tbuckley/cabot-search huggingface dataset:
Spontaneous Inflammation Resolution Inspired Nanoparticles Promote Neutrophil Apoptosis and Macrophage Efferocytosis for Acute Respiratory Distress Syndrome Treatment
Authors: Yi Wang, Ling‐Feng Zhang, Jiao‐Jiao Zhang, Si‐Si Yu, Wen‐Ling Li, Tian‐Jiao Zhou, Lei Xing, Jee‐Heon Jeong, Hu‐Lin Jiang
Journal: Advanced Healthcare Materials (2024)

During acute respiratory distress syndrome (ARDS), delayed apoptosis of neutrophils and impaired efferocytosis of macrophages constitute two critical limiting steps, leading to secondary inflammatory storm and posing a significant threat to human health. However, due to the failure of previous single target-centric treatments to effectively address these two limiting steps in controlling the inflammatory storm, no available therapies are approved for ARDS treatment. Herein, inspired by spontaneous inflammation resolution, two kinds of Apoptosis and Efferocytosis Restored Nanoparticles (AER NPs) are proposed to overcome these two limiting steps for counteracting severe inflammatory storm. For the first limiting step, neutrophil-targeted apoptosis-restored nanoparticles (AR NPs) accelerated the programmed apoptosis of inflammatory neutrophils. The resolution of the first limiting step facilitated the accumulation of macrophage-targeted and efferocytosis-restored nanoparticles (ER NPs), thereby restoring macrophage efferocytosis and alleviating the second limiting step. The results indicated that after sequential treatment with AER NPs, recruited neutrophils decreased to 13.86%, and macrophage efferocytosis increased to 563.24%. AER NPs promoted inflammation resolution and established a self-healing virtuous loop by addressing the two limiting steps, ultimately effectively treating ARDS. This work suggests that a strategy inspired by inflammation resolution holds promise as a potential approach for advancing inflammation therapy.
Dual‐Mechanism mRNA Delivery via Fluorinated‐Sorbitol Polyplexes: Enhancing Cellular Uptake and Endosomal Escape for COVID‐19 Vaccination
Authors: Arathy Vasukutty, Sahil Chahal, Kyung‐Hwa Lee, So‐Hee Park, Soo‐Min Kim, Eunkyung Shin, You‐Jin Kim, Dokeun Kim, Jung‐Ah Lee, Hye‐Sook Jeong, In‐Kyu Park
Journal: Advanced Healthcare Materials (2024)

Advancements in mRNA delivery nanoparticles have significantly improved the potential for treating challenging diseases. Due to the inherent immunogenicity and rapid degradation of mRNA, specialized nanoparticles are required for efficient intracellular uptake, endosomal escape, and protection from lysosomal degradation. Although current methods enable transgene expression but achieving a balance between efficiency and toxicity remains challenging. In this study, an effective mRNA delivery system is developed by modifying a cationic polymer with sorbitol and fluorine, resulting in fluorinated polyethyleneimine with sorbitol functionalization (PFS). This polyplex enhances mRNA delivery through improved cellular uptake via sorbitol channels and caveolae-mediated endocytosis, while fluorination facilitates endosomal escape and mitigates toxicity. The formulation demonstrated successful expression of Gaussian luciferase mRNA in both Raw 264.7 cells and Balb/c mice. Additionally, intramuscular administration of the SARS-CoV-2 spike mRNA vaccine elicited robust immune responses comparable to Moderna's LNP formulation. The vaccine effectively neutralized the Wuhan variant strain of SARS-CoV-2, as shown by PRNT
Nanocarrier‐Mediated RNA Delivery Platform as a Frontier Strategy for Hepatic Disease Treatment: Challenges and Opportunities
Authors: Jinhui Fan, Zhicheng Xiao, Yafen Dong, Fei Ye, Yan Qiu, Chuan Zhang, Xiaolan Yin, Yi Li, Tingfang Wang
Journal: Advanced Healthcare Materials (2024)

Hepatic diseases cause serious public health problems worldwide, and there is an urgent need to develop effective therapeutic agents. In recent years, significant progress is made in RNA therapy, and RNA molecules, such as mRNAs, siRNAs, miRNAs, and RNA aptamers, are shown to provide significant advantages in the treatment of hepatic diseases. However, the drawbacks of RNAs, such as their poor biological stability, easy degradation by nucleases in vivo, low bioavailability, and low concentrations in target tissues, significantly limit the clinical application of RNA-based drugs. Therefore, exploring and developing effective nanoscale delivery platforms for RNA therapeutics are of immense value. This review focuses on the different types of hepatic diseases and RNA therapeutics, summarizing various nanoscale delivery platforms and their strengths and weaknesses. Finally, the current status and future prospects of nanoscale delivery systems for RNA therapy are discussed.
State‐of‐the‐Art Synthesis of Porous Polymer Materials and Their Several Fantastic Biomedical Applications: a Review
Authors: Yohannis Wondwosen Ahmed, Alexandre Loukanov, Hsieh‐Chih Tsai
Journal: Advanced Healthcare Materials (2024)

Porous polymers, including hydrogels, covalent organic frameworks (COFs), and hyper crosslinked polymers (HCPs), have become essential in biomedical research for their tunable pore architectures, large surface areas, and functional versatility. This review provides a comprehensive overview of their classification and updated synthesis mechanisms, such as 3D printing, electrospinning, and molecular imprinting. Their pivotal roles in drug delivery, tissue engineering, wound healing, and photodynamic/photothermal therapies, focusing on how pore size, distribution, and architecture impact drug release, cellular interactions, and therapeutic outcomes, are explored. Key challenges, including biocompatibility, mechanical strength, controlled degradation, and scalability, are critically assessed alongside emerging strategies to enhance clinical potential. Finally, recent challenges and future perspectives, emphasizing the broader biomedical applications of porous polymers, are addressed. This work provides valuable insights for advancing next-generation biomedical innovations through these materials.
Area Selective Atomic Layer Deposition for the Use on Active Implants: An Overview of Available Process Technology
Authors: Nicolai Simon, Thomas Stieglitz, Volker Bucher
Journal: Advanced Healthcare Materials (2024)

Area-selective atomic layer deposition (ASD) is a bottom-up process that is of particular importance in the semiconductor industry, as it prevents edge defects and avoids cost-intensive lithography steps. This approach not only offers immense potential for the manufacture of active implants but can also be used to improve them. This review paper presents various processes that can be used for this purpose. It also identifies aspects that shall be considered when implementing such a process for medical applications. For example, the inherent selectivity can be used to produce new biosensors, the passivated ASD can be used to encapsulate polymer-based implants, and the activated ASD can be used to improve electrode performance. Finally, the aspects that shall be considered in a coating for active implants are highlighted. ASD therefore offers great potential for use on active implants.
An Antifreezing Scaffold‐Based Cryopreservation Platform of Stem Cells for Convenient Application in Wound Repair
Authors: Shengxi Zhou, Kun Zhang, Mengya Li, Kejun Qi, Danqi Jia, Fangxia Guan, Xiaojie Sui
Journal: Advanced Healthcare Materials (2024)

Efficient cryopreservation of stem cells is crucial to fabricating off-the-shelf cell products for tissue engineering and regeneration medicine. However, it remains challenging due to utilization of toxic cryoprotectants for reducing ice-related cryodamages to stem cells during freeze-thaw cycle, stringent post-thaw washing process, and further integration of stem cells with scaffolds to form tissue engineering constructs for downstream applications. Herein, a novel cryopreservation platform of stem cells based on an antifreezing polyvinylpyrrolidone/gellan gum/gelatin (PGG) scaffold together is reported with an L-proline assisted cell pre-dehydration strategy. Results show that this platform is capable of inhibiting extra-/intracellular ice, thus can achieve high cryoprotection efficacy to stem cells (≈95%) without using any toxic cryoprotectants and eliminate traditional washing process. Meanwhile, the post-thawed stem cells can maintain their proliferation, differentiation, and paracrine functionalities. More importantly, due to the biocompatibility and three dimensional structure of the PGG scaffold, the post-thawed stem cell-laden PGG scaffold can be directly used as tissue engineering constructs for wound repair by mitigating inflammation and promoting collagen deposition at regenerating tissue sites. This present work demonstrates the feasibility of antifreezing scaffold-based cryopreservation platform of stem cells, which may advance the off-the-shelf stem cell-laden tissue engineering constructs for clinical translation.
Oral Lactoferrin‐Responsive Formulation Anchoring around Inflammatory Bowel Region for IBD Therapy
Authors: Jinfan Yang, Ning Shang, Zhengqing Li, Ji Xu, Xin Zhou, Hui Zhou, Wen Luo, Peng Xu, Yucheng Zhou, Xueru Sheng, Zheng Zhu, Mingzhen Zhang, Xiaobin Ma, Mingqian Tan, Hao Wu
Journal: Advanced Healthcare Materials (2024)

Abstract Oral formulation is the ideal treatment method for inflammatory bowel disease (IBD) therapy, but the mucosal damage and diarrhea symptoms impede the drug retention around the inflammatory region, severely limiting IBD therapeutic efficacy. To address this, an oral astaxanthin (Ast) precise delivery formulation is developed with the selective Ast anchoring around the inflammatory region by the novel lactoferrin (LF)‐responsive flocculation. This formulation also heightens the apparent solubility of Ast with the minimized edible safety risks for the edible raw materials. For in vivo IBD therapy, the precise delivery formulation exhibits remarkable outcomes, including a significant increase in colon length and a 100% survival rate. Furthermore, it is verified that the mechanism of treatment is primarily attributed to the improved immunoregulation, epithelial repair, and gut microbiota remodeling after the LF‐responsive flocculation. This effective inflammatory‐responsive delivery design is instructive and valuable to develop more precise delivery systems for IBD therapy.
A Three‐In‐One Heptamethine Cyanine Dye Induces Endoplasmic Reticulum Stress and Apoptosis in Colorectal Cancer
Authors: Yoonbin Park, Juhui Yang, Moon Suk Kim, Hoon Hyun
Journal: Advanced Healthcare Materials (2024)

One of the most significant challenges for image-guided cancer-targeted therapy is to develop multifunctional optical contrast agents enabling simultaneous targeting and therapy. Herein, a feasible strategy is based on the incorporation of therapeutic moieties into the non-delocalized structure of polymethine indocyanines, known as the "structure-inherent targeting" concept. By possessing a rigid chloro-cyclohexenyl ring in the heptamethine cyanine backbone, a new type of multifunctional near-infrared fluorescent dye, Ph790H, that targets tumor without the need for additional targeting ligands is synthesized. Armed with a phthalimide pharmacophore holding a prominent position in medicinal chemistry, Ph790H simultaneously induces endoplasmic reticulum (ER) stress to exert targeted therapeutic effects on HT-29 colorectal cancer xenografts. In terms of molecular mechanism, the lipophilic cationic Ph790H can be actively internalized into HT-29 cells through clathrin-mediated endocytosis. Consequently, mitochondrial reactive oxygen species (ROS) overproduction further induces activation of ER stress, demonstrated by increased ROS concentration and decreased mitochondrial membrane potential, which contributes to cell apoptosis and inhibition of tumor growth. Overall, Ph790H represents an effective "three-in-one" agent for the integration of cancer targeting, imaging, and therapy, which may provide a practical strategy to develop multifunctional small molecule theranostic agents for simultaneous cancer diagnosis and therapy.
Emerging Functional Porous Scaffolds for Liver Tissue Engineering
Authors: Jinglin Wang, Danqing Huang, Dayu Chen, Haozhen Ren, Yuanjin Zhao
Journal: Advanced Healthcare Materials (2024)

Abstract Liver tissue engineering holds promising in synthesizing or regenerating livers, while the design of functional scaffold remains a challenge. Owing to the intricate simulation of extracellular matrix structure and performance, porous scaffolds have demonstrated advantages in creating liver microstructures and sustaining liver functions. Currently, various methods and processes have been employed to fabricate porous scaffolds, manipulating the properties and morphologies of materials to confer them with unique supportive functions. Additionally, scaffolds must also facilitate tissue growth and deliver cells, possessing therapeutic or regenerative effects. In this review, it is initially outline typical procedures for fabricating porous scaffolds and showcase various morphologies of microstructures. Subsequently, it is delved into the forms of cell loading in porous scaffolds, including scaffold‐based, scaffold‐free, and synergetic or bioassembly approaches. Lastly, the utilization of porous scaffolds in liver diseases, offering significant insights and future implications for liver regeneration research in tissue engineering is explored.
Distinct pathophysiological pathways support stratification of Sjögren's disease based on symptoms, clinical, and routine biological data
Authors: Yann Nguyen, Maxime Beydon, Jacques‐Eric Gottenberg, Jacques Morel, Aleth Perdriger, Emmanuelle Dernis, Divi Cornec, Valérie Devauchelle‐Pensec, Damien Sène, Philippe Dieudé, Marion Couderc, Anne‐Laure Fauchais, Claire Larroche, Olivier Vittecoq, Carine Salliot, Eric Hachulla, Véronique Le Guern, Xavier Mariette, Raphaèle Seror, Gaëtane Nocturne
Journal: Arthritis & Rheumatology (2024)

Objective Recently, three distinct phenotypes of Sjögren's disease (SjD) patients have been described, based on cluster analysis: B‐cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms (LSAHS). We aimed to assess whether these clusters were associated with distinct biomarkers and the prognostic value of IFN signature. Methods The ASSESS cohort is a 20‐year prospective cohort of SjD patients. The following biomarkers were compared: IFN‐α2, IFN‐γ, CXCL10, CXCL13, BAFF, IL7, FLT3, CCL19, and TNFRII. IFN signature was assessed using transcriptomic analysis. We then compared systemic and symptomatic evolution, and the risk of new immunosuppressant prescription and of lymphoma, according to the IFN signature across the three clusters. Results 395 patients (94% female, median age 53 [43‐63] years) were included. Higher levels of CXCL‐13, IL7, and TNF‐RII levels were found in the BALS and HSA clusters compared to the LSAHS cluster. A high IFN signature was mainly found in the BALS cluster (57%, vs. 48%, and 38% in the HSA and LSAHS clusters, respectively). This IFN signature was mainly driven by type I IFN, with higher levels of IFN‐ α2. In the BALS cluster, a high IFN signature was associated with a higher risk of new immunosuppressant treatment (HR 9.38; 95% CI 1.22‐72.16). All lymphoma occurred in patients with high IFN signature. Conclusion The three SjD clusters displayed distinct expression of IFN signature, and markers of T‐ and B‐cell activation, confirming distinct pathophysiological mechanisms. High IFN signature could predict systemic evolution in the BALS cluster.
Degradation products of magnesium implant synergistically enhance bone regeneration: Unraveling the roles of hydrogen gas and alkaline environment
Authors: Yuanming An, Haozhi Zhang, Shi'an Zhang, Yuantao Zhang, Lizhen Zheng, Xin Chen, Wenxue Tong, Jiankun Xu, Ling Qin
Journal: Bioactive Materials (2024)
Hyperreactive B cells instruct their elimination by T cells to curb autoinflammation and lymphomagenesis
Authors: Carina Diehl, Valeria Soberón, Seren Baygün, Yuanyuan Chu, Jonathan Mandelbaum, Laura Kraus, Thomas Engleitner, Martina Rudelius, Marco Fangazio, Christoph Daniel, Sabrina Bortoluzzi, Sabine Helmrath, Pankaj Singroul, Vanessa Gölling, Francisco Osorio Barrios, Gönül Seyhan, Lena Oßwald, Maike Kober-Hasslacher, Theodor Zeng, Rupert Öllinger, Ali M Afzali, Thomas Korn, Mohsen Honarpisheh, Maciej Lech, Qurrat Ul Ain, Joachim Pircher, Vanna Imširović, Vedrana Jelenčić, Felix M Wensveen, Verena Passerini, Stefanie Bärthel, Govind Bhagat, David Dominguez-Sola, Dieter Saur, Katja Steiger, Roland Rad, Laura Pasqualucci, Oliver Weigert, Marc Schmidt-Supprian
Journal: Immunity (2024)

B cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not. We resolved this apparent paradox by identifying a rheostat-like cytotoxic T cell checkpoint. Cytotoxicity was instructed by and directed against B cells with high intrinsic hyperresponsiveness, while less reactive cells were spared. Removing T cell control restored a linear relationship between intrinsic B cell reactivity and lethal lymphoproliferation, lymphomagenesis, and autoinflammation. We thus identify powerful T cell-mediated negative feedback control of inherited and acquired B cell pathogenicity and define a permissive window for autoimmunity to emerge.
Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine
Authors: Ganji Purnachandra Nagaraju, Madhu Sudhana Saddala, Jeremy B Foote, Ateeq M Khaliq, Ashiq Masood, Yuvasri Golivi, Dhana Sekhar Reddy Bandi, Sujith Sarvesh, Sudhir Putty Reddy, Jeffrey Switchenko, Julienne L Carstens, Mehmet Akce, Cameron Herting, Olatunji B Alese, Karina J Yoon, Upender Manne, Manoj K Bhasin, Gregory B Lesinski, Vikas P Sukhatme, Bassel F El-Rayes
Journal: Cell Reports Medicine (2024)

Pancreatic ductal adenocarcinoma (PDAC) has a minimal (<15%) 5-year existence, in part due to resistance to chemoradiotherapy. Previous research reveals the impact of paricalcitol (P) and hydroxychloroquine (H) on altering the lysosomal fusion, decreasing stromal burden, and triggering PDAC to chemotherapies. This investigation aims to elucidate the molecular properties of the H and P combination and their potential in sensitizing PDAC to gemcitabine (G). PH potentiates the effects of G in in vitro, orthotopic mouse models, and a patient-derived xenograft model of PDAC. Proteomic and single-cell RNA sequencing (RNA-seq) analyses reveal that GPH treatment upregulates autophagy and endoplasmic reticulum (ER) stress-related transcripts. GPH treatment decreases the number of Ki67, fibroblast-associated protein (FAP), and alpha-smooth muscle actin (SMA)-expressing fibroblasts with a decrease in autophagy-related transcripts. The GPH treatment increases M1 polarization and CD4
Adipocyte-derived ferroptotic signaling mitigates obesity
Authors: Xue Wang, Qian Wu, Meijuan Zhong, Ying Chen, Yudi Wang, Xin Li, Wenxi Zhao, Chaodong Ge, Xinhui Wang, Yingying Yu, Sisi Yang, Tianyi Wang, Enjun Xie, Wanting Shi, Junxia Min, Fudi Wang
Journal: Cell Metabolism (2024)

Ferroptosis is characterized as an iron-dependent and lipophilic form of cell death. However, it remains unclear what role ferroptosis has in adipose tissue function and activity. Here, we find a lower ferroptotic signature in the adipose tissue of individuals and mice with obesity. We further find that activation of ferroptotic signaling by a non-lethal dose of ferroptosis agonists significantly reduces lipid accumulation in primary adipocytes and high-fat diet (HFD)-fed mice. Notably, adipocyte-specific overexpression of acyl-coenzyme A synthetase long-chain family member 4 (Acsl4) or deletion of ferritin heavy chain (Fth) protects mice from HFD-induced adipose expansion and metabolic disorders via activation of ferroptotic signaling. Mechanistically, we find that 5,15-dihydroxyeicosatetraenoic acid (5,15-DiHETE) activates ferroptotic signaling, resulting in the degradation of hypoxia-inducible factor-1α (HIF1α), thereby derepressing a thermogenic program regulated by the c-Myc-peroxisome proliferator-activated receptor gamma coactivator-1 beta (Pgc1β) pathway. Our findings suggest that activating ferroptosis signaling in adipose tissues might help to prevent and treat obesity and its related metabolic disorders.
Disrupted methionine cycle triggers muscle atrophy in cancer cachexia through epigenetic regulation of REDD1
Authors: Kai Lin, Lulu Wei, Ranran Wang, Li Li, Shiyu Song, Fei Wang, Meiwei He, Wenyuan Pu, Jinglin Wang, Junaid Wazir, Wangsen Cao, Xiaozhong Yang, Eckardt Treuter, Rongrong Fan, Yongxiang Wang, Zhiqiang Huang, Hongwei Wang
Journal: Cell Metabolism (2024)
Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer
Authors: I-Chun Chen, Ching-Hung Lin, Dwan-Ying Chang, Tom Wei-Wu Chen, Ming-Yang Wang, Wei-Li Ma, Yi-Ting Lin, Shu-Min Huang, Chia-Lang Hsu, Yen-Shen Lu
Journal: Cell Reports Medicine (2024)

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.e., 64.3%) is achieved. Moreover, 5 of the 14 evaluable subjects exhibited partial responses (overall response rate = 35.7%). The combination of anti-PD1 antibody and anti-hormone therapy is associated with an enhanced immunoreactive microenvironment influencing treatment efficacy, as observed in pre- and post-treatment tumor samples through NanoString analysis. Post-treatment tumors are associated with increased immune response and immune cells. The findings indicate that combining HT with anti-PD1 antibody is a promising treatment strategy for patients with premenopausal ER+/HER2- MBC. This study was registered at ClinicalTrials.gov (NCT02990845).
Targeting P4HA1 promotes CD8+ T cell progenitor expansion toward immune memory and systemic anti-tumor immunity
Authors: Shijun Ma, Li-Teng Ong, Zemin Jiang, Wee Chyan Lee, Puay Leng Lee, Mubaraka Yusuf, Henrik J Ditzel, Yulan Wang, Qingfeng Chen, Wenyu Wang, Xiaojian Wu, Ern Yu Tan, Qiang Yu
Journal: Cancer Cell (2024)
Phocaeicola vulgatus shapes the long-term growth dynamics and evolutionary adaptations of Clostridioides difficile
Authors: Jordy Evan Sulaiman, Jaron Thompson, Pak Lun Kevin Cheung, Yili Qian, Jericha Mill, Isabella James, Hanhyeok Im, Eugenio I Vivas, Judith Simcox, Ophelia S Venturelli
Journal: Cell Host & Microbe (2024)