Wensheng Zheng

Cisplatin-induced acute kidney injury (AKI) remains a serious clinical complication, with excessive reactive oxygen species (ROS) recognized as key contributors. The natural antioxidant epigallocatechin-3-gallate (EGCG) shows promise in mitigating oxidative stress–related damage. However, its clinical application is limited by poor stability and low renal bioavailability. To address this, we developed a biocompatible nanoplatform by encapsulating EGCG within mesoporous polydopamine nanoparticles (EGCG-MPDA). Ultrasmall nanoparticles (<10 nm or <20 kDa) undergo rapid glomerular filtration and renal clearance, limiting therapeutic retention. While uncoated MPDA nanoparticles (∼200 nm) are large enough to avoid renal filtration, their size renders them highly susceptible to opsonization and MPS sequestration. To address this MPS-mediated clearance, we coated MPDA with a preclinically used BSA shell to create EGCG-MPDA@BSA. The biocompatible BSA corona acts as a “stealth” layer to attenuate opsonization, reduce early hepatic sequestration, and enhance interactions with peritubular endothelial cells, promoting nanoparticle passage into injured tubular epithelial cells. In a murine cisplatin-induced AKI model, EGCG-MPDA@BSA exhibited significantly enhanced therapeutic efficacy compared to uncoated nanoparticles and free EGCG. Transcriptomic and biochemical analyses revealed that its superior therapeutic efficacy arises from the activation of the Nrf2/HO-1/GPX4 antioxidant pathway, thereby alleviating oxidative stress, inflammation, and tubular damage. Collectively, this work presents an albumin corona strategy that enables effective renal retention of large nanoparticles, offering a safe, translatable approach for localized AKI therapy.

Melanoma is aggressive with limited treatment options. Paclitaxel (PTX) is effective but limited by poor solubility, systemic toxicity, and insufficient intratumoral retention. Here, we report an in situ needle-free platform that amplifies local PTX exposure via multiretention nanoscale mixed polymeric micelles composed of Soluplus and a dipotassium glycyrrhizinate-PEG-folic acid conjugate (DG-pp-FA). Needle-free intratumoral jet injection at the tumor site reduces needle-related barriers and discomfort. The micelles integrate thermoenabled local deposition and physical retention, pH-responsive stabilization and release in acidic tumor microenvironments, and folate-receptor targeting for enhanced uptake and selectivity. Central composite design optimization yielded stable micelles with a hydrodynamic size of 68 ± 3.8 nm, PDI of 0.08 ± 0.01, and 98 ± 0.11% PTX encapsulation efficiency, showing sustained release. Compared with free PTX, NF#PTX@Soluplus/DG-pp-FA improved tumor retention, increased cellular uptake, and more strongly inhibited melanoma proliferation, migration, and invasion. Single-cell sequencing, spatial transcriptomics, and proteomics revealed dual actions of direct tumor suppression and immune microenvironment remodeling, including increased leukocyte infiltration, extracellular matrix (ECM) reprogramming to improve penetration, enhanced immune activation, and reduced fibrosis. In vivo studies confirmed improved tumor localization, prolonged retention, lower toxicity, and good biocompatibility.

Radiotherapy for abdominal malignancies is limited by intestinal toxicity and secondary colorectal cancers. Here, we develop an oral, microbiota-responsive nano-amifostine (CS/PEC-AMF NPs) system that achieves site-specific radioprotection in the colorectum without compromising antitumor efficacy. By conjugating amifostine to pectin and encapsulating it with chitosan, the nanoparticles enable pH- and microbiota-triggered release in the large bowel, safeguarding drug bioactivity during gastrointestinal transit. In murine models, CS/PEC-AMF NPs attenuate both acute and chronic radiation-induced bowel injury, restore epithelial integrity, preserve stem cell populations, and promote tight junction repair. Integrated metagenomic and metabolomic analyses reveal that the system normalizes gut microbiota diversity and composition, increases short-chain fatty acid production, and facilitates macrophage polarization towards the anti-inflammatory M2 phenotype. Notably, the formulation synergistically enhances tumor suppression and extends survival in orthotopic colorectal tumor models undergoing radiotherapy and reduces the incidence of secondary colorectal tumors post-irradiation. Mechanistically, transcriptomic analysis demonstrates the suppression of proinflammatory pathways and the promotion of DNA repair programs. This study provides a paradigm for leveraging functional nanomaterials to orchestrate precise, tissue-specific radioprotection and immune modulation, addressing a key challenge in abdominal cancer therapy. Graphical abstract

Background: The sedative role of dexmedetomidine (DEX) in gastrointestinal endoscopic procedures is unclear. We performed this systematic review and meta-analysis to assess the efficacy and safety of sedation with DEX during gastrointestinal endoscopic procedures with a view to providing evidence-based references for clinical decision-making.Methods: The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that compared DEX with different sedatives comparators (such as propofol, midazolam, and ketamine) for sedation in a variety of adult gastrointestinal endoscopic procedures from inception to 1 July 2022. Standardized mean difference (SMD) and weighted mean difference (WMD) with 95% confidence interval (CI) or pooled risk ratios (RR) with 95% CI were used for continuous outcomes or dichotomous outcomes, respectively, and a random-effect model was selected regardless of the significance of the heterogeneity.Results: Forty studies with 2,955 patients were assessed, of which 1,333 patients were in the DEX group and 1,622 patients were in the control (without DEX) group. The results suggested that the primary outcomes of sedation level of DEX are comparable to other sedatives, with similar RSS score and patient satisfaction level, and better in some clinical outcomes, with a reduced risk of body movements or gagging (RR: 0.60; 95% CI: 0.37 to 0.97; p = 0.04; I² = 68%), and a reduced additional requirement for other sedatives, and increased endoscopist satisfaction level (SMD: 0.41; 95% CI: 0.05 to 0.77; p = 0.03; I² = 86%). In terms of secondary outcomes of adverse events, DEX may benefit patients in some clinical outcomes, with a reduced risk of hypoxia (RR:0.34; 95% CI: 0.20 to 0.55; p < 0.0001; I² = 52%) and cough (RR: 0.25; 95% CI: 0.12 to 0.54; p = 0.0004; I² = 0%), no significant difference in the risk of hypotension, while an increased risk of bradycardia (RR: 3.08; 95% CI: 2.12 to 4.48; p < 0.00001; I² = 6%).Conclusion: This meta-analysis indicates that DEX is a safe and effective sedative agent for gastrointestinal endoscopy because of its benefits for patients in some clinical outcomes. Remarkably, DEX is comparable to midazolam and propofol in terms of sedation level. In conclusion, DEX provides an additional option in sedation for gastrointestinal endoscopic procedures.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#searchadvanced

Background. Hepatocellular carcinoma (HCC), ranking as one of the most common malignant tumors, is one of the leading causes of cancer death, with a poor prognosis. Cuproptosis, a novel programmed cell death modality that has just been confirmed recently, may play an important role in HCC prognosis. Long noncoding RNA (LncRNA) is a key participant in tumorigenesis and immune responses. It may be of great significance to predict HCC based on cuproptosis genes and their related LncRNA. Methods. The sample data on HCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Combined with cuproptosis-related genes collected from the literature search, expression analysis was carried out to find cuproptosis genes and their related LncRNAs significantly expressed in HCC. The prognostic model was constructed by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression. The feasibility of these signature LncRNAs used for the evaluation of the overall survival rate in HCC patients as independent factors was investigated. The expression profile of cuproptosis, immune cell infiltration, and the status of somatic mutation were analyzed and compared. Results. A prognostic model of HCC consisting of seven cuproptosis gene-related LncRNA signatures was constructed. Multiple verification methods have showed that this model can accurately predict the prognosis of HCC patients. It was showed that the classified high-risk group under the risk score of this model had worse survival status, more significant expression of the immune function, and higher mutation frequency. During the analysis, the cuproptosis gene CDKN2A was found to be most closely related to LncRNA DDX11-AS1 in the expression profile of HCC patients. Conclusion. The cuproptosis-related signature LncRNA in HCC was identified, on the basis of which a model was constructed, and it was verified that it can be used to predict the prognosis of HCC patients. The potential role of these cuproptosis-related signature LncRNAs as new targets for disease therapy in antagonizing HCC development was discussed.