Higher Angiotensin-converting Enzyme Research Articles

Study on the Digestion-Induced Changes in the Characteristics and Bioactivity of Korean Native and Overseas Cattle-Derived Peptides.

This study was conducted to compare and analyze the changes in the biochemical characteristics and biological activity of peptide extracts derived from Chickso, Hanwoo, and Wagyu beef during digestion. The results of the in vitro digestion analysis revealed that the digestion rate, total free amino acid content, and antioxidant and antihypertensive activities of Chickso loin and shank myofibrillar proteins were significantly higher (p<0.05) than those of Hanwoo and Wagyu loin and shank myofibrillar proteins. Particularly, the peptide extracts of Chickso loin and shank had a high angiotensin-converting enzyme inhibitory activity. In mice in vivo digestion experiment, the blood serum of mice fed with Chickso loin peptide extract (<10 kDa) showed the highest antioxidant enzyme activity. Thus, Chickso peptide extracts were deemed to be similar or more bioactive than Hanwoo and Wagyu peptide extracts, and can be used as bioactive materials.

Mathematical modelling of the influence of ACE I/D polymorphism on blood pressure and antihypertensive therapy

The angiotensin-converting enzyme (ACE) gene (ACE) insertion/deletion (I/D) polymorphism raises the possibility of personalising ACE inhibitor therapy to optimise its efficiency and reduce side effects in genetically distinct subgroups. However, the extent of its influence among these subgroups is unknown. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of the ACE I/D polymorphism on haemodynamic parameters in humans undergoing antihypertensive therapy. The model showed that the dependence of blood pressure on serum ACE activity is a function of saturation and therefore, the lack of association between ACE I/D and blood pressure levels may be due to high ACE activity in specific populations. Additionally, in an extended model simulating the effects of different classes of antihypertensive drugs, we explored the relationship between ACE I/D and the efficacy of inhibitors of the renin–angiotensin–aldosterone system. The model predicted that the response of cardiovascular and renal parameters to treatment directly depends on ACE activity. However, significant differences in parameter changes were observed only between groups with high and low ACE levels, while different ACE I/D genotypes within the same group had similar changes in absolute values. We conclude that a single genetic variant is responsible for only a small fraction of heredity in treatment success and its predictive value is limited.

Nasopharyngeal angiotensin converting enzyme 2 (ACE2) expression as a risk-factor for SARS-CoV-2 transmission in concurrent hospital associated outbreaks

BackgroundWidespread human-to-human transmission of the severe acute respiratory syndrome coronavirus two (SARS-CoV-2) stems from a strong affinity for the cellular receptor angiotensin converting enzyme two (ACE2). We investigate the relationship between a patient’s nasopharyngeal ACE2 transcription and secondary transmission within a series of concurrent hospital associated SARS-CoV-2 outbreaks in British Columbia, Canada.MethodsEpidemiological case data from the outbreak investigations was merged with public health laboratory records and viral lineage calls, from whole genome sequencing, to reconstruct the concurrent outbreaks using infection tracing transmission network analysis. ACE2 transcription and RNA viral load were measured by quantitative real-time polymerase chain reaction. The transmission network was resolved to calculate the number of potential secondary cases. Bivariate and multivariable analyses using Poisson and Negative Binomial regression models was performed to estimate the association between ACE2 transcription the number of SARS-CoV-2 secondary cases.ResultsThe infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. Bivariate comparisons found that on average ACE2 transcription did not differ between patients and healthcare workers (P = 0.86). High ACE2 transcription was observed in 98.6% of transmission events, either the primary or secondary case had above average ACE2. Multivariable analysis found that the association between ACE2 transcription (log2 fold-change) and the number of secondary transmission events differs between patients and healthcare workers. In health care workers Negative Binomial regression estimated that a one-unit change in ACE2 transcription decreases the number of secondary cases (β = -0.132 (95%CI: -0.255 to -0.0181) adjusting for RNA viral load. Conversely, in patients a one-unit change in ACE2 transcription increases the number of secondary cases (β = 0.187 (95% CI: 0.0101 to 0.370) adjusting for RNA viral load. Sensitivity analysis found no significant relationship between ACE2 and secondary transmission in health care workers and confirmed the positive association among patients.ConclusionOur study suggests that ACE2 transcription has a positive association with SARS-CoV-2 secondary transmission in admitted inpatients, but not health care workers in concurrent hospital associated outbreaks, and it should be further investigated as a risk-factor for viral transmission.

Screening and molecular dynamics simulation of ACE inhibitory tripeptides derived from milk fermented with Lactobacillus delbrueckii QS306.

Peptides in milk fermented with Lactobacillus delbrueckii QS306 before and after ultrahigh pressure treatment were identified using proteomics. Subsequently, 16 stable tripeptides were screened out based on activity score prediction, PeptideCutter analysis, and hydrophobicity calculations. Among them, WRP, WSR, and YRP showed the best angiotensin-converting enzyme (ACE) inhibitory activity, and their semi-inhibitory concentrations were 46.707, 300.121, and 89.555 μM, respectively. WRP and WSR were competitive inhibitors, whereas YRP was non-competitive. Gastrointestinal simulation revealed that WRP and YRP had better gastrointestinal stability. The values of RMSD, ΔGbind, ΔGpol, and RSMF obtained from molecular dynamics simulation indicated that the interaction of WRP and ACE was stable. Thus, Lactobacillus delbrueckii QS306-fermented milk can serve as an important source of ACE inhibitory peptides both before and after ultrahigh pressure treatment. The strategy of in silico screening, activity evaluation, and molecular dynamics simulation adopted in this study can be applied to the large-scale screening of novel peptides with high ACE inhibitory activity.

TARGETED IMMUNOTHERAPY FOR HEPATOCELLULAR CARCINOMA: A CLINICAL CASE

Relevance: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. HCC is one of the most important problems of the oncology service of Kazakhstan, as it has a progressive course, late detection, low survival, and unfavorable prognosis.&#x0D; The study aimed to evaluate the use of targeted immunotherapy in treating hepatocellular carcinoma in a clinical example.&#x0D; Methods: The paper presents a clinical case of targeted immunotherapy in combination with Atezolizumab 1200 mg + Bevacizumab 800 mg, once every 3 weeks, in treating HCC in the Regional Oncology Center in Kyzylorda.&#x0D; Results: The first symptoms of liver damage appeared in 2018, at which time HCC was discovered. Viral hepatitis B was diagnosed in 2016. MRI OBP from 15.08.20: a picture of the right lobe of the liver in S5 – 9×7×6 cm, in S3 – 3.7 cm, in S7 – 3.0 cm, in S8 – 2.5 cm. During the follow-up examination (July 2021), the enzyme immunoassay revealed a high angiotensin-converting enzyme (ACE) level of 450.56 IU/ml; the abdominal CT scan showed no deterioration. Later, despite the therapy, ACE increased rapidly: 2,595.3 IU/ml (August 2021) and 2,142.25 IU/ml (September 2021), and the therapy was changed to Regorafenib. ACE continued to rise to 4,405 IU/ml (November 2021) and 18,005 IU/ml (December 2021). A control abdominal CT scan showed a moderate reduction in the size of the tumor.&#x0D; Taking into account a steady ACE increase, in February 2022, the patient was recommended therapy with Atezolizumab and Bevacizumab. In January 2023, the patient has already received 13 courses, and ACE continued to decrease: 1,932 IU/ml (January 2023), 53.38 IU/ml (February 2023), 16.07 IU/ml (March 2023), and the abdominal CT scan showed positive dynamics.&#x0D; Conclusion: Targeted immunotherapy showed its effectiveness in the described case of inoperable HCC and allowed the patient to continue living, working, and leading an active lifestyle for more than 18 months.

TARGETED IMMUNOTHERAPY FOR HEPATOCELLULAR CARCINOMA:&#x0D; A CLINICAL CASE

Relevance: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. HCC is one of the most important problems&#x0D; of the oncology service of Kazakhstan, as it has a progressive course, late detection, low survival, and unfavorable prognosis.&#x0D; The study aimed to evaluate the use of targeted immunotherapy in treating hepatocellular carcinoma in a clinical example.&#x0D; Methods: The paper presents a clinical case of targeted immunotherapy in combination with Atezolizumab 1200 mg + Bevacizumab 800 mg,&#x0D; once every 3 weeks, in treating HCC in the Regional Oncology Center in Kyzylorda.&#x0D; Results: The first symptoms of liver damage appeared in 2018, at which time HCC was discovered. Viral hepatitis B was diagnosed in 2016.&#x0D; MRI OBP from 15.08.20: a picture of the right lobe of the liver in S5 – 9×7×6 cm, in S3 – 3.7 cm, in S7 – 3.0 cm, in S8 – 2.5 cm. During the follow-up&#x0D; examination (July 2021), the enzyme immunoassay revealed a high angiotensin-converting enzyme (ACE) level of 450.56 IU/ml; the abdominal CT&#x0D; scan showed no deterioration. Later, despite the therapy, ACE increased rapidly: 2,595.3 IU/ml (August 2021) and 2,142.25 IU/ml (September 2021),&#x0D; and the therapy was changed to Regorafenib. ACE continued to rise to 4,405 IU/ml (November 2021) and 18,005 IU/ml (December 2021). A control&#x0D; abdominal CT scan showed a moderate reduction in the size of the tumor.&#x0D; Taking into account a steady ACE increase, in February 2022, the patient was recommended therapy with Atezolizumab and Bevacizumab. In&#x0D; January 2023, the patient has already received 13 courses, and ACE continued to decrease: 1,932 IU/ml (January 2023), 53.38 IU/ml (February&#x0D; 2023), 16.07 IU/ml (March 2023), and the abdominal CT scan showed positive dynamics.&#x0D; Conclusion: Targeted immunotherapy showed its effectiveness in the described case of inoperable HCC and allowed the patient to continue&#x0D; living, working, and leading an active lifestyle for more than 18 months.

Losartan Has a Comparable Effect to Human Recombinant ACE2 in Reducing Interleukin-6 (IL-6) Levels on Human Adipocytes Exposed to SARS-CoV-2 Spike Protein

BACKGROUND: High angiotensin-converting enzyme 2 (ACE2) expression in adipocyte cells facilitates the initiation of SARS-CoV-2 infection and triggers a cytokine storm. This finding suggests that obesity is an independent risk factor for the severity of the symptoms caused by COVID-19. The use of cardiovascular medications that focus on ACE2, such as angiotensin II receptor blockers, remains controversial, and their effects on inflammatory cytokine production and ACE2 expression in cells, especially adipocytes, remain inconsistent.METHODS: The human adipocytes were isolated from obese donor subcutaneous adipose tissue and infected with the subunit S1 spike protein from SARS-Cov-2. The adipocytes were later treated with either hrsACE2 or losartan. The levels of ACE2 and inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were measured using enzyme linked immunosorbent assay (ELISA). ACE2 and S1 spike protein binding assays were also performed. RESULTS: ACE2, IL-6, and TNF-α levels were significantly increased in human adipocyte cells infected with SARS-Cov-2 but not IL-1β. There was a statistically significant positive correlation between ACE2 and IL-6 (r=0.878, p&lt;0.001). Administration of losartan and hrsACE2 was shown to reduce ACE2 levels and its binding to the SARS-CoV-2 S1 spike protein, and IL-6 levels were statistically significant, but had no significant effect on IL-1β or TNF-α levels.CONCLUSION: This study shows that the administration of losartan in COVID-19 may not be harmful, but instead has a protective effect similar to that of hrsACE2 in preventing a cytokine storm, especially IL-6.KEYWORDS: obesity, SARS-CoV-2, losartan, IL-6, ACE2

Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease

Cognitive decline due to Alzheimer’s disease (AD) is frequent in the geriatric population, which has been disproportionately affected by the COVID-19 pandemic. In this study, we investigated the levels of angiotensin-converting enzyme 2 (ACE2), a regulator of the renin-angiotensin system and the main entry receptor of SARS-CoV-2 in host cells, in postmortem parietal cortex samples from two independent AD cohorts, totalling 142 persons. Higher concentrations of ACE2 protein (p < 0.01) and mRNA (p < 0.01) were found in individuals with a neuropathological diagnosis of AD compared to age-matched healthy control subjects. Brain levels of soluble ACE2 were inversely associated with cognitive scores (p = 0.02) and markers of pericytes (PDGFRβ, p = 0.02 and ANPEP, p = 0.007), but positively correlated with concentrations of soluble amyloid-β peptides (Aβ) (p = 0.01) and insoluble phospho-tau (S396/404, p = 0.002). However, no significant differences in ACE2 were observed in the 3xTg-AD mouse model of tau and Aβ neuropathology. Results from immunofluorescence and Western blots showed that ACE2 protein is predominantly localized in microvessels in the mouse brain whereas it is more frequently found in neurons in the human brain. The present data suggest that higher levels of soluble ACE2 in the human brain may contribute to AD, but their role in CNS infection by SARS-CoV-2 remains unclear.

Buffalo yogurt fermented with commercial starter and Lactobacillus plantarum originating from breast milk lowered blood pressure in pregnant hypertensive rats

Nutritional therapy, which may have advantages over medication, is being investigated as a novel treatment for pregnancy-induced hypertension. Several studies have shown that probiotic yogurt supplementation during pregnancy has beneficial effects on maternal and fetal health. In this study, fermented buffalo milk was produced with yogurt culture and Lactobacillus plantarum B, a probiotic isolated from healthy breast milk with high angiotensin-converting enzyme inhibitory activity. The fermentation conditions under which the angiotensin-converting enzyme (ACE) inhibitory activity reached 84.51% were optimized by the response surface method as follows: 2 × 106 cfu/mL of L. plantarum B, yogurt culture 2.5 × 105 cfu/mL, and 8 h at 37°C. The distribution of ACE inhibitory peptides from fermented buffalo milk and fermented cow milk were further analyzed by liquid chromatography-mass spectrometry. By searching according to the structural features of ACE inhibitory peptides, 29 and 11 peptides containing ACE inhibitory peptide features were found in fermented buffalo milk and fermented cow milk, respectively. To investigate the in vivo antihypertensive activity of fermented buffalo milk, 18 pregnant rats were divided into 3 groups (n = 6 in each group) and administered 10 mL of normal saline, yogurt (20 mg/kg), or labetalol hydrochloride (4 mg/kg) daily from the beginning of pregnancy to parturition. To induce hypertension, methyl nitrosoarginine (125 mg/kg) was injected subcutaneously every day from d 15 of pregnancy to the day of delivery. Blood pressure was not significantly changed in the yogurt and labetalol groups after induction of hypertension and was lower compared with the normal saline group, but there was no difference between the yogurt and labetalol groups. This implied that the buffalo yogurt had a preventive and antihypertensive effect in the pregnancy-induced hypertensive rat model. Further studies to determine the mechanism of action, as well as a randomized control trial, are warranted.

Potential antihypertensive activity of novel peptides from green basil leaves

Hypertension is among the risk factors of death globally. Novel antihypertensive peptides are alternative choices of antihypertensive assistance. This study aimed to discover novel antihypertensive peptides from green basil leaves. Two bioactive peptides with high angiotensin-converting enzyme inhibition (Asp-Leu-Ser-Ser-Ala-Pro; peptide 1) and antioxidant (Asp-Ser-Val-Ser-Ala-Ser-Pro; peptide 2) activities were gavaged to male Wistar rats induced with NG-nitro-l-arginine methyl-ester (L-NAME). L-NAME-treated rats (HT) had decreased body weights and levels of nitrite and nitrate, which are metabolites of nitric oxide. The levels of their glucose and liver function indicators increased as compared to normal rats. HT rats receiving antihypertensive drugs (HTD) showed higher low-density lipoprotein and low-density lipoprotein/high-density lipoprotein levels than HT rats. Peptide 1 seems to benefit the rat lipid profiles, liver functions, antioxidant, nitrite, nitrate, and angiotensin II peptide levels but not peptide 2. In conclusion, our findings indicate the antihypertensive potential related to vasodilation of peptides from green basil leaves.Graphical

A novel angiotensin-converting enzyme (ACE) inhibitory peptide from tilapia skin: Preparation, identification and its potential antihypertensive mechanism

To obtain food-derived peptides with high ACE inhibitory activity, tilapia skin was pretreated with steam explosion prior to enzymatic hydrolysis. The results showed that steam explosion pretreatment improved the hydrolysis efficiency and ACE inhibitory activity of fish skin hydrolysates. A novel ACE inhibitory peptide VGLFPSRSF (1009.17 Da) was obtained from steam-exploded fish skin hydrolysates. VGLFPSRSF had an IC50 value of 61.43 μM for ACE inhibitory activity, showing a non-competitive binding mode and gastrointestinal enzyme hydrolysis resistance. Molecular docking results showed that VGLFPSRSF interacted with ACE receptor protein through hydrogen bonding and hydrophobic interactions. Based on the results of network pharmacological analysis and molecular docking, VGLFPSRSF might regulate blood pressure through interaction with hypertensive targets such as AKT1, ACE, CD4, REN, and MMP9. Steam-exploded tilapia skin peptides had potential antihypertension activity and might be promising to achieve high-value utilization of fish skin by-products.

Production of marine bacterial metalloprotease A69 and evaluation of its potential in preparing soybean peptides with angiotensin-converting enzyme-inhibitory activity.

Marine bacteria secrete a variety of proteases, which are a good source to explore proteases with application value. However, only a few marine bacterial proteases with a potential in bioactive peptides preparation have been reported. The metalloprotease A69 from the marine bacterium Anoxybacillus caldiproteolyticus 1A02591 was successfully expressed in the food safe bacterium Bacillus subtilis as a secreted enzyme. A technique to efficiently produce protease A69 in a 15-L bioreactor was established, with a production of 8988 U mL-1 . Based on optimizing the hydrolysis parameters of A69 on soybean protein, a process for soybean protein peptides (SPs) preparation was set up, in which soybean protein was hydrolyzed by A69 at 4000 U g-1 and 60 °C for 3 h. The prepared SPs had a high content (> 90%) of peptides with a molecular mass less than 3000 Da and contained 18 amino acids. The prepared SPs showed high angiotensin-converting enzyme (ACE)-inhibitory activity, with an IC50 value of 0.135 mg mL-1 . Moreover, three ACE-inhibitory peptides, RPSYT, VLIVP and LAIPVNKP, were identified from the SPs using liquid chromatography-mass spectrometry analysis. The marine bacterial metalloprotease A69 has a promising potential for preparing SPs with good nutritional and potential antihypertensive effects, laying a good foundation for its industrial production and application. © 2023 Society of Chemical Industry.

Effects of angiotensin-converting enzyme on reproduction of Culex pipiens pallens

To investigate the role of angiotensin-converting enzyme (ACE) in the reproduction of Culex pipiens pallens, so as to provide insights into selection of targets for controlling mosquito vector populations. Cx. pipiens pallens was collected from Tangkou County, Shandong Province in 2009. Female and male mosquitoes were selected at 72 hours post-eclosion, and quantitative real-time reverse transcription PCR (qPCR) assay was used to detect the expression of ACE gene in the whole body and reproductive tissues of male mosquitoes and fertilized female mosquitoes before (0 h) and after blood meals (24, 48, 72 h), respectively. Then, 150 female and 150 male mosquitoes at 0 to 4 hours post-eclosion were selected and divided into the wild-type group (WT group), small interfering RNA-negative control group (siNC group) and small interfering RNA-ACE group (siACE group), of 50 mosquitoes in each group. Mosquitoes in the WT group were given no treatment, and mosquitoes in the siNC and siACE groups were given microinjection of siNC and siACE into the hemolymph at a dose of 0.3 μg per mosquito. The knockdown efficiency was checked using qPCR assay, and the reproductive phenotype of mosquitoes was observed. The relative ACE gene expression was higher in the whole body of male mosquitoes (5.467 ± 1.006) relative to females (1.199 ± 0.241) (t = 5.835, P = 0.004) at 72 h post-eclosion, and the highest ACE expression was seen in reproductive tissues of male mosquitoes (199.100 ± 24.429), which was 188.3 times higher than in remaining tissues (1.057 ± 0.340) (t = 6.602, P = 0.002). Blood meal induced high ACE expression in all body tissues of fertilized female mosquitoes, with peak expression at 24 h after blood meals (14.957 ± 2.815), which was 14.8 times higher than that before blood meals (1.009 ± 0.139) (P = 0.002). The transcriptional level of ACEs continued to increase in the ovaries of female mosquitoes after blood meals during the vitellogenesis phase, peaking at 48 h after blood meals (5.500 ± 0.734), which was 5.1 times higher than that before blood meals (1.072 ± 0.178) (P = 0.002). Small RNA interference targeting ACE resulted in a 57.2% reduction in ACE expression in female mosquitoes in the siACE group (0.430 ± 0.070) relative to the siNC group (1.002 ± 0.070) (P = 0.001), and a 41.1% reduction in male mosquitoes in the siACE group (0.588 ± 0.067) relative to the siNC group (1.008 ± 0.131) (P = 0.016). Knockdown of ACE expression resulted in a 48.0% decrease in the number of eggs laid by female mosquitoes in the siACE group [(94.000 ± 27.386) eggs] relative to the siNC group [(180.800 ± 27.386)] (P < 0.001), and a 45.0% decrease in the number of eggs laid by wild female mosquitoes mated with males in the siACE group [(104.500 ± 20.965) eggs] relative to the siNC group [(190.050 ± 10.698) eggs] (P < 0.001). Reduced ACE expression may inhibit the fecundity of male and female mosquitoes, and ACE may be as a potential target for mosquito vector population suppression.

Cigarette smoke increases susceptibility of alveolar macrophages to SARS-CoV-2 infection through inducing reactive oxygen species-upregulated angiotensin-converting enzyme 2 expression

Alveolar macrophages (AMs) are the drivers of pulmonary cytokine storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to investigate clinical–regulatory factors for the entrance protein of SARS-CoV-2, angiotensin–converting enzyme 2 (ACE2) in AMs. Human AMs were collected from 56 patients using bronchoalveolar lavage. ACE2 expression in AMs was positively correlated with smoking pack-year (Spearman’s r = 0.347, P = 0.038). In multivariate analysis, current smoking was associated with increased ACE2 in AMs (β-coefficient: 0.791, 95% CI 0.019–1.562, P = 0.045). In vitro study, ex-vivo human AMs with higher ACE2 were more susceptible to SARS-CoV-2 pseudovirus (CoV-2 PsV). Treating human AMs using cigarette smoking extract (CSE) increases the ACE2 and susceptibility to CoV-2 PsV. CSE did not significantly increase the ACE2 in AMs of reactive oxygen species (ROS) deficient Cybb–/– mice; however, exogenous ROS increased the ACE2 in Cybb–/– AMs. N-acetylcysteine (NAC) decreases ACE2 by suppressing intracellular ROS in human AMs. In conclusion, cigarette smoking increases the susceptibility to SARS-CoV-2 by increasing ROS–induced ACE2 expression of AMs. Further investigation into the preventive effect of NAC on the pulmonary complications of COVID-19 is required.

Screening of protein hydrolysates from malt rootlets and their relationship with technological properties

The malting industry produces a large quantity of by-products, and these have barely been explored in the research into their valorisation. Malt rootlets are rich in protein, and that content can be extracted to generate ingredients with a range of functionalities. Our study confirms that the extraction conditions for the type of enzyme and concentration, as well as the temperature, can affect the production yield and properties from malt rootlets protein hydrolysates. The pH effect was also studied, and it has only shown an effect on technological properties. Alcalase® can generate protein hydrolysates with higher protein content, reaching 33.2%, which in turn implies a higher emulsifying activity (up to 33.9% greater). On the other hand, Protamex® ensures a higher weight yield (up to 49.8%) and higher emulsifying stability, reaching 53.6%. In any case, protein hydrolysates do not improve foaming capacity on malt rootlets mainly due to relative low values of total protein content needed for these properties. All protein hydrolysates showed a high angiotensin-converting enzyme (ACE) inhibitory activity attributed to the similar amount of low molecular fraction (500–200 Da) present in all samples.

Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides.

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.

Serum angiotensin-converting enzyme levels indicating early sarcoidosis diagnosis and immunosuppressive therapy efficacy.

This study aimed to determine the new cut-off value of serum angiotensin-converting enzyme (ACE) levels for detecting patients with sarcoidosis and to examine the change in ACE levels after the initiation of immunosuppressive therapy. We retrospectively examined patients in whom serum ACE levels were measured for suspected sarcoidosis between 2009 and 2020 in our institution. For patients diagnosed with sarcoidosis, changes in ACE levels were also observed. Of the 3781 patients (51.1% men, 60.1±17.0years old), 477 were excluded for taking ACE inhibitors and/or immunosuppression agents or those with any diseases affecting serum ACE levels. In 3304 patients including 215 with sarcoidosis, serum ACE levels were 19.6IU/L [interquartile range, 15.1-31.5] in patients with sarcoidosis and 10.7 [8.4-16.5] in those without sarcoidosis (P<0.01), and the best cut-off value was 14.7IU/L with 0.865 of the area under the curves. Compared with the current ACE cut-off of 21.4, the sensitivity improved from 42.3 to 78.1 at the new cut-off, although specificity slightly decreased from 98.6 to 81.7. The ACE level significantly decreased more in those with immunosuppression therapy than in those without it (P for interaction <0.01), although it decreased in both groups (P<0.01). Because the sensitivity for detecting sarcoidosis is comparatively low at the current standard value, further examinations are needed for patients suspected of sarcoidosis with relatively high ACE levels in the normal range. In patients with sarcoidosis, ACE levels decreased after the initiation of immunosuppression therapy.

Reconsidering the role of receptors for SARS‐CoV‐2 in clear cell renal cell carcinoma: Friends or foes

Reconsidering the role of receptors for SARS‐CoV‐2 in clear cell renal cell carcinoma: Friends or foes

ACE- inhibitory and antioxidant activities in probiotic Cheddar cheese incorporatedwith Inulin and Whey Protein Concentrate

The aim of this study was to compare angiotensin-converting enzyme (ACE) - inhibitory and antioxidant activities of Cheddar and probiotic Cheddar cheese using Lactiplantibacillus plantarum DSM 20174 with inulin and whey protein concentrate (WPC). Water soluble extracts (WSE) of probiotic Cheddar cheese exhibited higher ACE-inhibitory activity than their Cheddar cheese counterparts. A similar trend was observed for antioxidant activity. The highest antioxidant activity(2183.55 μM of Trolox) was obtained when cheese supplemented with WPC and probiotic (PCW) after 6 months of ripening among all the samples followed by probiotic cheese with inulin (PCI).Similarly, PCW had highest ACE- inhibitory activity (88.51%)after 6 months of ripening. The electrophoretic and RP-HPLC profiles indicated that the rate of degradation of proteins resulted in formation of smaller peptides were highest in PCW followed by PCI among all the samples. The results suggest the potential use of WPC in presence of L. plantarum DSM 20174 for production of Cheddar cheese enhanced ACE-inhibitory and antioxidant properties.

Impact of ACE2 and TMPRSS2 Expression in Patients With Preeclampsia.

As maternal morbidity and mortality during pregnancy have increased during the COVID-19 pandemic, studies on pregnancy-related complications from SARS-CoV-2 infection are being actively conducted. Considering that pregnant women with COVID-19 may develop a preeclampsia (PE)-like syndrome, it is necessary to differentiate it from PE because true PE can result in an unfavorable perinatal outcome during a hasty delivery. We investigated the protein expression of transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) in placental samples from 42 normotensive (n=9) and PE (n=33) patients without SARS-CoV-2 infection. We isolated placental trophoblast cells from normotensive and PE patients without evidence of SARS-CoV-2 infection to determine the mRNA and protein expression levels of TMPRSS2 and ACE2. High ACE2 cytoplasmic expression in extravillous trophoblasts (EVTs) was correlated with lower fibrin deposition (p=0.017). In comparison with high nuclear TMPRSS2 expression, low nuclearTMPRSS2 expression in endothelial cells (ECs) was positively correlated with PE (p=0.005), significantly higher systolic blood pressure (p=0.006), and higher urine protein-to-creatinine ratio (p=0.022). In contrast, high cytoplasmic TMPRSS2 expression in fibroblasts (FBs) was correlated with higher urine protein-to-creatinine ratio (p=0.018). Trophoblast cells extracted from PE placental tissue showed lower mRNA levels for both ACE2 and TMPRSS2. TMPRSS2 nuclear expression in ECs and cytoplasmic expression in FBs of the placenta may be related to a trophoblast-independent PE mechanism, and TMPRSS2 could be a new biomarker to discriminate actual PE from a PE-like syndrome associated with COVID-19.