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Abstract Background Preeclampsia, a complex hypertensive disorder unique to pregnancy, significantly impacts maternal and fetal health worldwide, with a prevalence of 2–8%. This condition results from a complex interplay of genetic, environmental, and immunological factors. Aim and objectives This study aims to investigate the genetic predispositions to preeclampsia, focusing on specific gene polymorphisms among pregnant women at Central Hospital Auchi, Nigeria. Materials and methods We examined the endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), and tumor necrosis factor-alpha (TNF-α) genes in 200 pregnant women, equally divided between preeclamptic patients and normotensive controls. Results The eNOS G894T polymorphism was significantly associated with preeclampsia, with the T allele nearly doubling the risk. The VEGF C936T polymorphism's T allele also indicated a higher risk. The D allele in the ACE gene's insertion/deletion (I/D) polymorphism significantly increased the risk, as did the A allele in the TNF-α G308A polymorphism. Conclusions These findings highlight the importance of genetic factors in preeclampsia and suggest that genetic screening could improve risk stratification and early detection. Future research should integrate genetic, epigenetic, and environmental data to understand preeclampsia's multifaceted nature and develop targeted therapies. This study underscores the potential of personalized medicine in managing and reducing the risks associated with preeclampsia.

Given the side effects associated with synthetic antihypertensive drugs, there is a growing need among researchers to investigate angiotensin-converting enzyme (ACE) inhibitory peptides derived from food protein as safer therapeutic alternatives. This study used seabuckthorn (Hippophae rhamnoides L.) seed meal as the raw material, and the protein was extracted by alkaline extraction and acid precipitation. After enzymatic digestion, peptides with molecular weight less than 3 kDa were selected for study. The screened peptide had an IC50 value of 4.358 mg/mL on ACE with a non-competitive inhibition mechanism and good inhibition stability. By employing infrared (IR) analysis, exclusively β-fold and β-helix structures were identified in the hydrolysate, while no other structural motifs were detected. X-ray diffraction revealed that it had an irregular amorphous structure. The peptide contains 17 amino acids that are both highly acidic and hydrophobic, with glutamic acid ranking first in terms of the number of individual amino acids. Compared with the database (NCBI, Uniport), ten peptides with ACE inhibitory activity were detected, and molecular docking showed the mechanism of each peptide inhibiting ACE, FRVAWTEKNDGQRAPLANN, LIISVAYARVAKKLWLCNMIGDVT-TEQY, VIRSRASDGCLEVKEFEDIPP, AGGGG-GGGGGGSRRL, LQPREGPAGGTT-ALREELSLGPEAALDTPPAGP, DDEARINQLFL, FAVSTLTSYDWSDRDDATQGR-KL, RQLSLEGSGLGVEDLKDN, GGGGGGGGGGGGGGGIGGGGGGGGGGGAR, and KEALGEGCFGNRIDRIGD. According to the results, AGGGGGG-GGGGSRRL is more stable in binding to ACE and may have better inhibitory activity. It has been shown that seabuckthorn protein can be an alternative source of ACE inhibitory peptides.

Background: Preeclampsia, a complex hypertensive disorder unique to pregnancy, significantly impacts maternal and fetal health worldwide, with a prevalence of 2–8%. This condition results from a complex interplay of genetic, environmental, and immunological factors. Aim and objectives: This study aims to investigate the genetic predispositions to preeclampsia, focusing on specific gene polymorphisms among pregnant women at Central Hospital Auchi, Nigeria. Materials and methods: We examined the endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), and tumor necrosis factor-alpha (TNF-α) genes in 200 pregnant women, equally divided between preeclamptic patients and normotensive controls. Results: The eNOS G894T polymorphism was significantly associated with preeclampsia, with the T allele nearly doubling the risk. The VEGF C936T polymorphism's T allele also indicated a higher risk. The D allele in the ACE gene's insertion/deletion (I/D) polymorphism significantly increased the risk, as did the A allele in the TNF-α G308A polymorphism. Conclusions: These findings highlight the importance of genetic factors in preeclampsia and suggest that genetic screening could improve risk stratification and early detection. Future research should integrate genetic, epigenetic, and environmental data to understand preeclampsia's multifaceted nature and develop targeted therapies. This study underscores the potential of personalized medicine in managing and reducing the risks associated with preeclampsia. [ABSTRACT FROM AUTHOR]

Background and Aim: Inflammatory bowel disease is challenging to diagnose. Fecal biomarkers offer noninvasive solutions. The renin–angiotensin‐aldosterone system is implicated in intestinal inflammation. Angiotensin‐converting enzyme (ACE) and angiotensin‐converting enzyme 2 (ACE2) regulate its activity, but conflicting findings on these enzymes in colitis require further investigation. We aimed to assess ACE and ACE2 presence and activities in the feces, serum, and colon of 2,4,6‐trinitrobenzene sulfonic acid (TNBS)‐induced rats. Methods: Colitis was induced in male rats by rectal instillation of a 21% ethanolic TNBS solution. After rats' sacrifice, colonic portions, serum, and feces were collected. ACE and ACE2 presence in the feces was analyzed by western Blot, and colonic and serum enzymes' concentrations were quantified using ELISA kits. ACE activity was assessed using Hippuryl‐His‐Leu and Z‐Phe‐His‐Leu as substrates. ACE2 activity was assessed using Mca‐APK (Dnp) as a substrate in the presence and absence of DX600 (ACE2 inhibitor). Results: An ACE isoform of ~70 kDa was found only in the feces of TNBS‐induced rats. ACE concentration was higher than that of ACE2 in the serum and the inflamed colon. ACE N‐domain activity was higher than that of the C‐domain in all matrices. ACE2 activity was higher in the feces of TNBS‐induced animals compared to controls. Conclusion: A 70 kDa ACE isoform only detected in the feces of TNBS‐induced rats may have translational relevance. ACE N‐domain seems to play a significant role in regulating colonic lesions. Further research using human samples is necessary to validate these findings. [ABSTRACT FROM AUTHOR]

The renin–angiotensin system (RAS) is dysregulated in Alzheimer's disease (AD). In this study, we have explored the hypothesis that an -age--related imbalance in brain RAS is a trigger for RAS dysregulation in AD. We characterized RAS gene expression in the frontal cortex from (i) a cohort of normal aging (n = 99, age range = 19–96 years) and (ii) a case–control cohort (n = 209) including AD (n = 66), mixed dementia (VaD + AD; n = 50), pure vascular dementia (VaD; n = 42), and age-matched controls (n = 51). The AD, mixed dementia, and age-matched controls were further stratified by Braak tangle stage (BS): BS0–II (n = 48), BSIII–IV (n = 44), and BSV–VI (n = 85). Gene expression was calculated by quantitative PCR (qPCR) for ACE1 , AGTR1 , AGTR2 , ACE2 , LNPEP , and MAS1 using the 2−∆∆Cq method, after adjustment for reference genes (RPL13 and UBE2D2) and cell-specific calibrator genes (NEUN , GFAP , PECAM). ACE1 and AGTR1 , markers of classical RAS signaling, and AGTR2 gene expression were elevated in normal aging and gene expression in markers of protective downstream regulatory RAS signaling, including ACE2 , MAS1 , and LNPEP , were unchanged. In AD and mixed dementia, AGTR1 and AGTR2 gene expression were elevated in BSIII–IV and BSV–VI, respectively. MAS1 gene expression was reduced at BSV–VI and was inversely related to parenchymal Aβ and tau load. LNPEP gene expression was specifically elevated in VaD. These data provide novel insights into RAS signaling in normal aging and dementia. [ABSTRACT FROM AUTHOR]

This work was aimed to explore the antioxidative properties, bioavailability and the safety of bioactive peptides obtained by the enzymatic hydrolysis of ultrasound-treated (UO) and untreated (nUO) soybean okara proteins. Particularly, the peptidomic profiles of both hydrolysates were examined using an untargeted metabolomics technique for suspect screening that was specifically designed for the profiling of short-chain peptides and relied on ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and bioinformatics.Next, both UO and nUO hydrolysates reduce Dipeptidyl peptidase-IV (DPP-IV) enzyme activity until 39.54 ± 0.26 % and 43.29 ± 0.36 % respectively and inhibit angiotensin converting enzyme (ACE) activities by 30.54 ± 0.42 % and 30.76 ± 0.02 %, respectively. Moreover, they demonstrate to exerted antioxidant properties. Particularly, they show a comparable in vitro antioxidant activity but when the oxidative stress is induced by H2O2 in Caco-2 cells, UO hydrolysate is more active in lowering the levels of reactive oxygen species (ROS) and of lipid peroxidation induced of 48% and 20% respectively.In addition, UO- and nUO-derived peptides trans-epithelial transported by human differentiated intestinal cell monolayer, were identified. Lastly, the possible hepatotoxicity of UO and nUO hydrolysates in HepG2 cells has not been observed by measuring alanine transferase (ALT) and aspartate transferase (AST) levels and cytotoxic effects.

Angiotensin–converting enzyme (ACE) inhibitors are the primarily chosen drugs to treat various cardiovascular diseases, such as hypertension. Although the most recent guidelines do not differentiate among the various ACE inhibitory drugs, there are substantial pharmacological differences. Goal: Here, we tested if lipophilicity affects the efficacy of ACE inhibitory drugs when used as the first therapy in newly identified hypertensives in a prospective study. Methods: We tested the differences in the cardiovascular efficacy of the hydrophilic lisinopril (8.3 ± 3.0 mg/day) and the lipophilic enalapril (5.5 ± 2.3 mg/day) (n = 59 patients). The cardiovascular parameters were determined using sonography (flow-mediated dilation (FMD) in the brachial artery, intima-media thickness of the carotid artery), 24 h ambulatory blood pressure monitoring (peripheral arterial blood pressure), and arteriography (aortic blood pressure, augmentation index, and pulse wave velocity) before and after the initiation of ACE inhibitor therapy. Results: Both enalapril and lisinopril decreased blood pressure. However, lisinopril failed to improve arterial endothelial function (lack of effects on FMD) when compared to enalapril. Enalapril-mediated improved arterial endothelial function (FMD) positively correlated with its blood–pressure–lowering effect. In contrast, there was no correlation between the decrease in systolic blood pressure and FMD in the case of lisinopril treatment. Conclusion: The blood–pressure–lowering effects of ACE inhibitor drugs are independent of their lipophilicity. In contrast, the effects of ACE inhibition on arterial endothelial function are associated with lipophilicity: the hydrophilic lisinopril was unable to improve, while the lipophilic enalapril significantly improved endothelial function. Moreover, the effects on blood pressure and endothelial function did not correlate in lisinopril-treated patients, suggesting divergent mechanisms in the regulation of blood pressure and endothelial function upon ACE inhibitory treatment. [ABSTRACT FROM AUTHOR]

Background: Angiotensin‐converting enzyme (ACE) and ACE2 are two major enzymes of the renin–angiotensin–aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1‐7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats. Methods: Portions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats. Enzyme activity was evaluated by fluorometric assays using different substrates: Hippuryl‐His‐Leu for ACE‐C‐domain, Z‐Phe‐His‐Leu for ACE‐N‐domain, and Mca‐APK(Dnp) for ACE2. ACE and ACE2 concentration was assessed by ELISA. Ratios concerning concentrations and activities were calculated to evaluate the balance of the RAAS. Statistical analysis was performed using Friedman test followed by Dunn's multiple comparisons test or Wilcoxon matched‐pairs test whenever needed. Key Results: ACE and ACE2 are catalytically active in the intestinal content along the rat gut. The ACE N‐domain shows higher activity than the C‐domain both in the intestinal content and in the intestinal tissue. ACE and ACE2 are globally more active in the intestinal content than in the corresponding intestinal tissue. There was a distal‐to‐proximal prevalence of ACE2 over ACE in the intestinal tissue. Conclusions & Inferences: This work is the first to report the presence of catalytically active ACE and ACE2 in the rat intestinal content, supporting future research on the regulatory role of the intestinal RAAS on gut function and a putative link to the microbiome. [ABSTRACT FROM AUTHOR]

In this paper, the antihypertension effect of rice peptide (RP) was studied. With spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) as the research objects, RP disposable gastric and long-term gastric irrigation experiments were carried out and systolic blood pressure (SBP) was measured. At the end of the long-term gastric irrigation experiment, the content of nitric oxide (NO), angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and renin in the plasma and the activity of ACE were determined. The results showed that RP could reduce systolic pressure of SHR and had time-dose dependence while high-dose RP significantly reduced systolic pressure by 24.6 and 17.2 mmHg, respectively after a single and long-term gastric irrigation test. RP also could inhibit the activity of ACE and increase the release of NO. These results suggested that the decompression mechanism of RP is likely to be related to the regulation of the renin-angiotensin system (RAS) and NO.

Abstract Objective This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa). Methods We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger’s test, with the robustness of the findings verified by sensitivity analysis. Results Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14–2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11–2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11–2.80; DI vs. II: OR= 1.44, 95% CI: 0.99–2.10; DD vs. II: OR= 2.12, 95% CI: 1.15–3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger’s test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis. Conclusion ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients.

Chronic diseases, such as hypertension, cause great harm to human health. Conventional drugs have promising therapeutic effects, but also cause significant side effects. Food-sourced angiotensin-converting enzyme (ACE) inhibitory peptides are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, there is no systematic and effective screening method for ACE inhibitory peptides, and the lack of understanding of the sequence characteristics and molecular mechanism of these inhibitory peptides poses a major obstacle to the development of ACE inhibitory peptides. Through systematically calculating the binding effects of 160,000 tetrapeptides with ACE by molecular docking, we found that peptides with Tyr, Phe, His, Arg, and especially Trp were the characteristic amino acids of ACE inhibitory peptides. The tetrapeptides of WWNW, WRQF, WFRV, YYWK, WWDW, and WWTY rank in the top 10 peptides exhibiting significantly high ACE inhibiting behaviors, with IC50 values between 19.98 ± 8.19 μM and 36.76 ± 1.32 μM. Salt bridges, π–π stacking, π–cations, and hydrogen bonds contributed to the high binding characteristics of the inhibitors and ACE. Introducing eight Trp into rabbit skeletal muscle protein (no Trp in wide sequence) endowed the protein with a more than 90% ACE inhibition rate, further suggesting that meat with a high content of Trp could have potential utility in hypertension regulation. This study provides a clear direction for the development and screening of ACE inhibitory peptides. [ABSTRACT FROM AUTHOR]

Angiotensin–converting enzyme (ACE) inhibitors are the primarily chosen drugs to treat various cardiovascular diseases, such as hypertension. Although the most recent guidelines do not differentiate among the various ACE inhibitory drugs, there are substantial pharmacological differences. Goal: Here, we tested if lipophilicity affects the efficacy of ACE inhibitory drugs when used as the first therapy in newly identified hypertensives in a prospective study. Methods: We tested the differences in the cardiovascular efficacy of the hydrophilic lisinopril (8.3 ± 3.0 mg/day) and the lipophilic enalapril (5.5 ± 2.3 mg/day) (n = 59 patients). The cardiovascular parameters were determined using sonography (flow-mediated dilation (FMD) in the brachial artery, intima-media thickness of the carotid artery), 24 h ambulatory blood pressure monitoring (peripheral arterial blood pressure), and arteriography (aortic blood pressure, augmentation index, and pulse wave velocity) before and after the initiation of ACE inhibitor therapy. Results: Both enalapril and lisinopril decreased blood pressure. However, lisinopril failed to improve arterial endothelial function (lack of effects on FMD) when compared to enalapril. Enalapril-mediated improved arterial endothelial function (FMD) positively correlated with its blood–pressure–lowering effect. In contrast, there was no correlation between the decrease in systolic blood pressure and FMD in the case of lisinopril treatment. Conclusion: The blood–pressure–lowering effects of ACE inhibitor drugs are independent of their lipophilicity. In contrast, the effects of ACE inhibition on arterial endothelial function are associated with lipophilicity: the hydrophilic lisinopril was unable to improve, while the lipophilic enalapril significantly improved endothelial function. Moreover, the effects on blood pressure and endothelial function did not correlate in lisinopril-treated patients, suggesting divergent mechanisms in the regulation of blood pressure and endothelial function upon ACE inhibitory treatment.

Abstract Background and aims Gestational diabetes mellitus is well-defined as glucose intolerance first documented during pregnancy. In this study, we examined the possible associations between I/D polymorphism of the angiotensin-converting enzyme gene, the M235T variant of angiotensinogen gene, and the rs7950226 polymorphism of the ARNT-like protein-1 (BMAL1) gene and the risk for diabetes in Egyptian pregnant women. Subjects and methods This study recruited 160 gestational diabetes cases and 165 controls. Genomic DNA was derived from peripheral blood leukocytes and ACE gene (I/D) genotyping was performed using the method of polymerase chain reaction and the polymerase chain reaction-based restriction fragment length polymorphism was used for identifying the M235T variant of AGT gene and the rs7950226 polymorphism of the BMAL1. Results The II, ID, and DD genotypes of the ACE gene have significant differences in cases compared to controls (P = 0.000 and X 2 = 81.77). The M235T polymorphism of the AGT gene was increased with gestational diabetes risk. Furthermore, the AA genotype of the BMAL1 rs7950226 gene was significantly related to the gestational diabetes risk (P = 0.000 and X 2 = 52.82). Furthermore, the allele frequencies of the three variants have significant variances between cases and control. Conclusion This study suggested significant associations between ACE (DD), AGT (TT), and BMAL1 rs7950226 (AA) gene polymorphisms with gestational diabetes susceptibility and there was a possibility to identify that II + MM + GG as protective haplotypes and DD + TT + AA as risk haplotypes for gestational diabetes.

Ageing has been associated with comorbidities, systemic low-grade of inflammation, and immunosenescence. Hypertension is the most common morbidity and anti-hypertensives are used for more than 50%. Angiotensin-converting enzyme 1 inhibitors (ACEi) and angiotensin II receptor blockers (ARB) control blood pressure but also seem to play a role in comorbidities such as Alzheimer’s disease, sarcopenia and cancer. The impact of anti-hypertensives in comorbidities is due to the expression of renin-angiotensin system (RAS) in several tissues and body fluids. Angiotensin-converting enzyme 1 (ACE1) has been linked to oxidative stress, metabolism, and inflammation. The levels and activity of ACE1 are under genetic control and polymorphisms have been correlated with susceptibility to Alzheimer’s disease. In addition, some results found that ACEi and ARB users present delayed cognitive decline and reduced risk of dementia. Regarding to sarcopenia, RAS has been linked to the catabolic and anabolic pathways for muscle mass maintenance. In some studies, older adults using ACEi were highly benefited by exercise training. In cancer, RAS and its products have been shown to play a role since their inhibition in animal models modulates tumor microenvironment and improves the delivery of chemotherapy drugs. Clinically, the incidence of colorectal cancer is reduced in patients using ACEi and ARB. During the pandemic COVID-19 it was found that ACE2 receptor plays a role in the entry of SARS-CoV-2 into the host cell. ACE1 genotypes have been linked to an increased risk for COVID-19 and severe disease. In some studies COVID-19 patients taking ARB or ACEi presented better outcome.

Objective: This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa). Methods: We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger's test, with the robustness of the findings verified by sensitivity analysis. Results: Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14–2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11–2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11–2.80; DI vs. II: OR= 1.44, 95% CI: 0.99–2.10; DD vs. II: OR= 2.12, 95% CI: 1.15–3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger's test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis. Conclusion: ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients. [ABSTRACT FROM AUTHOR]

We investigated whether a functional insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) influenced antipsychotic treatment. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients' Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic-syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis. The ACE-I/D polymorphism was significantly associated with changes in PANSS psychopathology only (p < 0.05). Compared to ACE-II homozygous males, ACE-DD homozygous and ACE-ID heterozygous males manifested significantly greater decreases in PANSS positive score, PANSS excitement factor, and PANSS cognitive factor. ACE-DD homozygous females manifested higher decreases in PANSS depression factor compared to ACE-II homozygous and ACE-ID heterozygous females. The polymorphism's effect size was estimated as moderate to strong, while its contribution to the PANSS psychopathology ranged from ~5.4 to 8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicate that ACE-I/D polymorphism had a statistically significant but weak gender-specific impact on psychopathology data, and showed no association between ACE-I/D polymorphism and metabolic-syndrome-related parameters. [ABSTRACT FROM AUTHOR]

This work was aimed to explore the antioxidative properties, bioavailability and the safety of bioactive peptides obtained by the enzymatic hydrolysis of ultrasound-treated (UO) and untreated (nUO) soybean okara proteins. Particularly, the peptidomic profiles of both hydrolysates were examined using an untargeted metabolomics technique for suspect screening that was specifically designed for the profiling of short-chain peptides and relied on ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and bioinformatics. Next, both UO and nUO hydrolysates reduce Dipeptidyl peptidase-IV (DPP-IV) enzyme activity until 39.54 ± 0.26 % and 43.29 ± 0.36 % respectively and inhibit angiotensin converting enzyme (ACE) activities by 30.54 ± 0.42 % and 30.76 ± 0.02 %, respectively. Moreover, they demonstrate to exerted antioxidant properties. Particularly, they show a comparable in vitro antioxidant activity but when the oxidative stress is induced by H 2 O 2 in Caco-2 cells, UO hydrolysate is more active in lowering the levels of reactive oxygen species (ROS) and of lipid peroxidation induced of 48% and 20% respectively. In addition, UO- and nUO-derived peptides trans-epithelial transported by human differentiated intestinal cell monolayer, were identified. Lastly, the possible hepatotoxicity of UO and nUO hydrolysates in HepG2 cells has not been observed by measuring alanine transferase (ALT) and aspartate transferase (AST) levels and cytotoxic effects., Competing Interests: Authors declare no conflict of interest., (© 2024 The Authors.)

Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity. Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples. Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19. Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population. [ABSTRACT FROM AUTHOR]

Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity.Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples.Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19.Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population.

Chronic diseases, such as hypertension, cause great harm to human health. Conventional drugs have promising therapeutic effects, but also cause significant side effects. Food-sourced angiotensin-converting enzyme (ACE) inhibitory peptides are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, there is no systematic and effective screening method for ACE inhibitory peptides, and the lack of understanding of the sequence characteristics and molecular mechanism of these inhibitory peptides poses a major obstacle to the development of ACE inhibitory peptides. Through systematically calculating the binding effects of 160,000 tetrapeptides with ACE by molecular docking, we found that peptides with Tyr, Phe, His, Arg, and especially Trp were the characteristic amino acids of ACE inhibitory peptides. The tetrapeptides of WWNW, WRQF, WFRV, YYWK, WWDW, and WWTY rank in the top 10 peptides exhibiting significantly high ACE inhibiting behaviors, with IC50 values between 19.98 ± 8.19 μM and 36.76 ± 1.32 μM. Salt bridges, π–π stacking, π–cations, and hydrogen bonds contributed to the high binding characteristics of the inhibitors and ACE. Introducing eight Trp into rabbit skeletal muscle protein (no Trp in wide sequence) endowed the protein with a more than 90% ACE inhibition rate, further suggesting that meat with a high content of Trp could have potential utility in hypertension regulation. This study provides a clear direction for the development and screening of ACE inhibitory peptides.

Various reports examined the contribution of ACE I/D, IL-1β G > A and IL-4 VNTR with the susceptibility to RA but with conflicting findings. The goal of this study is to assess the impact of these three variants with the susceptibility, clinical and biochemical markers in addition to different composite indices of RA. This case-control survey enclosed 120 RA Egyptian patients who were emulated with 150 healthy controls from the same territory. Their genomic DNA was genotyped utilising the PCR approach. RA patients with ACE allele (D) and IL-4 VNTR allele (2 R) were expressively higher emulated with healthy controls (p <.05). Nevertheless, RA patients with IL-1β (A allele) failed to achieve an apparent significant emulated with healthy controls (p >.05). This work specifies a noteworthy association for ACE I/D and IL-4 VNTR but not IL-1β G > A polymorphisms with RA susceptibility among Egyptian subjects. [ABSTRACT FROM AUTHOR]

Asparagus (Asparagus officinalis L.) hard‐stem, woody bottom of the asparagus stalk, is a rich source of bioactive compounds and is discarded as an eco‐friendly agricultural waste. Therefore, we intended to explore the antioxidant, amino acid composition, and antihypertensive potentials of enzymatically hydrolysed asparagus hard‐stem. The treated samples exhibited higher total free amino acids (11437 mg 100 g−1), total phenolics (1749 mg 100 g−1), and ability to inhibit (78.38%) angiotensin‐converting enzyme (ACE) compared to control (ACE inhibition of 46.88%). Hydrophobic amino acids (39%) and gallic acid (48%) were the highly eluted bioactive compounds. The ability to inhibit ACE had been positively correlated with hydrophobic amino acids (r = 0.959–0.987) and gallic acid (r = 0.966), indicating the role of amino acids and phenolics in controlling ACE reactions. Thus, asparagus hard‐stem can be a potential source to develop natural health supplements for the management of hypertension and related health risks. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is a significant enzyme that regulates blood pressure. ACE inhibitors are often used in the treatment of hypertension. In this work, ACE was purified and characterized in one step with affinity chromatography from sheep kidneys. ACE was 10305-fold purified and specific activity was 19,075 EU/mg protein. The molecular weight and purity of ACE were found with SDS-PAGE and observed two bands at about 60 kDa and 70 kDa on the gel. The effects of reduced nicotinamide adenine dinucleotide (NADH), an antioxidant compound, on purified ACE activity were also researched. NADH on ACE activity showed an inhibition effect. The inhibition type of NADH was determined to be non-competitive inhibition by the Lineweaver–Burk chart and IC50 and Ki values for NADH were 244.33 and 175.08 µM, respectively. These results suggest that antioxidant substances might be efficient in preventing hypertension. Highlights: ACE was purified from sheep kidneys. Ki and IC50 for NADH were 175.08 and 244.33 µM, respectively. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a global respiratory disease with unique features that have placed all medical professionals in an alarming situation. Preeclampsia is a hypertensive disorder of pregnancy affecting 8%–10% of India's pregnant population. Assuming that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, the resulting symptoms are due to vasoconstriction, caused by disturbances in the renin–angiotensin system (RAS). Other features of preeclampsia include endothelial dysfunction due to placental ischemia, leading to imbalances in angiogenic and antiangiogenic factors which result in increased blood pressure, proteinuria, altered hepatic enzymes, renal failure, and thrombocytopenia, amongst others. The increased prevalence of preeclampsia that was seen among mothers with SARS-CoV-2 infection might be due to misdiagnosis, as COVID-19 and preeclampsia have coincidental medical features. The major similarities of SARS-CoV-2-infected and preeclamptic women are a rise in pro-inflammatory cytokines, and increased serum ferritin and thrombocytopenia. Therefore, differential diagnosis might be difficult in pregnant women with COVID-19 who present with hypertension and proteinuria, thrombocytopenia, or elevated liver enzymes. The most promising markers for earlier diagnosis of preeclampsia is soluble endoglin (sEng), pregnancy-associated plasma protein-A (PAPP-A), soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF). Due to placental hypoxia, sFlt-1 will be overproduced, thus inhibiting PlGF, and this alteration will be observed in the circulation five weeks or more before the onset of symptoms. The sFlt-1/PlGF ratio may also be modified via infectious states, but unregulated levels of those mediators are related to placental insufficiency. Hence, pregnant women with COVID-19 may develop a preeclampsia-like syndrome that might be differentiated properly by angiogenic markers to avoid unnecessary interventions and induced preterm labor. [ABSTRACT FROM AUTHOR]

Mami Ishihara, Akira Meguro, Mizuho Ishido, Masaki Takeuchi, Etsuko Shibuya, Nobuhisa Mizuki Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, JapanCorrespondence: Mami Ishihara; Akira Meguro Tel +81-45-787-2683Fax +81-45-781-9755Email mamitaiga7@gmail.com; akmeguro@yokohama-cu.ac.jpPurpose: Angiotensin-converting enzyme (ACE) is conventionally used as a biomarker in the diagnosis of uveitis associated with sarcoidosis, but its sensitivity is relatively low. In this study, we investigated whether serum soluble interleukin-2 receptor (sIL-2R) is also useful as a diagnostic marker, in addition to ACE, in the detection of uveitis associated with sarcoidosis.Patients and Methods: Data were analyzed from 126 patients with uveitis (52 sarcoidosis and 74 non-sarcoid uveitis) and 12 with primary intraocular lymphoma (PIOL) who had their serum sIL-2R and ACE levels measured.Results: Serum sIL-2R level was elevated in 69.2% of patients with sarcoid uveitis, 5.4% of those with non-sarcoid uveitis, and 16.7% of those with PIOL. The sensitivity and specificity of an elevated sIL-2R level for the detection of sarcoidosis were 69.2% and 93.0%, respectively. In contrast, serum ACE levels were elevated only in patients with sarcoid uveitis, with a sensitivity of 44.2% and specificity of 100%. Furthermore, serum sIL-2R and/or ACE level was elevated in 75.0% of patients with sarcoid uveitis, which is higher than those who had elevated serum ACE level only (44.2%, P = 0.0025). The sensitivity and specificity of elevated sIL-2R and/or ACE in detecting sarcoid uveitis were 75.0% and 93.0%, respectively. The PPV was 0.87, and the NPV was 0.86.Conclusion: Compared with the sensitivity of serum ACE levels alone, combined measurement of both serum sIL-2R and ACE levels improves sensitivity in the detection of uveitis associated with sarcoidosis. Nevertheless, serum ACE alone remains useful thanks to its high specificity in the differentiation of uveitis patients, with sarcoidosis from those without sarcoidosis.Keywords: sarcoid uveitis, soluble interleukin-2 receptors, sIL-2R, angiotensin-converting enzyme, ACE, primary intraocular lymphoma, PIOL

Coronavirus disease 2019 (COVID-19) is a global respiratory disease with unique features that have placed all medical professionals in an alarming situation. Preeclampsia is a hypertensive disorder of pregnancy affecting 8%–10% of India’s pregnant population. Assuming that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, the resulting symptoms are due to vasoconstriction, caused by disturbances in the renin–angiotensin system (RAS). Other features of preeclampsia include endothelial dysfunction due to placental ischemia, leading to imbalances in angiogenic and antiangiogenic factors which result in increased blood pressure, proteinuria, altered hepatic enzymes, renal failure, and thrombocytopenia, amongst others. The increased prevalence of preeclampsia that was seen among mothers with SARS-CoV-2 infection might be due to misdiagnosis, as COVID-19 and preeclampsia have coincidental medical features. The major similarities of SARS-CoV-2-infected and preeclamptic women are a rise in pro-inflammatory cytokines, and increased serum ferritin and thrombocytopenia. Therefore, differential diagnosis might be difficult in pregnant women with COVID-19 who present with hypertension and proteinuria, thrombocytopenia, or elevated liver enzymes. The most promising markers for earlier diagnosis of preeclampsia is soluble endoglin (sEng), pregnancy-associated plasma protein-A (PAPP-A), soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF). Due to placental hypoxia, sFlt-1 will be overproduced, thus inhibiting PlGF, and this alteration will be observed in the circulation five weeks or more before the onset of symptoms. The sFlt-1/PlGF ratio may also be modified via infectious states, but unregulated levels of those mediators are related to placental insufficiency. Hence, pregnant women with COVID-19 may develop a preeclampsia-like syndrome that might be differentiated properly by angiogenic markers to avoid unnecessary interventions and induced preterm labor.

Not only free amino acids and normal short-chain peptides but also modified amino acids, such as N -acetyl- and N -formyl amino acids, monoamines, polyamines, and modified peptides, such as isomerized aspartyl peptides, pyroglutamyl peptides, and diketopiperazines, were identified in Japanese fermented soy paste ( miso ) prepared using different fungal starters, rice, barley, and soybean- koji. One hour after oral administration of water extract of soybean- koji miso to rats, the modified peptides increased significantly in the lumen upon the ingestion, while the normal peptides did not. In the blood from the portal vein and abdominal vena cava, 17 and 15 diketopiperazines, 16 and 12 isomerized aspartyl peptides, and 2 and 1 pyroglutamyl peptides significantly increased to approximately 10-400 nM, respectively. The modified peptides, which increased in rat blood, showed angiotensin-converting enzyme (ACE) inhibitory activity in a dose-dependent manner, indicating multiple ACE inhibitory peptides with high bioavailability in miso. Among them, l-β-Asp-Pro showed the highest ACE inhibitory activity (IC 50 4.8 μM).

Angiotensin-converting enzyme (ACE, EC 3.4.15.1) plays a significant role in blood pressure regulation and inhibition of this enzyme is one of the significant drug targets for the treatment of hypertension. In this work, ACE was purified from sheep kidneys with the affinity chromatography method in one step. The purity and molecular weight of ACE were designated using the SDS-PAGE method and observed two bands at around 60 kDa and 70 kDa on the gel. The effects of nicotinamide (vitamin B 3) and reduced glutathione (GSH) peptide on purified ACE were researched. Nicotinamide and GSH peptide on purified ACE showed an inhibition effect. IC 50 values for nicotinamide and GSH were calculated as 14.3 μM and 7.3 μM, respectively. Type of inhibition and K i values for nicotinamide and GSH from the Lineweaver-Burk graph were determined. The type of inhibition for nicotinamide and GSH was determined as non-competitive inhibition. K i value was calculated as 15.4 μM for nicotinamide and 6.7 μM for GSH. Also, GSH peptide showed higher inhibitory activity on ACE activity than nicotinamide. In this study, it was concluded that nicotinamide and GSH peptide compounds, which show an inhibition effect on ACE activity, may have both protective and therapeutic effects against hypertension. [ABSTRACT FROM AUTHOR]

The severity of SARS-CoV-2 infection is associated with underlying cardiovascular or pulmonary pathological conditions. The fatality rate of this typical pneumonia has superseded the two previous coronavirus epidemics combined. Thus far, comprehensive diagnosis of SARS-CoV-2 remains essential for effective screening, detection, and disease monitoring. This allows employment of different life-saving interventions to lower the spread and mortality, whilst the development of labelled therapeutics is underway. In this perspective, the measurement of Angiotensin-converting enzyme (ACE) status is perceived as a potential prognostic biomarker for SARS-CoV-2 patients. This notion is based on the observation that SARS-CoV-2 infection via attachment to Angiotensin-converting enzyme-2 (ACE2) receptor, downregulates ACE2 expression. Thus leading to the inability to efficiently counter-regulate the damaging effects of its homolog; ACE. The perspective is further strengthened by the recommendations of therapeutics that attenuate the conversion of Angiotensin I to a vasoconstrictor; Angiotensin II as an effective treatment of SARS-CoV-2 infection. In addition, other off-labelled used drugs target the latter; restoration of multiple organ failure and or cytokine storm inhibition. Therefore, this suggests that ACE may be strongly implicated in the pathogenesis of SARS-CoV-2.

Angiotensin-converting enzyme (ACE, EC 3.4.15.1) in the renin-angiotensin system regulates blood pressure by catalyzing angiotensin I to the vasoconstrictor angiotensin II. In this study, the ACE was purified and characterized from sheep lung. The kinetic properties of the ACE were designated. The inhibition effect of captopril, a specific ACE inhibitor, was determined. ACE was purified from sheep lung using the affinity chromatography method in one step. NHS-activated Sepharose 4 Fast Flow as column filler and lisinopril as a ligand in this method used. The molecular weight and purity of ACE were designated using the SDS-PAGE method. Optimum temperature and optimum pH were found for purified ACE. KM and Vmax values from Lineweaver–Burk charts determined. The inhibition type, IC50, and Ki values of captopril on purified ACE were identified. ACE was 6405-fold purified from sheep lung by affinity chromatography in one step and specific activity was 16871 EU/mg protein. The purity and molecular weight of ACE were found with SDS-PAGE and observed two bands at around 60 kDa and 70 kDa on the gel. Optimum temperature and optimum pH were designated for purified ACE. Optimum temperature and pH were found as 40 °C and pH 7.4, respectively. Vmax and KM values were calculated to be 35.59 (µmol/min).mL−1 and 0.18 mM, respectively. IC50 value of captopril was found as 0.51 nM. The inhibition type of captopril was determined as non-competitive from the Lineweaver–Burk graph and the Ki value was 0.39 nM. As a result, it was observed in this study that the ACE enzyme can be successfully purified from sheep lungs in one step. Also, it was determined that captopril, which is a specific ACE inhibitor, has a significant inhibitory effect with a very low IC50 value of 0.51 nM. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID‐19) pandemic has affected the daily lives of millions of people worldwide and had caused significant mortality; hence, the assessment of therapeutic options is of great interest. The leading cause of death among COVID‐19 patients is acute respiratory distress syndrome caused by hyperinflammation secondary to cytokine release syndrome (CRS). Cytokines, such as tumor necrosis factor‐α, interleukin‐6, interferon‐γ and interleukin‐10, are the main mediators of CRS. Based on recent evidence, the angiotensin‐converting enzyme (ACE) II is known to be the target of the COVID‐19 spike protein, which enables the virus to penetrate human cells. ACE II also possesses an anti‐inflammatory role in many pathologies such as cardiovascular disease, hypertension, diabetes mellitus and other conditions, which are the main risk factors of poor prognosis in COVID‐19 infection. Changes in tissue ACE II levels are associated with many diseases and hyperinflammatory states, and it is assumed that elevated levels of ACE II could aggravate the course of COVID‐19 infection. Therefore, the use of renin–angiotensin–aldosterone system inhibitors (RASis) in COVID‐19 patients could be hypothetically considered, though sufficient evidence is not presented by the scientific community. In this work, based on the most recent pieces of evidence, the roles of RAS and RASi in immunologic interactions are addressed. Furthermore, the molecular and immunologic aspects of RASi and their potential significance in COVID‐19 are discussed. [ABSTRACT FROM AUTHOR]

Pumpkin ( Cucurbita moschata ) seed meal (PSM), the major byproduct of pumpkin seed oil industry, was used to prepare angiotensin-converting enzyme (ACE) inhibitory and angiotensin-converting enzyme 2 (ACE2) upregulating peptides. These peptides were isolated and purified from the PSM hydrolysate prepared using Neutrase 5.0 BG by ultrafiltration, Sephadex G-15 column chromatography, and reversed-phase high-performance liquid chromatography. Two peptides with significant ACE inhibition activity were identified as SNHANQLDFHP and PVQVLASAYR with IC 50 values of 172.07 and 90.69 μM, respectively. The C-terminal tripeptides of the two peptides contained Pro, Phe, and Tyr, respectively, and PVQVLASAYR also had Val in its N-terminal tripeptide, which was a favorable structure for ACE inhibition. Molecular docking results declared that the two peptides could interact with ACE through hydrogen bonds and hydrophobic interactions. Furthermore, the two peptides performed protective function on EA.hy926 cells by decreasing the secretion of endothelin-1, increasing the release of nitric oxide, and regulating the ACE2 activity. In vitro simulated gastrointestinal digestion showed the two peptides exhibited good stability against gastrointestinal enzyme digestion. In conclusion, PSM is a promising material for preparing antihypertensive peptides.

Background: Thymosin-α1 has been implicated into the treatment of novel respiratory virus Coronavirus Disease 2019 (COVID-19), but the underlying mechanisms are still disputable. Aim: Herein we aimed to reveal a previously unrecognized mechanism that thymosin-α1 prevents COVID-19 by binding with angiotensin-converting enzyme (ACE), which was inspired from the tool of network pharmacology. Methods: KEGG pathway enrichment of thymosin-α1 treating COVID-19 was analyzed by Database of Functional Annotation Bioinformatics Microarray Analysis, then core targets were validated by ligand binding kinetics assay and fluorometric detection of ACE and ACE2 enzymatic activity. The production of angiotensin I, angiotensin II, angiotensin (1–7) and angiotensin (1–9) were detected by enzyme linked immunosorbent assay. Results: We found that thymosin-α1 impaired the expressions of angiotensin-converting enzyme 2 and angiotensin (1–7) of human lung epithelial cells in a dose-dependent way (p < 0.001). In contrast, thymosin-α1 had no impact on their ACE and angiotensin (1–9) expressions but significantly inhibited the enzymatic activity of ACE (p > 0.05). Conclusion: The bioinformatic findings of network pharmacology and the corresponding pharmacological validations have revealed that thymosin-α1 treatment could decrease ACE2 expression in human lung epithelial cells, which strengthens the potential clinical applications of thymosin-α1 to prevent severe acute respiratory syndrome coronavirus 2 infection.

Angiotensin-converting enzyme (ACE)-inhibitory peptides extracted from food proteins can lower blood pressure by inhibiting ACE activity. A recent study showed that the inhibitory activity of IY (Ile-Tyr, a dipeptide derived from soybean protein) against ACE was much higher than that of LL (Leu-Leu), although they had similar hydrophobic and predicted activity values. It was difficult to reveal the deep molecular mechanism underlying this phenomenon by traditional experimental methods. The Apo and two complex systems (i.e., ACE–LL and ACE–IY) were therefore subjected to 1 μs long Gaussian accelerated molecular dynamics (GaMD) simulations. The results showed that the binding of IY can cause obvious contraction of the active site of ACE, mainly manifested by a significant lateral shift of α13, α14, and α15. In addition, hinge 2 and hinge 3 were more stable in the ACE–IY system, while these phenomena were not present in the ACE–LL system. Moreover, the α10 of the IY-bound ACE kept an inward state during the simulation progress, which facilitated the ACE to remain closed. However, for the LL-bound ACE, the α10 switched between two outward states. To sum up, our study provides detailed insights into inhibitor-induced conformational changes in ACE that may help in the design of specific inhibitors targeting ACE for the treatment of hypertension.

Background Our previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia patients compared with healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting schizophrenia was suggested. Methods ACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (n = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (n = 45) assessed at baseline (FEB-B) and also after 2 months (FEP-2M) of treatment with the atypical antipsychotic risperidone. Results ACE activity measurements showed significant differences among HC, FEP-B, and FEP-2M groups (F = 5.356, df = 2, P  = .005) as well as between HC and FEP-2M (post-hoc Tukey's multiple comparisons test, P  = .004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total Positive and Negative Syndrome Scale (r = −0.131, P  = .434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, P  = .392), but ACE activity level differences observed between these groups were influenced by age. Conclusions The importance of measuring the ACE activity in blood plasma, associated with ACE I/D genotyping to support the follow-up of FEP patients, did not show correlation with general symptom amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated. [ABSTRACT FROM AUTHOR]

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There are conflicting results of studies investigating the association between the tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) gene polymorphisms and Behcet's disease (BD). The aim of this meta-analysis is to assess the association between these gene polymorphisms and ocular involvement in BD. We identified relevant studies and reviewed the full-text manuscripts of the studies in order to select those for inclusion. Heterogeneity of studies was evaluated using Cochran Q-test and I-square index. To modify the heterogeneity in the variables we used random effects model. Meta-analysis was performed using STATA. We analyzed TNF-1031, −308 and ACE DD/II genotype difference between BD patients with and without uveitis. Among these polymorphic genetic loci TNF-308 AA genotype has a statistically significant protective effect against BD uveitis (OR = 0.45 vs 1.23, p =.017). Such a statistically significant effect was not seen for other studied genotypes. This meta-analysis revealed a significant protective effect of TNF-308 AA genotype against ocular involvement in Behcet's disease. [ABSTRACT FROM AUTHOR]

Introduction: Many studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and susceptibility to obstructive sleep apnoea (OSA). However, few have confirmed the relationship between ACE and OSA in the Chinese population. We performed a meta-analysis of studies relating the ACE I/D polymorphism to the risk of OSA in a Chinese population.Methods: We evaluated eligible published studies from several databases for this meta-analysis. Subgroup analyses were performed for hypertension. Pooled odds ratios and 95% confidence intervals were calculated using a fixed- or random-effects model.Results: Ten studies were identified to analyse the association between ACE I/D polymorphism and OSA risk. No marked associations were found in any genetic model (p>0.05). Subgroup analysis showed an association with hypertension (D vs. I, DD vs. II, ID vs. DD+II, DD+ID vs. II, ID vs. II; p<0.05), which was confirmed by sensitivity analyses. No obvious publication bias was found using Egger's test (p>0.05).Conclusions: The ACE I/D polymorphism was not associated with an increased risk of OSA in a Chinese population. However, within the hypertensive subgroup, we detected a significant association between the ACE polymorphism and OSA. More case-control investigations are required. [ABSTRACT FROM AUTHOR]

Genetic association studies about associations between angiotensin-converting enzyme (ACE) polymorphisms and intracranial hemorrhage (ICH) generated conflicting results. In this study, a meta-analysis was performed to better assess the relationship between ACE polymorphisms and ICH. PubMed, Medline, Embase, and CNKI were searched for eligible studies. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate associations between ACE polymorphisms and ICH. A total of 39 studies with 3839 cases and 5353 controls were analyzed. Pooled analyses showed that ACE insertion/deletion (I/D) polymorphism was significantly associated with ICH in the overall population (dominant model: P < 0.0001, OR = 0.70, 95% CI 0.60–0.82, I2 = 58%; recessive model: P < 0.0001, OR = 1.95, 95% CI 1.57–2.43, I2 = 66%; allele model: P < 0.0001, OR = 0.68, 95% CI 0.60–0.78, I2 = 75%). Further subgroup analyses yielded similar significant results in individuals of East Asian and South Asian descent, but not in individuals of European descent. This meta-analysis suggests that ACE I/D polymorphism might affect individual susceptibility to ICH in both East Asians and South Asians. These results indicate that this polymorphism could be used to identify individuals at higher susceptibility to ICH in Asians. [ABSTRACT FROM AUTHOR]

Finger millet (Eleusine coracana) contains high levels of calcium and polyphenols, which have a variety of beneficial functions. We tested the hypothesis that finger millet ethanol extracts (FEs) have an antihypertensive effect in spontaneously hypertensive rats (SHRs). The study groups were assigned as follows: (1) Wistar Kyoto rats (normal); (2) SHRs treated with saline (negative control); (3) SHRs treated with captopril 50 mg/kg bw (positive control); (4) SHRs treated with FE 250 mg/kg bw (FE250); and (5) SHRs treated with FE 500 mg/kg bw (FE500). FE supplementation improved the lipid profiles, including the triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, without deterioration in liver function. The thiobarbituric acid reactive substance concentration and superoxide dismutase activity significantly improved after the application of FE250 and FE500. Interestingly, FE250 and FE500 application dramatically reduced the systolic blood pressure. FE supplementation exhibited powerful control over the renin-angiotensin system by reducing the angiotensin-converting enzyme levels and renin mRNA expression in the kidney. Additionally, FE500 application ameliorated vascular remodeling, reversed the thickening media, and decreased the media thickness/lumen diameter ratio of the aorta. These results imply that FEs are a potent antihypertensive nutraceutical for regulating the renin–angiotensin system and simultaneously inhibiting oxidative stress.

This study aimed to examine whether Ocimum gratissimum (OG) has the Angiotensin-converting enzyme (ACE) inhibitory activity in vitro and in spontaneously hypertensive rats (SHRs). OG water extract exhibited an in vitro ACE-inhibition activity, with the 50% inhibition concentration (IC50) value being 56.3 μg/mL, which is higher than rutin’s 43.08 μg/mL. The main phenolic compound found in OG extract was rutin, according to the HPLC fractionation profile. The anti-hypertension effect in vivo was tested with SHRs. SHRs were fed orally with a distilled water, 100 or 500 mg/kg BW OG extract for 8 weeks. Systolic blood pressure, ACE levels in plasma and lung, and plasma endothelin-1 were significantly lower in the 500 mg/kg OG group compared with the SHRs group. These results suggested that OG extract has the ACE inhibition activity in vitro and also in SHRs, which may be due to its main component of phenolic compound, rutin.

Bioactive peptides (BPs) are a natural and important alternative to synthetic angiotensin-converting enzyme (ACE) inhibitors used in the treatment of hypertension. In this study, ACE was 3575-fold purified from human serum with the affinity chromatography process in one step. The molecular weight and purity of ACE were identified using the SDS-PAGE process and seen in two bands at around 60 kDa and 70 kDa on the gel. V max and K M values from the Lineweaver-Burk graphic were determined as 96.15 (µmol/min) mL -1 and 0.2 mM, respectively. The effects of Gly-Pro (GP), Arg-Gly-Asp-Ser (RGDS) and Ser-Asp-Gly-Arg-Gly (SDGRG) BPs on purified ACE were researched. Also, lisinopril was used as a reference inhibitor. GP, RGDS and SDGRG on purified ACE demonstrated an inhibitory effect. IC 50 values for these peptides were found as 184.71, 107.16 and 32.54 µM, respectively. K i values and type of inhibitory for GP, RGDS and SDGRG by the Lineweaver-Burk chart were found. The type of inhibitory for these peptides was calculated as reversible-competitive inhibitory. K i values for GP, RGDS and SDGRG were calculated to be 260.02, 63.44 and 11.42 µM, respectively. Also, the SDGRG indicated a higher inhibition effect on ACE activity than the GP and RGDS. The IC 50 value of lisinopril was designated as 0.35 nM. The inhibition type of lisinopril was designated as reversible noncompetitive inhibition from the Lineweaver-Burk chart and the K i value was 0.15 nM. Herein, it was concluded that GP, RGDS and SDGRG have ACE inhibitor potential.Communicated by Ramaswamy H. Sarma.

Bioactive peptides from protein hydrolysates with antihypertensive properties have a great effect in health, which warrants their pharmaceutical use. Nevertheless, the process of their production may affect their efficacy. In this study, we investigate the inhibitory activities of various hydrolysates on angiotensin-converting enzyme (ACE) in relation to the chemical diversity of corresponding bioactive peptides. This depends on the enzyme specificity and process conditions used for the production of hydrolysates. In order to mitigate the uncontrolled chemical alteration in bioactive peptides, we propose a computational approach using the random vector functional link (RVFL) network based on the sine-cosine algorithm (SCA) to find optimal processing parameters, and to predict the ACE inhibition activity. The SCA is used to determine the optimal configuration of RVFL, improving the prediction performance. The experimental results show that the performance measures of the proposed model are better than the state-of-the-art methods. • Present an alternative method to predict ACE Inhibition Activity. • Proposed method a modified random vector functional link (RVFL) network. • Using the sine-cosine algorithm (SCA) to find the optimal configuration of RVFL. • Results show that performance of proposed model is better than other methods. [ABSTRACT FROM AUTHOR]