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Platelet Jak2 deficiency accelerates atherosclerosis with increased inflammatory response
Zeolites as Photoactive Scaffolds for Efficient Photooxidation
Backflow H+ during interfacial polymerization matters to configure spatial charges of polyamide membranes
Chitosan-encapsulated Aloe vera nanoparticles outperform carrier-free forms in enhancing MSCs therapy for amikacin nephrotoxicity
Abstract Acute kidney injury (AKI) induced by nephrotoxic drugs like amikacin remains a clinical challenge, with mesenchymal stem cells (MSCs) showing limited efficacy due to poor survival and engraftment. While Aloe vera extract (AVE) possesses renoprotective properties, its bioactive compounds suffer from low bioavailability and instability. The study developed and characterized two nanoformulations of AVE; carrier-free nanoparticles (AVENPS) and chitosan-encapsulated nanoparticles (AVE-CSNPS), to enhance mesenchymal stem cells (MSCs) therapy for amikacin-induced kidney injury. In vitro bioactivities (antioxidant, anti-inflammatory, anticoagulant, and cytotoxicity) were evaluated for both nanoformulations. For in vivo assessment, amikacin-induced AKI mice received: MSCs alone, MSCs + AVE, MSCs + AVENPS, MSCs + CSNPS or MSCs + AVE-CSNPS. Phytochemical characterization revealed both formulations preserved key bioactive compounds, with AVE-CSNPS showing superior retention of flavonoids and essential minerals. Physicochemical analysis demonstrated AVE-CSNPS had optimal characteristics for drug delivery, including larger hydrodynamic size, higher positive zeta potential, and enhanced stability (PDI < 0.3). In vitro, AVE-CSNPS exhibited significantly stronger antioxidant, anti-inflammatory, and anticoagulant effects compared to AVENPS, while showing lower cytotoxicity. In vivo , the MSCs + AVE-CSNPS combination therapy most effectively restored kidney function, normalized oxidative stress markers and pro-inflammatory cytokines. These results demonstrated chitosan encapsulation significantly enhanced Aloe vera ’s therapeutic potential and MSCs synergy, offering a promising nano-enabled strategy for renal regeneration.
MilM from mildiomycin biosynthesis is an oxygen-, pyridoxal phosphate-dependent arginine hydroxylase
A General Metallaphotoredox Platform for <i>N</i>-Alkylated Sulfoximines as Bioisosteric Building Blocks
Bacterial RNA promotes proteostasis through inter-tissue communication in C. elegans
Abstract Life expectancy has been increasing over the last decades, which is not matched by an increase in healthspan. Besides genetic composition, environmental and nutritional factors influence both health- and lifespan. Diet is thought to be a major factor for healthy ageing. Here, we show that dietary RNA species improve proteostasis in C. elegans. Inherent bacterial-derived double stranded RNA reduces protein aggregation in a C. elegans muscle proteostasis model. This beneficial effect depends on low levels of systemic selective autophagy, the RNAi machinery in the germline, even when the RNA is delivered through ingestion in the intestine and the integrity of muscle cells. Our data suggest a requirement of inter-organ communication between the intestine, the germline and muscles. Our results demonstrate that bacterial-derived RNAs elicit a systemic response in C. elegans, which protects the animal from protein aggregation during ageing, which might extend healthspan.
Neutrophil-targeted drug secures first FDA approval for inflammatory lung disease
Degradation of CaMKII is stimulated by its active conformation
Air- and Water-Stable Sulfide Radical Cations Supported by Cyclic (Alkyl)(amino)carbenes
Author Correction: Impacts of convection, chemistry, and forest clearing on biogenic volatile organic compounds over the Amazon
BR-bodies facilitate adaptive responses and survival during copper stress in Caulobacter crescentus
Powering Molecular Motors with Light Across the Rainbow Using Quantum Dots
Structural insights into Wnt/β-catenin signaling regulation by LGR4, R-spondin, and ZNRF3
Abstract Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) plays a critical role in regulating the wingless-related integration site (Wnt) signaling pathway and is essential for organ development and carcinogenesis. LGR4, along with its ligand R-spondin (RSPO), potentiates Wnt/β-catenin signaling by recruiting its signaling suppressor, E3 ligase Zinc and Ring Finger 3 (ZNRF3), and inducing its membrane clearance. However, detailed mechanisms underlying this process remain unknown. In this study, we present the cryo-electron microscopy structures of human LGR4, the LGR4-RSPO2 and LGR4-RSPO2-ZNRF3 complexes. Upon RSPO2 binding, LGR4 undergoes no significant conformational changes in its transmembrane and extracellular domain structures or their relative orientations. LGR4, RSPO2, and ZNRF3 assemble into a 2:2:2 complex with the ZNRF3 dimer enclosed at the center. This ternary arrangement and forced dimerization of ZNRF3 likely underpin how LGR4 and RSPO2 potentiate Wnt/β-catenin signaling by sequestering ZNRF3 from Wnt receptors and facilitating its auto-inactivation. This study provides a structural basis for understanding the regulatory mechanism of Wnt/β-catenin signaling through the LGR4-RSPO2-ZNRF3 pathway and may offer opportunities for future drug development targeting this axis.