Linezolid, an oxazolidinone antibiotic, is widely used to treat multidrug-resistant tuberculosis and drug-resistant Gram-positive infections. However, prolonged use is associated with severe hematologic toxicity, the underlying mechanisms of which remain incompletely understood, particularly regarding the role of linezolid metabolites. Our clinical study indicates that elevated exposure to PNU142586, a primary metabolite of linezolid, is associated with an increased risk of linezolid-induced toxicity, even in the absence of renal impairment. To elucidate its mechanism, we identify DNA topoisomerase 2-α (TOP2A) and DNA topoisomerase 2-β (TOP2B) as primary targets of PNU142586 at molecular, cellular, and in vivo levels. PNU142586 disrupts replication and transcription by impeding DNA binding to TOP2A and TOP2B with a favorable conformation for cleavage and by inhibiting adenosine 5′-triphosphate hydrolysis, ultimately leading to antiproliferative and cytotoxic effects, including mitochondrial dysfunction. The present study thus provides mechanistic insight into linezolid-induced hematologic toxicity and offers a foundation for safer antibiotic development and improved clinical monitoring through biomarker identification.

The skin, recognized as the largest organ in the human body, serves a vital function in safeguarding against external threats. Severe damage to the skin can pose significant risks to human health. There is an urgent requirement for safe and effective therapies for wound healing. While phytotherapy has been widely utilized for various health conditions, the potential of Quercus glauca in promoting wound healing has not been thoroughly explored. Q. glauca is a cultivated crop known for its abundance of bioactive compounds. This study examined the wound-healing properties of Quercus glauca acorn seed coat water extract (QGASE). The findings from the study suggest that QGASE promotes wound closure in HF cells by upregulating essential markers related to the wound-healing process. Additionally, QGASE demonstrates antioxidant effects, mitigating oxidative stress and aiding in recovery from injuries induced by H₂O₂. In vivo experiments provide additional substantiation supporting the efficacy of QGASE in enhancing wound healing. The collective results indicate that QGASE may be a promising candidate for the development of innovative therapeutic strategies aimed at enhancing skin wound repair.

Osteoporosis is a common disease that increases the risk of fractures due to decreased bone density and weakens the bone microstructure. Preventing and diagnosing osteoporosis using the available drugs can be a costly affair with possible side effects. Therefore, natural product-derived therapeutics are promising alternatives. Our study demonstrated that the oat seedlings extract (OSE) inhibited the receptor activator of the nuclear factor κB ligand (RANKL)-induced osteoclastogenesis from the bone marrow-derived macrophages (BMMs). The OSE treatment significantly attenuated the RANKL-mediated induction of the tartrate-resistant acid phosphatase (TRAP) activity as well as the number of TRAP-positive (TRAP+) multinucleated cells (MNCs) counted through the TRAP staining in a dose-dependent manner. It was also confirmed that the OSE suppressed the formation of the TRAP+MNCs in the early stage of differentiation and not in the middle and late stages. The results of the real-time quantitative polymerase chain reaction (qPCR) and the western blotting showed that the OSE dramatically inhibited the mRNA and protein expressions of the osteoclastogenesis-mediated transcription factors such as the c-Fos and the nuclear factor-activated T cells c1 (NFATc1). In addition, the OSE strongly attenuated the mRNA induction of the c-Fos/NFATc1-dependent molecules such as the TRAP, the osteoclast-associatedimmunoglobulin-like receptor (OSCAR), the dendritic cell-specific transmembrane protein (DC-STAMP), and the cathepsin K. These results suggest that the naturally derived OSE may be useful for preventing bone diseases.

Background/Objectives: Wound repair-associated processes and the antioxidant properties of natural products play critical roles in skin wound healing and barrier restoration. Wound healing is a complex process characterized by a series of interconnected events that facilitate the self-repair of the skin following injury. Methods: This study aimed to evaluate the effects of Quercus acuta acorn bran extract (QAABE) on wound healing using human dermal fibroblast (HDF) cell cultures treated with QAABE. Additionally, in vivo experiments were conducted using a mouse model of skin injury to assess the wound-healing potential of the extract. Results: The results indicated that QAABE enhanced wound healing in vitro by upregulating extracellular matrix-related markers, including vimentin, Col1a1, Col3a1, endothelin, fibronectin, and VEGF at the mRNA level, and increasing the protein expression of vimentin, COL1A1, endothelin, and α-SMA. QAABE also exhibited reactive oxygen species (ROS)-scavenging activity. In the mouse skin injury model, QAABE treatment accelerated wound closure and was associated with reduced inflammatory responses. Conclusions: These findings suggest that QAABE may promote wound-healing-related responses in both in vitro and in vivo models, supporting its potential as a candidate for further investigation in wound-healing research.