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Frontiers in Endocrinology 2024The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk...
PURPOSE
The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk factors of AIS and explore the role of serum indicators such as angiotensin I (Ang I) in the prognosis of patients undergoing endovascular thrombectomy (EVT).
PATIENTS AND METHODS
Patients with AIS who underwent EVT and healthy controls were retrospectively enrolled in this study, and the patients were divided into a good or a poor prognosis group. We compared Ang I, blood routine indexes, biochemical indexes, electrolyte indexes, and coagulation indexes between patients and controls. We used univariate and multivariate logistic regression analyses to evaluate possible risk factors for AIS and the prognosis of patients undergoing EVT. Independent risk factors for the prognosis of patients undergoing EVT were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves (ROC).
RESULTS
Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. In addition, Ang I levels are lower in AIS compared to the controls. The level of Ang I was higher in the good prognosis group. Furthermore, we developed a nomogram to evaluate its ability to predict the prognosis of AIS after EVT. The AUC value of the combined ROC model (Ang I and albumin-globulin ratio (AGR)) was 0.859.
CONCLUSIONS
In conclusion, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. The combined Ang I and AGR model has a good predictive ability for the prognosis of AIS patients undergoing arterial thrombectomy.
Topics: Humans; Male; Female; Ischemic Stroke; Prognosis; Thrombectomy; Risk Factors; Middle Aged; Aged; Retrospective Studies; Endovascular Procedures; Fibrin Fibrinogen Degradation Products; Case-Control Studies; Biomarkers; ROC Curve
PubMed: 38919492
DOI: 10.3389/fendo.2024.1388871 -
Journal of the Science of Food and... Nov 2023Lycium ruthenicum Murray (LRM), a perennial shrub plant belonging to the Solanaceae family, is rich in anthocyanins, which have anti-inflammatory, antioxidant,...
BACKGROUND
Lycium ruthenicum Murray (LRM), a perennial shrub plant belonging to the Solanaceae family, is rich in anthocyanins, which have anti-inflammatory, antioxidant, lipid-lowering, intestinal flora regulating, and other pharmacological qualities. This study was primarily aimed to investigate the inhibitory effect of different anthocyanin purities from LRM on angiotensin-I-converting enzyme (ACE) activity in vitro. Moreover, the inhibitory mechanism was further analyzed by molecular docking technology.
RESULTS
Two main anthocyanin isomers were identified by ultra-performance liquid chromatography-tandem mass spectrometry and proton/carbon-13 nuclear magnetic resonance, namely petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-d-glucopyranoside) (trans-Pt3R5G) and petunidin-3-O-[rhamnopyranosyl-(cis-p-coumaroyl)]-5-O-(β-d-glucopyranoside) (cis-Pt3R5G), with a molar ratio of 9:1. Three purification grades of Pt3R5G all showed excellent inhibitory effects on ACE, with the half maximal inhibitory concentration (IC ) values being 0.562, 0.421, and 0.106 mg·mL . Increasing the purity may reduce the IC within a certain concentration range. An enzymatic kinetic experiment showed that the inhibitory effect of Pt3R5G on ACE was reversible and non-competitive: Pt3R5G and substrate were not in competition for the active sites of ACE. Molecular docking technology further revealed the possible mechanism was that Pt3R5G and ACE amino acid residues were interacting by hydrogen bonds to exert the inhibitory effect.
CONCLUSION
The results indicated that Pt3R5G from LRM was highly effective at inhibiting ACE activity in vitro, with the hydrogen bonds of Pt3R5G and ACE amino acid residues exerting the inhibition. As a potential plant-based ACE inhibitor, Pt3R5G can be used as a functional ingredient for antihypertensive effects. © 2023 Society of Chemical Industry.
PubMed: 37347844
DOI: 10.1002/jsfa.12803 -
Food Research International (Ottawa,... Dec 2023The molecular and biofunctional properties of protein and phenolic fractions in edible truffles remain largely unknown. This study examined the effect of ultrasonication...
Impact of ultrasonication on the contents, profiles and biofunctional properties of free and bound phenolics from white desert truffle (Tirmania nivea) and its protein fractions.
The molecular and biofunctional properties of protein and phenolic fractions in edible truffles remain largely unknown. This study examined the effect of ultrasonication on the contents, profiles, and bioactive properties of free and bound phenolics (FP and BP) from desert truffle (Tirmania nivea) and its protein fractions. Protein fractions from the Osborne extraction scheme were biochemically and structurally characterized. The albumin fraction showed the highest abundance (16.8%) and yield (35.8%). Total phenolic contents were the highest in non-sonicated samples (3.5-34.1 mg/g), particularly in the albumin fraction and in whole truffle. FP extracted at 30 °C (FP-30 °C) accounted for the largest proportion of total phenolics in all protein fractions, whereas BP-30 °C and FP-60 °C were predominant in non-sonicated and sonicated truffle, respectively. The highest antioxidant activity was obtained with FP-30 °C extracts from non-sonicated albumins, globulins and truffle (91.9, 72.7 and 30.0%), followed by BP-30 °C from non-sonicated albumins (25.4%) and FP-60 °C from sonicated glutelins-1 (24.2%). High inhibition of α-amylase was evidenced in several extracts, including FP-30 °C from non-sonicated glutelins-1 (99.2%) and FP-30 °C from sonicated globulins (72.4%). Several extracts also displayed high inhibition of angiotensin I-converting enzyme (ACE), including FP-60 °C from non-sonicated glutelins-1 (65.1%) and sonicated glutelins-1 (71.1%) and globulins (64.7%). Most extracts were rich in epicatechin, gallic acid, chlorogenic acid and catechin. Correlations between phenolic content, antioxidant activity, anti-α-amylase and anti-ACE activities were influenced by sonication. Sonication reduced the particle size of the proteins and modified their structural characteristics. These findings demonstrate that white desert truffle proteins co-occur with bioactive phenolics whose functionalities can be tailored by protein fractionation and sonication.
Topics: Antioxidants; Phenols; Catechin; alpha-Amylases; Albumins; Globulins; Glutens
PubMed: 37986408
DOI: 10.1016/j.foodres.2023.113453 -
Fundamental & Clinical Pharmacology Jun 2024The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue of modern cardiology. Over the past 10 years, there has been... (Review)
Review
BACKGROUND
The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue of modern cardiology. Over the past 10 years, there has been no significant reduction in mortality among patients with AMI. It is quite obvious that there is an urgent need to develop fundamentally new drugs for the treatment of AMI. Angiotensin 1-7 has some promise in this regard.
OBJECTIVE
The objective of this article is analysis of published data on the cardioprotective properties of angiotensin 1-7.
METHODS
PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study.
RESULTS
Angiotensin 1-7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart. Angiotensin 1-7 can prevent not only ischemic but also reperfusion cardiac injury. The activation of the Mas receptor plays a key role in these effects of angiotensin 1-7. Angiotensin 1-7 alleviates Ca overload of cardiomyocytes and reactive oxygen species production in ischemia/reperfusion (I/R) of the myocardium. It is possible that both effects are involved in angiotensin 1-7-triggered cardiac tolerance to I/R. Furthermore, angiotensin 1-7 inhibits apoptosis of cardiomyocytes and stimulates autophagy of cells. There is also indirect evidence suggesting that angiotensin 1-7 inhibits ferroptosis in cardiomyocytes. Moreover, angiotensin 1-7 possesses anti-inflammatory properties, possibly achieved through NF-kB activity inhibition. Phosphoinositide 3-kinase, Akt, and NO synthase are involved in the infarct-reducing effect of angiotensin 1-7. However, the specific end-effector of the cardioprotective impact of angiotensin 1-7 remains unknown.
CONCLUSION
The molecular nature of the end-effector of the infarct-limiting effect of angiotensin 1-7 has not been elucidated. Perhaps, this end-effector is the sarcolemmal K channel or the mitochondrial K channel.
Topics: Angiotensin I; Peptide Fragments; Humans; Myocardial Reperfusion Injury; Animals; Signal Transduction; Myocytes, Cardiac; Myocardial Infarction; Ventricular Remodeling; Cardiotonic Agents; Apoptosis
PubMed: 38311344
DOI: 10.1111/fcp.12983 -
Food Chemistry Jul 2024Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle...
The novel angiotensin-I-converting enzyme inhibitory peptides from Scomber japonicus muscle protein hydrolysates: QSAR-based screening, molecular docking, kinetic and stability studies.
Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle hydrolysates were screened, and their mechanisms of action and inhibition stability were explored. The quantitative structure-activity relationship (QSAR) model based on 5z-scale metrics was developed to rapidly screen for ACE-I peptides. Two novel potential ACE-I peptides (LTPFT, PLITT) were predicted through this model coupled with in silico screening, of which PLITT had the highest activity (IC: 48.73 ± 7.59 μM). PLITT inhibited ACE activity with a mixture of non-competitive and competitive mechanisms, and this inhibition mainly contributed to the hydrogen bonding based on molecular docking study. PLITT is stable under high temperatures, pH, glucose, and NaCl. The zinc ions (Zn) and copper ions (Cu) enhanced ACE-I activity. The study suggests that the QSAR model is effective in rapidly screening for ACE-I inhibitors, and PLITT can be supplemented in foods to lower blood pressure.
Topics: Molecular Docking Simulation; Quantitative Structure-Activity Relationship; Protein Hydrolysates; Peptides; Muscles; Ions; Angiotensins; Peptidyl-Dipeptidase A
PubMed: 38452536
DOI: 10.1016/j.foodchem.2024.138873 -
Molecules (Basel, Switzerland) Jul 2023Atlantic sea cucumber is a benthic marine echinoderm found in Northwest Atlantic waters and is harvested mainly for its body wall. The body wall, along with internal...
Atlantic sea cucumber is a benthic marine echinoderm found in Northwest Atlantic waters and is harvested mainly for its body wall. The body wall, along with internal organs and aquaphyrangeal bulb/flower, is a rich source of proteins, where the latter parts are often considered as processing discards. The objective of this research was to produce protein hydrolysates from sea cucumber tissues (body wall, flower, and internal organs) with bioactive properties associated with antioxidants, DNA and LDL cholesterol oxidation inhibition, and angiotensin-I-converting enzyme (ACE) inhibitory effects. The protein hydrolysates were prepared using food-grade commercial enzymes, namely Alcalase, Corolase, and Flavourzyme, individually and in combination, and found that the combination of enzymes exhibited stronger antioxidant potential than the individual enzymes, as well as their untreated counterparts. Similar trends were also observed for the DNA and LDL cholesterol oxidation inhibition and ACE-inhibitory properties of sea cucumber protein hydrolysates, mainly those that were prepared from the flower. Thus, the findings of this study revealed potential applications of sea cucumber-derived protein hydrolysates in functional foods, nutraceuticals, and dietary supplements, as well as natural therapeutics.
Topics: Animals; Antioxidants; Angiotensin-Converting Enzyme Inhibitors; Cucumaria; Sea Cucumbers; Protein Hydrolysates; Cholesterol, LDL; Peptidyl-Dipeptidase A
PubMed: 37446924
DOI: 10.3390/molecules28135263 -
Journal of Chromatography. B,... Jan 2024Cardiovascular diseases have cast a significant negative impact on the lives of millions worldwide. Over the years, extensive efforts have been dedicated to enhancing...
Cardiovascular diseases have cast a significant negative impact on the lives of millions worldwide. Over the years, extensive efforts have been dedicated to enhancing diagnostic and prognostic tools for these diseases. A growing body of evidence indicates that the angiotensin convertase enzyme (ACE) and the angiotensin convertase enzyme 2 (ACE2), and angiotensin peptide levels could hold a pivotal role in assisting clinicians with the management of cardiovascular conditions, notably hypertension and heart failure. However, despite the considerable body of knowledge in this domain, a void remains in the field of analytical methodologies for these molecules. In this study, we present a fully validated LC-MS/MS method for the precise quantitation of plasma angiotensin (1-7), (1-8), (1-9), and (1-10), following the guidelines set by the Clinical and Laboratory Standards Institute (CLSI). Our method not only enables the accurate quantification of angiotensin peptides but also provides a means to assess ACE and ACE2 activity. Remarkably, our method achieved a Lower Limit of Measurement Interval (LLMI) as low as 5 pg/mL. This has enabled the detection of angiotensin (1-7), (1-8), (1-9) and (1-10) and the accurate quantitation of angiotensin (1-7), (1-8) and (1-10) in all analyzed groups, including healthy controls, patients with high blood pressure, and patients with chronic kidney disease. To our knowledge, our method represents the most sensitive approach allowing for simultaneous quantitation of these four angiotensin peptides. A distinct advantage of our method, when compared to immunoassays, is its high sensitivity combined with comprehensive chromatographic separation of all currently known angiotensin peptides. This combination translates to an exceptional level of selectivity, underscoring the value and potential of our methodology in advancing cardiovascular disease research.
Topics: Humans; Liquid Chromatography-Mass Spectrometry; Chromatography, Liquid; Angiotensin-Converting Enzyme 2; Tandem Mass Spectrometry; Angiotensin I; Peptides; Angiotensin II; Cardiovascular Diseases; Peptide Fragments
PubMed: 38039597
DOI: 10.1016/j.jchromb.2023.123943 -
International Journal of Biological... May 2024This study aims to seek angiotensin-I-converting enzyme inhibitory (ACEi) peptides from walnut using different enzymatic hydrolysis, and further to validate the potent...
A novel angiotensin I-converting enzyme inhibitory peptide from walnut (Juglans sigillata) protein hydrolysates and its evaluation in Ang II-induced HUVECs and hypertensive rats.
This study aims to seek angiotensin-I-converting enzyme inhibitory (ACEi) peptides from walnut using different enzymatic hydrolysis, and further to validate the potent ACEi peptides identified and screened via peptidomics and in silico analysis against hypertension in spontaneously hypertensive rats (SHRs). Results showed that walnut protein hydrolysate (WPH) prepared by combination of alcalase and simulated gastrointestinal digestion exhibited high ACEi activity. WPH was separated via Sephadex-G25, and four peptides were identified, screened and verified based on their PeptideRanker score, structural characteristic and ACE inhibition. Interestingly, FDWLR showed the highest ACEi activity with IC value of 8.02 μg/mL, which might be related to its close affinity with ACE observed in molecular docking. Subsequently, high absorption and non-toxicity of FDWLR was predicted via in silico absorption, distribution, metabolism, excretion and toxicity. Furthermore, FDWLR exhibited positively vasoregulation in Ang II-induced human umbilical vein endothelial cells, and great blood pressure lowering effect in SHRs.
Topics: Juglans; Animals; Angiotensin-Converting Enzyme Inhibitors; Humans; Human Umbilical Vein Endothelial Cells; Protein Hydrolysates; Rats; Rats, Inbred SHR; Hypertension; Molecular Docking Simulation; Angiotensin II; Peptides; Male; Peptidyl-Dipeptidase A; Antihypertensive Agents; Blood Pressure; Plant Proteins
PubMed: 38556230
DOI: 10.1016/j.ijbiomac.2024.131152 -
Food Research International (Ottawa,... Dec 2023Dairy-derived angiotensin-I-converting enzyme inhibitory peptides (ANGICon-EIPs) have been regarded as a relatively safe supplementary diet-therapy strategy for... (Review)
Review
Dairy-derived angiotensin-I-converting enzyme inhibitory peptides (ANGICon-EIPs) have been regarded as a relatively safe supplementary diet-therapy strategy for individuals with hypertension, and short-chain peptides may have more relevant antihypertensive benefits due to their direct intestinal absorption. Our previous explorations have confirmed that endogenous goat milk short-chain peptides are also an essential source of ANGICon-EIPs. Nonetheless, there are limited explorations on endogenous ANGICon-EIPs owing to the limitations of the extraction and enrichment of endogenous peptides, currently. This review outlined ameliorated pre-treatment strategies, data acquisition methods, and tools for the prediction of peptide structure and function, aiming to provide creative ideas for discovering novel ANGICon-EIPs. Currently, deep learning-based peptide structure and function prediction algorithms have achieved significant advancements. The convolutional neural network (CNN) and peptide sequence-based multi-label deep learning approach for determining the multi-functionalities of bioactive peptides (MLBP) can predict multiple peptide functions with absolute true value and accuracy of 0.699 and 0.708, respectively. Utilizing peptide sequence input, torsion angles, and inter-residue distance to train neural networks, APPTEST predicted the average backbone root mean square deviation (RMSD) value of peptide (5-40 aa) structures as low as 1.96 Å. Overall, with the exploration of more neural network architectures, deep learning could be considered a critical research tool to reduce the cost and improve the efficiency of identifying novel endogenous ANGICon-EIPs.
Topics: Humans; Deep Learning; Proteins; Neural Networks, Computer; Peptides; Amino Acid Sequence
PubMed: 37986483
DOI: 10.1016/j.foodres.2023.113640 -
Molecules (Basel, Switzerland) Mar 2024Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However,...
Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the protein (P) and had low IC values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of .
Topics: Angiotensin-Converting Enzyme Inhibitors; Molecular Docking Simulation; Peptidyl-Dipeptidase A; Chromatography, Liquid; Reproducibility of Results; Tandem Mass Spectrometry; Peptides; Angiotensins
PubMed: 38474646
DOI: 10.3390/molecules29051134