caixia Li, Juntao Li, Peng Sun, Yan Guo, Ting Li, Dongshu Wang, Kangfeng Wang, Yufei Lyu, Xiankai Liu, Xiang Li, Jun Wu, Li Zhu, Hengliang Wang
Journal: Biomaterials (2024)

Modular self-assembling nanoparticle vaccines, represent a cutting-edge approach in immunology with the potential to revolutionize vaccine design and efficacy. Although many innovative efficient modular self-assembling nanoparticles have been designed for vaccination, the immune activation characteristics underlying such strong protection remain poorly understood, limiting the further expansion of such nanocarrier. Here, we prepared a novel modular nanovaccine, which self-assembled via a pentamer cholera toxin B subunit (CTB) domain and an unnatural trimer domain, presenting S. Paratyphi A O-polysaccharide antigen, and investigated its rapid immune activation mechanism. The nanovaccine efficiently targets draining lymph nodes and antigen-presenting cells, facilitating co-localization with Golgi and endoplasmic reticulum. In addition, dendritic cells, macrophages, B cells, and neutrophils potentially participate in antigen presentation, unveiling a dynamic change of the vaccines in lymph nodes. Single-cell RNA sequencing at early stage and iN vivo/iN vitro experiments reveal its potent humoral immune response capabilities and protection effects. This nanoparticle outperforms traditional CTB carriers in eliciting robust prophylactic effects in various infection models. This work not only provides a promising and efficient candidate vaccine, but also promotes the design and application of the new type of self-assembled nanoparticle, offering a safe and promising vaccination strategy for infection diseases.
Newborn screening for SCID and severe T lymphocytopenia in Europe
Authors: Maartje Blom, Maarja Soomann, Pere Soler-Palacín, Anna Šedivá, Asbjørg Stray-Pedersen, Rolf Zetterström, Carsten Speckmann, Andrew R Gennery, Mirjam van der Burg
Journal: Journal of Allergy and Clinical Immunology (2024)

Initiation of newborn screening (NBS) programs in Europe dates back to the 1960s. One of the most recent expansions of NBS programs was the addition of severe combined immunodeficiency (SCID) based on detection of T-cell receptor excision circles (TRECs). In this review, we present an overview of the current situation in Europe. To avoid a biased overview based on only published results, a 37-item survey on TREC-based NBS was sent to representatives of 46 European countries. With a response rate of 83%, we collected data of 38 countries. Seventeen of the 38 European countries that have completed the survey have nationally or regionally implemented TREC-based NBS. The survey results emphasize similarities and differences as well as common practices and challenges in TREC-based NBS. Because TRECs are a general surrogate marker for severe T lymphocytopenia, conditions other than SCID are also identified. Therefore, the initial definition of the target disease as "SCID" might need to be reconsidered and extended to "SCID and severe T lymphocytopenia." Even though complete harmonization of TREC-based NBS programs across Europe will remain challenging, collaboration and close partnerships will help in the move toward universal TREC-based screening for all newborns, resulting in more infants with SCID and severe T lymphocytopenia being detected each year.
Nationwide prevalence and geographic variation of idiopathic intracranial hypertension among women in the United States
Authors: Muhammad A. Fraz, B. Michelle Kim, John J. Chen, Flora Lum, Jinbo Chen, Grant T. Liu, Ali G. Hamedani, Sejal Amin, Paul A. Edwards, Divya Srikumaran, Fasika Woreta, Jeffrey S. Schultz, Anurag Shrivastava, Baseer Ahmad, Paul Bryar, Dustin French, Brian L. Vanderbeek, Suzann Pershing, Sophia Y. Wang, Anne M. Lynch, Jenna Patnaik, Saleha Munir, Wuqaas Munir, Joshua Stein, Lindsey DeLott, Brian C. Stagg, Barbara Wirostko, Brian McMillian, Arsham Sheybani, Soshian Sarrapour, Kristen Nwanyanwu, Michael Deiner, Catherine Sun, Robert Feldman, Rajeev Ramachandran
Journal: Ophthalmology (2024)
A 3D-Printed Microdevice Encapsulates Vascularized Islets Composed of iPSC-derived β-like Cells and Microvascular Fragments for Type 1 Diabetes Treatment
Authors: Shuang Chen, Wenshuang Wang, Lanlin Shen, Haofan Liu, Jing Luo, Yushuang Ren, Susu Cui, Yixin Ye, Gang Shi, Fuyi Cheng, Xiaolan Su, Lei Dai, Maling Gou, Hongxin Deng
Journal: Biomaterials (2024)
N6-Methyladenosine modification of circDcbld2 in Kupffer cells promotes hepatic fibrosis via targeting miR-144-3p/Et-1 axis
Authors: Sai Zhu, Xin Chen, Lijiao Sun, Xiaofeng Li, Yu Chen, Liangyun Li, Xiaoguo Suo, Chuanhui Xu, Minglu Ji, Jianan Wang, Hua Wang, Lei Zhang, Xiaoming Meng, Cheng Huang, Jun Li
Journal: Acta Pharmaceutica Sinica B (2024)

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N 6-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.
TPX2 serves as a novel target for expanding the utility of PARPi in pancreatic cancer through conferring synthetic lethality
Authors: Mingming Xiao, Rong Tang, Haoqi Pan, Jing Yang, Xuhui Tong, He Xu, Yanmei Guo, Yalan Lei, Di Wu, Yubin Lei, Yamei Han, Zhilong Ma, Wei Wang, Jin Xu, Xianjun Yu, Si Shi
Journal: Gut (2024)

Background PARP inhibitors (PARPi) have been licensed for the maintenance therapy of patients with metastatic pancreatic cancer carrying pathogenic germline BRCA1/2 mutations. However, mutations in BRCA1/2 are notably rare in pancreatic cancer. Objective There is a significant unmet clinical need to broaden the utility of PARPi. Design RNA sequencing was performed to screen potential targets for PARPi sensitivity. The synthetic lethal effects were verified in patient-derived xenograft (PDX), xenograft and patient-derived organoid models. Mechanisms were explored via LC‒MS/MS, coimmunoprecipitation, laser microirradiation, immunofluorescence, the homologous recombination (HR) or non-homologous end joining (NHEJ) reporter system, in situ proximity ligation assay and live-cell time-lapse imaging analyses. Results Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is an exploitable vulnerability. TPX2 was downregulated in PDX models sensitive to PARPi, and TPX2 inhibition conferred synthetic lethality to PARPi both in vitro and in vivo . Mechanistically, TPX2 functions in a cell cycle-dependent manner. In the S/G2 phase, ATM-mediated TPX2 S634 phosphorylation promotes BRCA1 recruitment to double-strand breaks (DSBs) for HR repair, whereas non-phosphorylated TPX2 interacts with 53BP1 to recruit it for NHEJ. The balance between phosphorylated and non-phosphorylated TPX2 determines the DSB repair pathway choice. During mitosis, TPX2 phosphorylation enhances Aurora A activity, promoting mitotic progression and chromosomal stability. Targeting TPX2 S634 phosphorylation with a cell-penetrating peptide causes genomic instability and mitotic catastrophe and enhances PARPi sensitivity. Additionally, the inhibition of TPX2 or S634 phosphorylation combined with gemcitabine further sensitised pancreatic cancer to PARPi. Conclusions Our findings revealed the dual-functional significance of TPX2 in controlling DNA DSB repair pathway choice and mitotic progression, suggesting a potential therapeutic strategy involving PARPi for patients with pancreatic cancer.
List of Critical Drugs in Dermatology: Results of a Delphi Consensus in France
Authors: Guillaume Chaby, Sébastien Barbarot, Florence Corgibet, Jean Noel Dauendorffer, Nicole Jouan, Marc Reverte, Stéphane Honoré, Gaëlle Quereux, Olivier Chosidow, Henri Adamski, Jean-Michel Amici, Mathieu Bataille, Claire Bernier, Marie Beylot Barry, Priscille Carvalho Lallement, Marie Caucanas, Frédéric Caux, Olivier Chosidow, Elisa Cinotti, Nadège Cordel, Jean-Charles Crepin, Anne-Céline Davaine, Tu Anh Duong, Caroline Dutriaux, Antoine Fauconneau, Jean-Yves Gourhant, Pascale Huet, Marie Hélène Jegou, Denis Jullien, Florence Le Duff, Cédric Lenormand, Catherine Lok, Elisabeth Lorier Roy, Sandra Ly, Josefina Marco Bonnet, Annabel Maruani, Brigitte Milpied, Laurent Misery, Christèle Nicolas, Isabelle Ollivier, Saskia Oro, Catherine Pannequin, Eve Pepin, Antoine Petit, Antoinette Petit Roland, Daniel Plantier, Gaëlle Quereux, Marie-Aleth Richard, Mahtab Samimi, Martine Schollhammer, Jean-François Sei, Delphine Staumont, Davy Beauger, Gwendoline Felker, Pierre Albaladejo
Journal: British Journal of Dermatology (2024)

Drug shortages have increased in recent years, and every country worldwide has been affected. The French Ministry of Health asked various scientific societies to establish a list of ‘critical’ drugs for each specialty. The aim of this list is to enable the public authorities to control the chain of production and guarantee the availability of drugs. We present the list of critical dermatological drugs, which is the result of a strong consensus between all representative entities of the French Society of Dermatology.
Bridging organ transcriptomics for advancing multiple organ toxicity assessment with a generative AI approach
Authors: Ting Li, Xi Chen, Weida Tong
Journal: npj Digital Medicine (2024)

Abstract Translational research in toxicology has significantly benefited from transcriptomic profiling, particularly in drug safety. However, its application has predominantly focused on limited organs, notably the liver, due to resource constraints. This paper presents TransTox, an innovative AI model using a generative adversarial network (GAN) method to facilitate the bidirectional translation of transcriptomic profiles between the liver and kidney under drug treatment. TransTox demonstrates robust performance, validated across independent datasets and laboratories. First, the concordance between real experimental data and synthetic data generated by TransTox was demonstrated in characterizing toxicity mechanisms compared to real experimental settings. Second, TransTox proved valuable in gene expression predictive models, where synthetic data could be used to develop gene expression predictive models or serve as “digital twins” for diagnostic applications. The TransTox approach holds the potential for multi-organ toxicity assessment with AI and advancing the field of precision toxicology.
Author Correction: Branched-chain α-ketoacids aerobically activate HIF1α signalling in vascular cells
Authors: Wusheng Xiao, Nishith Shrimali, Niv Vigder, William M. Oldham, Clary B. Clish, Huamei He, Samantha J. Wong, Bradley M. Wertheim, Elena Arons, Marcia C. Haigis, Jane A. Leopold, Joseph Loscalzo
Journal: Nature Metabolism (2024)
Lessons learned from 20 years of preclinical testing in pediatric cancers
Authors: Malcolm A Smith, Peter J Houghton, Richard B Lock, John M Maris, Richard Gorlick, Raushan T Kurmasheva, Xiao-Nan Li, Beverly A Teicher, Jeffrey H Chuang, Filemon S Dela Cruz, Michael A Dyer, Andrew L Kung, Michael W Lloyd, Yael P Mossé, Timothy M Stearns, Elizabeth A Stewart, Carol J Bult, Stephen W Erickson
Journal: Pharmacology & Therapeutics (2024)
YTHDC1 is a therapeutic target for B-cell acute lymphoblastic leukemia by attenuating DNA damage response through the KMT2C-H3K4me1/me3 epigenetic axis
Authors: Xinxin Li, Minhua Zheng, Shoubao Ma, Fengze Nie, Zhiqiang Yin, Yanan Liang, Xianchun Yan, Weihong Wen, Jianhua Yu, Yingmin Liang, Siyong Huang, Hua Han
Journal: Leukemia (2024)
UC-MSCs based on biomimetic microniche exert excellent regulatory effects on acute brain inflammation through advantageous properties
Authors: Bichun Zhao, Chao Wang, Manqiang Sun, Xiaocao Ma, Quan Zeng, Jiafei Xi, Junnian Zhou, Xuetao Pei, Yali Jia, Wen Yue
Journal: Biomaterials (2024)