Genome-Wide Analysis in Drosophila Reveals the Genetic Basis of Variation in Age-Specific Physical Performance and Response to ACE Inhibition

Despite impressive results in restoring physical performance in rodent models, treatment with renin–angiotensin system (RAS) inhibitors, such as Lisinopril, have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs, such as RAS inhibitors, remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult. Here, using 126 genetically distinct lines of Drosophila melanogaster, we tested the effects of Lisinopril on age-specific climbing speed and endurance. Our data show that functional response and sensitivity to Lisinopril treatment ranges from significant protection against physical decline to increased weakness depending on genotype and age. Furthermore, genome-wide analyses led to identification of evolutionarily conserved genes in the WNT signaling pathway as being significantly associated with variations in physical performance traits and sensitivity to Lisinopril treatment. Genetic knockdown of genes in the WNT signaling pathway, Axin, frizzled, nemo, and wingless, diminished or abolished the effects of Lisinopril treatment on climbing speed traits. Our results implicate these genes as contributors to the genotype- and age-specific effects of Lisinopril treatment and because they have orthologs in humans, they are potential therapeutic targets for improvement of resiliency. Our approach should be widely applicable for identifying genomic variants that predict age- and sex-dependent responses to any type of pharmaceutical treatment.

Recent Advances in Applications of Bioactive Egg Compounds in Nonfood Sectors

Egg, a highly nutritious food, contains high-quality proteins, vitamins, and minerals. This food has been reported for its potential pharmacological properties, including antibacterial, anti-cancer, anti-inflammatory, angiotensin-converting enzyme (ACE) inhibition, immunomodulatory effects, and use in tissue engineering applications. The significance of eggs and their components in disease prevention and treatment is worth more attention. Eggs not only have been known as a “functional food” to combat diseases and facilitate the promotion of optimal health, but also have numerous industrial applications. The current review focuses on different perceptions and non-food applications of eggs, including cosmetics. The versatility of eggs from an industrial perspective makes them a potential candidate for further exploration of several novel components.

Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor

Background: In this study, the profile of urinary EGF excretion (uEGF/uCreat) was mapped in children presenting with prolonged proteinuria or with nephrotic syndrome refractory to or dependent of steroids. We investigated whether uEGF/uCreat could be linked to the underlying biopsy result, taking into account its response to immunosuppressive medication and to ACE inhibition, as well as genetic predisposition.Methods: Ninety-eight pediatric patients with initial presentation of nephrotic syndrome or prolonged proteinuria were included in this study, along with 49 healthy controls and 20 pediatric Alport patients. All patients had a normal kidney function and were normotensive during the course of the study, whether or not under ACE inhibition. In repeated urine samples, uEGF was measured and concentration was normalized by urine creatinine. In order to compare diagnosis on kidney biopsy, genetic predisposition and response of uEGF/uCreat to immunosuppression and to ACE inhibition, uEGF/uCreat is studied in a linear mixed effects model.Results: Patients with Minimal Change Disease (MCD) showed a significantly different profile of uEGF/uCreat in comparison to healthy children, as well as compared to patients with Focal Segmental Glomerulosclerosis (FSGS) or another glomerulopathy on kidney biopsy. The response of uEGF/uCreat to ACE inhibition was absent in minimal change disease and contrasted with an impressive beneficial effect of ACE inhibition on uEGF/uCreat in FSGS and other proteinuric glomerulopathies. Absence of a genetic predisposition was also associated with a significantly lower uEGF/uCreat.Conclusions: Despite preserved kidney function, children with a proteinuric or nephrotic glomerular disease on kidney biopsy show a significantly lower uEGF/uCreat, indicative of early tubulo-interstitial damage, which appears reversible under ACE inhibition in any underlying glomerulopathy except in minimal change disease. In view of the distinct profile of uEGF/uCreat in minimal change disease compared to other glomerulopathies, and the link between genetic predisposition and uEGF/uCreat, our study suggests that uEGF/uCreat can be a helpful tool to decide on the need for a renal biopsy in order to differentiate minimal change disease from other proteinuric glomerular diseases.

A UPLC-DAD-Based Bio-Screening Assay for the Evaluation of the Angiotensin Converting Enzyme Inhibitory Potential of Plant Extracts and Compounds: Pyrroquinazoline Alkaloids from Adhatoda vasica as a Case Study

Angiotensin converting enzyme (ACE) plays a crucial role in regulating blood pressure in the human body. Identification of potential ACE inhibitors from medicinal plants supported the idea of repurposing these medicinal plants against hypertension. A method based on ultra-performance liquid chromatography (UPLC) coupled with a diode array detector (DAD) was used for the rapid screening of plant extracts and purified compounds to determine their ACE inhibitory activity. Hippuryl-histidiyl-leucine (HHL) was used as a substrate, which is converted into hippuric acid (HA) by the action of ACE. A calibration curve of the substrate HHL was developed with the linear regression 0.999. The limits of detection and quantification of this method were found to be 0.134 and 0.4061 mM, respectively. Different parameters of ACE inhibitory assay were optimized, including concentration, incubation time and temperature. The ACE inhibition potential of Adhatoda vasica (methanolic-aqueous extract) and its isolated pyrroquinazoline alkaloids, vasicinol (1), vasicine (2) and vasicinone (3) was evaluated. Compounds 1–3 were characterized by various spectroscopic techniques. The IC50 values of vasicinol (1), vasicine (2) and vasicinone (3) were found to be 6.45, 2.60 and 13.49 mM, respectively. Molecular docking studies of compounds 1–3 were also performed. Among these compounds, vasicinol (1) binds as effectively as captopril, a standard drug of ACE inhibition.

Angiotensin II and the Renal Hemodynamic Response to an Isolated Increased Renal Venous Pressure in Rats

Elevated central venous pressure increases renal venous pressure (RVP) which can affect kidney function. We previously demonstrated that increased RVP reduces renal blood flow (RBF), glomerular filtration rate (GFR), and renal vascular conductance (RVC). We now investigate whether the RAS and RBF autoregulation are involved in the renal hemodynamic response to increased RVP. Angiotensin II (ANG II) levels were clamped by infusion of ANG II after administration of an angiotensin-converting enzyme (ACE) inhibitor in male Lewis rats. This did not prevent the decrease in ipsilateral RBF (−1.9±0.4ml/min, p<0.05) and GFR (−0.77±0.18ml/min, p<0.05) upon increased RVP; however, it prevented the reduction in RVC entirely. Systemically, the RVP-induced decline in mean arterial pressure (MAP) was more pronounced in ANG II clamped animals vs. controls (−22.4±4.1 vs. −9.9±2.3mmHg, p<0.05), whereas the decrease in heart rate (HR) was less (−5±6bpm vs. −23±4bpm, p<0.05). In animals given vasopressin to maintain a comparable MAP after ACE inhibition (ACEi), increased RVP did not impact MAP and HR. RVC also did not change (0.018±0.008ml/minˑmmHg), and the reduction of GFR was no longer significant (−0.54±0.15ml/min). Furthermore, RBF autoregulation remained intact and was reset to a lower level when RVP was increased. In conclusion, RVP-induced renal vasoconstriction is attenuated when ANG II is clamped or inhibited. The systemic effect of increased RVP, a decrease in HR related to a mild decrease in blood pressure, is attenuated also during ANG II clamp. Last, RBF autoregulation remains intact when RVP is elevated and is reduced to lower levels of RBF. This suggests that in venous congestion, the intact RBF autoregulation could be partially responsible for the vasoconstriction.

Edible Seaweeds: A Potential Novel Source of Bioactive Metabolites and Nutraceuticals With Human Health Benefits

There has been an increase in human health concerns, and seaweeds are considered as a potential functional food which can decrease the risk of many diseases, as they contain various bioactive compounds. Seaweeds are of nutritional interest and a rich source of natural bioactive compounds including antioxidants, flavonoids, phenolic compounds, and alkaloids that can be used as an alternative source of food material. Seaweeds contain a high amount of vitamins such as A, D, E, C, and B, and minerals including calcium, potassium, magnesium and iron. Seaweeds containing carrageenan, agar and other polysaccharides not only act as a source of fiber but also can act as prebiotics which may benefit the bacteria present in the large intestine. The lack of technologies to process seaweeds for human consumption at an industrial scale is a serious limitation on growth of the seaweed-based functional foods sector. Seaweeds are one of the most extensively used functional foods, with a long history in Asian countries. Now they are also being explored by many Western and European countries. Evidence from epidemiological research suggests that regular consumption of a marine algae-based diet may boost immunity against a number of diseases including COVID-19 novel virus by angiotensin-I-converting enzyme (ACE) inhibition.

Milk Fermentation by Lacticaseibacillus rhamnosus GG and Streptococcus thermophilus SY-102: Proteolytic Profile and ACE-Inhibitory Activity

Health benefits of probiotics and production of inhibitors of angiotensin converting enzyme (ACE) released during milk fermentation are well known. That is why in this investigation the proteolytic profile and ACE inhibitory capacity of peptide fractions from protein hydrolysis of milk during fermentation processes was analyzed. Milk fermentation was carried out inoculating 106 CFU of L. rhamnosus GG, S. thermophilus SY-102 and with both bacteria. The proteolytic profile was determined using: TNBS, SDS-PAGE and SEC-HPLC techniques. In vitro ACE inhibition capacity was measured. The pH of 4.5 was reached at 56 h when the milk was fermented with L. rhamnosus, at 12 h with S. thermophillus and at 41 h in the co-culture. Production of free amino groups corresponded with the profile of low molecular weight peptides observed by SDS-PAGE and SEC-HPLC. Co-culture fermentation showed both the highest concentration of low molecular weight peptides and the ACE inhibitory activity (>80%). Results indicated that the combination of lactic cultures could be useful in manufacture of fermented milk with an added value that goes beyond basic nutrition, such as the production of ACE-inhibitory peptides.