Considering the significant impact of total cholesterol (TC) and vascular endothelin-1 (ET-1) on children sepsis outcomes, this research aimed to explore the association between the levels of plasma cholesterol and vascular endothelin-1 and the severity of sepsis and evaluated its clinical implications. In this study, we examined 250 pediatric patients diagnosed with sepsis between February 2019 and April 2021, collecting data on their plasma levels of TC and ET-1. Depending on the observed outcomes, the participants were divided into 2 categories: a group with a positive prognosis (control group, n = 100) and a group with a negative prognosis (n = 50). We assessed the significance of plasma TC and ET-1 levels in forecasting the outcomes for these pediatric patients. Patients in the group with a poor prognosis experienced notably longer hospital stays and higher treatment expenses than those in the control group (P < .05). Within the first 24 hours of admission and again on days 3 and 7, the levels of ET-1 were significantly higher in the poor prognosis group, whereas plasma TC levels were notably lower in comparison to the control group (P < .05). A Spearman correlation analysis identified a significant correlation between the levels of plasma TC and ET-1 and the severity of sepsis among the children (P < .05). The diagnostic performance for the severity of sepsis in children, as measured by the area under the curve (AUC), was 0.805 for plasma TC, 0.777 for ET-1 levels, and 0.938 when both were combined. This investigation underscores a meaningful relationship between the levels of plasma TC and ET-1 in pediatric sepsis patients, suggesting these biomarkers are highly valuable in predicting patient outcomes. High levels of ET-1 and low levels of TC in these patients signify a grave condition and a poor prognosis.

OBJECTIVE: To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV).
METHODS: A total of 70 patients with CV were randomized into an observation group and a control group, 35 cases in each group. In the observation group, nape seven needles combined with pressing moxibustion was delivered, once a day, 6 times a week, for consecutive 2 weeks. In the control group, betahistine hydrochloride tablet and aceclofenac dispersible tablet were given orally, for 2 weeks and 3 days respectively. Before and after treatment, the evaluation scale for cervical vertigo (ESCV) score was observed, the plasma levels of neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected, the hemorheologic and hemodynamic indexes were measured, and the clinical efficacy was evaluated after treatment in the two groups.
RESULTS: After treatment, the scores of dizziness, daily life and work ability, psychological and social adaptability, and headache, as well as the total scores of ESCV were increased compared with those before treatment (P<0.01, P<0.05) in the two groups, and the score and total score of neck and shoulder pain of ESCV was increased compared with that before treatment (P<0.01) in the observation group; each sub-item score and total score of ESCV in the observation group were higher than those in the control group (P<0.01, P<0.05). After treatment, the plasma levels of NPY and ET-1 were decreased compared with those before treatment (P<0.01), while the plasma levels of CGRP were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the plasma levels of NPY and ET-1 in the observation group were lower than those in the control group (P<0.01), the plasma level of CGRP in the observation group was higher than that in the control group (P<0.01). After treatment, the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity were decreased compared with those before treatment (P<0.01, P<0.05), the mean velocity of basilar artery (BA), left vertebral artery (LVA) and right vertebral artery (RVA) were increased compared with those before treatment (P<0.05) in the two groups; the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity in the observation group were lower than those in the control group (P<0.01), and the mean velocity of BA, LVA and RVA in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 91.4% (32/35), which was superior to 71.4% (25/35) in the control group (P<0.05).
CONCLUSIONS: Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.
目的：观察项七针联合压灸治疗颈性眩晕（CV）的临床疗效。方法：将70例CV患者随机分为观察组和对照组，每组35例。观察组采用项七针联合压灸治疗，每日1次，每周6次，连续治疗2周。对照组予口服盐酸倍他司汀片（2周）和醋氯芬酸分散片（3 d）。分别于治疗前后观察两组患者颈性眩晕症状与功能评估量表（ESCV）评分，检测血浆神经肽Y（NPY）、内皮素-1（ET-1）、降钙素基因相关肽（CGRP）含量及血液流变学、血流动力学指标，并于治疗后评定两组临床疗效。结果：治疗后，两组患者ESCV眩晕、日常生活及工作能力、心理及社会适应能力、头痛评分及总分较治疗前升高（P<0.01，P<0.05），观察组患者颈肩痛评分较治疗前升高（P<0.01）；观察组患者ESCV各项评分及总分均高于对照组（P<0.01，P<0.05）。治疗后，两组患者血浆NPY和ET-1含量较治疗前降低（P<0.01），血浆CGRP含量较治疗前升高(P<0.01，P<0.05)；观察组患者血浆NPY、ET-1含量低于对照组（P<0.01），血浆CGRP含量高于对照组（P<0.01）。治疗后，两组患者全血高切黏度、血浆黏度、全血低切黏度均较治疗前降低（P<0.01，P<0.05），基底动脉（BA）、左侧椎动脉（LVA）、右侧椎动脉（RVA）平均血流速度均较治疗前升高（P<0.05）；观察组患者全血高切黏度、血浆黏度及全血低切黏度均低于对照组（P<0.01），BA、LVA、RVA平均血流速度均高于对照组（P<0.05）。观察组总有效率为91.4%（32/35），高于对照组的71.4%（25/35，P<0.05）。结论：项七针联合压灸可有效减轻CV患者临床症状，改善血液流变学及血流动力学。.

High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.

UNASSIGNED: Schistosomiasis (SM) is a parasitic disease caused by Schistosoma mansoni. SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM.
UNASSIGNED: Uninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123.
UNASSIGNED: The fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs.
UNASSIGNED: Our data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.

Graphene, when electrified, generates far-infrared radiation within the wavelength range of 4 μm to 14 μm. This range closely aligns with the far-infrared band (3 μm to 15 μm), which produces unique physiological effects. Contraction and relaxation of vascular smooth muscle play a significant role in primary hypertension, involving the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway and the renin-angiotensin-aldosterone system. This study utilized spontaneously hypertensive rats (SHRs) as an untr-HT to investigate the impact of far-infrared radiation at specific wavelengths generated by electrified graphene on vascular smooth muscle and blood pressure. After 7 weeks, the blood pressure of the untr-HT group rats decreased significantly with a notable reduction in the number of vascular wall cells and the thickness of the vascular wall, as well as a decreased ratio of vessel wall thickness to lumen diameter. Additionally, blood flow perfusion significantly increased, and the expression of F-actin in vascular smooth muscle myosin decreased significantly. Serum levels of angiotensin II (Ang-II) and endothelin 1 (ET-1) were significantly reduced, while nitric oxide synthase (eNOS) expression increased significantly. At the protein level, eNOS expression decreased significantly, while α-SMA expression increased significantly in aortic tissue. At the gene level, expressions of eNOS and α-SMA in aortic tissue significantly increased. Furthermore, the content of nitric oxide (NO) in the SHR\'s aortic tissue increased significantly. These findings confirm that graphene far-infrared radiation enhances microcirculation, regulates cytokines affecting vascular smooth muscle contraction, and modifies vascular morphology and smooth muscle phenotype, offering relief for primary hypertension.

BACKGROUND: Experimental hepatopulmonary syndrome (HPS) is best reproduced in the rat common bile duct ligation (CBDL) model. Vildagliptin (Vild) is an anti-hyperglycemic drug that exerts beneficial anti-inflammatory, anti-oxidant and anti-fibrotic effects. Therefore, the present search aimed to explore the possible effectiveness of Vild in CBDL-induced HPS model.
METHODS: Four groups of male Wistar rats which weigh 220-270 g were used, including the normal control group, the sham control group, the CBDL group and CBDL+Vild group. The first three groups received i.p. saline, while the last group was treated with i.p. Vild (10 mg/kg/day) from the 15th to 28th day of the experiment.
RESULTS: CBDL decreased the survivability and body weight of rats, increased diameter of the pulmonary vessels, and altered the arterial blood gases and the liver function parameters. Additionally, it increased the pulmonary expressions of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) mRNA as well as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) proteins. The CBDL rats also exhibited elevation of the pulmonary interleukin-6 (IL-6), dipeptidyl peptidase-4 (DPP-4) and nitric oxide (NO) levels along with reduction of the pulmonary total anti-oxidant capacity and glucagon-like peptide-1 (GLP-1) levels. Vild mitigated these alterations and improved the histopathological abnormalities caused by CBDL.
CONCLUSIONS: Vild effectively attenuated CBDL-induced HPS through its anti-oxidant and anti-inflammatory effects along with its modulatory effects on ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling implicated in the regulation of intrapulmonary vasodilatation and angiogenesis, respectively.

The intrarenal endothelin (ET) system is an established moderator of kidney physiology and mechanistic contributor to the pathophysiology and progression of chronic kidney disease in humans and rodents. The aim of the present study was to characterize ET system by combining single cell RNA sequencing (scRNA-seq) data with immunolocalization in human and rodent kidneys of both sexes. Using publicly available scRNA-seq data, we assessed sex and kidney disease status (human), age and sex (rats), and diurnal expression (mice) on the kidney ET system expression. In normal human biopsies of both sexes and in rodent kidney samples, the endothelin-converting enzyme-1 (ECE1) and ET-1 were prominent in the glomeruli and endothelium. These data agreed with the scRNA-seq data from these three species, with ECE1/Ece1 mRNA enriched in the endothelium. However, the EDN1/Edn1 gene (encodes ET-1) was rarely detected, even though it was immunolocalized within the kidneys, and plasma and urinary ET-1 excretion are easily measured. Within each species, there were some sex-specific differences. For example, in kidney biopsies from living donors, men had a greater glomerular endothelial cell endothelin receptor B (Ednrb) compared with women. In mice, females had greater kidney endothelial cell Ednrb than male mice. As commercially available antibodies did not work in all species, and RNA expression did not always correlate with protein levels, multiple approaches should be considered to maintain required rigor and reproducibility of the pre- and clinical studies evaluating the intrarenal ET system.

The levels of endothelins were assessed in menopausal women with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) in the acute phase of the moderate COVID-19. Women under observation (age 45-69 years) were divided into two groups. Control group consisted of women (n=16) who did not have COVID-19, were not vaccinated, and had no antibodies to SARS-CoV-2 (IgG). The main group included women (n=63) in the acute phase of the moderate COVID-19 accompanied by pneumonia. According to the clinical and anamnestic data analysis, the main group was divided into subgroups: without AH and T2DM (n=21); with AH and without T2DM (n=32); and with AH and T2DM (n=10). The parameters of clinical blood analysis, as well as endothelin-1, endothelin-2, and endothelin-3 levels were assessed. In women with a moderate COVID-19, the endothelin-1 and endothelin-2 levels were increased compared to the control regardless of AH and T2DM status. We found no statistically significant differences in the studied parameters of endothelial dysfunction between the subgroups of menopausal women in the acute phase of the moderate COVID-19.

This chapter discusses the role of cardiac neural crest cells in the formation of the septum that divides the cardiac arterial pole into separate systemic and pulmonary arteries. Further, cardiac neural crest cells directly support the normal development and patterning of derivatives of the caudal pharyngeal arches, including the great arteries, thymus, thyroid, and parathyroids. Recently, cardiac neural crest cells have also been shown to indirectly influence the development of the secondary heart field, another derivative of the caudal pharynx, by modulating signaling in the pharynx. The contribution and function of the cardiac neural crest cells has been learned in avian models; most of the genes associated with cardiac neural crest function have been identified using mouse models. Together these studies show that the neural crest cells may not only critical for normal cardiovascular development but also may be involved secondarily because they represent a major component in the complex tissue interactions in the caudal pharynx and outflow tract. Cardiac neural crest cells span from the caudal pharynx into the outflow tract, and therefore may be susceptible to any perturbation in or by other cells in these regions. Thus, understanding congenital cardiac outflow malformations in human sequences of malformations resulting from genetic and/or environmental insults necessarily requires better understanding the role of cardiac neural crest cells in cardiac development.

The high-grade serous ovarian cancer (HG-SOC) tumor microenvironment (TME) is constellated by cellular elements and a network of soluble constituents that contribute to tumor progression. In the multitude of the secreted molecules, the endothelin-1 (ET-1) has emerged to be implicated in the tumor/TME interplay; however, the molecular mechanisms induced by the ET-1-driven feed-forward loops (FFL) and associated with the HG-SOC metastatic potential need to be further investigated. The tracking of the patient-derived (PD) HG-SOC cell transcriptome by RNA-seq identified the vascular endothelial growth factor (VEGF) gene and its associated signature among those mostly up-regulated by ET-1 and down-modulated by the dual ET-1R antagonist macitentan. Within the ligand-receptor pairs concurrently expressed in PD-HG-SOC cells, endothelial cells and activated fibroblasts, we discovered two intertwined FFL, the ET-1/ET-1R and VEGF/VEGF receptors, concurrently activated by ET-1 and shutting-down by macitentan, or by the anti-VEGF antibody bevacizumab. In parallel, we observed that ET-1 fine-tuned the tumoral and stromal secretome toward a pro-invasive pattern. Into the fray of the HG-SOC/TME double and triple co-cultures, the secretion of ET-1 and VEGF, that share a common co-regulation, was inhibited upon the administration of macitentan. Functionally, macitentan, mimicking the effect of bevacizumab, interfered with the HG-SOC/TME FFL-driven communication that fuels the HG-SOC invasive behavior. The identification of ET-1 and VEGF FFL as tumor and TME actionable vulnerabilities, reveals how ET-1R blockade, targeting the HG-SOC cells and the TME simultaneously, may represent an effective therapeutic option for HG-SOC patients.