Therapeutic Potential of PDA@CeO2 in Suppressing Hepatic Stellate Cell Activation and Preventing Liver Fibrosis.

Objective: Liver fibrosis replaces healthy tissue with scar tissue, potentially leading to cirrhosis and cancer. ROS drive this process by activating hepatic stellate cells. This study tests the hepatoprotective effects of PDA@CeO nanoparticles in scavenging ROS, inhibiting HSC activation, and delaying fibrosis, using 2D-SWE to assess treatment efficacy.

Nose-to-brain delivery of targeted lipid nanoparticles as two-pronged -amyloid nanoscavenger for Alzheimer's disease therapy.

Alzheimer's disease (AD), characterized by -amyloid (A) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating -mangostin (-M) and -site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of -M with the transcriptional silencing of BACE1 siB, thereby simultaneously inhibiting A production and enhancing its clearance.

Ferroptosis boosting system based on a sonodynamic therapy cascade-augmented strategy for triple-negative breast cancer therapy.

One of the novel forms of programmed cell death, ferroptosis, has recently emerged as a hopeful treatment strategy for triple-negative breast cancer (TNBC). However, insufficient levels of intracellular reactive oxygen species (ROS) and high levels of ROS scavengers in the tumor microenvironment (TME), such as glutathione (GSH), hamper the efficacy of ferroptosis therapy. In this study, the introduction of manganese dioxide nanoparticles (MnO NPs) generated cytotoxic hydroxyl radicals (⋅OH) in the TME.

RGD-Functionalized Ginsenoside Rg3 Liposomes for Alleviating Oxidative Stress and Choroidal Neovascularization in Age-Related Macular Degeneration.

Background And Aim: Age-related macular degeneration (AMD) is a leading cause of vision loss owing to choroidal neovascularization (CNV) and retinal vascular abnormalities. Current anti-VEGF therapies often exhibit limited efficacy in approximately 50% of patients owing to the complex pathological microenvironment, including elevated reactive oxygen species (ROS) levels. This study aimed to develop a multitargeted therapeutic strategy for AMD by leveraging the antioxidant and anti-angiogenic properties of ginsenoside Rg3 (Rg3).

Enhanced BBB penetration and microglia-targeting nanomodulator for the two-pronged modulation of chronically activated microglia-mediated neuroinflammation in Alzheimer's disease.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management.

Targeting Delivery of Dexamethasone to Inflamed Joints by Albumin-Binding Peptide Modified Liposomes for Rheumatoid Arthritis Therapy.

Introduction: Delivering the anti-inflammatory dexamethasone in nanoformulations is important for reducing off-target effects when treating rheumatoid arthritis. Nanoformulations can be targeted to sites of inflammation by modifying the nanoparticles with albumin before administration, but such particles can be unstable in vivo.

Methods: Here, we have developed and validated an alternative targeting in which dexamethasone-loaded liposomes were modified with a 46-residue peptide called "albumin-binding domain", such that the liposomes would adsorb endogenous albumin after administration.

A nasally administrated reactive oxygen species-responsive carrier-free gene delivery nanosystem for Alzheimer's disease combination therapy.

Combination therapies targeting multiple pathways are needed in order to improve treatment outcomes in Alzheimer's disease (AD) due to its complex pathogenesis. Amyloid-β and microglia-mediated neuroinflammation significantly contribute to AD pathogenesis. Amyloid-β-related nucleic acid drugs have demonstrated considerable potential in AD treatment; however, their clinical translation is limited by complex synthesis processes and carrier toxicity.

MnGA with multiple enzyme-like properties for acute wound healing by reducing oxidative stress and modulating signaling pathways.

Nanozymes with specific catalytic activity inhibit inflammation and promote wound healing efficiently and safely. In this work, multifunctional manganese-based nanozymes (MnGA) with antioxidant properties were successfully constructed via a simple coordination reaction in which manganese chloride was used as the manganese source and gallic acid (GA) was used as the ligand solution. MnGA possesses both catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities and a reactive nitrogen species (RNS) scavenging capacity, which enables it to efficiently inhibit the inflammatory response.

Counteracting Alzheimer's disease normalizing neurovascular unit with a self-regulated multi-functional nano-modulator.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy.

A Novel Nanoscale Phase-Change Contrast Agent Evaluates the Hepatic Fibrosis Through Targeting Hepatic Stellate Cell Platelet-Derived Factor Beta Receptor by Ultrasound in Vitro.

Objective: As a reversible condition at its early stages, liver fibrosis can progress to cirrhosis and hepatocellular carcinoma, underscoring the importance of early detection for preventing severe outcomes and improving prognosis. To address this issue, we developed a platelet-derived growth factor receptor β (PDGFRβ)-targeted nanoscale phase-change contrast agent to target activated hepatic stellate cells (aHSC) and enable ultrasound imaging as a foundation for the early evaluation of liver fibrosis.

Methods: PDGFR-β antibody-modified phase-change contrast agents (PPCAs) were synthesized utilizing film hydration and ultrasonic emulsification with perfluoropentane (PFP) encapsulated.

Histopathological characteristics of PRRS and expression profiles of viral receptors in the piglet immune system.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets.

Choroid plexus CCL2‒CCR2 signaling orchestrates macrophage recruitment and cerebrospinal fluid hypersecretion in hydrocephalus.

The choroid plexus (ChP) serves as the principal origin of cerebrospinal fluid (CSF). CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus recently. Nevertheless, the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain ill-defined.

Ultrasound-Responsive Nanodelivery System of GPC3-Targeting and Sonosensitizer for Visualized Hepatocellular Carcinoma Therapy.

Purpose: The incidence of hepatocellular carcinoma (HCC) is continuously increasing, and the mortality rate remains high. Thus, more effective strategies are needed to improve the treatment of HCC.

Methods: In this study, we report the use of a visualized glypican-3 (GPC3)-targeting nanodelivery system (named GC-NBs) in combination with sonodynamic therapy (SDT) to enhance the therapeutic efficacy for treating HCC.

Salicylic acid modulates secondary metabolism and enhanced colchicine accumulation in long yellow daylily ().

Salicylic acid (SA) is an essential phytoregulator that is widely used to promote the synthesis of high-value nutraceuticals in plants. However, its application in daylily, an ornamental plant highly valued in traditional Chinese medicine, has not been reported. Herein, we investigated the exogenous SA-induced physiological, transcriptional and biochemical changes in long yellow daylily (LYD).

Targeting Inflammatory Lesions Facilitated by Galactosylation Modified Delivery System Eudragit/Gal-PLGA@Honokiol for the treatment of Ulcerative Colitis.

Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis, and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC.

Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction.

Objective: Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR.

Metal coordination nanotheranostics mediated by nucleoside metabolic inhibitors potentiate STING pathway activation for cancer metalloimmunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an effective way to initiate an immune response against tumors, and the research on agonists targeting STING has become a new hotspot in the development of antitumor drugs. However, as a novel STING agonist, the limited bioavailability and activation routes of manganese ions (Mn) significantly hinder its antitumor effects. To address these challenges, we have designed a metal-coordinated nucleoside metabolic inhibitor (gemcitabine, Gem)-induced metal nanotheranostic (MGP) with PEGylation.

Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches.

A special microenvironment called the "pre-metastatic niche" is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation.

Interactions between nanoparticles and pathological changes of vascular in Alzheimer's disease.

Emerging evidence suggests that vascular pathological changes play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The dysfunction of the cerebral vasculature occurs in the early course of AD, characterized by alterations in vascular morphology, diminished cerebral blood flow (CBF), impairment of the neurovascular unit (NVU), vasculature inflammation, and cerebral amyloid angiopathy. Vascular dysfunction not only facilitates the influx of neurotoxic substances into the brain, triggering inflammation and immune responses but also hampers the efflux of toxic proteins such as Aβ from the brain, thereby contributing to neurodegenerative changes in AD.

Lipid-mediated protein corona regulation with increased apolipoprotein A-I recruitment for glioma targeting.

Protein corona has long been a source of concern, as it might impair the targeting efficacy of targeted drug delivery systems. However, engineered up-regulating the adsorption of certain functional serum proteins could provide nanoparticles with specific targeting drug delivery capacity. Herein, apolipoprotein A-I absorption increased nanoparticles (SPC-PLGA NPs), composed with the Food and Drug Administration approved intravenously injectable soybean phosphatidylcholine (SPC) and poly (DL-lactide-co-glycolide) (PLGA), were fabricated for enhanced glioma targeting.

Hyaluronic acid-functionalized DDAB/PLGA nanoparticles for improved oral delivery of magnolol in the treatment of ulcerative colitis.

Dysfunction of the mucosal barrier as well as local inflammation are major challenges in the treatment of ulcerative colitis (UC). Mag, a natural compound derived from traditional Chinese medicine, has been shown to have anti-inflammatory and mucosal protection properties. However, its poor gastrointestinal stability as well as its insufficient accumulation in inflamed colonic lesions limit its potential use as an alternative therapeutic drug in UC.