Angiogenin Levels Research Articles

Chlorin e6-loaded sonosensitive magnetic nanoliposomes conjugated with the magnetic field for enhancing anti-tumor effect of sonodynamic therapy

In sonodynamic therapy (SDT), when Chlorin e6 (Ce6) accumulates in tumor tissues, its anti-tumor effect can be achieved by ultrasound activation. To increase the local drug concentration of Ce6 in tumor cells, we had established a novel drug delivery system, Ce6-loaded sonosensitive magnetic nanoliposome (Ce6/SML), which realized the targeting delivery by the external magnetic field. It was worth mentioning that the targeting release of Ce6/SML and the activation on Ce6 could be achieved simultaneously by ultrasound of SDT. In our study, after Ce6 was loaded into the sonosensitive magnetic nanoliposome (SML), the values of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in vitro and in vivo were determined, indicating the activation on Ce6 of ultrasound. The delivery system also displayed the tumor-targeting ability and anti-tumor activity, which associated with the determined tumor growth and expression levels of angiogenin (ANG), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α). In conclusion, the Ce6/SML-SDT-Targeted delivery system could effectively enhance the anti-tumor activity of SDT and had a great potential application for the treatment of malignant tumors located in deep tissues.

Exosomal Angiogenin as a Potential Biomarker in Amyotrophic Lateral Sclerosis

Abstract—Exosomes are extracellular vesicles that represent an important mode of intercellular communication. It is thought that exosomes can carry biologically active molecules associated with the progressive spreading of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease characterized by the progressive death of motor neurons. Angiogenin is likely to be important in the pathogenesis of ALS. This paper analyzes the content of angiogenin in blood plasma, CSF, and exosome fractions obtained from blood plasma and CSF in ALS. The study included 30 patients with ALS and 26 age and gender matched healthy controls. The relative amount of angiogenin in plasma and CSF was significantly higher than in exosome fractions (p < 0.05). A comparison of angiogenin content in plasma and exosome fraction revealed lower angiogenin levels in patients with ALS compared to healthy volunteers (p < 0.05), which may indicate a protective role of angiogenin. Higher concentrations of angiogenin in plasma and its exosome fractions tended to correlate with better functional states in patients. Therefore, a reduction of angiogenin levels in plasma and the exosome fraction from plasma may be a marker of disease progression, but these data need to be confirmed in a larger cohort.

Preliminary Assessment of Burn Depth by Paper-Based ELISA for the Detection of Angiogenin in Burn Blister Fluid-A Proof of Concept.

Rapid assessment of burn depth is important for burn wound management. Superficial partial-thickness burn (SPTB) wounds heal without scars, but deep partial-thickness burn (DPTB) wounds require a longer healing time and have a higher risk of scar formation. We previously found that DPTB blister fluid displayed a higher angiogenin level than SPTB blister fluid by conventional ELISA. In this study, we developed a paper-based ELISA (P-ELISA) technique for rapid assessment of angiogenin concentration in burn blister fluid. We collected six samples of SPTB blister fluid, six samples of DPTB blister fluid, and seven normal healthy serum samples for analysis. We again chose ELISA to measure and compare angiogenin levels across all of our samples, but we developed a P-ELISA tool and compared sample results from that tool to the results from conventional ELISA. As with conventional ELISA, DPTB blister fluid displayed higher angiogenin levels than SPTB in P-ELISA. Furthermore, our P-ELISA results showed a moderate correlation with conventional ELISA results. This new diagnostic technique facilitates rapid and convenient assessment of burn depth by evaluating a key molecule in burn blister fluid. It presents a novel and easy-to-learn approach that may be suitable for clinically determining burn depth with diagnostic precision.

Modifiers of Endothelial Permeability in the Setting of CAR-t Therapy Related Immune Cell Associated Neurotoxicity Syndrome

Background Chimeric Antigen Receptor T-cell therapy (CAR-t) for patients with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL) is associated with high overall remission rates but also with significant complications. Cytokine release syndrome (CRS) and Immune Cell Associated Neurotoxicity Syndrome (ICANS) are life-threatening sequelae that may occur in CAR-t recipients. ICANS presents with varying symptoms ranging from confusion to seizure and cerebral edema. There is no consensus on specific biological events that incite ICANS. Blood brain barrier (BBB) permeability is altered in CD19 CAR-t therapy, but the cause of altered BBB permeability is not clear. IL6 targeted interventions that control symptoms of CRS are ineffective against ICANS, suggesting these entities have separate pathologic mechanisms. Criteria for ICANS severity grading and guidelines for supportive care management are published, but there is no universal predictor of ICANS. Identification of manipulable biologic factors to predict the onset of ICANS would represent significant progress for clinical management of ICANS. Methods We collected plasma samples from 12 adult patients with varying ICANS severity following CAR-t therapy, aged 24-74 years. Diagnoses were diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B cell lymphoma (PMBCL) in varying stages of progression or relapse. Pre-CAR-t, midpoint and 7 or 8 day post CAR-t samples were evaluated with multiplex cytokine arrays to quantify relative levels of 105 angiogenic cytokines. Results were compared between two groups: patients who did not develop ICANS (n=5), and patients who developed any grade of ICANS (n=7; 2 patients grade 0-2, 5 patients grade 3-4). Results There was a trend toward higher baseline relative levels of two angiogenic factors, ApoA1 and Angiogenin, in patients with ICANS relative to those without. Interestingly, ApoA1 increased over time in patients who did not develop ICANS; a 320 +/- 56 % increase in ApoA1 occurred from baseline to day 7/8. In contrast, ApoA1 decreased to 88 +/- 25% of baseline by day 7/8 in patients who developed ICANS (No ICANS vs ICANS; p=0.003). Similarly, Angiogenin increased by 289 +/- 77% over baseline by day 7/8 in patients who did not develop ICANS, while it decreased to 98 +/- 24 % of baseline by day 7/8 in patients who developed ICANS (No ICANS vs ICANS, p = 0.03). Conclusion Our data suggests that ApoA1 and Angiogenin levels at baseline, and changes in ApoA1 or Angiogenin over time, may indicate risk of ICANS. This correlation requires validation in a larger patient population as well as quantification of absolute ApoA1 and Angiogenin concentrations in blood. If ApoA1 and Angiogenin baseline levels are indeed correlated with the risk of ICANS, this may represent major progress in clinical management of ICANS.

Perivascular Stem Cells Suppress Inflammasome Activation during Inflammatory Responses in Macrophages.

Background and ObjectivesPerivascular stem cells (PVCs) have been identified as precursors of mesenchymal stem cells (MSCs) that offer promising prospects for application in the development of cellular therapies. Although PVCs have been demonstrated to have greater therapeutic potential compared to bone marrow and adipose tissue-derived MSCs in various diseases, the regulatory role of PVCs on inflammasome activation during macrophage-mediated inflammatory responses has not been investigated.Methods and ResultsIn this study, we found that the PVC secretome effectively alleviates secretion of both caspase-1 and interleukin-1β in lipopolysaccharide-primed and activated human and murine macrophages by blocking inflammasome activation and attenuating the production of mitochondrial reactive oxygen species (ROS). We further showed that the PVC secretome significantly reduces inflammatory responses and endoplasmic reticulum stress in peritoneal macrophages in a mouse model of monosodium urate-induced peritonitis. A cytokine antibody array analysis revealed that the PVC secretome contains high levels of serpin E1 and angiogenin, which may be responsible for the inhibitory effects on mitochondrial ROS generation as well as on inflammasome activation.ConclusionsOur results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.

EXPRESS: Angiogenic Profile Identifies Pulmonary Hypertension in Children with Down Syndrome.

Past studies have shown that lung angiogenic signaling may be abnormal in children with Down syndrome, but whether differences in circulating angiogenic proteins can identify pulmonary hypertension in children with Down syndrome is unknown. A prospective study of 78 children from birth to 21 years of age was conducted to evaluate clinical data, echocardiograms, and cardiac catheterizations. Four patient populations were enrolled, including children with Down syndrome who have pulmonary hypertension (Down syndrome + pulmonary hypertension, n = 12); control children without Down syndrome who have pulmonary hypertension (C + pulmonary hypertension, n = 15); children with Down syndrome without a known diagnosis of pulmonary hypertension (Down syndrome − pulmonary hypertension, n = 26); and children without Down syndrome or a known diagnosis of pulmonary hypertension (C − pulmonary hypertension, n = 25). Blood samples were collected at enrollment and concentrations for 11 proteins were evaluated. A classification tree was created to identify angiogenic peptide signals that may be associated with pulmonary hypertension in children with Down syndrome compared with controls. Findings identified elevated endostatin levels (>4.98 log10 pg/ml) were associated with Down syndrome. Platelet-derived growth factor AA levels (>2.51 log10 pg/ml) were higher in non-Down syndrome patients with pulmonary hypertension (C + pulmonary hypertension), whereas lower angiogenin (<5.428 log10 pg/ml) or lower angiogenin with elevated angiopoietin-1 levels (>3.59 log10 pg/ml) distinguished pulmonary hypertension in those with Down syndrome from the other groups. This study suggests that children with Down syndrome have high endostatin levels, but low levels of angiogenin levels in children with Down syndrome more often identified pulmonary hypertension than Down syndrome subjects without pulmonary hypertension or non-Down syndrome children. We speculate that these changes in circulating peptides support the concept of dysregulated angiogenesis in children with Down syndrome and pulmonary hypertension, which may further support potential utility as biomarkers for identifying subjects with Down syndrome at risk for pulmonary hypertension in this population.

Melatonin protects the heart and endothelium against high fructose corn syrup consumption-induced cardiovascular toxicity via SIRT-1 signaling.

High fructose corn syrup (HFCS) has been shown to cause cardiovascular toxicity via oxidative stress and inflammation. The aim of this study is to demonstrate the protective effects of melatonin (MLT) against HFCS-induced endothelial and cardiac dysfunction via oxidative stress and inflammation. Thirty-two Sprague Dawley male rats were distributed into three groups as control, HFCS, and HFCS + MLT. HFCS form F55 was prepared as 20% fructose syrup solution and given to the rats through drinking water for 10 weeks, and MLT administrated 10 mg/kg/day orally for last 6 weeks in addition to F55. After decapitation, blood and half of the heart samples were collected for biochemical analysis and other half of the tissues for histopathological and immunohistochemical analysis. Aspartate transaminase, creatine kinase MB, lactate dehydrogenase, total oxidant status and oxidative stress index, and caspase-3 levels increased and total antioxidant status levels decreased significantly in HFCS group. MLT treatment reversed all these parameters. Histopathologically, hyperemia, endothelial cell damage and increased levels of angiogenin, C-reactive protein, inducible nitric oxide synthase, myeloperoxidase and decreased sirtuin-1 (SIRT-1) expressions were observed in HFCS group. MLT ameliorated all these changes. MLT has an anti-inflammatory, antioxidant, antiapoptotic effects on HFCS-induced cardiovascular toxicity through enhancing the expression of SIRT-1.

Blockade of angiogenin by thalidomide inhibits the tumorigenesis of murine hemangioendothelioma.

Thalidomide, a well-known immunomodulatory compound, has an anti-angiogenic activity, which may be utilized for the treatment of angiogenesis-related diseases such as hemangioendothelioma. The aim of the present study was to investigate both the antitumor role of thalidomide on hemangioendothelioma and the underlying mechanism. By using the xenograft mouse model, we found that thalidomide can inhibit the progression of hemangioendothelioma in vivo. Moreover, thalidomide shows no effect on the proliferation of hemangioendothelioma endothelial cell (EOMA), but significantly impairs the pro-angiogenic capacity of the EOMA cells in vitro. By qRT-PCR screening, we observed that the expression of angiogenin was downregulated by thalidomide treatment. We next performed tissue array analysis and found a positive correlation between angiogenin expression level and hemangioendothelioma occurrence in patients. Moreover, we confirmed that the antitumoral role of thalidomide is dependent on angiogenin expression both in vivo and in vitro. Taken together, we concluded that thalidomide can inhibit the progression of hemangioendothelioma by downregulating the expression of pro-angiogenic factor angiogenin and therefore can be used as a potent therapeutic to treat hemangioendothelioma.

Nailfold capillary changes in adult new-onset dermatomyositis: a prospective cross-sectional study.

It is to prospectively analyze nailfold capillaroscopy (NC) findings in new-onset dermatomyositis (DM) and to correlate NC findings with serum angiogenic cytokines and DM clinical and laboratory features. Twenty-three patients with DM who experienced < 12months of symptoms were included in the study. To assess serum cytokine levels, 23 age-, sex-, and ethnicity-matched healthy volunteers were used. NC characteristics and DM activity parameters were analyzed. Significantly higher serum angiogenin (ANG) and vascular endothelial growth factor-1 (VEGF1) levels were observed in DM patients than in controls. Capillary density and avascular areas correlated positively and negatively, respectively, with serum levels of ANG. Moreover, the capillary density correlated inversely with the number of enlarged and giant capillaries and avascular areas. The number of enlarged capillaries correlated positively with patient and physician visual analogue scales (VAS), the presence of a facial rash, giant capillaries, and microhemorrhages. Giant capillaries had a positive correlation with physician and cutaneous VAS, enlarged capillaries, avascular areas, microhemorrhages and bushy capillaries, and a negative correlation with capillary density. Microhemorrhages correlated positively with the "V-neck" sign and physician VAS. VEGF1 showed no relationship with the NC parameters with DM-related clinical and laboratory features. Additionally, 15 out of 23 patients were assessed prospectively after 3.21years. All patients had a major clinical response with significant improvement in all NC parameters, except for enlarged and bushy capillaries. The NC may be a useful tool to assess disease activity in recent-onset DM, and it can also reinforce the role of ANG in the angiogenesis of this myopathy.

4-Hexylresorcinol and silk sericin increase the expression of vascular endothelial growth factor via different pathways

Angiogenesis plays an important role in active inflammation and wound healing. Our results showed that silk sericin and 4-hexylresorcinol (4HR) increased vascular endothelial growth factor (VEGF) expression in a dose-dependent manner in RAW264.7 cells. Unlike 4HR, silk sericin increased the expression of hypoxia inducible factor-1α (HIF-1α) and HIF-2α. Pretreatment with an HIF inhibitor decreased the sericin-induced increase in VEGF expression. However, the HIF inhibitor did not affect the 4HR-induced increase in VEGF expression. An inhibitor of matrix metalloproteinase (MMP) declined the 4HR-induced increase in VEGF expression. Silk sericin increased production of reactive oxygen species (ROS), whereas 4HR decreased ROS. M1 markers were increased by silk sericin treatment, and M2 markers were increased by 4HR treatment. VEGF and angiogenin expression were higher in rats treated with a 4HR-incorporated silk mat than in rats treated with a silk mat alone. In conclusion, silk sericin and 4HR increased VEGF expression in RAW264.7 cells via HIF-mediated and MMP-mediated pathways, respectively. Silk sericin exerted like pro-oxidant effects and 4HR exerted anti-oxidant effects. Rats treated with a 4HR-incorporated silk mat showed higher levels of VEGF and angiogenin than those treated with a silk mat alone.

The association between serum angiogenin and osteopontin levels and coronary collateral circulation in patients with chronic total occlusion.

Objective:A well-developed coronary collateral circulation lowers both in-hospital and long-term morbidity and mortality limiting the infarct. Angiogenin (AGN) and osteopontin (OPN) are known to be potent inducers of angiogenesis. The aim of the present study was to investigate the relationship between serum ANG and OPN levels and collateral filling grade in subjects with stable coronary artery disease (SCAD).Methods:A total of 122 age- and gender-matched consecutive patients who were found to have total occlusion (n=70) and no significant stenosis in epicardial coronary arteries (n=52) who underwent coronary angiography due to SCAD between January 2015 and July 2017 were included in the study. AGN and OPN levels were measured using enzyme-linked immunosorbent assay. Coronary collateral circulation was graded using Rentrop’s classification of collateral filling.Results:A total of 52 patients (61.60±11.78 years, 61.5% male) without significant epicardial coronary artery stenosis and 70 patients (62.87±8.24 years, 65.7% male) with totally occluded coronary arteries were included in the study. Subjects with total occlusion had significantly higher levels of AGN [122.00 (79.00–623.00) pg/mL vs. 98.00 (18.00–160.00) pg/mL, p<0.001] and OPN [1863.50 (125.00–6500.00) pg/mL vs. 451.00 (112.00–1850.00) pg/mL, p<0.001] than those without significant stenosis. In addition, AGN [127.00 (87.00–623.00) pg/mL vs. 110.00 (79.00–188.00) pg/mL, p=0.011] and OPN [2681.00 (126.00–6500.00) pg/mL vs. 649.00 (125.00–4255.00) pg/mL, p=0.001] levels were significantly higher in patients with better developed collaterals. Serum AGN and OPN levels were found to be significantly associated with coronary collateral development.Conclusion:AGN and OPN are associated with better developed coronary collateral circulation and may have therapeutic implications for the promotion of coronary collateral development.

Repeated arctigenin treatment produces antidepressant- and anxiolytic-like effects in mice

Depression is the root of various diseases. It is one of the most debilitating conditions globally. Antidepressant drugs are usually the first-line of depression treatment. Arctigenin (ARC), one of active ingredient of Arctium lappa L, has been found to exert neuroprotective, anti-decrepitude, and anti-inflammatory activities. Thus, the aim of this study was to investigate the potential antidepressant- and anxiolytic-like effects of ARC using acute and chronic mild stress (CMS) mice model. ICR mice model received acute stress or chronic mild stress assessed by open field test (OFT), novelty suppressed feeding (NSF), sucrose preference test (SPT), forced-swimming test (FST), and tail suspension test (TST). After the final test, blood was collected to detect the serum levels of angiogenin (ANG), thrombopoietin (TPO), and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay (ELISA). The behavioral results showed that repeated ARC (10, 30 mg/kg) administration significantly relieved the antidepressant- and anxiolytic-like effects. And repeated ARC administration at the dose of 10 and 30 mg/kg could significantly block depressive- and anxiety-like behaviors caused by CMS. Finally, ELISA results showed that ARC administration increased the serum levels of angiogenin (ANG), thrombopoietin (TPO), and vascular endothelial growth factor (VEGF). Results showed that chronic ARC administration produces antidepressant- and anxiolytic-like effects, which provides direct evidence for the first time that ARC may be a novel strategy for the treatment of depression and even stress-related disorders. The present data supports further exploration for developing ARC administration as a novel therapeutic strategy for depression and even stress-related disorders.

Angiogenin and osteopontin levels are associated with better developed coronary collateral circulation in patients with stable coronary artery disease

Angiogenin and osteopontin levels are associated with better developed coronary collateral circulation in patients with stable coronary artery disease

Relevance of serum angiogenic cytokines in adult patients with dermatomyositis

BackgroundUntil now, there are few studies evaluating serum levels of angiogenic cytokines in dermatomyositis (DM). Therefore, the aims of the present study were: (a) to analyze systematically and simultaneously serum levels of angiogenin (ANG), angiopoietin (ANGPT)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-1 and − 2, platelet derived growth factor (PDGF)-AA and -BB in DM; (b) to correlate the serum level of these cytokines with the DM clinical and laboratory features.MethodsThis is a cross sectional study, in which 48 patients with DM aged 18 to 45 years were gender-, age- and ethnicity-matched with 48 healthy individuals (control group). The serum levels of cytokines analyses were performed by multiplex immunoassay. The parameters of DM activity were based on the scores established by the International Myositis Assessment & Clinical Studies Group.ResultsThe mean ages, gender frequencies and ethnicities were comparable between the patients with DM and the control group. A significantly higher serum FGF-1 and FGF-2 levels (P < 0.001 and P < 0.001, respectively), lower VEGF and PDGF-AA levels (P = 0.009 and P = 0.022), and comparable ANG, ANGPT-1 and PDGF-BB levels were observed in DM patients compared to controls. There was a tendency for cytokines (with the exceptions of VEGF and PDGF-BB) to correlate positively with the DM activity parameters, whereas FGF-2 correlated inversely. Moreover, FGF-1 strongly correlated with DM cutaneous manifestations.ConclusionsThe present data provide the relevance of different serum angiogenic cytokines in patients with DM. Additional studies will be needed to validate the data obtained in this work.

SuHeXiang Essential Oil Inhalation Produces Antidepressant- and Anxiolytic-Like Effects in Adult Mice.

SuHeXiang (SHX) has been used to treat a wide range of diseases, including those related to the central nervous system. However, the effects of SHX on mood disorders are still elusive. This study aimed to investigate the effects of SHX essential oil on stress-induced depression of mice. In an acute stress-induced depression model, mice inhaled vehicle (1% Tween 80) for 10 min or 10% SHX for 10 or 30 min once daily for 12 continuous days. In the chronic mild stress (CMS)-induced depression model, mice were exposed to a 28-d CMS treatment. Tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and novelty suppressed feeding (NSF) test were conducted. In addition, serum levels of angiogenin (ANG), thrombopoietin (TPO), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA) assays. The results showed that in mice exposed to acute stress, repeated SHX inhalation exerted significant antidepressant and anxiolytic activities, and also reduced the serum levels of ANG, TPO, IL-6, and TNF-α. It also significantly reversed the depressive and anxiety-like behaviors, and reduced the serum levels of ANG and TPO in mice exposed to CMS. This is the first report to show that SHX inhalation could produce significant antidepressant and anxiolytic-like effects. These effects might be mediated by SHX ability to modulate the inflammatory response, and reduce dysfunction of vascular genesis and thrombosis. These results support further exploration for developing SHX inhalation as a novel therapeutic strategy for depression and stress-related disorders.

Autophagy mediates enhancement of proangiogenic activity by hypoxia in mesenchymal stromal/stem cells

Mesenchymal stromal/stem cells (MSCs) have been promising source for regenerative cell therapy in ischemic diseases. To improve efficacy of MSC therapy, various priming methods have been developed, and hypoxic priming has been reported to enhance therapeutic efficacy of MSCs by increasing secretion level of growth factors and cytokines. Recently, it has been reported that bone marrow MSCs primed with hypoxic condition show an increase of autophagy. Here, we addressed whether proangiogenic activity increased by hypoxic condition is associated with autophagy. Wharton's jelly derived MSCs primed with hypoxia showed increase of autophagy with increased hypoxia inducible factor-1α level, and conditioned medium (CM) derived from these cells showed increased levels of migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared to non-primed MSCs-derived CM. Pretreatment with autophagy inhibitor 3-methyladenine or chloroquine prior to exposure of hypoxia resulted in reduction of migration and tube formation of HUVECs. CM obtained under hypoxic condition from MSCs in which autophagy activity was inhibited by ATG5 and ATG7 siRNA treatment also showed decrease of migration and tube formation of HUVECs. Accordingly, secretion levels of angiogenin and VEGF that were markedly increased upon hypoxia exposure was decreased by ATG5/7 knockdown. Therefore, it may be suggested that autophagy plays an important role in hypoxia-driven enhancement of paracrine effect of MSCs.

Predominance of CD14+ Cells in Burn Blister Fluids.

Burn blister fluid contains several angiogenic factors to promote wound neovascularization. In our previous study, we found that deep partial-thickness burn (DPTB) wounds showed higher expression levels of angiogenin to enhance vascularization compared with superficial partial-thickness burn wounds. Neovascularization is a complex process that involves an interaction between circulating angiogenic cells and mediators. We hypothesized that in addition to angiogenic factors burn blisters may contain specific cell types. The aim of the present study was to characterize the specific cells present in burn blisters. Twenty-four burn blister fluid samples were obtained with informed consent from patients with superficial partial-thickness burn (n = 16) or DPTB (n = 8) wounds. Blister cells were isolated from individual intact blisters and characterized with flow cytometry analysis using CD14, CD34, vascular endothelial growth factor receptor 2, and CD133 markers. CD14 and CD34 blister cells were also isolated using a magnetic-activated cell sorting system to examine their potential for endothelial differentiation. Angiogenin levels in the burn blister fluids were evaluated with enzyme-linked immunosorbent assay. CD14 cells were the most highly represented cell type in the burn fluids of both groups, although a significantly greater percentage of CD14 cells were observed in DPTB fluids. CD14 blister cells had a higher potency to differentiate into functional endothelial cells as compared with CD34 cells. The proportion of CD14 cells gradually increased after burn injury. In contrast to CD14 cells, angiogenin showed the highest expression levels at day 1 postburn. With regard to burn wound neovascularization, angiogenin expression was partially correlated with CD14 blister cells in the burn fluids. We provide the first report on the characterization of blister cells in burn fluids. Our data suggest that CD14 blister cells may play a role in burn wound neovascularization. Measurement of CD14 blister cells serves as a possible tool for assessing burn wound status.

Blue-light filtering alters angiogenic signaling in human retinal pigmented epithelial cells culture model

BackgroundLight exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD.MethodsThree experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines.ResultsA significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions.ConclusionsFollowing light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein-pretreated conditions in a similar manner.

A Comparative Study of the Predictive Values of Urinary Acute Kidney Injury Markers Angiogenin and Kidney Injury Molecule 1 for the Outcomes of Kidney Allografts.

Whether injury-related molecules in urines of individuals with ischemia-reperfusion injury (IRI) are independent predictors of graft outcomes and provide additional information compared with usual risk factors remains to be established. We explored a cohort of 244 kidney transplant recipients who systematically had a urine collection 10 days after transplantation. The injury-related markers kidney injury molecule-1 (KIM-1) and angiogenin (ANG) levels in urines were measured. We determined the prognostic values of these markers on graft outcomes. Urinary KIM-1 and ANG concentrations were strongly correlated to each other and were significantly and independently associated with cold ischemia time, delayed graft function, and plasma creatinine 10 days after transplantation, indicating that these markers reflect the severity of IRI. However, urinary ANG and KIM-1 were not predictive of histological changes on protocol biopsies performed 3 and 12 months after transplantation. Finally, urinary ANG and urinary KIM-1 were not associated with graft survival. Together, our results indicate that, in a cohort of 244 kidney transplant recipients, urinary ANG and KIM-1 levels in a single measurement 10 days after transplantation reflect the severity of IRI after kidney transplantation, but are neither independent predictors of renal function, histological changes and graft survival.

Tanshinone IIA inhibits β-catenin/VEGF-mediated angiogenesis by targeting TGF-β1 in normoxic and HIF-1α in hypoxic microenvironments in human colorectal cancer

In a previous study, we demonstrated that Tanshinone IIA effectively inhibits CRC angiogenesis in vivo, but the underlying mechanisms were not elucidated. In this report, we describe experiments in which HIF-1α levels were manipulated to probe the effect of hypoxia on CRC cell angiogenesis. We studied the effects of Tan IIA on CRC pro-angiogenic factor and on human umbilical vein endothelial cell angiogenesis in normoxia and hypoxia. Our results show that Tan IIA not only lowers HIF-1α levels and inhibits secretion of VEGF and bFGF, but also efficiently suppresses the proliferation, tube formation and metastasis of HUVECs. Interruption of the HIF-1α/β-catenin/TCF3/LEF1 signaling pathway occurs in the hypoxic microenvironment. The mechanism involves HIF-1α inhibition of TGF-β1 secretion, which drives angiogenesis by promoting β-catenin nuclear localization and TCF/LEF activation. To test an improved delivery system for Tan IIA, we loaded the drug into mesoporous silica nanoparticles (MSN-NH2) and found that it effectively targets HIF-1α overexpression in a mouse colon tumor model. Finally, Tan IIA sodium sulfonate exhibits anti-angiogenesis activity in CRC patients by reducing levels of angiogenin, VEGF and bFGF expression. Our research provides a new anti-angiogenesis strategy and strengthens support for the use of Tan IIA as an angiogenesis inhibitor.