tbuckley/cabot-search huggingface dataset:
Chitosan‐Based Hydrogels as Antibacterial/Antioxidant/Anti‐Inflammation Multifunctional Dressings for Chronic Wound Healing
Authors: Jingchen Xu, Lili Chang, Yuhuan Xiong, Qiang Peng
Journal: Advanced Healthcare Materials (2024)

Abstract Due to repeated microbial infection, persistent inflammation, excessive oxidative stress, and cell dysfunction, chronic wounds are difficult to heal, posing a serious threat to public health. Therefore, developing multifunctional wound dressings that can regulate the complex microenvironment of chronic wounds and enhance cellular function holds great significance. Recently, chitosan has emerged as a promising biopolymer for wound healing due to its excellent biocompatibility, biodegradability, and versatile bioactivity. The aim of this review is to provide a comprehensive understanding of the mechanisms of delayed chronic wound healing and discuss the healing–promoting properties of chitosan and its derivatives, such as good biocompatibility, antibacterial activity, hemostatic capacity, and the ability to promote tissue regeneration. On this basis, the potential applications of chitosan‐based hydrogels are summarized in chronic wound healing, including providing a suitable microenvironment, eliminating bacterial infections, promoting hemostasis, inhibiting chronic inflammation, alleviating oxidative stress, and promoting tissue regeneration. In addition, the concerns and perspectives for the clinical application of chitosan‐based hydrogels are also discussed.
Hydrogen Sulfide Delivery System Based on Salting‐Out Effect for Enhancing Synergistic Photothermal and Photodynamic Cancer Therapies
Authors: Aimei Zhang, Qingyun Wei, Yuhan Zheng, Mengyuan Ma, Tao Cao, Qichen Zhan, Peng Cao
Journal: Advanced Healthcare Materials (2024)

Abstract The simultaneous application of photothermal therapy (PTT) and photodynamic therapy (PDT) offers substantial advantages in cancer treatment. However, their synergistic anticancer efficacy is often limited by tumor hypoxia, and thermotolerance induced by high expression of heat shock proteins (HSP). Fortunately, hydrogen sulfide (H 2 S), known for its direct cytotoxic effect on tumor cells, has been recognized for its ability to enhance PTT and PDT. The effectiveness of H 2 S in these therapies is challenged by its low loading efficiency, poor stability, and short diffusion distance. To address these issues, a nanoscale emulsion drop template created through the salting‐out effect is employed to construct a robust H 2 S delivery system. Polydopamine (PDA), chosen for its interfacial polymerization tendency and excellent photothermal conversion rate, is utilized as a carrier for the H 2 S donor (ADT) and Zinc phthalocyanine (ZnPc) to fabricate a novel nanomedicine termed APZ NPs. The temperature‐responsive APZ NPs are designed to release H 2 S during the PTT process. Elevated H 2 S levels promoted vasodilation, thereby enhancing the enhanced permeability and retention effect (EPR) of APZ NPs within solid tumors. This strategy effectively alleviated tumor hypoxia by disrupting the mitochondrial respiratory chain and mitigated tumor cell heat tolerance by inhibiting HSP expression.
Carbon Dots in the Pathological Microenvironment: ROS Producers or Scavengers?
Authors: Chen Dong, Yanan Wang, Tianxiang Chen, Wenzhi Ren, Changyong Gao, Xuehua Ma, Xiang Gao, Aiguo Wu
Journal: Advanced Healthcare Materials (2024)

Reactive oxygen species (ROS), as metabolic byproducts, play pivotal role in physiological and pathological processes. Recently, studies on the regulation of ROS levels for disease treatments have attracted extensive attention, mainly involving the ROS-induced toxicity therapy mediated by ROS producers and antioxidant therapy by ROS scavengers. Nanotechnology advancements have led to the development of numerous nanomaterials with ROS-modulating capabilities, among which carbon dots (CDs) standing out as noteworthy ROS-modulating nanomedicines own their distinctive physicochemical properties, high stability, and excellent biocompatibility. Despite progress in treating ROS-related diseases based on CDs, critical issues such as rational design principles for their regulation remain underexplored. The primary cause of these issues may stem from the intricate amalgamation of core structure, defects, and surface states, inherent to CDs, which poses challenges in establishing a consistent generalization. This review succinctly summarizes the recently progress of ROS-modulated approaches using CDs in disease treatment. Specifically, it investigates established therapeutic strategies based on CDs-regulated ROS, emphasizing the interplay between intrinsic structure and ROS generation or scavenging ability. The conclusion raises several unresolved key scientific issues and prominent technological bottlenecks, and explores future perspectives for the comprehensive development of CDs-based ROS-modulating therapy.
Porous Photocrosslinkable Hydrogel Functionalized with USC Derived Small Extracellular Vesicles for Corpus Spongiosum Repair
Authors: Lin Wang, Mingming Yu, Yunlong Yang, Yiqing Lv, Hua Xie, Jiasheng Chen, Xufeng Peng, Zhiwei Peng, Lijun Zhou, Yang Wang, Yichen Huang, Fang Chen
Journal: Advanced Healthcare Materials (2024)

Reconstruction of a full-thickness spongy urethra is difficult because a corpus spongiosum (CS) defect cannot be repaired using self-healing or substitution urethroplasty. Small extracellular vesicles (sEVs) secreted by urine-derived stem cells (USC-sEVs) strongly promote vascular regeneration. In this study, it is aimed to explore whether USC-sEVs promote the repair of CS defects. To prolong the in vivo effects of USC-sEVs, a void-forming photoinduced imine crosslinking hydrogel (vHG) is prepared and mixed with the USC-sEV suspension. vHG encapsulated with USC-sEVs (vHG-sEVs) is used to repair a CS defect with length of 1.5 cm and width of 0.8 cm. The results show that vHG-sEVs promote the regeneration and repair of CS defects. Histological analysis reveals abundant sinusoid-like vascular structures in the vHG-sEV group. Photoacoustic microscopy indicates that blood flow and microvascular structure of the defect area in the vHG-sEV group are similar to those in the normal CS group. This study confirms that the in situ-formed vHG-sEV patch appears to be a valid and promising strategy for repairing CS defects.
Xeno Nucleic Acids as Functional Materials: From Biophysical Properties to Application
Authors: Tianyuan Bian, Yufeng Pei, Shitao Gao, Songtao Zhou, Xinyu Sun, Mingdong Dong, Jie Song
Journal: Advanced Healthcare Materials (2024)

Xeno nucleic acid (XNA) are artificial nucleic acids, in which the chemical composition of the sugar moiety is changed. These modifications impart distinct physical and chemical properties to XNAs, leading to changes in their biological, chemical, and physical stability. Additionally, these alterations influence the binding dynamics of XNAs to their target molecules. Consequently, XNAs find expanded applications as functional materials in diverse fields. This review provides a comprehensive summary of the distinctive biophysical properties exhibited by various modified XNAs and explores their applications as innovative functional materials in expanded fields.
Donor Sex and Passage Conditions Influence MSC Osteogenic Response in Mineralized Collagen Scaffolds
Authors: Vasiliki Kolliopoulos, Aleczandria Tiffany, Maxwell Polanek, Brendan A. C. Harley
Journal: Advanced Healthcare Materials (2024)

Abstract Contemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their multi‐potent potential and ability to generate a pro‐regenerative secretome. While many have reported the influence of matrix environment on MSC osteogenic response, few have investigated the effects of donor and sex. Here, a well‐defined mineralized collagen scaffold is used to study the influence of passage number and donor‐reported sex on MSC proliferation and osteogenic potential. A library of bone marrow and adipose tissue‐derived stem cells from eight donors to examine donor viability in osteogenic capacity in mineralized collagen scaffolds is obtained. MSCs displayed reduced proliferative capacity as a function of passage duration. Further, MSCs showed significant sex‐associated variability in osteogenic capacity. Notably, MSCs from male donors displayed significantly higher cell proliferation while MSCs from female donors displayed significantly higher osteogenic response via increased alkaline phosphate activity, osteoprotegerin release, and mineral formation in vitro. The study highlights the essentiality of including donor‐reported sex as an experimental variable and reporting culture expansion in future studies of biomaterial regenerative potential.
Supramolecular Modulator Assisted Cryo‐Engineered Porous Cu‐DNA Nano‐Vehicles for Versatile Theranostic Agent Delivery
Authors: Cui Ren, Fang Wang, Xiaoyi Meng, Ruiang Zhou, Zhaogang Sun, Yue Cheng, Hongqian Chu, Yong Wang
Journal: Advanced Healthcare Materials (2024)

Abstract DNA nanotechnology combines structural design with therapeutic functions via programmable DNA motifs, but faces challenges in drug loading capacity. Herein a pore‐engineering strategy is reported to develop a highly porous, universal DNA nano‐vehicle through coordination self‐assembly, cryo‐engineering, and supramolecular chemistry, adapting to diverse cargo loading with desired theranostic agents. Thus, the complex synthesis and compatibility challenges typically associated with switching between different drug carriers are avoided. To this end, Cu 2+ and nucleic acid therapeutic G3139 self‐assemble into a prefabricated solid nanostructure, which subsequently undergoes ultrafast freezing and sublimation to introduce porosity, forming highly porous Cu‐G3139 nanoparticles (CG NPs). The porous CG NPs efficiently accommodate diverse therapeutic molecules, from chemotherapeutics to non‐chemotherapeutic agents, facilitated by positively‐charged cyclodextrin. As a proof‐of‐concept, the photosensitizer indocyanine green (ICG) is loaded and coated with tannic acid (TA) to form CICG@TA, enabling remarkable photothermal and fluorescence imaging‐guided synergistic tumor ablation. This work represents the first demonstration of sublimation‐induced pore formation in metal‐DNA hybrid nanoparticles without chemical etching, offering a scalable “plug‐and‐play” platform for personalized cancer therapy without redesign. This versatile pore‐engineering strategy, merging supramolecular chemistry with cryo‐engineered porosity, opens up new avenues for efficient, customized multidrug delivery for diverse tumor theranostic applications.
Dual‐Layer Nanoengineered Urinary Catheters for Enhanced Antimicrobial Efficacy and Reduced Cytotoxicity
Authors: Dong‐Sung Won, Hyun Lee, Yubeen Park, Minjung Chae, Yu‐Chan Kim, Bumjin Lim, Min‐Ho Kang, Myoung‐Ryul Ok, Hyun‐Do Jung, Jung‐Hoon Park
Journal: Advanced Healthcare Materials (2024)

Abstract Catheter‐associated urinary tract infection (CAUTI) is the most common healthcare‐associated infection; however, current therapeutic strategies remain insufficient for standard clinical application. A novel urinary catheter featuring a dual‐layer nanoengineering approach using zinc (Zn) and silver nanoparticles (AgNPs) is successfully fabricated. This design targets microbial resistance, minimizes cytotoxicity, and maintains long‐term efficacy. The inner AgNPs layer provides immediate antibacterial effects against the UTI pathogens, while the outer porous Zn layer controls zero‐order Ag release and generates reactive oxygen species, thus enhancing long‐term bactericidal performance. Enhanced antibacterial properties of Zn/AgNPs‐coated catheters are observed, resulting in 99.9% of E. coli and 99.7% of S. aureus reduction, respectively. The Zn/AgNPs‐coated catheter significantly suppresses biofilm with sludge formation compared to AgNP‐coated and uncoated catheters (all, p &lt; 0.05). The Zn/AgNP‐coated catheter in a rabbit model demonstrated a durable, effective barrier against bacterial colonization, maintaining antimicrobial properties during the catheter indwelling period with significantly reduced inflammation and epithelial disruption compared with AgNP and uncoated groups. This innovation has the potential to revolutionize the design of antimicrobial medical devices, particularly for applications requiring long‐term implantation. Although further preclinical studies are required to verify its efficacy and safety, this strategy seems to be a promising approach to preventing CAUTI‐related complications.
Non-cigarette tobacco products, aryl-hydrocarbon receptor repressor gene methylation and smoking-related health outcomes
Authors: Christina M Eckhardt, Pallavi Balte, Jack E Morris, Surya P Bhatt, David Couper, Jessica Fetterman, Neal Freedman, David R Jacobs, Lifang Hou, Ravi Kalhan, Yongmei Liu, Laura Loehr, Pamela L Lutsey, Joseph E Schwartz, Wendy White, Sachin Yende, Stephanie J London, Tiffany R Sanchez, Elizabeth C Oelsner
Journal: Thorax (2024)

Introduction Cigarette smoking leads to altered DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) gene. However, it remains unknown whether pipe or cigar smoking is associated with AHRR methylation. We evaluated associations of non-cigarette tobacco use with AHRR methylation and determined if AHRR methylation was associated with smoking-related health outcomes. Methods Data were pooled across four population-based cohorts that enrolled participants from 1985 to 2002. Tobacco exposures were evaluated using smoking questionnaires. AHRR cg05575921 methylation was measured in peripheral blood leucocyte DNA. Spirometry and respiratory symptoms were evaluated at the time of methylation measurements and in subsequent visits. Vital status was monitored using the National Death Index. Results Among 8252 adults (mean age 56.7±10.3 years, 58.1% women, 40.6% black), 4857 (58.9%) participants used cigarettes and 634 (7.7%) used non-cigarette tobacco products. Exclusive use of non-cigarette tobacco products was independently associated with lower AHRR methylation (−2.44 units, 95% CI −4.42 to −0.45), though to a lesser extent than exclusive use of cigarettes (−6.01 units, 95% CI −6.01 to −4.10). Among participants who exclusively used non-cigarette tobacco products, reduced AHRR methylation was associated with increased respiratory symptom burden (OR 1.60, 95% CI 1.03 to 2.68) and higher all-cause mortality (log-rank p=0.02). Conclusion Pipe and cigar smoking were independently associated with lower AHRR methylation in a multiethnic cohort of US adults. Among users of non-cigarette tobacco products, lower AHRR methylation was associated with poor respiratory health outcomes and increased mortality. AHRR methylation may identify non-cigarette tobacco users with an increased risk of adverse smoking-related health outcomes.
CD206<sup>+</sup>macrophages are relevant non-invasive imaging biomarkers and therapeutic targets in experimental lung fibrosis
Authors: Lenny Pommerolle, Guillaume Beltramo, Leo Biziorek, Marin Truchi, Alexandre Magno Maneschy Dias, Lucile Dondaine, Julie Tanguy, Nicolas Pernet, Victor Goncalves, Alexanne Bouchard, Marie Monterrat, Grégoire Savary, Nicolas Pottier, Kjetil Ask, Martin R J Kolb, Bernard Mari, Carmen Garrido, Bertrand Collin, Philippe Bonniaud, Olivier Burgy, Françoise Goirand, Pierre-Simon Bellaye
Journal: Thorax (2024)

Background Interstitial lung diseases (ILDs) include a large number of diseases associated with progressive pulmonary fibrosis (PPF), including idiopathic pulmonary fibrosis (IPF). Despite the rarity of each of the fibrotic ILDs individually, they cumulatively affect a considerable number of patients. PPF is characterised by an excessive collagen deposition leading to functional decline. Objectives Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression. CD206-expressing M2 macrophages are involved in fibrosis progression, and whether they may be relevant therapeutic targets or biomarkers remains an open question. Results In our study, CD206 + lung macrophages were monitored in bleomycin-induced lung fibrosis in mice by combining flow cytometry, scRNAseq and in vivo molecular imaging using a single photon emission computed tomography (SPECT) radiopharmaceutical, 99m Tc-tilmanocept. The antifibrotic effect of the inhibition of M2 macrophage polarisation with a JAK inhibitor, tofacitinib, was assessed in vivo. We demonstrate that CD206-targeted in vivo SPECT imaging with 99m Tc-tilmanocept was able to accurately detect and quantify the increase in CD206 + macrophages from early to advanced stages of experimental fibrosis and ex vivo in lung biopsies from patients with IPF. CD206-targeted imaging also specifically detected a decrease in CD206 + lung macrophages on nintedanib and tofacitinib treatment. Importantly, early in vivo imaging of CD206 + macrophages allowed the prediction of experimental lung fibrosis progression as well as nintedanib and tofacitinib efficacy. Conclusions These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF.
Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee
Authors: Anne Monette, Sarah Warren, J Carl Barrett, Charlie Garnett-Benson, Kurt A Schalper, Janis M Taube, Brian Topp, Alexandra Snyder
Journal: Journal for ImmunoTherapy of Cancer (2024)

Therapies targeting the programmed cell death protein-1/programmed death-ligand 1 (PD-L1) (abbreviated as PD-(L)1) axis are a significant advancement in the treatment of many tumor types. However, many patients receiving these agents fail to respond or have an initial response followed by cancer progression. For these patients, while subsequent immunotherapies that either target a different axis of immune biology or non-immune combination therapies are reasonable treatment options, the lack of predictive biomarkers to follow-on agents is impeding progress in the field. This review summarizes the current knowledge of mechanisms driving resistance to PD-(L)1 therapies, the state of biomarker development along this axis, and inherent challenges in future biomarker development for these immunotherapies. Innovation in the development and application of novel biomarkers and patient selection strategies for PD-(L)1 agents is required to accelerate the delivery of effective treatments to the patients most likely to respond.
Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors
Authors: Patrick Tiongco Magahis, Tara Corso, Pamela Livingstone, Erika Tom, Amitabh Srivastava, Michael Postow, David Faleck
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Limited data exist for management strategies targeting immunotherapy-related enteritis (irEnteritis). Systemic corticosteroids are commonly used but often are limited by adverse events. Enteric corticosteroids such as budesonide offer an attractive alternative; however, the ileocolonic release of enteric-coated budesonide has limited utility for diffuse enteritis. Open-capsule budesonide (OCB) is a novel therapeutic approach that offers drug delivery throughout the small bowel. We report outcomes in patients treated with OCB for confirmed or suspected irEnteritis. Methods This retrospective cohort included all individuals treated with OCB for irEnteritis at Memorial Sloan Kettering from July 2018 to August 2023. Primary outcomes included clinical response, clinical remission, and corticosteroid-free remission following OCB. Secondary outcomes were OCB-related adverse events and efficacy by gastrointestinal toxicity location. Results 19 patients (53% female) with irEnteritis were treated with OCB. All patients presented with diarrhea; 15 (79%) reported anorexia with median 6 kg weight loss. 17 patients (89%) underwent esophagogastroduodenoscopy with biopsies revealing enteritis in all; 8 (42%) had concomitant colitis. 15 (79%) patients were treated previously with systemic corticosteroids: 8 (53%) were corticosteroid-dependent while 7 (47%) demonstrated non-response. 18 patients (95%) achieved clinical response, 15 (79%) attained clinical remission, and 11 (58%) had corticosteroid-free remission. Response to OCB was rapid with improvement noted after a median 4 days. 14 (74%) patients restored their pre-irEnteritis weight by OCB cessation. One mild, self-resolving adverse event was reported. Conclusions OCB is a safe and effective therapy for irEnteritis. OCB avoids systemic immunosuppression and successfully achieves clinical response and remission even in patients previously nonresponsive to systemic corticosteroids. Future studies are needed to optimize indications and duration.
Clinical efficacy of tezepelumab in pre‐selected non‐type 2 asthma patients
Authors: T. C. (Timothy) Chin‐See‐Chong, J. P. M. (Johanna) van der Valk, J. A. (Janice) Layhadi, M. H. (Mohamed) Shamji, J. H. (Jasper) Kappen
Journal: Allergy (2024)
Osteoporotic fractures: an unrecognized adverse event of immune checkpoint inhibitors?
Authors: Manar Elsayed, Carrie Ye
Journal: Journal for ImmunoTherapy of Cancer (2024)

The widespread use of immune checkpoint inhibitors (ICIs) in clinical practice has broadened our understanding of their immune-related adverse events (irAEs). IrAEs, including musculoskeletal adverse events, remain a significant concern. While ICI-associated arthritis is a well-documented musculoskeletal side effect of ICI therapy, the direct effects of ICIs on bone in patients with cancer are poorly understood. There is emerging evidence to support the hypothesis that ICIs adversely impact bone turnover and can lead to osteoporosis and fragility fractures, which are not currently recognized as irAEs.
HBcrAg values may predict virological and immunological responses to pegIFN-α in NUC-suppressed HBeAg-negative chronic hepatitis B
Authors: Andrea Vecchi, Marzia Rossi, Camilla Tiezzi, Paola Fisicaro, Sara Doselli, Elena Adelina Gabor, Amalia Penna, Ilaria Montali, Camilla Ceccatelli Berti, Valentina Reverberi, Anna Montali, Simon P Fletcher, Elisabetta Degasperi, Dana Sambarino, Diletta Laccabue, Floriana Facchetti, Simona Schivazappa, Elisabetta Loggi, Barbara Coco, Daniela Cavallone, Elena Rosselli Del Turco, Marco Massari, Giuseppe Pedrazzi, Gabriele Missale, Gabriella Verucchi, Pietro Andreone, Maurizia Rossana Brunetto, Pietro Lampertico, Carlo Ferrari, Carolina Boni
Journal: Gut (2024)

Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on.