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Abstract Background Hypertrophic scar (HS), a fibroproliferative disorder caused by aberrant wound healing following skin injuries such as burns, lacerations and surgery, is characterized by invasive proliferation of fibroblasts and excessive extracellular matrix (ECM) accumulation. The dysregulation of autophagy is the pathological basis of HS formation. Previously, angiopoietin-2 (ANGPT2) was found to be overexpressed in HS fibroblasts (HSFs) compared with normal skin fibroblasts. However, whether ANGPT2 participates in the process of HS formation and the potential molecular mechanisms are not clear. Objective This study is intended to figure out the role of ANGPT2 and ANGPT2-mediated autophagy during the development of HS. Methods RT-qPCR was used to detect ANGPT2 expression in HS tissues and HSFs. HSFs were transfected with sh-ANGPT2 to knock down ANGPT2 expression and then treated with MHT1485, the mTOR agonist. The effects of sh-ANGPT2 or MHT1485 on the proliferation, migration, autophagy and ECM accumulation of HSFs were evaluated by CCK-8 assay, Transwell assay and western blotting. The expression of PI3K/Akt/mTOR pathway-related molecules (p-PI3K, p-Akt and p-mTOR) was assessed by western blotting. Results ANGPT2 expression was markedly upregulated in HS tissues and HSFs. ANGPT2 knockdown decreased the expression of p-PI3K, p-Akt and p-mTOR. ANGPT2 knockdown activated autophagy and inhibited the proliferation, migration, and ECM accumulation of HSFs. Additionally, the treatment of MHT1485, the mTOR agonist, on ANGPT2-downregulated HSFs, partially reversed the influence of ANGPT2 knockdown on HSFs. Study limitations The study lacks the establishment of more stable in vivo animal models of HS for investigating the effects of ANGPT2 on HS formation in experimental animals. Conclusions ANGPT2 downregulation represses growth, migration, and ECM accumulation of HSFs via autophagy activation by suppressing the PI3K/Akt/mTOR pathway. Our study provides a novel potential therapeutic target for HS.
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ABSTRACT Introduction: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. Methods: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Results: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients — but not NYHA III/IV patients — was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). Conclusion: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.
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Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.
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Objective:To explore the relationship between the expression of angiopoietin 1 (ANGPT1) and Smadhomolog 9 (Smad9) genes in cancer tissues and tumor metastasis, invasion behavior and prognosis in patients with lung adenocarcinoma.Methods:Sixty patients with lung adenocarcinoma in Chengwu Hospital Affiliated to Shandong First Medical University from October 2018 to December 2019 were selected as the research objects. The expressions of ANGPT1 and Smad9 mRNA in cancer tissues and adjacent tissues were compared, as well as the expressions of ANGPT1 and Smad9 mRNA in cancer tissues of patients with different tumor metastasis and invasion behaviors. The relationship between ANGPT1 and Smad9 mRNA expression and tumor metastasis and invasion behavior of lung adenocarcinoma were analyzed, and the 1-year survival rate of patients with lung adenocarcinoma was calculated. The 1-year survival rate of patients with different ANGPT1 and SMAD9 mRNA expression levels were compared.Results:The relative expression of ANGPT1 mRNA and Smad9 mRNA in cancer tissues were lower than those in adjacent tissues: 2.45 ± 0.26 vs. 11.18 ± 0.93, 4.23 ± 0.31 vs. 7.58 ± 0.65, the differences were statistically significant ( P<0.05). There were significant differences in the relative gene expression of ANGPT1 and Smad9 mRNA in different clinical stages, tumor diameter, degree of differentiation, lymph node metastasis and pleural invasion ( P<0.05). Spearman correlation analysis showed that the expression of ANGPT1 and Smad9 mRNA were negatively correlated with clinical stage, tumor diameter, lymph node metastasis and pleural invasion ( r = - 0.517, - 0.539, - 0.606, - 0.679, P<0.05), and positively correlated with the degree of differentiation ( r = 0.628, P<0.05). The 1-year survival rate of 58 patients was 72.41%. Kaplan-Meier curve analysis showed that the 1-year survival rate of patients with low expression of ANGPT1 and Smad9 mRNA in cancer tissues were were lower than those in patients with high expression ( P<0.05). Conclusions:Down-regulation of ANGPT1 and Smad9 genes in cancer tissues will accelerate the metastasis and invasion behavior of lung adenocarcinoma. Up-regulating the expression of both genes can be a potential way to improve survival.
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Objective:To study the relationship between the dynamic changes of angiopoietin-2 (Ang-2) and surfactant protein D (SP-D) in pediatric acute respiratory distress syndrome (pARDS) and the severity and prognosis of the disease.Methods:Using nested case-control study method, 80 children with pneumonia complicated with pARDS admitted to PICU at Fujian Maternal and Child Health Hospital from June 2018 to May 2021 were selected as pARDS group, and 19 healthy children with corresponding age were selected as control group.According to the oxygenation, the children in pARDS group were divided into three subgroups: mild group (23 cases), moderate group (32 cases) and severe group (25 cases). According to the prognosis at discharge, the children in pARDS group were divided into survival group (67 cases) and death group (13 cases). Ang-2 and SP-D were detected by enzyme-linked immunosorbent assay.The levels of Ang-2 and SP-D in children with pARDS of different severity on the first day were compared; The changes of Ang-2 and SP-D levels on the 1st, 3rd and 8th day of children in survival group and death group were compared, and the receiver operating characteristic (ROC) curve was plotted to compare the predictive value of Ang-2 and SP-D for pARDS prognosis.Results:(1) The levels of Ang-2 and SP-D on the first day in pARDS group were significantly higher than those in control group( P<0.001). (2) The levels of Ang-2 and SP-D on the first day in children with pARDS of different severity levels were significantly different ( P<0.001), and the levels of Ang-2 and SP-D increased gradually with the increase of disease severity.(3) The levels of Ang-2 and SP-D in death group were significantly higher than those in survival group on the 1st, 3rd and 8th day ( P<0.05). (4) Prognostic efficacy of Ang-2 and SP-D levels in pARDS group at different time points: when the areas under the ROC curve predicted by Ang-2 on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.808, 0.981 and 0.989, respectively; the optimal cut-off values were 6 000 pg/mL, 6 971 pg/mL and 4 171 pg/mL, respectively; the sensitivity was 84.6%, 92.3% and 92.3%, respectively; and the specificity was 76.1%, 97.0% and 98.5%, respectively.The areas under the ROC curve predicted by SP-D on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.689, 0.993 and 0.983, respectively; the optimal cut-off values were 13544 pg/mL, 16003 pg/mL and 12294 pg/mL, respectively; the sensitivity was 84.6%, 100.0% and 100.0%, respectively; and the specificity was 46.3%, 98.5% and 97.0%, respectively. Conclusion:Serum Ang-2 and SP-D levels in children with pARDS increase with the aggravation of the disease.The dynamic changes of Ang-2 and SP-D in children with pARDS with different prognosis are different during the course of disease, and monitoring serum Ang-2 and SP-D during the course of disease has a certain predictive value for clinical outcome.
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Angiopoietin-like protein 4 (ANGPTL4) is involved in the regulation of glucose and lipid metabolism and angiogenesis, and is closely related to tumorigenesis, development, invasion and metastasis. The abnormal expression of ANGPTL4 gene can promote or inhibit the growth and proliferation of tumor cells and play a tumor-promoting or anti-tumor role in the occurrence and development of tumors. To explore the role of ANGPTL4 gene in the occurrence and development of different tumors can provide reference for evaluating the diagnosis, prognosis and curative effect of tumors.
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Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.
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This study aimed to investigate the effect of sulfasalazine in preventing and treating intra-abdominal sepsis-induced acute respiratory distress syndrome (ARDS) in a rat model. Forty male Wistar albino rats were used. The rats were randomly divided into four equal groups, and sepsis was induced in 30 rats by intraperitoneal administration of a fecal saline solution prepared from rat feces. Group 1: normal control (n=10) [non-surgical], Group 2: fecal intraperitoneal injection (FIP) (n=10) [untreated septic group], Group 3: FIP+saline (placebo) (n=10) [saline administered intraperitoneally], Group 4 (n=10): FIP+sulfasalazine [250 mg/kg per day administered intraperitoneally]. Computed tomography was performed and blood samples were collected for biochemical and blood gas analysis. The lungs were removed for histopathological studies. Statistically significant reductions in interleukin (IL)-6, IL1-β, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), and angiopoietin-2 (ANG-2) levels were observed in the sulfasalazine group compared to the FIP+saline group (P<0.001). Nrf2 levels were significantly higher in the sulfasalazine-treated group than in the FIP and FIP+saline groups (P<0.01). Lung tissue scores were significantly reduced in the sulfasalazine group compared to the other sepsis groups. The Hounsfield unit (HU) value was significantly lower in the sulfasalazine group than in the FIP+saline group (P<0.001). PaO2 values were significantly higher in the sulfasalazine-treated group than in the FIP+saline-treated group (P<0.05). Sulfasalazine was shown to be effective in preventing and treating ARDS.
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Objective @# To investigate the effects of angiopoietin 4 (ANGPT4) on the odontogenic differentiation of human dental pulp stem cells. @* Methods @#This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Human premolars were fixed, decalcified, dehydrated, embedded, and sectioned. Immunofluorescence staining was used to observe the expression and localization of ANGPT4. Human dental pulp stem cells (hDPSCs) were isolated and cultured in vitro. The growth state and morphology of hDPSCs were observed under an inverted phase contrast microscope. The expression of cell surface-related molecular markers was detected by flow cytometry. Alkaline phosphatase and alizarin red S staining were used to detect the odontogenic differentiation potential of hDPSCs. Oil-red O staining was used to detect the adipogenic differentiation potential of hDPSCs. RNA was extracted from hDPSCs at different time points after odontogenic induction, and RT-qPCR was used to analyze the mRNA expression of ANGPT4 and odontogenic-related genes during the odontogenic differentiation of hDPSCs in vitro. siRNA gene silencing technology was used to silence the expression of ANGPT4 in hDPSCs, and the silencing efficiency was detected by RT-qPCR and Western Blot. After silencing ANGPT4 in hDPSCs for 24 h, odontogenic induction was performed. Alkaline phosphatase and alizarin red S staining were performed on the 7th and 14th of induction to detect the odontogenic differentiation ability of hDPSCs after silencing ANGPT4@*Results @# Immunofluorescence staining of human premolars showed that ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone. hDPSCs were in good condition after 14 days of isolation and culture. Under the microscope, multiple cell colonies were observed, and the cell morphology was uniform and long spindle-shaped. The results of flow cytometry showed that hDPSCs expressed mesenchymal stem cell markers CD105 (90.42%) and CD90 (97.15%), but did not express hematopoietic cell markers CD45 (0.01%) and CD34 (0.08%). After odontogenic and adipogenic induction of hDPSCs, alkaline phosphatase staining, alizarin red S staining and oil red O staining were positive. The results of RT-qPCR after the odontogenic induction of hDPSCs showed that ANGPT4 was highly expressed on the 5th, 7th, 11th and 14th days of differentiation of hDPSCs (P<0.05), with the highest expression level on the 5th day. After hDPSCs were transfected with si-ANGPT4, the expression of ANGPT4 mRNA and protein was significantly down-regulated (P<0.05). The results of alkaline phosphatase staining showed that ALP staining intensity and area in the si-ANGPT4 group were significantly lower than those in the negative control. Alizarin red S staining showed that the formation of calcium nodules in the si-ANGPT4 group was significantly lower than that in the negative control.@* Conclusion@#ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone of human premolars. ANGPT4 may be a factor to promote the odontogenic differentiation of hDPSCs.
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@#Angiopoietin-like 4(ANGPTL4)is one of the angiopoietin family members and plays a regulatory role in lipid metabolism,glucose homeostasis,inflammatory signal transduction,angiogenesis and vascular permeability.Inflammatory reaction in tumor microenvironment regulates tumor progression,and tumor angiogenesis plays a vital role in tumor growth and metastasis,so ANGPTL4 is closely related to tumor occurrence and development.Many studies have shown that ANGPTL4 plays an important regulatory role in tumor growth,anoikis resistance,tumor angiogenesis and tumor metastasis.This paper reviews the role of ANGPTL4 in tumor progression.
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Objective:To observe the expression of angiopoietin-like protein 4 (ANGPTL4) signaling pathway in adenine-induced chronic kidney disease (CKD) rat model, and to explore the role of this pathway in renal fibrosis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into control group (saline, intragastric administration, n=15) and CKD group (250 mg·kg -1·d -1 2.5% adenine, intragastric administration, n=21). At the end of the 1st, 2nd and 4th week, 5 rats were randomly selected from each group. Renal function and 24-hour urinary protein quantity were measured. HE and Masson staining were used to observe the pathological changes of kidneys. Immunohistochemistry and real-time PCR were used to detect renal protein and mRNA expressions of hypoxia-inducible factor-1α (HIF-1α), ANGPTL4, bone morphogenetic protein 7 (BMP7), Smad1, α-smooth muscle actin (α-SMA) and type Ⅰ collagen (Col-Ⅰ). Pearson correlation analysis was used to analyze the correlation between the different indicators. Results:(1) Compared with the control group, the expression levels of serum creatinine and blood urea nitrogen in CKD group were higher at each time point, and the expression levels of 24-hour urinary protein quantity were higher at the end of the 2nd and 4th week (all P < 0.05). (2) HE and Masson staining showed that there were obvious renal structural disorders and collagen fiber deposition at each time point in CKD group compared with the control group, which got worse with time. (3) The results of immunohistochemistry and real-time PCR showed that compared with the control group, the protein and mRNA expression levels of ANGPTL4, α-SMA and Col-Ⅰ were higher, while the protein and mRNA expression levels of BMP7 and Smad1 were lower at the end of the 1st, 2nd and 4th week, and the protein and mRNA expression levels of HIF-1α were higher at the end of 2nd and 4th week in CKD group (all P < 0.05). (4) Correlation analysis results showed that HIF-1α and ANGPTL4 mRNA expression were positively correlated with α-SMA mRNA ( r=0.919, P < 0.001; r=0.757, P < 0.001), and also positively correlated with Col-Ⅰ mRNA ( r=0.925, P < 0.001; r=0.777, P < 0.001). HIF-1α mRNA expression was positively correlated with ANGPTL4 mRNA ( r=0.766, P < 0.001). There were significant negative correlations between HIF-1α, ANGPTL4 mRNA and BMP7 mRNA ( r=-0.652, P < 0.001; r=-0.741, P < 0.001). Conclusions:ANGPTL4 signaling pathway may be activated in adenine-induced CKD rat model, and involved in the renal fibrosis process of CKD.
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Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.
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Objective:To investigate the expression of serum angiopoietin-2(Ang-2)in elderly community acquired pneumonia(CAP)patients and to evaluate the correlation between Ang-2 levels and the severity of CAP.Methods:As a case-control study, a total of 118 hospitalized elderly CAP patients were selected.According to the severity of CAP, patients were divided into the general pneumonia group( n=67)and the severe pneumonia group( n=51). At the same time, 40 elderly healthy people without pneumonia were selected as the control group.Serum Ang-2, interleukin-6(IL-6), procalcitonin(PCT)and C-reactive protein(CRP)levels were measured, and CURB-65 scores were obtained for patients with CAP. Results:Serum levels of Ang-2, IL-6, PCT and CRP in elderly CAP patients were significantly higher than those in the control group, and the differences were statistically significant( H=70.698, 25.752, 15.982, 30.588, all P<0.001). Spearman correlation analysis showed that Ang-2 levels were positively correlated with IL-6, PCT, CRP, and CURB-65 scores( r=0.715, 0.531, 0.558, 0.450, all P<0.001). Using Ang-2 as a predictor for severe pneumonia in community-dwelling elderly patients, the area under the ROC curve(AUC)was 0.866(95% CI: 0.809-0.924), the optimal cutoff point was 5.24 μg/L, and the corresponding sensitivity and specificity were 72.5% and 84.1%. Conclusions:Serum Ang-2 levels in elderly patients with CAP are significantly higher than those in healthy people, and are correlated with the severity of CAP.The detection of Ang-2 levels is helpful for early intervention management and improved prognosis of elderly CAP patients.
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ObjectiveTo observe the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation， apoptosis， and migration of cancer-relative endothelial （CRE） cells， and to decipher the mechanism of XLJDP in regulating angiopoietin2 （Ang2） to maintain CRE cell homeostasis and inhibit tumor neovascularization. MethodHuman umbilical vein endothelial cell line （HUVEC-c） was induced into CRE cells in the human colorectal cancer HCT-116 cell-conditioned medium. The CRE cells were assigned into the blank group， conditioned medium group， and XLJDP groups （1， 2， 3 g·L-1） and treated for 48 h. The proliferation of CRE cells was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. The morphological changes of CRE cells were observed via an inverted microscope. The apoptosis rate was detected by flow cytometry. Wound healing test and Transwell migration assay were employed to detect the 2D/3D migration ability of CRE cells. The protein levels of vimentin， N-cadherin， matrix metalloproteinase-9 （MMP-9）， and Ang2 in CRE cells were measured by Western blot. ResultThe MTT results showed that the cell viability was higher in the conditioned medium group than in the blank group （P<0.05）. Compared with the conditioned medium group， XLJDP decreased the cell proliferation rate （P<0.01） and changed the cell morphology. The total apoptosis rates of all the XLJDP groups were higher than that of the conditioned medium group （P<0.01）. The 2D and 3D migration abilities of the conditioned medium group were higher than those of the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations weakened the 2D migration ability （P<0.01） and medium- and high-concentration XLJDP weakened the 3D migration ability （P<0.01）. The protein levels of N-cadherin， Vimentin， MMP-9， and Ang2 were up-regulated in the conditioned medium group compared with those in the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations down-regulated the protein level of Ang2 （P<0.05， P<0.01）， and medium- and high-concentration XLJDP down-regulated those of N-cadherin， vimentin， and MMP-9 protein （P<0.01）. ConclusionXLJDP may inhibit the proliferation， migration， differentiation， and apoptosis of CRE cells by down-regulating the expression of Ang2， inhibiting tumor neovascularization， and maintaining the cell homeostasis.
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ObjectiveTo study the effects of Chinese herbal compound Youguiwan on angiogenesis of rats with ovarian dysfunction caused by natural aging and its relationship with chemokine interleukin 8 （CXCL8）/CXC chemokine receptor 1/2 （CXCR1/2） signaling pathway， angiopoietin 1 （Ang-1）， and angiopoietin 2 （Ang-2）， so as to explore its mechanism in improving the ovarian function. MethodFifty six female SD rats were randomly divided into the young control group （n=8） and modeling group （n=48， ovarian dysfunction caused by natural aging）. Rats in both the young control and modeling groups were routinely fed， during which the ones in the modeling group underwent exfoliative cytology of vaginal smears for five to seven days. The ones presented with prolonged estrous cycle， followed by continuous estrus and repeated pseudopregnancy revealed by vaginal cytology during four consecutive estrous cycles indicated early aging， and the young rats with keratinocyte proliferation index higher than 50% for 10 consecutive days were classified into the young control group. The successfully modeled rats were randomly divided into the early-aged group， estrogen （65 μg·kg-1·d-1） group， Zuoguiwan （33 g·kg-1·d-1） group， as well as the low-， medium-， and high-dose （1.2， 2.4， 4.8 g·kg-1·d-1） Youguiwan groups. Rats in the young control group and the early-aged group were gavaged with the same volume of normal saline for 30 days. After the experiment， the morphological changes in rat ovary were observed by hematoxylin-eosin （HE） staining. The protein expression levels of chemokines CXCL8， CXCR1， CXCR2， Ang-1， and Ang-2 in rat ovary were detected by Western blotting and immunohistochemistry， and the mRNA expression levels of CXCL8， CXCR1， CXCR2， Ang-1， and Ang-2 by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the young control group， the early-aged group exhibited reduced number of growing follicles， corpus luteum， and blood vessels at all levels， elevated atretic follicles （P<0.01）， up-regulated protein and mRNA expression of CXCL8， CXCR1， and CXCR2 in the ovarian tissue （P<0.01）， and down-regulated Ang-1 and Ang-2 protein and mRNA expression （P<0.05）. Compared with the early-aged group， each medication remarkably increased the number of growing follicles， corpus luteum， and blood vessels （P<0.05）， lowered the number of atretic follicles （P<0.05）， down-regulated the protein and mRNA expression levels of CXCL8， CXCR1， and CXCR2 in the ovarian tissue （P<0.05）， and up-regulated the protein and mRNA expression levels of Ang-1 and Ang-2 （P<0.05）. ConclusionYouguiwan down-regulates the levels of CXCL8， CXCR1， and CXCR2 in rat ovary and up-regulates the levels of Ang-1 and Ang-2 to promote ovarian angiogenesis and improve rat ovarian function.
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OBJECTIVE@#To detect whether Danlou Tablet (DLT) regulates the hypoxia-induced factor (HIF)-1α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia (CIH)-induced dyslipidemia and arteriosclerosis.@*METHODS@#The mature adipocytes were obtained from 3T3-L1 cell culturation and allocated into 8 groups including control groups (Groups 1 and 5, 0.1 mL of cell culture grade water); DLT groups (Groups 2 and 6, 0.1 mL of 1,000 µg/mL DLT submicron powder solution); dimethyloxalylglycine (DMOG) groups (Groups 3 and 7, DMOG and 0.1 mL of cell culture grade water); DMOG plus DLT groups (Groups 4 and 8, DMOG and 0.1 mL of 1,000 µg/mL DLT submicron powder solution). Groups 1-4 used mature adipocytes and groups 5-8 used HIF-1 α-siRNA lentivirus-transfected mature adipocytes. After 24-h treatment, real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1 α and Angptl4. In animal experiments, the CIH model in ApoE-/- mice was established. Sixteen mice were complete randomly divided into 4 groups including sham group, CIH model group [intermittent hypoxia and normal saline (2 mL/time) gavage once a day]; Angptl4 Ab group [intermittent hypoxia and Angptl4 antibody (30 mg/kg) intraperitoneally injected every week]; DLT group [intermittent hypoxia and DLT (250 mg/kg) once a day], 4 mice in each group. After 4-week treatment, enzyme linked immunosorbent assay was used to detect the expression levels of serum total cholesterol (TC) and triglyceride (TG). Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques.@*RESULTS@#Angptl4 expression was dependent on HIF-1 α, with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α -transfected cells. DLT inhibited HIF-1 α and Angptl4 mRNA expression (P<0.05 or P<0.01) and reduced HIF-1 α and Angptl4 protein expressions with DMOG in mature adipocytes (all P<0.01), as the effect on HIF-1 α protein also existed in the presence of siHIF-1 α (P<0.01). ApoE-/- mice treated with CIH had increased TG and TC levels (all P<0.01) and atherosclerotic plaque. Angptl4 antibody and DLT both reduce TG and TC levels (all P<0.01), as well as reducing atherosclerotic plaque areas, narrowing arterial wall thickness and alleviating atherosclerotic lesion symptoms to some extent.@*CONCLUSION@#DLT had positive effects in improving dyslipidemia and arteriosclerosis by inhibiting Angptl4 protein level through HIF-1 α-Angptl4 mRNA signaling pathway.
Subject(s)
Animals , Mice , Angiopoietin-Like Protein 4/genetics , Apolipoproteins E , Atherosclerosis/metabolism , Drugs, Chinese Herbal , Dyslipidemias/genetics , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Plaque, Atherosclerotic , Powders , RNA, Messenger/genetics , Signal Transduction , Triglycerides , WaterABSTRACT
ABSTRACT Objective: To investigate the serum levels of a vascular endothelial growth factor (VEGF), an angiogenic factor and a soluble angiopoietin receptor Tie-2 (sTie-2) in patients with essential hypertension. Methods: In the present study 90 individuals (56 males and 34 females, mean age 48 ± 7 years) have been divided into 3 groups: 30 patients with hypertension, 30 healthy individuals with a family history of hypertension and 30 healthy individuals with no family history of hypertension. All individuals have been evaluated in terms of blood pressure and biochemical parameters. The levels of VEGF and Tie-2 receptor have been evaluated by using the enzyme-linked immunosorbent assay method. Results: The findings suggested that the serum VEGF, sTie-2 receptor, low-density lipoprotein and triglycerides levels in the hypertensive patients were significantly higher than those in the control group (p < 0.05). However, the level of high-density lipoprotein cholesterol in the patients was significantly lower than in those in the control group (p < 0.05). In correlation analysis, a positive correlation was found statistically significant between the values of VEGF and sTie-2 (r = 0.405, p = 0.026). Conclusion: As a result of this study, our data indicate that serum levels of VEGF and Tie-2 receptor may be related to the primary hypertension. This study could inspire to further studies to explore the roles of VEGF and Tie-2 receptor in essential hypertension.
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Objective:To investigate the effect of propranolol on angiopoietin and its receptor in the nude mouse model of infantile hemangioma, so as to clarify the mechanism of propranolol in the treatment of hemangioma.Methods:The proliferative hemangioma tissue from the 980 Hospital of PLA was transplanted into the back of 50 female nude mice during May 2015 to Sept. 2016. After establishment of the hemangioma model, the nude mice were randomly divided into two groups, 25 in each group. The experimental group was gavaged with 0.4 ml propranolol every 2 days, and the control group was gavaged with normal saline every 2 days. The mice were killed in batches on the 7th, 14th, 21st and 28th day, the tumor morphology was observed by HE staining. The expression of VEGF, Ang1, Ang2 and Tie2 protein in hemangiomas was detected by immunohistochemistry and Western blot.Results:After 28 days, the hemangioma in propranolol group showed regression phase. The endothelial cells of hemangioma decreased, and the nuclear staining became shallow, the lumen enlarged, and fibrous connective tissue could be seen between the blood vessels. The expression of VEGF, Ang2 and Tie2 was lower than those in the control group ( P<0.05), and the expression of VEGF, Ang2 and Tie2 was decreased by 47.1%, 34.7% and 37.5%, respectively, while the expression of Ang1 was increased by 40.5% compared with the control group ( P<0.05). Conclusions:Propranolol may inhibit the growth of hemangioma in nude mice by promoting the expression of Ang1 and inhibiting the expression of VEGF, Ang2 and Tie2.
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Objective:To investigate the expression and ratio of serum angiopoietin-1/-2 (sAng-1/-2) in patients with cervical cancer and its relationship with clinicopathological features and prognosis.Methods:Eighty-seven patients with cervical cancer (FIGO Ⅰa1-Ⅳ) who were admitted to the First Affiliated Hospital of Shihezi University School of Medicine from September 2015 to December 2017 were selected as subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of sAng-1 and sAng-2 in serum samples of 87 patients at admission. The correlation between the sAng-1 and sAng-2 levels was analyzed by statistical analysis.Results:The expression of sAng-1 in patients with Ⅰa1-Ⅱa2 was significantly higher than those in advanced stage of Ⅱb-Ⅳ ( P<0.05). The expression of sAng-2 in patients with Ⅱb-Ⅳ or adenocarcinoma was significantly higher than that of patients with Ⅰa1-Ⅱa2 or squamous cell carcinoma ( P<0.05). The ratio of sAng-2/sAng-1 in patients with lymph node metastasis or Ⅱb-Ⅳ stage was higher than that in patients without lymph node metastasis or Ⅰa1-Ⅱa2 ( P<0.05). In addition, the expression level of sAng-2 and sAng-2/sAng-1 ratio in cervical cancer patients were related to the 3-year overall survival (OS) and pregression-free survival (PFS) ( P<0.05). Conclusions:The expression of sAng-1 and sAng-2 in patients with cervical cancer may be related to tumor pathological type, disease progression or prognosis. The expression of sAng-2 or the ratio of sAng-2/sAng-1 may be tumor markers to evaluate the prognosis of patients with cervical cancer.
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Objective@#To investigate the effect of a comprehensive exercise intervention program combined with diet control on ANGPTL2 and vascular endothelial function in obese male adolescents, and to provide theoretual basis for exercise to reduce the risk of cardiovascular disease in obese male adolescents.@*Methods@#Forty two obese male adolescents and 10 healthy male adolescents were selected, a comprehensive intervention of 6 weeks of exercise combined with diet control was carried out on obese male adolescents, and changes in morphological function, glucose and lipid metabolism, inflammation level and vascular endothelial function were measured before and after the intervention.@*Results@#After 6 weeks of comprehensive intervention, the morphological and functional indicators of obese adolescents were significantly reduced:weight, BMI, waist circumference, waist to hip ratio, systolic blood pressure, diastolic blood pressure ( P <0.05); blood lipid levels significantly decreased, including TC, TG and LDL-C ( P <0.05); inflammation levels significantly decreased, including TNF α and ANGPTL2 ( P <0.05); Vascular endothelial function significantly improved:RHI, NO/ET-1, NO, AI( P <0.05). Before and after 6 weeks of comprehensive intervention, the ANGPTL2 of obese adolescents was significantly correlated with weight ( r =0.37), BMI ( r =0.45), RHI ( r =-0.46), NO/ET-1 ( r =-0.41), NO( r =-0.45), and AI ( r =0.33)( P <0.05).@*Conclusion@#The comprehensive intervention can effectively improve the morphological function, blood lipid level and vascular endothelial function of obese male adolescents, and reduce the circulating level of ANGPTL2. ANGPTL2 may be involved in the process of comprehensive intervention to improve the vascular endothelial function of obese adolescents.