Novel reduced heteropolyacid nanoparticles for effective treatment of drug-induced liver injury by manipulating reactive oxygen and nitrogen species and inflammatory signals.

With the rapid advancements in biomedicine, the use of clinical drugs has surged sharply. However, potential hepatotoxicity limits drug exploitation and widespread usage, posing serious threats to patient health. Hepatotoxic drugs disrupt liver enzyme levels and cause refractory pathological damage, creating a challenge in the application of diverse first-line drugs. The activation and deterioration of reactive oxygen and nitrogen species (RONS) and inflammatory signals are key pathological mechanisms of drug-induced liver injury (DILI). Herein, a novel reduced heteropolyacid nanoparticle (RNP) has been developed, possessing high RONS-scavenging ability, strong anti-inflammatory activity, and excellent biosafety. These features enable it to swiftly restore the redox and immune balance of the liver. Intravenous administration of RNP effectively scavenged RONS storm, reversing liver oxidative stress and restoring normal mitochondrial membrane potential and function. Furthermore, by inhibiting c-Jun-N-terminal kinase phosphorylation, RNP facilitated the restoration of nuclear factor erythroid 2-related factor 2-mediated endogenous antioxidant signaling, ultimately rescuing the liver function and tissue morphology in acetaminophen-induced DILI mice. Crucially, the high biocompatible RNP exhibited superior efficacy in the DILI mouse model compared to the clinical antioxidant N-acetylcysteine. This targeted therapeutic approach, tailored to address the onset and progression of DILI, offers valuable new insights into controlling the condition and restoring liver structure and function.

Precisely Inhibiting Excessive Intestinal Epithelial Cell Apoptosis to Efficiently Treat Inflammatory Bowel Disease with Oral Pifithrin-α Embedded Nanomedicine (OPEN).

The increased incidence of inflammatory bowel disease (IBD) has seriously affected the life quality of patients. IBD develops due to excessive intestinal epithelial cell (IEC) apoptosis, disrupting the gut barrier, colonizing harmful bacteria, and initiating persistent inflammation. The current therapeutic approaches that reduce inflammation are limited. Although IBD can be treated significantly by directly preventing IEC apoptosis, achieving this therapeutic approach remains challenging. Accordingly, the authors are the first to develop an oral pifithrin-α (PFTα, a highly specific p53 inhibitor) embedded nanomedicine (OPEN) to effectively treat IBD by inhibiting excessive IEC apoptosis. As a major hub for various stressors, p53 is a central determinant of cell fate, and its inhibition can effectively reduce excessive IEC apoptosis. The tailored OPEN can precisely inhibit the off-target and inactivation resulting from PFTα entry into the bloodstream. Subsequently, it persistently targets IBD lesions with high specificity to inhibit the pathological events caused by excessive IEC apoptosis. Eventually, OPEN exerts a significant curative effect compared with the clinical first-line drugs 5-aminosalicylic acid (5-ASA) and dexamethasone (DEX). Consequently, the OPEN therapeutic strategy provides new insights into comprehensive IBD therapy.

Selenium Nanodots (SENDs) as Antioxidants and Antioxidant-Prodrugs to Rescue Islet ß Cells in Type 2 Diabetes Mellitus by Restoring Mitophagy and Alleviating Endoplasmic Reticulum Stress.

Preventing islet ß-cells death is crucial for treating type 2 diabetes mellitus (T2DM). Currently, clinical drugs are being developed to improve the quality of T2DM care and self-care, but drugs focused on reducing islets ß-cell death are lacking. Given that ß-cell death in T2DM is dominated ultimately by excessive reactive oxygen species (ROS), eliminating excessive ROS in ß-cells is a highly promising therapeutic strategy. Nevertheless, no antioxidants have been approved for T2DM therapy because most of them cannot meet the long-term and stable elimination of ROS in ß-cells without eliciting toxic side-effects. Here, it is proposed to restore the endogenous antioxidant capacity of ß-cells to efficiently prevent ß-cell death using selenium nanodots (SENDs), a prodrug of the antioxidant enzyme glutathione peroxidase 1 (GPX1). SENDs not only scavenge ROS effectively, but also "send" selenium precisely to ß-cells with ROS response to greatly enhance the antioxidant capacity of ß-cells by increasing GPX1 expression. Therefore, SENDs greatly rescue ß-cells by restoring mitophagy and alleviating endoplasmic reticulum stress (ERS), and demonstrate much stronger efficacy than the first-line drug metformin for T2DM treatment. Overall, this strategy highlights the great clinical application prospects of SENDs, offering a paradigm for an antioxidant enzyme prodrug for T2DM treatment.

Facile Synthesis of Holmium-Based Nanoparticles as a CT and MRI Dual-Modal Imaging for Cancer Diagnosis.

The rapid development of medical imaging has boosted the abilities of modern medicine. As single modality imaging limits complex cancer diagnostics, dual-modal imaging has come into the spotlight in clinical settings. The rare earth element Holmium (Ho) has intrinsic paramagnetism and great X-ray attenuation due to its high atomic number. These features endow Ho with good potential to be a nanoprobe in combined x-ray computed tomography (CT) and T2-weighted magnetic resonance imaging (MRI). Herein, we present a facile strategy for preparing HoF3 nanoparticles (HoF3 NPs) with modification by PEG 4000. The functional PEG-HoF3 NPs have good water solubility, low cytotoxicity, and biocompatibility as a dual-modal contrast agent. Currently, there is limited systematic and intensive investigation of Ho-based nanomaterials for dual-modal imaging. Our PEG-HoF3 NPs provide a new direction to realize in vitro and vivo CT/MRI imaging, as well as validation of Ho-based nanomaterials will verify their potential for biomedical applications.

The impacts of the built environment on the incidence rate of COVID-19: A case study of King County, Washington.

With COVID-19 prevalent worldwide, current studies have focused on the factors influencing the epidemic. In particular, the built environment deserves immediate attention to produce place-specific strategies to prevent the further spread of coronavirus. This research assessed the impact of the built environment on the incidence rate in King County, US and explored methods of researching infectious diseases in urban areas. Using principal component analysis and the Pearson correlation coefficient to process the data, we built multiple linear regression and geographically weighted regression models at the ZIP code scale. Results indicated that although socioeconomic indicators were the primary factors influencing COVID-19, the built environment affected COVID-19 cases from different aspects. Built environment density was positively associated with incidence rates. Specifically, increased open space was conducive to reducing incidence rates. Within each community, overcrowded households led to an increase in incidence rates. This study confirmed previous research into the importance of socioeconomic variables and extended the discussion on spatial and temporal variation in the impacts of urban density on the spread of COVID, effectively guiding sustainable urban development.