Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFß1/Smad2/3 signaling pathways.

Objectives: Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin's function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. Materials and Methods: 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. Results: In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-ß1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients' serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-ß1, collagen production, and phosphorylation of Smad2/3. Conclusion: The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-ß/Smad pathway.

Establishment and validation of an ultrasound-based nomogram with risk stratification for short disease-free survival in breast cancer.

PURPOSE: This retrospective study aimed to develop and validate an Ultrasound (US)-based nomogram to predict short disease-free survival (short-DFS, less than 120 months DFS) in breast cancer (BC). METHODS: Nomogram was established based on a training data of 311 BC patients by multivariable logistic regression, and were assessed by discrimination, calibration, and clinical usefulness. Risk stratification was performed by X-tile. An independent testing data of 200 patients with BC was used for external validation. RESULTS: Nine predictors including three US features and six clinical parameters were screened into the nomogram by Lasso (log λ = -3.594) in training data. Better performance was obtained in the training data (C-index: 0.942) and testing data (C-index: 0.914). Calibration analysis indicated optimal agreement between nomogram predictions and actual observations (p = 0.67). Decision curve analysis showed a great clinical benefit (Youden index: 0.634). Three risk levels are low-risk (<184.0), moderate-risk (184.0-345.3) and high-risk (>345.3). Our nomograms had larger area under the receiver operating characteristic (ROC) curves compared with Magee Equation and Nottingham Prognostic models (0.942 vs. 0.824, 0.790). CONCLUSION: The US-based nomogram and the practical score system facilitate individualized prediction of short-DFS to optimize clinical decisions and improve prognosis in patients with BC.

Circulating Small Extracellular Vesicle-Derived miR-342-5p Ameliorates Beta-Amyloid Formation via Targeting Beta-site APP Cleaving Enzyme 1 in Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder with progressive cognitive impairment in the elderly. Beta-amyloid (Aß) formation and its accumulation in the brain constitute one of the pathological hallmarks of AD. Until now, how to modulate Aß formation in hippocampal neurons remains a big challenge. Herein, we investigated whether the exosomal transfer of microRNA (miR) relates to amyloid pathology in the recipient neuron cells. We isolated circulating small extracellular vesicles (sEVs) from AD patients and healthy controls, determined the miR-342-5p level in the sEVs by RT-PCR, and evaluated its diagnostic performance in AD. Then, we took advantage of biomolecular assays to estimate the role of miR-342-5p in modulating the amyloid pathway, including amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), and Aß42. Furthermore, we subjected HT22 cells to the sEVs from the hippocampal tissues of transgenic APP mice (Exo-APP) or C57BL/6 littermates (Exo-CTL), and the Exo-APP enriched with miR-342-5p mimics or the control to assess the effect of the sEVs' delivery of miR-342-5p on Aß formation. We observed a lower level of miR-342-5p in the circulating sEVs from AD patients compared with healthy controls. MiR-342-5p participated in Aß formation by modulating BACE1 expression, specifically binding its 3'-untranslated region (UTR) sequence. Exo-APP distinctly promoted Aß42 formation in the recipient cells compared to Exo-CTL. Intriguingly, miR-342-5p enrichment in Exo-APP ameliorated amyloid pathology in the recipient cells. Our study indicated that miR-342-5p was dysregulated in human circulating sEVs from AD patients; sEV transfer of miR-342-5p ameliorates Aß formation by modulating BACE1 expression. These findings highlight the promising potential of exosomal miRNAs in AD clinical therapy.

Assessing Whether Morphological Changes in Axillary Lymph Node Have Already Occurred Prior to Metastasis in Breast Cancer Patients by Ultrasound.

Background and Objectives: Whether the morphological changes in axillary lymph node (ALN) have occurred prior to metastasis remains unclear in breast cancer (BC) patients. The aim of this study is to investigate the influence of BC for the morphology of non-metastasis ALN (N−) and, further, to improve the performance of ultrasound (US) examination for metastasis ALN (N+). Materials and Methods: In this retrospective study, 653 patients with breast mass were enrolled and divided into normal group of 202 patients with benign breast tumor, N− group of 233 BC patients with negative ALN and N+ group of 218 BC patients with positive ALN. US features of ALN were evaluated and analyzed according to long (L) and short (S) diameter, the (L/S) axis ratio, cortical thickness, lymph node edge, replaced hilum and color Doppler flow imaging (CDFI). Results: ALN US features of short diameter, replaced hilum, cortical thickness and CDFI have significant statistical differences in N− group comparing with normal group and N+ group, respectively (p < 0.05). Conclusions: Therefore, BC can affect ALN and lead to US morphological changes whether lymph node metastasis is present, which reduces the sensitivity of axillary US. The combination of US and other examination methods should be applied to improve the diagnostic performance of N+.

Aspirin in combination with gastrodin protects cardiac function and mitigates gastric mucosal injury in response to myocardial ischemia/reperfusion.

Myocardial ischemia/reperfusion (I/R) injury after percutaneous coronary intervention (PCI) is common in acute myocardial infarction. Aspirin is commonly prescribed as anti-thrombotic therapy with coronary heart disease (CHD). However, long-term use of aspirin causes severe gastric mucosal damage. Gastrodin is a Chinese natural medicine with anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of combined therapy with aspirin and gastrodin on the myocardial and gastric mucosal injury in response to myocardial I/R injury and underlying mechanisms using the Sprague-Dawley (SD) rat model. Our results demonstrated that myocardial I/R caused significant cardiac dysfunction and gastric mucosal damage. Administration of aspirin led to significantly reduce myocardial infarction size and myocardial enzyme release, as well as significantly improved cardiac function through exerting anti-inflammatory effects. However, aspirin exacerbated gastric mucosal damage by increasing the levels of inflammatory mediators and endothelin (ET) while reducing prostaglandin E2 (PGE2) levels. The combined treatment with aspirin and gastrodin not only significantly protected gastric mucosa by normalizing the expression levels of the inflammatory factors, ET and PGE2, but also significantly reduced myocardial infarction size and improved cardiac function by inhibiting inflammation in response to I/R. The combination therapy also dramatically down-regulated the levels of pyroptosis-related proteins in the myocardium and gastric mucosa. The combination therapy showed obviously reduced level of thromboxane B2 (TXB2), which was simultaneously accompanied with increased levels of the tissue plasminogen activator (t-PA). This suggested that gastrodin did not inhibit the anti-thrombotic function of aspirin. Accordingly, aspirin in combination with gasrtodin protected the structural and functional integrity of the heart and stomach by suppressing pyroptosis and inflammation. Therefore, combination of aspirin and gastrodin is a promising treatment for cardiac dysfunction and gastric mucosa injury after myocardial I/R.

Predictive Value of Ultrasound Characteristics for Disease-Free Survival in Breast Cancer.

The main objective of this study was to determine the predictive value of US characteristics for disease-free survival (DFS) in BC patients. We retrospectively analyzed the ultrasonic images and clinical data of BC patients who had previously undergone breast surgery at least 10 years before study enrollment and divided them into a case group and a control group according to the cutoff value of 120 months for DFS. Correlation analysis was performed to identify US characteristics as independent predictors for DFS by multivariable logistic regression and Kaplan−Meier survival analysis. A total of 374 patients were collected, including 174 patients in the case group with short-DFS and 200 patients in the control group with long-DFS. Three US characteristics (size on US, mass shape, mass growth orientation) and two clinical factors (axillary lymph node (ALN), molecular subtypes) were identified as independent predictors for DFS (p < 0.05). The ROC curve showed good performance of the multivariate linear regression model with the area under the curve being 0.777. The US characteristics of large size, irregular shape, and nonparallel orientation were significantly associated with short-DFS, which is a promising supplementary for clinicians to optimize clinical decisions and improve prognosis in BC patients.

Profiling of Serum Exosome MiRNA Reveals the Potential of a MiRNA Panel as Diagnostic Biomarker for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the older adults. Although much effort has been made in the analyses of diagnostic biomarkers, such as amyloid-ß, tau, and neurofilament light chain, identifying peripheral blood-based biomarkers is in extremely urgent need for their minimal invasiveness and more convenience. Here we characterized the miRNA profile by RNA sequencing in human serum exosomes from AD patients and healthy controls (HC) to investigate its potential for AD diagnosis. Subsequently, Gene Ontology analysis and pathway analysis were performed for the targeted genes from the differentially expressed miRNAs. These basic functions were differentially enriched, including cell adhesion, regulation of transcription, and the ubiquitin system. Functional network analysis highlighted the pathways of proteoglycans in cancer, viral carcinogenesis, signaling pathways regulating pluripotency of stem cells, and cellular senescence in AD. A total of 24 miRNAs showed significantly differential expression between AD and HC with more than ± 2.0-fold change at p value < 0.05 and at least 50 reads for each sample. Logistic regression analysis established a model for AD prediction by serum exosomal miR-30b-5p, miR-22-3p, and miR-378a-3p. Sequencing results were validated using quantitative reverse transcription PCR. The data showed that miR-30b-5p, miR-22-3p, and miR-378a-3p were significantly deregulated in AD, with area under the curve (AUC) of 0.668, 0.637, and 0.718, respectively. The combination of the three miRs gained a better diagnostic capability with AUC of 0.880. This finding revealed a miR panel as potential biomarker in the peripheral blood to distinguish AD from HC.

Proteomic profiling of biomarkers by MALDI-TOF mass spectrometry for the diagnosis of tracheobronchial stenosis after tracheobronchial tuberculosis.

Tracheobronchial tuberculosis (TB) leads to airway stenosis, irreversible airway damage and even death. The present study aimed to identify biomarkers for the diagnosis of tracheobronchial stenosis (TBS) secondary to tracheobronchial TB. A cohort was recruited, including patients with TBS after tracheobronchial TB, TBS after tracheal intubation or tracheotomy (TIT) and no stenosis of early-stage lung cancer,. Proteomic profiling was performed to gain insight into the mechanisms of the pathological processes. Differentially expressed proteins in the serum and bronchial alveolar lavage fluid (BALF) from patients were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Subsequently, ELISA was performed to validate the changes of protein levels in an additional cohort. MALDI-TOF MS revealed that 8 peptides in the serum, including myeloid-associated differentiation marker, keratin type I cytoskeletal 18, fibrinogen α-chain, angiotensinogen (AGT), apolipoprotein A-I (APOAI), clusterin and two uncharacterized peptides, and nine peptides in BALF, including argininosuccinate lyase, APOAI, AGT and five uncharacterized peptides, were differentially expressed (molecular-weight range, 1,000-10,000 Da) in the TB group compared with the TIT group. The ELISA results indicated that the changes in the protein levels had a similar trend as those identified by proteomic profiling. In conclusion, the present study identified proteins that may serve as potential biomarkers and provide novel insight into the molecular mechanisms underlying TBS after tracheobronchial TB.

KCNQ1OT1 facilitates progression of non-small-cell lung carcinoma via modulating miRNA-27b-3p/HSP90AA1 axis.

Long noncoding RNA KCNQ1OT1 participates in the regulation of imprinted genes within the kcnq1 domain. But its roles in carcinogenesis and metastasis remain largely elusive. Herein, we evaluated its potential in non-small-cell lung cancer (NSCLC) progression. We demonstrated that the KCNQ1OT1 level was upregulated in NSCLC tissues and cell lines. High KCNQ1OT1 level correlated with poor overall and progression-free survival in NSCLC patients. KCNQ1OT1 facilitated proliferation, migration, and invasion in H460 cells. Furthermore, knockdown of KCNQ1OT1 reduced the expression of HSP90AA1. KCNQ1OT1 presented a positive correlation with HSP90AA1 which predicted the tumor progression in NSCLC from The Cancer Genome Atlas database. Intriguingly, KCNQ1OT1 modulated HSP90AA1 expression by sponging miR-27b-3p. MiR-27b-3p counteracted the effect of KCNQ1OT1 on HSP90AA1 expression, H460 cell migration, and invasion. These data revealed a role for KCNQ1OT1 as an oncogene through miR-27b-3p/HSP90AA1 axis during NSCLC progression.

Gastric fundus splenosis with hemangioma masquerading as a gastrointestinal stromal tumor in a patient with schistosomiasis and cirrhosis who underwent splenectomy: A case report and literature review.

RATIONALE: Splenosis is the heterotopic auto-transplantation of the splenic tissues. Gastric splenosis in a rare location mimics a gastrointestinal stromal tumor (GIST). Gastric splenosis with hemangioma has not been reported throughout the literature. PATIENT CONCERNS: We report a case of a 74-year-old schistosomiasis cirrhosis splenectomy woman diagnosed with gastric fundus mass. Preoperative computed tomography and endoscopic ultrasonography revealed findings suggestive of a GIST. DIAGNOSES: The mass located in the gastric fundus muscularis propria, measuring 3.9 × 2.8 × 2.4 cm with a dark red color, was removed by surgery. In the mass, a 1 × 1-cm red-purple nodule was also found. On microscopic examination, a well-formed splenic tissue divided into two compartments-white pulp and red pulp-separated by an ill-defined interphase known as the marginal zone. However, a nodule in the heterotopic spleen was mainly composed of larger thin-walled muscular vessels. The final diagnosis was gastric splenosis with hemangioma. INTERVENTIONS: After discussion in a multidisciplinary conference, the patient was considered for a GIST resection under gastroscopy. In the process of peeling, the surface of the mucosal, submucosal, muscle layers and the tumor surface were diffusely oozing. The effect of electrocoagulation and hemostasis was extremely poor. Therefore, endoscopic surgery was arrested. After dealing with the patient's family, a combination of laparoscopic-gastroscope double-mirror surgery was decided in accordance with the principle of minimally invasive surgery to preserve the stomach. Owing to several adhesions and concealed the location of tumor, we stopped the double-mirror combination surgery plan. Considering the great possibility of a malignant GIST, we still decided to continue the traditional surgical resection. The tumor was then removed via surgery OUTCOMES:: The patient was favorable with healing and discharged on postoperative day 10. LESSONS: Gastric splenosis with an associated hemangioma is the first well-documented case. Its pathogenesis may be direct implantation. Appropriate medical history taking and Tc-99 m heat-denatured RBC spleen scintigraphy (Tc-99MHDRS) are valuable for its diagnosis; however, pathology is the gold standard. Surgery is a reasonable treatment for gastric splenosis with hemangioma.

Assessing Risk Category of Breast Cancer by Ultrasound Imaging Characteristics.

The purpose of our study was to assess the potential clinical value of ultrasound imaging in predicting risk category in patients with breast cancer. Three hundred thirty-six patients were enrolled and divided into a high-risk group (99, 29.5%) and mid- to low-risk group (237, 70.5%) according to the St. Gallen risk criteria. All data were retrospectively collected to analyze correlations between ultrasound features and risk category. The results revealed that the ultrasound features of irregular shape (p= 0.002), vertical growth orientation (p= 0.002), angular contour (p= 0.022) and high color Doppler flow imaging grade (p= 0.001) tended to be present in images of the high-risk group. Therefore, tumor ultrasound features should be recognized as an ideal option for determination of risk category in patients with breast cancer.

Serum lipoprotein and RBC rigidity index to predict cerebral infarction in patients with carotid artery stenosis.

OBJECTIVE: This study aims to determine the risk factors and to predict the occurrence of cerebral infarction in patients with carotid artery stenosis. METHODS: Two hundred and one subjects with carotid artery stenosis were retrospectively selected from Jinshan Branch of Shanghai Sixth People's Hospital, 115 cases of which with cerebral infarction and 86 without it. Clinical tests were performed including coagulation indices, fasting glucose, serum lipid, and blood rheology. Logistic regression analyses were used to identify the risk factors. Regression model was established, and receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value. RESULTS: Our data indicated that apolipoprotein AI (OR = 0.051, 95% CI: 0.009-0.295), lipoprotein (a) (OR = 1.003, 95% CI: 1.001-1.005), and RBC rigidity index (OR = 0.383, 95% CI: 0.209-0.702) were independent risk factors. Area under the curve (AUC) of the regression model = 0.78, with the sensitivity of 73.9% (95% CI: 64.9%-81.7%) and specificity of 69.2% (95% CI: 52.4%-83.0%). Prediction probability was determined while logistic regression score >0.748 defaulted as high-risk status. High-risk ratios were 80% in progressive cerebral infarction and 72% in nonprogressive cerebral infarction (P > .05), respectively, while significant differences were found when both compared with controls (P < .001). CONCLUSIONS: We show herein that the regression model based on apolipoprotein AI, lipoprotein (a), and RBC IR is a promising tool to predict the occurrence of cerebral infarction in patients with carotid artery stenosis. However, identification of novel diagnostic markers for progressive cerebral infarction is still necessary.

Ultrasound Features of Breast Cancer for Predicting Axillary Lymph Node Metastasis.

OBJECTIVES: The purpose of this study was to assess the clinical value of ultrasound (US) features of breast lesions for predicting the risk of axillary lymph node metastasis in patients with breast cancer. METHODS: In this retrospective study, 425 patients with breast cancer were recruited, and their preoperative US features and postoperative pathologic results were collected. The association of these US features of breast cancer with axillary lymph node metastasis was determined by univariate and multivariate analyses. RESULTS: Among the 425 patients, 200 (47.1%) had axillary lymph node metastasis, and 225 (52.9%) did not. The parameters of tumor shape, color Doppler flow imaging grades, histologic grade, and E-cadherin level were significantly and independently associated with axillary lymph node metastasis (P < .05 for all). CONCLUSIONS: Axillary lymph node metastasis was prone to happen in patients with US features of an irregular tumor shape and higher color Doppler flow imaging grades. Ultrasound imaging provides a promising tool for predicting axillary lymph node metastasis in patients with breast cancer.

Lobular capillary hemangioma of the tracheobronchial tree: A case report and literature review.

RATIONALE: Lobular capillary hemangioma (LCH) of the tracheobronchial tree is a rare benign tumor, whose characteristics and treatments remain relatively unknown. PATIENT CONCERNS: A 39-year-old man with hemoptysis caused by neoplasm in the bronchus intermedius was admitted to our hospital. DIAGNOSES: The patient was diagnosed with LCH. INTERVENTIONS: The lesions were removed with biopsy forceps, and cryotherapy was performed. OUTCOMES: After follow up for more than 2 years, no recurrence was found. LESSONS: Airway LCH can be treated by excisional biopsy, cryotherapy, APC, laser, radiotherapy, and surgery. Cryotherapy is worthy of recommendation.

Autophagy as a target for hematological malignancy therapy.

Autophagy is an essential metabolic pathway by which the intracellular unwanted materials are digested within lysosomes for cellular homeostasis. It provides energy and building blocks upon starvation or other stresses. Autophagy even contributes to cell death especially under apoptosis incompetent conditions depending on the cellular contexts. Dysfunction of autophagy involves in the initiation and progression of multiple diseases and their treatments. But its principles and clinical applications have not been fully elucidated yet. Basal autophagy may serve as a tumor suppressive mechanism during tumorigenesis; nevertheless, excessive autophagy even works as a pro-survival pathway in already established cancers. Recently, mounting evidence highlighted its key roles in the genesis and therapy of various hematological malignancies. The combinations of autophagy inhibitors (such as chloroquine) with some first-line drugs, as well as novel autophagy-based manipulations, including Bcl-2 family regulation, caspase-dependent cleavage of ATG proteins and microRNA replacement are clinically or experimentally applied, representing promising approaches for their clinical treatments. This review is therefore to discuss the recent progress in autophagy machinery and its association with hematological malignancy therapy.

The roles of integrin ß4 in vascular endothelial cells.

Integrin heterodimers play diverse and important roles in physiological and pathological processes, such as cell adhesion, migration, proliferation, differentiation, angiogenesis, and tumor progression, via the outside-in and/or inside-out signaling pathways. Aberrant functions of integrins have been implicated in the causation and intervention of multiple diseases. Integrin ß(4), a laminin-5 (LN5) receptor, mainly locates in the adhesion structure of hemidesmosome (HD). Most of the previous researches concentrated on the role of integrin ß(4) in cancer and cancer therapy, and a few focused on the physiological roles of normal mammalian cells. Recently, accumulating data reveal that integrin ß(4) participates in cell death, macroautophagy (hereafter autophagy), senescence, and differentiation regulations in various cell types including human umbilical vein endothelial cells (HUVECs), mesenchymal stem cells, and mouse neural cells, implying the key roles of integrin ß(4) in the physiological alteration of mammalian cells. Thus, the elucidation of integrin ß(4)-mediated signaling may undoubtedly contribute to novel therapeutic strategies for various human diseases, such as vascular and neural disorders. We have reviewed the roles of integrin ß(4) in neural cells. In the present review we will discuss the recent research progress in the inherent functions and pharmacological modulation of integrin ß(4) in vascular endothelial cells.

Distinct patterns of autophagy evoked by two benzoxazine derivatives in vascular endothelial cells.

Macroautophagy (referred to as autophagy) is an evolutionarily conserved, bulk-destruction process in eukaryotes. During this process, the cytoplasm containing long-lived proteins and organelles is engulfed into double-membrane autophagosomes, and ultimately undergoes enzymatic degradation within lysosomes. Autophagy serves as a prosurvival machinery, or it may contribute to cell death. Accumulating evidence indicates that autophagy is involved in the pathogenesis and intervention of various human diseases. Pharmacological autophagy modulators are arousing interest from biologists and clinical physicians in light of their potential for disease therapy and increasing our understanding of the mechanism of autophagy. In this study, we identified two autophagy enhancers, 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (ABO) and 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO), in human umbilical vein endothelial cells (HUVEC s) by autophagy assays, and demonstrate that ABO and DBO could stimulate autophagy in an mtor-independent and mtor-dependent manner, respectively; ABO-stimulated autophagy was attributed to the elevation of the Ca2+ channel annexin A7 (ANXA7), whereas DBO's effect was due to the level of intracellular reactive oxygen species (ROS). Importantly, we found that ANXA7 was essential for autophagy induction via modulating the intracellular calcium concentration ([Ca2+]i) in HUVEC s. In summary, our work introduced two distinct autophagy enhancers and highlighted the critical role of ANXA7 in endothelial autophagy.

Discovery of a benzoxazine derivative promoting angiogenesis in vitro and in vivo.

Angiogenesis is a multi-step process that refers to the growth of new vessels from pre-existing ones. Endothelial proliferation, migration, and tube formation constitute a critical step in angiogenesis. Recently, we demonstrated that a novel benzoxazine derivative, 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (ABO) could improve the proliferation of human umbilical vein endothelial cells (HUVECs) without basic fibroblast growth factor (bFGF) and serum. In this study, we further tested its effect on endothelial angiogenesis with Matrigel assay, migration assay, and in vivo chick chorioallantoic membrane (CAM) assay. Our results showed that ABO effectively facilitated cell migration and promoted capillary-like tube formation in vitro and in vivo. To elucidate the underlying mechanisms, we examined intracellular reactive oxygen species (ROS) level/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide dismutase (SOD) activities, nitric oxide (NO) level/endothelial nitric oxide synthase (eNOS) activity, and mitochondrial membrane potential (MMP). Our data indicated that ABO depressed ROS with inhibition of NADPH oxidase instead of SOD activity, stimulated NO production and eNOS activation, and restored MMP in HUVECs. Our findings suggest that ABO is a promising tool for exploring the mechanisms of angiogenesis and may have a therapeutic potential in ischemic pathologies.

Promotion of autophagy and inhibition of apoptosis by low concentrations of cadmium in vascular endothelial cells.

Recent reports, highlighting the relationships of cadmium exposure and vascular diseases, indicated that vascular endothelial cell was the target of cadmium (Cd) toxicity. However, the underlying mechanisms have not been fully elucidated. In this study, we evaluated the internalization of Cd2+ into human umbilical vein endothelial cells (HUVECs) by a novel Cd2+-selective sensor suitable for living cells. Then, we detected apoptosis in the treated cells. Our results showed that Cd2+ at low concentrations (< 10 micromol/l) inhibited apoptosis induced by deprivation of serum and basic fibroblast growth factor (bFGF). To investigate the corresponding molecular mechanisms, we employed acridine orange staining and Western blotting of MAP1 LC3 to detect autophagy, and analyzed the levels of integrin beta4, caveolin-1 and activity of PC-PLC. Our results showed that low concentrations of Cd2+ promoted autophagy and depressed the levels of integrin beta4, caveolin-1 and PC-PLC activity. The data suggested that autophagy played a key role in Cd2+ induced endothelial dysfunction; integrin beta4, caveolin-1 and PC-PLC might be the targets of Cd2+ in vascular endothelial cells.

[Effects of endothelial cells on renewal and differentiation of neural stem cells].

It is well established that neural stem cells (NSCs) are not randomly distributed throughout the brain, but rather are concentrated around blood vessels. Although NSCs lie in a vascular niche, there is no direct evidence for a functional relationship between the NSCs and blood vessel component cells. It is reported that endothelial cells release soluble factors that stimulate the self-renewal of NSCs, inhibit their differentiation, and enhance their neuron production. Endothelial coculture can activate Notch to promote self-renewal. Furthermore, vascular endothelial growth factor (VEGF) plays a significant role in neural cells; it stimulates the growth and differentiation of astrocytes in the central nervous system (CNS). Therefore, beyond their traditional role as structural components of blood vessels, endothelial cells are not only critical component of the neural stem cell niche, but they also are able to enhance neurogenesis, possibly through the secretion of brain-derived neurotrophic factor.