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Objective: Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is a very important factor in the regulation of blood pressure. Also, the inhibition of ACE with natural compounds has been a very important research area in the treatment of high blood pressure. ACE was purified and characterized from sheep plasma. Molecular docking studies and the inhibition effect of thiamine, riboflavin, and captopril on ACE were investigated. Methods: Herein, ACE was purified from sheep plasma by affinity chromatography. The effect of thiamine and riboflavin on ACE was researched. Molecular docking studies were performed to understand the molecular interactions between thiamine, riboflavin, and captopril with ACE. Results: The purification coefficient was found to be 8636 fold. The binding energy of thiamine, riboflavin, and captopril was found to be -6.7 kcal/mol, -8.1 kcal/mol, and -5.5 kcal/mol, respectively. Thiamine conformed to three conventional hydrogen bonds with ASP:415, HIS:513, and LYS:454. Riboflavin formed four conventional hydrogen bonds with GLN:281, GLU:376, THR:282, and TYR:520. Captopril formed two conventional hydrogen bonds with ARG:124, one conventional hydrogen bond with TYR:62 and ASN:85, and one carbon-hydrogen bond with ASN:66. Molecular docking results showed that thiamine, riboflavin, and captopril interacted with ACE through hydrogen bonding and hydrophobic interactions. Thiamine and riboflavin indicated significant inhibition effects on ACE. The IC50 values of thiamine, riboflavin, and captopril were found as 960.56 µM, 11.02 µM, and 1.60 nM, respectively. Ki values for thiamine, riboflavin, and captopril were determined as 1352.04 µM, 12.30 µM, and 1.06 nM, respectively. Conclusion: In this work, it was concluded that thiamine and riboflavin may have preventive and therapeutical impacts against high blood pressure with their ACE inhibitor effect. Thiamine and riboflavin showed a lower inhibitory effect with a higher IC50 than captopril. However, when the inhibitory effect of thiamine and riboflavin vitamins is compared to captopril, it is concluded that they may be natural inhibitors with fewer side effects. [ABSTRACT FROM AUTHOR]

Overactivation of the angiotensin-converting enzyme (ACE)/angiotensin II type 1 receptor (AT1R) pathway leads to vasoconstriction and elevated blood pressure. Persicaria minor (Huds.) Opiz is an herbal plant known for its antioxidant, anti-hyperlipidemic, and anti-atherosclerotic properties, with bioactive compounds that exhibit antihypertensive effects. Therefore, this study aimed to evaluate the antihypertensive effects of the standardized aqueous extract of P. minor leaf (AEPM) through the ACE/AT1R pathway in human umbilical vein endothelial cells (HUVECs) induced with phorbol 12-myristate 13-acetate (PMA). HUVECs were stimulated with PMA to induce ACE, with or without AEPM or captopril treatment, for 24 h. Subsequently, ACE mRNA expression, ACE protein levels, ACE activity, angiotensin II levels, and AT1R expression were measured. The results demonstrated that AEPM treatment significantly reduced ACE mRNA expression, ACE protein levels, ACE activity, angiotensin II levels, and AT1R expression in PMA-induced HUVECs. The modulatory effects of AEPM on the ACE/AT1R pathway were comparable to those of captopril. Ex vivo experiments further confirmed that AEPM reduced the contraction responses of rat aortic rings to PMA. In conclusion, P. minor effectively inhibits the ACE/AT1R pathway in PMA-induced HUVECs, suggesting its potential as a natural antihypertensive agent. [ABSTRACT FROM AUTHOR]

The relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and psoriasis remains unclear. This study aims to analyze the association between ACE gene I/D polymorphism and the risk of psoriasis vulgaris in the Chinese Han population and to examine the correlation between ACE gene I/D polymorphism and psoriasis with comorbid hypertension and diabetes. Methods: A total of 358 patients with psoriasis vulgaris and 347 age- and sex-matched healthy volunteers from the Chinese Han population were selected. Clinical data, including blood pressure and fasting blood glucose, were collected from the patients. The ACE gene I/D polymorphism was analyzed using polymerase chain reaction (PCR). The association between ACE gene I/D polymorphism and psoriasis vulgaris, as well as comorbid hypertension and diabetes, was analyzed using the Pearson χ²-test. Results: The frequency of the ACE II genotype (OR = 1.84, 95% CI = 1.30, 2.61; P < 0.01) and the I allele (OR = 1.51, 95% CI = 1.22, 1.86; P < 0.01) was significantly higher in psoriasis patients compared to the control group. Conversely, the frequency of the ACE DD genotype (OR = 0.62, 95% CI = 0.44, 0.87; P < 0.01) and the D allele (OR = 0.66, 95% CI = 0.54, 0.82; P < 0.01) was significantly lower in psoriasis patients compared to the control group. No statistically significant differences were observed when stratified by blood pressure and blood glucose abnormalities (P > 0.05). Conclusion: The ACE II genotype and I allele are risk factors for psoriasis vulgaris in the Northern Chinese Han population. [ABSTRACT FROM AUTHOR]

Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group. [ABSTRACT FROM AUTHOR]

Simple Summary: The protein α-zein from corn has been studied both in vivo and in vitro for its potential to target treatments for non-communicable chronic diseases. This biological activity is achieved through the hydrolysis of the protein, which produces bioactive peptides. The study involved scientific research and a literature review to gather evidence of the biological activity of corn peptides. Additionally, databases and bioinformatics tools were utilized to simulate the enzymatic digestion of α-zein and confirm the bioactivity of the resulting peptides. The study discovered that the primary bioactivity is the inhibition of ACE, followed by the inhibition of DPP-IV and DPP-III, which are targets for treating hypertension and type-2 diabetes. In conclusion, conducting an in silico evaluation before proceeding to in vitro or in vivo studies can be efficient and cost-effective and contribute to better usage of corn gluten meals. Studies have shown that corn (Zea mays L.) proteins, mainly α-zein, have the potential to act on therapeutic targets related to non-communicable chronic diseases, such as high blood pressure and type 2 diabetes. Enzymatic hydrolysis of proteins present in foods can result in a great diversity of peptides with different structures and possible bioactivities. A review of recent scientific research papers was performed to show evidence of the bioactive properties of corn peptides by in vitro assays. The α-zein amino acid sequences were identified in the UniProtKB protein database and then analyzed in the BIOPEP database to simulate enzymatic digestion and verify the potential biological action of the resulting peptides. The peptides found in the BIOPEP database were categorized according to the probability of presenting biological action using the PeptideRanker database. The aim was to use existing data to identify in silico the potential for obtaining biologically active peptides from α-zein, the main storage protein of corn. The analysis showed that the majority of peptide fragments were related to the inhibition of angiotensin-converting enzyme, followed by the inhibition of dipeptidyl peptidase IV and dipeptidyl peptidase III. Many drugs used to treat high blood pressure and type 2 diabetes work by inhibiting these enzymes, suggesting that corn peptides could be potential alternative agents. In vitro studies found that the primary bioactivity observed was antioxidative action. Both in vitro and in silico approaches are valuable for evaluating the bioactive properties resulting from protein hydrolysis, such as those found in α-zein. However, conducting in vitro studies based on prior in silico evaluation can be more efficient and cost-effective. [ABSTRACT FROM AUTHOR]

The aim of the work is to determine the influence of angiotensin-converting enzyme (ACE) gene polymorphism on the course and effectiveness of antihypertensive therapy using the ACE inhibitor lisinopril and the beta-blocker carvedilol in patients with comorbidity of arterial hypertension and type 2 diabetes. Materials and methods. The study was carried out based on the Department of arterial hypertension and kidney disease of the L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine. The study included 106 patients with arterial hypertension of the 2nd degree, stage II and diabetes mellitus type 2, the average age was 54.3 ± 5.3 years. All patients were divided into three groups. The first group consisted of 48 patients with the A/A genotype of the polymorphic marker 2350 A/G of the angiotensin-converting enzyme gene, the second group included 22 patients with the A/G genotype, and the third group included 36 patients with the G/G genotype. DNA of peripheral blood leukocytes was used to study the single-nucleotide polymorphism of marker 2350 A/G of the angiotensin-converting enzyme gene. A combination of lisinopril and carvedilol was used as antihypertensive therapy. Results. Direct correlations were established between the presence of A/G and G/G genotypes of the single-nucleotide polymorphism 2350 A/G of the angiotensin-converting enzyme gene with an increased body mass index (p < 0.001), higher levels of systolic and diastolic blood pressure (p < 0.001), with an increased level of fasting blood glucose (p < 0.05), the HOMA-IR (p < 0.05), an increased level of low-density lipoproteins (p < 0.05) and triglycerides of the blood (p < 0.05). Positive correlations of the specified polymorphisms with an increase in the mass index of the myocardium of the left ventricle were also established (p < 0.001). As a result of the treatment, a significant decrease in blood pressure, both systolic and diastolic, was observed in all patients (p < 0.001). A statistically significant decrease in the left ventricular myocardial mass index was found (p < 0.001) in all groups of patients. At the same time, the reduction of left ventricular myocardial hypertrophy was statistically more pronounced in patients with genotype A/A than in patients with genotypes A/G and G/G (p < 0.05). In three groups of patients, a significant (p < 0.05) decrease in BMI was observed under the influence of diet therapy and drug treatment. Among the comparison groups of patients, the statistically most significant decrease of this indicator in treatment dynamics was found in individuals with the A/A genotype. A significant decrease in fasting blood glucose levels, HOMA-IR insulin resistance index, and markers of atherogenic dyslipidemia was revealed in both patients with the A/A genotype and those with the A/G and G/G genotypes (p < 0.05). The decrease in the level of insulin resistance (IR) in patients after treatment in all studied groups had positive correlations with the decrease in indicators of left ventricular hypertrophy (LVH) (p < 0.05). Positive correlations were also observed in patients of all observation groups between a decrease in body mass index (BMI) after treatment and a decrease in LVH (p < 0.05). There were no statistically significant differences between the studied parameters between the A/G and G/G groups, both before and after treatment. This confirms that the G allele of the polymorphic marker 2350 A/G of the ACE gene is associated with the development of hypertension and LVH. Conclusions. The therapy with the combination of lisinopril and carvedilol in patients with hypertension and type 2 diabetes contributed to the effective reduction of blood pressure in three groups of patients. It was established that patients with genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene had more pronounced hypertrophic changes of the myocardium than patients with genotype A/A before the start of treatment. Antihypertensive therapy was the most effective in reducing myocardial hypertrophy in patients with the A/A genotype of the polymorphic marker 2350 A/G of the ACE gene. It was found that the presence of genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene can be used as a predictor not only of the development of LVH but also of metabolic disorders associated with increased BMI, glycemia and insulin resistance, expressed by shifts in atherogenic dyslipidemia in patients with comorbid hypertension and type 2 diabetes. It was established that a decrease in the degree of LVH accompanied by a decrease in IR and BMI. It has been proven that the use of antihypertensive therapy with the use of carvedilol and lisinopril in the treatment regimen in patients with unfavourable genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene is effective and contributes to marked regression of LVH. It was determined that patients with the AA genotype of the polymorphic marker 2350 A/G of the ACE gene have the greatest prerequisite for the effective reduction of LVH after treatment, which was considered a favourable prognostic sign.

Objective To investigate the changes of angiotensin-converting enzyme （ACE） and angiotensin-converting enzyme 2 （ACE2） levels in children with severe Mycoplasma pneumoniae pneumonia （SMPP） and evaluates their clinical values in predicting the severity of SMPP. Methods A total of 71 children with Mycoplasma pneumoniae pneumonia （MPP group） and 63 with severe Mycoplasma pneumoniae pneumonia （SMPP group） admitted to the Second Hospital of Lanzhou University from October 2020 to December 2023 were recruited in this study. Additionally， 20 healthy children undergoing routine health check-ups during this period were selected as the control group. The serum concentrations of ACE and ACE2 in the three groups were measured using the enzyme-linked immunosorbent assay （ELISA）， and laboratory test results were collected for comparison and correlation analysis between the MPP and SMPP groups. The receiver operating characteristic （ROC） curve was delineated to assess the predictive values of one single index or combined for SMPP. Results In the three groups， the serum ACE level was the highest in the SMPP group and the lowest in the healthy control group. The serum ACE2 level was the highest in the MPP group and the lowest in the healthy control group （all P < 0.008）. Compared to the MPP group， the SMPP group exhibited significantly elevated white blood cell count （WBC）， neutrophil percentage （NE%）， C-reactive protein （CRP）， serum amyloid A protein （SAA）， procalcitonin （PCT）， interleukin-6 （IL-6）， erythrocyte sedimentation rate （ESR）， and D-dimer （all P < 0.001） and these indexes were positively correlated with ACE levels （all P < 0.05）， but negatively correlated with ACE2 levels （all P < 0.05）. The lymphocyte percentage （LY%） was significantly reduced （P < 0.001）， which was positively correlated with ACE2 levels （P < 0.05）， whereas negatively correlated with ACE levels （P < 0.05）. Lactate dehydrogenase （LDH） was elevated （P < 0.05）， which was negatively correlated with ACE2 levels （P < 0.05）， but not correlated with ACE levels （P > 0.05）. The monocyte percentage （MO%） showed neither significant difference nor correlation （both P > 0.05）. ROC curve analysis revealed that ACE， ACE2， CRP， D-dimer， LDH， and combined detection of ACE+ACE2， CRP+D-dimer+LDH all had predictive values for SMPP. Among them， the combined detection of ACE+ACE2 showed the highest predictive value， with an AUC of 0.991 and 95% CI： 0.981-1.000. Conclusion The levels of ACE and ACE2 are likely associated with the onset and progression of SMPP in children， and both ACE and ACE2 serve as good indicators for predicting SMPP.

This study aimed to investigate the structure-function relationship of angiotensin-converting enzyme (ACE) inhibitory peptides and to elucidate the action mechanism of food-derived ACE inhibitory peptides. Based on the amino acid sequences of recently reported ACE inhibitory pentapeptides and their half-maximal inhibitory concentration (IC50) values, a library of ACE inhibitory pentapeptides was generated and the structures of the ACE inhibitory pentapeptides were characterized using three amino acid descriptors, Z-scales, VHSE and SVHEHS. A partial least square (PLS) model for describing the quantitative structure-activity relationship (QSAR) of the ACE inhibitory peptides with the hydrophobic properties, steric properties, and electrical properties of amino acids as the independent variables and the lg IC50 of the ACE inhibitory pentapeptides as the dependent variable was established using Matlab software. The results showed that the R2 and Q2 of the QSAR model based on Z-scales descriptor were 0.641 1 and 0.536 9, respectively, and Gln-Arg-Pro-Asn-Met showed higher ACE inhibitory activity as predicted by this model. The predicted and measured IC50 were 0.051 7 and (0.040 0 ± 0.008 3) μmol/L, respectively, and the error between them was 0.011 7 μmol/L. The R2 and Q2 of the QSAR model based on VHSE descriptor were 0.763 6 and 0.508 1, respectively, and Leu-Arg-Ala-Phe-Gln exhibited better ACE inhibitory activity as predicted by this model. The predicted and measured IC50 were 0.043 8 and (0.027 3 ± 0.005 3) μmol/L, respectively, and the error between them was 0.016 5 μmol/L. The R2 and Q2 of the QSAR model based on SVHEHS descriptor were 0.840 5 and 0.400 5, respectively, and Leu-Arg-Ala-Phe-Gln displayed better ACE inhibitory activity as predicted by this model. The predicted and measured IC50 were 0.005 5 and (0.031 2 ± 0.004 2) μmol/L, and the error between them was 0.025 7 μmol/L. Among the three QSAR models, the one based on SVHEHS descriptor had the strongest fitting capability but weak predictive capacity, while the models based on Z-scales and VHSE descriptors could allow good QSAR analysis of the pentapeptides. Our modeling analysis showed that the activity of the ACE inhibitory peptides was negatively correlated with the hydrophobic characteristics of amino acids and positively correlated with the steric characteristics of amino acids. Molecular docking of three ACE inhibitory peptides to ACE protein (2X8J) showed that all the ACE inhibitory peptides could bind to ACE protein. This study provides a new tool for developing ACE inhibitory peptides and a theoretical basis for the development and application of food-derived ACE inhibitory peptides.

Novel and sensitive analytical technique was proposed for estimating perindopril (angiotensin-converting enzyme (ACE) inhibitor) in formulations using acidic dye as chromogenic reagent. The study was established on the development of colour species formation between perindopril erbumine and chromogenic reagent such as azocarmine G (ACG). Proposed method consists formation of an ion-pair association complex with azocarmine-G. The optical density was measured at λmax of 540 nm. Regression analysis of proposed method showed that the linearity lies within the concentration limits of 20-100 µg mL-1. Molar absorptivity (∈max) values of developed method are found to be as 3.22 x 10Á L mol-1 cm-1. Investigated method was found to have linear correlation coefficient (r) value of 0.9999. Proposed method obeyed Lambert-Beer' law with reproducible results. Percentage recovery was found to be within the limits of 99.7 - 100.1 (± 0.41 SD, ± 0.57 SD). All the parameters were validated statistically. [ABSTRACT FROM AUTHOR]

At present, the angiotensin‐converting enzyme (ACE) I/D polymorphism was considered to be associated to the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the association between it and the risk of COPD in different ethnic groups is still unclear. The purpose of this study is to conduct an updated meta‐analysis of the association between them; collect literatures published before 10 February 2023 by searching PubMed, Embase, MEDLINE, CBM, CNKI, Wanfang, and VIP Chinese scientific databases; and display the analysis results by drawing forest plots. At the same time, publication bias, sensitivity analysis, and trial sequential analysis (TSA) were performed to evaluate the stability and reliability of the results. In the overall population, the result of the DD versus II model showed the association with the risk of COPD ([OR] = 1.30, 95% CI [1.08, 1.56]), and there were no associations in other genetic models (p > 0.05). In Caucasians, the results of all genetic models showed no associations (p > 0.05). In Asians, the results of D versus I, DD versus II, and DD versus II + ID models showed the associations with the risk of COPD (D vs. I: [OR] = 1.48, 95% CI [1.14, 1.93]; DD vs. II: [OR] = 2.04, 95% CI [1.53, 2.72]; DD vs. II + ID: [OR] = 2.19, 95% CI [1.45, 3.29]), while the results of ID versus II and DD + ID versus II models showed no associations (p > 0.05). Therefore, the D allele and "DD" genotype variation of the ACE I/D gene polymorphism are associated with susceptibility to COPD in Asians but not in Caucasians. [ABSTRACT FROM AUTHOR]

Activation of the renin–angiotensin–aldosterone system (RAAS) plays an important pathophysiological role in hypertension. Increased mRNA levels of the angiotensinogen angiotensin-converting enzyme, angiotensin type 1 receptor gene, Agtr1a, and the aldosterone synthase gene, CYP11B2, have been reported in the heart, blood vessels, and kidneys in salt-sensitive hypertension. However, the mechanism of gene regulation in each component of the RAAS in cardiovascular and renal tissues is unclear. Epigenetic mechanisms, which are important for regulating gene expression, include DNA methylation, histone post-translational modifications, and microRNA (miRNA) regulation. A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in visceral adipose tissue and the heart of salt-sensitive hypertensive rats. Several miRNAs influence AGT expression and are associated with cardiovascular diseases. Expression of both ACE and ACE2 genes is regulated by DNA methylation, histone modifications, and miRNAs. Expression of both angiotensinogen and CYP11B2 is reversibly regulated by epigenetic modifications and is related to salt-sensitive hypertension. The mineralocorticoid receptor (MR) exists in cardiovascular and renal tissues, in which many miRNAs influence expression and contribute to the pathogenesis of hypertension. Expression of the 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene is also regulated by methylation and miRNAs. Epigenetic regulation of renal and vascular HSD11B2 is an important pathogenetic mechanism for salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Isoleucine-proline-proline (Ile-Pro-Pro, IPP) is a natural food source tripeptide that inhibits angiotensin-converting enzyme (ACE) activity. The aim of this study was to determine the central and peripheral roles of IPP in attenuating sympathetic activity, oxidative stress and hypertension. Male Sprague-Dawley rats were subjected to sham-operated surgery (Sham) or two-kidney one-clip (2K1C) surgery to induce renovascular hypertension. Renal sympathetic nerve activity and blood pressure were recorded. Bilateral microinjections of IPP to hypothalamic paraventricular nucleus (PVN) attenuated sympathetic activity (-16.1 ± 2.5%, P < 0.001) and hypertension (-8.7 ± 1.5 mmHg, P < 0.01) in 2K1C rats by inhibiting ACE activity and subsequent angiotensin II and superoxide production in the PVN. Intravenous injections of IPP also attenuated sympathetic activity (-15.1 ± 2.1%, P < 0.001) and hypertension (-16.8 ± 2.3 mmHg, P < 0.001) via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. The duration of the effects of the intravenous IPP was longer than those of the PVN microinjection, but the sympatho-inhibitory effect of intravenous injections occurred later than that of the PVN microinjection. Intraperitoneal injection of IPP (400 pmol/day for 20 days) attenuated hypertension and vascular remodeling via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. These results indicate that IPP attenuates hypertension and sympathetic activity by inhibiting ACE activity and oxidative stress. The sympathoinhibitory effect of peripheral IPP is mainly caused by the ACE inhibition in PVN, and the antihypertensive effect is related to the sympathoinhibition and the arterial ACE inhibition. Long-term intraperitoneal IPP therapy attenuates hypertension, oxidative stress and vascular remodeling. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes of angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) levels in children with severe Mycoplasma pneumoniae pneumonia (SMPP) and evaluates their clinical values in predicting the severity of SMPP. Methods A total of 71 children with Mycoplasma pneumoniae pneumonia (MPP group) and 63 with severe Mycoplasma pneumoniae pneumonia (SMPP group) admitted to the Second Hospital of Lanzhou University from October 2020 to December 2023 were recruited in this study. Additionally, 20 healthy children undergoing routine health check-ups during this period were selected as the control group. The serum concentrations of ACE and ACE2 in the three groups were measured using the enzyme-linked immunosorbent assay (ELISA), and laboratory test results were collected for comparison and correlation analysis between the MPP and SMPP groups. The receiver operating characteristic (ROC) curve was delineated to assess the predictive values of one single index or combined for SMPP. Results In the three groups, the serum ACE level was the highest in the SMPP group and the lowest in the healthy control group. The serum ACE2 level was the highest in the MPP group and the lowest in the healthy control group (all P < 0.008). Compared to the MPP group, the SMPP group exhibited significantly elevated white blood cell count (WBC), neutrophil percentage (NE%), C-reactive protein (CRP), serum amyloid A protein (SAA), procalcitonin (PCT), interleukin-6 (IL6), erythrocyte sedimentation rate (ESR), and D-dimer (all P < 0.001) and these indexes were positively correlated with ACE levels (all P < 0.05), but negatively correlated with ACE2 levels (all P < 0.05). The lymphocyte percentage (LY%) was significantly reduced (P < 0.001), which was positively correlated with ACE2 levels (P < 0.05), whereas negatively correlated with ACE levels (P < 0.05). Lactate dehydrogenase (LDH) was elevated (P < 0.05), which was negatively correlated with ACE2 levels (P < 0.05), but not correlated with ACE levels (P > 0.05). The monocyte percentage (MO%) showed neither significant difference nor correlation (both P > 0.05). ROC curve analysis revealed that ACE, ACE2, CRP, D-dimer, LDH, and combined detection of ACE+ACE2, CRP+D-dimer+LDH all had predictive values for SMPP. Among them, the combined detection of ACE+ACE2 showed the highest predictive value, with an AUC of 0.991 and 95% CI: 0.981-1.000. Conclusion The levels of ACE and ACE2 are likely associated with the onset and progression of SMPP in children, and both ACE and ACE2 serve as good indicators for predicting SMPP. [ABSTRACT FROM AUTHOR]

Inhibition of Angiotensin-converting enzyme I (ACE I) is a modern therapeutic approach to treatment of hypertension. In recent years, research into natural ACE peptide inhibitors without side effects has become important. The aim of this study is to isolate and characterize novel bioactive peptides from skim and/or whole cow's milk fermented with selected lactobacillus strains. Several homo/heterofermentative strains of the Lactobacillus species of dairy origin have been pre-selected and different milk fermented samples have been studied. A protocol for analyses was designed and the milk proteins were separated by centrifugation at 4°C at 10000 × g, with molecular mass cut off (MWCO) membranes of 3 and 10 kDa. The samples with molecular mass below 3 kDa were further separated by ultrafiltration by dialysis cell (cut off membrane 1 kDa) by continuous stirring at room temperature. The milk fractions under 1 kDa molecular mass were characterized by UPLC-MS. The ACE-inhibitory activity was determined using the FAPGG (N-[3-(2-Furyl) acryloyl]-L-phenylalanyl-glycyl-glycine) degradation method. All tested samples (1 kDa) exhibit ACE I inhibitory activity with IC50 in a range of 6 - 37 mg mL-1. In silico logP prediction of selected peptides was used to assess whether lipophilicity of the compounds falls within the so-called "therapeutically relevant pharmacokinetic space". [ABSTRACT FROM AUTHOR]

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Grifola frondosa, a high-protein edible mushroom, exhibited potential antihypertensive effects through ACE inhibition. The ACE was expressed in vascular smooth muscle cells (VSMCs) and transported via exosomes. This study prepared low molecular weight GFP through enzymatic hydrolysis, showing strong ACE inhibition. Ang II increased ACE expression and activity in VSMCs, inducing phenotype switching by up-regulating α-SMA and OPN. GFP reduced Ang II’s stimulating effects. Exosomes from Ang II-treated (Ang II-Exos) or GFP-treated (GFP-Exos) VSMCs had particle sizes under 200 nm with positive biomarkers CD63 and Tsg101. Co-culture experiments revealed higher ACE loading in Ang II-Exos than in VSMCs, but significantly lower in GFP-Exos. Ang II-Exos promoted VSMC proliferation, migration, inflammation, and phenotypic switching, while GFP-Exos significantly reduced these effects by inhibiting ACE activity and regulating the NF-κB pathway. GFP effectively mitigated Ang II-induced VSMC dysfunction by modulating exosome-mediated ACE loading and phenotypic transformation.

This study aimed to screen peptides with antihypertensive effects from the α-chymotrypsin hydrolysate of Sebastes schlegelii (SSA). SSA demonstrated ACE inhibitory activity with an IC50 value of 0.062 ± 0.001 mg/mL. The SSA significantly reduced body weight and systolic blood pressure in the SHR spontaneously hypertensive rat (SHR) model and improved hypertension-induced vasopathy and interstitial fibrosis in heart and vascular tissues, indicating the presence of ACE inhibitory peptides contributing to cardiovascular health. Peptide composition analysis identified fractions of SSA with potent ACE inhibitory activity, particularly those with molecular weights of 5 kDa or less. Further evaluation of ACE activity using Sephadex G-10 separated SSA fractions led to the amino acid sequence analysis of the most effective fraction (SSA-F1). Molecular docking simulations predicted that peptides from SSA-F1 inhibit ACE activity by binding to its active sites. This research suggests the potential of peptides from S. schlegelii for clinical hypertension treatment.

This study investigated the effect of anaerobic treatment on the non-volatile components and angiotensin-converting enzyme (ACE) inhibitory activity in purple-colored leaf tea. Results showed that after 8 h of anaerobic treatment, the γ-aminobutyric acid (GABA) content significantly increased from 0.02 mg/g to 1.72 mg/g (p

Abstract Recent years have seen a resurgence of interest for the renin–angiotensin–aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II—angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin–angiotensin–aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin–angiotensin–aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin–angiotensin–aldosterone system alterations in septic shock should help to decipher patients’ phenotypes and to implement targeted interventions.

Abstract Angiotensin-converting enzyme (ACE) is closely related to cardiometabolic risk factors and atherosclerosis. This study aims to investigate whether the insertion/deletion (I/D) variant of ACE gene impacts cardiometabolic risk factors, premature coronary artery disease (PCAD), and severity of coronary lesions. PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 22, 2023. 94,270 individuals were included for the analysis. Carriers of DD genotype had higher levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist circumference (WC) than carriers of II or ID genotypes. In addition, carriers of DD genotype were at high risk of PCAD and multiple vessel lesions. The impacts of ACE I/D variant on lipid levels were significant in American individuals but stronger in male individuals. In contrast, the impacts of ACE I/D variant on PCAD and severity of coronary lesions were primarily significant in Caucasian individuals. This study indicates that the ACE I/D variant has a slight but significant impact on cardiometabolic risk factors, PCAD, and severity of coronary lesions. Angiotensin-converting enzyme inhibitors (ACEI) may benefit high-risk populations with ACE DD genotype to prevent PCAD and multiple vessel lesions. PROSPERO registration number: CRD42023426732

Abstract. Camel milk is widely used in arid desert areas, and it is of great importance from a health standpoint due to its chemical content and health benefits, which increase after fermentation as a result of the decomposition of its components by lactic acid bacteria. Among these components are the proteins that, when decomposed, produce bioactive peptides that help in the prevention and treatment of many diseases. Thus, it is considered a functional food for human nutrition and to treat health problems in these areas due to its high nutritional value and ease of digestion. It has been proven that camel milk has many beneficial health effects, such as anti-bacterial activities because it contains lactoferrin, lysozyme, immune globulin, and lactoperoxidase, in addition to its ability to adjust cholesterol and blood sugar, and its possession of antioxidant, angiotensin-converting enzyme inhibitor, and anti-cancer activities, and to treat digestive system problems. The effectiveness of these activities increases after fermenting camel milk with Lactic acid bacteria and probiotics are a result of the activity of these bacteria to break down the milk components of fats, proteins and carbohydrates into fatty acids, peptides and polysaccharides that are beneficial from a health standpoint and contribute to prolonging the shelf life of fermented products made from camel milk..

The most prevalent cardiovascular illness in the world, hypertension, is a significant public health issue in both developed and developing nations. A major risk of cardiovascular disease and high blood pressure is morbidity and mortality. Among all the classes of antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibition has been considered an effective therapeutic approach for the management of hypertension. ACE catalyzes the conversion of inactive angiotensin I into a potent vasoconstrictor, angiotensin II. Angiotensin II results in raising blood pressure by increasing peripheral resistance, heart rate, and cardiac output. There are a number of disorders associated with the cardiovascular system which is frequently treated with ACE inhibitors. Nowadays, various synthetic ACE inhibitors are used in clinical use to treat hypertension. There have been numerous negative side effects related to synthetic ACE inhibitors. Look for natural resources that can be exploited to produce ACE inhibitors that are reliable, safe, benign, and more cost-effective approaches. This review focuses on ACE inhibitors from natural source for the control hypertension. Additionally, a valid statistical analysis of data using a one-sample t-test on data that was collected at random and valued looks at whether the sample's mean is statistically different from or equal to a known or predicted mean value.

Recent years have seen a resurgence of interest for the renin–angiotensin–aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II—angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin–angiotensin–aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin–angiotensin–aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin–angiotensin–aldosterone system alterations in septic shock should help to decipher patients' phenotypes and to implement targeted interventions. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE) is closely related to cardiometabolic risk factors and atherosclerosis. This study aims to investigate whether the insertion/deletion (I/D) variant of ACE gene impacts cardiometabolic risk factors, premature coronary artery disease (PCAD), and severity of coronary lesions. PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 22, 2023. 94,270 individuals were included for the analysis. Carriers of DD genotype had higher levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist circumference (WC) than carriers of II or ID genotypes. In addition, carriers of DD genotype were at high risk of PCAD and multiple vessel lesions. The impacts of ACE I/D variant on lipid levels were significant in American individuals but stronger in male individuals. In contrast, the impacts of ACE I/D variant on PCAD and severity of coronary lesions were primarily significant in Caucasian individuals. This study indicates that the ACE I/D variant has a slight but significant impact on cardiometabolic risk factors, PCAD, and severity of coronary lesions. Angiotensin-converting enzyme inhibitors (ACEI) may benefit high-risk populations with ACE DD genotype to prevent PCAD and multiple vessel lesions. PROSPERO registration number: CRD42023426732 [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable. The understanding of the pathogenesis of IBD remains unclear. In this study, we found that ace (angiotensin-converting enzyme), expressed abundantly in the intestine, plays an important role in IBD. The deletion of ace in zebrafish caused intestinal inflammation with increased expression of the inflammatory marker genes interleukin 1 beta (il1b), matrix metallopeptidase 9 (mmp9), myeloid-specific peroxidase (mpx), leukocyte cell-derived chemotaxin-2-like (lect2l), and chemokine (C-X-C motif) ligand 8b (cxcl8b). Moreover, the secretion of mucus in the ace−/− mutants was significantly higher than that in the wild-type zebrafish, validating the phenotype of intestinal inflammation. This was further confirmed by the IBD model constructed using dextran sodium sulfate (DSS), in which the mutant zebrafish had a higher susceptibility to enteritis. Our study reveals the role of ace in intestinal homeostasis, providing a new target for potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

In the study, papain was used to hydrolyze tilapia (Oreochromis mossambicus) skin to obtain a tilapia skin hydrolysate (TSH) with dual angiotensin‐converting enzyme (ACE) and dipeptidyl peptidase IV (DPP‐IV) inhibitory activities. The resulting TSH was sequentially fractionated by ultrafiltration, size exclusion separation chromatography, and reverse‐phase high‐performance liquid chromatography. Its inhibitory effects on ACE and DPP‐IV were determined by commercial reagent kits. Two peptides purified from TSH were identified as Gly‐Pro‐Leu‐Gly‐Ala‐Leu (GPLGAL) and Lys‐Pro‐Ala‐Gly‐Asn (KPAGN) by the ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Inhibitory concentration (IC50) of GPLGAL on ACE and DPP‐IV were 117.20 ± 1.69 and 187.10 ± 2.75 µM, respectively. IC50 of KPAGN on ACE and DPP‐IV were 137.40 ± 2.33 and 259.20 ± 2.85 µM, respectively. The molecular simulation demonstrated that the binding affinities of GPLGAL to ACE and DPP‐IV proteins were −8.5 and −7.4 kcal/mol, respectively, whereas those of KPAGN to ACE and DPP‐IV proteins were −7.9 and −6.7 kcal/mol, respectively. GPLGAL interacted with 21 amino acid residues of the ACE active site, whereas KPAGN engaged with 19 amino acid residues. Additionally, GPLGAL interacted with 10 amino acid residues of the DPP‐IV active site, whereas KPAGN engaged with 13 amino acid residues. The two peptides predominantly occupied the active sites of ACE (His513, Tyr523, and Ala354) and DPP‐IV (Tyr662 and Arg125) through hydrogen bonding. This leads to the deactivation of ACE and DPP‐IV. Practical Application: Accelerate tilapia skin development and high‐value utilization; provide foundation for preparing the peptides with dual ACE and DPP‐IV inhibiting activity. [ABSTRACT FROM AUTHOR]

Hypertension remains a significant global health concern, contributing significantly to cardiovascular diseases and mortality rates. The inhibition of angiotensin-converting enzyme (ACE) plays a crucial role in alleviating high blood pressure. We investigated the potential of finger millets (Eleusine coracana) as a natural remedy for hypertension by isolating and characterizing its ACE-inhibitory compound. First, we evaluated the ACE-inhibitory activity of the finger millet ethanol extract and subsequently proceeded with solvent fractionation. Among the solvent fractions, the ethyl acetate fraction exhibited the highest ACE inhibitory activity and was further fractionated. Using preparative high-performance liquid chromatography, the ethyl acetate fraction was separated into four subfractions, with fraction 2 (F2) exhibiting the highest ACE inhibitory activity. Subsequent 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR analyses confirmed that the isolated compound from F2 was catechin. Furthermore, molecular docking studies indicated that catechin has the potential to act as an ACE inhibitor. These findings suggest that finger millets, particularly as a source of catechin, have the potential to be used as a natural antihypertensive. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare the performance of direct amplification of viral nucleic acid from transport medium to extracted nucleic acid for polymerase chain reaction (PCR), sequencing, and genotyping applications. Methods XpressAmp lysate and extracted total nucleic acid from viral transport medium containing nasopharyngeal specimens were evaluated across different molecular applications to determine performance characteristics. Results SARS-CoV-2 quantitative PCR and angiotensin-converting enzyme (ACE) genotyping assays worked well with XpressAmp lysate, almost equal with or better than extracted nucleic acid in some specimens. However, XpressAmp completely failed to perform in next-generation sequencing for strain typing. Both protocols failed to detect ACE2 expression in viral transport medium. Conclusion Direct amplification of viral nucleic acid from viral transport medium containing nasopharyngeal specimen works well for molecular assays with low thresholds of quality; however, it does have limitations with assays that require high quality nucleic acid for input. Use of the XpressAmp protocol significantly improves turnaround time and allows for easy ramp-up of PCR and genotyping assays. [ABSTRACT FROM AUTHOR]

Purpose Orolingual angioedema (OA) secondary to administration of thrombolytic therapy is a rare, but serious, known adverse effect. Despite the lack of robust evidence for their use, C1 esterase inhibitors are recommended by guidelines for the treatment of refractory thrombolytic-associated OA. This report highlights the use of a C1 esterase inhibitor in a patient with tenecteplase-associated OA unresolved by antihistamine and corticosteroid therapy. Summary A 67-year-old white male with a history of hypertension managed with lisinopril presented to the emergency department with acute onset of slurred speech and left-sided hemiparesis. Following workup, an outside hospital's neurology stroke team suspected an acute infarct and determined the patient to be a candidate for tenecteplase. Approximately 1 hour after tenecteplase administration, the patient began complaining of dyspnea and mild oral angioedema. Immediate interventions for OA management included intravenous therapy with dexamethasone 10 mg, diphenhydramine 25 mg, and famotidine 20 mg. After an additional 30 minutes, the patient's OA symptoms continued to progress and a C1 esterase inhibitor (Berinert) was administered. Shortly after administration of the C1 esterase inhibitor, the patient's symptoms continued to worsen, ultimately leading to endotracheal intubation. Following intubation, symptom improvement was noted, and the patient was safely extubated after 30 hours. Conclusion Although rare, OA is a potentially life-threatening complication of tenecteplase therapy and requires prompt pharmacological intervention to optimize patient outcomes. Currently, no single agent or treatment algorithm exists that has shown significant efficacy or safety in the setting of thrombolytic-associated OA. Until data are available for C1 esterase inhibitors in this application, these inhibitors should only be considered if there is continued symptom progression after intravenous administration of corticosteroids and antihistamines. [ABSTRACT FROM AUTHOR]

Background: Hypertension in pregnancy is a vascular disorder that occurs before pregnancy or arises during pregnancy that there were 30% of cases of maternal death. Moringa oleifera's potential to lower blood pressure can be utilized as an alternative antihypertensive during pregnancy, minimizing the risk of preeclampsia. Objective: The purpose of this study was to determine the molecular target of Moringa oleifera is intended to optimize pharmacodynamic activity based on the interaction pattern of the compounds with the ACE inhibitor (PDB ID: 1O86). Methods: Molecular docking is carried out using Autodock 4.0 program (AutoDock Tools). Results: According to the binding energy value and ACE inhibitory interaction, α-Rhamnopyranosyl, β-Sitosterol, and Sinalbin are prospective Moringa oleifera compounds as alternative antihypertensive. These potential compounds can inhibit ACE with binding energy -8.23; -9.27; -9.14 kcal/mol. Pharmacokinetic predictions reported that the potential compounds are absorbed in the intestine and indicates as molecules are tightly bound to plasma proteins and, as well as CYP3A4 and CYP2C9 inhibitors. The prediction of toxicity indicates that the potential compounds are classified as drug-induced acute liver failure with low carcinogens. Conclusion: α-Rhamnopyranosyl, β-Sitosterol and Sinalbin can be suitable lead compounds for synthetic drugs for antihypertensive agents. [ABSTRACT FROM AUTHOR]

The D allele has been identified as being linked to cardiovascular disease since the discovery of an insertion/deletion (I/D) polymorphism in the ACE gene, this polymorphism has been found to have significant associations with a variety of cardiovascular risk factors. Recent findings indicate a rising prevalence of metabolic disorders among rural populations in developing nations. Research on health matters has been predominantly focused on urban populations, with relatively less attention given to their rural counterparts Hence, the present study attempts to estimate the prevalence of ACE gene I/D polymorphism and explore its association with various cardiovascular risk factors among Rural Yadav population from India. In the present study, 207 (Male 47, Female 160) members of the Yadav community participated in the cross-sectional study. All the socio-demographic factors, somatometric (anthropometric) variables, and the intravenous blood was collected and Physiological (blood pressure), and biochemical (fasting glucose and lipid profile) parameters were measured as recommended by the American Heart Association, allele-specific PCR of the ACE gene I/D polymorphism was carried out, the PCR products were genotyped on 2% agarose gel Electrophoresis and ACE gene polymorphism was analysed for its association with various cardiovascular risk factors. Among the analysed individuals, 34 (16.4%) were found to have the II genotype, 58 (28.0%) had the ID genotype, and 115 (55.6%) had the DD genotype. The allele frequency of the I allele was found to be 0.31, and the frequency of the D allele was 0.69. The frequency of the DD genotype was found to be significantly higher among individuals with high TC, high TG, and low non-HDL levels (p value < 0.05). When considered collectively, the findings of this study are consistent with the hypothesis that the DD genotype of ACE polymorphism represents a correlation with cardiovascular disease risk factors in this population. [ABSTRACT FROM AUTHOR]

ABSTRACT At present, the angiotensin‐converting enzyme (ACE) I/D polymorphism was considered to be associated to the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the association between it and the risk of COPD in different ethnic groups is still unclear. The purpose of this study is to conduct an updated meta‐analysis of the association between them; collect literatures published before 10 February 2023 by searching PubMed, Embase, MEDLINE, CBM, CNKI, Wanfang, and VIP Chinese scientific databases; and display the analysis results by drawing forest plots. At the same time, publication bias, sensitivity analysis, and trial sequential analysis (TSA) were performed to evaluate the stability and reliability of the results. In the overall population, the result of the DD versus II model showed the association with the risk of COPD ([OR] = 1.30, 95% CI [1.08, 1.56]), and there were no associations in other genetic models (p > 0.05). In Caucasians, the results of all genetic models showed no associations (p > 0.05). In Asians, the results of D versus I, DD versus II, and DD versus II + ID models showed the associations with the risk of COPD (D vs. I: [OR] = 1.48, 95% CI [1.14, 1.93]; DD vs. II: [OR] = 2.04, 95% CI [1.53, 2.72]; DD vs. II + ID: [OR] = 2.19, 95% CI [1.45, 3.29]), while the results of ID versus II and DD + ID versus II models showed no associations (p > 0.05). Therefore, the D allele and “DD” genotype variation of the ACE I/D gene polymorphism are associated with susceptibility to COPD in Asians but not in Caucasians.

It is known that the dysfunction of the endothelium has crucial role in many pathological conditions and underlines adverse cardiovascular events. The aim of our study was to determine biologically active substances in the blood that affect endothelial function and homocysteine level in adolescents with rheumatic diseases. Materials and methods. We examined 68 patients with rheumatic diseases, among them 25 patients with systemic lupus erythematosus (SLE) and 43 patients with juvenile idiopathic arthritis (JIA). Obtained results were compared with similar indicators of peers from the control group. All patients received basic therapy for 12 or more months at the time of examination. Biologically active substances (Homocysteine (Hcy), vascular endothelial growth factor (VEGF), high-sensitivity C-reactive protein (hs-CRP)) were studied by enzyme-linked immunosorbent assay, brain natriuretic peptide (NT-proBNP) by competitive immunoassay, and angiotensin-converting enzyme (ACE) by turbidimetric FAPGG kinetics method. Results. Patients with rheumatic diseases had a significantly higher level of BNP (p < 0.01). These changes were most significant in patients with SLE. The level of Hcy did not differ from the similar indicator of the control group, but in patients with SLE it was significantly higher (p < 0.01) than in patients with JIA. Conclusions. In patients with rheumatic diseases, biologically active substances level affecting the endothelium function depends on the disease. Biologically active substances affecting the function of the endothelium were within normal values. Thus, in children with SLE compared with JIA children, an increase in Hcy and NT-proBNP, and a decrease in ACE and hs-CRP protein were found. In children with JIA, normal levels of Hcy and ACE are accompanied by an increase in NT-proBNP and hs-CRP. In adolescents aged 10–18 years with SLE and JIA, multidirectional changes in biologically active substances and homocysteine, affecting the endothelial function of blood vessels were found.

This study aimed to investigate the impact of Monascus on bioactive peptides, particularly angiotensin-converting enzyme (ACE) inhibitory peptides, during cheese maturation. The content of soluble nitrogen, α-glucosidase and ACE inhibitory activities during the ripening process were investigated. Cheese not inoculated with Monascus as a control group. The peptide profile of Monascus cheese was identified. The potential bioactive peptides were screened by bioinformatics and molecular docking, and the selected peptides were synthesized and evaluated. The results showed that compared with the control group, the pH 4.6 soluble nitrogen content (pH 4.6-SN) and trichloroacetic acid soluble nitrogen (TCA-SN) of Monascus cheese were increased by 57.98% and 38.34%, and the α-glucosidase and ACE inhibitory activities were increased by 32.21% and 73.98%, respectively. A total of 1 796 peptides were identified in the extract of Monascus cheese, including 51 ACE inhibitory peptides, 28 antioxidant peptides and 7 glucose-lowering peptides. Two ACE inhibitory peptides YPFPGPI and FPEVFGK were selected, whose half-maximal inhibitory concentration values were 207.31 and 410.61 μmol/L, respectively. The inhibition type was non-competitive. This study has provided a rapid screening method for ACE inhibitory peptides, and has proved that the addition of Monascus in cheese can effectively improve the ACE inhibitory activity, which provides a reference for exploring the potential functional properties of Monascus cheese.

The efficacy of the antihypertensive therapy may be related to genetic factors that can influence not only the degree of the blood pressure (BP) elevation but also contribute to the interindividual variability of response to the antihypertensive treatment.The aim of the work was to study pharmacodynamic parameters of the therapy efficacy with angiotensin II receptor blockers in the form of monotherapy and as part of combined drugs in patients with the arterial hypertension depending on the genetic features of patients – polymorphism of the gene encoding angiotensin-converting enzyme, or I/D-polymorphism.Materials and methods. The study included 179 patients of the Moscow region with a first-diagnosed arterial hypertension (AH) of 1–2 degree, including 141 (78.8%) women and 38 (21.2%) men aged from 32 to 69 years. By a simple randomization method, the patients were randomly allocated into groups receiving irbesartan and valsartan as mono- or combination therapy with hydrochlorthiazide. After 3 weeks of this pharmacotherapy, the presence of rs4646994 Alu Ins / Del genetic polymorphism of the angiotensin-converting enzyme (ACE) gene and the minimum equilibrium concentration of angiotensin II receptor blockers (ARBs) were determined.Results. The patients treated with irbesartan, the D/D genotype carriers, were significantly less likely to reach the target BP and more likely to require a pharmacotherapy intensification compared to I/D heterozygotes (p=0.042 and p=0.058, respectively) and I/I homozygotes (p=0.011 and p=0.011, respectively). The patients treated with valsartan, the D/D genotype carriers, significantly more often reached the target BP and significantly less often required a pharmacotherapy intensification than the I/D genotype carriers (p=0.05 and p=0.05, respectively). Herewith, at the end of the study, according to the results of the office BP measurements and daily BP monitoring, the target BP achievement was not significantly correlated with the I/D polymorphism of the ACE gene.Conclusion. When personalizing the AH therapy in patients of the Moscow region, the genotype I/I carriers by I/D polymorphism of the ACE gene, can be recommended irbesartan in the form of mono- or bicomponent therapy as a starting therapy of ARBs; the D/D genotype carriers can be recommended valsartan. A more pronounced decrease in the daytime systolic BP (SBP), the daytime diastolic BP (DBP) and the nighttime SBP variabilities in the valsartan group of patients, the D allele carriers may indicate a more persistent effect of the antihypertensive therapy.

Overactivation of the angiotensin-converting enzyme (ACE)/angiotensin II type 1 receptor (AT1R) pathway leads to vasoconstriction and elevated blood pressure. Persicaria minor (Huds.) Opiz is an herbal plant known for its antioxidant, anti-hyperlipidemic, and anti-atherosclerotic properties, with bioactive compounds that exhibit antihypertensive effects. Therefore, this study aimed to evaluate the antihypertensive effects of the standardized aqueous extract of P. minor leaf (AEPM) through the ACE/AT1R pathway in human umbilical vein endothelial cells (HUVECs) induced with phorbol 12-myristate 13-acetate (PMA). HUVECs were stimulated with PMA to induce ACE, with or without AEPM or captopril treatment, for 24 h. Subsequently, ACE mRNA expression, ACE protein levels, ACE activity, angiotensin II levels, and AT1R expression were measured. The results demonstrated that AEPM treatment significantly reduced ACE mRNA expression, ACE protein levels, ACE activity, angiotensin II levels, and AT1R expression in PMA-induced HUVECs. The modulatory effects of AEPM on the ACE/AT1R pathway were comparable to those of captopril. Ex vivo experiments further confirmed that AEPM reduced the contraction responses of rat aortic rings to PMA. In conclusion, P. minor effectively inhibits the ACE/AT1R pathway in PMA-induced HUVECs, suggesting its potential as a natural antihypertensive agent.

COVID-19 infection caused by SARS-CoV-2 continues to cause significant mortality and morbidity. ACE2 is a key regulator of the renin–angiotensin–aldosterone system (RAAS). Differences in COVID-19 severity are thought to be due to the imbalance of RAAS/ACE mutations. This retrospective study evaluated the detection and genetic susceptibility to SARS-CoV-2 infection in 202 children ≤3 years of age living in the Amazon region in 2021. The angiotensin-converting enzyme ACE I/D (rs4646994) and ACE2 G8790A (rs2285666) polymorphisms were detected by SYBR GREEN real-time PCR and PCR-RFLP/Alul digestion, respectively. SARS-CoV-2 detection was performed by RT-qPCR in feces and saliva samples collected simultaneously from the same children presenting acute gastroenteritis (AGE) or acute respiratory infection (ARI). The frequency of SARS-CoV-2 detected by qRT-PCR in children was low (5.9%, 12/202), although higher in the group of children with AGE (8.9%, 9/101) than with ARI (2.9%, 3/101). Susceptibility to SARS-CoV-2 infection was not verified due to the low frequency. Homozygous II (rs4646994) children were the majority (87.1%, 176/202). Boys with genotype A (rs2285666) were more susceptible to ARI and pneumonia symptoms than AGE (OR = 3.8, 95% CI 1.4–10.3, p 0.007). Boys with genotype G (rs4646994) or the combination II + G were more susceptible to acquiring AGE. Surveillance, along with understanding their causes, is crucial to controlling ARI and COVID-19 in children living in low-income countries.

The identification of pathological links among metabolic disorders, kidney ailments, and cardiovascular conditions has given rise to the concept of cardiovascular–kidney–metabolic (CKM) syndrome. Emerging prenatal risk factors seem to increase the likelihood of CKM syndrome across an individual's lifespan. The renin–angiotensin system (RAS) plays a crucial role in maternal–fetal health and maintaining homeostasis in cardiovascular, metabolic, and kidney functions. This review consolidates current preclinical evidence detailing how dysregulation of the RAS during pregnancy and lactation leads to CKM characteristics in offspring, elucidating the underlying mechanisms. The multi-organ effects of RAS, influencing fetal programming and triggering CKM traits in offspring, suggest it as a promising reprogramming strategy. Additionally, we present an overview of interventions targeting the RAS to prevent CKM traits. This comprehensive review of the potential role of the RAS in the early-life programming of CKM syndrome aims to expedite the clinical translation process, ultimately enhancing outcomes in cardiovascular–kidney–metabolic health. [ABSTRACT FROM AUTHOR]

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Acute pancreatitis is caused by trypsinogen activation in acinar cells caused by various injury forms (gallstone, high triglycerides, alcohol, etc.). Viral pancreatitis is a clinically rare disease type, which is easily neglected by clinicians and causes serious adverse consequences. Viral pancreatitis involves the entry of viruses into pancreatic cells, triggering inflammation, immune response activation, and enzymatic autodigestion, leading to tissue damage and potential complications. At present, there are few available reports on viral pancreatitis, most of which are case reports. This review brings attention to clinicians by describing the incidence of viral pancreatitis to enhance clinical understanding and patient care. [ABSTRACT FROM AUTHOR]

The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia. [ABSTRACT FROM AUTHOR]

Aqueous extracts of calyx from Hibiscus sabdariffa (HS) (roselle) are highly appreciated for their nutritional and therapeutic effects, especially as anti-hypertensive substances. This study aimed to evaluate their anti-hypertensive potential through an in vitro inhibition assay of angiotensin-converting enzyme (ACE) and hypertension precursor enzymes and to assess the in vivo diuretic activity of HS. Results showed that HS extract inhibited enzymes belonging to several classes, such as α-amylase, trypsin, chymotrypsin, xanthine oxidase, lipoxygenase, and angiotensin-converting enzyme. In particular, enzymatic kinetics of ACE indicated a competitive inhibition fashion of HS extract. Furthermore, the extracts showed remarkable diuretic and natriuretic effects at doses of 50 mg/kg/bw, 100 mg/kg/b.w, and 200 mg/kg.b.w. These activities can be explained by the high content of phenolic compounds and essential amino acids. Roselle could be a potential source of nutraceuticals and anti-hypertensive bioactive compounds. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB), a type of microorganism widely used in functional foods, has gained notable research attention in recent years. Certain strains possess the proteolytic ability to release potentially antihypertensive peptides from dairy proteins, which prompted us to explore the LAB strains from an understudied and unique ingredient, Daqu. We screened for 67 strains of LAB strains from traditional Daqu using the calcium dissolution ring method. Sixteen strains exhibiting angiotensin-converting enzyme inhibition (ACE-I) activity exceeding 50% were chosen for 16S rDNA sequencing and safety assessment. It is noteworthy that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 exhibited significant ACE-I activity, which was the result of strain fermentation in reconstituted skim milk. These 2 strains did not exhibit hemolytic activity or antibiotic resistance. They also did not produce biogenic amines and showed high survival rates in the gastrointestinal tract. Additionally, Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 fermented milk exhibited a notable reduction in blood pressure levels in spontaneously hypertensive rats (SHR) compared with negative controls in SHR. Importantly, no adverse effect was observed in normal Wistar-Kyoto rats. Through the analysis of physiological, serum, and urine-related indicators, it was observed that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 have the potential to promote weight gain in SHR, alleviate excessive heart rate, improve renal function indicators, and effectively regulate blood sugar and uric acid levels in SHR. These 2 strains showed optimal properties in lowering blood pressure and have the potential to be used in functional dairy products in the future. [ABSTRACT FROM AUTHOR]

Trandolapril is an oral angiotensin-converting enzyme (ACE) inhibitor approved by the USFDA for the therapy of hypertension and congestive heart failure. This paper describes the validation of zero- and first-order derivative UV spectrophotometric methods for the estimation of trandolapril in bulk and in its marketed tablet formulation. Preliminary spectrophotometric determination of the drug was carried out in phosphate buffer pH 2.0 or 0.1 N HCl. A total of 17 parametric method variants were investigated out of which three variants employing peak–zero (P–0) and peak–peak (P–P) techniques were validated with respect to linearity, accuracy, precision, and robustness. The developed methods were also assessed for stability indicating potential in force degraded solutions. Linearity was observed in the concentration range of 1.0–70.0 μg/mL with an excellent correlation coefficient (r2) ranging from 0.9981 to 0.9998. The limits of assay detection values were found for the range of 0.88–1.23 μg/mL, and quantitation limits ranged from 2.66 to 6.09 μg/mL for the proposed methods. The proposed methods were extended to the quantification of the drug in its marketed tablet formulation with good recoveries (90–98%). [ABSTRACT FROM AUTHOR]

Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara , including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin. Using FRET (fluorescence resonance energy transfer) substrate assays, we demonstrated that Bc-7a strongly inhibits the two domains of angiotensin converting enzyme (K i < 1 μM). Our findings contribute to the repertoire of biologically active peptides from snake venoms capable of inhibiting angiotensin-converting enzyme (ACE), beyond current known structural motifs and precursors. In summary, we report a novel snake venom peptide with ACE inhibitory activity, suggesting its potential contribution to the hypotensive effect observed in envenomation. [Display omitted] • A total of 197 peptides were identified in the venom of Bothrops cotiara. • A novel peptide is an angiotensin converting enzyme inhibitor. • This peptide inhibitor is a fragment of a snake venom metalloproteinase. [ABSTRACT FROM AUTHOR]