EZH2, a histone methyltransferase, contributes significantly to cancer cell survival and proliferation. Although various EZH2 inhibitors have demonstrated promise in treating lymphoma, they have not fully managed to curb lymphoma cell proliferation despite effective reduction of the H3K27me3 mark. We used MS1943, an EZH2 selective degrader, which successfully diminishes EZH2 levels in lymphoma cells. Additionally, lapatinib, a dual inhibitor of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases, targets a receptor protein that regulates cell growth and division. The overexpression of this protein is often observed in lymphoma cells. Our study aims to combine these two therapeutic targets to stimulate apoptosis pathways and potentially suppress Burkitt’s lymphoma cell survival and proliferation in a complementary and synergistic manner. We observed that a combination of MS1943 and lapatinib induced apoptosis in Daudi cells and caused cell cycle arrest at the S and G2/M phases in both Ramos and Daudi cells. This strategy, using a combination of MS1943 and lapatinib, presents a promising therapeutic approach for treating lymphoma and potentially Burkitt’s lymphoma.

Osteoarthritis (OA) is a prevalent age-associated joint disease marked by progressive cartilage loss, subchondral bone remodeling, osteophyte formation, and low-grade inflammation. In OA, articular chondrocytes shift from a stable extracellular matrix (ECM)-maintaining state toward a hypertrophy-like program with increased collagen type X alpha 1 chain (COL10A1), runt-related transcription factor 2 (RUNX2), and matrix metalloproteinase 13 (MMP-13), promoting ECM degradation, calcification, and pro-angiogenic remodeling. Ageing lowers the threshold for this conversion by reshaping stress responses and signaling through senescence and the senescence-associated secretory phenotype (SASP), oxidative stress, mitochondrial dysfunction, impaired autophagy, and epigenetic drift. Context-dependent modules including Wnt/β-catenin, transforming growth factor-β and bone morphogenetic protein (TGF-β and BMP), Indian hedgehog and parathyroid hormone-related protein (IHH and PTHrP), hypoxia-inducible factor 1α and hypoxia-inducible factor 2α (HIF-1α and HIF-2α), Notch, nuclear factor κB (NF-κB), and metabolic regulators such as fibroblast growth factor 19 (FGF19) and AMP-activated protein kinase (AMPK) interact and converge on shared executors. We synthesize primary mechanistic evidence using a trigger, gate, and executor framework that highlights crosstalk and convergence, and we critically appraise in vivo, ex vivo, and three-dimensional in vitro platforms, emphasizing age mismatch as a major translational bias. We also evaluate therapeutic strategies and constraints that determine clinical interpretability, including cartilage-restricted delivery, patient stratification, and mechanism-aligned structural and molecular outcome metrics alongside symptom assessment. This evidence-tiered network perspective positions chondrocyte hypertrophy as a tractable phenotype-level node for advancing disease-modifying OA drugs (DMOADs).

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by extracellular matrix (ECM) breakdown, inflammation, and pain-associated functional impairment. Current pharmacological treatments primarily provide symptomatic relief without preventing cartilage degeneration. Kaempferia parviflora extract (KPE), rich in polymethoxyflavonoids, has been reported to have anti-inflammatory properties; however, its in vivo effects on cartilage homeostasis in OA remain incompletely defined. Methods: A monosodium iodoacetate (MIA)–induced rat model of knee OA was used to evaluate the therapeutic effects of KPE. Following OA induction, rats received oral KPE at low, medium, or high doses for 19 days. Pain-associated functional impairment was assessed by static weight-bearing analysis. Cartilage integrity was evaluated histologically, serum inflammatory and cartilage degradation biomarkers were quantified, and expression of matrix-degrading enzymes and their endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), was analyzed in articular cartilage. Results: MIA injection induced marked joint dysfunction, including an approximately 50% reduction in weight bearing on the affected limb. While KPE did not significantly reduce acute knee swelling, all KPE doses significantly improved weight-bearing imbalance compared with MIA controls. Histological analysis demonstrated preservation of cartilage structure and proteoglycan content in KPE-treated groups. Serum CTX-II levels were significantly reduced across all KPE doses, indicating attenuation of collagen degradation. Systemic inflammatory markers showed differential modulation: significant reductions in serum CRP and COX-2 at medium and high doses, while PGE2 showed a consistent downward trend that did not reach statistical significance. In articular cartilage, KPE treatment restored TIMP-1 expression, whereas modulation of individual MMPs was modest and variable. Conclusions: KPE alleviates OA-associated functional impairment and cartilage degeneration in an experimental OA model. The therapeutic effects are associated with reinforcement of TIMP-1–mediated matrix homeostasis and modulation of inflammatory pathways, supporting the potential of KPE as a natural adjunct candidate for OA management.

Hye Ryoung Shin, Taekil Eom and Wan-Su Choi. BSL 2023;29:144-51. https://doi.org/10.15616/BSL.2023.29.3.144

Osteoarthritis (OA) is a mechanically regulated whole-joint disease in which vascular remodeling may actively contribute to inflammation, structural deterioration, and pain. This review proposes the mechanovascular axis as a framework linking altered joint mechanics to endothelial and vascular responses across the synovium, osteochondral junction, subchondral bone, meniscus, and osteophytes. Abnormal loading, tissue deformation, extracellular matrix remodeling, and fluid-related forces can influence endothelial mechanosensing and multicellular responses that affect barrier function, angiogenesis, vascular invasion, sensory nerve growth, and vascular–bone coupling. A central distinction is that vascular permeability and angiogenesis are related but non-equivalent processes. Permeability alters transvascular exchange and endothelial immune-gatekeeping, whereas angiogenesis reorganizes vascular networks and may support osteochondral invasion, subchondral remodeling, and neurovascular growth. Their relative importance varies by compartment and disease stage, and current evidence does not support a universal sequence in which mechanical overload first induces permeability and subsequently drives angiogenesis. Instead, distinct vascular responses may arise in parallel and interact reciprocally with inflammation, tissue remodeling, pain-related changes in joint use, and further mechanical imbalance. Direct evidence linking defined OA-associated mechanical perturbations to endothelial barrier dysfunction remains limited, and commonly used measures of vascularity, perfusion, permeability, junctional remodeling, and leukocyte trafficking are not interchangeable. Establishing mechanovascular causality will require longitudinal, compartment-resolved models that quantify mechanical exposure and vascular function within the same joint. Therapeutic strategies should selectively correct pathological mechanics–vascular coupling while preserving physiological loading, perfusion, barrier function, bone turnover, and tissue repair.