The prevalence of osteoarthritis (OA) notably surges with age and weight gain. The most common clinical therapeutic drugs are painkillers, yet they cannot impede the deteriorating course of OA. Thus, understanding OA’s pathogenesis and devising effective therapies is crucial. It is generally recognized that inflammation, pyroptosis, and OA progression are tightly linked. The activation of NLRP3 inflammasome can lead to the discharge of the pro-inflammatory cytokines Interleukin-1β and IL-18, intensifying subsequent inflammatory reactions and promoting OA development. Conversely, the imbalance caused by deacetylase-regulated NLRP3 inflammasome underlies the chronic mild inflammation related to degenerative diseases. Therefore, this article expounds on the mechanism of OA pathogenesis and the role of histone deacetylases (HDACs) in NLRP3 inflammasome-triggered OA, and illustrates the application of HDAC inhibitors in OA, striving to provide more insights into novel OA treatment approaches.

The human gut microbiota serves as a critical hub for host metabolic and immune regulation. Disruption of its homeostasis is closely associated with diseases such as Inflammatory Bowel Disease (IBD), metabolic syndrome, and colorectal cancer. Modern dietary and environmental factors are known to exacerbate this dysbiosis, highlighting the need for innovative interventions capable of modulating the gut ecosystem. Within this context, this review explores the potential of edible fungi, focusing on culinary mushrooms (e.g., Lentinula edodes) and medicinal fungi such as Ganoderma lucidum and Phellinus linteus, which are widely studied in Asia for their health benefits. While consumed as functional foods for their nutritional properties in some countries, they are used in traditional medicine in others. This review examines the role of their bioactive components (e.g., polysaccharides, terpenoids) in remodeling the gut microbiome, thereby highlighting their application in functional foods and dietary interventions. This review systematically examines the pathological mechanisms underlying gut dysbiosis and elucidates how bioactive fungal components (e.g., β-glucans, ganoderic acids) improve intestinal barrier function and immune homeostasis by modulating the composition of the gut microbiota, enhancing the production of SCFAs (short-chain fatty acids), and inhibiting the colonization of pathogens. Current evidence, primarily from preclinical studies, suggests that bioactive fungal components, such as β-glucans from Ganoderma lucidum and polysaccharides from Trametes versicolor, may impart health benefits against metabolic disorders and neoplasms. These benefits are mediated through the modulation of microbiota-derived metabolites (e.g., SCFAs) and epigenetic remodeling mechanisms (e.g., HDAC (Histone Deacetylase) inhibition), suggesting their potential application in functional foods and nutritional strategies. metabolites (e.g., SCFAs) and epigenetic remodeling mechanisms (e.g., HDAC inhibition). However, critical gaps persist, particularly in translating these preclinical findings to humans. Key challenges include understanding their bioavailability, establishing human-relevant dose-response relationships, and elucidating spatiotemporal dynamics within microbiota-host interaction networks. Addressing these gaps requires integration with multi-omics technologies and well-designed clinical trials. Multi-omics and organoid models should be integrated by future research to advance precision medicine applications of fungal-derived therapies.

Disorders of skin wound healing and the repair of full-thickness skin defects remain significant clinical challenges. Natural polysaccharide-based hydrogels, with their excellent biocompatibility, tunable degradability, and multifunctional properties (e.g., antibacterial, antioxidant, and pro-angiogenic), have emerged as key materials for designing wound dressings and skin tissue engineering scaffolds. This review systematically summarizes recent advances in polysaccharide hydrogels—including chitosan, hyaluronic acid, and alginate—focusing on material types, crosslinking strategies, and functional modifications, with particular emphasis on their dual applications in wound healing (acute and chronic wounds) and skin tissue engineering. In wound healing, these hydrogels regulate the microenvironment through multiple mechanisms, including anti-inflammatory, antioxidant, pro-angiogenic, and immunomodulatory effects. In skin tissue engineering, their three-dimensional porous structures mimic the extracellular matrix, supporting cell adhesion, proliferation, and tissue regeneration. Finally, we discuss the challenges and future prospects for the clinical translation and commercialization of natural polysaccharide hydrogels.

Background: Skin injuries, such as chronic wounds and inflammatory skin diseases, often face limitations in treatment efficacy due to the low efficiency of transdermal drug delivery and insufficient local concentrations. Curcumin (CUR), a natural compound with anti-inflammatory and antioxidant properties, has demonstrated potential in the repair of skin damage; however, its clinical application is hindered by its physicochemical characteristics. This study constructs a novel nanocomposite drug delivery system: CUR-loaded micellar nanocomposite gel (CUR-M-DMNs-Gel). A composite system is used to achieve the efficient solubilization and enhanced transdermal permeation of CUR, thereby providing a novel formulation approach for the treatment of skin diseases. Methods: CUR-loaded micellar (CUR-M) utilizes CUR as the core active ingredient, which possesses multiple pharmacological effects including anti-inflammatory and antioxidant properties. TPGS serves as a micellar carrier that not only enhances the solubility and stability of CUR through its amphiphilic structure but also facilitates drug absorption and transport within the body. In dissolvable microneedles (DMNs), PVP K30 forms a stable three-dimensional network structure through entanglement of polymer chains, ensuring sufficient mechanical strength for effective penetration of the skin barrier. Meanwhile, PVP K90, with its higher molecular weight, enhances the backing’s support and toughness to prevent needle breakage during application. The incorporation of hyaluronic acid (HA) improves both the moisture retention and adhesion properties at the needle tips, ensuring gradual dissolution and release of loaded CUR-M within the skin. In CUR-loaded micellar gel (CUR-M-Gel), PVP K30 increases both adhesive and cohesive forces in the gel through chain entanglement and hydrogen-bonding interactions. Tartaric acid precisely regulates pH levels to adjust crosslinking density; glycerol provides a long-lasting moisturizing environment for the gel; aluminum chloride enhances mechanical stability and controlled drug-release capabilities; NP-700 optimizes dispersion characteristics and compatibility within the system. Results: In vitro experiments demonstrated that the CUR-M-DMNs-Gel composite system exhibited enhanced transdermal penetration, with a cumulative transdermal efficiency significantly surpassing that of single-component formulations. In the mouse skin defect model, CUR-M-DMNs-Gel facilitated collagen deposition and effectively inhibited the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β). In the mouse skin photoaging model, CUR-M-DMNs-Gel markedly reduced dermal thickness, alleviated damage to elastic fibers, and suppressed inflammatory responses. Conclusions: The CUR-M-DMNs-Gel system can enhance wound healing through subcutaneous localization, achieving long-term sustained efficacy. This innovative approach offers new insights into the treatment of skin injuries.

MiRNAs are small non-coding RNA molecules that play critical roles in the regulation of gene expression and have been closely associated with various diseases, including cancer. These molecules significantly influence the cell cycle of tumor cells and control programmed cell death (apoptosis). Currently, research on miRNAs has become a major focus in developing cancer therapies. Osteosarcoma, a malignant neoplasm predominantly occurring during adolescence and later in life, is characterized by a high propensity for metastasis. This review explores the role of miRNAs in the initiation and progression of cancer, highlighting their potential as predictive biomarkers for disease. It discusses the mechanisms by which natural products modulate miRNA activity to influence apoptosis, ferroptosis, and autophagy in osteosarcoma cells, aiming to identify new strategies for osteosarcoma treatment. Recent studies on how natural products regulate miRNAs to reduce tumor cell resistance to chemotherapy are also reviewed. Furthermore, the review elaborates on how natural products regulate m6A modifications to influence miRNA expression, thereby exerting antitumor effects. In this process, interactions between m6A modifications and miRNAs have been identified, with both jointly influencing tumorigenesis and cancer progression, offering a new perspective in osteosarcoma treatment. These approaches could help uncover novel regulatory mechanisms in osteosarcoma pathways and provide a theoretical foundation for developing new drugs and identifying novel therapeutic targets.

Background: Photoaging, induced by chronic ultraviolet (UV) exposure, is a multifactorial skin disorder characterized by oxidative stress, inflammation, and extracellular matrix degradation. Ganoderma lucidum glycoprotein (Gl-Gp) exhibits potent antioxidant activity, but its topical application is limited by poor transdermal permeability. This study aimed to develop a microemulsion-based system to enhance Gl-Gp delivery and evaluate its anti-photoaging efficacy. Methods: Gl-Gp was extracted and purified from G. lucidum fruiting bodies and structurally characterized for O-glycosidic linkages and O-GlcNAc modifications. Fourier-transform infrared (FT-IR) spectroscopy further confirmed the polysaccharide–protein complex structure of Gl-Gp. A water-in-oil Gl-Gp microemulsion was prepared and assessed in vitro for antioxidant and cytoprotective effects in HaCaT cells, including reactive oxygen species (ROS) reduction, mitochondrial membrane potential stabilization, and apoptosis inhibition. Transdermal penetration was compared with aqueous Gl-Gp. In vivo efficacy was evaluated in a UV-induced rat model by measuring skin morphology, histology, oxidative stress markers, matrix metalloproteinases, and proinflammatory cytokines. Results: The microemulsion enhanced Gl-Gp stability and transdermal delivery. In vitro, it reduced ROS, preserved mitochondrial function, and decreased apoptosis in HaCaT cells. In rats, topical application attenuated erythema and epidermal hyperplasia, promoted dermal restoration, increased SOD and GSH-Px activities, and decreased MDA, hydroxyproline, MMPs, and inflammatory mediators. Conclusions: The Gl-Gp microemulsion exerts antioxidant, anti-inflammatory, and anti-collagen-degrading effects, representing a promising strategy for transdermal delivery and topical prevention of photoaging.