Search Results (1,062)

Objectives: To primarily determine the effect of a previous cesarean section on Doppler studies of the uterine artery, umbilical artery, and umbilical vein. Patients and Methods: This prospective study was conducted on singleton pregnancies between 18 and 22 weeks of gestation, including both women with and without a previous cesarean section. Doppler studies of the uterine artery, umbilical artery, and umbilical vein indices were performed during mid-trimester fetal ultrasound scans. Doppler indices and pregnancy outcomes were compared between the two groups. Results: A total of 351 pregnancies, including 74 women with a previous cesarean section and 277 women with an unscarred uterus, underwent Doppler studies. The uterine artery pulsatility index (PI) and resistance index (RI) were significantly higher in women with a previous cesarean section (p < 0.001). Moreover, both univariate and multivariate analyses demonstrated that a previous cesarean section was significantly associated with an increase in uterine artery PI, RI, and the rate of abnormal uterine artery PI, defined as values above the 95th percentile (p = 0.034). Other Doppler study results, as well as pregnancy outcomes, were comparable between the two groups. Conclusions: Pregnant women with a previous cesarean section have significantly higher uterine artery resistance, and a higher rate of abnormal uterine artery PI during mid-pregnancy. Therefore, a cesarean section may be detrimental to uterine arterial health. However, no significant adverse clinical outcomes were observed. Full article

Hantaviruses are emerging zoonotic pathogens responsible for two severe clinical syndromes: (i) haemorrhagic fever with renal syndrome (HFRS) and (ii) hantavirus cardiopulmonary syndrome (HCPS), collectively causing more than 200,000 human cases annually worldwide. Despite their public-health importance, the molecular mechanisms governing the host response and the population-level dynamics of rodent-to-human spillover remain incompletely characterised. The timeliness of this framework is underscored by the April–May 2026 outbreak of Andes orthohantavirus aboard the MV Hondius cruise ship, the first such cluster in a maritime setting, with three deaths reported across multiple countries. This event revealed critical gaps in existing models that treat humans solely as dead-end spillover hosts. Our coupled Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model assumes no human-to-human transmission and is therefore designed for hantavirus strains where spillover does not lead to secondary human cases, specifically Hantaan virus (HTNV), Puumala virus (PUUV), Sin Nombre virus (SNV), and Dobrava-Belgrade virus (DOBV). The Andes virus (ANDV) outbreak aboard the MV Hondius is used as a real-world case study to assess the boundaries of our model and to motivate future extensions, not as a direct validation target for its quantitative predictions. Here, we present an integrated computational study combining three complementary analyses. First, we performed a preliminary phylogenetic analysis of the viral sequence, identifying Orthohantavirus andesense as the likely etiological agent responsible for the vessel-associated outbreak. Second, we carried out a downstream transcriptomic analysis of Hantaan virus (HTNV)-infected human umbilical vein endothelial cells (HUVECs), using publicly available RNA-seq data (GEO accession GSE133751, $n=3$ per group). This analysis identified 184 upregulated and 19 downregulated genes, highlighting a transcriptional response dominated by interferon-stimulated genes (ISGs), including CXCL10, CXCL11, MX2, DDX58, IRF7, STAT1, OASL, and CMPK2. We then constructed a protein–protein interaction (PPI) network using STRING, comprising 176 nodes and 3210 edges, and applied a composite network centrality score to rank putative regulatory hubs. This analysis identified ISG15, IRF1, CXCL10, STAT1, and DDX58 as the most central nodes. Pathway enrichment analysis confirmed a strong activation of interferon signalling (Reactome, $p=1.3\times {10}^{-63}$), antiviral defence mechanisms (Gene Ontology, $p=3.8\times {10}^{-58}$), and NF-$\kappa$B-related pathways, together with a concurrent suppression of ribosomal translation. Finally, we developed a coupled SEIRD epidemiological model that explicitly represents rodent-to-rodent and rodent-to-human transmission with logistic rodent population growth. Preliminary simulation analysis demonstrates that reducing human exposure to rodent excreta is substantially more effective than rodent population control alone for reducing human disease burden, and that rodent control in isolation can paradoxically increase human cases through a dilution-like effect. The integrated framework provides molecular and epidemiological insights relevant to hantavirus surveillance, therapeutic target identification, and public-health intervention design. Full article

Hyperglycemia aggravates colorectal cancer (CRC) progression by driving inflammatory pathways and facilitating tumor–endothelial cell adhesion. Ginger extract exhibits well-known anti-inflammatory properties; however, its pharmacological efficacy under such metabolic stress conditions remains largely unclear. In this study, the effects of a fermented ginger extract prepared using natural deep eutectic solvents (FNGE) were examined on high-glucose-induced pathogenesis in human CRC cells. DLD-1 cells were exposed to high-glucose conditions with or without FNGE treatment. The expression of inflammatory mediators (cyclooxygenase-2 [COX-2], prostaglandin E2 [PGE2], interleukin [IL-6], and IL-8), the adhesion capacity of CRC cells to human umbilical vein endothelial cells (HUVECs), and activation of the NF-κB signaling pathway were examined. FNGE treatment significantly and dose-dependently attenuated the high-glucose-induced upregulation of COX-2 mRNA and PGE2 secretion, while concurrently suppressing the expression of IL-6 and IL-8. Furthermore, FNGE pretreatment markedly impaired CRC cell adhesion to HUVECs. Mechanistic analyses, including targeted COX-2 knockdown and pharmacological inhibition, revealed that FNGE exerts its anti-inflammatory and anti-adhesive effects primarily through the suppression of NF-κB activation, a master transcriptional regulator of these pathogenic pathways. These in vitro findings demonstrated that FNGE effectively mitigates high glucose-mediated inflammation and endothelial adhesion in CRC cells by downregulating the NF-κB/COX-2 signaling axis. Thus, this study provides a preliminary biochemical basis for the potential application of green-extracted phytochemicals under metabolic stress, highlighting the need for future in vivo validation to confirm their translational relevance. Full article

Background/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs-induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVECs) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin exhibited a partial and limited protective effect on endothelial cells against CaCe-dEVs-induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer-cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation. Full article

Background: The fetal circulatory system is characterized by the presence of physiological vascular shunts—the ductus venosus, foramen ovale, and ductus arteriosus—which enable a significant portion of blood to bypass the pulmonary circulation and partially the hepatic portal system. This mechanism ensures preferential delivery of oxygenated blood to the brain, heart, and upper body. Agenesis of the ductus venosus (ADV) is a rare vascular anomaly associated with diverse anatomical variations and clinical outcomes. Objectives: This systematic review aimed to determine the prevalence of ADV and to assess the frequency of intrahepatic and extrahepatic types. Additional objectives were to identify the most common drainage sites of the umbilical vein (UV) in extrahepatic ADV, evaluate the genetic abnormalities, congenital heart defects, and extracardiac anomalies most frequently associated with ADV, and establish the prognosis of affected fetuses. Methods: A comprehensive literature search was conducted in the PubMed, Embase, and Web of Science databases using predefined and precise inclusion criteria. Results: The overall prevalence of ADV in the general population was 0.05%. The intrahepatic and extrahepatic types occurred with comparable frequencies, accounting for 51.2% and 48.8% of cases, respectively. In extrahepatic ADV, the most common drainage site of the UV was the right atrium (48%). The most frequent genetic abnormalities were trisomy 21 (12%) and Turner syndrome (6%). Among congenital heart defects, ventricular septal defect (22.7%) and atrioventricular septal defect (8.8%) were most prevalent. Functional consequences were observed in 37.4% of fetuses with isolated ADV, most commonly cardiomegaly. Conclusions: ADV is a rare fetal vascular anomaly. With the increasing availability and utilization of prenatal diagnostic techniques, expanding knowledge of this condition and its clinical implications is essential for accurate diagnosis, management, and prognostic assessment. Full article

Thrombosis remains a critical challenge for blood-contacting implants, with early-stage protein adsorption and platelet activation playing decisive roles. In this study, we constructed a TiO₂/CuO semiconductor heterojunction on titanium surfaces to generate a stable built-in electric field, creating a self-activated bioelectric microenvironment without external stimulation. We evaluated its cytocompatibility and hemocompatibility through static in vitro assays. To distinguish the contributions of surface chemistry, topography, and bioelectric cues, we include control groups of Ti (untreated), TNW (TiO₂ network, topography control), and Ti/CuO (CuO nanoparticles without heterojunction, Cu²⁺ release control). The heterojunction significantly enhances human umbilical vein endothelial cell (HUVEC) adhesion and proliferation while simultaneously suppressing fibrinogen adsorption, platelet adhesion/activation (as assessed by morphological changes), and whole-blood cell adhesion. Compared with Ti/CuO, the heterojunction (TCH) induces substantially stronger endothelialization and anticoagulant effects despite similar Cu²⁺ release levels (~0.047 μM, far below the reported pro-angiogenic threshold of ~5.0 μM), indicating a predominant role of the built-in electric field. This study preliminarily demonstrates a previously unrecognized role of bioelectric cues in modulating early blood–material interactions. Following rigorous validation under physiologically relevant dynamic flow conditions and in vivo models, interfacial bioelectric engineering emerges as a promising new strategy for designing anticoagulant biomaterials. Full article

Myocardial infarction (MI) triggers excessive oxidative stress, a detrimental immune response, and insufficient angiogenesis, which collectively impede effective cardiac repair. This study developed a multifunctional composite polysaccharide hydrogel, termed KgXd^gel, based on konjac glucomannan (KGM) and xanthan gum (XG) functionalized with gallic acid (GA) and dopamine (DA), respectively, to integrate reactive oxygen species (ROS) scavenging, macrophage polarization, and pro-angiogenic activities. In vitro assays demonstrated that the KgXd^gel hydrogel exhibited excellent cytocompatibility, effectively scavenged ROS, promoted the polarization of macrophages towards the reparative M2 phenotype, and enhanced the migration and tube formation of human umbilical vein endothelial cells. In a rat MI model, treatment with KgXd^gel significantly improved cardiac function (e.g., left ventricular ejection fraction, LVEF; left ventricular fractional shortening, LVFS), attenuated left ventricular dilation (LVIDs), and favorably modulated the post-infarction microenvironment. This was evidenced by the upregulation of the M2 marker CD163 and the angiogenic factor VEGF, alongside the downregulation of pro-inflammatory cytokines (e.g., IL-1β, TNF-α) and the M1 marker iNOS. These findings conclusively demonstrate that the KgXd^gel hydrogel synergistically promotes cardiac repair post-MI through its integrated antioxidant, immunomodulatory, and pro-angiogenic functions, presenting a promising multi-targeted therapeutic strategy. Full article

Stress-induced premature senescence (SIPS) of endothelial cells can cause endothelial dysfunction. As a first-line antidiabetic agent, the specific role of metformin in SIPS has not yet been clarified. In this study, an in vitro SIPS model was induced by exposing human umbilical vein endothelial cells (HUVECs) to hydrogen peroxide (H₂O₂), and the effects of metformin on cell senescence, proliferation, migration, tube formation, and mitochondrial function were evaluated. Gene expressions altered by metformin were profiled via transcriptome sequencing. Specifically, the potential involvement of migrasome-mediated mitocytosis in metformin-driven effects was examined using confocal microscopy and siRNA-mediated silencing. The results showed that metformin significantly reduced SA-β-gal activity and restored the migration and tube-forming capacities of H₂O₂-induced senescent HUVECs. Moreover, metformin regulated mitochondrial dynamics, restored mitochondrial membrane potential, and attenuated intracellular oxidative stress. Notably, transcriptomic and functional analyses suggested that metformin enhanced migrasome formation and migrasome-mediated mitocytosis. Inhibition of migrasome formation by siTSPAN4 abolished the protective effect of metformin against SIPS. Collectively, these findings demonstrate that metformin alleviates early SIPS-associated changes in HUVECs and suggest that migrasome-mediated mitocytosis contributes to this protection by ameliorating mitochondrial dysfunction. This provides novel mechanistic insight into the vascular protective effects of metformin. Full article

This study aimed to evaluate whether serum from patients with primary antiphospholipid syndrome (APS) is associated with changes in the expression of long non-coding RNAs (lncRNAs) in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured with serum from 12 female patients with APS or 8 age-matched healthy female controls. The expression levels of HIF1A-AS1, OIP5-AS1, and GAS5 were quantified by RT-qPCR. Exposure of HUVECs to APS serum was associated with reduced expression of HIF1A-AS1 and OIP5-AS1 compared with cells stimulated with control serum. The median HIF1A-AS1 expression levels were 0.08 a.u. (interquartile range, 0.06–0.10) in APS-stimulated cells versus 0.14 a.u. (0.08–0.16) in controls (p = 0.044). Likewise, OIP5-AS1 levels were 0.09 a.u. (0.01–0.16) in APS-stimulated cells versus 2.24 a.u. (0.70–3.55) in controls (p = 0.018). In contrast, GAS5 expression did not differ significantly between groups (340 a.u. (310–3940 versus 358 a.u. (163–445); p = 0.290). In this proof-of-concept study, serum from APS patients was associated with selective downregulation of HIF1A-AS1 and OIP5-AS1 in endothelial cells. These findings support a potential link between circulating APS-related factors and endothelial lncRNA expression; however, no mechanistic or functional conclusions can be drawn. Full article

Background: Diabetic vascular complications are a major cause of poor prognosis in patients with diabetes mellitus (DM). Mitophagy activation is a potential therapeutic target for type 2 diabetes mellitus (T2DM), but the role of low-intensity pulsed ultrasound (LIPUS) in this context remains unclear. Methods: The biological effects of LIPUS on endothelial cells under high glucose conditions were systematically evaluated using high glucose-treated human umbilical vein endothelial cells (HUVECs) and aortic tissues from diabetic rats as models, in combination with bioinformatics analysis and standard molecular and cellular biology techniques. Histological staining was further used to assess the protective role of LIPUS in the aortas of diabetic rats. Results: Bioinformatics analysis predicted that high glucose induces mitochondrial dysfunction, suppresses autophagy in HUVECs, impairs endothelial cell function, and activates fibroblasts. In vitro results were in agreement with these predictions. LIPUS treatment significantly counteracted these effects, restoring migration (p < 0.001) and angiogenesis (p < 0.05), increasing proliferation (p < 0.001), and decreasing apoptosis (p < 0.05). Mechanistically, LIPUS enhanced mitophagy, and its therapeutic effects were markedly diminished upon addition of the autophagy inhibitor 3-Methyladenine (3-MA). In vivo, LIPUS attenuated aortic endothelial damage and reduced collagen deposition in diabetic rats (p < 0.01). Conclusions: LIPUS may ameliorate hyperglycemia-induced endothelial cell dysfunction by activating mitophagy, and it also attenuates pathological damage in the abdominal aorta of diabetic rats, thereby providing experimental evidence for its application in the treatment of diabetic macrovascular complications. Full article

Background and objective: Umbilical cord abnormalities (UCAs) such as hypercoiling, velamentous or marginal cord insertion, or reduced Wharton’s jelly are associated with umbilical thrombosis. UCAs increase the risk of vascular obstruction and impaired fetal blood flow, resulting in hypoxia or stillbirth. We examined the association between the UCAs and the umbilical cord thrombosis. Methods: According to PRISMA, five electronic databases (PubMed, Scopus, Embase, Cochrane Library, and Clinicaltrial.gov) were screened. Only studies that analyzed umbilical cord insertion abnormalities and abnormalities of the umbilical cord associated with thrombosis were included in this systematic review. Studies without thrombosis were excluded (PROSPERO ID: CRD420251087525). Results: Only 12 articles out of 1105 screened records satisfied the inclusion criteria, comprising 3 retrospective cohort studies, 3 case series and 6 case reports. The publication years ranged from 1983 to 2025. A total of 126 cases of umbilical vascular thromboembolism (UVTE) were identified, among which 84 cases of UCAs represented by 16 cases of stricture, 14 cases of hypercoiling, 16 cases of too-short cords (≤40 cm), 11 cases of too-long cords (≥70 cm), 5 cases of velamentous or furcate cord insertions, 12 cases of nuchal cord insertions, 13 cases of funistisis, 11 cases of true knots, and 3 cases of Wharton jelly abnormalities. Conclusions: UCAs, including true knots, abnormal coiling, and furcate or velamentous cord insertion, were highly associated with UVTE. Future studies should involve developing standardized criteria for the diagnosis and reporting of UCAs. Full article

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers. Full article

Background: Preterm infants with bradycardia at birth often undergo immediate cord clamping (ICC) followed by resuscitation with positive pressure ventilation (PPV), chest compressions (CCs) and umbilical venous catheter (UVC) epinephrine. Resuscitation with an intact cord (PPV during delayed umbilical cord clamping—DCC) stabilizes cardiac output but delays UVC placement. Objective: To evaluate the feasibility of direct epinephrine injection into the umbilical vein during DCC (DCC + direct-epinephrine) compared with ICC and epinephrine administered through a UVC (ICC + cath-epinephrine), and to explore differences in return of spontaneous circulation (ROSC) and need for CCs between these approaches. Methods: Eleven preterm lambs (125–127 d gestation) were asphyxiated by cord compression to decrease heart rate (HR) to <30/min. In the ICC + cath-epinephrine group, the cord was immediately cut, lambs received PPV followed by CCs if HR < 60/min, and epinephrine was administered after UVC placement. In the DCC + direct-epinephrine group, cord compression was released when HR < 30/min and PPV was initiated. If HR remained <60/min, epinephrine was injected into the UV using a 25G needle. If ROSC was achieved, DCC was continued for 2 min. If HR < 100/min, the cord was cut and resuscitation was continued as outlined above. Plasma epinephrine concentrations were analyzed. Results: All lambs required epinephrine. Time to epinephrine was shorter with DCC + direct-epinephrine, 1.0 (0.7, 1.6) vs. 3.7 min (3.2, 5.2). Fewer lambs with DCC + direct-epinephrine needed CC (2/6 vs. 5/5, p = 0.06). ROSC success and plasma epinephrine concentrations were similar. Post-ROSC, heart rates and mean blood pressures tended to be higher in the ICC + cath-epinephrine group. Conclusions: In this perinatal lamb model of asphyxial bradycardia, resuscitation with an intact cord with direct umbilical venous epinephrine injection is feasible. Larger studies are required to determine whether this approach reduces the need for CC or improves clinically meaningful outcomes. Full article

Background/Objectives: Diabetic foot ulcers (DFUs) are a common and challenging complication of diabetes, significantly impacting the quality of life for patients due to impaired wound healing. Exploring effective and targeted therapies for DFUs is therefore both important and meaningful. Sulforaphane (SFN), a natural bioactive compound found in cruciferous vegetables, shows promise in this area. However, its role and underlying mechanisms in promoting wound healing in DFUs have not been fully understood. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured under high-glucose conditions to establish an in vitro diabetic model. Cell viability, inflammation, apoptosis, and mitochondrial function were assessed. The expression and activation of Nrf2 were examined following SFN treatment. Additionally, Nrf2 overexpression was performed to validate its role in mediating the protective effects of SFN under high-glucose stress. Results: High-glucose conditions significantly reduced HUVEC viability and increased inflammation, apoptosis, and mitochondrial dysfunction. Treatment with SFN effectively counteracted these detrimental effects. SFN robustly activated Nrf2 signaling, and overexpression of Nrf2 recapitulated the protective effects of SFN, attenuating cellular damage under high-glucose conditions. Conclusions: SFN activates Nrf2 expression and protects HUVECs from high-glucose-induced injury by improving cell viability, mitochondrial function, and inflammatory response. These findings suggest that SFN may serve as a promising targeted therapy for diabetic foot ulcers. Full article

Background/Objectives: Plant-derived phytochemicals are being increasingly explored for their ability to treat various illnesses, especially those affecting the vasculature. High mobility group box 1 (HMGB1) acts as a crucial mediator during the late phase of sepsis, promoting the secretion of pro-inflammatory cytokines and thereby fueling inflammation and systemic complications. Higher plasma HMGB1 levels not only hinder accurate diagnosis and prognosis but also worsen disease outcomes in inflammatory states. Picropodophyllotoxin (PPT), a key bioactive ingredient isolated from the root of Podophyllum hexandrum, has shown a range of beneficial effects, including anti-cancer and anti-proliferative actions, across several tumor types. Nevertheless, its possible involvement in HMGB1-driven severe vascular inflammation remains unexplored. The current work aimed to investigate whether PPT could influence lipopolysaccharide (LPS)-induced HMGB1 activity and its related inflammatory signaling in human umbilical vein endothelial cells (HUVECs). Methods: A combination of in vitro and in vivo approaches was used to assess the anti-inflammatory action of PPT. These included measurements of endothelial barrier function, cell survival, leukocyte attachment and migration, levels of cell adhesion molecules, and the release of pro-inflammatory factors. Both cultured human endothelial cells and mouse disease models were used to thoroughly evaluate how PPT affects HMGB1-triggered inflammatory reactions. Results: The findings showed that PPT markedly reduced HMGB1 movement from inside HUVECs to the outside, thereby limiting its release into the environment. Moreover, PPT effectively decreased neutrophil sticking and migration, lowered the appearance of HMGB1 receptors, and prevented the activation of nuclear factor-κB (NF-κB), a master switch in inflammatory signaling. At the same time, PPT treatment strongly lowered tumor necrosis factor-α (TNF-α) production, adding to its anti-inflammatory profile. Conclusions: Taken together, these results indicate that PPT potently inhibits HMGB1-driven inflammatory processes by acting at several levels of the inflammatory cascade, such as HMGB1 movement, receptor binding, NF-κB activation, and subsequent cytokine release. Therefore, PPT stands out as a hopeful therapeutic option for HMGB1-related inflammatory diseases and deserves further exploration in preclinical and clinical studies. Full article