Vascular Conditions Research Articles

Ultrasonic registration of myopic changes in the eye of Japanese quail chicks raised under the different spectrum of everyday illumination

Abstract High-resolution ultrasound techniques are employed in ophthalmology for detecting age-related changes in the eyeball’s structure, diagnosing tumours and vascular conditions. Meanwhile, acoustic microscopy methods are widely used in laboratory animal research. Our experiments utilised a short ultrasonic pulse (30-80 MHz) and B/Z-scan mode with dynamic focusing. This study utilised these parameters to measure various ocular dimensions, including the longitudinal and transverse size of the eyeball, the thickness of the lens, and the scleral-cornea, vitreous and chorioretinal complex. The sample comprised individuals of varying ages, an adult bird (65 days), and chicks across four age stages (10, 23, 36, 45 days), all studied in situ. The method enabled observation of age-related alterations in ocular structures throughout the ontogenesis of the animal, illuminated daily using an incandescent lamp alongside yellow and blue light filters. The outcomes illustrate that the measurement technique’s sensitivity detects an anterior-posterior axis (APA) escalation of quail eyes with an error range of ±15 microns. The method’s sensitivity adequately analysed the impact of the spectral composition of everyday lighting on deviations in eye development.

Vascular disease and ischemic stroke in patients with atrial fibrillation: Temporal trends and age-related differences

Background and aimsWe examined temporal trends and age-related differences in the prevalence of vascular diseases and in their association with ischemic stroke (IS) risk in patients with atrial fibrillation (AF). MethodsThe registry-based FinACAF study covered all patients with AF in Finland during 2007–2018. Incidence rate ratios (IRRs) of IS were computed with Poisson regression, and the interaction of vascular diseases with age and calendar year period was assessed. ResultsWe identified 229,565 patients (50.0 % female; mean age 72.7 years) with incident AF. The overall prevalence of any vascular disease was 28.6 %, and the prevalence increased from 2007 to 2018, primarily among patients over 75 years. Overall, 5909 (2.6 %) patients experienced IS within the first year after AF diagnosis. Crude IS rate decreased continuously during the study period in both patients with and without vascular diseases, with the rates remaining consistently higher in patients with vascular diseases. Vascular diseases were independently associated with higher IS incidence among patients under 65 years (adjusted IRR with 95 % confidence interval 1.35 (1.10–1.66)), while among older patients, only peripheral artery disease was associated with IS, and other vascular conditions had no association with IS. No interactions between the calendar year period and vascular diseases with IS rate were observed. ConclusionsThe association between vascular diseases and IS has remained stable over time and vascular diseases were independently associated with higher incidence of IS particularly in patients with AF under the age of 65.

Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks.

Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE. We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses. We found that 196, 115, and 74 metabolites were associated (P<0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD. While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds.

Elevation and distraction of the Tibial periosteum in the management of chronic ischemic lower limb diseases.

This study investigates the effectiveness of tibia periosteum distraction (TPD) applied to the tibial periosteum, an innovative approach grounded in Ilizarov's tension-stress theory, for the treatment of ischemic diabetic foot and vasculitic foot conditions. A retrospective analysis was conducted on 33 patients (36 limbs) who underwent TPD between June 2019 and May 2022. The study comprised 21 males (23 limbs) and 12 females (13 limbs), aged 41 to 80 years (mean age: 63.4 years). Diabetic foot accounted for 27 cases, thromboangiitis obliterans for 2 cases, and arterial occlusive disease for 4 cases. The distribution of affected limbs included 15 left feet and 21 right feet. Periosteum traction commenced on the third postoperative day at a rate of approximately 0.75mm/day, adjusted biweekly. The traction device was removed after two weeks. Evaluation included capillary refill and wound healing assessment, along with pre- and postoperative analysis of foot skin temperature, ankle-brachial index (ABI), visual analogue scale (VAS) pain scores, and peripheral blood oxygen saturation. CT angiography (CTA) was utilized to assess vascular conditions in both lower limbs. All 33 patients were successfully followed up for a duration ranging from 4 to 24 weeks (mean: 11.03 weeks). VAS pain scores significantly decreased from preoperative (5.09 ± 1.70, range: 2-8) to postoperative two weeks (2.24 ± 0.90, range: 1-4) (t = 9.44, p < .001). Oxygen saturation levels increased from 83.88% ± 11.82% (range: 58%-97%) preoperatively to 91.36% ± 5.69% (range: 76%-98%) at two weeks postoperatively (t = -4.21, p < .001). Foot skin temperature also showed a significant increase (t = -3.98, p < .001). Capillary refill test at two weeks postoperatively demonstrated notable improvement. CTA revealed evident neovascularization in the operated limbs compared to preoperative conditions. Wound improvement was significant in all 33 patients within two months postoperatively. TPD emerges as a promising technique for chronic ischemic lower limb diseases, demonstrating favorable preliminary outcomes in wound healing promotion and amputation rate reduction. Nevertheless, large-scale randomized controlled trials are essential to further validate its efficacy.

Dermatophlebology: Understanding dermal responses to venous disease.

Dermatophlebology refers to the study of dermal alterations that occur with transmitted high venous pressure. These changes may range from telangiectasia, complex dermal vascular conditions, and all changes in Clinical Etiology Anatomical Pathophysiology classes IV-VI. Understanding the underlying pathophysiology is essential to treating the skin manifestations of venous disease.

S-adenosyl-L-methionine supplementation alleviates aortic dissection by decreasing inflammatory infiltration

Methionine, an indispensable amino acid crucial for dietary balance, intricately governs metabolic pathways. Disruption in its equilibrium has the potential to heighten homocysteine levels in both plasma and tissues, posing a conceivable risk of inducing inflammation and detriment to the integrity of vascular endothelial cells. The intricate interplay between methionine metabolism, with a specific focus on S-adenosyl-L-methionine (SAM), and the onset of thoracic aortic dissection (TAD) remains enigmatic despite acknowledging the pivotal role of inflammation in this vascular condition. In an established murine model induced by β-aminopropionitrile monofumarate (BAPN), we delved into the repercussions of supplementing with S-adenosyl-L-methionine (SAM) on the progression of TAD. Our observations uncovered a noteworthy improvement in aortic dissection and rupture rates, accompanied by a marked reduction in mortality upon SAM supplementation. Notably, SAM supplementation exhibited a considerable protective effect against BAPN-induced degradation of elastin and the extracellular matrix. Furthermore, SAM supplementation demonstrated a robust inhibitory influence on the infiltration of immune cells, particularly neutrophils and macrophages. It also manifested a notable reduction in the inflammatory polarization of macrophages, evident through diminished accumulation of MHC-IIhigh macrophages and reduced expression of inflammatory cytokines such as IL1β and TNFα in macrophages. Simultaneously, SAM supplementation exerted a suppressive effect on the activation of CD4 + and CD8 + T cells within the aorta. This was evidenced by an elevated proportion of CD44- CD62L + naïve T cells and a concurrent decrease in CD44 + CD62L- effector T cells. In summary, our findings strongly suggest that the supplementation of SAM exhibits remarkable efficacy in alleviating BAPN-induced aortic inflammation, consequently impeding the progression of thoracic aortic dissection.

EUS-Guided Vascular Interventions: Recent Advances.

Endoscopic ultrasound (EUS)-guided vascular interventions were first reported in 2000 in a study that evaluated the utility of EUS in sclerotherapy of esophageal varices. Currently, gastric variceal therapy and portosystemic pressure gradient (PPG) measurements are the most widely utilized applications. Ectopic variceal obliteration, splenic artery embolization, aneurysm/pseudoaneurysm treatment, portal venous sampling, and portosystemic shunt creation using EUS are some of the other emerging interventions. Since the release of the American Gastroenterological Association (AGA)'s commentary in 2023, which primarily endorses EUS-guided gastric variceal therapy and EUS-PPG measurement, several new studies have been published supporting the use of EUS for various vascular conditions. In this review, we present the recent advances in this field, critically appraising new studies and trials.

Clinical features of pulmonary hypertension in lymphangioleiomyomatosis

Objective: To describe the prevalence of lymphangioleiomyomatosis-pulmonary hypertension (LAM-PH), to explore the clinical features of patients with LAM-PH, and to evaluate the role of pulmonary artery optical coherence tomography (OCT) in the diagnosis of LAM-PH. Methods: Among 234 patients diagnosed with LAM in our center from June 2017 to August 2023, echocardiography was performed in 167 patients, 15 patients with PH indicated by echocardiography were selected as the LAM-PH group. From the remaining 152 patients, 32 patients were randomly selected as the control group. We compared the demographic data, clinical manifestations, pulmonary function, blood gas analysis, and serum vascular endothelial growth factor D (VEGF-D) levels between the two groups. We also evaluated the data from right heart catheterization in five patients and the images from optical coherence tomography of pulmonary arteries in two patients. Results: Echocardiography showed pulmonary hypertension in 15 patients (8.98%). Compared with the control group, LAM-PH group had a higher proportion of patients receiving oxygen therapy. Patients with PH had lower FEV1, FVC, FEV1/FVC, DLCO and higher serum VEGF-D levels compared with those without PH. Right heart catheterization was performed in five patients. Five patients had a pre-capillary pattern and three of these patients had severe pulmonary hypertension. Optical coherence tomography showed that there were no obvious abnormalities in the intima and lumen of the blood vessels in the two patients. Conclusions: The prevalence of PH in LAM is low. Patients in the LAM-PH group had more severe hypoxemia, worse lung function and higher serum VEGF-D levels than those in the control group. PH in LAM is mainly pre-capillary. Optical coherence tomography can evaluate the pulmonary artery vascular condition and help to identify the cause of pulmonary hypertension in LAM patients.

Age-Disturbed Vascular Extracellular Matrix Links to Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is a common but life-threatening vascular condition in men at an advanced age. However, the underlying mechanisms of age-increased incidence and mortality of AAA remain elusive. Here, we performed RNA sequencing (RNA-seq) of mouse aortas from males (young: 3-month, n = 4 vs old: 23-month, n = 4) and integrated with the data sets of human aortas (young: 20-39, n = 47 vs old: 60-79 years, n = 92) from GTEx project and the data set (GSE183464) for AAA to search for age-shifted aortic aneurysm genes, their relevant biological processes, and signaling pathways. Angiotensin II-induced AAA in mice was used to verify the critical findings. We found 1001 genes transcriptionally changed with ages in both mouse and human. Most age-increased genes were enriched intracellularly and the relevant biological processes included mitochondrial function and translational controls, whereas the age-decreased genes were largely localized in extracellular regions and cell periphery and the involved biological processes were associated with extracellular matrix (ECM). Fifty-one were known genes for AAA and found dominantly in extracellular region. The common age-shifted vascular genes and known aortic aneurysm genes had shared functional influences on ECM organization, apoptosis, and angiogenesis. Aorta with angiotensin II-induced AAA exhibited similar phenotypic changes in ECM to that in old mice. Together, we present a conserved transcriptional signature for aortic aging and provide evidence that mitochondrial dysfunction and the imbalanced ribosomal homeostasis act likely as driven-forces for aortic aging and age-disturbed ECM is the substrate for developing AAA.

Using Simulation Models to Train Clinicians in the Use of Point-of-Care Ultrasound.

The use of point-of-care ultrasound (POCUS) has shown to be a beneficial non-invasive vascular access assessment method by clinicians, which can provide critical elements of visual and measurable information that proves to be useful in the context of vascular access cannulation, in combination with the practical skill of the clinician performing the cannulation. However, the use of POCUS in this context is to practically train and enable individuals who are novices in using this technique to become proficient in performing this task subsequently on patients in a careful and successful way. The simulation of these vascular conditions may be useful to help healthcare professionals learn, understand, apply, and establish such practical skills for vascular cannulation safely to achieve the desired outcomes. This project intended, through the attendance of a half-day workshop, to establish skills to use POCUS in connection with simulation models and perform specific tasks to enable clinicians to use this method in their clinical practice for vascular access cannulation in patients. A mixed-methods longitudinal study design was used to evaluate the effect of a point-of-care ultrasound workshop for peripheral intravenous cannula insertion, including specific tasks for the participants to be performed on simulation models. A total of 81 individuals participated in 11 half-day workshops through 2021 and 2022. Offering a workshop that uses simulation models in combination with various POCUS devices is useful in establishing this newly learned skill in clinicians, such as measurements of depth, caliper, and direction of a vein with POCUS prior to cannulation providing essential anatomical facts to the operator, which increases the likelihood of first-time success in cannulation.

Patient height and American Society of Anesthesiologists class as significant risk factors for posterior fossa surgery in the semisitting position.

To optimize surgical positioning for posterior fossa surgery (PFS) using the semisitting position (SSP) to avoid venous air embolism (VAE) and its possible life-threatening consequences, the authors evaluated their experiences with the SSP by analyzing a large cohort of PFS patients. A retrospective analysis of the charts of 202 consecutive PFS patients (median age 54 years, IQR 41-61 years; 121 females) with various tumor or vascular conditions who underwent surgery in an SSP between 2019 and 2022 was performed. Age, sex, weight, height, BMI, American Society of Anesthesiologists (ASA) class, histology, duration of surgery, and length of hospital stay were assessed. Transesophageal echocardiography was used pre- and intraoperatively to monitor for and assess the degree of VAE. Altogether, VAE occurred in 30 of 202 (14.9%) patients, with clinically relevant VAE occurring in 14 of 202 (7%) patients. The grades of VAE were I, III, and IV in 16 (8%), 4 (2%), and 10 (5%) patients, respectively. Patient height (p = 0.04), ASA class (p = 0.03), and ASA class ≤ II (p = 0.02) remained the only preoperative statistically significant risk factors for intraoperative VAE, with a median height of 178 cm (IQR 172-184 cm) in patients with clinically relevant VAE compared with 170 cm (IQR 164-176 cm) in those without VAE. In summary, the data demonstrate that SSP can be used safely for PFS when taking special care to optimize positioning in tall and lower-grade ASA patients intraoperatively.

New Therapeutic Strategies in Retinal Vascular Diseases: A Lipid Target, Phosphatidylserine, and Annexin A5-A Future Theranostic Pairing in Ophthalmology.

Despite progress in the management of patients with retinal vascular and degenerative diseases, there is still an unmet clinical need for safe and effective therapeutic options with novel mechanisms of action. Recent mechanistic insights into the pathogenesis of retinal diseases with a prominent vascular component, such as retinal vein occlusion (RVO), diabetic retinopathy (DR) and wet age-related macular degeneration (AMD), may open up new treatment paradigms that reach beyond the inhibition of vascular endothelial growth factor (VEGF). Phosphatidylserine (PS) is a novel lipid target that is linked to the pathophysiology of several human diseases, including retinal diseases. PS acts upstream of VEGF and complement signaling pathways. Annexin A5 is a protein that targets PS and inhibits PS signaling. This review explores the current understanding of the potential roles of PS as a target and Annexin A5 as a therapeutic. The clinical development status of Annexin A5 as a therapeutic and the potential utility of PS-Annexin A5 as a theranostic pairing in retinal vascular conditions in particular is described.

Severe Circulatory Disturbance in Optic Disc, Retina, and Choroid Following Sub-Tenon Triamcinolone Acetonide Injection for Posterior Scleritis.

To report a rare case of optic disc and chorioretinal vascular occlusions in the right eye following sub-Tenon injection of triamcinolone acetonide (STTA) in an older male patient with scleritis and to discuss the associated risk factors and potential alternative therapies. The medical history and clinical examination, including fundoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), were conducted to diagnose and evaluate the extent of vascular occlusion after STTA. An extensive literature review was undertaken to ascertain the associated risks and consider other treatment options for scleritis. Severe circulatory disturbances in the optic disc and chorioretinal regions of the right eye developed after STTA for exacerbated scleritis, as confirmed by FA and ICGA, resulting in a significant decrease in visual acuity. A complex medical history encompassing ophthalmic and systemic health issues may have contributed to this negative outcome. A literature review pointed out the potential complications of STTA and highlighted alternative approaches to scleritis management. Cautious application of STTA in treating scleritis is crucial, especially in patients with pre-existing vascular or ocular conditions. Thus, a multidisciplinary approach and a careful assessment of various treatment options are vital to minimize the risk of severe complications and improve patient outcomes.

Association of neuroticism with incident dementia, neuroimaging outcomes, and cognitive function.

Higher neuroticism might be associated with dementia risk. Here we investigated modification by genetic predisposition to dementia, mediation by mental health and vascular conditions, neuroimaging outcomes, and cognitive function. Cox proportional-hazards models were used to assess the association between neuroticism score and incident dementia over up to 15 years in 1,74,164 participants. Cross-sectional analyses on dementia-related neuroimaging outcomes and cognitive function were conducted in 39,459 dementia-free participants. Higher neuroticism was associated with an 11% higher risk of incident dementia, especially vascular dementia (15% higher risk), regardless of genetic predisposition to dementia. Mental and vascular conditions mediated the association of neuroticism with all-cause dementia and vascular dementia. Neuroticism was associated with higher cerebrovascular pathology, lower gray matter volume, and worse function across multiple cognitive domains. Neuroticism could represent a risk factor for dementia, and vascular and mental health might drive these associations. Neuroticism was associated with an increased risk of incident all-cause dementia, particularly vascular dementia. Associations were not modified by genetic predisposition to dementia. Associations were largely mediated by mental and vascular conditions. Neuroticism was associated with increased cerebrovascular pathology and lower gray matter volume. Neuroticism was associated with worse function across multiple cognitive domains.

Dissecting the role of cannabinoids in vascular health and disease.

Cannabis, often recognized as the most widely used illegal psychoactive substance globally, has seen a shift in its legal status in several countries and regions for both recreational and medicinal uses. This change has brought to light new evidence linking cannabis consumption to various vascular conditions. Specifically, there is an association between cannabis use and atherosclerosis, along with conditions such as arteritis, reversible vasospasm, and incidents of aortic aneurysm or dissection. Recent research has started to reveal the mechanisms connecting cannabinoid compounds to atherosclerosis development. It is well known that the primary biological roles of cannabinoids operate through the activation of cannabinoid receptor types 1 and 2. Manipulation of the endocannabinoid system, either genetically or pharmacologically, is emerging as a promising approach to address metabolic dysfunctions related to obesity. Additionally, numerous studies have demonstrated the vasorelaxant properties and potential atheroprotective benefits of cannabinoids. In preclinical trials, cannabidiol is being explored as a treatment option for monocrotaline-induced pulmonary arterial hypertension. Although existing literature suggests a direct role of cannabinoids in the pathogenesis of atherosclerosis, the correlation between cannabinoids and other vascular diseases was only reported in some case series or observational studies, and its role and precise mechanisms remain unclear. Therefore, it is necessary to summarize and update previously published studies. This review article aims to summarize the latest clinical and experimental research findings on the relationship between cannabis use and vascular diseases. It also seeks to shed light on the potential mechanisms underlying these associations, offering a comprehensive view of current knowledge in this evolving field of study.

Sleep duration, chronotype, health and lifestyle factors affect cognition: a UK Biobank cross-sectional study

ObjectiveTo explore the nuanced relationship between sleep patterns, chronotype, quality and the influence of health and lifestyle factors on cognitive performance.Design, setting, participantsThis cross-sectional analysis used ordinary least squares regression...

A Fully Biodegradable and Ultra‐Sensitive Crack‐Based Strain Sensor for Biomechanical Signal Monitoring

AbstractA fully biodegradable, ultra‐sensitive, and soft strain sensor is pivotal for temporary, real‐time monitoring of microdeformations, crucial in disease diagnosis, surgical precision, and prognosis of muscular, and vascular conditions. Nevertheless, the strain sensitivity of previous biodegradable sensors, denoted by gauge factor (GF) up to ≈100, falls short of requirements for complex biomedical monitoring scenarios, specifically monitoring cardio‐cerebrovascular diseases with microscale variations in vascular surface strain. Here, a fully biodegradable, ultra‐sensitive crack‐based flexible strain sensor is introduced achieving GF of 1355 at 1.5% strain through integration of molybdenum (Mo) film, molybdenum trioxide (MoO3) adhesion layer, and polycaprolactone (PCL) substrate. Analysis of crack morphology of biodegradable thin‐film metals, including Mo, tungsten (W), and magnesium (Mg), reveals material‐dependent sensitivity and repeatability of crack‐based strain sensors. The effect of the adhesion layer and polymer substrate is also investigated. Overall morphological studies on the sensor present a comprehensive understanding of metal film cracking behavior and corresponding performance characterization, showing significant potential for highly sensitive sensors. A hybrid membrane composed of candelilla wax (Cw), beeswax (Bw), and polybutylene adipate‐co‐terephthalate (PBAT) is introduced to provide hydrophobic, yet flexible encapsulation. In vivo, short‐term (≈3 days) monitoring of vascular pulsatility underscores the potential of the sensing tool for rapid, accurate, and temporal disease diagnosis and treatment.

Stem cell-derived exosomes prevent the development of thoracic aortic aneurysm/dissection by inhibiting AIM2 inflammasome and pyroptosis

Thoracic aortic aneurysm/dissection (TAAD) is a severe vascular condition associated with life-threatening complications, and its underlying molecular mechanisms remain largely unexplored. Previous research indicates that the aberrant activation of cytosolic DNA and its receptors plays a crucial role in vascular inflammation and dysfunction. Specifically, Absent in Melanoma 2 (AIM2), an intracellular DNA receptor, can trigger the inflammasome pathway, leading to extracellular matrix destruction. In this investigation, we delved into the mechanism underlying AIM2 activation in TAAD development and explored the potential of exosomes to impede TAAD progression by suppressing AIM2 expression. Our findings revealed that heightened AIM2 expression and activation contribute to TAAD development by fostering vascular inflammation and disrupting vascular homeostasis. Activated AIM2 induces pyroptosis through the recruitment of the deubiquitination enzyme USP21, which stabilizes AIM2 by reducing its ubiquitination and degradation. Moreover, we demonstrated that exosome-derived miR-485-5p exerts an anti-inflammatory and protective effect on the thoracic aorta by inhibiting AIM2 activation. This study introduces novel perspectives for the treatment of TAAD.

Epstein-Barr virus causes vascular abnormalities in epithelial malignancies through upregulating ANXA3-HIF-1α-VEGF pathway.

Angiogenesis is one of the characteristics of malignant tumors, and persistent generation of abnormal tumor blood vessels is an important factor contributing to tumor treatment resistance. Epstein-Barr virus (EBV) is a highly prevalent DNA oncogenic virus that is associated with the development of various epithelial malignancies. However, the relationship between EBV infection and tumor vascular abnormalities as well as its underlying mechanisms is still unclear. In this study, we found that compared to EBV-uninfected tumors, EBV-infected tumors were more angiogenic, but the neovascularization was mostly immature vessels without pericyte attachment in both clinical patient tumor samples and mouse xenograft models; These immature vessels exhibited aberrant functionality, characterized by poor blood perfusion and increased vascular permeability. The vascular abnormalities caused by EBV infection exacerbated tumor hypoxia and was responsible for accelerated tumor growth. Mechanistically, EBV infection upregulated ANXA3-HIF-1α-VEGF pathway. Silencing the ANXA3 gene or neutralizing ANXA3 with an antibody can diminish vascular abnormalities, thereby increasing immune cell infiltration and alleviating treatment resistance. Finally, a new therapy combining ANXA3 blockade and NK cell + PD1 antibody significantly inhibited the growth of EBV-infected xenografts in mice. In conclusion, our study identified a previously unrecognized role for EBV infection in tumor vascular abnormalities and revealed its underlying mechanism that upregulated the ANXA3-HIF-1α-VEGF pathway. ANXA3 is a potential therapeutic target for EBV-infected tumors and ANXA3 blockade to improve vascular conditions, in combination with NK cell + PD1 antibody therapy, holds promise as an effective treatment strategy for EBV-associated epithelial malignancies.

MiR-483-5p-Containing exosomes treatment ameliorated deep vein thrombosis‑induced inflammatory response

Peripheral vascular condition, known as deep vein thrombosis (DVT), is a common ailment that may lead to deadly pulmonary embolism. Inflammation is closely connected to venous thrombosis, which results in blood stasis, leading to ischemia and hypoxia, as indicated by research. The objective of this research was to investigate the mechanism by which exosomes derived from adipose stem cells (ADSCs) prevent deep vein thrombosis.Our data showed that Exo-483 effectively reduced the thrombus weight in DVT rats by intravenous injection. Exo-483 decreased the expression of tissue factor (TF) protein, the influx of inflammatory cells into the thrombosed vein wall, and the levels of cytokines in the serum. Furthermore, Exo-483 suppressed the expression of Mitogen-activated protein kinase 1 (MAPK1) and decreased the expression of NLRP3 inflammasomes. In an oxygen-glucose deprivation (OGD) cell model, the tube-forming and migratory abilities of primary human umbilical vein endothelial cells (HUVEC) and EA.hy926 cells were suppressed by Exo-483 pretreatment.Exo-483 is also linked to regulating Dynamin-related protein 1 (DRP1) production downstream of MAPK1.By decreasing the mitochondrial localization and phosphorylation at the S616 site of DRP1, it diminishes the expression of NLRP3 inflammasomes. Moreover, according to Bioinformatics analysis, miR-483-5p was anticipated to target MAPK1.The research conducted by our team revealed that the miR-483-5p exosome derived from ADSCs exhibited anti-inflammatory properties through the modulation of downstream DRP1-NLRP3 expression by targeting MAPK1.The findings of this research propose that miR-483-5p may be regarded as an innovative treatment target for DVT.