Is there a relationship between the keratoconus and the peripapillary choroidal vasculature?

PURPOSE: To evaluate the peripapillary/parapapillary choroidal vascular parameters in the keratoconus (KC) and to determine the relationship between topography parameters and the peripapillary/parapapillary choroidal vascular parameters. METHOD: Ninety eyes of ninety patients with different stages of KC and 29 eyes of twenty-nine patients without KC were enrolled in the study. Patients with KC were divided into three groups according to the Amsler-Krumeich classification scale. The choroidal vasculature was assessed by choroidal vascular parameters [such as parapapillary choroidal microvascular density (pCMVd) and peripapillary choroidal vascularity index (pCVI)]. These parameters were also evaluated for correlation with other parameters. RESULT: The retinal nerve fibre layer thickness (RNFLT) of the superior-temporal area and the pCVI were decreased in group 3 compared to the control group (superiror-temporal RNFLT: 122.27 ± 21.43 vs 139.90 ± 21.7, p = 0.01 and pCVI: 67.04 ± 4.14 vs 69.99 ± 4.38, p = 0.04). The superior-temporal RNFLT was decreased in group 3 compared to group 2 (122.27 ± 21.43 vs 141.83 ± 25.58, p = 0.006). There was a negative correlation between pCVI and average simulated keratometry (mean sim K), but this association was weak (r = - 0.29 p = 0.001). CONCLUSION: This study demonstrated that there may be changes in pCVI in patients with grade 3 KC and that there may be an association between pCVI and mean sim K. As KC grade increases, pCVI may decrease. Furthermore, pCVI may have a negative correlation with mean sim K.

Inter-eye asymmetry of microvascular density in patients on hydroxychloroquine therapy by optical coherence tomography angiography.

AIMS: To explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA). METHODS: 40 subjects were enrolled in this cross-sectional study, including 20 systemic lupus erythematasus patients currently treated with HCQ (40 eyes) and 20 age- and sex-matched normal controls (NCs, 40 eyes). OCTA images were obtained to measure macular and peripapillary mircrovasculatures and microstructures, including vessel density, retinal nerver fiber layer thickness, and peripapillary ganglion cell-inner plexiform layer thickness. The absolute values of the difference between right and left eyes were taken as a measure of inter-eye asymmetry. RESULTS: Macular whole image vessel density (wiVD-M) and perifoveal vessel density (pfVD) of superficial capillary plexus (SCP) were notably reduced in both the right and left eyes of the HCQ treatment group compared with NCs. Specifically, SLE patients treated with HCQ have higher inter-eye asymmetry of wiVD-M of SCP (2.28 ± 1.03 vs 1.27 ± 0.79, p < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, p = 0.04) compared with NCs. There were no significant differences in inter-eye asymmetry of structure parameters. Inter-eye asymmetry of wiVD-M of SCP (AUC = 0.80, p < 0.01) and pfVD of SCP (AUC = 0.71, p = 0.02) exhibited greater discrimination power. CONCLUSION: SLE Patients treated with HCQ exhibited a notably higher inter-eye vessel density asymmetry compared to that of NCs. Thus, inter-eye vessel density asymmetry could be used to screen for HCQ retinal toxicity.

Retinal perfusion related to visual field within the same asymmetric thyroid-associated ophthalmopathy.

PURPOSE: To quantify interocular differences in the retinal microvasculature between disparate eyes and explore associations between the retinal microvasculature and visual field abnormalities within the same asymmetric thyroid-associated ophthalmopathy (TAO) patients. METHODS: Within the same asymmetric TAO eye, the eye with a severer visual field abnormality (based on the mean deviation [MD]) was considered a severe eye, and the fellow eye was considered mild. The densities of radial peripapillary capillary (RPC) and superficial retinal capillary plexuses (SRCP) were determined using optical coherence tomography angiography. Interocular differences in RPC and SRCP densities were analyzed. A generalized estimating equation (GEE) was used to form a predictive model for visual field abnormalities. Pearson's correlation was used to show the correlation between MD and the densities of RPC and SRCP. RESULTS: In 57 asymmetric TAO patients, the global RPC density in severe eyes was lower than that in mild eyes (P < 0.001), but there was no significant difference in SRCP density between the two groups (P = 0.114). In a multivariate GEE model with MD as the outcome, MD was associated only with global RPC density (coefficient ß=0.327, P < 0.001). The global RPC density was correlated with MD (r = 0.360, P = 0.003) in severe eyes, but not in mild eyes (r = 0.179, P = 0.092). No significant correlation was observed between global SRCP density and MD in either group (Both P > 0.05). CONCLUSIONS: RPC density decreased significantly and correlated with visual field abnormalities in severe eyes of TAO patients. Alterations in RPC density may contribute to visual field abnormalities in TAO eyes.

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.

Close relationship between mediators of inflammation and pancreatic cancer: Our experience.

In this editorial, we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer. Cancer of the pancreas remains one of the deadliest cancer types. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends of pancreatic cancer incidence and mortality vary considerably worldwide. A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this editorial, we highlight the foundational studies that have driven our understanding of these processes. In our experimental center, we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer. We focused on the role of mast cells (MCs). MCs contain pro-angiogenic factors, including tryptase, that are associated with increased angiogenesis in various tumors. In this editorial, we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue. The assessment includes the density of c-Kit receptor-positive MCs, the density of tryptase-positive MCs, the area of tryptase-positive MCs, and angiogenesis in terms of microvascularization density.

Young blood-mediated cerebromicrovascular rejuvenation through heterochronic parabiosis: enhancing blood-brain barrier integrity and capillarization in the aged mouse brain.

Age-related cerebromicrovascular changes, including blood-brain barrier (BBB) disruption and microvascular rarefaction, play a significant role in the development of vascular cognitive impairment (VCI) and neurodegenerative diseases. Utilizing the unique model of heterochronic parabiosis, which involves surgically joining young and old animals, we investigated the influence of systemic factors on these vascular changes. Our study employed heterochronic parabiosis to explore the effects of young and aged systemic environments on cerebromicrovascular aging in mice. We evaluated microvascular density and BBB integrity in parabiotic pairs equipped with chronic cranial windows, using intravital two-photon imaging techniques. Our results indicate that short-term exposure to young systemic factors leads to both functional and structural rejuvenation of cerebral microcirculation. Notably, we observed a marked decrease in capillary density and an increase in BBB permeability to fluorescent tracers in the cortices of aged mice undergoing isochronic parabiosis (20-month-old C57BL/6 mice [A-(A)]; 6 weeks of parabiosis), compared to young isochronic parabionts (6-month-old, [Y-(Y)]). However, aged heterochronic parabionts (A-(Y)) exposed to young blood exhibited a significant increase in cortical capillary density and restoration of BBB integrity. In contrast, young mice exposed to old blood from aged parabionts (Y-(A)) rapidly developed cerebromicrovascular aging traits, evidenced by reduced capillary density and increased BBB permeability. These findings underscore the profound impact of systemic factors in regulating cerebromicrovascular aging. The rejuvenation observed in the endothelium, following exposure to young blood, suggests the existence of anti-geronic elements that counteract microvascular aging. Conversely, pro-geronic factors in aged blood appear to accelerate cerebromicrovascular aging. Further research is needed to assess whether the rejuvenating effects of young blood factors could extend to other age-related cerebromicrovascular pathologies, such as microvascular amyloid deposition and increased microvascular fragility.

Retinal Vascular Changes in Heart Failure with Preserved Ejection Fraction Using Optical Coherence Tomography Angiography.

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

Role of CD34-immunopositive Microvascular Density in Juvenile Nasopharyngeal Angiofibroma.

Objective: To assess the microvascular density (MVD) in juvenile nasopharyngeal angiofibroma (JNA) with CD34 immunostaining and evaluate its relationship with clinico-demographic features. Methods: This prospective study included patients with JNA undergoing endoscopic excision. The histopathological specimen was stained using CD-34 antibodies to calculate MVD. MVD and clinico-demographic features were correlated. Results: The study included 12 patients with a median age of 15.5 years. The mean MVD was 39 vessels/high power field (range 5 to 151 vessels). MVD was significantly associated only with the volume of tumour (r = 0.65, p = 0.02). The recurrence occurred in one patient with an MVD of 107. The median follow-up was 38 months. Conclusion: MVD is significantly associated with tumour volume in JNA, which implies a robust role of angiogenesis in the pathology of the tumour. Also, higher MVD may be a risk factor for recurrence.

Negative impact of ratio of the microvascular area to tumor area on the response to EGFR-TKI in non-small cell lung cancer with an EGFR mutation.

Background: The clinical impact of tumor microvessels on the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC) is unclear. Thus, the aim of this study was to investigate whether a tumor microenvironment, abundant in microvessels, affects EGFR-TKI efficacy in patients with NSCLC and EGFR mutations. Methods: We retrospectively studied the data of 40 post-operative patients with recurrent NSCLC and EGFR mutations who received EGFR-TKIs as a first-line treatment at Kumamoto University Hospital from January 2010 to February 2021. Tumor sections were retrieved from the tissue registry and analyzed for CD34-positive microvessels using immunohistochemical techniques. The ratio of microvascular area to tumor area (RMV), which is the CD34-positive microvascular area compared to the total tumor area, was measured using StrataQuest. The predictive value of RMV on treatment outcome, assessed via progression-free survival (PFS), was evaluated using a multivariate Cox proportional hazard model. Results: The median PFS in the high RMV group (≥0.058) was significantly shorter than that in the low RMV group [<0.058; 296 days, 95% confidence interval (CI): 217-374 vs. 918 days, 95% CI: 279-1,556, P=0.002]. Multivariate analysis revealed that high RMV was an independent negative predictor of PFS (hazard ratio, 3.21; 95% CI: 1.18-8.76, P=0.022). Conclusions: High RMV may critically affect EGFR-TKI resistance in patients with NSCLC and EGFR mutations.

Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound.

The purpose of this study was to investigate whether doxorubicin nanobubbles (DOX-NB) combined with diagnostic ultrasound (DUS) irradiation could downregulate the expression of carbonic anhydrase IX (CAIX) in mouse xenograft nasopharyngeal carcinoma (NPC) model. In this study, the prepared DOX-NB was round and well dispersed. The average diameter of DOX-NB was 250.9 ± 50.8 nm, with an average polydispersity of 0.321 ± 0.05. The cumulative release of DOX in the DOX-NB + DUS group was significantly higher compared with that of the DOX-NB group (p < 0.05). DOX-NB combined with DUS irradiation could significantly inhibit cell viability (p < 0.05). The expression of CAIX and microvessel density (MVD) in the xenografted tumors was the lowest in the DOX-NB + DUS group compared with that of other groups (p < 0.05). In conclusion, DOX-NB combined with DUS irradiation could improve DOX-NB drug release and synergistically inhibit NPC cell activity. DOX-NB combined with DUS irradiation can downregulate the expression of CAIX in mouse xenograft NPC model. This may be due to the synergistic effect of DUS combined with DOX-NB in reducing MVD in NPC.

Evaluation of the diagnostic utility of MCAM-1 (CD146) in a group of common gynecological cancers: A case-control study.

Objective: MCAM-1 (CD146) is an endothelial cell adhesion molecule belonging to the immunoglobulin superfamily. Recent studies have identified CD146 expression as a critical marker for tumor progression, migration, and metastasis in various malignancies. This study aimed to evaluate CD146 immunohistochemical expression in various gynecological cancers. Materials and Methods: This study was conducted in a tertiary medical center in central India. A total of 49 gynecological cancer cases and 16 site-matched controls were included. The cases comprised 27 cervical, 10 endometrial, 10 ovarian, and two miscellaneous cancers. CD146 immunohistochemistry was performed and assessed for immunoreactivity score (IRS), microvascular density (MVD), and microvascular caliber (MVC). An IRS of 5 or more was considered CD146 positive. Results: The p-values for CD146 positivity for cases vs. control were 0.0531, 0.0580, and 0.007 for cervical, endometrial, and ovarian sites, respectively. The mean MVD was found to be significantly higher in cases compared with benign tissues (p-value <0.00001), and the mean MVC of cases was found to be smaller when compared with the controls (p-value <0.0001). Conclusion: MVD by CD146 was found to be higher in gynecological malignancies, highlighting its role in cancer neo-angiogenesis and its potential therapeutic role. CD146 epithelial expression was also significantly higher in ovarian cancers. Further studies with a larger sample size are required to confirm that this protein may be a potential theognostic target in gynecological cancers.

Decreased retinal capillary density as a beneficial response to 24-week high-speed circuit resistant training in healthy older adults.

PURPOSE: To determine the changes in retinal microvascular density after a 24-week high-speed circuit resistance training program (HSCT) in healthy older adults. METHODS: Thirty healthy older adults were recruited and randomly assigned to either a training group (HSCT) or a non-training (CON) group. Fifteen subjects (age 73.3 ± 7.76 yrs) in the HSCT group exercised three times per week on non-consecutive days for 24 weeks. Fifteen subjects in the CON group (age 72.2 ± 6.04 yrs) did not have formal physical training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at the 24-week follow-up. The vessel densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured. RESULTS: There were no demographic differences between the study groups. There were significant decreases in the retinal vessel densities of RVN, SVP and DVP in the HSCT group (P < 0.05). However, there were no significant changes in all three vascular measurements in the CON group (P > 0.05), although the changes showed a decreasing trend. The decreased vessel densities were doubled in the HSCT group in comparison to the CON group. However, the differences between groups did not reach a significant level (P > 0.05). CONCLUSIONS: This is the first study to reveal the decreased retinal vessel densities as a possible imaging marker for the beneficial effects of the 24-week HSCT program in older adults.

Sublingual microcirculatory alterations in Chagas disease: an observational study in an endemic rural population

BACKGROUND Chagas disease is a systemic illness with widespread microvascular involvement. Experimental and clinical studies suggest that functional and structural microcirculatory abnormalities might be relevant to the disease progression. OBJECTIVES To show the presence of sublingual microcirculatory alterations in patients with chronic Chagas disease. METHODS This was a cross-sectional study including adult patients with serologic diagnosis of Chagas disease (n = 41) and control volunteers with negative serology (n = 38), from an endemic rural population. Study participants underwent clinical, electrocardiographic, echocardiographic, and sublingual videomicroscopic assessment. Videos were acquired by a sidestream-dark-field (SDF) imaging device and evaluated by a software-assisted analysis (AVA 3.2 software). FINDINGS Most of Chagas disease patients were in the indeterminate phase (n = 34) and had lower heart rate and more echocardiographic abnormalities than control group (50 vs. 26%, p = 0.03). They also exhibited higher small microvessels total and perfused vascular density (20.12 ± 2.33 vs. 19.05 ± 2.25 and 20.03 ± 2.28 vs. 19.01 ± 2.25 mm/mm2, p < 0.05 for both). Other microvascular variables did not differ between groups. MAIN CONCLUSIONS Patients with chronic Chagas disease exhibited increases in sublingual total and perfused microvascular density. Angiogenesis might be the underlying mechanism. The videomicroscopic assessment of mucosal sublingual microcirculation might be an additional tool in the monitoring of Chagas disease.

The Predictive Role of the Histopathological Scoring System in Adipose Tumors-Lipoma, Atypical Lipomatous Tumor, and Liposarcoma.

Lipomatous tumors are the most frequent soft tissue neoplasms. Sometimes their differential diagnosis is difficult to perform only by microscopic analysis. This study aims to create a histopathological scoring system and highlight the impact of intratumoral microvascular density. This study was conducted over 10 years. We analyzed the main pathogenic pathways (MDM2 and CDK4), as well as the tumor microvascularization (CD31 and CD34) by immunohistochemical tests. We also analyzed the status of the MDM2 gene by CISH. These data, together with the clinical and histopathological information, were statistically analyzed by appropriate tests. We identified 112 eligible cases, with most of the patients being in their sixth decade of life, with a slight predominance of the female sex. We found important associations like tumor location linked to nuclear pleomorphism severity and microvascularization density correlated with atypia severity. Also, we observed that a maximum diameter of a tumor of at least 69 mm is associated with the presence of tumor necrosis. The score designed in this study shows an increased sensitivity and specificity for the diagnosis of lipomas (100%, respectively, 97%), atypical lipomatous tumors (93.8%, respectively, 82.3%), and liposarcomas (100%, respectively, 90.5%). This present study enhances the present data by bringing to attention the histopathological score with a role in differential diagnosis, as well as in the prediction of immunohistochemical and genetic tests. Also, we highlighted the importance of microvascular density, especially in the diagnosis of liposarcomas.

Dietary nitrate accelerates the healing of infected skin wounds in mice by increasing microvascular density.

As skin injuries resulting from acute trauma, burns, and chronic diseases present significant challenges to healthcare systems worldwide, the promotion of skin wound healing remains an unmet therapeutic area. Dietary nitrate serves as a crucial pathway for the production of nitric oxide, which plays various physiological roles in the body, including vasodilation, increased blood flow, and antioxidant activity. However, the impact of dietary nitrate on skin wound healing remains uncertain. This study aimed to investigate the role of dietary nitrate in infected skin wound healing using a mouse model. We created a full-thickness wound infection model in mice and examine the effects of dietary nitrate (0.5 mmol/kg/d and 1 mmol/kg/d) on wound healing. The results demonstrated that dietary nitrate significantly increased serum nitrate and nitrite levels, leading to accelerated wound healing by increasing microvascular density, promoting collagen deposition and re-epithelialization. Moreover, nitrate supplementation exhibited a certain degree of reduction in inflammatory factors within the body. Our study also found that 1 mmol/kg/d nitrate has a more effective therapeutic effect and can increase blood perfusion and expedite the formation of new blood vessels, thereby promoting skin wound healing. These results indicate that dietary nitrate presents a novel therapeutic approach for infected skin wound healing.

Microvessel density (Cluster of Differentiation-34 & Vascular Endothelial growth factor) in Nasopharyngeal Angiofibroma: Clinical correlation.

BACKGROUND: The literature on microvessel density (MVD) signifying neoangiogenesis/tumour-activity in juvenile nasopharyngeal angiofibroma (JNA) is limited. Accordingly, this study evaluates and correlates MVD characteristics with clinical parameters/aggressiveness/recurrence. MATERIAL AND METHODS: Sixty-two paraffin blocks of JNA were studied histopathologically and MVD was assessed following immunohistochemistry using VEGF and CD34 as vascular markers. A clinical correlation of MVD was undertaken in 43 cases. RESULTS: MVD scores of VEGF and CD34 showed strong inter-correlation. The 'age', 'duration of disease' and 'haemoglobin%' were the only clinical parameters that revealed significance with MVD. Significantly higher MVD scores were appreciated in recurrent cases as well as some other clinical differences from upfront cases. CONCLUSION: This is the first study of MVD with CD34 and VEGF simultaneously depicting clinical correlation. The strong correlation, supports a prognostic role of MVD scores in JNA and this can be better established in a larger multicentre study involving comprehensive examination of tumour dimensions.

Search for Inhibitors of Mycobacterium tuberculosis Transketolase in a Series of Sulfo-Substituted Compounds.

As a result of the computer screening of a library of sulfo-substituted compounds, molecules capable of binding to the active site of transketolase from Mycobacterium tuberculosis were identified. An experimental verification of the inhibitory activity of the most promising compound, STK045765, against a highly purified recombinant enzyme preparation was carried out. It was shown that the STK045765 molecule competes for the binding site of the pyrophosphate group of the thiamine diphosphate cofactor and, at a micromolar concentrations, is able to suppress the activity of mycobacterial transketolase. The discovered furansulfonate scaffold may serve as the basis for the creation of anti-tuberculosis drugs.

Cell Therapy: A New Technology for Cerebral Circulation Restoration after Ischemia/Reperfusion.

Cell therapy with mesenchymal stem cells (MSCs) may be a promising technique for cerebral blood flow restoration after transient ischemia. Before a practical application of the cell material, 7-9 days are required for its cultivation. We studied the efficacy of human MSC (hMSC) transplantation performed 7 days after cerebral ischemia/reperfusion (I/R) to help recover cerebral circulation. The intravital micrograph technique was used to comparatively evaluate the vasculature density in the pia mater and the reactivity of the pial arteries in response to acetylcholine (ACh) in rats after I/R (clamping of both carotid arteries and a simultaneous decrease in and strict maintenance of the mean BP at 45 ± 2 mm Hg for 12 min) and with/without hMSC transplantation. Perfusion (P) in the sensorimotor cortex was assessed using laser dopplerography. After 14 and 21 days, the vasculature density in I/R-affected rats was 1.2- to 1.4-fold and 1.2- to 1.3-fold lower, respectively, than that in the controls. The number of ACh-dilated arteries decreased 1.6- to 1.9-fold and 1.2- to 1.7-fold 14 and 21 days after I/R, respectively. After 21 days, the P level decreased 1.6-fold, on average. Administration of hMSCs on day 7 after I/R resulted in complete recovery of the vasculature density by day 14. ACh-mediated dilatation fully recovered only in arteries of less than 40 µm in diameter within 21 days. After 21 days, the P level was 1.2-fold lower than that in the controls but significantly higher than that in rats after I/R without hMSCs. Delayed administration of MSCs after a transient cerebral ischemic attack affords the time for the procedures required to prepare cell material for transplantation and provides a good therapeutic response in the pial microvasculature.

Association of retinal microvascular density and complexity with incident coronary heart disease.

BACKGROUND AND AIMS: The high mortality rate and huge disease burden of coronary heart disease (CHD) highlight the importance of its early detection and timely intervention. Given the non-invasive nature of fundus photography and recent development in the quantification of retinal microvascular parameters with deep learning techniques, our study aims to investigate the association between incident CHD and retinal microvascular parameters. METHODS: UK Biobanks participants with gradable fundus images and without a history of diagnosed CHD at recruitment were included for analysis. A fully automated artificial intelligence system was used to extract quantitative measurements that represent the density and complexity of the retinal microvasculature, including fractal dimension (Df), number of vascular segments (NS), vascular skeleton density (VSD) and vascular area density (VAD). RESULTS: A total of 57,947 participants (mean age 55.6 ± 8.1 years; 56% female) without a history of diagnosed CHD were included. During a median follow-up of 11.0 (interquartile range, 10.88 to 11.19) years, 3211 incident CHD events occurred. In multivariable Cox proportional hazards models, we found decreasing Df (adjusted HR = 0.80, 95% CI, 0.65-0.98, p = 0.033), lower NS of arteries (adjusted HR = 0.69, 95% CI, 0.54-0.88, p = 0.002) and venules (adjusted HR = 0.77, 95% CI, 0.61-0.97, p = 0.024), and reduced arterial VSD (adjusted HR = 0.72, 95% CI, 0.57-0.91, p = 0.007) and venous VSD (adjusted HR = 0.78, 95% CI, 0.62-0.98, p = 0.034) were related to an increased risk of incident CHD. CONCLUSIONS: Our study revealed a significant association between retinal microvascular parameters and incident CHD. As the lower complexity and density of the retinal vascular network may indicate an increased risk of incident CHD, this may empower its prediction with the quantitative measurements of retinal structure.

Relationship of microvascular density on histological and immunohistochemical features in endometrioid adenocarcinomas of the uterus: experimental study.

The most common malignant tumors of the uterus are endometrioid adenocarcinomas (EA). Their prognosis depends on the qualitative characteristics of the neoplastic cells and their stroma. The neovascularization of EA tissues and level of microvascular density (MVD) influence tumor progression. Our study aims to establish the relationship between MVD in EA tissue and the histological and immunohistochemical features of tumors. Materials and methods: The authors studied 30 cases of endometrial ЕА and compared their histological and immunohistochemical characteristics with the MVD of tumor tissues. Results: Our study indicated that MVD in EA tissue depends on the grade of the tumors and their FIGO stage. Increased MVD was correlated with a depression of E-cadherin and PR expression and enhanced expression of VEGF and Ki-67. MVD enhancement during VEGF overexpression is a manifestation of the functional activity of these proteins. The increase in MVD was accompanied by more frequent metastasis of the EA to the lymph nodes. Conclusion: EA progression is accompanied by qualitative and quantitative variations of parenchymal and stromal patterns of tumors. Dedifferentiation of EA leads to overexpression of VEGF, which becomes diffuse in tumors cells, resulting in an increase of adenocarcinomas' MVD and their metastatic potential. Correlations between histological and immunohistochemical features of EAs indicate the synchronicity of the occurrence and progression of morphological and immunological anaplasia, which can be used in predicting the course of the disease.