The effects of consuming hemp seed protein (HSP) as well as its hydrolysate-derived bioactive peptide (HSP+) on blood pressure (BP) has not, to our knowledge, been investigated in humans.
We aimed to investigate how consumption of HSP and its hydrolysate modulates 24-h systolic (SBP) and diastolic BP (DBP) and plasma biomarkers of BP compared with casein.
In a double-blind, randomized, crossover design trial, 35 adults who had mild hypertension with SBP between 130 and 160 mmHg and DBP ≤110 mmHg were recruited. Participants were randomly assigned to varying sequences of 3 6-wk treatments, 50 g casein/d, 50 g HSP/d, or 45 g HSP plus 5 g HSP-derived bioactive peptides/d (HSP+), separated by a 2-wk washout period. Treatment effects were assessed with a linear mixed model with repeated measures.
Compared with casein, after HSP+ consumption, 24-h SBP and 24-h DBP decreased from 135.1 and 80.0 mmHg to 128.1 ± 1.6 (P < 0.0001) and 76.0 ± 1.4 mmHg (P < 0.0001), respectively, whereas these values were 133.5 ± 1.6 and 78.9 ± 1.4 mmHg after HSP consumption (P < 0.0001). There were no differences between the HSP and HSP+ consumption in plasma angiotensin-converting enzyme (ACE) activity, renin, or nitric oxide (NO) concentrations. However, these 2 treatments were able to lower both ACE and renin activities and raise NO concentration in plasma compared with casein.
These results suggest that hemp protein consumption, as well as in combination with bioactive peptides, may have a role in the dietary management of hypertension. This trial was registered at clinicaltrials.gov as NCT03508895.

Food-derived peptides with low molecular weight, high bioavailability, and good absorptivity have been exploited as angiotensin-converting enzyme (ACE) inhibitors. In the present study, in-vitro inhibition kinetics of peanut peptides, in silico screening, validation of ACE inhibitory activity, molecular dynamics (MD) simulations, and HUVEC cells were performed to systematically identify the inhibitory mechanism of ACE interacting with peanut peptides. The results indicate that FPHPP, FPHY, and FPHFD peptides have good thermal, pH, and digestive stability. MD trajectories elucidate the dynamic correlation between peptides and ACE and verify the specific binding interaction. Noteworthily, FPHPP is the best inhibitor with a strongest binding affinity and significantly increases NO, SOD production, and AT2R expression, and decreases ROS, MDA, ET-1 levels, ACE, and AT1R accumulation in Ang II-injury HUVEC cells.

Hypertension is one of the most typical causes of morbidity and mortality. The present study investigated the possible antihypertensive cardiovascular effects of an herbal mixture extract of Hibiscus, Corn silk, Marjoram, and Chamomile. HPLC analysis of the water extract prepared from the aerial parts of four plants and their mixture was done to detect the most predominant compounds. A safety study was done prior to the efficacy study to determine the dose and ensure the extract\'s safety in female rats. Hypertension was induced in ovariectomized and non-ovariectomized rats by oral administration of 50 mg/kg of LName for 30 days; the hypertensive rats were classified into non-ovariectomized and ovariectomized untreated groups, treated groups with high and low doses of the mixture(150,300 mg/kg) given to ovariectomized and non-ovariectomized hypertensive groups and a standard group treated with angiotensin-converting enzyme inhibitor. The untreated group showed significant elevation of blood pressure, heart rate, cholesterol, triglycerides, malondialdehyde, cyclic adenosine monophosphate, angiotensin-converting enzyme, C-reactive protein, and significantly lowered reduced glutathione, high-density lipoprotein, and endothelial nitric oxide synthase. Treatment significantly counteracted the effects of L Name. The mixture provides a promising natural cardiovascular regulating supplement owing to its high contents of flavonoids.

Risk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk factors for prenatal exposures to medications with teratogenic risk can guide strategies to reduce exposure.
This study aimed to identify medications with known or potential teratogenic risk commonly used during pregnancy among privately insured persons.
We used the Merative™ MarketScan® Commercial Database to identify pregnancies with live or nonlive (ectopic pregnancies, spontaneous and elective abortions, stillbirths) outcomes among persons aged 12 to 55 years from 2011 to 2018. Start/end dates of medication exposure and pregnancy outcomes were identified via an adapted algorithm based on validation studies. We required continuous health plan enrollment from 90 days before conception until 30 days after the pregnancy end date. Medications with known or potential teratogenic risk were selected from TERIS (Teratogen Information System) and drug monographs based on the level of risk and quality of evidence (138 with known and 60 with potential risk). We defined prenatal exposure on the basis of ≥1 outpatient pharmacy claim or medical encounter for medication administration during target pregnancy periods considering medication risk profiles (eg, risk only in the first trimester or at a certain dose threshold). Sex hormones and hormone analogs, and abortion and postpartum/abortion hemorrhage treatments were not considered as teratogenic medications because of challenges in separating pregnancy-related indications, nor were opioids (because of complex risk-benefit considerations) or antiobesity medications if their only teratogenic mechanism was weight loss.
Among all pregnancies, the 10 medications with known teratogenic risk and the highest prenatal exposures were sulfamethoxazole/trimethoprim (1988 per 100,000 pregnancy-years), high-dose fluconazole (1248), topiramate (351), lisinopril (144), warfarin (57), losartan (56), carbamazepine (50), valproate (49), vedolizumab (28 since 2015), and valsartan (25). Prevalence of exposure to sulfamethoxazole/trimethoprim decreased from 2346 to 1453 per 100,000 pregnancy-years from 2011 to 2018, but prevalence of exposure to vedolizumab increased 6-fold since its approval in 2015. Prenatal exposures in the first trimester were higher among nonlive pregnancies than among live-birth pregnancies, with the largest difference observed for warfarin (nonlive 370 vs live birth 78), followed by valproate (258 vs 86) and topiramate (1728 vs 674). Prenatal exposures to medications with potential teratogenic risk were most prevalent for low-dose fluconazole (6495), metoprolol (1325), and atenolol (448). The largest first-trimester exposure differences between nonlive and live-birth pregnancies were observed for lithium (242 vs 89), gabapentin (1639 vs 653), and duloxetine (1914 vs 860). Steady increases in hydralazine and gabapentin exposures were observed during the study years, whereas atenolol exposure decreased (561 to 280).
Several medications with teratogenic risk for which there are potentially safer alternatives continue to be used during pregnancy. The fluctuating rates of prenatal exposure observed for select teratogenic medications suggest that regular reevaluation of risk mitigation strategies is needed. Future research focusing on understanding the clinical context of medication use is necessary to develop effective strategies for reducing exposures to medications with teratogenic risk during pregnancy.

Radiolabeled neurotensin analogs have been developed as candidates for theranostic use against neurotensin subtype 1 receptor (NTS1R)-expressing cancer. However, their fast degradation by two major peptidases, neprilysin (NEP) and angiotensin-converting enzyme (ACE), has hitherto limited clinical success. We have recently shown that palmitoylation at the ε-amine of Lys7 in [99mTc]Tc-[Lys7]DT1 (DT1, N4-Gly-Arg-Arg-Pro-Tyr-Ile-Leu-OH, N4 = 6-(carboxy)-1,4,8,11-tetraazaundecane) led to the fully stabilized [99mTc]Tc-DT9 analog, displaying high uptake in human pancreatic cancer AsPC-1 xenografts but unfavorable pharmacokinetics in mice. Aiming to improve the in vivo stability of [99mTc]Tc-DT1 without compromising pharmacokinetics, we now introduce three new [99mTc]Tc-DT1 mimics, carrying different pendant groups at the ε-amine of Lys7: MPBA (4-(4-methylphenyl)butyric acid)-[99mTc]Tc-DT10; MPBA via a PEG4-linker-[99mTc]Tc-DT11; or a hydrophilic PEG6 chain-[99mTc]Tc-DT12. The impact of these modifications on receptor affinity and internalization was studied in NTS1R-positive cells. The effects on stability and AsPC-1 tumor uptake were assessed in mice without or during NEP/ACE inhibition. Unlike [99mTc]Tc-DT10, the longer-chain modified [99mTc]Tc-DT11 and [99mTc]Tc-DT12 were significantly stabilized in vivo, resulting in markedly improved tumor uptake compared to [99mTc]Tc-DT1. [99mTc]Tc-DT11 was found to achieve the highest AsPC-1 tumor values and good pharmacokinetics, either without or during NEP inhibition, qualifying for further validation in patients with NTS1R-positive tumors using SPECT/CT.

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

BACKGROUND: The renin-angiotensin system (RAS) has been associated with inflammatory bowel disease (IBD), supporting translational relevance of RAS blockers. Comparability of study design/outcomes is fundamental for data analysis/discussion.
OBJECTIVE: We aimed at evaluating the heterogeneity among protocols and outcomes to study the effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in IBD.
METHODS: This study was performed and reported in accordance with the Cochrane recommendations and PRISMA (PROSPERO-CRD42022323853). Systematic searches were performed in PubMed, Scopus and Web of Science. Studies that met the inclusion criteria were selected. Quality assessment of the studies was done with the SYRCLES\'s risk of bias tools for animal studies.
RESULTS: Thirty-five pre-clinical studies and six clinical studies were included. Chemical induction of colitis was the most used model, but variable doses of the induction agent were reported. All studies reported at least a disease activity index, a macroscopic score, or a histologic assessment, but these scores were methodologically heterogeneous and reported for different characteristics. Great heterogeneity was also found in drug interventions. Inflammatory markers assessed as outcomes were different across studies.
CONCLUSIONS: Lack of standardization of protocols and outcomes among studies threatens the evidence on how RAS blockers influence IBD outcomes.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has resulted in a global pandemic. Methodology: We used a two-step polymerase chain reaction to detect the ACE genotype and ELISA kits to detect the cytokine factor. We also used proteomics to identify the immune pathway related to the ACE protein expression. Result: In this study, we found that the angiotensin-converting enzyme (ACE) deletion polymorphism was associated with the susceptibility to COVID-19 in a risk-dependent manner among the Chinese population. D/D genotype distributions were higher in the COVID-19 disease group than in the control group (D/D odds ratio is 3.87 for mild (p value < 0.0001), 2.59 for moderate (p value = 0.0002), and 4.05 for severe symptoms (p value < 0.0001), logic regression analysis. Moreover, genotype-specific cytokine storms and immune responses were found enriched in patients with the ACE deletion polymorphism, suggesting the contribution to the susceptibility to COVID-19. Finally, we identified the immune pathway such as the complement system related to the ACE protein expression of patients by lung and plasma proteomics. Conclusion: Our results demonstrated that it is very important to consider gene polymorphisms in the population to discover a host-based COVID-19 vaccine and drug design for preventive and precision medicine.

BACKGROUND: The effect of renin-angiotensin system (RAS) blockade either by angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) susceptibility, mortality and severity is inadequately described. We examined the association between RAS blockade and COVID-19 diagnosis and prognosis in a large population-based cohort of patients with hypertension (HTN).
METHODS: This is a cohort study using regional health records. We identified all individuals aged 18-95 years from 87 healthcare reference areas of the main health provider in Catalonia (Spain), with a history of HTN from primary care records. Data were linked to COVID-19 test results, hospital, pharmacy and mortality records from 1 March 2020 to 14 August 2020. We defined exposure to RAS blockers as the dispensation of ACEi/ARBs during the 3 months before COVID-19 diagnosis or 1 March 2020. Primary outcomes were: COVID-19 infection and severe progression in hospitalized patients with COVID-19 (the composite of need for invasive respiratory support or death). For both outcomes and for each exposure of interest (RAS blockade, ACEi or ARB) we estimated associations in age-, sex-, healthcare area- and propensity score-matched samples.
RESULTS: From a cohort of 1 365 215 inhabitants we identified 305 972 patients with HTN history. Recent use of ACEi/ARBs in patients with HTN was associated with a lower 6-month cumulative incidence of COVID-19 diagnosis {3.78% [95% confidence interval (CI) 3.69-3.86%] versus 4.53% (95% CI 4.40-4.65%); P < 0.001}. In the 12 344 patients with COVID-19 infection, the use of ACEi/ARBs was not associated with a higher risk of hospitalization with need for invasive respiratory support or death [OR = 0.91 (0.71-1.15); P = 0.426].
CONCLUSIONS: RAS blockade in patients with HTN is not associated with higher risk of COVID-19 infection or with a worse progression of the disease.

In this article, the selective inhibition of several tyrosine-containing dipeptides on N and C domain of ACE (angiotensin-converting enzyme) was studied, and the interaction mode of ACE and inhibitors was simulated by molecular docking. MTT assay was used to detect the effect of dipeptide on human umbilical vein endothelial cells (HUVEC). The results showed that the food-derived dipeptides AY (Ala-Tyr), LY (Leu-Tyr), and IY (Ile-Tyr) containing tyrosine at the C-terminal were favorable structures for selective inhibition of ACE C-domain. These dipeptides showed competitive and mixed inhibition patterns, while the dipeptides EY (Glu-Tyr), RY (Arg-Tyr), FY (Phe-Tyr), and SY (Ser-Tyr) showed noncompetitive inhibition. Food-derived dipeptides containing tyrosine have no cytotoxicity on HUVEC cells, which provides a basis for the application of food-derived tyrosine dipeptides as antihypertensive peptides. This study provides a theoretical basis for exploring the selective inhibition mechanism of ACE inhibitory peptides containing tyrosine residue. PRACTICAL APPLICATIONS: Angiotensin-converting enzyme (ACE) is a two-domain dipeptidyl carboxypeptidase, which is a key enzyme to regulate blood pressure. ACE has two active sites, C- and N-domain, which have high catalytic activity. Although the amino acid sequences of the two active sites have 60% similarity, there are some differences in structure and function. The action mechanism of ACE domain should be clarified, and the structure-activity relationship between inhibitors and ACE domain has not been systematically studied. The aim of this study was to identify the selective inhibitory effect of food-derived tyrosine dipeptides on the domain of ACE. This provides a new idea for finding new antihypertensive drugs with less side effects.