Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L^-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.
Humans ; Animals ; Rats ; Stigmasterol ; Phosphorylation ; Endothelial Cells ; Molecular Docking Simulation ; Reperfusion Injury ; Blood-Brain Barrier ; Glucose ; Microvessels ; Oxygen

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H₂O₂ and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT₁R) and AT₂R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H₂O₂ and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H₂O₂. The mRNAs of renal microvascular AT₁R and AT₂R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.
Angiotensin II/pharmacology* ; Animals ; Arterioles/metabolism* ; Captopril/pharmacology* ; Hydrogen Peroxide/pharmacology* ; Kidney ; Mice

OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.
Adult ; Aged ; Angiography ; Corneal Dystrophies, Hereditary/physiopathology* ; Female ; Humans ; Male ; Microvascular Density ; Microvessels/physiopathology* ; Middle Aged ; Retinal Diseases/physiopathology* ; Retinal Vessels/physiopathology* ; Tomography, Optical Coherence

The design of wall filter in ultrasonic microvascular imaging directly affects the resolution of blood flow imaging. We compared the traditional polynomial regression wall filter algorithm and two algorithms based on singular value decomposition (SVD), Full-SVD algorithm and RS-RSVD algorithm (random sampling based on random singular value decomposition) through experiments with simulated data and human renal entity data imaging experiments. The experimental results showed that the filtering effect of the traditional polynomial regression wall filter algorithm was limited, however, Full-SVD algorithm and RS-RSVD algorithm could better extract the micro blood flow signal from the tissue or noise signal. When RS-RSVD algorithm was randomly divided into 16 blocks, the signal-to-noise ratio was the same as that of Full-SVD algorithm, reduces the contrast-to-noise ratio by 2.05 dB, and reduces the execution time by 90.41%. RS-RSVD algorithm can improve the operation efficiency and is more conducive to the real-time imaging of high frame rate ultrasound microvessels.
Algorithms ; Humans ; Microvessels/diagnostic imaging* ; Signal-To-Noise Ratio ; Ultrasonics ; Ultrasonography/methods*

OBJECTIVES: Central serous chorioretinopathy (CSC) is generally a common fundus disease in young and middle-aged Asian men. Acute and chronic CSC can lead to different degrees of injury to the retinal blood flow. This study aims to observe and compare the blood flow density in different retinal capillary layers in patients with acute and chronic CSC using optical coherence tomography angiography (OCTA) technology. METHODS: Twelve patients with acute CSC and 8 patients with chronic CSC including 12 eyes with acute CSC (acute CSC eye group), 11 eyes with chronic CSC (chronic CSC eye group), and 17 normal eyes (normal eye group) were enrolled in this study. All patients underwent 3 mm×3 mm, 6 mm×6 mm macular OCTA scanning. The retinal microvascu-lature was divided into superficial vascular complexes (SVC), intermediate capillary plexuses (ICP), and deep capillary plexuses (DCP) using the projection resolved-OCTA algorithm. Inner retina includes SVC, ICP, and DCP. The vessel density in each retinal layer and the inner retina were calculated and compared. RESULTS: Macular OCTA scanning of 3 mm×3 mm showed that there was no significant difference in blood flow density of SVC and ICP among the 3 groups (both P>0.05); blood flow density of DCP and inner retina in the chronic CSC eye group was significantly lower than that in the acute CSC eye group and the normal eye group (all P<0.05); there was no significant difference in retinal blood flow density of different layer between the acute CSC eye group and the normal eye group (all P>0.05). Macular OCTA scanning of 6 mm×6 mm showed that inner retinal blood flow density of the chronic CSC eye group was significantly lower than that of the acute CSC eye group and the normal eye group (both P<0.05); there was no significant difference in blood flow density of SVC among the 3 groups (P>0.05). CONCLUSIONS The vessel density of DCP and inner retina in the eyes with chronic CSC are significantly reduced, which may result in impaired visual function. Therefore, we recommend that patients with acute CSC should be properly treated to avoid progressing into chronic CSC.
Central Serous Chorioretinopathy/diagnostic imaging* ; Fluorescein Angiography/methods* ; Humans ; Male ; Microvessels/diagnostic imaging* ; Middle Aged ; Retina ; Tomography, Optical Coherence/methods*

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Microvascular invasion (MVI) is considered the major risk factor for postoperative recurrence and metastasis in HCC. The diagnosis of MVI relies on the postoperative pathological assessment of the tumor tissues. Seeking non-invasive methods and biomarkers for evaluation of MVI before surgery has important clinical implications for guiding surgical treatment and improving patients' survival. Recent studies have reported the applications of radiomics technique in prediction of MVI in HCC and showed promising results. Herein we summarized the research progress in CT- or MRI-based radiomics models for prediction of MVI in HCC to provide helpful thinking for further research in this field.
Biomarkers ; Carcinoma, Hepatocellular/pathology* ; Humans ; Liver Neoplasms/pathology* ; Magnetic Resonance Imaging ; Microvessels/pathology* ; Neoplasm Invasiveness/pathology* ; Retrospective Studies ; Tomography, X-Ray Computed/methods*

Hepatocellular carcinoma (HCC) is a kind of highly aggressive tumor of the digestive system. Several studies have confirmed that microvascular invasion (MVI) is an independent risk factor for early recurrence and poor prognosis of HCC after surgery. Currently, pathological examination is the gold standard for diagnosing MVI. This paper summarizes concept, prognosis, preoperative prediction and treatment plan based on literature review of MVI in HCC.
Carcinoma, Hepatocellular/pathology* ; Humans ; Liver Neoplasms/pathology* ; Microvessels/pathology* ; Neoplasm Invasiveness/pathology* ; Prognosis ; Retrospective Studies

Artifacts ; Blood Vessels ; Brain ; Child ; Female ; Hemangioma ; Humans ; Kidney ; Lymph Nodes ; Microvessels ; Ovary ; Testis ; Thyroid Gland ; Ultrasonography ; Ultrasonography, Doppler, Color ; Urinary Bladder

Cerebral pericytes are perivascular cells that stabilize blood vessels. Little is known about the plasticity of pericytes in the adult brain in vivo. Recently, using state-of-the-art technologies, including two-photon microscopy in combination with sophisticated Cre/loxP in vivo tracing techniques, a novel role of pericytes was revealed in vascular remodeling in the adult brain. Strikingly, after pericyte ablation, neighboring pericytes expand their processes and prevent vascular dilatation. This new knowledge provides insights into pericyte plasticity in the adult brain.
Animals ; Brain ; blood supply ; physiology ; physiopathology ; Brain Diseases ; physiopathology ; Capillaries ; physiology ; Cellular Microenvironment ; Diabetic Retinopathy ; physiopathology ; Endothelial Cells ; physiology ; Humans ; Pericytes ; physiology ; Vascular Remodeling

OBJECTIVE: To investigate the clinical significance of bone marrow microvessel density(MVD) and angiogenesis related factors in multipic myeloma(MM). METHODS: Twenty cases of MM and 20 cases of simple fracture were selected and enrolled in MM group and control group respectively. The clinical data and results of laboratorial tests were collected; the bone marrow MVD of patients was detected by using the modified plastic-embedded pathologic sections of bone marrow tissue and histochemistry staining, the expression levels of amgiogenesis-related factors including VEGF, TNF-α, HGF, TGF-α, TGF-β1, bFGF, Ang-Ⅰ, Ang-Ⅱ in bone marrow supernatant were detected by ELISA; the mRNA expression levels of above-mentioned cytokines in bone marrow mononuclear cells were detected by real time-PCR; the pearson correlation analysis was used to analyze the correlation of MVD with VEGF, HGF and bFGF levels. RESULTS: The MVD in MM group was significantly higher than that in control group (P＜0.001); the mRNA expression of VEGF, TGF-α, TGF-β1 and HGF in bone marrow mononuclear cells of MM group was higher than that of control group(P＜0.001); the levels of VEGF, HGF, bFGF and THF-α in bone marrow supernatant of MM group were higher than those in control group(P＜0.05), moreover, the MVD positively correlated with levels of VEGF, HGF and bFGF in bone marrow(r=0.488, 0.472 and 0.457). CONCLUSION The MVD and levels vessel-related factors in bone marrow supernatant of MM patients increase, among which the levels of VEGF and HGF in bone marrow supernatant are consistant with those mRNA expression level in bone marrow mononuclear cells, moreover, the MVD possitively cerrelates with levels of VEGF, HGF and bFGF in bone marrow supernatant, suggesting that the changes of bone marrow microenvironment vassel-related factors play an important role in angiogenesis and pathogenesis of multiple myeloma.
Bone Marrow ; Bone Marrow Cells ; Humans ; Microvessels ; Multiple Myeloma ; Neovascularization, Pathologic ; Tumor Microenvironment