BACKGROUND Hypertension is a chronic cardiovascular disease characterized by persistently elevated arterial blood pressure.It is not only a significant risk factor for cardio-vascular and cerebrovascular diseases(such...BACKGROUND Hypertension is a chronic cardiovascular disease characterized by persistently elevated arterial blood pressure.It is not only a significant risk factor for cardio-vascular and cerebrovascular diseases(such as myocardial infarction and stroke)but also closely related to multiple organ damages(such as kidney disease and retinopathy),imposing a heavy health and economic burden on individuals and society.AIM To investigate the expression differences and relationships of endothelin-1(ET-1),interleukin-6(IL-6),stem cell factor(SCF),and its receptor(c-kit)in hypertensive patients with or without depression.METHODS A retrospective analysis was conducted on the clinical data of 163 hypertensive patients admitted to our hospital from March 2022 to January 2024.Based on the presence of depression,patients were divided into Group A(n=77,with depre-ssion)and Group B(n=86,without depression).Serum levels of ET-1 and IL-6 were measured using radioimmunoassay,while serum levels of SCF and c-kit were measured using ELISA.The differences in ET-1,IL-6,SCF,and c-kit levels between Groups A and B were compared.Additionally,the differences in these biomarkers among patients with varying degrees of depression in Group A were analyzed.Pearson correlation analysis was used to examine the relationship between ET-1,IL-6,SCF,c-kit levels,and Hamilton depression rating scale(HAMD)scores.Multivariate logistic regression analysis was performed to identify factors influencing hypertension with depression.The diagnostic efficacy of individual and combined biomarkers was analyzed using receiver operating characteristic(ROC)curves.Comparative statistical analysis of the area under the curve(AUC)values was performed using DeLong’s test to assess the superiority of combined biomarker detection.RESULTS The levels of ET-1 and IL-6 in Group A were significantly higher than those in Group B,while the levels of SCF and c-kit were significantly lower in Group A compared to Group B(P<0.05).In the severe depression subgroup,ET-1 and IL-6 levels were higher than those in the mild-to-moderate depression subgroup,while SCF and c-kit levels were lower(P<0.05).Pearson correlation analysis showed that ET-1 and IL-6 levels were positively correlated with HAMD scores(r=0.442,0.463,P<0.05),while SCF and c-kit levels were negatively correlated with HAMD scores(r=-0.429,-0.394,P<0.05).Multivariate logistic regression analysis revealed that high ET-1,high IL-6,low SCF,and low c-kit were independent influencing factors for hypertension with depression(P<0.05).ROC analysis revealed AUCs of 0.746(ET-1),0.801(IL-6),0.732(SCF),0.779(c-kit),and 0.884(combination).The combined diagnosis demonstrated significantly higher AUC than individual markers(DeLong's test,P<0.01),with superior sensitivity(90.24%)and specificity(85.37%).CONCLUSION Compared to patients with hypertension alone,patients with hypertension and depression exhibited higher serum levels of ET-1 and IL-6 and lower levels of SCF and c-kit.High ET-1,high IL-6,low SCF,and low c-kit were inde-pendent influencing factors for hypertension with depression.The combination of ET-1,IL-6,SCF,and c-kit demonstrated significant diagnostic value for hypertension with depression.展开更多
Background:Colorectal cancer(CRC)is a predominant contributor to global cancer-associated mortality worldwide.Oxaliplatin(OXP),a foundational chemotherapeutic agent for CRC,often exhibits limited efficacy due to the e...Background:Colorectal cancer(CRC)is a predominant contributor to global cancer-associated mortality worldwide.Oxaliplatin(OXP),a foundational chemotherapeutic agent for CRC,often exhibits limited efficacy due to the emergence of drug resistance.Although endothelin-1(EDN1)has been implicated in tumor drug resistance,its role in oxaliplatin resistance in CRC remains poorly defined.This work aimed to define how EDN1 contributes to oxaliplatin resistance and to explore its potential as a therapeutic target.Methods:Public genomic datasets were analyzed to confirm EDN1 upregulation in colorectal cancer(CRC)and its association with poor prognosis.EDN1 expression was modulated in parental and oxaliplatin-resistant CRC cell lines via shRNA knockdown and lentiviral overexpression.Functional assays,including drug sensitivity,flow cytometry,and 5-Ethynyl-2′-deoxyuridine(EdU)proliferation,were conducted to assess resistance.Mechanistic studies employed dual-luciferase reporter assays,Western blotting,co-immunoprecipitation,and immunofluorescence.CRC-derived subcutaneous xenograft models were used to evaluate the therapeutic efficacy of EDN1 targeting in vivo.Results:The study identifies EDN1 as a pivotal mediator of oxaliplatin resistance in CRC.EDN1 expression is markedly upregulated in oxaliplatin-resistant CRC cells and is significantly associated with poor patient survival outcomes.Mechanistically,EDN1 overexpression activates the Yes-associated protein(YAP)signaling by promoting the nuclear translocation of β-arrestin1(β-arr1),thereby facilitating chemoresistance.Importantly,the combinatorial inhibition of EDN1,in conjunctionwith oxaliplatin treatment,substantially enhances apoptosis and suppresses tumor growth both in vitro and in vivo.Conclusion:The study demonstrates that EDN1 governs oxaliplatin resistance through theβ-arr1/YAP axis and provides preclinical evidence for targeting EDN1 to overcome chemoresistance in CRC.展开更多
Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells （RGCs） in a rat chronic ocular hypertension （COH） model. Here, we investigated the expression of endothelin...Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells （RGCs） in a rat chronic ocular hypertension （COH） model. Here, we investigated the expression of endothelin-1 （ET-1）, a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure （IOP） was induced in the right eye of SD rats using argon laser photocoagulation. （1） The expression of ET-1, ETA and ETB in normal and COH retinas was studied. （2） Some COH rats were fed daily with Lycium barbarum Polysaccharides （LBP） using 1 mg/kg or phosphate-buffered saline （PBS） for 3 weeks （started 1 week before photocoagulation）. The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that （1） Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. （2） After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. （3） By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.展开更多
AIM： To examine the ability of FT-1 to affect the cell functions of PSCs and the underlying molecular mechanisms. METHODS： PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase, a...AIM： To examine the ability of FT-1 to affect the cell functions of PSCs and the underlying molecular mechanisms. METHODS： PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase, and cells between passages two and five were used. Expression of ET-1 and FT receptors was assessed by reverse transcription-PCR and immunostaining. Phosphorylation of myosin regulatory light chain （MLC）, extracellular-signal regulated kinase （FRK）, and Akt was examined by Western blotting. Contraction of PSCs was assessed on hydrated collagen lattices. Cell migration was examined using modified Boyden chambers. Ceil proliferation was assessed by measuring the incorporation of 5-bromo-2＇- deoxyuridine. RESULTS： Culture-activated PSCs expressed ETA and ETB receptors, and ET-1. ET-1 induced phosphorylation of NLC and FRK, but not Akt. ET-1 induced contraction and migration, but did not alter proliferation of PSCs. FT-1-induced contraction was inhibited by an ETA receptor antagonist BQ-123 and an ETB receptor antagonist BQ-788, whereas migration was inhibited by BQ-788 but not by BQ-123. A Rho kinase inhibitor Y-27632 abolished both contraction and migration. CONCLUSION： ET-1 induced contraction and migration of PSCs through El receptors and activation of Rho-Rho kinase. ETA and FTB receptors play different roles in the regulation of these cellular functions in response to ET-1.展开更多
Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coron...Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coronary heart disease were randomly divided into a treatment group(n=45) treated by Liandou Qingmai Recipe and a standard treatment group(control group,n=56),with a normal group of 16 health persons set up.Changes of ET-1,NO,IL-6 and IL-10 levels were measured before treatment and after treatment for two weeks.And the data were analyzed by SPSS 16.0 statistic software.Results:Before treatment,the levels of ET-1,IL-6 and IL-10 levels were significantly higher and NO was significantly lower in the patients with coronary heart disease than those in the normal group(90.7±12.7 ng/L vs 41.8±13.5 ng/L,9.17±0.18 ng/L vs 1.10±0.08 ng/L,1.94±0.26 ng/L vs 1.09±0.06 ng/L,and 92.2±17.7 μmol/L vs 124.5±27.2 μmol/L;all P<0.05),with no significant differences in the levels of ET-1,NO,IL-6 and IL-10 between the treatment group and the control group(P>0.05);After treatment,ET-1 and IL-6 significantly decreased in the treatment group and the control group,and NO increased in the treatment group;And IL-6 level was significantly lower and NO level was higher in the treatment group than those in the control group(4.48±1.22 ng/L vs 5.13±1.85 ng/L,117.4±22.3 μmol/L vs 92.4±17.1 μmol/L;both P<0.05);There was a positive correlation between IL-6 and IL-10,and a negative correlation between NO and IL-10(r=0.142,r=-0.152;both P<0.05).Conclusion:Liandou Qingmai Recipe can decline IL-6,IL-10 and ET-1 levels,and raise NO level in patients with coronary heart disease on the basis of standard treatment,so as to inhibit endothelial inflammatory response,improve vascular endothelial function,with stronger anti-AS action;And vascular endothelial lesion is related with inflammatory response.展开更多
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups,...To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups, with 6rats in each group: sham-operation group, simple ischemia group, ischemia-reperfusion group and treatment group (L-THP group). Cerebral ATP, lactate,ET-1 and NO levels were measured in all groups. Our results showed that treat-ment with L-THP could increase cerebral ATP levels, but decrease cerebral lac-tate, ET-1 and NO concentrations during ischemia-reperfusion in the treatmentgroup. It is concluded that L-THP could improve cerebral energy metabolism and protect the injured brain tissue, the mechanism of which might be related to suppression of overproduction of ET-1 and NO.展开更多
AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surger...AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function.展开更多
AIM: To assess the effect of non-selective ETA/B (LU 302872)and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerul...AIM: To assess the effect of non-selective ETA/B (LU 302872)and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP.METHODS: Male Wistar rats with caerulein-induced AP,lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w.of each antagonist. Edema, inflammatory infiltration,necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase,and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates.RESULTS: In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P＜0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82±0.06 at higher dose (P＜0.05) vs 0.58±0.06 in untreated AP. The nonselective antagonist increased slightly the vacuolization score to 2.41±0.07 at higher dose (P＜0.01) vs 1.88±0.08in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum,autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups.%FAT/TPT in untreated AP increased about four times (18.4±3.8 vs4.8±1.3 in control group without AP, P＜0.001).Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation.CONCLUSION: The treatment with endothelin-1 receptors (non-selective ETA/B and selective ETA) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.展开更多
Endothelin-1（ET-1）, a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine（TAU）, a naturally occurring free amino acid, is known for its neuropro...Endothelin-1（ET-1）, a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine（TAU）, a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co-or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.展开更多
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is st...Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.展开更多
OBJECTIVE： To observe the influence of moxibustion temperature on blood lipids, endothelin-1（ET-1）, nitric oxide（NO）, and ET-1/NO in hyperlipidemia patients. METHODS： Forty-two primary hyperlipidemia patients we...OBJECTIVE： To observe the influence of moxibustion temperature on blood lipids, endothelin-1（ET-1）, nitric oxide（NO）, and ET-1/NO in hyperlipidemia patients. METHODS： Forty-two primary hyperlipidemia patients were randomly divided into two groups of 21 and treated with moxibustion at different temperatures. Moxibustion was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group and 4 cm in the control group, 10 min per point, once every other day. Skin temperature was precisely measured with a thermometer during moxibustion. After a 12-week treatment, seven measurements of blood lipids, ET-1, and NO were recorded. RESULTS： Total cholesterol and triglyceride, were lower in the treatment group than in the control group（P0.05）. Serum ET-1 and ET-1/NO was obvi-ously lowered in the treatment group（P0.001）. Moxibustion regulated NO and ET-1/NO in the treatment group much better than in the control group. CONCLUSION： Moxibustion can regulate blood lipids and clear blood vessels. Moxibustion at 45℃has a better effect than moxibustion at 38℃ on regulating blood lipids and protecting vascular endothelial function, indicating that suitable temperature influences the curative effect of moxibustion.展开更多
AIM： To gain molecular insights into the expression and functions of endothelin-1 （ET-1） in pancreatic stellate cells （PSC）.METHODS： PSCs were isolated from rat pancreas tissue, cultured, and stimulated with ET-...AIM： To gain molecular insights into the expression and functions of endothelin-1 （ET-1） in pancreatic stellate cells （PSC）.METHODS： PSCs were isolated from rat pancreas tissue, cultured, and stimulated with ET-1 or other extracellular mediators. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2＇-deoxyuridine into DNA and cell migration was studied in a transwell chamber assay. Gene expression at the level of mRNA was quantified by real-time Polymerase chain reaction. Expression and phosphorylation of proteins were monitored by immunoblotting, applying an infrared imaging technology. ET-1 levels in cell culture supernatants were determined by an enzyme immunometric assay. To study DNA binding of individual transcription factors, electrophoretic mobility shift assays were performed.RESULTS： Among several mediators tested, transforming growth factor-β1 and tumour necrosis factor-α displayed the strongest stimulatory effects on ET-1 secretion. The cytokines induced binding of Smad3 and NF-κB, respectively, to oligonucleotides derived from the ET-1 promoter, implicating both transcription factors in the induction of ET-1 gene expression. In accordance with previous studies, ET-1 was found to stimulate migration but not proliferation of PSC. Stimulation of ET-1 receptors led to the activation of two distinct rnitogen-activated protein kinases, p38 and extracellular signal-regulated kinases （ERK）1/2, as well as the transcription factor activator protein-1. At the mRNA level, enhanced expression of the PSC activation marker, α-smooth muscle actin and two proinflammatory cytokines, interleukin （IL）-1β and IL-6, was observed. CONCLUSION： This study provides novel lines of evidence for profibrogenic and proinflammatory actions of ET-1 in the pancreas, encouraging further studies with ET-1 inhibitors in chronic pancreatitis.展开更多
Objective: To compare the levels of p38 mitogen-activated protein kinase (MAPK), soluble endoglin and endothelin-1 in the serum of patients with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet...Objective: To compare the levels of p38 mitogen-activated protein kinase (MAPK), soluble endoglin and endothelin-1 in the serum of patients with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and normal pregnancies. Methods: This study was an observational analytic cross-sectional study performed at Wahidin Sudirohusodo Hospital, Makassar, Indonesia, in the period of 5th February 2016 to 20th January 2017. P38 MAPK, soluble endoglin and endothelin-1 levels of patients with normal pregnancies, severe preeclampsia and HELLP syndrome were measured by enzyme-linked immunoabsorbentassay technique, using kits of human soluble endoglin, endothelin-1 and p38 MAPK, Quantikine immunoassay: R&D System Inc. Results: Level of serum p38 MAPK in HELLP syndrome group was higher than in severe preeclampsia and normal pregnancy groups. Soluble endoglin and endothelin-1 levels in pregnancies with severe preeclampsia and HELLP syndrome were higher than normal pregnancy but there was no significant difference between these two groups (P>0.05). Levels of p38 MAPK, soluble endoglin and endothelin-1 also had a positive linear correlation with systolic and diastolic blood pressures (P<0.05). Conclusions: P38 MAPK in serum may be a marker for evidence of the severe hypoxia and its application may be considered for the diagnosis of HELLP syndrome.展开更多
Objective To investigate whether plasma big endothelin-1(ET-1) predicts ventricular arrythmias(VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator(ICD) indication patigents. Methods ...Objective To investigate whether plasma big endothelin-1(ET-1) predicts ventricular arrythmias(VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator(ICD) indication patigents. Methods In total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1(< 0.38 pmol/L, n = 68), tertile 2(0.38–0.7 pmol/L, n = 69), and tertile 3(> 0.7 pmol/L, n = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation. Results During a mean follow-up period of 25.6 ± 13.9 months, 38(18.4%) VAs and 78(37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class(r = 0.165, P = 0.018), serum creatinine concentration(Scr;r = 0.147, P = 0.034), high-sensitivity C-reactive protein(hs-CRP;r = 0.217, P = 0.002), Lg NT-pro BNP(r = 0.463, P < 0.001), left ventricular end diastolic diameter(LVEDD;r = 0.234, P = 0.039) and negatively correlated with left ventricular ejection fraction(LVEF;r =-0.181, P = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events(P < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs(hazard ratio(HR) = 3.477, 95% confidence interval(CI): 1.352–8.940, P = 0.010, tertile 2 vs. tertile 1;HR = 4.112, 95% CI: 1.604–10.540, P = 0.003, tertile 3 vs. tertile 1) and end-stage events(HR = 2.804, 95% CI: 1.354–5.806, P = 0.005, tertile 2 vs. tertile 1;HR = 4.652, 95% CI: 2.288–9.459, P < 0.001, tertile 3 vs. tertile 1). Conclusions In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.展开更多
文摘BACKGROUND Hypertension is a chronic cardiovascular disease characterized by persistently elevated arterial blood pressure.It is not only a significant risk factor for cardio-vascular and cerebrovascular diseases(such as myocardial infarction and stroke)but also closely related to multiple organ damages(such as kidney disease and retinopathy),imposing a heavy health and economic burden on individuals and society.AIM To investigate the expression differences and relationships of endothelin-1(ET-1),interleukin-6(IL-6),stem cell factor(SCF),and its receptor(c-kit)in hypertensive patients with or without depression.METHODS A retrospective analysis was conducted on the clinical data of 163 hypertensive patients admitted to our hospital from March 2022 to January 2024.Based on the presence of depression,patients were divided into Group A(n=77,with depre-ssion)and Group B(n=86,without depression).Serum levels of ET-1 and IL-6 were measured using radioimmunoassay,while serum levels of SCF and c-kit were measured using ELISA.The differences in ET-1,IL-6,SCF,and c-kit levels between Groups A and B were compared.Additionally,the differences in these biomarkers among patients with varying degrees of depression in Group A were analyzed.Pearson correlation analysis was used to examine the relationship between ET-1,IL-6,SCF,c-kit levels,and Hamilton depression rating scale(HAMD)scores.Multivariate logistic regression analysis was performed to identify factors influencing hypertension with depression.The diagnostic efficacy of individual and combined biomarkers was analyzed using receiver operating characteristic(ROC)curves.Comparative statistical analysis of the area under the curve(AUC)values was performed using DeLong’s test to assess the superiority of combined biomarker detection.RESULTS The levels of ET-1 and IL-6 in Group A were significantly higher than those in Group B,while the levels of SCF and c-kit were significantly lower in Group A compared to Group B(P<0.05).In the severe depression subgroup,ET-1 and IL-6 levels were higher than those in the mild-to-moderate depression subgroup,while SCF and c-kit levels were lower(P<0.05).Pearson correlation analysis showed that ET-1 and IL-6 levels were positively correlated with HAMD scores(r=0.442,0.463,P<0.05),while SCF and c-kit levels were negatively correlated with HAMD scores(r=-0.429,-0.394,P<0.05).Multivariate logistic regression analysis revealed that high ET-1,high IL-6,low SCF,and low c-kit were independent influencing factors for hypertension with depression(P<0.05).ROC analysis revealed AUCs of 0.746(ET-1),0.801(IL-6),0.732(SCF),0.779(c-kit),and 0.884(combination).The combined diagnosis demonstrated significantly higher AUC than individual markers(DeLong's test,P<0.01),with superior sensitivity(90.24%)and specificity(85.37%).CONCLUSION Compared to patients with hypertension alone,patients with hypertension and depression exhibited higher serum levels of ET-1 and IL-6 and lower levels of SCF and c-kit.High ET-1,high IL-6,low SCF,and low c-kit were inde-pendent influencing factors for hypertension with depression.The combination of ET-1,IL-6,SCF,and c-kit demonstrated significant diagnostic value for hypertension with depression.
基金supported by theNationalNatural Science Foundation of China(82302909,92359302,82472087)National Key Research And Development Plan(2022YFC3401000)+4 种基金Guangdong Basic and Applied Basic Research Foundation(2024A1515010552)Guangdong Provincial Key Areas R&D Programs of“Precision Medicine and Stem Cells”(2023B1111020005)the Natural Science Foundation for Outstanding Youth Team Project of Guangdong Province(2024B1515040030)Natural Science Foundation of Fujian Province(2024J011004)Fujian Provincial Health and Medical High Level Talent Team(XM050005).
文摘Background:Colorectal cancer(CRC)is a predominant contributor to global cancer-associated mortality worldwide.Oxaliplatin(OXP),a foundational chemotherapeutic agent for CRC,often exhibits limited efficacy due to the emergence of drug resistance.Although endothelin-1(EDN1)has been implicated in tumor drug resistance,its role in oxaliplatin resistance in CRC remains poorly defined.This work aimed to define how EDN1 contributes to oxaliplatin resistance and to explore its potential as a therapeutic target.Methods:Public genomic datasets were analyzed to confirm EDN1 upregulation in colorectal cancer(CRC)and its association with poor prognosis.EDN1 expression was modulated in parental and oxaliplatin-resistant CRC cell lines via shRNA knockdown and lentiviral overexpression.Functional assays,including drug sensitivity,flow cytometry,and 5-Ethynyl-2′-deoxyuridine(EdU)proliferation,were conducted to assess resistance.Mechanistic studies employed dual-luciferase reporter assays,Western blotting,co-immunoprecipitation,and immunofluorescence.CRC-derived subcutaneous xenograft models were used to evaluate the therapeutic efficacy of EDN1 targeting in vivo.Results:The study identifies EDN1 as a pivotal mediator of oxaliplatin resistance in CRC.EDN1 expression is markedly upregulated in oxaliplatin-resistant CRC cells and is significantly associated with poor patient survival outcomes.Mechanistically,EDN1 overexpression activates the Yes-associated protein(YAP)signaling by promoting the nuclear translocation of β-arrestin1(β-arr1),thereby facilitating chemoresistance.Importantly,the combinatorial inhibition of EDN1,in conjunctionwith oxaliplatin treatment,substantially enhances apoptosis and suppresses tumor growth both in vitro and in vivo.Conclusion:The study demonstrates that EDN1 governs oxaliplatin resistance through theβ-arr1/YAP axis and provides preclinical evidence for targeting EDN1 to overcome chemoresistance in CRC.
基金supported by the Azalea (1972) Education fund to KFSo and RCCCFundamental Research Fund for The Centre Universities,No.21609101
文摘Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells （RGCs） in a rat chronic ocular hypertension （COH） model. Here, we investigated the expression of endothelin-1 （ET-1）, a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure （IOP） was induced in the right eye of SD rats using argon laser photocoagulation. （1） The expression of ET-1, ETA and ETB in normal and COH retinas was studied. （2） Some COH rats were fed daily with Lycium barbarum Polysaccharides （LBP） using 1 mg/kg or phosphate-buffered saline （PBS） for 3 weeks （started 1 week before photocoagulation）. The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that （1） Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. （2） After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. （3） By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.
基金Supported by Grant-in-Aid for Encouragement of Young Scientists from Japan Society for the Promotion of Science, No. 16590572 (to AM.)by Pancreas Research Foundation of Japan, No. 01-01 (to AM.)by the Kanae Foundation for Life and Socio-Medical Science(to AM)by the Uehara Memorial Foundation (to AM)
文摘AIM： To examine the ability of FT-1 to affect the cell functions of PSCs and the underlying molecular mechanisms. METHODS： PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase, and cells between passages two and five were used. Expression of ET-1 and FT receptors was assessed by reverse transcription-PCR and immunostaining. Phosphorylation of myosin regulatory light chain （MLC）, extracellular-signal regulated kinase （FRK）, and Akt was examined by Western blotting. Contraction of PSCs was assessed on hydrated collagen lattices. Cell migration was examined using modified Boyden chambers. Ceil proliferation was assessed by measuring the incorporation of 5-bromo-2＇- deoxyuridine. RESULTS： Culture-activated PSCs expressed ETA and ETB receptors, and ET-1. ET-1 induced phosphorylation of NLC and FRK, but not Akt. ET-1 induced contraction and migration, but did not alter proliferation of PSCs. FT-1-induced contraction was inhibited by an ETA receptor antagonist BQ-123 and an ETB receptor antagonist BQ-788, whereas migration was inhibited by BQ-788 but not by BQ-123. A Rho kinase inhibitor Y-27632 abolished both contraction and migration. CONCLUSION： ET-1 induced contraction and migration of PSCs through El receptors and activation of Rho-Rho kinase. ETA and FTB receptors play different roles in the regulation of these cellular functions in response to ET-1.
基金supported by Bureau of Traditional Chinese Medicine of Jiangsu Province (No. HZ07097)
文摘Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coronary heart disease were randomly divided into a treatment group(n=45) treated by Liandou Qingmai Recipe and a standard treatment group(control group,n=56),with a normal group of 16 health persons set up.Changes of ET-1,NO,IL-6 and IL-10 levels were measured before treatment and after treatment for two weeks.And the data were analyzed by SPSS 16.0 statistic software.Results:Before treatment,the levels of ET-1,IL-6 and IL-10 levels were significantly higher and NO was significantly lower in the patients with coronary heart disease than those in the normal group(90.7±12.7 ng/L vs 41.8±13.5 ng/L,9.17±0.18 ng/L vs 1.10±0.08 ng/L,1.94±0.26 ng/L vs 1.09±0.06 ng/L,and 92.2±17.7 μmol/L vs 124.5±27.2 μmol/L;all P<0.05),with no significant differences in the levels of ET-1,NO,IL-6 and IL-10 between the treatment group and the control group(P>0.05);After treatment,ET-1 and IL-6 significantly decreased in the treatment group and the control group,and NO increased in the treatment group;And IL-6 level was significantly lower and NO level was higher in the treatment group than those in the control group(4.48±1.22 ng/L vs 5.13±1.85 ng/L,117.4±22.3 μmol/L vs 92.4±17.1 μmol/L;both P<0.05);There was a positive correlation between IL-6 and IL-10,and a negative correlation between NO and IL-10(r=0.142,r=-0.152;both P<0.05).Conclusion:Liandou Qingmai Recipe can decline IL-6,IL-10 and ET-1 levels,and raise NO level in patients with coronary heart disease on the basis of standard treatment,so as to inhibit endothelial inflammatory response,improve vascular endothelial function,with stronger anti-AS action;And vascular endothelial lesion is related with inflammatory response.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
文摘To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups, with 6rats in each group: sham-operation group, simple ischemia group, ischemia-reperfusion group and treatment group (L-THP group). Cerebral ATP, lactate,ET-1 and NO levels were measured in all groups. Our results showed that treat-ment with L-THP could increase cerebral ATP levels, but decrease cerebral lac-tate, ET-1 and NO concentrations during ischemia-reperfusion in the treatmentgroup. It is concluded that L-THP could improve cerebral energy metabolism and protect the injured brain tissue, the mechanism of which might be related to suppression of overproduction of ET-1 and NO.
基金Supported by Indiana University department of surgery and Lilly INGEN research fund provided support for the Research performed in this manuscript
文摘AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function.
基金Supported by the Medical University of Bialystok within the Project #30-12770
文摘AIM: To assess the effect of non-selective ETA/B (LU 302872)and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP.METHODS: Male Wistar rats with caerulein-induced AP,lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w.of each antagonist. Edema, inflammatory infiltration,necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase,and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates.RESULTS: In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P＜0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82±0.06 at higher dose (P＜0.05) vs 0.58±0.06 in untreated AP. The nonselective antagonist increased slightly the vacuolization score to 2.41±0.07 at higher dose (P＜0.01) vs 1.88±0.08in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum,autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups.%FAT/TPT in untreated AP increased about four times (18.4±3.8 vs4.8±1.3 in control group without AP, P＜0.001).Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation.CONCLUSION: The treatment with endothelin-1 receptors (non-selective ETA/B and selective ETA) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.
基金the financial support by Universiti Teknologi MARA under grant No.600-IRMI/DANA5/3/BESTARI(006/2017)
文摘Endothelin-1（ET-1）, a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine（TAU）, a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co-or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.
文摘OBJECTIVE： To observe the influence of moxibustion temperature on blood lipids, endothelin-1（ET-1）, nitric oxide（NO）, and ET-1/NO in hyperlipidemia patients. METHODS： Forty-two primary hyperlipidemia patients were randomly divided into two groups of 21 and treated with moxibustion at different temperatures. Moxibustion was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group and 4 cm in the control group, 10 min per point, once every other day. Skin temperature was precisely measured with a thermometer during moxibustion. After a 12-week treatment, seven measurements of blood lipids, ET-1, and NO were recorded. RESULTS： Total cholesterol and triglyceride, were lower in the treatment group than in the control group（P0.05）. Serum ET-1 and ET-1/NO was obvi-ously lowered in the treatment group（P0.001）. Moxibustion regulated NO and ET-1/NO in the treatment group much better than in the control group. CONCLUSION： Moxibustion can regulate blood lipids and clear blood vessels. Moxibustion at 45℃has a better effect than moxibustion at 38℃ on regulating blood lipids and protecting vascular endothelial function, indicating that suitable temperature influences the curative effect of moxibustion.
基金Supported by A grant from the Deutsche Forschungsgemeinschaft (Ja 819/3-2)
文摘AIM： To gain molecular insights into the expression and functions of endothelin-1 （ET-1） in pancreatic stellate cells （PSC）.METHODS： PSCs were isolated from rat pancreas tissue, cultured, and stimulated with ET-1 or other extracellular mediators. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2＇-deoxyuridine into DNA and cell migration was studied in a transwell chamber assay. Gene expression at the level of mRNA was quantified by real-time Polymerase chain reaction. Expression and phosphorylation of proteins were monitored by immunoblotting, applying an infrared imaging technology. ET-1 levels in cell culture supernatants were determined by an enzyme immunometric assay. To study DNA binding of individual transcription factors, electrophoretic mobility shift assays were performed.RESULTS： Among several mediators tested, transforming growth factor-β1 and tumour necrosis factor-α displayed the strongest stimulatory effects on ET-1 secretion. The cytokines induced binding of Smad3 and NF-κB, respectively, to oligonucleotides derived from the ET-1 promoter, implicating both transcription factors in the induction of ET-1 gene expression. In accordance with previous studies, ET-1 was found to stimulate migration but not proliferation of PSC. Stimulation of ET-1 receptors led to the activation of two distinct rnitogen-activated protein kinases, p38 and extracellular signal-regulated kinases （ERK）1/2, as well as the transcription factor activator protein-1. At the mRNA level, enhanced expression of the PSC activation marker, α-smooth muscle actin and two proinflammatory cytokines, interleukin （IL）-1β and IL-6, was observed. CONCLUSION： This study provides novel lines of evidence for profibrogenic and proinflammatory actions of ET-1 in the pancreas, encouraging further studies with ET-1 inhibitors in chronic pancreatitis.
文摘Objective: To compare the levels of p38 mitogen-activated protein kinase (MAPK), soluble endoglin and endothelin-1 in the serum of patients with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and normal pregnancies. Methods: This study was an observational analytic cross-sectional study performed at Wahidin Sudirohusodo Hospital, Makassar, Indonesia, in the period of 5th February 2016 to 20th January 2017. P38 MAPK, soluble endoglin and endothelin-1 levels of patients with normal pregnancies, severe preeclampsia and HELLP syndrome were measured by enzyme-linked immunoabsorbentassay technique, using kits of human soluble endoglin, endothelin-1 and p38 MAPK, Quantikine immunoassay: R&D System Inc. Results: Level of serum p38 MAPK in HELLP syndrome group was higher than in severe preeclampsia and normal pregnancy groups. Soluble endoglin and endothelin-1 levels in pregnancies with severe preeclampsia and HELLP syndrome were higher than normal pregnancy but there was no significant difference between these two groups (P>0.05). Levels of p38 MAPK, soluble endoglin and endothelin-1 also had a positive linear correlation with systolic and diastolic blood pressures (P<0.05). Conclusions: P38 MAPK in serum may be a marker for evidence of the severe hypoxia and its application may be considered for the diagnosis of HELLP syndrome.
基金supported by Natural Science Foundation of China(81470466)。
文摘Objective To investigate whether plasma big endothelin-1(ET-1) predicts ventricular arrythmias(VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator(ICD) indication patigents. Methods In total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1(< 0.38 pmol/L, n = 68), tertile 2(0.38–0.7 pmol/L, n = 69), and tertile 3(> 0.7 pmol/L, n = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation. Results During a mean follow-up period of 25.6 ± 13.9 months, 38(18.4%) VAs and 78(37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class(r = 0.165, P = 0.018), serum creatinine concentration(Scr;r = 0.147, P = 0.034), high-sensitivity C-reactive protein(hs-CRP;r = 0.217, P = 0.002), Lg NT-pro BNP(r = 0.463, P < 0.001), left ventricular end diastolic diameter(LVEDD;r = 0.234, P = 0.039) and negatively correlated with left ventricular ejection fraction(LVEF;r =-0.181, P = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events(P < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs(hazard ratio(HR) = 3.477, 95% confidence interval(CI): 1.352–8.940, P = 0.010, tertile 2 vs. tertile 1;HR = 4.112, 95% CI: 1.604–10.540, P = 0.003, tertile 3 vs. tertile 1) and end-stage events(HR = 2.804, 95% CI: 1.354–5.806, P = 0.005, tertile 2 vs. tertile 1;HR = 4.652, 95% CI: 2.288–9.459, P < 0.001, tertile 3 vs. tertile 1). Conclusions In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.
