Search Results (1,882)

The family Carabidae, one of the largest families within Coleoptera, represents one of the most important groups of predatory insects and bioindicators in ecosystems, playing significant roles in agricultural pest control and ecological environment assessment. However, the phylogenetic relationships within this family remain poorly resolved, and publicly available mitochondrial genome data remain limited. In this study, we employed high-throughput sequencing to determine and report for the first time the complete mitogenomes of four carabid species—Poecilus fortipes (Chaudoir, 1850) and Poecilus gebleri (Dejean, 1828) from the subfamily Pterostichinae, and Pristosia nitidula (A. Morawitz, 1862) and Cephalosdrophus marinae (Lassalle & Marcilhac, 1999) from the subfamily Platyninae—as well as to resequence Carabus brandti Faldermann, 1835 from the subfamily Carabinae. Using 124 carabid mitochondrial genome sequences obtained from NCBI, this study reconstructed the phylogenetic relationships among 21 subfamilies within Carabidae. The results showed that the sizes of mitochondrial genomes ranged from 15,800 to 17,352 bp in length and contained 37 typical genes and a control region. Combined with previously reported mitogenomic data, we found all protein-coding genes (PCGs) initiated with standard start codons ATN or TTG and ended with TAN or an incomplete stop codon single T. Evolutionary rate analysis (Ka/Ks) revealed ATP8 was the fastest-evolving gene, whereas COX1 was the slowest. Except for tRNA-Ser (AGN), whose DHU arm simply formed a loop, and tRNA-Phe (C. marinae), whose TΨC loop was absent, the rest of the tRNA sequences could be folded into a typical cloverleaf secondary structure. Our results suggest that the phylogenetic position and taxonomic status of Cicindelinae remain unresolved, with alternative placements recovered depending on the dataset analyzed. The monophyly of most carabid subfamilies was confirmed, with the exception of Brachininae, Trechinae, Licininae, and Platyninae. The findings of this study provide valuable insights into carabid phylogeny. Further refinement of the phylogenetic relationships within the family can be achieved by additional nuclear markers, broader taxon sampling, and complementary phylogenomic datasets. Full article

Centella asiatica (L.) Urban extracts are widely used in food, cosmetic, and pharmaceutical products. Conventional solvent extraction requires organic solvents and often produces dark green extracts due to chlorophyll co-extraction, limiting their industrial applications. This study developed an environmentally friendly aqueous two-phase system (ATPS) for the simultaneous extraction of triterpenoids of Centella asiatica. Response surface methodology with a central composite design was employed to optimize ethanol concentration, ammonium sulfate concentration, and temperature. A rapid and validated HPLC method for quantification of four triterpenoids—madecassoside, asiaticoside, madecassic acid, and asiatic acid—was developed and validated on a Poroshell 120 SB-C18 column (3.0 × 150 mm, 2.7 microns) at 40 °C. The developed method for all four triterpenoids was rapid (14 min run time) with acceptable system suitability, specificity, linearity (R > 0.9995), accuracy (98.42–101.52%), precision (0.16–1.36%), LOD (0.04–0.64 µg/mL), and LOQ (0.13–1.93 µg/mL). The ANOVA data from the central composite design of response surface methodology for total triterpenoid content were fitted with quadratic models, yielding acceptable R² (>0.97), adjusted R² (>0.95), and predicted R² (>0.80). The optimum extraction conditions were 18.29% w/w ethanol, 33.93% w/w ammonium sulfate, and 60.04 °C, yielding a total triterpenoid content of 30.53 mg g⁻¹ dry weight. The optimized ATPS produced higher yields of madecassoside (13.15 mg g⁻¹), asiaticoside (9.02 mg g⁻¹), madecassic acid (5.26 mg g⁻¹), and asiatic acid (3.10 mg g⁻¹) than conventional ethanol extraction while simultaneously reducing chlorophyll-derived coloration. This ATPS extraction strategy provides a sustainable approach for producing suitable Centella asiatica extracts for cosmeceutical and pharmaceutical applications. Full article

Aeromonas hydrophila is a globally distributed aquatic pathogen. Antibiotic overuse in traditional management practices has intensified problems such as antimicrobial resistance and environmental pollution, creating an urgent need for safe alternatives. This study characterized a BLIS produced by Leuconostoc falkenbergense SBL-85-2, which shows potential as an antibiotic alternative in aquaculture. L. falkenbergense SBL-85-2 exhibited no hemolytic activity, lacked typical high-risk virulence factors, and only low-identity vancomycin-related intrinsic genes (vanT and vanY) were identified by the CARD database, which may preliminarily indicate its potential biosafety for aquatic applications. The BLIS exhibited marked activity against A. hydrophila, with an inhibition zone of 39.14 ± 0.65 mm, as well as other critical pathogens including Aeromonas rivipollensis, Aeromonas salmonicida, Escherichia coli, Salmonella Typhimurium, Staphylococcus aureus, and Vagococcus fluvialis. Furthermore, the BLIS exhibited remarkable thermal stability (retained 87.18 ± 0.14% activity after treatment at 100 °C for 10 min) and UV stability (92.67 ± 0.75% residual activity after 3 h exposure) coupled with sensitivity to proteases, confirming its proteinaceous nature. Molecular weight determination indicated that the BLIS is a low-molecular-weight peptide (<2.7 kDa). Mechanistically, the BLIS disrupted bacterial cell membrane integrity, ultimately resulting in the leakage of cellular contents and a time-dependent reduction in intracellular ATP levels (reduced by 69.16 ± 4.10% at 2 h), exerting its antimicrobial effect. Collectively, our results indicate that this BLIS combines potent antibacterial efficacy with a favorable biosafety profile, suggesting its significant potential for the biological control of A. hydrophila in aquaculture. Full article

The hepatocyte growth factor (HGF)/c-Met signaling pathway plays a central role in cellular proliferation, survival, migration, invasion, angiogenesis, and therapeutic resistance. Aberrant c-Met activation, driven by gene amplification, overexpression, activating mutations, exon 14-skipping alterations, or ligand-dependent stimulation, drives the development and progression of many solid tumors, positioning c-Met as a key target for anticancer drug development. The clinical effectiveness of c-Met-targeted treatments such as crizotinib, capmatinib, tepotinib, savolitinib, and cabozantinib has confirmed c-Met as a viable oncogenic driver for therapy, leading to the development of various next-generation inhibitors with different structures. This review provides a comprehensive perspective on small-molecule c-Met inhibitors from the perspectives of medicinal chemistry and structure-based drug design, encompassing approved drugs, investigational agents, natural-product-inspired leads, and emerging multitarget anticancer therapeutics. Particular emphasis is given to the principles of molecular recognition that govern c-Met inhibition. This includes the structure of the kinase domain, interactions at the ATP-binding site, recognition of the hinge region, and the different binding modes of Type I, Type II, and allosteric inhibitors. The design, synthesis, biological evaluation, and structure–activity relationships of diverse heterocyclic scaffolds that have shaped c-Met inhibitor discovery are critically analyzed. Key medicinal chemistry strategies, including scaffold hopping, bioisosteric replacement, conformational optimization, molecular hybridization, and multitarget pharmacophore integration, are discussed in the context of potency, selectivity, resistance management, and drug-like properties. Particular attention is given to the integration of structural biology, molecular docking, binding-mode analysis, and structure-guided optimization approaches that have enabled the development of potent c-Met-directed inhibitors. In addition, recent advances in dual- and multitarget agents that simultaneously modulate c-Met and complementary therapeutic targets, including VEGFR-2, EGFR, AXL, MER, PARP1, CDK2, and tubulin, are highlighted as promising strategies for overcoming pathway redundancy and acquired resistance. This review summarizes contemporary structure-based and medicinal chemistry principles underlying c-Met inhibitor discovery, critically evaluates the relationship between biochemical potency and therapeutic efficacy, and provides a framework for the rational design of next-generation c-Met-targeted and multitarget anticancer agents. Full article

Preservation of mitochondrial integrity has emerged as a central hub in the anti-inflammatory effect of exercise. This narrative review advances a framework in which mitochondrial damage-associated molecular patterns (mtDAMPs) serve as the mechanistic bridge between exercise and inflammation. Mitochondrial dysfunction releases mtDAMPs, including mitochondrial DNA (mtDNA), reactive oxygen species, cardiolipin, N-formyl peptides, and ATP, which activate cGAS–STING, the NLRP3 inflammasome, TLR9, AIM2, ZBP1, and NF-κB signaling. Crosstalk among these pathways allows mild mitochondrial damage to escalate into chronic inflammation. Exercise opposes this cascade through the AMPK–PGC-1α axis, which coordinately activates four mitochondrial quality control (MQC) modules: biogenesis, antioxidant defense, dynamics, and mitophagy. The cardiovascular system illustrates this framework, as myocardial inflammation runs mainly through mtDNA–cGAS–STING signaling and vascular inflammation through oxidized mtDNA–NLRP3 signaling, while cardiovascular aging engages both axes at once. Throughout, exercise refers to repeated training rather than to a single bout, and the framework targets middle-aged and older adults with, or at risk of, cardiovascular disease. The upstream half of the sequence, in which training raises mitochondrial content and antioxidant capacity, rests on human muscle biopsy data; the downstream half remains largely preclinical. MQC is therefore proposed as a testable target rather than an established one. Full article

Total joint arthroplasty is a surgical procedure with rising global incidence. Although a strong postoperative inflammatory response is necessary for tissue repair following primary arthroplasty, it may prove to be harmful if excessive or prolonged. This could compromise osseointegration, increase pain, and delay the detection of periprosthetic joint infection. This narrative review examines the principal inflammatory pathways activated by primary arthroplasty. Damage-associated molecular patterns produced by injury and cell death, such as High Mobility Group Box 1 Protein, cell-free DNA, extracellular ATP, histones, and heat shock proteins, trigger innate immune activation following surgical trauma. These mediators use inflammasome pathways and pattern recognition receptors to intensify inflammatory signaling. The acute-phase trajectory, characterized by increases in C-reactive protein and erythrocyte sedimentation rate, alongside the role of interleukin-6 as a precursor factor, is examined together with synovial markers to facilitate the differentiation between septic and aseptic inflammation. Cytokine signaling cascades (JAK-STAT, NF-κB, MAPK) and the RANK/RANKL/OPG axis at the bone-immune interface are also considered. This manuscript highlights relevant inflammatory pathways, clinically significant biomarkers, and pathway-guided management strategies to provide an overview of the current research on the biological mechanisms underlying perioperative inflammation in primary arthroplasty. No inflammatory biomarker has yet been validated as a predictor of aseptic loosening. Full article

Escherichia coli is a common porcine diarrheal pathogen transmitted via the fecal–oral route through contaminated environments and feed. This study evaluated the antimicrobial potential of a bacteriocin-like substance produced by Loigolactobacillus coryniformis WYQ-2 isolated from pickled vegetables. Its physicochemical stability, molecular mass, and antimicrobial spectrum were characterized, and the mode of action against Escherichia coli was investigated through intracellular ATP quantification, live/dead staining, and scanning electron microscopy (SEM). The substance exhibited broad-spectrum antibacterial activity, with the strongest inhibition against Escherichia coli (the diameter of the inhibition zone reached 41.35 mm). It remained stable under prolonged UV irradiation (0–2.5 h), under heating at 100 °C, and within the pH range of 3.0–9.0. Molecular mass determination revealed a low-molecular-weight peptide (<2.7 kDa). Protease susceptibility tests showed activity was reduced by trypsin and papain, slightly sensitive to proteinase K, yet relatively stable toward other tested proteases. Mechanistically, ATP levels declined markedly within 0.5–2 h of treatment, while live/dead staining and SEM confirmed membrane disruption, deformation, and surface indentations in treated Escherichia coli cells. These findings demonstrate that the WYQ-2-derived bacteriocin-like substance possesses favorable physicochemical traits and exerts antibacterial action primarily by compromising membrane integrity, highlighting its promise as a natural alternative for controlling porcine diarrheal diseases. Full article

The HB (homeobox) transcription factor family plays important roles in plant growth, development, morphogenesis, and stress responses; however, its involvement in longan (Dimocarpus longan Lour.) fruit energy metabolism remains unclear. In this study, 32 DlHB family members were identified in the longan genome, and their physicochemical properties, phylogenetic relationships, gene structures, conserved motifs, conserved domains, tissue-specific expression patterns, promoter cis-acting elements, and collinearity relationships were systematically analyzed. The DlHB family was classified into four subfamilies, HD-ZIP I–IV, with substantial divergence in structural composition, expression patterns, and putative regulatory features. Our previous work showed that 1.5% chitosan (CTS) treatment improved postharvest longan fruit quality through modulation of energy metabolism, and the corresponding CTS-treatment transcriptome was therefore used here to screen energy-metabolism-associated DlHB candidates. DlHB22 was selected as a representative candidate, and its CTS-responsive expression was independently confirmed by qRT-PCR. Exogenous ATP treatment was then used as an independent physiological validation of the relationship between energy metabolism and postharvest storability; ATP-treated fruit showed reduced deterioration together with higher ATP, ADP, and AMP contents and higher activities of H+-ATPase, Ca²+-ATPase, cytochrome c oxidase (CCO), and succinate dehydrogenase (SDH) at 15 d, although adenylate energy charge (AEC) was lower than in the control. DlHB22 localized predominantly to the nucleus. Heterologous overexpression of DlHB22 in tomato accelerated fruit color transition and ripening progression and altered ATP, ADP, and AMP contents, AEC, and the activities of H+-ATPase, Ca²+-ATPase, CCO, and SDH. Transcriptome analysis of DlHB22-overexpressing tomato fruit revealed broad transcriptional changes in pathways associated with central carbon metabolism, energy metabolism, glutathione metabolism, hormone signaling, and MAPK signaling, and qRT-PCR validation of six representative DEGs was consistent with the RNA-seq trends. Because tomato is climacteric whereas longan is non-climacteric, the heterologous tomato results demonstrate the regulatory potential of DlHB22 but do not establish an identical native ripening pathway in longan. Overall, DlHB22 is best regarded as a candidate transcription factor associated with longan fruit energy metabolism, whose native regulatory mechanism requires direct validation in longan. Full article

Sperm activation and movement are essential in freshwater fishes, where limited energy reserves and a short motility duration require rapid ATP-driven motility regulated by osmolality and ions. However, the physiological and molecular mechanisms underlying osmolality and ion regulation in mandarin fish (Siniperca chuatsi) remain unclear, and ions in aquaculture systems may exert additional effects. Here, we integrated physiology with transcriptomic and proteomic analyses to characterize the effects of osmolality and ions on sperm motility and identify key genes, proteins, and regulatory networks involved in sperm activation and movement. Low osmolality (<50 mOsm/kg) promoted sperm activation, with sperm motility progressively decreasing as osmolality increased. Although relatively high osmolality supported motility maintenance, the initial motility was comparatively low, indicating the limited energy reserves of freshwater fish spermatozoa. Na⁺ and K⁺ activation media enhanced motility, whereas Ca²⁺ supplementation suppressed activation. Ca²⁺ levels below a 1:500 molar ratio (<0.06 mM) did not significantly affect sperm motility, indicating the importance of limiting Ca²⁺ exposure during fertilization. Multi-omics analyses identified six differentially expressed genes, including grin3bb, cacna1c, and chrna7, and 35 differentially expressed proteins, including ATP1B, PRKCB, and CPT1A, as key molecules associated with Na⁺, K⁺, and Ca²⁺ signaling and energy metabolism. The calcium signaling pathway, cAMP signaling pathway, and oxidative phosphorylation were significantly enriched in KEGG enrichment analysis, while Gene Ontology (GO) enrichment analysis identified ion signaling and energy metabolism, including ion transport, the ATP metabolic process, and the glycolytic process. Our findings provide a putative regulatory network for sperm activation and movement in mandarin fish and a basis for optimizing artificial fertilization. Full article

Microbiologically influenced corrosion (MIC) at oral biomaterial interfaces is viewed as an ecological phenomenon, yet how microbial composition and interspecies interactions shape corrosion remains unclear. Here, we investigated whether oral microbial community composition and interspecies interactions contribute to medical 316L stainless steel corrosion. Consortia-enhanced Cr and Fe release and localized surface pitting, with marked inter-subject variability. Interface-associated biofilms exhibited trends toward compositional shifts and showed enrichment of predicted pathways for fermentation and riboflavin metabolism, along with higher genome-based metabolic interaction potential than planktonic communities. Extracellular riboflavin accumulated in MIC systems and correlated positively with dissolved Cr and Fe concentrations. In perturbation assays, riboflavin supplementation increased corrosion current density (i_corr) and metal dissolution, whereas roseoflavin reduced extracellular riboflavin availability and corrosion-related parameters without marked changes in the measured biofilm biomass or surface-associated ATP levels. A defined three-strain consortium (C. tsuruhatensis, R. erythropolis, and T. aromatica) reconstituted the S3 high-corrosion phenotype, including elevated i_corr, extracellular riboflavin accumulation, and induced pitting, consistent with a proposed riboflavin-linked model involving species-dependent metabolic interactions. These findings suggest that extracellular riboflavin may represent a candidate redox-active factor associated with microbial community interactions and corrosion activity, providing an ecological framework for understanding microbiota-associated corrosion resistance at oral biomaterial interfaces. Full article

Background: Branched-chain amino acid (BCAA) is involved in glucose and lipid metabolism and energy homeostasis, but whether its effects on maternal metabolism and offspring growth during lactation depend on dietary protein level remains unclear. Methods: C57BL/6J lactating dams were randomized after delivery to a normal-protein control group (CN, 20% protein), low-protein group (LP, 10% protein), CN + BCAA group (CNB), or LP + BCAA group (LPB) (n = 11/group). Maternal body composition, glucose and lipid metabolism, hepatic energy status, oxidative stress indices, and pup litter weight gain were assessed. Results: The LP diet reduced maternal body weight, pup litter weight gain, and glucose responses during the intraperitoneal pyruvate tolerance test (IPPTT), and increased hepatic lipid deposition and oxidative stress. BCAA supplementation increased pup litter weight gain under normal-protein conditions, but decreased maternal food intake and offspring growth under low-protein conditions. Metabolically, BCAA supplementation reduced the homeostasis model assessment of insulin resistance (HOMA-IR) and hepatic PEPCK1 activity under normal-protein conditions, while partially restoring IPPTT glucose responses and increasing hepatic PEPCK1 activity under low-protein conditions. In addition, BCAA supplementation reduced hepatic lipid deposition and ATP content at both protein levels. Notably, under low-protein conditions, BCAA supplementation increased serum β-hydroxybutyrate (β-HB), while alleviating hepatic oxidative stress. Conclusions: BCAA supplementation exerted opposite effects on offspring growth during lactation under different maternal dietary protein levels. These effects may be related to differential changes in maternal glucose and lipid metabolism and hepatic energy status, suggesting that BCAA supplementation during lactation should be evaluated according to maternal dietary protein level. Full article

Autophagy plays a central role in cellular homeostasis and metabolic adaptation, and its dysregulation has been implicated in metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). This study investigated the biological effects of a chemically characterised multi-component nutraceutical formulation using an integrated in vitro gut–liver–muscle axis model under lipotoxic and inflammatory conditions induced by free fatty acids (FFAs) and lipopolysaccharide (LPS). The principal bioactive constituents were quantified in both the individual extracts and the final formulation before biological testing. Caco-2, HepG2, and C2C12 cells were sequentially exposed to conditioned media to reproduce inter-organ metabolic interactions. The Supplement preserved intestinal barrier integrity by maintaining transepithelial electrical resistance and tight junction protein expression. In HepG2 cells, it preserved telomerase levels, improved markers of cellular metabolic adaptation, modulated AMPK/mTOR and SIRT1 signalling, and promoted autophagy-related responses, including increased LC3-II/I ratio, reduced p62 accumulation, and preservation of lysosomal markers. In skeletal muscle cells, exposure to conditioned medium derived from formulation-treated compartments was associated with improved cellular bioenergetics, reduced oxidative stress and inflammatory mediators, and enhanced ATP and glycogen levels under exercise-like conditions. Overall, these findings provide preliminary evidence that the chemically characterised formulation modulates interconnected pathways involved in intestinal barrier function, hepatic autophagy-related processes, and skeletal muscle metabolic adaptation under the experimental conditions employed. Full article

Oxidative damage is closely associated with the gradual decline in boar sperm quality during liquid storage at 17 °C. To determine whether L-histidine (L-His) could limit this deterioration, semen was diluted with an extender containing 0, 1, 10, 100, or 1000 μM L-His. Motility and acrosomal integrity were measured throughout storage. On day 7, mitochondrial membrane potential (MMP) and ATP content were determined together with intracellular probe oxidation, membrane lipid oxidation, and Annexin V-FITC/PI staining patterns. The stored sperm were subsequently exposed to capacitating conditions and tested for their ability to bind to oviductal explants. The most favorable responses were observed with 100 μM L-His. Compared with untreated semen, this group retained higher motility and acrosomal integrity and showed higher MMP and ATP content (p < 0.05). It also exhibited less intracellular probe oxidation and membrane lipid oxidation, together with lower proportions of Annexin V-positive and membrane-compromised sperm. Following capacitation induction, sperm stored with 100 μM L-His showed increased tyrosine phosphorylation and higher proportions of capacitated sperm. Their binding index to oviductal explants was also higher than that of the control group. These findings indicate that supplementation with 100 μM L-His can improve the preservation quality of boar sperm during extended liquid storage at 17 °C and maintain functional characteristics of stored sperm, providing new insights into the potential use of L-His as a semen extender supplement for prolonged storage. Full article

In vitro maturation (IVM) of oocytes is a critical initial step in mammalian in vitro production (IVP), and its quality directly influences the developmental competence of subsequent embryos. Oxidative stress is a major constraint on oocyte quality, which can be mitigated by exogenous antioxidants. In this study, porcine oocytes were matured in IVM medium supplemented with the antioxidant N-acetyl-L-cysteine (NAC; 0, 0.5, 1.5, and 4 mM) to evaluate its effects on maturation rate, antioxidant capacity, mitochondrial function, vitrification–warming survival rate, post-warming ROS levels, and early embryonic developmental rate. To elucidate the molecular mechanisms underlying the effects of NAC on porcine oocyte maturation, we conducted single-cell transcriptome sequencing. The results showed that, versus the control, 1.5 mM NAC substantially enhanced the IVM rate (p < 0.05), reduced ROS levels (p < 0.05), and increased mitochondrial activity, as assessed by MitoTracker, mitochondrial membrane potential (MMP), and ATP content (p < 0.05). These results suggest that 1.5 mM NAC relieves oxidative stress in oocytes and improves mitochondrial function. However, NAC addition showed no significant differences in vitrification–warming survival rate and post-warming ROS levels relative to the control group (p > 0.05). In addition, 1.5 mM NAC markedly improved the cleavage rate and blastocyst rate of porcine oocytes after in vitro fertilization (IVF, p < 0.05), and also enhanced the cleavage rate after parthenogenetic activation (PA, p < 0.05). Single-cell transcriptome sequencing revealed that, versus the control, differentially expressed genes (DEGs) identified after 1.5 mM NAC supplementation were mainly enriched in pathways related to oxidative phosphorylation (OXPHOS), spliceosome, and ubiquinone/terpenoid-quinone biosynthesis. Among these, the OXPHOS pathway showed the most significant enrichment, with upregulated expression of pathway-related genes such as COX6C, CYCS, and SDHD. The accuracy of the transcriptomic results was further validated by qPCR. In conclusion, supplementing with 1.5 mM NAC relieved oxidative stress, improved mitochondrial function, and thereby promoted oocyte maturation and improved oocyte quality, ultimately facilitating subsequent IVF early embryonic development. Full article

Osteoarthritis (OA) is increasingly recognized as a mechanically driven whole-joint disease in which abnormal mechanotransduction initiates a cascade of mitochondrial dysfunction, chronic inflammation, and progressive cartilage degeneration. Among the mechanosensitive molecules identified to date, Piezo1 has emerged as a key mechanosensitive regulator linking pathological mechanical loading to intracellular calcium signaling and downstream cellular responses. Growing evidence indicates that persistent Piezo1 activation promotes mitochondrial calcium overload, excessive reactive oxygen species production, ATP depletion, mitochondrial membrane depolarization, and impaired mitophagy, ultimately amplifying chondrocyte dysfunction and extracellular matrix degradation. In parallel, mitochondrial damage triggers immunometabolic reprogramming through activation of the cGAS–STING pathway and the NLRP3 inflammasome. It also promotes pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6. Together, these responses may contribute to a self-perpetuating cycle of inflammation and tissue destruction. This review provides a comprehensive synthesis of recent advances regarding the role of Piezo1 in OA, focusing on the mechanistic links between mechanotransduction, mitochondrial dysfunction, mitophagy, and immunometabolic dysregulation. We further discuss the contribution of mitochondrial quality-control pathways, including PINK1/Parkin-, BNIP3-, and FUNDC1-mediated mitophagy, as well as alterations in mitochondrial dynamics involving DRP1, MFN1, MFN2, and OPA1. Emerging experimental models are discussed as valuable tools for accelerating therapeutic discovery. Finally, we critically evaluate current therapeutic strategies targeting the Piezo1–mitochondria axis, including mechanosensitive channel modulation, mitochondrial protection, mitophagy enhancement, gene therapy, biomaterial-assisted delivery, and nanomedicine. Collectively, current evidence supports the Piezo1–mitochondria–immune axis as an important mechanistic framework contributing to OA pathogenesis and as a potential therapeutic target. Integrating mechanobiology, mitochondrial medicine, and precision-engineered experimental models may facilitate the development of next-generation disease-modifying therapies capable of slowing or preventing osteoarthritis progression. Full article