Inhibiting histone deacetylase 6 suppresses the proliferation of microvascular endothelial cells by epigenetically activating miR-375-3p, potentially contributing to bone loss during mechanical unloading.

BACKGROUND: Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear. METHODS: We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRT‒PCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCK‒8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region. RESULTS: Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions. CONCLUSION: Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss.

Microvascular and cellular dysfunctions in Alzheimer's disease: an integrative analysis perspective.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by memory loss, cognitive decline, personality changes, and various neurological symptoms. The role of blood-brain barrier (BBB) injury, extracellular matrix (ECM) abnormalities, and oligodendrocytes (ODCs) dysfunction in AD has gained increasing attention, yet the detailed pathogenesis remains elusive. This study integrates single-cell sequencing of AD patients' cerebrovascular system with a genome-wide association analysis. It aims to elucidate the associations and potential mechanisms behind pericytes injury, ECM disorder, and ODCs dysfunction in AD pathogenesis. Finally, we identified that abnormalities in the pericyte PI3K-AKT-FOXO signaling pathway may be involved in the pathogenic process of AD. This comprehensive approach sheds new light on the complex etiology of AD and opens avenues for advanced research into its pathogenesis and therapeutic strategies.

Superb microvascular ultrasound is a promising non-invasive diagnostic tool to assess a ventriculoperitoneal shunt system function: a feasibility study.

The objective of this pilot study was to assess the reliability of superb microvascular ultrasound (SMI) for the measurement of the cerebrospinal fluid (CSF) flow within VPS systems as an indirect sign for shunt dysfunction. Asymptomatic hydrocephalus patients, with a VPS system implanted between 2017 and 2021, were prospectively enrolled in the study. Using SMI, the CSF flow within the proximal and distal catheters were analysed. Before and after pumping the shunt reservoir, intraabdominal free fluid, optical nerve sheath diameter (ONSD), and papilla diameter (PD) were evaluated and correlated with the amount of valve activation. Nineteen patients were included. A flow was detectable in 100% (N = 19) patients in the proximal and in 89.5% (N = 17) in the distal catheter. The distal catheter tip was detectable in 27.7% (N = 5) patients. Free intraabdominal fluid was initially detected in 21.4% (N = 4) patients and in 57.9% (N = 11) at the end of the examination (P = 0.049). ONSD was significantly lower after pump activation (4.4 ± 0.9 mm versus 4.1 ± 0.8 mm, P = 0.049). Both peak velocity and flow volume per second were higher in proximal compared to distal catheters (32.2 ± 45.2 versus 5.6 ± 3.7 cm/sec, P = 0.015; 16.6 ± 9.5 ml/sec versus 5.1 ± 4.0 ml/sec, P = 0.001, respectively). No correlation was found between the number of pump activations and the changes in ONSD (P = 0.975) or PD (P = 0.820). SMI appears to be a very promising non-invasive diagnostic tool to assess CSF flow within the VPS systems and therefore affirm their function. Furthermore, appearance of free intraperitoneal fluid followed by repeated compression of a shunt reservoir indicates an intact functioning shunt system.

Retinal microvascular changes in patients with pancreatitis and their clinical significance.

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Can microvascular damage predict disease severity in patients with systemic sclerosis?

INTRODUCTION: Systemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC). MATERIALS AND METHODS: A retrospective study of patients with SSc and a NVC performed within the first 6 months after diagnosis was conducted. Visceral involvement in the first 3 years of the disease and NVC findings were collected. The severity of microvascular damage was classified into four categories, according to the worsening of the NVC patterns. The severity of organ involvement was assessed by the disease severity scale of Medsger for each organ and as a global measure of disease severity, the simple summation was used. RESULTS: A total of 86 patients with SSc were included. A moderate correlation was found between the severity of microvascular damage and the global measure of disease severity (r=0.55, p<0.001), the severity of peripheral vascular involvement (r=0.43, p<0.001) and the severity of skin involvement (r=0.34, p=0.001). The presence of a late scleroderma pattern in NVC were predictive in univariate analysis of digital ulcers (OR 6.03, 95% CI 1.52-23.86, p=0.01), muscular involvement (OR 13.09, 95% CI 1.09-156.78, p=0.04), calcinosis (OR 27.22, 95% CI 5.56-133.33, p<0.001) and worse global disease severity score (OR 1.67, 95% CI 1.17-2.38, p=0.005). Multivariate analysis adjusted for disease duration and gender confirmed late pattern as an independent predictor of calcinosis (OR 42.89, 95% CI 5.53-332.85, p<0.001). DISCUSSION AND CONCLUSION: In this study, the worsening of NVC pattern in SSc was associated with the overall disease severity, the severity of peripheral vascular involvement and extension of skin involvement. This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement.

Multi-transcriptomics analysis of microvascular invasion-related malignant cells and development of a machine learning-based prognostic model in hepatocellular carcinoma.

Background: Microvascular invasion (MVI) stands as a pivotal pathological hallmark of hepatocellular carcinoma (HCC), closely linked to unfavorable prognosis, early recurrence, and metastatic progression. However, the precise mechanistic underpinnings governing its onset and advancement remain elusive. Methods: In this research, we downloaded bulk RNA-seq data from the TCGA and HCCDB repositories, single-cell RNA-seq data from the GEO database, and spatial transcriptomics data from the CNCB database. Leveraging the Scissor algorithm, we delineated prognosis-related cell subpopulations and discerned a distinct MVI-related malignant cell subtype. A comprehensive exploration of these malignant cell subpopulations was undertaken through pseudotime analysis and cell-cell communication scrutiny. Furthermore, we engineered a prognostic model grounded in MVI-related genes, employing 101 algorithm combinations integrated by 10 machine-learning algorithms on the TCGA training set. Rigorous evaluation ensued on internal testing sets and external validation sets, employing C-index, calibration curves, and decision curve analysis (DCA). Results: Pseudotime analysis indicated that malignant cells, showing a positive correlation with MVI, were primarily concentrated in the early to middle stages of differentiation, correlating with an unfavorable prognosis. Importantly, these cells showed significant enrichment in the MYC pathway and were involved in extensive interactions with diverse cell types via the MIF signaling pathway. The association of malignant cells with the MVI phenotype was corroborated through validation in spatial transcriptomics data. The prognostic model we devised demonstrated exceptional sensitivity and specificity, surpassing the performance of most previously published models. Calibration curves and DCA underscored the clinical utility of this model. Conclusions: Through integrated multi-transcriptomics analysis, we delineated MVI-related malignant cells and elucidated their biological functions. This study provided novel insights for managing HCC, with the constructed prognostic model offering valuable support for clinical decision-making.

Imaging and Quantification of the Hepatic Vasculature of Mice Using Ultrafast Doppler Ultrasound.

Non-invasive in vivo imaging of the vasculature is a powerful tool for studying disease mechanisms in rodents. To achieve high sensitivity imaging of the microvasculature using Doppler ultrasound methods, imaging modalities employing the concept of ultrafast imaging are preferred. By increasing the frame rate of the ultrasound scanner to thousands of frames per second, it becomes possible to improve the sensitivity of the blood flow down to 2 mm/s and to obtain functional information about the microcirculation in comparison to a sensitivity of around 1 cm/s in conventional Doppler modes. While Ultrafast Doppler ultrasound (UFUS) imaging has become adopted in neuroscience, where it can capture brain activity through neurovascular coupling, it presents greater challenges when imaging the vasculature of abdominal organs due to larger motions linked to breathing. The liver, positioned anatomically under the diaphragm, is particularly susceptible to out-of-plane movement and oscillating respiratory motion. These artifacts not only adversely affect Doppler imaging but also complicate the anatomical analysis of vascular structures and the computation of vascular parameters. Here, we present a qualitative and quantitative imaging analysis of the hepatic vasculature in mice by UFUS. We identify major anatomical vascular structures and provide graphical illustrations of the hepatic macroscopical anatomy, comparing it to an in-depth anatomical assessment of the hepatic vasculature based on Doppler readouts. Additionally, we have developed a quantification protocol for robust measurements of hepatic blood volume of the microvasculature over time. To contemplate further research, qualitative vascular analysis provides a comprehensive overview and suggests a standardized terminology for researchers working with mouse models of liver disease. Furthermore, it offers the opportunity to apply ultrasound as a non-invasive complementary method to inspect hepatic vascular defects in vivo and measure functional microvascular alterations deep within the organ before unraveling blood vessel anomalies at the micron scale levels using ex vivo staining on tissue sections.

Early and Late Treatment Influence on Chorioretinal Microvasculature in Vogt-Koyanagi-Harada Patients Using Optical Coherence Tomography Angiography.

Purpose: To study the impact of early and late treatment on chorioretinal microvasculature in Vogt-Koyanagi-Harada (VKH) disease using optical coherence tomography angiography (OCTA). Methods: A total of 103 patients with VKH disease were divided into early (group 1, starting treatment within 2 months after disease onset) and late (group 2, starting treatment 2 months after disease onset) treatment groups. Flow area (FA) and vessel density (VD) of the retinal superficial vascular complex (SVC) and deep vascular complex (DVC), FA of the choriocapillaris, three-dimensional choroidal vascular volume (CVV), and choroidal vascularity index (CVI) were analyzed and compared to 103 healthy individuals. The relationship between the final best-corrected visual acuity (BCVA) and the aforementioned parameters was also analyzed. Results: FA of the SVC (all P < 0.05, except 0-1 mm P = 0.087), DVC (all P < 0.05), choriocapillaris (1-2.5 mm P = 0.033), and CVV (all P < 0.05) were lower in group 2 as compared to group 1. Compared to healthy controls, FA of the SVC (all P < 0.001, except 0-1 mm P = 0.104) and DVC (all P < 0.05), VD of the SVC (1-2.5 mm P = 0.001) and DVC (1-5 mm P = 0.003, 2.5-5 mm P < 0.001), FA of the choriocapillaris (all P < 0.05), and CVV (total area P = 0.049, 1-5 mm P = 0.045, 2.5-5 mm P = 0.041) were lower in group 2, while FA (all P < 0.05, except 0-1 mm P = 0.925) and VD (1-5 mm P = 0.003, 2.5-5 mm P = 0.004) of the DVC and FA of the choriocapillaris (total area P = 0.007, 0-1 mm P < 0.001, 1-2.5 mm P = 0.007) were lower in group 1. There was no significant difference concerning CVI among groups (all P > 0.05). FA of the SVC, DVC, and choriocapillaris and VD of DVC and CVI were negatively associated with the final logarithm of the minimum angle of resolution BCVA. Conclusions: Patients with VKH disease who are treated within 2 months of disease onset showed a better chorioretinal microvascular outcome as defined by OCTA compared to those treated late. Translational Relevance: Our study employs OCTA to design three-dimensional metrics for the retina and choroid, bridging the gap between traditional two-dimensional OCTA findings and enhanced clinical outcomes for patients with VKH disease.

Dynamic optical coherence tomography unveils subclinical, vascular differences across actinic keratosis grades I-III.

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub-surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D-OCT) to characterize microvessels in AK I-III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I-III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D-OCT. On D-OCT, vessel shapes, -pattern and -direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D-OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty-seven patients with AK I-III (n = 207) and PD (n = 87) were included. Qualitative D-OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 µm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p < 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non-specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p < 0.001). Vessel direction changed in AK II-III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I-II than PD (p ≤ 0.025), whereas diameter remained constant. D-OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D-OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades.

Improved microvascular imaging with optical coherence tomography using 3D neural networks and a channel attention mechanism.

Skin microvasculature is vital for human cardiovascular health and thermoregulation, but its imaging and analysis presents significant challenges. Statistical methods such as speckle decorrelation in optical coherence tomography angiography (OCTA) often require multiple co-located B-scans, leading to lengthy acquisitions prone to motion artefacts. Deep learning has shown promise in enhancing accuracy and reducing measurement time by leveraging local information. However, both statistical and deep learning methods typically focus solely on processing individual 2D B-scans, neglecting contextual information from neighbouring B-scans. This limitation compromises spatial context and disregards the 3D features within tissue, potentially affecting OCTA image accuracy. In this study, we propose a novel approach utilising 3D convolutional neural networks (CNNs) to address this limitation. By considering the 3D spatial context, these 3D CNNs mitigate information loss, preserving fine details and boundaries in OCTA images. Our method reduces the required number of B-scans while enhancing accuracy, thereby increasing clinical applicability. This advancement holds promise for improving clinical practices and understanding skin microvascular dynamics crucial for cardiovascular health and thermoregulation.

Assessment of the utility of two-dimensional shear wave elastography and superb microvascular imaging in postoperative patients with biliary atresia.

PURPOSE: We aimed to investigate whether prediction of liver fibrosis using two-dimensional shear wave elastography (2D-SWE) and vascular tree grading using superb microvascular imaging (SMI) are useful for postoperative follow-up in patients with biliary atresia (BA). METHODS: We retrospectively collected data from medical records of 134 patients who underwent ultrasound examination with 2D-SWE or SMI, including 13 postoperative patients with BA and 121 non-BA patients. We investigated the distribution of liver stiffness values with SWE and vascular tree grading with SMI and evaluated correlations between these findings and biochemical indices of liver fibrosis in postoperative BA patients. RESULTS: The SWE values of the BA group were not significantly different from that of any other disease groups in non-BA patients. In postoperative BA patients, SWE values correlated significantly with aspartate aminotransferase to platelet ratio index (Spearman rank correlation coefficient [rs] = 0.6380, p = 0.0256) and with the Fib-4 index (rs = 0.6526, p = 0.0214). SMI vascular tree grading of the BA group was significantly higher than that of the choledochal cyst group (p = 0.0008) and other hepatobiliary disorder group (p = 0.0030). In postoperative BA patients, SMI vascular tree grading was not positively correlated with any biochemical marker of fibrosis. CONCLUSION: 2D-SWE appears to be useful for follow-up in postoperative BA patients.

Peripheral Ganglion Cell Complex Thickness and Retinal Microvasculature in Myopia Using Wide-Field Swept-Source OCT.

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Effects of Modulating BMP9, BMPR2, and AQP1 on BMP Signaling in Human Pulmonary Microvascular Endothelial Cells.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive increase in mean pulmonary arterial pressure. Mutations in the BMPR2 and AQP1 genes have been described in familial PAH. The bone morphogenetic proteins BMP9 and BMP10 bind with high affinity to BMPR2. Administration of BMP9 has been proposed as a potential therapeutic strategy against PAH, although recent conflicting evidence dispute the effect of such a practice. Considering the involvement of the above molecules in PAH onset, progression, and therapeutic value, we examined the effects of modulation of BMP9, BMPR2, and AQP1 on BMP9, BMP10, BMPR2, AQP1, and TGFB1 expression in human pulmonary microvascular endothelial cells in vitro. Our results demonstrated that silencing the BMPR2 gene resulted in increased expression of its two main ligands, namely BMP9 and BMP10. Exogenous administration of BMP9 caused the return of BMP10 to basal levels, while it restored the decreased AQP1 protein levels and the decreased TGFB1 mRNA and protein expression levels caused by BMPR2 silencing. Moreover, AQP1 gene silencing also resulted in increased expression of BMP9 and BMP10. Our results might possibly imply that the effect of exogenously administered BMP9 on molecules participating in the BMP signaling pathway could depend on the expression levels of BMPR2. Taken together, these results may provide insight into the highly complex interactions of the BMP signaling pathway.

Exosomes derived from endothelial progenitor cells ameliorate LPS-induced brain microvascular endothelial cells injury by delivering miR-126a-5p.

Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.

Role of Combining Grayscale Findings With Superb Microvascular Imaging and Shear Wave Elastography in Standardization and Management of NON-MASS Breast Lesions.

ABSTRACT: The non-mass breast lesions on ultrasound (US) are a group of challenging pathology. We aimed to standardize these grayscale findings and investigate the effectiveness of superb microvascular imaging (SMI) and shear wave elastography (SWE). A total of 195 lesions were evaluated by B-mode US, SWE, and SMI in the same session. A "NON-MASS model" was built on grayscale US to group the lesions only as areas and those with associated features: microcalcifications, architectural distortion, ductal changes, and microcysts. The mean stiffness parameters Emean, Eratio, and mean vascular index (VI) were recorded following consecutive measurements. Besides, the microvascularity was graded based on Adler's classification (grades 0 to 3). Lesions were divided into 3 groups: benign, category B3, and malignant. One hundred twelve (57.4%) lesions were benign, 23 (11.8%) were B3, and 60 were (30.8%) in the malignant category. Thirty-eight (19.5%) lesions were observed only as an area, whereas associated features were present in 157 lesions (80.5%). Distortion was the only associated feature predicting malignancy among the grayscale findings (P < 0.001). There was a significant difference between malignant and nonmalignant (benign and B3) groups in terms of Adler's grade, Emean, Eratio, and VI values (P < 0.001). Sensitivity, specificity, and accuracy increased when advanced imaging parameters were added to grayscale findings (P < 0.001). In the presence of microcalcifications, architectural distortion, high elasticity, and hypervascularity in the "NON-MASS" imaging model, the suspicion of malignancy increases. The non-mass findings and advanced imaging techniques have the potential to find greater coverage in the following versions of BI-RADS atlas.

Inner Retinal Microvasculature With Refraction in Juvenile Rhesus Monkeys.

Purpose: To characterize inner retinal microvasculature of rhesus monkeys with a range of refractive errors using optical coherence tomography angiography. Method: Refractive error was induced in right eyes of 18 rhesus monkeys. At 327 to 347 days of age, axial length and spherical equivalent refraction (SER) were measured, and optical coherence tomography and optical coherence tomography angiography scans (Spectralis, Heidelberg) were collected. Magnification-corrected metrics included foveal avascular zone area and perfusion density, fractal dimension, and lacunarity of the superficial vascular complex (SVC) and deep vascular complex (DVC) in the central 1-mm diameter and 1.0- to 1.5-mm, 1.5- to 2.0-mm, and 2.0- to 2.5-mm annuli. Pearson correlations were used to explore relationships. Results: The mean SER and axial length were 0.78 ± 4.02 D (-7.12 to +7.13 D) and 17.96 ± 1.08 mm (16.41 to 19.93 mm), respectively. The foveal avascular zone area and SVC perfusion density were correlated with retinal thickness for the central 1 mm (P < 0.05). SVC perfusion density of 2.0- to 2.5-mm annulus decreased with increasing axial length (P < 0.001). SVC and DVC fractal dimensions of 2.0- to 2.5-mm were correlated with axial length and SER, and DVC lacunarity of 1.5- to 2.0-mm annulus was correlated with axial length (P < 0.05). Conclusions: Several inner retinal microvasculature parameters were associated with increasing axial length and SER in juvenile rhesus monkeys. These findings suggest that changes in retinal microvasculature could be indicators of refractive error development. Translational Relevance: In juvenile rhesus monkeys, increasing myopic refraction and axial length are associated with alterations in the inner retinal microvasculature, which may have implications in myopia-related changes in humans.

Severe hypoglycaemia-induced microglial inflammation damages microvascular endothelial cells, leading to retinal destruction.

Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1ß, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage.

Secretome of brain microvascular endothelial cells promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage.

Cell-based therapeutic strategies have been proposed as an alternative for brain and blood vessels repair after stroke, but their clinical application is hampered by potential adverse effects. We therefore tested the hypothesis that secretome of these cells might be used instead to still focus on cell-based therapeutic strategies. We therefore characterized the composition and the effect of the secretome of brain microvascular endothelial cells (BMECs) on primary in vitro human models of angiogenesis and vascular barrier. Two different secretome batches produced in high scale (scHSP) were analysed by mass spectrometry. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used as well as in vitro models of EC monolayer (CMECs) and blood-brain barrier (BBB). Cells were also exposed to oxygen-glucose deprivation (OGD) conditions and treated with scHSP during reoxygenation. Protein yield and composition of scHSP batches showed good reproducibility. scHSP increased CD34+-EC proliferation, tubulogenesis, and migration. Proteomic analysis of scHSP revealed the presence of growth factors and proteins modulating cell metabolism and inflammatory pathways. scHSP improved the integrity of CMECs, and upregulated the expression of junctional proteins. Such effects were mediated through the activation of the interferon pathway and downregulation of Wnt signalling. Furthermore, OGD altered the permeability of both CMECs and BBB, while scHSP prevented the OGD-induced vascular leakage in both models. These effects were mediated through upregulation of junctional proteins and regulation of MAPK/VEGFR2. Finally, our results highlight the possibility of using secretome from BMECs as a therapeutic alternative to promote brain angiogenesis and to protect from ischemia-induced vascular leakage.