Search Results (4,263)

Perlecan, a major heparan sulfate proteoglycan in the vascular basement membrane, plays an essential role in maintaining endothelial barrier integrity, regulating fibroblast growth factor-2 signaling, and exerting anticoagulant activity. Although alterations in perlecan expression are implicated in the initiation and progression of atherosclerosis, the upstream regulatory mechanisms remain unclear. In this study, we investigated the effects of extracellular ATP on perlecan expression in vascular endothelial cells. ATP, but not ADP or adenosine, suppressed perlecan expression at both mRNA and protein levels in a time- and concentration-dependent manner. This suppression was recovered by knockdown of P2Y2 receptor (P2Y2R), but not by P2X4 receptor, P2X7 receptor, or P2Y1 receptor knockdown, indicating the selective involvement of P2Y2R. Mechanistically, ATP reduced Akt phosphorylation mediated by P2Y2R, and inhibition of Akt by inhibitors decreased perlecan expression, whereas inhibitors of phosphoinositide 3-kinase, mammalian target of rapamycin complex 1, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinases did not exhibit this recovery effect. These results suggest that ATP downregulates perlecan synthesis via the P2Y2R-mediated inhibition of Akt signaling. Given that ATP is markedly elevated under pathological conditions, such as inflammation and platelet activation, suppression of perlecan synthesis is an important mechanism by which ATP promotes vascular disease progression. Full article

Background: Polybacterial infections associated with periodontitis are increasingly linked to systemic vascular complications, yet the underlying endothelial mechanisms remain unclear. This study investigated how a consortium of red-complex bacteria (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and orange complex (Fusobacterium nucleatum) affects oxidative stress, inflammation, metabolism, and apoptosis in endothelial cells, and whether L-Sepiapterin [a tetrahydrobiopterin (BH4) precursor via salvage pathway] or bardoxolone methyl (CDDO-Me) [a potent nuclear factor erythroid 2-related factor 2 (Nrf2) activator)] could provide protection. Methods: Human umbilical vein endothelial cells (HUVECs) were infected for 12–72 h and treated with L-Sepiapterin or CDDO-Me. Nitric oxide (NO), BH4, and reactive oxygen species (ROS) levels were quantified, and mRNA expression of key genes regulating nitric oxide synthase activity, antioxidant defense, inflammation (TLR4/NF-κB, cytokines), metabolism (PI3K-AKT-PEA-15), and apoptosis (FAS–caspase pathway) was analyzed. Results: Infection markedly reduced NO and BH4, elevated ROS, activated TLR4/NF-κB and proinflammatory cytokines, disrupted PI3K/AKT signaling, and triggered endothelial apoptosis. Treatments with L-Sepiapterin and CDDO-Me restored NO bioavailability, reduced oxidative and inflammatory responses, normalized metabolic gene expression, and attenuated apoptosis, with CDDO-Me showing more promising effects. This study provides the mechanistic insight linking periodontal polybacterial infection to endothelial dysfunction and metabolic impairment such as diabetes, suggesting that redox-modulating strategies such as L-Sepiapterin and CDDO-Me may help prevent vascular damage associated with periodontal disease. Full article

Branching structures such as vascular networks are representative morphological patterns in living systems, and they often arise from collective cell migration. Angiogenesis, the sprouting of new blood vessels from pre-existing ones, is a fundamental process in development. Experimental and theoretical studies have demonstrated that sprout formation depends on the collective movements and shapes of endothelial cells, as well as the remodelling of the extracellular matrix. Many discrete models have been proposed to describe cell dynamics, successfully reproducing vascular patterns and collective behaviours. In this study, we present a two-dimensional mathematical model that represents each endothelial cell as an ellipse and incorporates the effects of the extracellular matrix. We performed computer simulations under two scenarios: invasion from a pre-formed sprout and collective advancement into an extracellular matrix region. The results show that the extracellular matrix helps maintain linear sprout extension and suppresses the formation of dispersed or curved branches, while elongated cell shapes promote sprouting more effectively than round cells. The model also reproduces experimentally observed behaviours such as tip-cell replacement and the mixing of cells within sprouts. These findings highlight the importance of integrating cell shape and extracellular matrix remodelling to understand early blood vessel formation. Full article

Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H₂O₂) or by subjecting retinal neuronal cells to 8 h of oxygen–glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties. Full article

Colon cancer (CC) is a common malignancy characterized by poor prognostic outcomes and considerable mortality. Oxaliplatin (OXP) is commonly used in the treatment of CC; however, its efficacy may be limited by side effects and the development of resistance. β-sitosterol (β-Sit), a phytosterol derived from plants, has been documented to be effective in the treatment of tumors. This study aimed to investigate the potential of β-Sit to enhance the antitumor efficacy of OXP in COLO-205 cells, focusing on apoptosis induction and suppression of the vascular endothelial growth factor A (VEGF-A)/survival pathway. Molecular docking studies were performed to assess the binding affinity of β-Sit with the target proteins B-cell lymphoma 2 (Bcl-2), phosphoinositide 3-kinase (PI3K), and VEGF receptor-2 (VEGFR-2). COLO-205 cells were treated with OXP, β-Sit, or a combination of OXP + β-Sit for 48 h. The combination treatment substantially lowered the IC₅₀ achieved with 3.24 µM of OXP and 36.01 µM of β-Sit, compared to 25.64 µM for OXP alone and 275.9 µM for β-Sit alone, demonstrating a pronounced synergistic impact. The combined therapy altered the cell cycle distribution by decreasing the number of cells in the G0/G, S, and G2/M phases, coupled with an increase in the Sub-G1 population. Furthermore, apoptosis was augmented by a shift in cell death from necrosis to late apoptosis, as indicated by an increased BAX/BCL2 ratio relative to each treatment alone. Moreover, the inhibitory effect on angiogenesis was enhanced via the reduction of VEGF-A, and β-catenin and nuclear factor κB (NF-κB-p65) were suppressed, thereby preventing the growth and survival of resistant cancer cells. Additionally, molecular docking supported high binding affinities of β-Sit to Bcl-2, PI3K, and VEGFR-2. This study highlights the potential of β-Sit to enhance the anti-cancer efficacy of OXP in CC. Full article

Curcuma phaeocaulis, a perennial herb of the ginger family, has been used to treat many diseases in traditional medicine systems. This study aimed to extract, isolate, and purify a homogeneous polysaccharide from C. phaeocaulis, conduct preliminary structural characterization, and evaluate its antioxidant activity at the cellular level. The structure of the purified polysaccharide (CPAP-1) was characterized using size exclusion chromatography (SEC), chemical derivatization analysis (CDA), GC-MS, FT-IR, and NMR. The results showed that CPAP-1 has an apparent molecular weight of 118.122 kDa and is hypothesized to be an arabinogalactan with a backbone composed of →3,6)-β-d-Galp-(1→ and →3)-β-d-Galp-(1→ residues, a structure that is relatively novel in Curcuma longa. In vitro antioxidant assays demonstrated that CPAP-1 possesses potent antioxidative stress activity, effectively scavenging both DPPH and hydroxyl radicals. Furthermore, cellular experiments revealed that at concentrations of 500 and 750 mg/L, CPAP-1 significantly protected human umbilical vein endothelial cells (HUVECs) against H₂O₂-induced oxidative damage. In conclusion, these findings suggest that CPAP-1 could be developed as a natural antioxidant, functional food, or therapeutic agent for preventing and mitigating oxidative stress-related vascular injury, providing a theoretical basis for further development and application. Full article

The treatment of wounds, most of which are complications of chronic diseases, poses a significant clinical challenge. Hybrid systems based on hyaluronic acid containing growth factors are a promising prospect for the treatment of chronic wounds. Hyaluronic acid supports fibroblast proliferation, migration, and adhesion to the wound site, and stimulates collagen production. Growth factors (GF), such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF), influence the normal proliferation and migration of keratinocytes and fibroblasts. This review aims to summarise the current state of knowledge regarding their therapeutic potential. Google Scholar, Web of Science, and Medline (PubMed) databases were searched. Eighteen studies, including basic, preclinical, and clinical studies, were included in the review. The studies confirm the therapeutic potential of the developed formulations. Collagen/hyaluronic acid and alginate/hyaluronic acid systems are biocompatible and biodegradable matrices that provide a moist wound environment, which promotes cell migration and proliferation. EGF stimulates the proliferation and migration of keratinocytes, which accelerates re-epithelialisation. bFGF supports angiogenesis by stimulating the proliferation and migration of vascular endothelial cells. The effect of these actions indirectly leads to increased production of VEGF and HGF cytokines, which support the formation of granulation tissue. The VEGF-containing dressing stimulated vascularisation and the production of collagen type-1 and fibronectin. Only one clinical study conducted in this field indicates the need for further research in this area. Full article

This study presents a protocol for co-culturing pancreatic islet cell clusters derived from pancreatic tissue with human umbilical vein endothelial cells (HUVECs) on Matrigel using a specialized culture medium to form vascularized pancreatic islet organoids. We established a novel culture system for vascularized pancreatic islet organoids and compared the survival and insulin secretion capabilities of pancreatic islet cells in the presence and absence of glucose stimulation. Our results indicate that matrix adhesive materials can effectively facilitate the self-assembly of the vascularized endothelial cell–pancreatic islet organoids complex. Vascularized HUVEC prolongs the survival of pancreatic islet organoids in vitro. Moreover, the interaction between vascularized HUVEC and pancreatic islets significantly enhances the insulin secretion ability in response to glucose stimulation. This study reports a protocol for the long-term in vitro culture of pancreatic islet organoids, offering methods for the vascularization of pancreatic islet organoids on Matrigel. These data contribute to the understanding of how vascularization impacts the fate and function of pancreatic islet organoids, although the specific mechanism still requires further clarification. Full article

Ischemic stroke remains one of the most catastrophic diseases in neurology, in which, due to a disturbance in the cerebral blood flow, the brain is acutely deprived of its oxygen and glucose oligomer, which in turn rapidly leads to energetic collapse and progressive cellular death. There is now increasing evidence that this type of stroke is not simply a type of ‘oxidative stress’ but rather a programmable loss-of-redox homeostasis, within which electron flow and the balance of oxidants/reductants are cumulatively displaced at the level of the single molecule and at the level of the cellular area. The advances being made in cryo-electron microscopy, lipidomics, and spatial omics are coupled with the introduction of a redox code produced by the interaction of the couples NADH/NAD⁺, NADPH/NADP⁺, GSH/GSSG, BH₄/BH₂, and NO/SNO, which determine the end results of the fates of the neurons, glia, endothelium, and pericytes. Within the mitochondria, pathophysiological events, including reverse electron transport, succinate overflow, and permeability transition, are found to be the first events after reperfusion, while signals intercommunicating via ER–mitochondria contact, peroxisomes, and nanotunnels control injury propagation. At the level of the tissue, events such as the constriction of the pericytes, the degradation of the glycocalyx, and the formation of neutrophil extracellular traps underlie microvascular failure (at least), despite the effective recanalization of the vessels. Systemic influences such as microbiome products, oxidized lipids, and free mitochondrial DNA in cells determine the redox imbalance, but this generally occurs outside the brain. We aim to synthesize how the progressive stages of ischemic injury evolve from the cessation of flow to the collapse of the cell structure. Within seconds of injury, there is reverse electron transport (RET) through mitochondrial complex I, with bursts of superoxide (O₂•⁻) and hydrogen peroxide (H₂O₂) being produced, which depletes the stores of superoxide dismutase, catalase, and glutathione peroxidase. Accumulated succinate and iron-induced lipid peroxidation trigger ferroptosis, while xanthine oxidase and NOX2/NOX4, as well as uncoupled eNOS/nNOS, lead to oxidative and nitrosative stress. These cascades compromise the function of neuronal mitochondria, the glial antioxidant capacity, and endothelial–pericyte integrity, leading to the degradation of the glycocalyx with microvascular constriction. Stroke, therefore, represents a continuum of redox disequilibrium, a coordinated biochemical failure linking the mitochondrial metabolism with membrane integrity and vascular homeostasis. Full article

The vascular endothelium serves as a critical barrier preventing the transmigration of monocytes, circulating lipoproteins, and other molecules into the subendothelial space, and plays a vital role in regulating vascular tone. A dysfunctional and inflamed endothelial layer in response to disturbed blood flow or other proatherogenic risk factors is the initiating event in the pathogenesis of atherosclerosis, suggesting the importance of an intact and properly functioning endothelium in preventing the onset and progression of this disease. Accumulated evidence demonstrates the significant role of matricellular proteins, which are non-structural and secretory extracellular matrix (ECM) proteins, in the development of atherosclerosis. These proteins exert multifaceted effects on endothelial cells (ECs) ranging from reactive oxygen species (ROS) production, endoplasmic reticulum stress, and expression of adhesion molecules to autophagy and compromised barrier function via stimulating various molecular mechanisms. Given the critical roles of these processes in EC function and atherosclerosis, a better understanding of signaling pathways governed by matricellular proteins in ECs is required to develop therapeutic strategies for suppressing or preventing atherosclerosis and related cardiovascular diseases (CVDs). This review comprehensively summarizes the existing literature on the diverse roles of matricellular proteins in regulating EC inflammation and function, and highlights their potential as viable therapeutic targets for maintaining vascular health and inhibiting the progression of atherosclerosis. Full article

Background/Objectives: Endothelial dysfunction plays a central role in the development of cardiovascular diseases. β-Casomorphin-7 (BCM-7), a biologically active peptide generated during the digestion of A1 β-casein, is presumed to contribute to this process; however, its direct effects on endothelial cells have not been previously investigated. Here, we aimed to assess whether BCM-7 treatment induces endothelial cell dysfunction through inflammatory cytokines and reactive oxygen species (ROS). Methods: In our study, we analyzed the effects of BCM-7 (5 µg/mL) in combination with lipopolysaccharide (LPS, 100 ng/mL) on human umbilical vein endothelial cells (HUVECs/TERT2). The cell viability, apoptosis, necrosis, and intracellular reactive oxygen species were measured. Furthermore, proinflammatory cytokines and enzymes involved in the regulation of inflammation were assessed with quantitative real-time PCR. The gene and protein expression of enzymes that regulate inflammation and vascular function, thus maintaining endothelial homeostasis were assessed. Results: BCM-7 enhanced intracellular ROS production p ≤ 0.001, increased the expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) p ≤ 0.001, and was more effective when used in combination with LPS p ≤ 0.001. It decreased the expression of cyclooxygenase-1 (COX-1) p ≤ 0.05, during 4 h of exposure, whereas it increased the expression of cyclooxygenase-2 (COX-2) p ≤ 0.001, lipoxygenase-5 (LOX-5) p ≤ 0.01, and nitric oxide synthase 3 (NOS3) p ≤ 0.001; prostaglandin D2 synthase (PTGDS) (p ≤ 0.05), expression was also increased after short treatment. Conclusions: Our results suggest that BCM-7 may contribute to the development of endothelial dysfunction, especially in the presence of LPS, by enhancing oxidative stress and inflammatory response. Full article

Background/Objectives: Endothelial activation by lipopolysaccharides (LPS) contributes to inflammation and the development of cardiovascular disease, making n-3 polyunsaturated fatty acids (PUFAs) potential modulators capable of mitigating endothelial dysfunction. The current study examines the effects of long-chain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), along with their precursor, α-linolenic acid (ALA), on oxidative stress, adhesion molecule expression, and cytokine milieu in LPS-stimulated human aortic endothelial cells (HAECs). Methods: HAECs (fifth passage) were cultured in control medium under standard conditions: ~37 °C, 5% CO₂, ≥80% humidity. Cells were incubated in control basal cell medium or medium supplemented with ALA, EPA, DHA, and their combination (50 µM; n = 5 per group). After 48 h, cells were treated overnight (~16 h) with LPS from E. coli (0.75 and 1 µg/mL). HAECs and supernatants were collected for flow cytometry, Luminex, and ELISA assays. Significance was assessed using two-way analysis of variance ANOVA, followed by post hoc analyses (p < 0.05). Spearman’s correlation analysis was performed between markers, and p-values were adjusted using the Benjamini–Hochberg (BH) correction. Results: PUFA supplementation, particularly with DHA and ALA, significantly reduced intracellular reactive oxygen species (ROS) production and the expression of adhesion molecules (ICAM-1, E-selectin) in HAECs under both basal and LPS-stimulated inflammatory conditions. All PUFAs reduced pro-inflammatory cytokine levels (IFNγ, TNFα, IL-6), while ALA increased IL-1α and endoglin expression, indicating differential immunomodulatory effects. EPA exhibited antioxidant and anti-inflammatory effects primarily at higher LPS concentrations. Correlation analysis demonstrated strong interdependence between oxidative stress, inflammatory markers, and vascular activation, further confirming PUFA-mediated endothelial protection. Conclusions: PUFA supplementation produced molecule-specific effects on endothelial inflammation. DHA and ALA consistently showed anti-inflammatory and antioxidative effects, while EPA’s beneficial effect was more pronounced under inflammatory conditions, emphasising the importance of PUFA type and context in managing vascular inflammation. Full article

Excessive dietary salt intake remains a critical and underestimated global health concern, strongly associated with increased cardiovascular disease risk. While the relationship between salt and arterial hypertension is well established, accumulating evidence highlights additional, blood pressure-independent mechanisms linking high salt intake with the progression of atherosclerosis. Beyond its hypertensive effects, high dietary salt directly damages the vascular endothelium by disrupting the glycocalyx, reducing nitric oxide synthesis, and increasing endothelial stiffness and inflammation. Excess sodium also impairs glycosaminoglycan buffering capacity and promotes immune cell adhesion, even in normotensive individuals. Furthermore, salt-induced dysbiosis of the gut microbiota alters the metabolic and inflammatory environment, lowering beneficial short-chain fatty acids and increasing pro-atherogenic metabolites such as trimethylamine N-oxide. Recent findings also implicate salt-driven modulation of hematopoiesis via Th17 cytokines, which enhances the production of pro-inflammatory monocytes that accelerate plaque development. These findings support the notion that high salt intake may be an independent and modifiable residual risk factor for atherosclerotic cardiovascular disease. Reducing dietary sodium—particularly from processed foods—should therefore remain a central component of both primary and secondary cardiovascular prevention. Although the optimal range of salt intake remains under discussion, a moderate reduction to below 5 g/day is considered safe and beneficial. Full article

Hemodynamics significantly impact the biology of endothelial cells (ECs) lining the blood vessels. ECs are exposed to various hemodynamic forces, particularly frictional shear stress from flowing blood. While physiological flows are critical for the normal functioning of ECs, abnormal flow dynamics, known as disturbed flows, may trigger endothelial dysfunction leading to atherosclerosis and other vascular conditions. Such flows can occur due to sudden geometrical variations and vascular abnormalities in the cardiovascular system. In the current study, a microfluidic system was used to investigate the impact of different flow conditions (i.e, normal vs. disturbed) on ECs in vitro. We particularly explored the relationship between specific flow patterns and cellular pathways linked to oxidative stress and inflammation related to atherosclerosis. Here, we utilized a 2D cell culture perfusion system featuring an immortalized human vascular endothelial cell line (EA.hy926) connected to a modified peristaltic pump system to generate either steady laminar flows, representing healthy conditions, or disturbed oscillatory flows, representing diseased conditions. EA.hy926 were exposed to an oscillatory flow shear stress of 0.5 dynes/cm² or a laminar flow shear stress of 2 dynes/cm² up to 24 h. Following flow exposure, cells were harvested from the perfusion chamber for quantitative PCR analysis of gene expression. Reactive oxygen species (ROS) generation under various shear stress conditions was also measured using DCFDA/H2DCFDA fluorescent assays. Under oscillatory shear stress flow conditions (0.5 dynes/cm²), EA.hy926 ECs showed a 3.5-fold increase in the transcription factor nuclear factor (NFκ-B) and a remarkable 28.6-fold increase in cyclooxygenase-2 (COX-2) mRNA expression, which are both proinflammatory markers, compared to static culture. Transforming growth factor-beta (TGFβ) mRNA expression was downregulated in oscillatory and laminar flow conditions compared to the static culture. Apoptosis marker transcription factor Jun (C-Jun) mRNA expression increased in both flow conditions. Apoptosis marker C/EBP homologous protein (CHOP) mRNA levels increased significantly in oscillatory flow, with no difference in laminar flow. Endothelial nitric oxide synthase (eNOS) mRNA expression was significantly decreased in cells exposed to oscillatory flow, whereas there was no change in laminar flow. Endothelin-1 (ET-1) mRNA expression levels dropped significantly by 0.5- and 0.8-fold in cells exposed to oscillatory and laminar flow, respectively. ECs subjected to oscillatory flow exhibited a significant increase in ROS at both 4 and 24 h compared to the control and laminar flow. Laminar flow-treated cells exhibited a ROS generation pattern similar to that of static culture, but at a significantly lower level. Overall, by exposing ECs to disturbed and normal flows with varying shear stresses, significant changes in gene expression related to inflammation, endothelial function, and oxidative stress were observed. In this study, we present a practical, optimized system as an in vitro model that can be employed to investigate flow-associated diseases, such as atherosclerosis and aortic aneurysm, thereby supporting the understanding of the underlying molecular mechanisms. Full article

Background/Objectives: To elucidate the differential transcriptional and intercellular signaling features of tumor components across various cancers, we conducted a comparative analysis using single-cell RNA sequencing (scRNA-seq). This technology enables detailed characterization of tumor ecosystems and may explain variations in tumor behavior among distinct cancer types. Methods: We analyzed publicly available scRNA-seq datasets (GEO) from seven cancer types—pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), thyroid cancer (TC), gastric cancer (GC), and colorectal cancer (CRC)—to define their unique molecular characteristics and intercellular interactions. Results: PDAC displayed a distinct tumor microenvironment (TME) dominated by myeloid cells (~42%), including abundant CXCR1/CXCR2-expressing tumor-associated neutrophils (TANs) that preferentially interacted with immune rather than cancer cells. The competitive receptor ACKR1 was minimally expressed on endothelial cells, consistent with PDAC hypo-vascularity. In HCC, tumor cells lacked EPCAM and expressed complement and stem cell markers; cancer-associated fibroblasts (CAFs) were scarce, and stellate cells expressed the pericyte marker RGS5. CAFs were abundant in ESCC and BC, with IGF1/2 expression, while in GC, these markers were uniquely found in plasma cells. Since BC and GC subtypes exhibit distinct TME patterns, it is necessary to perform subtype-specific analyses for these cancers. TC showed high expression of tumor-suppressor genes, including HOPX, in tumor cells. Differential interactions and the presence of “dominant signaling cell populations “ with dominant outgoing signals may underlie the heterogeneity in tumor aggressiveness across these cancers. Conclusions: Comparative scRNA-seq analysis of multiple cancers reveals distinct tumor phenotypes and cell–cell communication patterns, offering insights into the molecular architecture of human solid tumors. Full article