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Abstract Introduction: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. Methods: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg−1.min−1, and serial doses of apelin-13 (50, 150 and 450 μg.kg−1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. Results: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). Conclusion: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.
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Objective:To investigate the effect and the neural mechanisms of Apelin-13 on the behavior changes of posttraumatic stress disorder (PTSD) model mice.Methods:Totally 32 SPF grade male C57BL/6J mice aged 6 weeks were divided into 4 groups randomly ( n=8 in each group): control group, model group, normal saline group and Apelin-13 group.The mice model of PTSD was established by single-prolonged stress (SPS) method. The mice in normal saline group and Apelin-13 group were respectively given lateral ventricular microinjection of 0.9% sodium chloride solution (2 μL) and Apelin-13 (1.5 μg/μL, 2 μL)after PTSD modeling. The behaviors of mice were evaluated by open field test, elevated plus maze test and Morris water maze test.The morphological structure and numerical changes of hippocampal neurons were observed by hematoxylin and eosin (HE) staining.The expression of phosphoinositide 3-kinase(PI3K), phosphorylated-PI3K(p-PI3K), protein kinase B(Akt), phosphorylated-Akt (p-Akt), forkhead box O3a (FoxO3a), phosphorylated-FoxO3a(p-FoxO3a), autophagy-related proteins including microtubule-associated protein 1 light chain 3(LC3) and sequestosome 1(p62) were detected by Western blot. SPSS 26.0 software was used for data analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA.The comparison of other data among multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by LSD test and Tamhane test. Result:(1) Open field test results showed statistically significant differences in the central area activity distance and residence time in central area among mice in the four groups ( F=15.37, 9.63, both P<0.05). The central area activity distance ((0.06±0.03) m) and residence time ((2.48±1.02) s) of the mice in model group were lower than those of the control group ((0.19±0.05) m, (15.00±8.91) s)(both P<0.05). And the central area activity distance((0.12±0.04)m)and the residence time((13.56±7.64)s)were higher than those of model group((0.06±0.03)m, (2.48±1.02)s)and normal saline group((0.06±0.02)m, (2.82±1.52)s)(all P<0.05). Elevated plus maze test results showed statistically significant differences in the numbers and time entering open arms among the four groups ( F=10.74, 19.12, both P<0.05). The numbers((4.50±2.51) times) and the time ((26.95±17.48) s) entering the open arm of mice in model group were both lower than those of the control group ((13.75±4.71) times, (103.75±42.43)s) and Apelin-13 group ((10.00±5.18) times, (55.98±19.49) s) (all P<0.05). Morris water maze test results showed that in the 4-day learning and training phase, the time and group interaction of escape latency was not significant among the four groups ( F=1.15, P=0.34), but time main effect and group main effect were significant ( F=131.65, 16.98, both P<0.05). On the 2nd to 4th day, mice in model group showed significantly increased escape latency than mice in control group and Apelin-13 group(both P<0.05). And the numbers crossing original platform and the time in the target quadrant of Apelin-13 group were both higher than those of model group and normal saline group (all P<0.05). (2) HE staining results showed that neurons in the hippocampal CA1 and CA3 area of mice in model group and normal saline group were swollen and arranged loosely.The hippocampal neurons in control group and Apelin-13 group were arranged neatly and densely. (3) Western blot results showed statistically significant differences in the protein expression of p-PI3K, p-Akt, p-FoxO3a, p62 and the ratio of LC3Ⅱ/LC3Ⅰ among the four groups ( F=21.37, 37.35, 20.71, 13.26, 37.65, all P<0.05). The protein expression of p-PI3K, p-Akt, p-FoxO3a and p62 in Apelin-13 group((0.92±0.07), (0.90±0.09), (0.89±0.13), (1.03±0.08)) were higher than those in model group((0.59±0.04), (0.50±0.07), (0.49±0.11), (0.68±0.04)) and normal saline group((0.61±0.06), (0.50±0.08), (0.53±0.11), (0.70±0.05))(all P<0.05), and the ratio of LC3Ⅱ/LC3Ⅰ in Apelin-13 group(0.60±0.06) was lower than those in model group(0.92±0.10) and normal saline group(0.99±0.05) (both P<0.05). Conclusion:Apelin-13 can alleviate the anxiety-like behavior and impaired spatial learning and memory in PTSD model mice. The mechanism may be related to the up-regulation of PI3K/Akt/FoxO3a autophagy pathway.
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Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms.Methods Human renal podocytes were divided into four experimental groups:control group,high glucose(HG)group(glucose 25 mmol/L,48 h),Apelin intervention HG group(Ape-lin-13 1 μmol/L,48 h)and Apelin group(Apelin-13 1 μmol/L,48 h).The podocyte apoptosis was observed by TUNEL staining,the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot,and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation.The 8-week-old male mice were divided into three experimental groups:control group,diabetes group(intraperito-neal injection of streptozotocin 150 mg/kg,only one time)and Apelin intervention DM group(intraperitoneal injection of Apelin-13 0.3 μmol/kg,daily).The morphology of renal was observed by PAS staining and trans-mission electron microscopy.Plasma creatinine(Cr),urea nitrogen,urinary albumin and creatinine were de-tected by ELISA kit.The level of creatinine clearance rate(Ccr)and urinary albumin/creatinine(ACR)was calculated.Results Compared with the control group,the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly(P＜0.05),and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised.Meanwhile,compared with the HG group,the number of apoptosis,the expression of FUNDC1(P＜0.05),and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group.Animal experiments showed that the kidney structure of the control group was intact.In the DM group,the num-ber of podocytes decreased significantly,the foot processes were fused and dropped off.In the Apelin intervention DM group,podocyte lesions were less severe than those in the DM group.Compared with the control group,the level of plasma Cr,BUN and urine ACR in the DM group increased,while the level of Ccr decreased significantly(P＜0.05).However,compared with the DM group,the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte ap-optosis by inhibiting the expression of mitochondrial membrane protein FUNDC1,which may contribute to allevia-tion of diabetic nephropathy.
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OBJECTIVE@#To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS).@*METHODS@#Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot.@*RESULTS@#Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05).@*CONCLUSION@#Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.
Subject(s)
Mice , Animals , Apelin , Tissue Plasminogen Activator/metabolism , Quercetin/therapeutic use , AMP-Activated Protein Kinases/metabolism , Sirtuin 1/metabolism , Signal Transduction/physiology , Atherosclerosis/metabolism , Apolipoproteins EABSTRACT
Aim To explore the effects of putative receptor protein related to ATI (APJ) homodimer on the behaviors-the proliferation, migration and tube formation of human umbilical vein endothelial cells (HU-VECs). Methods HUVECs at logarithmic growth stage were randomly divided into PBS, Apelin-13 + TM1 (APJ monomer group) and Apelin-13 + PBS group (APJ homodimer group). Western blot and Matrix-Assisted Laser Desorption/Ionization Time of Fligh Mass Spectrometry (MALDI-TOF MS) were used to detect the expression of APJ and APJ homodimer in HUVECs, respectively. Real-Time Cell Analyzers (RT-CA) was used to detect the concentration of the maximum effect of Apelin-13. Cell viability was detected by CCK-8. The cell migration ability was detected by scratch test, and the number of tubes formed on matri-gel that made artificial basement membrane was counted. Results Western blot and MALDI-TOF MS showed that APJ and APJ homodimer were expressed in HUVECs. The EC50 of Apelin-13 was 2.26 x 10
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AIM:To analyze the correlation between serum nesfatin-1, apelin and heme oxygenase-1(HO-1)levels and the severity of diabetic retinopathy(DR).METHODS:Totally 100 patients with type 2 diabetes mellitus(T2DM)who were admitted to the hospital from September 2020 to September 2022 were selected. They were divided into non-DR(NDR)group(35 cases), nonproliferative DR(NPDR)group(33 cases)and proliferative DR(PDR)group(32 cases)according to the condition of fundus lesions. Another 30 healthy individuals who received health check-ups in the hospital during the same period were selected as the control group. Serum nesfatin-1, apelin and HO-1 levels in each group were detected, and panretinal ischemia index(ISI)was evaluated.RESULTS:Serum nesfatin-1 and HO-1 levels in the T2DM patients were lower, and apelin level was higher as compared with the control group. The levels of nesfatin-1 and HO-1 in the PDR group were the lowest, while the apelin level was the highest. Panretinal ISI in the PDR group was higher than that in the NPDR group(4.56±0.57 vs. 2.05±0.29, P&#x003C;0.05). Correlation analysis found that serum nesfatin-1 and HO-1 levels were negatively correlated with panretinal ISI in patients with DR, while apelin level was positively correlated with panretinal ISI. The receiver operator characteristic(ROC)curve analysis found that the areas under the curves of serum nesfatin-1, apelin and HO-1 for predicting PDR were 0.842, 0.833 and 0.807 respectively.CONCLUSION:Serum nesfatin-1, apelin and HO-1 levels are closely related to the severity of DR. Dynamic monitoring of serum nesfatin-1, apelin and HO-1 levels is important for the early detection of PDR.
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Objective:To investigate the relationship between the level of Apelin-13 and coronary artery lesion (CAL) in patients with Kawasaki disease (KD), and assess the predictive value of Apelin-13 for CAL in acute phase of KD.Methods:A total of 240 children with KD treated in Chengdu Women and Children′s Central Hospital from September 2017 to October 2019 were recruited, and were divided into KD with CAL (KD-CAL) group and KD without CAL (KD-NCAL) group.Thirty children with acute upper respiratory infection and 30 healthy children were recruited into the febrile control group and the healthy control group, respectively.Blood routine and serum levels of albumin, C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Apelin-13 were mea-sured in KD children prior to intravenous gamma globulin injection and after the diagnosis of children in the febrile control group and physical examination of children in the healthy control group.The clinical data of children in each group were compared, and the risk factors of KD complicated with CAL and the predictive value of Apelin-13 were determined by using receiver operating characteristic (ROC) curve and multiple Logistic regression analysis. Results:Apelin-13 and hemoglobin in children with KD were significantly decreased compared with those in the healthy control group and fever control group (all P<0.001). However, white blood cell(WBC) count, platelet count, CRP and NT-proBNP in KD group were significantly increased compared with those in the healthy control group and fever control group (all P<0.001). Serum albumin in KD children was significantly lower than that in the healthy control group ( P=0.004), and there was no difference when compared with the fever control group ( P=0.485). Apelin-13 and hemoglobin were significantly decreased in KD-CAL group compared with KD-NCAL group ( t=10.102, P<0.001; t=2.034, P=0.043), while NT-proBNP and CRP were significantly increased ( t=5.982, 3.728, all P<0.001). Multiple logistic regression analysis showed that Apelin-13 and NT-proBNP were independent predictors of CAL in KD.The ROC curve analysis showed that the cut-off value of Apelin-13 for predicting CAL was 2.99 μg/L, with an area under the curve (AUC) of 0.869 (95% CI: 0.820-0.909), sensitivity of 77.78% and specificity of 88.67%.While NT-proBNP cutoff value of 822 ng/L yielded sensitivity of 57.78% and specificity of 84.62% for predicting CAL with an AUC of 0.718(95% CI: 0.656-0.774). Conclusions:Apelin-13 plays a protective role in KD complicated with CAL, and could be used to predict CAL in the acute phase of KD.
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Sepsis is a serious life-threatening organ dysfunction disease caused by the body′s response to infection, which is the main cause of death in patients admitted to ICU.The occurrence, development and prognosis of sepsis are closely related to metabolism and regulation of inflammatory response.Adipose tissue not only participates in energy storage and metabolism, but also, as an important endocrine organ, secretes a variety of adipokines with pro-inflammatory or anti-inflammatory activities, and thus participates in the occurrence and development of sepsis.There are many kinds of adipokines, and different adipokines play different roles in sepsis and sepsis-related organ damage.Some adipokines such as adiponectin, adipokine complement Clq/tumor necrosis factor-associated protein 3, vaspin, irisin and Apelin are closely related with the pathogenesis and prognosis of organ injury in sepsis.
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Resumo Fundamento: Os efeitos benéficos do elabela no sistema cardiovascular foram demonstrados em estudos. Objetivo: Comparar os níveis séricos de elabela de pacientes com oclusão total crônica (OTC) com pacientes controle com artérias coronárias normais e investigar se há correlação com o desenvolvimento colateral. Métodos: Estudo transversal e prospectivo. O estudo incluiu cinquenta pacientes (28,0% mulheres, idade média 61,6±7,3 anos) com OTC em pelo menos um vaso coronário e 50 pacientes (38% mulheres, idade média 60,7±6,38 anos) com artérias coronárias normais. Os pacientes do grupo OTC foram divididos em dois grupos: Rentrop 0-1, composto por pacientes com fraco desenvolvimento colateral e Rentrop 2-3, composto por pacientes com bom desenvolvimento colateral. Além da idade, sexo, características demográficas e exames laboratoriais de rotina dos pacientes, foram medidos os níveis de elabela. Resultados: As características demográficas e os valores laboratoriais mostraram-se semelhantes em ambos os grupos. Ao passo que o nível médio de NT-proBNP e troponina estava maior no grupo OTC, o nível médio de elabela estava menor (p<0,05 para todos). Na análise de regressão multivariada, os níveis de NT-proBNP e elabela foram considerados preditores independentes para OTC. Além disso, o nível de elabela apresentou-se estatisticamente maior em pacientes do grupo Rentrop 2-3 em comparação com os pacientes do grupo Rentrop 0-1 (p<0,05). Conclusões: Em nosso estudo, mostramos que o nível médio de elabela estava baixo em pacientes com OTC em comparação com pacientes normais. Além disso, constatamos que o nível de elabela é inferior em pacientes com desenvolvimento colateral fraco em comparação com pacientes com bom desenvolvimento colateral. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)
Abstract Background: The beneficial effects of Elabela on the cardiovascular system have been shown in studies. Objective: To compare serum Elabela levels of chronic total occlusion (CTO) patients with control patients with normal coronary arteries, and to investigate whether there is a correlation with collateral development. Methods: The study was planned cross-sectionally and prospectively. Fifty patients (28.0% female, mean age 61.6±7.3years) with CTO in at least one coronary vessel and 50 patients (38% female, mean age 60,7±6.38 years) with normal coronary arteries were included in the study. Patients in the CTO group were divided into two groups as Rentrop 0-1, those with weak collateral development, and Rentrop 2-3 with good collateral development. In addition to the age, sex, demographic characteristics and routine laboratory tests of the patients, Elabela levels were measured. Results: Demographic characteristics and laboratory values were similar in both groups. While the mean NT-proBNP and troponin were higher in the CTO group, the Elabela mean was lower (p <0.05 for all). In the multivariate regression analysis, NT-proBNP and Elabela levels were found to be independent predictors for CTO. Also, Elabela level was found to be statistically higher in Rentrop class 2-3 patients compared to Rentrop class 0-1 patients (p<0.05). Conclusion: In our study, we showed that the average Elabela level was low in CTO patients compared to normal patients. In addition, we found the level of Elabela to be lower in patients with weak collateral development compared to patients with good collateral development. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)
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Humans , Male , Female , Aged , Coronary Occlusion , Angina, Stable , Chronic Disease , Multivariate Analysis , Coronary Angiography , Collateral Circulation , Coronary Vessels , Middle AgedABSTRACT
Abstract Introduction: In this study, we aimed to investigate the impact of transcatheter aortic valve implantation (TAVI) on serum apelin levels in patients with severe symptomatic aortic valve stenosis (AS). Methods: Forty-six consecutive patients (76.9±7.4 years, n=27 women) who underwent TAVI and 45 age- and sex-matched control subjects were included in the study. Echocardiographic parameters, serum apelin, pro-brain natriuretic peptide (Pro-BNP), and troponin I levels were compared between the groups. In addition, the preprocedural and first-month follow-up echocardiographic parameters and serum apelin values of TAVI patients were compared. Results: Serum median troponin I and Pro-BNP levels were significantly higher and serum apelin levels were significantly lower in TAVI patients before TAVI procedure than in the control subjects (P<0.001, for all). Median troponin I and Pro-BNP levels were significantly decreased and apelin levels were significantly increased after TAVI procedure compared to the peri-procedural levels. There was a significant and moderate negative correlation between Pro-BNP and apelin levels measured before and after TAVI procedure. A statistically significant and strong negative correlation was found between aortic valve area and Pro-BNP level before TAVI procedure, while a statistically significant but weak positive correlation was found between valve area and apelin level. Conclusion: In our study, apelin levels were significantly lower and Pro-BNP levels were higher in AS patients compared with the control group. Moreover, after TAVI procedure, a significant increase in apelin levels and a significant decrease in Pro-BNP levels were observed. There was also a negative and moderate correlation between apelin and Pro-BNP levels.
Subject(s)
Humans , Female , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Transcatheter Aortic Valve Replacement , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Echocardiography , Treatment Outcome , Constriction, Pathologic , ApelinABSTRACT
Endoplasmic reticulum stress (ERS) is closely related to the development of Parkinson' s disease (PD). Apelin, an endogenous peptide, has a remarkable neuroprotective effect. However, its protective mechanism is still unclear. In the present study, we investigate the molecular mechanism of Apelin-17 reducing the apoptosis of SH-SY5Y cells induced by 1-methyl-4- phenylpyridine (MPP
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Objective: To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.Methods: Sixty-six patients were randomly divided into a control group and an observation group according to the random number table method, with 33 cases in each group. Patients in the control group were treated with exenatide and metformin, while patients in the observation group were treated with additional acupoint thread-embedding. After 12-week treatment, the obesity-related indicators, including body mass index (BMI), waist circumference and body fat rate, the glycometabolism indicators, including fasting blood glucose, 2 h postprandial blood glucose and glycosylated hemoglobin, and the lipid metabolism indicators, including total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), as well as serum apelin and GLP-1 levels were observed in patients of the two groups. Results: After treatment, the BMI, waist circumference and body fat rate of patients in the two groups were all reduced (all P<0.05), and were lower in the observation group than in the control group (all P<0.05); the fasting blood glucose, 2 h postprandial blood glucose and glycosylated hemoglobin levels of patients in both groups were all decreased (all P<0.05), and were significantly lower in the observation group than in the control group (all P<0.05); the TC level was decreased (P<0.05), while the TG and LDL-C levels did not change significantly in the control group (both P>0.05); the TC, TG and LDL-C levels were all significantly reduced in the observation group (all P<0.05), lower than those in the control group (all P<0.05); the serum apelin level was decreased (P<0.05) and the serum GLP-1 level was increased (P<0.05) in the observation group, statistically different from those in the control group (both P<0.05). Conclusion: Combined with the conventional medication, acupoint thread-embedding therapy can significantly improve the obesity-related indicators, glycometabolism and lipid metabolism in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen. This may be achieved by regulating the serum apelin and GLP-1 levels.
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OBJECTIVE: To explore the association of serum Apelin level, silicosis stage and lung function in patients with occupational silicosis(hereinafter referred to as silicosis). METHODS: A case-control study was conducted. A total of 85 patients with silicosis were selected as the silicosis group(44, 28 and 13 patients with stage Ⅰ, Ⅱ and Ⅲ silicosis, respectively), and 120 healthy individuals without occupational hazard exposure were selected as the control group. Serum samples were collected from the cases of the two groups and the level of Apelin was determined by enzyme-linked immunosorbent assay. The pulmonary function of the silicosis group was examined. RESULTS: The median and the 25 th and 75 th percentiles \[M(P_(25),P_(75))\] of serum Apelin levels in the control group and silicosis group were 1.29(0.92, 1.77) and 0.80(0.62, 1.04) mg/L, respectively. The level of serum Apelin M(P_(25),P_(75)) in stage Ⅰ, Ⅱ and Ⅲ silicosis patients was 1.03(0.82, 1.31), 0.66(0.60, 0.80) and 0.50(0.30, 0.65) mg/L, respectively. The results of multiple linear regression analysis showed that the level of serum Apelin in the silicosis group was higher than that in the control group after excluding the influence of age and smoking(P<0.01). The level of serum Apelin decreased with the increase of silicosis stage in the silicosis group(P<0.001). Serum Apelin level in silicosis group was positively correlated with lung vital capacity, forced vital capacity, forced expiratory volume in the first second, and forced expiratory flow between 25% and 75%(all P<0.05). CONCLUSION: The lower level of serum Apein in silicosis patients, the more serious the disease and the more serious the damage to lung function. Apelin is of significance in the diagnosis, staging, treatment appraisal and prognostic evaluation of silicosis, and it can be use as a potential therapeutic target for silicosis.
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Elabela is a newly discovered peptide in recent years.It is the endogenous ligand of Apelin receptor(APJ)and plays an important role in embryonic development and adult organs.Elabela-APJ axis is closely related to organ fibrosis.Elabela can protect the functions of heart and kidney by antagonizing renin-angiotensin system and regulating blood pressure.In addition,it can prevent kidney and heart fibrosis by down-regulating the expression of fibrosis and inflammatory factors.However,there is a positive correlation between the level of Elabela and the degree of liver fibrosis,suggesting that Elabela may play a role in promoting liver fibrosis.This review aims to explore the role of Elabela-APJ axis in renal fibrosis,cardiac fibrosis,and liver fibrosis,and to provide a new therapeutic target for organ fibrosis.
Subject(s)
Female , Humans , Pregnancy , Apelin , Apelin Receptors , Blood Pressure , Fibrosis , Peptide HormonesABSTRACT
Objective:To investigate the changes in the expression of toll like receptor 4 (TLR4), pentamerin-3 (PTX3) and Apelin in the blood of patients with sepsis and their relationship with the condition and prognosis.Methods:From March 2015 to March 2020, 82 patients with sepsis in the First People′s Hospital of Chenzou were retrospectively selected, including 22 patients in septic shock group, 34 patients in severe sepsis group and 26 patients in general sepsis group. 82 healthy people in the same period were selected as the control group. The expression of serum TLR4, PTX3, Apelin, Sequential Organ Dysfunction Score (SOFA), Acute Physiology and Chronic Health Score System Ⅱ (APACHE Ⅱ) were measured and compared. The relationship between the expression of serum TLR4, PTX3 and Apelin and the scores of SOFA and APACHE Ⅱ in patients with sepsis were analyzed. The general data and the expression of serum TLR4, PTX3 and Apelin in patients with sepsis with different prognosis (28 day survival and death) were counted. The influencing factors of prognosis in patients with sepsis were observed, and the predictive significance of serum TLR4, PTX3 and Apelin on the prognosis of patients with sepsis was analyzed.Results:Comparison of serum TLR4, PTX3 and Apelin level in the groups: septic shock group>severe sepsis group>general sepsis group>control group ( P<0.05); The serum level of TLR4, PTX3 and Apelin in patients with high SOFA and APACHE Ⅱ scores were higher than those in patients with low SOFA and APACHE Ⅱ scores ( P<0.05); Pearson correlation showed that serum level of TLR4, PTX3 and Apelin was positively correlated with the SOFA and APACHE Ⅱ scores of sepsis patients ( P<0.05); The levels of serum TLR4, PTX3, Apelin and the scores of SOFA and APACHE Ⅱ in the dead patients with sepsis were higher than those in survival patients ( P<0.05); Logistic regression analysis found that serum level of TLR4, PTX3, Apelin, SOFA score, and APACHE Ⅱ score were all important risk factors for 28 day death of sepsis patients ( P<0.05); The receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of combined blood indexes (TLR4, PTX3 and Apelin) in predicting the prognosis of patients with sepsis were 85.71% and 85.25%. Conclusions:The expression of serum TLR4, PTX3 and Apelin in patients with sepsis can be significantly increased, which is related to the patient′s condition and prognosis and can provide a certain basis for clinical diagnosis and treatment.
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ABSTRACT Objective: This study investigated whether ELABELA plays a role in the differential diagnosis of benign and malignant lesions of the thyroid gland. Subjects and methods: Of the 87 patients included in the study, 12 had undergone surgery for benign thyroid diseases, 30 had papillary thyroid cancer without invasion and/or lymph node metastasis in the surrounding tissues in the pathology report, and 45 had papillary thyroid cancer with invasion and/or lymph node metastasis in the surrounding tissues. Results: In the macrocarcinoma group, the proportion of patients with severe ELABELA staining (61.1%) was higher than that in the adenoma (50%) and microcarcinoma (23.8%) groups, while the proportion of those with mild to moderate staining was lower (p < 0.001). In the microcarcinoma group, the proportion of patients with severe staining was lower than that in the adenoma group, while the proportion of those with mild to moderate staining was higher (p < 0.001). In papillary thyroid carcinomas, the rates of moderate and severe staining in the classical variant, mild staining in the follicular variant, severe staining in the classical + follicular variant, and severe staining in the oncocytic variant were higher. Conclusion: To the best of our knowledge, this study is the first to be conducted on this subject. In this study, ELABELA was not found to be significant in the differential diagnosis of benign and malignant lesions of the thyroid gland. In papillary thyroid carcinomas, severe ELABELA staining patterns were more common in macrocarcinoma patients than in microcarcinoma patients.
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Humans , Thyroid Neoplasms/diagnosis , Carcinoma, Papillary/diagnosis , Diagnosis, Differential , Thyroid Cancer, Papillary/diagnosisABSTRACT
BACKGROUND: Elabela is a new type of endogenous receptor of APJ discovered in recent years. It is widely distributed in the adult cardiovascular system and has a certain influence on cardiovascular diseases. However, the effect of Elabela on the differentiation of stem cells into cardiomyocytes and the expression of APJ in cardiomyocyte differentiation has not been studied yet. OBJECTIVE: To investigate the effect of Elabela on the differentiation of Wharton’s jelly-derived mesenchymal stem cells into cardiomyocytes. METHODS: The frozen mesenchymal stem cells were resuscitated. 5-Azacytidine was used to induce Wharton’s jelly-derived mesenchymal stem cells to differentiate into cardiomyocytes when the cell confluence reached 80%-90%. After 24 hours, the medium was replaced by low-glucose medium containing Elabela and 10% fetal bovine serum in the experimental group, and by low-glucose medium containing 10% fetal bovine serum in the control group. At 7, 14, 21, and 28 days after induction, cell morphology was observed. The total RNA and total protein of each group were collected. The myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein expression levels were detected by real-time fluorescent quantitative PCR and western blot assay. The expression of APJ in the induced cardiomyocytes was detected by real-time fluorescent quantitative PCR and flow cytometry. RESULTS AND CONCLUSION: (1) The expression levels of myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein were higher in the experimental group than in the control group in all stages of differentiation, and the expression of APJ was also higher in the experimental group than in the control group. (2) In summary, Elabela plays a certain promoting role in the differentiation of Wharton’s jelly-derived mesenchymal stem cells into oriented cardiomyocytes. Elabela, as another agonist of APJ, can promote the expression of APJ during the induced cell differentiation.
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@#AIM: To analyze the function and mechanism of Apelin-13 in preventing the apoptosis of retinal Müller cells induced by hypoxia.<p>METHODS: In the research, the retinal Müller cells are regarded as research subjects, and the control group, hypoxia group and experiment group are set up. The cells of control group are cultivated in normal environment. The cells of hypoxia group are cultivated in hypoxia environment. The cells of experiment group are cultivated in hypoxia environment and are treated with the Apelin-13(1μmol/L). MTT method is used to monitor the changing of the cell viability, and the crystal violet staining method is adopted to observe the cell morphology. In addition, the immunofluorescence staining method is used to test the expression of GFAP and YAP and the TUNEL staining method is used to monitor the cell apoptosis situation and the apoptosis index is calculated. The protein staining method is used to observe the changing of the expression of p-LATS1, p-YAP, LATS1 and YAP protein. <p>RESULTS:The separated and extracted Müller cells grow on the wall and show elongation, polygon and circular shapes. The cytoplasm is plentiful and the cell nucleus show circular shape. The GFAP expression of the cell is positive. The treatment with 0.1, 1, 10μmol/L Apelin-13 can obviously prevent the Müller cell viability decreasing induced by hypoxia(<i>P</i><0.05 or <i>P</i><0.01). Compared with the control group, the cell apoptosis index of hypoxia group is obviously increased(<i>P</i><0.01). However, compared with the hypoxia group, the cell apoptosis index of experiment group is obviously decreased(<i>P</i><0.01). The p-LATS1 and p-YAP protein expression of the control group and hypoxia group does not have big difference. Compared with hypoxia group, the p-LATS1 and p-YAP protein expression of experiment group is obviously decreased(<i>P</i><0.01). The YAP protein expression of cell nucleus of control group and hypoxia group does not have great difference. Compared with hypoxia group, the cell nucleus expression of YAP cell is gretaly increased(<i>P</i><0.01). <p>CONCLUSION: Apelin-13 can be used to prevent the retinal Müller cells apoptosis caused by the hypoxia, which may be related to the regulation of YAP into the nucleus.
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@#AIM: To analyze the function and mechanism of Apelin-13 in preventing the apoptosis of retinal Müller cells induced by hypoxia.<p>METHODS: In the research, the retinal Müller cells are regarded as research subjects, and the control group, hypoxia group and experiment group are set up. The cells of control group are cultivated in normal environment. The cells of hypoxia group are cultivated in hypoxia environment. The cells of experiment group are cultivated in hypoxia environment and are treated with the Apelin-13(1μmol/L). MTT method is used to monitor the changing of the cell viability, and the crystal violet staining method is adopted to observe the cell morphology. In addition, the immunofluorescence staining method is used to test the expression of GFAP and YAP and the TUNEL staining method is used to monitor the cell apoptosis situation and the apoptosis index is calculated. The protein staining method is used to observe the changing of the expression of p-LATS1, p-YAP, LATS1 and YAP protein. <p>RESULTS:The separated and extracted Müller cells grow on the wall and show elongation, polygon and circular shapes. The cytoplasm is plentiful and the cell nucleus show circular shape. The GFAP expression of the cell is positive. The treatment with 0.1, 1, 10μmol/L Apelin-13 can obviously prevent the Müller cell viability decreasing induced by hypoxia(<i>P</i><0.05 or <i>P</i><0.01). Compared with the control group, the cell apoptosis index of hypoxia group is obviously increased(<i>P</i><0.01). However, compared with the hypoxia group, the cell apoptosis index of experiment group is obviously decreased(<i>P</i><0.01). The p-LATS1 and p-YAP protein expression of the control group and hypoxia group does not have big difference. Compared with hypoxia group, the p-LATS1 and p-YAP protein expression of experiment group is obviously decreased(<i>P</i><0.01). The YAP protein expression of cell nucleus of control group and hypoxia group does not have great difference. Compared with hypoxia group, the cell nucleus expression of YAP cell is gretaly increased(<i>P</i><0.01). <p>CONCLUSION: Apelin-13 can be used to prevent the retinal Müller cells apoptosis caused by the hypoxia, which may be related to the regulation of YAP into the nucleus.
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ABSTRACT Objective: In this study, we aimed to evaluate serum irisin and apelin levels in patients with subclinical hypothyroidism (SCH) when they were subclinical hypothyroid and become euthyroid after levothyroxine therapy and association of these adipokines with markers of atherosclerosis such as serum homocysteine levels and carotid intima-media thickness (IMT). Subjects and methods: The study included 160 patients with newly diagnosed subclinical hypothyroidism due to Hashimoto's thyroiditis and 86 euthyroid healty subjects. Serum glucose and lipid profile, insulin, HOMA, TSH, free T3, free T4, anti-thyroperoxidase and anti-thyroglobulin antibodies, homocysteine, apelin and irisin levels were measured in all study subjects. Thyroid and carotid ultrasound examinations were performed. The subclinical hypothyroid group was reevaluated after 12-weeks of levothyroxine therapy when they became euthyroid. Results: Clinical characteristics of the patient and control group were similar. Glucose, insulin and HOMA levels, lipid parameters and free T3 were similar between the two groups.. Serum homocystein was higher and apelin was lower in patients with SCH, but irisin levels were similar between the two groups. While thyroid volume was lower, carotid IMT was significantly greater in patients with SCH (pCarotidIMT:0,01). After 12-weeks of levothyroxine therapy, all the studied parameters remained unchanged except, serum freeT4, TSH, homocystein and apelin. While homocystein decreased (p: 0,001), apelin increased significantly (p = 0,049). In multivariate analysis, low apelin levels significantly contributed to carotid IMT (p = 0,041). Conclusions: Apelin-APJ system may play a role in vascular and cardiac dysfunction in patients with SCH and treatment of this condition may improve the risk of cardiovascular disease.