ET-1 Levels Research Articles

CircYTHDF1/miR-19b-3p/YTHDF1 axis contributes to pregnancy-induced hypertension development by enhancing vascular endothelial cell injury

ABSTRACT Objective The biological role of circ_0004858 (circYTHDF1) in pregnancy-induced hypertension (PIH) and the underlying mechanisms were unknown, and which were explored in this study. Methods ELISA was employed to detect the level of inflammatory cytokines and biochemical parameters; flow cytometry was employed to detect cell apoptosis; western blot and qRT-PCR were employed to examine expression level. Results The level of IL-1β, TNF-α, IL-6, TGF-β1, ET-1, and Ang-II were significantly elevated in the peripheral blood of PIH patients. The co-culture of HUVEC and CD4+ T cells isolated from the peripheral blood of PIH patients significantly elevated the apoptosis and expression level of NRF2/HO-1 but reduced the protein level of ferroptosis-related markers (GPX4, FSP, and CoQ10B) in HUVEC. Also, the expression of circYTHDF1 and YTHDF1 were markedly up-regulated in HUVEC co-cultured with CD4+ T cells isolated from PIH patients, but miR-19b-3p expression was markedly down-regulated, and the similar results were observed in Ang-II-treated HUVEC. Based on the predicted binding sites, the luciferase reporter assay confirmed the interaction between miR-19b-3p and circYTHDF1 or YTHDF1. The results of qRT-PCR and western blot further demonstrated that circYTHDF1 competitively bound to miR-19b-3p to up-regulate YTHDF1 in HUVEC. Functionally, deleting circYTHDF1markedly reduced ferroptosis and apoptosis in Ang-II-treated HUVEC, but both which were reversed by miR-19b-3p inhibitor, suggesting the involvement of circYTHDF1/miR-19b-3p/YTHDF1 axis in vascular endothelial cell injury in PIH. Conclusions This study may provide a novel insight into the pathogenesis of PIH as well as a new treatment strategy.

Long-term prognostic value of multiple circulating biomarkers for ventricular arrhythmias in patients with left ventricular hypertrabeculation

Abstract Background Left ventricular hypertrabeculation (LVHT) is a rare morphologic phenotype of the heart with heterogeneous manifestations and variable prognosis [1,2]. Ventricular arrhythmia (VA) has been recognized as an independent risk factor that significantly impacts the mortality of LVHT patients [1,3]. However, knowledge regarding the prognosis and risk stratification of VAs in LVHT is currently limited. Purpose To explore the long-term predictive value of multiple circulating biomarkers reflecting cardiac function, endothelial function, inflammation, and oxidative stress for the development of VAs in LVHT patients. Methods This longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2012 and December 2020 at a national-level medical center. All participants possessed thorough profiles of multiple biomarkers [N-terminal pro-brain natriuretic peptide, big endothelin-1 (big ET-1), high-sensitivity C-reactive protein, uric acid and free fatty acid] and had no previously documented ventricular arrhythmic events. The cohort were followed annually until October 2022. VA was defined as a composite of non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, and appropriate therapy of implantable cardioverter defibrillator. Potential predictors for VAs in the LVHT cohort were evaluated by multivariable Cox regression. Restricted cubic spline (RCS) analysis was employed to explore the nonlinear association between plasma big ET-1 and clinical outcomes. Differences in the cumulative incidence of VAs according to big ET-1 levels and/or the extent of hypertrabeculation were analyzed by Kaplan-Meier curves. Results A total of 265 morphologically diagnosed LVHT patients (44.2 ± 17.0 years, 65.7% male) were included in this study. Over a median follow-up of 4.34 years, 82 (30.9%) patients experienced ventricular arrhythmic events. Multivariable Cox regression analysis identified that baseline levels of big ET-1 (hazard ratio 1.513, 95% confidence interval 1.136-2.013) and isolated hypertrabeculation in left ventricular lateral wall (LVLW) (hazard ratio 1.810, 95% confidence interval 1.023-3.202) were independently associated with the occurrence of VAs. RCS analysis illustrated that the susceptibility to VAs was remarkably raised with the increase of big ET-1 levels. LVHT patients with higher plasma big ET-1 suffered from more severe cardiac dysfunction and remodeling. Individuals who displayed elevated concentrations of big ET-1 and isolated LVLW hypertrabeculation were at a significantly greater risk of developing VAs. Conclusions Introducing routine assessments for plasma big ET-1 and the extent of hypertrabeculation at baseline can offer valuable support in the risk stratification and clinical management of ventricular arrhythmic events in patients with LVHT.Prognositc value of big ET-1 for VAsbig ET-1/LVLW hypertrabeculation & VAs

Yiqihuoxue decoction (GSC) inhibits mitochondrial fission through the AMPK pathway to ameliorate EPCs senescence and optimize vascular aging transplantation regimens

BackgroundDuring the aging process, the number and functional activity of endothelial progenitor cells (EPCs) are impaired, leading to the unsatisfactory efficacy of transplantation. Previous studies demonstrated that Yiqihuoxue decoction (Ginseng-Sanqi-Chuanxiong, GSC) exerts anti-vascular aging effects. The purpose of this study is to evaluated the effects of GSC on D-galactose (D-gal)induced senescence and the underlying mechanisms.MethodsThe levels of cellular senescence-related markers P16, P21, P53, AMPK and p-AMPK were detected by Western blot analysis (WB). SA-β-gal staining was used to evaluate cell senescence. EPCs function was measured by CCK-8, Transwell cell migration and cell adhesion assay. The morphological changes of mitochondria were detected by confocal microscopy. The protein and mRNA expression of mitochondrial fusion fission Drp1, Mff, Fis1, Mfn1, Mfn2 and Opa1 in mitochondria were detect using WB and RT–qPCR. Mitochondrial membrane potential, mtROS and ATP of EPCs were measured using IF. H&E staining was used to observe the pathological changes and IMT of the aorta. The expressions of AGEs, MMP-2 and VEGF in aorta were measured using Immunohistochemical (IHC). The levels of SOD, MDA, NO and ET-1 in serum were detected by SOD, MDA and NO kits.ResultsIn vitro, GSC ameliorated the senescence of EPCs induced by D-gal and reduced the expression of P16, P21 and P53. The mitochondrial morphology of EPCs was restored, the expression of mitochondrial Drp1, Mff and Fis1 protein was decreased, the levels of mtROS and ATP were decreased, and mitochondrial function was improved. Meanwhile, the expression of AMPK and p-AMPK increased. The improvement effects of GSC on aging and mitochondrial morphology and function were were hindered after adding AMPK inhibitor. In vivo, GSC improved EPCs efficiency, ameliorated aortic structural disorder and decreased IMT in aging mice. The serum SOD level increased and MDA level decreased, indicating the improvement of antioxidant capacity. Increased NO content and ET-1 content suggested improvement of vascular endothelial function. The changes observed in SOD and MMP-2 suggested a reduction in vascular stiffness and the degree of vascular damage. The decreased expression of P21 and P53 indicates the delay of vascular senescence.

Pathophysiological dynamics of acute myocardial infarction rats under chronic psychological stress at different time points

There is a lack of in-depth research on the impacts and changes in chronic psychological stress (CPS) on the cardiovascular system after acute myocardial infarction (AMI). This study aims to explore the comorbid mechanism and dynamic evolution of AMI exposed to CPS. 120 Wistar rats were randomly divided into Sham Operation group, Sham Operation + Chronic Unpredictable Mild Stress (CUMS) group, AMI group and AMI + CUMS group, with each group further divided into subgroups at days 7, 14, and 28. The AMI model was created by ligating the left anterior descending coronary artery, and CUMS model was used to induce CPS in rats. Behavioral changes were assessed through open field tests and sucrose preference tests. Cardiac function and structure were evaluated via echocardiography. The serum levels of TNFα, IL-6, NO, ET, CK-MB, cTNT, and ANP were measured using assay kits. Pathological changes in cardiac and brain tissues were observed under an optical microscope. Comparative analysis across different models revealed that CUMS significantly reduced behavioral activities in rats, with an interaction between CUMS and AMI affecting total distance (P < 0.05). Both CUMS and AMI significantly reduced cardiac function indicators, with their interaction effects on LVEF, LVFS, and CO (P < 0.05). AMI significantly altered cardiac structural parameters, particularly on day 28 (P < 0.05); while the impact of CUMS on cardiac structure was not significant, except for a notable reduction in LVAW/s on day 7 in AMI + CUMS group (P < 0.05). AMI caused significant changes in the serum biomarkers, while CUMS only significantly increased cTnT on day 7, ANP, TNFα, and IL-6 on day 14, and CK-MB on day 28, with their interaction effects on the three myocardial injury markers and TNFα (P < 0.05). Comparative analysis across different time points demonstrated that behavioral activity, cardiac function, CK-MB, cTnT, ANP, TNFα, and ET levels decreased significantly over time in the AMI model rats, while the left ventricular mass increased significantly (P < 0.05). Pathologically, compared with stress or AMI alone, the AMI + CUMS group exhibited more severe myocardia cellular degeneration and inflammatory infiltration, causing larger infract areas in myocardial tissue, as well as cell number decreases and morphological changes in hippocampal tissue. AMI with CPS exacerbates myocardial injury through sustained inflammation and endothelial dysfunction, leading to heart-brain pathology manifestations characterized by decreased cardiac function and hippocampal tissue damage.

Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.

This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

Evaluation of changes in the global longitudinal strain for left ventricular function before and after eight weeks of taking high dose of atorvastatin in patients with coronary slow flow phenomenon

BackgroundCoronary Slow Flow Phenomenon (CSFP) is a well-recognized clinical entity characterized by delayed opacification of coronary arteries in the presence of a normal coronary angiogram. The objective of this study was determined and compared left ventricle (LV)strain in patients with CSFP before and after receiving a high-dose atorvastatin.Materials and methodsThis cross-sectional study was conducted on 51 patients with CSFP from the beginning of 2021 to the end of September 2022. Trans-thoracic Echocardiogram (TTE) was performed by an echocardiography specialist. Thereafter, the patient’s basic information was entered into the researcher’s checklist after treatment with atorvastatin 40 mg daily for eight consecutive weeks. After eight weeks, the patients were subjected again to TTE. The data were analyzed in SPSS statistical software.ResultsThe mean LV-GLS before taking atorvastatin was − 16.53%±3.63%. The mean LV-GLS after taking atorvastatin was 17.57%±3.53% (P.value = 0.01). The mean LV function before taking atorvastatin was 48.82%±9.19%. Meanwhile, the mean LV function after taking atorvastatin was 50.59%±7.91% (P = 0.01). There was no significantly change in left atrium volume (49.88 ± 0.68 vs. 49.9 + 0.67) after 8 weeks taking atorvastatin (P = 0.884).ConclusionThe plasma ET-1 levels are elevated in CSFP patients, and atorvastatin improves coronary flow and endothelial function. As evidenced by the results of this study, the daily intake of 40 mg of oral atorvastatin during eight consecutive weeks in patients with CSFP significantly improved LV strain and LV function, however atorvastatin does not have a significant effect on improving the right ventricular function and pulmonary artery systolic pressure.

Effects of Dezocine and Propofol Combination on Plasma 5-HT and ET Levels in Stroke Patients Undergoing Thrombolysis

Objective: To investigate the effect of dezocine combined with propofol on brain metabolism in patients undergoing cerebral thrombosis thrombolysis. Methods: A total of 86 stroke patients admitted between July 2022 and December 2023 were randomly divided into two groups: Group A (study group) and Group B (control group), with 43 patients in each group. Both groups underwent intra-arterial thrombolysis therapy. Group B received dezocine for anesthesia, while Group A received a combination of dezocine and propofol. Plasma concentrations of 5-hydroxytryptamine and endothelin, as well as brain metabolic indicators, were compared between the two groups immediately after anesthesia, at 1 hour post-reperfusion, and 3 hours post-reperfusion. Results: There were no significant differences in the levels of 5-hydroxytryptamine and endothelin between the two groups immediately after anesthesia and at 1 hour post-reperfusion (P &gt; 0.05). However, at 3 hours post-reperfusion, the levels of 5-hydroxytryptamine and endothelin in Group A were significantly lower than those in Group B. Furthermore, in Group A, the levels of 5-hydroxytryptamine and endothelin at 3 hours post-reperfusion were lower compared to the levels at 1 hour post-reperfusion (P &lt; 0.05). Conclusion: Dezocine combined with propofol can effectively improve the quality of anesthesia and has a minimal effect on brain metabolic indices, suggesting reduced damage to brain metabolism.

Effect of aortic smooth muscle BK channels on mediating chronic intermittent hypoxia-induced vascular dysfunction.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

Color Doppler Imaging, Endothelin-1, Corneal Biomechanics and Scleral Rigidity in Asymmetric Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) presents a multifaceted etiopathogenesis involving ischemic, inflammatory, and genetic components. This study investigates the correlation between ocular hemodynamics, scleral rigidity (SR), and plasma endothelin-1 (ET1) levels in treatment-naive patients with asymmetrical AMD. This study included 20 treatment-naive patients (12 females and 8 males) with an average age of 76.4 ± 3.7 years, who presented with AMD with neovascular membrane formation (nAMD) in one eye, and intermediate grade 2 AMD (iAMD) in the other eye. The control group consisted of 20 healthy subjects (13 females and 7 males) with a mean age of 74.7 ± 3.9 years. All patients and healthy controls underwent color Doppler imaging (i) of the ophthalmic artery (OA), short posterior ciliary arteries (SPCAs), and central retinal artery (CRA); Plasma ET-1 levels were measured for all patients and healthy subjects. Corneal biomechanics were assessed using an Ocular Response Analyzer and two indices were obtained: corneal hysteresis (CH) and corneal resistance factor (CRF). Results showed reduced blood flow velocities and increased resistance indices in AMD eyes, particularly affecting the short posterior ciliary arteries. According to mechanical theory, ARMD eyes exhibited elevated scleral rigidity and corneal resistance factor compared to controls, with a notable rise in SR in neovascular AMD (nAMD) eyes. As per the chronic subacute inflammation theory, plasma ET-1 levels were significantly higher in AMD patients, correlating with abnormal SPCAs blood flow and increased resistance indices. Findings suggest a multifactorial etiology of AMD involving an increase of ET-1 plasma levels with biomechanic damages of corneal and scleral tissue in nAMD.

Vericiguat on C-reactive Protein Level and Prognosis in Patients with Hypertensive Heart Failure.

Hypertensive heart failure (HHF) has a high incidence and poor prognosis. This article evaluated the efficacy and safety of Vericiguat in HHF and analyzed the relationship between C-reactive protein (CRP) levels and patient prognosis. 110 HHF patients were divided into Placebo and Vericiguat groups. Cardiac function was assessed by echocardiography and 6-minute walk test (6MWT). Blood samples were collected to detect the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), endothelin (ET-1), nitric oxide (NO), and CRP. Left ventricular end systolic diameter (LVESD) and left ventricular end diastolic dimension (LVEDD) were reduced, the left ventricular ejection fraction (LVEF) and 6MWT were increased, and the serum levels of NT-proBNP, cTnI, ET-1, NO, and CRP were decreased in Vericiguat group as against Placebo group; The total effective rate was 76.4% in Placebo group and 92.7% in Vericiguat group (P < 0.05). The adverse reaction rate was 10.9% and 9.1% (P > 0.05). The proportion of persons with poor prognosis and no improvement of cardiac function in patients with highly expressed CRP before treatment was higher as against patients with low expression of CRP (P < 0.05). Highly expressed CRP is an independent risk factor for poor prognosis. Vericiguat is safe and effective in improving cardiac function in HHF patients.

Pharmacodynamics of Qingxin Jieyu Granules for treatment of atherosclerosis and its regulatory mechanism for lipid metabolism

To elucidate the therapeutic mechanism of Qingxin Jieyu Granule (QXJYG) against atherosclerosis (AS) based on network pharmacology. The major targets and pathways of QXJYG against AS were analyzed using network pharmacology. Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline, atorvastatin (13.15 mg/kg), or QXJYG at 0.99, 1.98, and 3.96 g/kg for 8 weeks (n=6). Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta. Blood lipids and serum levels of Ang Ⅱ, ET-1, TXA2, PGI2, and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA. The expressions of LOX-1, PPARγ, RXRα, p-P65, VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry. The rat models of AS showed obvious abdominal aorta wall thickening, increased pulse wave velocity and pulse index, decreased inner diameter of the abdominal aorta, elevated levels of TC, LDL-C, Ang Ⅱ, ET-1 and TXA2, and lowered levels of HDL-C and PGI2. QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta, decreased serum levels of TC, LDL-C, Ang Ⅱ, ET-1 and TXA2, and increased the levels of HDL-C and PGI2. Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism, PPAR and NF-κB pathways. Consistently, treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1, P-P65, VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats. QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level, reducing LOX-1 expression, activating PPARγ and RXRα, and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Angiotensin-converting enzyme inhibitors provide a protective effect on hypoxia-induced injury in human coronary artery endothelial cells via Nrf2 signaling and PLVAP.

Angiotensin-converting enzyme inhibitors (ACEIs) were reported to protect from hypoxia-induced oxidative stress in coronary endothelial cells (CECs) after acute myocardial infarction (AMI). Nrf2 shows a protective effect in hypoxia-induced CECs after AMI. Plasmalemma vesicle-associated protein (PLVAP) plays a pivotal role in angiogenesis after AMI. To explore the protective effect of ACEIs and the involved mechanisms under hypoxia challenge. Human coronary endothelial cells (HCAECs) were used to establish hypoxia-induced oxidative stress injury in vitro. Flow cytometry was used to evaluate the protective effect of ACEI on hypoxia conditions.ET-1, NO, ROS, and VEGF were detected by ELISA. HO-1, Nrf2, and Keap-1, the pivotal member in the Nrf2 signaling pathway, eNOS and PLVAP were detected in HEAECs treated with ACEI by immunofluorescence, qPCR, and western blotting. The hypoxia ACEI or Nrf2 agonist groups showed higher cell viability compared with the hypoxia control group at 24 (61.75±1.16 or 61.23±0.59 vs. 44.24±0.58, both P < 0.05) and 48 h (41.85±1.19 or 59.64±1.13 vs. 22.98±0.25, both P < 0.05). ACEI decreased the levels of ET-1 and ROS under hypoxia challenge at 24 and 48 h (all P < 0.05); ACEI increased the VEGF and NO levels (all P < 0.05). ACEI promoted the expression level of eNOS, HO-1, Nrf2 and PLVAP but inhibited Keap-1 expression at the mRNA and protein levels (all P < 0.05). Blockade of the Nrf2 signaling pathway significantly decreased the expression level of PLVAP. ACEI protects hypoxia-treated HEAECs by activating the Nrf2 signaling pathway and upregulating the expression of PLVAP.

Dual-circulation: influence mechanism of ETS's carbon reduction and its spatiotemporal characteristics based on intensity modified SDID model

Traditional DID models overlook variations in policy intensity, causing estimation deviations from the actual situation and a limited understanding of the influence mechanism. In response, the Intensity Modified SDID Model is built to examine the influence mechanism of ETS's carbon reductions. Moreover, through model extensions, the study explores the spatiotemporal characteristics and heterogeneities of ETS’s effects. Results show that: (1) "Dual-circulation" influence mechanism is confirmed, where ETS directly contributes to carbon reductions (2.70% to 10.0% impact) through external pathways, and internal pathways continuously strengthen reduction effects, comprehensive mechanisms are thereby formed and enhanced based on interaction among internal and external pathways. (2) Reasonable ETS levels are estimated and proposed to achieve "Dual Carbon Target", constraining nationwide carbon quotas by 20 billion tons/year, increasing carbon trading volumes by 80 thousand tons/year, and elevating the carbon trading prices by 100 RMB (14 USD) per ton. (3) ETS's carbon reduction effects are identified with temporal and spatial characteristics, temporally, effects peak in the 4th period (Event+4) but diminish in the 5th period (Event+5), spatially, effects peak in areas distancing around 1000 km but disappear beyond 1500 km. (4) ETS also has synergistic effects with atmospheric pollution reduction, including industrial emissions of sulfur dioxide and smoke (dust), but are insignificant to industrial emissions of wastewater and solid waste.

Study of Banxia Xiexin Prescription Combined with Diet Nursing on Improving the Clinical Symptoms, Inflammatory Factor Levels and Prognosis of Hospitalized Patients with Peptic Ulcer

Western medicine is the first choice for the clinical treatment of peptic ulcer (PU), which can quickly improve the symptoms of patients. However, the efficacy of western medicine can be influenced by PU patients’ unhealthy lifestyle and other factors, leading to various adverse reactions during and after treatment. Therefore, it is necessary to actively find ways to increase the efficacy of PU patients without increasing adverse reactions. Traditional Chinese Medicine (TCM) treatment for PU focuses on warming and tonifying deficiencies and alleviating urgency. The medicinal composition of Banxia Xiexin Decoction is Pinellia, Scutellaria baicalensis, Zingiberis rhizoma, fried licorice, Rhizoma coptidis and jujube, etc. β-sitosterol, 6-gingerol and berberine, the active components of Pinellia, Zingiberis rhizoma and Rhizoma coptidis, have been proved to have anti-ulcer effects. In this study, a rat model of PU was established in the animal experiment, and it was found that Banxia Xiexin prescription could effectively reduce the levels of ET-1 and NO in PU rats (P &lt; 0.05). In the clinical trial, the Western Medicine convention (W-Con) group consisted of 61 PU patients who were hospitalized in our facility from 2020.01 to 2022.12 and received conventional western medicine treatment, while the Banxia combination (B-Com) group included PU patients who received Banxia xiexin decoction along with dietary care during the same period. The analysis of treatment outcomes between the two groups revealed that patients treated with Banxia Xiexin decoction combined with dietary care exhibited more significant improvements in clinical symptoms and inflammatory state compared to those relying solely on traditional western medicine (P &lt; 0.05). In addition, we found that combined diet care helped to improve the prognosis of patients (P &lt; 0.05). Therefore, this study suggests that Banxia Xiexin decoction combined with diet nursing can be used as an optimal treatment for PU patients. Banxia Xiexin decoction can effectively treat PU, which may be the main active ingredients in Banxia Xiexin decoction, such as β-sitosterol, 6-gingerol and berberine, which have anti-ulcer effects.

A combined in vitro and in silico study of the inhibitory mechanism of angiotensin-converting enzyme with peanut peptides

Food-derived peptides with low molecular weight, high bioavailability, and good absorptivity have been exploited as angiotensin-converting enzyme (ACE) inhibitors. In the present study, in-vitro inhibition kinetics of peanut peptides, in silico screening, validation of ACE inhibitory activity, molecular dynamics (MD) simulations, and HUVEC cells were performed to systematically identify the inhibitory mechanism of ACE interacting with peanut peptides. The results indicate that FPHPP, FPHY, and FPHFD peptides have good thermal, pH, and digestive stability. MD trajectories elucidate the dynamic correlation between peptides and ACE and verify the specific binding interaction. Noteworthily, FPHPP is the best inhibitor with a strongest binding affinity and significantly increases NO, SOD production, and AT2R expression, and decreases ROS, MDA, ET-1 levels, ACE, and AT1R accumulation in Ang II-injury HUVEC cells.

Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm.

Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic variants in a cohort of European patients with angina and unobstructed coronary arteries who underwent acetylcholine (ACh) provocation testing. A candidate association analysis of 208 genes previously associated with cardiovascular conditions was performed using genotyped and imputed variants in patients grouped in epicardial (focal, diffuse) CAS (n = 119) and microvascular CAS (n = 87). Patients with a negative ACh test result (n = 45) served as controls. We found no association below the genome-wide significance threshold of p < 5 × 10-8, thus not confirming variants in ALDH2, NOS3, and ROCK2 previously reported in CAS patients of Asian ancestry. However, the analysis identified suggestive associations (p < 10-05) for the groups of focal epicardial CAS (CDH13) and diffuse epicardial CAS (HDAC9, EDN1). Downstream analysis of the potential EDN1 risk locus showed that CAS patients have significantly increased plasma endothelin-1 levels (ET-1) compared to controls. An EDN1 haplotype comprising rs9349379 and rs2070698 was significantly associated to ET-1 levels (p = 0.01). In summary, we suggest EDN1 as potential genetic risk loci for patients with diffuse epicardial CAS, and European ancestry. Plasma ET-1 levels may serve as a potential cardiac marker.

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2- + NO3-) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1β (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.

Effect of Orthosiphon stamineus Extract on HIF-1Α, Endothelin-1, and VEGFR-2 Gene Expression in NRK-52E Renal Tubular Cells Subjected to Glucotixicity

This study aimed to investigate the impact of Orthosiphon stamineus extract on gene expression in NRK-52E cells under conditions of glucotoxicity. Gene expression analysis using RT-PCR was conducted following exposure of cultured NRK-52E cells to glucotoxic conditions and various concentrations of Orthosiphon stamineus extract. The results revealed a dose-dependent decrease in HIF-1α, ET-1 and VEGFR-2 gene expression levels upon treatment with Orthosiphon stamineus extract. The diverse array of phytochemicals found within Orthosiphon demonstrates a significant impact on the biochemical pathways implicated in the pathogenesis of the disease. Additionally, molecular docking studies suggested the potential inhibition of Rho-kinase as a mechanistic explanation for this observed effect. These findings suggest that Orthosiphon stamineus extract may possess renoprotective properties against glucotoxicity-induced cellular damage. This study contributes to understanding potential therapeutic interventions for managing renal complications associated with conditions such as diabetes.

The Effect of Swimming Aerobic Physical Exercise On White Rats (Rattus Novergicus) Of the Wistar Strain That Are Obese

Women are more likely to be obese and at risk of hypertension and coronary heart disease than men. Genetic factors influence it. Physical exercise can reduce obesity, especially on endothelial factors such as ET-1 and NO. This research explores the effect of swimming physical training on the expression of endothelin-1 and receptor-A in obese mouse models. This type of research is a true experiment carried out on 12 adult female Wistar rats (Rattus norvegicus) as research samples. The research procedures were carried out by caring for test animals, raising rats until they were obese, not giving treatment (control), physical training in the form of swimming exercises, and finally, examination of ET-1, ET-A, blood sugar levels, and total cholesterol levels. The data obtained was analyzed using SPSS. The research results of the normality test for the treatment group were more significant than 0.05 in the ET-1 examination of 0.315 and ET-A of 0.261. ET-1 levels were 92.5 pg/ml and ET-A levels were 62.5 pg/ml. Their blood sugar level was 167 mg/dL. The research concluded that in mouse tests, physical training was better for increasing ET-1 levels and reducing ET-A levels. Swimming and aerobics are better at lowering blood sugar levels.

Shizao decoction for cirrhotic ascites: assessing potential targets based on network analysis combined with pharmacokinetics and metabolomics.

Introduction: Shizao decoction (SZD) is a traditional Chinese medicine decoction that has therapeutic effects on cirrhotic ascites (CAS). Because of the unclear treatment mechanism, in the current study, the anti-CAS activity of SZD and molecular mechanisms were analyzed by network analysis combined with pharmacokinetics and metabolomics. Methods: Firstly, we assessed the anti-CAS efficacy of SZD by hematoxylin-eosin (H&E), liver function tests, NO and ET-1 levels, and portal venous pressure. Secondly, network analysis was applied to dig out the metabolites, targets, and pathways related to SZD and CAS. Then, the pharmacokinetics of the pharmacokinetically relevant metabolites (PRM) were analyzed. Thirdly, the serum and urine metabolic biomarkers of rats with CAS were identified using metabolomics by comparing them with the SZD treatment group. In addition, MetaboAnalyst was utilized to conduct metabolic pathway analysis. Finally, the correlation analysis established a dynamic connection between absorbed PRM from SZD and CAS-associated endogenous metabolites. Results: Pharmacodynamic analysis indicated that SZD effectively mitigated liver injury symptoms by ameliorating inflammatory cell infiltration in CAS rats. The network analysis results indicated that twelve RPM contribute to the therapeutic efficacy of SZD against CAS; the key signaling pathways involved might be hepatitis B and PI3K-Akt. Pharmacokinetics results showed that the 12 RPM were efficiently absorbed into rat plasma, ensuring desirable bioavailability. The metabolomic analysis yielded 21 and 23 significantly distinct metabolites from the serum and urine, respectively. The 12 bioavailable SZD-PRM, such as luteolin, apigenin, and rutin, may be associated with various CAS-altered metabolites related to tryptophan metabolism, alpha-linolenic acid metabolism, glycine metabolism, etc. Discussion: A novel paradigm was provided in this study to identify the potential mechanisms of pharmacological effects derived from a traditional Chinese medicine decoction.