Snake envenoming triggers a complex inflammatory response that substantially contributes to local tissue destruction and systemic complications. Among the innate immune pathways implicated in venom-induced injury, the nucleotide-binding oligomerization domain (NOD-), leucine-rich repeat (LRR-), and pyrin domain-containing protein 3 (NLRP3) inflammasome has emerged as a key sensor-effector platform linking tissue damage, ionic imbalance, reactive oxygen species (ROS), lipid mediators, and cytokine maturation. Experimental studies indicate that crude venoms and isolated snake toxins, including Lys49 and Asp49 phospholipase A2 (PLA2), metalloproteinases, and C-type lectin/C-type lectin-like proteins, can activate NLRP3 inflammasome-dependent signaling, leading to caspase-1 activation, interleukin (IL)-1β release, and, in some settings, pyroptotic cell death. These findings position the NLRP3 inflammasome as a promising adjunctive therapeutic target in snakebite envenoming, although causal evidence remains restricted to selected toxin models and broader validation across venom classes is still required. This review summarizes the current understanding of NLRP3 inflammasome biology in the context of snake venoms and toxins, discusses the molecular mechanisms proposed for inflammasome priming and activation, and highlights unresolved questions relevant to toxinology, immunology, and adjunctive therapy development. Recent literature also places venom-derived molecules within the broader framework of NLRP3 inflammasome modulation, reinforcing the idea that venoms may serve both as drivers of pathology and as sources of pharmacological leads.
Glioblastoma (GBM) exhibits extensive metabolic reprogramming, including glucose and glutamine (Gln) addiction, with Gln being converted into glutamate by glutaminase, encoded by the GLS and GLS2 genes. GLS2 acts as a context-dependent tumor suppressor, although the underlying mechanisms remain poorly understood. GLS2 is silenced in GBM, and we previously showed that its re-expression modulates pyruvate dehydrogenase (PDH) activity and tricarboxylic acid cycle (TCAC) metabolism, suggesting a distinct metabolic rewiring associated with its tumor-suppressive function. LN229 and T98G GBM cell lines were used as experimental models. Metabolomic profiling by liquid chromatography-mass spectrometry was performed to compare changes in central metabolic pathways following GLS2 or GLS overexpression. Glutaminase and PDH enzymatic activities were measured, and Western blotting was performed to assess GLS, GLS2, and PDHA1 protein levels and PDHA1 phosphorylation. A Seahorse analyzer was employed to quantify real-time ATP production derived from glycolysis and oxidative phosphorylation. Overexpression of GLS2, but not GLS, in LN229 cells caused the accumulation of TCAC-related metabolites, except for citrate, whose depletion is attributed to GLS2’s effect on PDH phosphorylation, causing reduced PDH activity. This was accompanied by decreased levels of several acyl-carnitines. Furthermore, GLS2 induced the accumulation of glucose/fructose, while reducing levels of glucose-6-phosphate and pentose-phosphates, consistent with altered glycolysis. GLS2 also diminished the ATP/AMP ratio, confirmed by a reduced ATP synthesis rate, particularly glycolytic ATP, whereas mitochondrial ATP production remained unaltered. GLS2 exerts an isoenzyme-specific effect on Gln and glucose metabolism in GBM, likely modulating the glycolysis/pentose-phosphate pathway (PPP)-TCAC-axis.
Dexamethasone (DEX) exerts pleiotropic effects that extend beyond classical glucocorticoid receptor signaling and include interactions with the renin–angiotensin system (RAS). Growing evidence indicates that DEX regulates both systemic and tissue-specific RAS activity through genomic and non-genomic mechanisms, affecting the expression and activity of key components, including angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), and angiotensin receptors AT1 and AT2. This mini-review summarizes current evidence on DEX-induced RAS modulation and its physiological and pathological implications. Depending on dose, duration, and biological context, DEX may exert both beneficial and adverse effects. Short-term exposure can suppress renin activity and aldosterone secretion and may provide protective effects in selected acute pathological conditions. In contrast, prolonged or high-dose treatment may promote hypertension, electrolyte imbalance, cardiac remodeling, and tissue dysfunction through dysregulation of RAS signaling. DEX also alters local RAS activity in bone, contributing to osteoporosis and osteonecrosis by enhancing osteoclast activity and impairing osteoblast function. In the kidney and lung, DEX-mediated RAS modulation affects fluid homeostasis, inflammatory responses, and susceptibility to tissue injury. Prenatal exposure to DEX may further induce long-term RAS programming, increasing the risk of cardiovascular, renal, and skeletal disorders in adulthood. Collectively, DEX–RAS interactions represent an important but often overlooked aspect of glucocorticoid pharmacology and may contribute to both the therapeutic and adverse effects of DEX.
Tumor angiogenesis is a hallmark of cancer, influencing oxygen delivery, immune cell trafficking, and therapeutic response. Although anti-angiogenic therapies have achieved clinical relevance, their efficacy remains limited by tumor heterogeneity, adaptive resistance, and insufficient functional assessment of tumor vasculature. In this review, we evaluate preclinical models of tumor angiogenesis with a focus on their ability to generate quantitative and physiologically relevant readouts. We discuss established assays such as tube formation, fibrin bead assay, aortic ring, and chorioallantoic membrane (CAM) models, alongside emerging systems including vascularized organoids and organ-on-a-chip platforms, as well as zebrafish and murine tumor models. Particular emphasis is placed on advanced imaging modalities enabling longitudinal assessment of perfusion, permeability, and vascular remodeling, as well as on the growing role of artificial intelligence (AI) in automated and quantitative data interpretation. We further highlight the integration of single-cell and multi-omics approaches for resolving endothelial heterogeneity and tumor–stroma interactions. By linking biologically relevant models with functional imaging and computational analysis, this review outlines strategies to improve the predictive power and translational relevance of angiogenesis research.
Cisplatin is an anti-neoplastic treatment widely used to treat pediatric cancers. Negative effects of cisplatin treatment on bone mass have previously been reported; however, long-term effects of cisplatin on skeletal health and potential sex differences have largely been unexplored. Four-week-old BALB/c mice were treated with cisplatin (4 mg/kg, intraperitoneally, twice weekly for four weeks). At 13 weeks of age, we assessed structural changes in the tibiofemoral region using microcomputed tomography. We also quantified, using immunohistochemistry and confocal microscopy, the density of tartrate-resistant acid phosphatase+ (TRAcP+) osteoclasts, sclerostin+ osteocytes, and osterix+ (OSX+) osteoblasts, within the femoral metaphysis of female and male mice treated with cisplatin during the juvenile period. At 13 weeks of age, both female and male mice treated with cisplatin showed a significantly greater decrease in trabecular, but not cortical, bone mass in the tibiofemoral region than saline-treated mice. This decrease in trabecular bone mass was significantly greater in females than in males. The density of TRAcP+ osteoclasts on the trabecular surfaces of the femur was higher in mice treated with cisplatin than in those in the saline group, independent of sex. Cisplatin treatment did not alter the density of sclerostin+ osteocytes or OSX+ osteoblasts in the femoral metaphyseal bone marrow compared with the saline group. These findings suggest that cisplatin induced sex-dependent and long-term complications in the skeletal system, which may partially explain the greater incidence of fractures in childhood cancer survivors.
