Latest ArticlesRadiation-induced gastrointestinal toxicity during abdominal/pelvic radiotherapy for solid malignancies remains a global clinical challenge, with current radioprotective agents demonstrating suboptimal efficacy and systemic toxicity. This study systematically investigates the radioprotective efficacy and mechanisms of purified spores derived from three clinically approved Bacillus species (B. coagulans, B. subtilis, and B. licheniformis). All the three spores exhibit significantly superior X-ray resistance and colonization efficiency to their parent probiotics. Based on this, it is found that these spores significantly reduce X-ray induced injury in intestine and colon tissues by rescuing radiation-induced crypts/villi damage, preventing apoptosis of intestinal epithelial cells, alleviating inflammation level and enhancing the intestinal barrier functions. Moreover, 16S ribosomal DNA (rDNA) sequencing results demonstrate that Bacillus spores can inhibit harmful bacteria while increase relative abundance of probiotics, especially Lactobacillus. Consequently, oral administration of these spores obviously alleviates bodyweight loss and promotes weight gain of mice received total abdominal X-ray radiation, among which mice in the BCS (spores of B. coagulans) group achieves full bodyweight recovery. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome.
Sensorineural hearing loss (SNHL) is a prevalent global health issue, primarily caused by excessive generation of reactive oxygen species (ROS) due to acoustic trauma, aging, and ototoxic drugs. Natural antioxidant enzymes, such as catalase (CAT), possess remarkable ROS scavenging capabilities and hold significant potential for SNHL treatment. However, their clinical application is hindered by inefficient delivery and limited stability. Here, we introduce a novel peptide-oligosaccharide conjugate, sELP-ON, which forms coacervate microdroplets via liquid–liquid phase separation. These microdroplets efficiently encapsulate and stably carry CAT, releasing it in a glutathione-triggered, redox-responsive manner. The CAT-loaded sELP-ON (sELP-ON@CAT) enhanced cellular uptake through direct cytoplasmic internalization and demonstrates a more robust ROS scavenging activity than naked CAT treatment. Local administration of sELP-ON@CAT in an acoustic injury mouse model effectively rescues hearing loss by reducing cochlear ROS levels, thereby mitigating hair cell loss, ribbon synapse depletion, stria vascularis shrinkage and spiral ganglion neuron degeneration. In summary, our innovative coacervate microdroplet system enables targeted, redox-responsive cytoplasmic delivery of macromolecular antioxidants, offering a novel and effective strategy for treating SNHL.
Nanotechnological advancements have established stimuli-responsive nanomaterials as a pivotal strategy for spatiotemporally controlled drug delivery in precision biomedicine. Metal-organic frameworks (MOFs), crystalline porous materials constructed from metal ions/clusters and organic ligands through coordination bonds, exhibit exceptional drug delivery potential owing to their high surface area, tunable pore size, and facile functionalization. This review systematically analyzes recent advances in MOF-based drug delivery, with a focus on synthesis strategies, stimulus-responsive mechanisms, and biomedical applications. A key contribution of this review is the systematic classification of stimuli-responsive mechanisms, covering triggers such as pH, temperature, magnetic fields, humidity, and biological stimuli (e.g., redox factors, enzymes, adenosine triphosphate (ATP), ions, and hydrogen sulfide (H2S)). This framework provides a blueprint for designing targeted drug delivery platforms. By synthesizing cutting-edge research and emerging trends, this review offers actionable insights to advance stimuli-responsive MOF drug delivery systems (DDS).
Marine ecosystems represent one of the most valuable yet underexplored sources of diverse bioactive compounds with significant potential for economic, healthcare, and environmental applications. Marine-derived bioactive compounds have emerged as promising active ingredients, exhibiting antibacterial, antiviral, anticancer, anti-inflammatory, and antioxidant properties, among others, with growing use in cosmetics and food supplements. Ongoing research in this area is aligned with the United Nations Sustainable Development Goals, particularly Goal 12, which relates to responsible production and consumption. The environmentally friendly extraction of these bioactive compounds from marine sources offers a path toward greener industrial practices and a more sustainable global economy. This review provides a comprehensive overview of the current state of the art on the main classes of marine bioactive compounds, their natural sources, green extraction methods, and their applications in health-related fields, including cosmetics and food supplements. Despite their potential, the use of marine bioactive compounds remains limited. Current research is largely based on in vitro studies using compound mixtures, with limited data on regulatory frameworks and human safety. To unlock their full therapeutic potential, future research should focus on: the standardization of clinical trial protocols, the isolation and characterization of individual compounds, and the expansion of in vivo studies in both animals and humans.
Hydrogel bioadhesives, known for their ability to rapidly inhibit bleeding and minimize damage to surrounding tissues, are revolutionizing traditional surgical procedures. The interfacial force between hydrogel bioadhesives and tissue is critical for achieving strong adhesion in wound healing applications. However, preformed hydrogel bioadhesives cannot achieve seamless closure of irregular shape wounds and tend to detach in bleeding environments, limiting their practical applications. In this study, we developed an in-situ photopolymerization hydrogel bioadhesive (IPHB) method to fully seal irregular shape wounds in bleeding conditions within 5 min, eliminating the need for risky artery-blocking procedures. The fluidic hydrogel precursor solution can infiltrate micro- and nanostructured wound, penetrate tissues, and rapidly form an adhesive hydrogel under ultraviolet (UV) irradiation through strong topological entanglement at the interface. The resulting hydrogel demonstrates excellent stretchability, low swelling, and intrinsic antibacterial properties. The IPHB method was successfully employed to seal kidney wounds in a living pig, achieving rapid hemostasis and promoting wound healing without harming healthy tissues. This innovative approach significantly reduces surgical duration and enhances safety. Notably, this study marks the first application of a hydrogel bioadhesive for kidney wound treatment in a living pig, paving the way for safer and more efficient surgical practices.
Diabetic foot ulcers (DFUs) pose substantial clinical challenges due to their high prevalence, intricate pathophysiology, and recalcitrance to conventional therapeutic interventions. Traditional treatment paradigms frequently overlook the multidimensional aspects of DFUs, resulting in protracted healing trajectories and escalated risks of adverse sequelae. To address this critical diabetes-related complication, this comprehensive review delves into the pioneering application of biomaterials as microenvironmental modulators, underscoring their transformative potential in accelerating wound repair. By synthesizing in vivo, in vitro, and clinical evidence, we elucidate the mechanistic underpinnings and translational promise of these advanced materials. Our objective is to engage scholarly readers with state-of-the-art advancements in biomaterial engineering, emphasizing their pivotal contribution to paradigm shifts in DFU management strategies.
Wound healing remains a significant challenge in medical science due to the complexity of the process. Hydrogels have emerged as promising materials for wound management, yet achieving non-cytotoxicity, biodegradability, and mechanical robustness in a single formulation continues to be a research focus. This study aims to develop polysulfonate-polyvinyl alcohol (PVA)/poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPs) membranes reinforced with ZnO nanoparticles (NPs) and g-C3N4 to meet these requirements. The fabricated membranes were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and atomic force microscopy (AFM), and were subjected to various biological evaluations including swelling ratios, water vapor transmission rates (WVTR), antibacterial activity, cytotoxicity, and in-vivo wound healing in a mouse model. The membranes exhibited mechanical strengths of 42.6 MPa and strains up to 183.35%. XRD and FTIR confirmed the successful incorporation of ZnO NPs and g-C3N4, while SEM and AFM revealed a rough surface morphology conducive to cell adhesion. The membranes achieved moisture retention rates over 90%, WVTR values up to 71.66 h g−1 m−2, and swelling ratios as high as 116.06%. Cytotoxicity tests demonstrated cellular viability exceeding 84.37%, and antibacterial assays showed significant inhibition zones. In vivo studies indicated an 88.26% wound healing rate within 9 days, surpassing traditional dressings and saline treatments. These results suggest that PAMPs/PVA/g-C3N4/ZnO membranes are found to be highly effective for wound dressing applications, combining superior mechanical properties, biocompatibility, and enhanced healing efficacy.
The development of organic dyes with fluorescence in the second near-infrared (NIR-Ⅱ, 1000–1700 nm) biological window is crucial for deep-tissue tumor phototheranostics. Herein, we synthesized a thienothiadiazole-based NIR-Ⅱ fluorescent dye TTDOC with donor-acceptor-donor (D-A-D) molecular architecture for photoacoustic/fluorescence imaging-guided photothermal therapy (PTT). NIR-Ⅱ dye TTDOC, taking electron-deficient thienothiadiazole as an acceptor and triphenylamine as a donor, exhibited a high fluorescence quantum yield of 1.7% in dichloromethane (IR-1061 as standard, 1.7% in dichloromethane). Upon encapsulation in biocompatible polymer F-127, TTDOC nanoparticles (NPs) were formulated with NIR absorption and fluorescence band covering 900–1150 nm, and demonstrated an outstanding photothermal conversion efficiency (η) of 51.6% upon 808 nm photoirradiation. In vivo studies, including fluorescence and photoacoustic imaging, revealed that TTDOC NPs effectively accumulated in tumor tissues, reaching maximal tumor enrichment at 20 h post-injection. In vitro and in vivo results confirmed the ability of TTDOC NPs to enable efficient photoacoustic/fluorescence imaging-guided PTT, offering a promising strategy for deep-tissue tumor treatment.
Neutrophil extracellular traps (NETs) are a significant unfavorable factor for wound healing in diabetes. Citrullination of histone by peptidyl arginine deiminase 4 (PAD4) is the prerequisite for NETs formation. Therefore, PAD4 inhibitors are a promising NETs-targeting strategy to accelerate diabetic wound healing. Herein, a virtual screening workflow incorporating molecular docking and molecular dynamics was performed on a library of U.S. Food and Drug Administration (FDA)-approved drugs, resulting in the identification of gliquidone as a new PAD4 inhibitor. Gliquidone binds directly to PAD4, inhibits its activity, and interrupts NETs formation in neutrophils, which in turn rescues functional impairment in fibroblasts. Furthermore, in streptozotocin-induced diabetic mice, gliquidone accelerates wound healing. Taken together, gliquidone was successfully identified as a new PAD4 inhibitor through a computer-aided virtual screening pipeline, which might be a therapeutic agent against diabetic foot ulcers.
Glutaminyl cyclase (QC), a key enzyme catalyzing the pyroglutamate modification of bioactive peptides, has emerged as a promising pharmacological target in cancer and other human diseases. Inhibition of QC activity represents a potential therapeutic strategy for diseases associated with QC dysregulation, suggesting that QC inhibitors might be as promising therapeutic approach for these diseases. Building upon our previous lead compound 1 (half maximal inhibitory concentration (IC50): Golgi resident QC (gQC), 3.22 µmol/L; secretory QC (sQC), 4.04 µmol/L), we performed systematic structural optimization to develop novel 3,4-disubstituted indole-2-ketone derivatives. Structure-activity relationship (SAR) studies identified highly active gQC and sQC inhibitors (compounds 24, 28, and 29) with significantly enhanced QC inhibitory activity. Among them, 28 exhibited superior inhibitory activity against gQC (IC50 = 0.095 µmol/L) compared to sQC (IC50 = 1.33 µmol/L), and could most significantly improve the thermal stability of gQC protein. Using compound 17 with similar structure but 130 times lower gQC inhibitory activity than 28 as a negative control, the in vitro anti-tumor activity study found that 28 can bind to gQC in MDA-MB-231 breast cancer cells and significantly inhibit the growth and migration, by affecting cell proliferation and inducing G0/G1 phase cell cycle arrest. In nude mice bearing MDA-MB-231 cell xenograft, intratumor injection of 28 (25 mg/kg) produced 40.6% inhibition rates. This work not only provides structural basis and new leads for drug discovery targeting QC, but also presents compelling evidence supporting QC, especially gQC as a potential target for breast cancer therapy.