Search Results (8,989)

Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of nine most abundant, naturally occurring urinary COL(I)-derived peptides on human endothelial cells at physiological concentrations, using cell migration assays, mass spectrometry-based proteomics, flow cytometry, and AlphaFold 3. While none of the peptides significantly altered endothelial migration by themselves at physiological concentrations, full-length COL(I) increased cell migration, which was inhibited by Peptide 1 (²²⁹NGDDGEAGKPGRPGERGPpGp²⁴⁹). This peptide uniquely contains the DGEA and GRPGER motifs, interacting with integrin α2β1. Flow cytometry confirmed the presence of integrin α2β1 on human endothelial cells, and AlphaFold 3 modeling predicted an interaction between Peptide 1 and integrin α2. Mass spectrometry-based proteomics investigating signaling pathways revealed that COL(I) triggered phosphorylation events linked to integrin α2β1 activation and cell migration, which were absent in COL(I) plus peptide 1-treated cells. These findings identify Peptide 1 as a biologically active COL(I)-derived peptide at a physiological concentration capable of modulating collagen-induced cell migration, and provide a foundation for further investigation into its mechanisms of action and role in urine excretion. Full article

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article

Fine particulate matter (PM_2.5) exposure has been linked to increased lung damage due to compromised vascular barrier function, while 3-deoxysappanchalcone (3-DSC), a chalcone derived from Caesalpinia sappan, is known for its pharmacological benefits such as anti-cancer, anti-inflammatory, and antioxidant effects; however, its potential role in mitigating PM_2.5-induced pulmonary damage remains unexplored. To confirm the inhibitory effects of 3-DSC on PM_2.5-induced pulmonary injury, this research focused on evaluating how 3-DSC influences PM_2.5-induced disruption of the barrier of the endothelial cells (ECs) in the lungs and the resulting pulmonary inflammation. Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were assessed in PM_2.5-treated ECs and mice. This study demonstrated that 3-DSC effectively neutralized the reactive oxygen species (ROS) generated by PM_2.5 exposure in the lung endothelial cells, suppressing ROS-triggered p38 MAPK activation while enhancing Akt signaling pathways critical to preserving vascular barrier function. In animal models, 3-DSC administration markedly decreased vascular permeability, attenuated the influx of immune cells into the lung tissue, and lowered inflammatory mediators like cytokines in the airways of PM_2.5-exposed mice. These data suggest that 3-DSC might exert protective effects on PM_2.5-induced inflammatory lung injury and vascular hyperpermeability. Full article

Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article

Background: Metabolic syndrome (MetS) is a complex clinical condition characterized by the coexistence of interrelated metabolic abnormalities that significantly increase the risk of cardiovascular diseases and type 2 diabetes mellitus. Endocan—an endothelial cell-specific molecule—is considered a biomarker of endothelial dysfunction and inflammation. This study aimed to evaluate the relationship between serum endocan levels and the severity of MetS, assessed using the MetS-Z score. Methods: This study included 120 patients with MetS and 50 healthy controls. MetS was diagnosed according to the NCEP-ATP III criteria. MetS-Z scores were calculated using the MetS Severity Calculator. Serum levels of endocan, sICAM-1, and sVCAM-1 were measured using the ELISA method. Results: Serum levels of endocan, sICAM-1, and sVCAM-1 were significantly higher in the MetS group compared to the control group (all p < 0.001). When the MetS group was divided into tertiles based on MetS-Z scores, stepwise and statistically significant increases were observed in the levels of endocan and other endothelial markers from the lowest to highest tertile (p < 0.0001). Correlation analysis revealed a strong positive association between the MetS-Z score and serum endocan levels (r = 0.584, p < 0.0001). ROC curve analysis showed that endocan has high diagnostic accuracy for identifying MetS (AUC = 0.967, p = 0.0001), with a cutoff value of >88.0 ng/L. Conclusions: Circulating levels of endocan were significantly increased in MetS and were associated with the severity of MetS, suggesting that endocan may play a role in the cellular response to endothelial dysfunction-related injury in patients with MetS. Full article

Background/Objectives: Infectious endophthalmitis is a vision-threatening complication of intraocular surgery and intravitreal injections. Standard treatment involves intravitreal antibiotics; however, concerns regarding multidrug resistance and vancomycin-associated hemorrhagic occlusive retinal vasculitis (HORV) highlight the need for alternative antimicrobial strategies. This study aimed to evaluate the clinical efficacy and safety of a protocol combining intravitreal injection of 1.25% povidone-iodine (PI) with intraoperative irrigation using low concentrations of vancomycin and ceftazidime. Methods: We retrospectively analyzed 11 eyes from patients diagnosed with postoperative or injection-related endophthalmitis. Six of the eleven cases received an initial intravitreal injection of 1.25% PI, followed by pars plana vitrectomy with irrigation using balanced salt solution PLUS containing vancomycin (20 μg/mL) and ceftazidime (40 μg/mL). A second intravitreal PI injection was administered at the end of surgery in all cases. Additional PI injections were administered postoperatively based on clinical response. Clinical outcomes included best-corrected visual acuity (BCVA), microbial culture results, corneal endothelial cell density, and visual field testing. Results: All eyes achieved complete infection resolution without recurrence. The mean BCVA improved significantly from 2.18 logMAR at baseline to 0.296 logMAR at final follow-up (p < 0.001). No adverse events were observed on specular microscopy or visual field assessment. The protocol was well tolerated, and repeated PI injections showed no signs of ocular toxicity. Conclusions: This combination protocol provides a safe and effective treatment strategy for infectious endophthalmitis. It enables rapid and complete infection resolution while minimizing the risks associated with intravitreal antibiotics. These findings support further investigation of this protocol as a practical and globally accessible alternative to standard intravitreal antimicrobial therapy. Full article

Background and Objectives: Posterior chamber phakic implantable contact lenses (Phakic-ICL) are widely used for refractive correction due to their efficacy and safety, including minimal corneal endothelial cell loss. The Collamer-based EVO+ Visian implantable contact lens (ICL), manufactured from Collamer, which is a blend of collagen and hydroxyethyl methacrylate (HEMA), has demonstrated excellent long-term biocompatibility and optical clarity. Recently, hydrophilic acrylic Phakic-ICLs, such as the Implantable Phakic Contact Lens (IPCL), have been introduced. This study investigated the material differences among Phakic-ICLs and their interaction with fibronectin (FN), which has been reported to adhere to intraocular lens (IOL) surfaces following implantation. The aim was to compare Collamer, IPCL, and LENTIS lenses (used as control) in terms of FN distribution and cell adhesion using a small number of explanted Phakic-ICLs. Materials and Methods: Three lens types were analyzed: a Collamer Phakic-ICL (EVO+ Visian ICL), a hydrophilic acrylic IPCL, and a hydrophilic acrylic phakic-IOL (LENTIS). FN distribution and cell adhesion were evaluated across different regions of each lens. An in vitro FN-coating experiment was conducted to assess its effect on cell adhesion. Results: All lenses demonstrated minimal FN deposition and cellular adhesion in the central optical zone. A thin FN film was observed on the haptics of Collamer lenses, while FN adhesion was weaker or absent on IPCL and LENTIS surfaces. Following FN coating, Collamer lenses supported more uniform FN film formation; however, this did not significantly enhance cell adhesion. Conclusions: Collamer, which contains collagen, promotes FN film formation. Although FN film formation was enhanced, the low cell-adhesive properties of HEMA resulted in minimal cell adhesion even with FN presence. This characteristic may contribute to the long-term transparency and biocompatibility observed clinically. In contrast, hydrophilic acrylic materials used in IPCL and LENTIS demonstrated limited FN interaction. These material differences may influence extracellular matrix protein deposition and biocompatibility in clinical settings, warranting further investigation. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis are cardiometabolic twin disorders with shared underlying pathophysiological mechanisms such as insulin resistance and chronic inflammation. This review explores the salient role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in linking hepatic dysfunction to cardiovascular disease. Findings in mice with genetic modulation of Ceacam1 gene established a critical role for CEACAM1 protein in regulating insulin and lipid metabolism and endothelial integrity and modulating immune response. Loss of CEACAM1 in hepatocytes impairs insulin clearance, causing chronic hyperinsulinemia, a process that ultimately leads to insulin resistance and hepatic and extra-hepatic fat accumulation, which in turn causes inflammatory infiltration. This prompts a paradigm shift that positions impaired hepatic CEACAM1 function as a mechanistic underpinning of the link between insulin resistance, MASH, and atherosclerosis. Full article

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management. Full article

Preeclampsia (PE) is a multifactorial hypertensive disorder unique to pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. Its pathogenesis involves placental dysfunction and an exaggerated maternal inflammatory response. Uric acid (UA), traditionally regarded as a marker of renal impairment, is increasingly recognized as an active contributor to the development of PE. Elevated UA levels are associated with oxidative stress, endothelial dysfunction, immune activation, and reduced renal clearance. Clinically, UA is measured in the second and third trimesters to assess disease severity and guide obstetric management, with higher levels correlating with early-onset PE and adverse perinatal outcomes. Its predictive accuracy improves when combined with other clinical and biochemical markers, particularly in low-resource settings. Mechanistically, UA and its monosodium urate crystals can activate the NLRP3 inflammasome, a cytosolic multiprotein complex of the innate immune system. This activation promotes the release of IL-1β and IL-18, exacerbating placental, vascular, and renal inflammation. NLRP3 inflammasome activation has been documented in placental tissues, immune cells, and kidneys of women with PE and is associated with hypertension, proteinuria, and endothelial injury. Experimental studies indicate that targeting UA metabolism or inhibiting NLRP3 activation, using agents such as allopurinol, metformin, or MCC950, can mitigate the clinical and histopathological features of PE. These findings support the dual role of UA as both a biomarker and a potential therapeutic target in the management of the disease. Full article

Background: Patients with primary angle-closure disease (PACD), those with no history of acute angle-closure glaucoma or laser iridotomy, rarely present with prominent corneal endothelial cell density (CECD) loss. To identify factors associated with decreased CECD in PACD, anterior segment parameters were compared in patients with PACD and normal CECD and patients with PACD and decreased CECD, using anterior segment optical coherence tomography (AS-OCT). Patients and Methods: Ten patients with PACD and CECD of less than 1500/mm² without a history of cataract surgery, acute angle-closure glaucoma, or prior laser glaucoma procedures were identified at the Kyorin Eye Center from January 2018 to July 2023. Patients with an obvious corneal guttata or apparent corneal edema were also excluded. Seventeen patients with PACD and normal CECD (normal CECD group) were used as the control. Simultaneous biometry of all anterior segment structures, including the cornea, anterior chamber, and iris, were assessed using a swept-source AS-OCT system. Results: Corneal curvature radius was significantly larger in the decreased CECD group compared with the corneal refractive power in the normal CECD group (p = 0.022, Mann–Whitney test). However, no significant differences were detected in other anterior segment morphology parameters. Multiple regression analysis with CECD as the dependent variable revealed that a large corneal curvature radius was a significant explanatory variable associated with corneal endothelial loss. Conclusions: Flattened corneal curvature may be a risk factor for corneal endothelial loss in patients with PACD. Full article

The human skin microbiota, a complex community of bacterial, fungal, and viral organisms, plays a crucial role in maintaining skin homeostasis and regulating host-pathogen interactions. Dysbiosis within this microbial ecosystem has been implicated in various dermatological conditions, including acne vulgaris, psoriasis, seborrheic dermatitis, and atopic dermatitis. This review, for the first time, provides recent advancements in all four layers of omic technologies—metagenomics, metatranscriptomics, metaproteomics, and metabolomics—offering comprehensive insights into microbial diversity, in the context of functional skin modeling. Thus, this review explores the application of these omic tools to in vitro skin models, providing an integrated framework for understanding the molecular mechanisms underlying skin–microbiota interactions in both healthy and pathological contexts. We highlight the importance of developing advanced in vitro skin models, including the integration of immune components and endothelial cells, to accurately replicate the cutaneous microenvironment. Moreover, we discuss the potential of these models to identify novel therapeutic targets, enabling the design of personalized treatments aimed at restoring microbial balance, reinforcing the skin barrier, and modulating inflammation. As the field progresses, the incorporation of multi-omic approaches into skin-microbiome research will be pivotal in unraveling the complex interactions between host and microbiota, ultimately advancing therapeutic strategies for skin-related diseases. Full article

Multiple myeloma (MM) is an incurable malignancy characterized by the proliferation of abnormal plasma cells within the bone marrow, followed by potential dissemination to extramedullary sites. The bone marrow barrier (BMB) plays a pivotal role in plasma cell homing and disease progression. Bone marrow endothelial cells (BMECs) and bone marrow stromal cells (BMSCs), through their interactions with MM cells, secrete adhesion molecules, angiogenic cytokines, anti-apoptotic factors, and growth-promoting signals that support MM cell survival and proliferation. This review examines the components of the BMB and the major pathways involved in MM pathogenesis. Targeting the interactions between MM cells and the BMB may offer novel therapeutic opportunities. Full article

Cell migration assays provide valuable insights into pathological conditions, such as tumor metastasis and immune cell infiltration, and the regenerative capacity of tissues. In vitro tools commonly used for cell migration studies exploit commercial transwell systems, whose functionalities can be improved through engineering of the pore pattern. In this context, we propose the fabrication of a transwell-like device pursued by combining the proton beam writing (PBW) technique with wet etching onto thin layers of polydimethylsiloxane (PDMS). The resulting transwell-like device incorporates a PDMS membrane with finely controllable pore patterning that was used to study the arrangement and migration behavior of HCMEC/D3 cells, a well-established human brain microvascular endothelial cell model widely used to study vascular maturation in the brain. A comparison between commercial polycarbonate membranes and the PBW-holed membranes highlights the impact of the ordering of the pattern and porosity on cellular growth, self-organization, and transmigration by combining fluorescent microscopy and advanced digital processing. Endothelial cells were found to exhibit distinctive clustering, alignment, and migratory behavior close to the pores of the designed PBW-holed membrane. This is indicative of activation patterns associated with cytoskeletal remodeling, a critical element in the angiogenic process. This study stands up as a novel approach toward the development of more biomimetic barrier models (such as organ-on-chips). Full article