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Osteoarthritis (OA) is associated with metabolic imbalance of articular cartilage and an increase of intracellular reactive oxygen species (ROS). Synergistic therapy based on the codelivery of ROS scavengers and antisense oligonucleotides (ASO) into chondrocytes has the potential to effectively treat OA. Here, we developed a novel biocompatible metal‐organic framework (MOF)‐encapsulated nanozyme/ASO delivery platform (miR/IrO2@ZIF‐8) for OA treatment. IrO2 nanoparticles with the catalytic activities of superoxide dismutase/catalase were synthesized using a hydrothermal method, resulting in excellent ROS scavenging performance. IrO2 was further loaded into zeolitic imidazolate framework‐8 (ZIF‐8) to maintain its catalytic efficacy and regulate its size, surface charge, and biocompatibility to enhance the therapeutic effect of the platform. As an effective ASO delivery carrier, the synthesized IrO2@ZIF‐8 exhibited high antagomiR‐181a loading and lysosomal escape capacity, enabling it to rebalance cartilage metabolism. In vitro experiments showed that miR/IrO2@ZIF‐8 could restore ROS levels, mitochondrial membrane potential, and lipid peroxidation in chondrocytes. At the same time, the expression levels of proinflammatory markers (IL‐1β, IL‐6, and COX‐2) as well as the extracellular matrix degrading enzymes (ADAMTS‐5 and MMP13) were downregulated, indicating effective antioxidant, anti‐inflammatory, and anticartilage degradation effects. Notably, miR/IrO2@ZIF‐8 was able to deliver IrO2 nanoparticles and antagomiR‐181a to the cartilage tissue at a depth of up to 1.5 mm, thus solving the problems of poor permeability and difficult retention of drugs in cartilage tissue. This further improves the synergistic therapeutic effect on OA by inhibiting cartilage degradation. The combination of MOF‐encapsulated IrO2 nanozymes with antagomiR‐181a has an excellent therapeutic effect on OA, offering a promising translational medicine paradigm. [ABSTRACT FROM AUTHOR]

Objective. A target of low-density lipoprotein cholesterol (LDL-C)

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR‐200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF‐1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein‐diacetate assays. Enzyme‐linked immunosorbent assay was used to evaluate 8‐oxo‐7,8‐dihydro‐2′deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real‐time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR‐200a/b/c‐3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR‐200a/b/c‐3p expression, and suppressed ATM and GLI2. MiR‐200a/b/c‐3p inhibition ameliorated HG‐induced cell proliferation and DNA damage repair repression. MiR‐200a/b/c‐3p targeted ATM. Then, the silenced ATM reversed the miR‐200a/b/c‐3p inhibition‐mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG‐induced cell proliferation and DNA damage repair inhibition via miR‐200a/b/c‐3p. MiR‐200a/b/c‐3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR‐200/ATM axis to enhance diabetic wound healing in DFU. [ABSTRACT FROM AUTHOR]