Cisplatin resistance remains a major clinical challenge in cancer therapy, often driven by the upregulation of DNA repair pathways. Here, we present a dual-functional nanotherapeutic system (HFn-NERiP-Pt(IV)) combining a glutathione-responsive PROTAC (NERiP) with a ferritin nanocarrier for targeted ERCC1/XPF degradation and enhanced platinum delivery. NERiP selectively degrades ERCC1/XPF upon release in reductive tumor environments, suppressing nucleotide excision repair and enhancing platinum cytotoxicity.
View Article and Find Full Text PDFBackground: Human spermatogonial stem cells (SSCs) exhibit a remarkable capacity for proliferation, crucial for sustaining spermatogenesis throughout life. While the Cullin-RING E3 ubiquitin ligase 2 (CRL2) complex is known to regulate various cellular functions, its precise role in human SSCs has not been fully elucidated. This study aimed to investigate a novel variant of the CRL2 complex, termed CRL2, and its role in SSC function.
View Article and Find Full Text PDFACS Appl Mater Interfaces
August 2025
Enzyme catalysis plays a fundamental role in biological systems, particularly in multienzyme cascade reactions that achieve efficient and precise transformation of complex substrates through synergistic cooperation. These cascades exemplify the high-level division of labor and ordered regulation intrinsic to natural catalytic networks. Inspired by such biological systems, nanozymes, which are artificial catalytic materials that combine the physicochemical properties of nanomaterials with enzyme-like activities, have emerged as a promising platform for constructing multistep catalytic processes.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
July 2025
Skin defects caused by inflammation, burns, or infections typically require functional wound dressings to promote healing. Hydrogels with three-dimensional hydrophilic porous structures provide a favorable microenvironment for the migration and proliferation of cells involved in wound healing. As a key biomolecular component of the extracellular matrix (ECM), collagen can self-assemble into collagen-based hydrogels.
View Article and Find Full Text PDFTourette syndrome (TS) is a neurodevelopmental disorder characterized by tics that significantly impair childhood development. Volatile oil from Acori graminei Rhizoma (VOA), known for its anti-inflammatory and neuroprotective properties, holds therapeutic potential for TS, though its molecular mechanisms remain undefined. In this study, VOA was extracted via hydrodistillation (yield: 1.
View Article and Find Full Text PDFAdv Sci (Weinh)
July 2025
Food-grade lipid nanoparticles (FLNs) have been widely used as functional carriers of various nutrients and clinical drugs; however, the potential for FLNs to induce substantial biological effects is often overlooked. Here, it is found that FLNs are first delivered to the early endosomes and then preferentially fused with lipid droplets (LDs) after entering the cells through endocytosis. This process leads to a notable LDs accumulation, which in turn triggers autophagy via the AMPK-mTOR-ULK1 signaling pathway.
View Article and Find Full Text PDFIn the testes, spermatogonial stem cells (SSCs) maintain normal spermatogenesis through the dual potential of self-renewal and differentiation, which is essential for male fertility. Myotubularin-associated protein 7 (MTMR7), as a vital member of MTMR family with phosphatase activity, is involved in a variety of membrane transport processes through regulating the levels of phosphoinositides (PIPs). Our earlier research demonstrated that MTMR7 controls the cell cycle and maintains homeostasis in mouse SSCs by inhibiting PI3K/AKT signaling.
View Article and Find Full Text PDFEthnopharmacological Relevance: Gastrointestinal motility disorders (GMD) severely impact quality of life, with rising global prevalence linked to modern dietary and lifestyle changes. Traditional Chinese medicine (TCM), rooted in the "holistic regulation" philosophy and centuries of empirical application, demonstrates unique advantages in restoring gastrointestinal homeostasis. Historical records and modern clinical practices validate the efficacy of herbal compounds, bioactive phytochemicals, and external therapies in modulating intestinal pacemaker systems.
View Article and Find Full Text PDFJ Ethnopharmacol
July 2025
Ethnopharmacological Relevance: Epilepsy (EP) is a chronic neurological disease, and the clinical treatment of EP is dominated by modern drugs, but one-third of the patients have drug-resistant reactions, which seriously affects the quality of patients' survival. Traditional Chinese medicine (TCM), however, as a promising resource, plays a unique advantage in improving the clinical symptoms of EP and alleviating the adverse effects of modern drug therapy. A large number of studies in recent years have reported that TCM plays an important role in EP treatment by regulating voltage-gated ion channels (VGICs).
View Article and Find Full Text PDFCarbohydr Polym
September 2025
Resistant starch, recognized as a prebiotic, has demonstrated significant potential in alleviating various disease models but its intestinal safety study has been always overlooked. Banana starch (BS), a rich source of resistant starch, and its derived nanoparticles have been implicated in intestinal barrier dysfunction in our previous study. However, the short-term effects of BS consumption on gut health in healthy bodies remain unclear.
View Article and Find Full Text PDFStimulator of interferon genes (STING) represents a promising therapeutic target for cancer and infectious diseases due to its ability to activate innate immune responses. Herein, we describe the discovery of 3-(fluoro-imidazolyl) pyridazine derivatives as potent STING agonists. Our comprehensive investigation, including structural and functional analysis as well as molecular dynamics simulation, suggests that appropriate spatial dimensions may play a crucial role in determining agonist efficacy.
View Article and Find Full Text PDFFront Aging Neurosci
April 2025
Background: Alzheimer's disease (AD) is the fastest-growing neurodegenerative disorder globally, with patient numbers expected to rise to 130 million by 2050. Insomnia, a prevalent comorbidity, exhibits a bidirectional relationship with AD: insomnia accelerates AD pathology, while AD worsens sleep disorders. This relationship has emerged as a key area of research.
View Article and Find Full Text PDFRationale: The utilization of anti-inflammatory therapy for treating brain diseases holds promise; however, research on intranasal administration of drug compounds remains limited. Quantitative data, particularly pharmacokinetics, are scant, and direct evidence of the distribution of intranasally administered recombinant interleukin 10 (rIL-10) within the brain is lacking.
Methods: Employing fluorescent labeling, in vivo imaging, and confocal microscopy, we meticulously monitored the distribution and delivery pathways of intranasally administered rIL-10 in the brain.
Front Pharmacol
March 2025
Unlabelled: Myocardial fibrosis (MF) involves the activation and excessive proliferation of cardiac fibroblasts (CFs) in the extracellular matrix, leading to increased collagen expression that impairs cardiac function. Currently, there are no effective pharmacological treatments for MF. Traditional Chinese Medicine (TCM), particularly Bunge [Lamiaceae; radix et rhizoma], has gained attention for its potential in treating MF.
View Article and Find Full Text PDFAm J Transl Res
March 2025
Objectives: SPRY (repeats in splA and RyR) domain-containing SOCS (suppressor of cytokine signaling) box protein 1 (SPSB1) is an E3 ligase adaptor protein that has been implicated in various cellular processes and physiological pathways. However, its role in spermatogenesis remains poorly understood. The objective of this study was to investigate the impact of SPSB1 deficiency on spermatogenesis and male fertility in mice.
View Article and Find Full Text PDFAm J Transl Res
March 2025
Objectives: As a crucial member of the Suppressor of Cytokine Signaling (SOCS) family, SOCS7 regulates various physiological processes, including insulin resistance, inflammation, and tumor suppression. However, its role in male germ cells remains poorly understood. This study aims to investigate the function of SOCS7 in spermatogenesis and uncover its potential regulatory mechanisms.
View Article and Find Full Text PDFBackground: Spermatogenesis, the process by which male germ cells develop into mature spermatozoa, is a complex and highly regulated phenomenon crucial for male fertility. Various molecular pathways, including ubiquitination, play critical roles in this process. Ubiquitination regulates multiple stages of spermatogenesis by controlling cell remodeling and protein metabolism.
View Article and Find Full Text PDFFront Bioeng Biotechnol
March 2025
Bacterial resistance remains a significant challenge, necessitating the development of new antibacterial strategies. This study introduces a rapidly synthesized L-histidine- FeO (L-His-FeO) nanozyme with enhanced peroxidase (POD)-like activity, designed to improve antibacterial efficacy and accelerate the healing of bacteria-infected wounds. We successfully synthesized L-His-FeO using an ultrafast, room-temperature synthesis method, and observed its anti-infection effect and explored its anti-infection mechanism through and antibacterial experiments.
View Article and Find Full Text PDFThe E3 ubiquitin ligase RNF187, also known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 is indispensable for the proliferation and migration of GC-1 cells derived from mouse spermatogonia and GC-2 cells derived from spermatocytes. However, it remains unclear whether RNF187 plays a crucial role in the self-renewal and migration of human spermatogonial stem cells (SSCs).
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
April 2025
Purpose: Microglial activation plays a pivotal role in the pathogenesis of retinal degeneration, contributing to neuroinflammation within the retina. Previous studies identified that nicotinamide riboside (NR) mitigated light-induced retinal degeneration (LIRD) and inhibited microglial activation. The cGAS-STING signaling pathway has been recognized as a key mediator of inflammation in response to cellular stress and tissue damage.
View Article and Find Full Text PDFIEEE Trans Neural Syst Rehabil Eng
January 2025
Mastication plays an important role in effective food digestion and nutrient absorption. Therefore, regulating masticatory force in people with declining mastication function is significant for maintaining health and quality of life. In this study, we tested the effect of tactile augmentation on mastication force.
View Article and Find Full Text PDFGlaucoma filtration surgery (GFS) effectively lowers intraocular pressure in glaucoma patients, but postoperative bleb fibrosis often leads to surgical failure. Artesunate (ART) has demonstrated antifibrotic potential; however, its clinical use is limited by poor solubility and rapid degradation. This study aimed to develop chitosan-ART nanoparticles (CS@ART NPs) to improve ART's therapeutic efficacy in preventing bleb fibrosis.
View Article and Find Full Text PDFEthnopharmacological Relevance: Chinese herbal medicine constitutes a substantial cultural and scientific resource for the Chinese nation, attracting considerable scholarly interest due to its intrinsic characteristics of "multi-component, multi-target, and multi-pathway" interactions. Simultaneously, it aligns accurately with the intricate and continuously evolving progression of non-small cell lung cancer (NSCLC). Furthermore, contemporary pharmacological studies indicate that natural herbaceous plants and their bioactive compounds exhibit a diverse array of biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects, among others.
View Article and Find Full Text PDFMedComm (2020)
March 2025
Stroke is a leading risk factor for disability and death. Necroptosis is involved in stroke pathogenesis. However, the molecular mechanisms underlying necroptosis in stroke remain unclear.
View Article and Find Full Text PDFA new ursane triterpenoid, actichinone (3-oxo-2α,24-dihydroxyurs-12-en-28-oic acid, 1), was isolated from the roots of a kiwi plant Actinidia chinensis Planch, together with 18 known triterpenoids (2-19). The structure of actichinone (1) was established by extensive spectroscopic analysis. Actichinone (1) showed the most potent lipid-lowering activity in the oleic acid (OA)-induced primary mouse hepatocytes and the structure-activity relationships (SARs) were analyzed.
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