Platelet Endothelial Cell Adhesion Molecule-1 Research Articles

Aloe vera and the Proliferative Phase of Cutaneous Wound Healing: Status Quo Report on Active Principles, Mechanisms, and Applications.

Aloe vera is commonly used as traditional medicine for cutaneous wound healing. Nonetheless, the wound healing mechanisms of Aloe vera remain unclear. This review aims to provide insight into the molecular mechanisms of Aloe vera in promoting cutaneous wound healing, with particular emphasis on the mechanisms that stimulate cell proliferation and migration. Aloe vera has been shown to upregulate growth factors such as keratinocyte growth factor-1 (KGF-1), transforming growth factor-β (TGF-β), cyclin D1, insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and microfibril-associated glycoprotein 4 (MFAP4), as well as collagen, fibrillin, elastin, α-smooth muscle actin (α-SMA), integrins, and platelet endothelial cell adhesion molecule 1 (PECAM-1, also known as CD31), while downregulating the expression of matrix metalloproteinases (MMPs). In addition, Aloe vera was also found to upregulate PI3K/Akt and MAPK pathways, as well as the TGF-β signalling pathway via Smad proteins. Furthermore, molecular docking studies revealed that certain chemical constituents of Aloe vera bind to some of the forementioned growth factors or signalling molecules. With regards to current applications, although human clinical trials have reported positive results from using Aloe vera in healing open wounds and burns and alleviating some inflammatory skin diseases, the current commercial uses of Aloe vera remain largely focused on cosmetic products. Thus, greater advances are required to promote the use of Aloe vera products in clinical settings.

Associations of Circulating Platelet Endothelial Cell Adhesion Molecule-1 Levels With Progression of Cerebral Small-Vessel Disease, Cognitive Decline, and Incident Dementia.

The association between platelet endothelial cell adhesion molecule-1 (PECAM-1) with cerebral small-vessel disease and cognition in dementia-free subjects remains uninvestigated. A prospective cohort of dementia-free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice-yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM-1 levels with cerebral small-vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function Z scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM-1 levels were 0.790 (interquartile range, 0.645-0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM-1 tertile had greater cross-sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67-9.01]; P=0.023), age-related white matter change scores (β=1.39 [95% CI, 0.12-2.67]; P=0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19-5.62]; P=0.016). Of the 204 participants with follow-up data (median, 60.0 [interquartile range, 60.0-60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM-1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35-15.13]; P=0.024; second tertile: AHR, 3.28 [95% CI, 1.02-10.60]; P=0.047). The lowest PECAM-1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06-8.24]; P=0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05-4.65]; P=0.036), and decline in executive function (β=-0.45 [95% CI, -0.76 to -0.14]; P=0.004), and Montreal Cognitive Assessment (β=-1.32 [95% CI, -2.30 to -0.35]; P=0.008) scores. In dementia-free subjects, lower circulating PECAM-1 levels are associated with greater cerebral small-vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.

Evaluating the Biodegradability and Cellular Compatibility of Mg-Zn-Nd Alloy for Vascular Stent Application.

The study is designed to evaluate the corrosion behavior, biocompatibility, and cytotoxicity of a novel magnesium alloy, Mg-2Zn-0.5Nd (ZN20), for potential use as biodegradable scaffolding in cerebrovascular stents. Magnesium alloy (AZ31) and ZN20 are co-cultured with Human Umbilical Vein Endothelial Cells (HUVEC)and human neuroblastoma cell (SH-SY5Y), respectively. The corrosion of AZ31 and ZN20 in different time periods is detected by electron microscope, the effects of AZ31 and ZN20 on the expression level of inflammatory factors are detected by ELISA, the PH value of cells in each group is detected, and the cell proliferation is detected by cck-8. Cell-related apoptosis protein, the expression of Platelet endothelial cell adhesion molecule-1 (CD31)and VE-cad is detected, and the pathological analysis of rat vascular tissue is carried out by HE experiment. In contrast to the AZ31 group, ZN20 exhibits mild, uniform corrosion and does not significantly deter HUVEC proliferation or increase inflammatory markers and In vivo testing reveals better endothelization with ZN20, as demonstrated by higher expression of endothelial markers CD31, and intact endothelial structure group. Western blotting shows favorable expression levels of apoptotic and anti-apoptotic markers in the ZN20 group. ZN20 alloy demonstrates enhanced corrosion resistance, favorable endothelial compatibility, and reduced cytotoxicity, endorsing its safe application in vascular stent use.

Maternal supplementation spermidine during gestation improves placental angiogenesis and reproductive performance of high prolific sows

Spermidine (SPD) is a widely recognized polyamine compound found in mammalian cells and plays a key role in various cellular processes. We propose that SPD may enhance placental vascular development in pregnant sows, leading to increased birth weight of piglets. Six hundred and nine sows at 60 days of gestation were randomly assigned into a basal diet (CON group), basal diet supplemented 10 mg/kg of SPD (SPD1 group), and basal diet supplemented 20 mg/kg of SPD (SPD2 group), respectively. Compared with the CON, SPD1 significantly increased the average number of healthy piglets per litter and the placental efficiency (P < .05), while the average number of mummified fetus per litter and the percentage of weak piglets significantly decreased (P < .05). In the plasma metabolomics, SPD content in plasma of sows (P = .075) and umbilical cord plasma of piglets (P = .078) had an increasing trend in response to SPD1. Furthermore, SPD1 increased the expression of the vascular endothelial cell marker protein, platelet endothelial cell adhesionmolecule-1 (PECAM-1/CD31) and the density of placental stromal vessels (P < .05). Moreover, as compared to CON, SPD2 significantly decreased the average number of mummified fetus per litter (P < .05), while the placental efficiency and the expression of amino acid transporter solute carrier (SLC) family 7, member7 (SLC7A7) and glucose transporters SLC2A2) and SLC5A4 in placental tissue significantly increased (P < .05). These results suggest that maternal supplementation of SPD during pregnancy increased healthy litter number, and promoted placental tissue development. Our findings provide evidence that maternal SPD has the potential to improve the production performance of sows.

Engineered Biomimetic Nanoparticles-Mediated Targeting Delivery of Allicin Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Ferroptosis.

Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed. In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR. We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression. Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction.

Reprogramming metabolic microenvironment for nerve regeneration via waterborne polylactic acid-polyurethane copolymer scaffolds

Cell metabolism, as the key driver of inflammation, revascularization and even subsequent tissue regeneration, is controlled by and also conversely influenced by signal transduction. Incorporation of cell metabolism into tissue engineering research holds immense potential for in-situ treatment repair and further understanding of the host-biomaterial cues in body response. In this study, an anti-inflammatory waterborne polyurethane scaffold incorporated with poly-l-lactic acid (PLLA) block was served to repair nerve injuries (LAx-WPU). Lactate was released through the degradation of LAx-WPU scaffolds, and the content increased with the addition of PLLA block over the degradation times. Thenceforth, the production of adenosine triphosphate (ATP) in primary neurons and neuronal axon growth were achieved by taking up lactate through monocarboxylate transporters (MCT2) for energy metabolism under glucose-free environment treated with LAx-WPU degradation solution. After LAx-WPU was implanted to repair brain nerve defects in rats, filamentous neurons elongation, rapid vascularization, and nerve tissue regeneration were realized up to 28 days with the positive expression of microtubule-associated protein (MAP2), β-tubulin (Tuj1), and platelet endothelial cell adhesion molecule (CD31) in the scaffolds. Results highlighted that the LAx-WPU scaffolds up-regulated not only the ATP-ADP-AMP purine metabolism compounds to mainly bridge neuroactive ligand-receptor interaction genes, cAMP pathway genes, and calcium pathway genes for neurocytes but also the ATP-GMP purine metabolism to angiogenesis in Gene Ontology (GO) analysis. Further analysis in reverse showed axonal regeneration is restrained by the inhibition of MCT2, proving LAx-WPU promoted nerve repair depended on lactate for energy. Therefore, LAx-WPU scaffolds construct an expected way to modulate the metabolic microenvironment for inducing nerve regeneration by intrinsic biomaterial metabolism cues without any bioactive factors.

Serum EpCAM or PECAM Levels and Risk of Ischemic Stroke: A Two-Sample Mendelian Randomization Study.

Elevated serum Epithelial cell adhesion molecule (EpCAM) or Platelet endothelial cell adhesion molecule (PECAM) are associated with ischemic stroke (IS), but the causality remains unclear. A two-sample Mendelian randomization (MR) study was performed to examine the causal effect of serum EpCAM or PECAM levels on the risk of IS subtypes.The study utilized GWAS datasets from European and African American populations to identify SNPs associated with serum EpCAM and PECAM levels as instrumental variables. These were then used in MR analyses for IS subtypes, employing multiple methods including IVW, weighted median, MR-Egger, and maximum likelihood. Sensitivity analyses were conducted to validate the results. No significant causal association was observed for EpCAM levels with any of three IS subtypes. Main IVW MR analysis indicated that serum PECAM levels were negatively related to the incidence of large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES), especially CES. Sensitivity analyses confirmed the robustness of these results. Our study reveals a negative correlation between genetically predicted PECAM levels and ischemic stroke risk, particularly for cardioembolic stroke, suggesting PECAM's potential as a biomarker for risk stratification. While no clear causal relationship was found for EpCAM, these findings have significant implications for stroke prevention and treatment strategies. Further research is needed to validate these results and explore their clinical applications, potentially leading to more personalized approaches in stroke management.

NIR stimulated epigallocatechin gallate loaded polydopamine with enhanced antibacterial and ROS scavenging abilities for improved infectious wound healing

Infectious wound healing is complicated with and limited by infection and oxidative stress at the wound site. In recent years, various evidences suggest that nanozymes with multiple enzymatic activities have enabled the development of novel strategies for infectious wound healing. In this study, epigallocatechin gallate loaded polydopamine (P@E) was developed to act as a potent reactive oxygen species (ROS) scavenger for scavenging ROS, alleviating inflammatory responses, and promoting infectious wound healing. Combining with near infrared (NIR) irradiation, P@E presented excellent antibacterial ability of Escherichia coli (E. coli, 93.6%) and methicillin-resistant Staphylococcus aureus (MRSA, 87.6%). Specifically, P@E+NIR exhibited the most potent antioxidant, anti-inflammatory and cell proliferation behaviors through down-regulating intracellular ROS levels (81.9% and 94.3% for NIH3T3 and RAW264.7 respectively) and inducible nitric oxide synthase (iNOS) expression level (55.7%), and up-regulating the expression levels of arginase-1 (Arg-1, 71.4%), heat shock protein 70 (HSP70, 48.6%) and platelet endothelial cell adhesion molecule (CD31, 35.3%) compared to control group. Meanwhile, it also efficiently induced M2 directional polarization of lipopolysaccharide induced murine macrophages to achieve anti-inflammation, indicated by the down-regulation of CD86 (86.2%), and up-regulation of CD206 (85.6%). Significantly, it was also observed that P@E+NIR presented the excellent behaviors of inhibiting wound infection, alleviating wound inflammation, as well as promoting skin tissue repairing. Altogether, it has developed the strategy of using P@E combining with NIR irradiation for the synergistic enhanced healing of infectious skin wound, which can serve as a promising therapeutic strategy for its clinical treatment.

NLRP3 inhibitor combined with Yimusake improves erectile dysfunction in rats with diabetes mellitus through the attenuation of pyroptosis

Erectile dysfunction (ED) is a prevalent complication associated with diabetes mellitus (DM), yet pharmacological treatments for diabetes-related erectile dysfunction (DMED) continue to be inadequate in clinical settings. Our previous studies have indicated that there is a close correlation between ED and pyroptosis, but the specific mechanism remains unclear. In this study, we sought to explore the therapeutic effects of DMED through the modulation of NLRP3, aiming to elucidate its potential molecular mechanisms. The DMED rat model was established via intraperitoneal injection of streptozotocin. The rats were randomly assigned to the control group, the DMED group, the Yimusake group, the MCC950 (NLRP3 inhibitor) group, and the MCC950+Yimusake group. Erectile function of rats was observed by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). HE staining was performed to observe the histopathological changes in penile; immunofluorescence was performed to measure the level of CD31 (Platelet endothelial cell adhesion molecule-1) in penile. Besides, immunohistochemistry, RT-qPCR and Western blot were performed to demonstrate the expression of NLRP3, caspase-1, IL-1β and eNOS. After treatment with the MCC950 and Yimusake, the number of blood sinusoids and small vessels significantly reduced in penile tissue; NLRP3, caspase-1, IL-1β proteins and mRNA expression decreased, eNOS protein and mRNA expression increased. Compare with the Y group and the MCC950 group, MCC950+Yimusake group had a more significant effect. MCC950 and Yimusake might potentially suppress pyroptosis in the penile tissue of DMED rats by modulating the NLRP3/caspase-1 pathway, thus enhancing erectile function. This discovery could offer a promising therapeutic approach for individuals with DMED.

Amorphous zinc phosphate nanoclusters loaded polycarbonate thermosensitive hydrogel: An innovative strategy for promoting wound healing

Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.

Decreased levels of L-selectin and platelet-endothelial cell adhesion molecule-1 in children with autism spectrum disorder.

This study aimed to ascertain the serum levels of selectins (E, L, P) and platelet-endothelial adhesion molecule-1 (PECAM-1) in preschool children with autism spectrum disorder (ASD) and to establish a comparison with the levels observed in healthy controls. The study included 34 children aged 2-7 years diagnosed with ASD (ASD group) and 34 randomly selected healthy children matched for age and sex to the ASD group. The children were free of any genetic or physical disease, clinically active infection, or medication use. The sociodemographic data form was completed by all parents. The Childhood Autism Rating Scale (CARS) and the Autism Behavior Checklist (ABC) were administered to the patient group, and the Aberrant Behavior Checklist (AbBC) was completed by the families of all children. Serum selectin (E, L, P) and PECAM-1 levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. The results showed that the levels of both L-selectin (p = 0.007) and PECAM-1 (p = 0.019) were significantly lower in the ASD group than in the control group. No significant difference was observed between the groups concerning E-selectin and P-selectin levels (p > 0.05). It was observed that P-selectin variables were statistically significant in predicting the presence of ASD (p = 0.019). A remarkable inverse correlation was found between the AbBC irritability subscale score and L-selectin (r = -0.296, p = 0.014) and PECAM-1 (r = -0.276, p = 0. 023); the AbBC Lethargy-Social Withdrawal subscale score and E-Selectin (r = -0.239, p = 0.049), L-Selectin (r = -0.297, p = 0.014) and PECAM-1 (r = -0.264, p = 0.029); L-Selectin levels and the AbBC stereotypic behavior subscale (r = -0.248, p = 0.042). No statistically significant relationship was observed between selectins (E, L, P) and PECAM-1 levels and CARS scale, ABC subscale or total scores and age variables (p > 0.05). These study results suggest that L-selectin, P-selectin and PECAM-1 may play a role in the pathophysiology of ASD.

Differential effects of macrophage subtype-specific cytokines on fibroblast proliferation and endothelial cell function in co-culture system.

Macrophages are involved in several critical activities associated with tissue repair and regeneration. Current approaches in regenerative medicine are focusing on leveraging the innate immune response to accelerate tissue regeneration and improve long-term healing outcomes. Of particular interest in this regard are the currently known, four main M2 macrophage subtypes: M2interleukin (IL)-4,IL-13, M2IC, M2IL-10, M2non-selective adenosine receptor agonists (NECA) (M2IL-4,IL-13 → M2NECA). In this study, rat bone marrow-derived macrophages (M0) were polarized to each of the four subtypes M2IL-4,IL-13 → M2NECA and cultured for 72 h in vitro. Luminex assay results highlighted increased production of tissue inhibitor of metalloproteinases-1 (TIMP-1) for M2IL-4,IL-13, higher amounts of transforming growth factor-beta 1 (TGF-β1) for M2IL-10, and elevated vascular endothelial growth factor A (VEGF-A) from M2NECA. Co-culture experiments performed with M2IL-10 macrophages and L929 fibroblasts highlighted the increased production of soluble collagen within the media as well as higher amounts of collagen in the extracellular matrix. Human umbilical vein endothelial cells (HUVECs) were co-cultured with M2NECA macrophages, which demonstrated an increase in intercellular adhesion molecule (ICAM) and platelet endothelial cell adhesion molecule (PECAM), as well as increased formation of endothelial tubes. The findings of this study emphasize a critical demand for further characterization and analyses of distinct M2 subtypes and careful selection of specific macrophage populations for regeneration of specific tissue types. The current, broad classification of "M2" may be sufficient in many general tissue engineering applications, but, as conditions are constantly in flux within the microenvironment in vivo, a higher degree of specificity and control over the initial M2 subtype could result in more consistent long-term outcomes where macrophages are utilized as part of an overall regenerative strategy.

Enhanced diabetic foot ulcer treatment with a chitosan-based thermosensitive hydrogel loaded self-assembled multi-functional nanoparticles for antibacterial and angiogenic effects

Inhibiting bacterial growth and promoting angiogenesis are essential for enhancing wound healing in diabetic patients. Excessive oxidative stress at the wound site can also lead to an accumulation of reactive oxygen species. To address these challenges, a smart thermosensitive hydrogel loaded with therapeutic agents was developed. This formulation features self-assembled nanoparticles named CIZ, consisting of chlorogenic acid (CA), indocyanine green (ICG), and zinc ions (Zn2+). These nanoparticles are loaded into a chitosan-β-glycerophosphate hydrogel, named CIZ@G, which enables rapid gel formation under photothermal effects. The hydrogel demonstrates good biocompatibility and effectively releases drugs into diabetic foot ulcers (DFU) wound. Benefiting from the dual actions of CA and zinc ions, the hydrogel exhibits potent antioxidative and anti-inflammatory effects, enhances the expression of vascular endothelial growth factor (VEGF) and Platelet endothelial cell adhesion molecule-1 (CD31), and promotes angiogenesis. Both in vitro and in vivo experiments confirm that CIZ@G can effectively inhibit the growth of Staphylococcus aureus post-laser irradiation and accelerate wound remodeling within 14 days. This approach offers a new strategy for the treatment of diabetic foot ulcers (DFU), potentially transforming patient care in this challenging clinical area.

Mechanistic insights into the impact of WIN 55, 212-2, a synthetic cannabinoid, on adhesion molecules PECAM-1 and VE-cadherin in HeLa cells: implications on cancer processes

The endocannabinoid (eCB) system comprises endogenous ligands, cannabinoid receptors (CBRs), and their regulatory proteins; its alteration leads to many diseases including cancer. Thus, becomes a therapeutic target for synthetic cannabinoids aimed to control cancer cell proliferation, migration, adhesion, and invasion. However, little is known about adhesion molecules regulation through CBRs activation. The aim of this study was to evaluate the effects of a CB1/CB2 agonist, WIN-55, 212-2 (WIN), on the regulation of adhesion molecules platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial cadherin (VE-cadherin) in HeLa cells. CBRs expression was evaluated by immunofluorescence staining in HeLa cells and cell viability (thiazolyl blue tetrazolium bromide), cell adhesion (crystal violet), adhesion molecules expression and location (Western blot and immunofluorescence staining assays) were all assessed on cells treated with different WIN concentrations. Receptors CB1, CB2, and G-protein-coupled receptor 55 were expressed in HeLa cells. Additionally, biphasic effects were observed in their metabolic activity and adhesive properties: low WIN concentrations resulted in significant increases whereas, high ones decreased them compared to controls (p < 0.0001), demonstrating that WIN elicits opposite effects depending on the concentration and exposure time. PECAM-1 was detected in HeLa cell’s cytoplasm, membrane, and perinuclear region, whereas VE-cadherin had a nuclear distribution. There were no significant differences in PECAM-1 and VE-cadherin expression and location, suggesting that WIN does not modulate these proteins. These findings support the potential use of WIN due to its anticancer properties without dysregulating adhesion molecules. WIN possible contribution to inhibit cancer progression should be further investigated.

Multifunctional Chi-Ag@HMPB@CBD nanocomposites for eradicating multidrug-resistant bacteria and promoting diabetic damaged tissue repair

Injured tissues are vulnerable to polymicrobial infection, resulting in insufficient blood supply, excessive oxidative stress, and inflammation, seriously affecting skin regeneration. Therefore, there is an urgent need to develop effective strategies to treat multiple bacterial infections and damaged tissues and tissue repair for clinical treatment. Herein, we designed new nano-complexes of Chi-Ag@HMPB@CBD NPs via hollow mesoporous Prussian blue nanoparticles (HMPB NPs) loaded with cannabidiol (CBD) and chitosan-modified silver nanoparticles (Chi-Ag NPs) to treat multiple bacterial infected damaged tissues. In vitro experiments show that Chi-Ag@HMPB@CBD NPs synergizes with CBD and Chi-Ag NPs to effectively kill the mixture of Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) via disrupting the cell membranes and established biofilms. Meanwhile, Chi-Ag@HMPB@CBD NPs can decompose H2O2 and increase O2 levels, thereby alleviating microenvironmental hypoxia and protecting cells from oxidative stress damage. Moreover, Chi-Ag@HMPB@CBD NPs can promote Human Umbilical Vein Endothelial Cells (HUVECs) proliferation, migration, and neovascularization by inhibiting Matrix Metalloprotein-9 (MMP-9) expression. In vivo experiments show that Chi-Ag@HMPB@CBD NPs exhibit high efficacy against mixed infections of E. coli and MRSA, accelerating damaged tissue repair via upregulating levels of Vascular Endothelial Growth Factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD31). Collectively, this study demonstrates that Chi-Ag@HMPB@CBD NPs are versatile nanomaterials with a great potential in clinical treatment of mixed bacterial-infected damaged tissue repair.

Insulin-Induced Gene 1-Enhance Secretion of BMSC Exosome Enriched in miR-132-3p Promoting Wound Healing in Diabetic Mice.

Chronic diabetic wounds represent a significant clinical challenge because of impaired healing processes, which require innovative therapeutic strategies. This study explores the therapeutic efficacy of insulin-induced gene 1-induced bone marrow mesenchymal stem cell exosomes (Insig1-exos) in promoting wound healing in diabetic mice. We demonstrated that Insig1 enhanced the secretion of bone marrow mesenchymal stem cell-derived exosomes, which are enriched with miR-132-3p. Through a series of in vitro and in vivo experiments, these exosomes significantly promoted the proliferation, migration, and angiogenesis of dermal fibroblasts under high-glucose conditions. They also regulated key wound-healing factors, including matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-β1, and platelet endothelial cell adhesion molecule-1, thereby accelerating wound closure in diabetic mice. Histological analysis showed that Insig1-exos were more effective in promoting epithelialization, enhancing collagen deposition, and reducing inflammation. Additionally, inhibition of miR-132-3p notably diminished these therapeutic effects, underscoring its pivotal role in the wound-healing mechanism facilitated by Insig1-exos. This study elucidates the molecular mechanisms through which Insig1-exos promotes diabetic wound healing, highlighting miR-132-3p as a key mediator. These findings provide new strategies and theoretical foundations for treating diabetes-related skin injuries.

LAIR-1 and PECAM-1 function via the same signaling pathway to inhibit GPVI-mediated platelet activation

BackgroundInhibition of platelet responsiveness is important for controlling thrombosis. It is well established that platelet endothelial cell adhesion molecule-1 (PECAM-1) serves as a physiological negative regulator of platelet-collagen interactions. We recently demonstrated that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a negative regulator of platelet production and reactivity. It is however not known if LAIR-1 and PECAM-1 function in the same or different inhibitory pathways. ObjectivesIn this study, we investigated the role of LAIR-1 alongside PECAM-1 in megakaryocyte development and platelet production and determined the functional redundancy through characterization of a LAIR-1/PECAM-1 double knockout (DKO) mouse model. MethodsLAIR-1 and PECAM-1 expression in megakaryocytes were evaluated by western blotting. Megakaryocyte ploidy and proplatelet formation were evaluated by flow cytometry and fluorescent microscopy. Platelet function and signalling were compared in wild-type, LAIR-1−/−, PECAM-1−/− and DKO mice using aggregometry, flow cytometry and western blotting. Thrombosis was evaluated using the FeCl3 carotid artery model. ResultsWe show that LAIR-1/PECAM-1 DKO mice exhibit a 17% increase in platelet count. Bone marrow-derived megakaryocytes from all 3 mouse models had normal ploidy in vitro, suggesting that neither LAIR-1 nor PECAM-1 regulates megakaryocyte development. Furthermore, relative to wild-type platelets, platelets derived from LAIR-1, PECAM-1, and DKO mice were equally hyperresponsive to collagen in vitro, indicating that LAIR-1 and PECAM-1 participate in the same inhibitory pathway. Interestingly, DKO mice exhibited normal thrombus formation in vivo due to DKO mouse platelets lacking the enhanced Src family kinase activation previously shown in platelets from LAIR-1-deficient mice. ConclusionFindings from this study reveal that LAIR-1 and PECAM-1 act to inhibit GPVI-mediated platelet activation via the same signaling pathway. Mice lacking LAIR-1 and PECAM-1 do not however exhibit an increase in thrombus formation despite minor increase in platelet count and reactivity to collagen. This study adds to the growing evidence that immunoreceptor tyrosine-based inhibition motif–containing receptors are important regulators of platelet count and function.

Elucidating the molecular basis of PECAM-1 and Tie2 interaction from binding dynamics and complex formation

BackgroundEndothelial hyperpermeability-induced vascular dysfunction is a prevalent and significant characteristic in critical illnesses such as sepsis and other conditions marked by acute systemic inflammation. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and Tie2 serve as transmembrane receptors within endothelial cells (ECs), playing pivotal roles not only in maintaining EC-EC junctions but also in influencing vasculogenesis, vessel homeostasis, and vascular remodeling. ObjectivesAt present, the molecular basis of the PECAM-1-Tie2 interaction remains inadequately elucidated. In the study, recombinant soluble PECAM-1 (sPECAM-1) and Tie2 (sTie2) were expressed by Drosophila S2 and HEK293 expression systems, respectively. The interactions between sPECAM-1 and sTie2 were investigated using the Surface Plasmon Resonance (SPR) and size-exclusion chromatography methods. An immunofluorescence assay was used to detect the binding of sPECAM-1 and sTie2 on endothelial cells. ResultsPECAM-1 was found to bind with sTie2 in a sodium and pH-dependent manner as confirmed by the ELISA, the D5-D6 domains of PECAM-1 might play a crucial role in binding with sTie2. Surface Plasmon Resonance (SPR) results showed that the full length of sPECAM-1 has the strongest binding affinity (KD = 48.4 nM) with sTie2, compared to sPECAM-1-D1-D4 and sPECAM-1-D1-D2. This result is consistent with that in the ELISA. In addition, size-exclusion chromatography demonstrated that sPECAM-1, sTie2, and Ang1 can form a ternary complex. ConclusionIn this study, we determined that sPECAM-1 binds to sTie2 in a pH and sodium-dependent manner. The full length of sPECAM-1 has the strongest binding affinity, and the D5-D6 domains in sPECAM-1 play a crucial role in the interaction between sPECAM-1 and sTie2.

Effects of Sweetgum Oil on Experimental Chronic Gastritis in Rat Model

Background: Sweetgum oil has been traditionally used to treat wounds, respiratory tract problems, osteoarthritis and various stomach ailments. In this study, the effects of sweetgum oil on ethanol-induced chronic gastritis in rats were investigated. Methods: Thirty Wistar albino rats were divided into 5 groups. Group 1 served as control and received no treatment. Except for control, all animals received oral doses of 8 g/kg of 56% ethanol twice a week for 4 weeks to induce gastritis. Group 2, the ethanol group received only ethanol. Group 3 was treated with the conventional treatment of 20 mg/kg omeprazole daily for 2 weeks. Group 4 was treated with 150 mg/kg of sweetgum oil dissolved in olive oil daily for 2 weeks. Group 5 was treated orally with 0.6 ml olive oil daily for 2 weeks. Result: Histopathological and immunohistochemical examinations were performed on the stomach samples. Ethanol caused severe erosive ulcerative lesions in the gastric mucosa and inflammatory cell infiltrations in the propria mucosa. In immunohistochemical examination, marked increases in interleukin-10 (IL-10), interleukin-1β (IL-β) and platelet endothelial cell adhesion molecule 1 (PECAM-1) expressions were observed in this group. Omeprazole treatment significantly reduced these pathological findings. Sweetgum oil provided significant improvement in histopathological and immunohistochemical findings, but the protection was not as effective as omeprazole. Moderate healing effects were also observed with olive oil. Sweetgum oil has a curative effect on chronic gastritis, although it is not as effective as omeprazole. Moreover, olive oil has a curative effect on gastritis.

Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial Permeability and Sepsis Severity.

Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability. Herein, we investigated the possible association between EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) and endothelial permeability and sepsis severity. Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) directly or after pretreatment with permeability-modifying reagents such as angiopoietin-1, prostacyclin, or vascular endothelial growth factor (VEGF) to alter TNF-α-induced endothelial hyperpermeability. Endothelial permeability was measured using the dextran assay or transendothelial electrical resistance. Additionally, a prospective cross-sectional observational study was conducted to analyze circulating EDEV levels in patients with sepsis. EDEVs were examined in HUVEC culture supernatants or patient plasma (nonsepsis, n = 30; sepsis, n = 30; septic shock, n = 42) using flow cytometry. The Wilcoxon rank-sum test was used for comparisons between 2 groups. Comparisons among 3 or more groups were performed using the Steel-Dwass test. Spearman's test was used for correlation analysis. Statistical significance was set at P < .05. TNF-α stimulation of HUVECs significantly increased EDEV release and endothelial permeability. Pretreatment with angiopoietin-1 or prostacyclin suppressed the TNF-α-induced increase in endothelial permeability and inhibited the release of PECAM+ and VE-cadherin+ EDEVs. In contrast, pretreatment with VEGF increased TNF-α-induced endothelial permeability and the release of PECAM+ and VE-cadherin+ EDEVs. However, pretreatment with permeability-modifying reagents did not affect the release of EDEVs expressing inflammatory stimulus-inducible endothelial adhesion molecules such as E-selectin, intracellular adhesion molecule-1, or vascular cell adhesion molecule-1. The number of PECAM+ EDEVs on admission in the septic-shock group (232 [124, 590]/μL) was significantly higher (P = .043) than that in the sepsis group (138 [77,267]/μL), with an average treatment effect of 98/μL (95% confidence interval [CI], 2-270/μL), and the number of VE-cadherin+ EDEVs in the septic-shock group (173 [76,339]/μL) was also significantly higher (P = .004) than that in the sepsis group (81 [42,159]/μL), with an average treatment effect (ATE) of 79/μL (95% CI, 19-171/μL); these EDEV levels remained elevated until day 5. EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.