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Journal of Personalized Medicine Aug 2023Diabetic retinopathy (DR) is a complex and multifactorial pathology encompassing environmental, metabolic, and polygenic influences. Among the genes possibly involved in... (Review)
Review
No Association of Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) Gene Polymorphism in the Susceptibility to Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients: An Updated Meta-Analysis.
Diabetic retinopathy (DR) is a complex and multifactorial pathology encompassing environmental, metabolic, and polygenic influences. Among the genes possibly involved in the development and progression of DR, the () gene stands out, which presents an insertion (I) or deletion (D) polymorphism of a 287 bp Alu repetitive sequence in intron 16. Thus, this study aimed to perform a systematic review with meta-analysis to elucidate the relationship between the gene (I/D) polymorphism (rs1799752) and the development and progression of DR in type 2 diabetic patients. PubMed/MEDLINE, Embase, Web of Science, and Scopus databases were systematically searched to retrieve articles that investigated the association between gene (I/D) polymorphism in DR patients. Sixteen articles were included in the systematic review. The results describe no significant association between the polymorphism and DR risk (OR = 1.12; CI = 0.96-1.31; and = 0.1359) for genotypic analysis by the dominant model (II vs. ID+DD). Moreover, we also observed no significant association between the D allele on the allele frequency analysis (I vs. D) and the DR risk (OR = 1.10; CI = 0.98-1.23; and = 0.1182). Forest plot analysis revealed that the discrepancy between previous studies most likely arose from variations in their sample sizes. In conclusion, I/D polymorphism appears to be not involved in the susceptibility to and progression of the DR in type 2 diabetic patients.
PubMed: 37763076
DOI: 10.3390/jpm13091308 -
Marine Drugs Aug 2023The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, . The protein was hydrolyzed...
The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, . The protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC value of 0.007 μM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that -derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.
Topics: Animals; Peptidyl-Dipeptidase A; Molecular Docking Simulation; Mytilidae; Peptides; Zinc
PubMed: 37623739
DOI: 10.3390/md21080458 -
BMC Pulmonary Medicine Nov 2023Angiotensin (Ang)-(1-7) can reduce airway inflammation and airway remodeling in allergic asthma. Autophagy-related 5 (ATG5) has attracted wide attentions in asthma....
BACKGROUND
Angiotensin (Ang)-(1-7) can reduce airway inflammation and airway remodeling in allergic asthma. Autophagy-related 5 (ATG5) has attracted wide attentions in asthma. However, the effects of Ang-(1-7) on ATG5-mediated autophagy in allergic asthma are unclear.
METHODS
In this study, human bronchial epithelial cell (BEAS-2B) and human bronchial smooth muscle cell (HBSMC) were treated with different dose of Ang-(1-7) to observe changes of cell viability. Changes of ATG5 protein expression were measured in 10 ng/mL of interleukin (IL)-13-treated cells. Transfection of ATG5 small interference RNA (siRNA) or ATG5 cDNA in cells was used to analyze the effects of ATG5 on secretion of cytokines in the IL-13-treated cells. The effects of Ang-(1-7) were compared to the effects of ATG5 siRNA transfection or ATG5 cDNA transfection in the IL-13-treated cells. In wild-type (WT) mice and ATG5 knockout (ATG5) mice, ovalbumin (OVA)-induced airway inflammation, fibrosis and autophagy were observed. In the OVA-induced WT mice, Ang-(1-7) treatment was performed to observe its effects on airway inflammation, fibrosis and autophagy.
RESULTS
The results showed that ATG5 protein level was decreased with Ang-(1-7) dose administration in the IL-13-treated BEAS-2B and IL13-treated HBSMC. Ang-(1-7) played similar results to ATG5 siRNA that it suppressed the secretion of IL-25 and IL-13 in the IL-13-treated BEAS-2B cells, and inhibited the expression of transforming growth factor (TGF)-β1 and α-smooth muscle actin (α-SMA) protein in the IL-13-treated HBSMC cells. ATG5 cDNA treatment significantly increased the secretion of IL-25 and IL-13 and expression of TGF-β1 and α-SMA protein in IL-13-treated cells. Ang-(1-7) treatment suppressed the effects of ATG5 cDNA in the IL-13-treated cells. In OVA-induced WT mice, Ang-(1-7) treatment suppressed airway inflammation, remodeling and autophagy. ATG5 knockout also suppressed the airway inflammation, remodeling and autophagy.
CONCLUSIONS
Ang-(1-7) treatment suppressed airway inflammation and remodeling in allergic asthma through inhibiting ATG5, providing an underlying mechanism of Ang-(1-7) for allergic asthma treatment.
Topics: Humans; Animals; Mice; Lung; Ovalbumin; Interleukin-13; Airway Remodeling; Autophagy-Related Protein 5; DNA, Complementary; Asthma; Transforming Growth Factor beta1; Inflammation; RNA, Small Interfering; Fibrosis; Disease Models, Animal; Mice, Inbred BALB C
PubMed: 37919667
DOI: 10.1186/s12890-023-02719-7 -
Frontiers in Endocrinology 2024The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk...
PURPOSE
The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk factors of AIS and explore the role of serum indicators such as angiotensin I (Ang I) in the prognosis of patients undergoing endovascular thrombectomy (EVT).
PATIENTS AND METHODS
Patients with AIS who underwent EVT and healthy controls were retrospectively enrolled in this study, and the patients were divided into a good or a poor prognosis group. We compared Ang I, blood routine indexes, biochemical indexes, electrolyte indexes, and coagulation indexes between patients and controls. We used univariate and multivariate logistic regression analyses to evaluate possible risk factors for AIS and the prognosis of patients undergoing EVT. Independent risk factors for the prognosis of patients undergoing EVT were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves (ROC).
RESULTS
Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. In addition, Ang I levels are lower in AIS compared to the controls. The level of Ang I was higher in the good prognosis group. Furthermore, we developed a nomogram to evaluate its ability to predict the prognosis of AIS after EVT. The AUC value of the combined ROC model (Ang I and albumin-globulin ratio (AGR)) was 0.859.
CONCLUSIONS
In conclusion, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. The combined Ang I and AGR model has a good predictive ability for the prognosis of AIS patients undergoing arterial thrombectomy.
Topics: Humans; Male; Female; Ischemic Stroke; Prognosis; Thrombectomy; Risk Factors; Middle Aged; Aged; Retrospective Studies; Endovascular Procedures; Fibrin Fibrinogen Degradation Products; Case-Control Studies; Biomarkers; ROC Curve
PubMed: 38919492
DOI: 10.3389/fendo.2024.1388871 -
Critical Reviews in Food Science and... 2024This study comprehensively reviewed the effect of controlled enzymatic hydrolysis on the bioactivity of pulse protein hydrolysates (PPHs). Proteolysis results in the... (Review)
Review
This study comprehensively reviewed the effect of controlled enzymatic hydrolysis on the bioactivity of pulse protein hydrolysates (PPHs). Proteolysis results in the partial structural unfolding of pulse proteins with an increase in buried hydrophobic groups of peptide sequences. The use of PPHs in a dose-dependent manner can enhance free radical scavenging and improve antioxidant activities regarding inhibition of lipid oxidation, ferric reducing power, metal ion chelation, and β-carotene bleaching inhibition. Ultrafiltered peptide fractions with low molecular weights imparted angiotensin-I converting enzyme (ACE) inhibitory effects during in vitro simulated gastrointestinal digestion and in vivo conditions. Ultrasonication, high-pressure pretreatments, and glycosylation as post-treatments can improve the antiradical, antioxidant, and ACE inhibitory activities of PPHs. The electrostatic attachment of pulse peptides to microbial cells can inhibit the growth and activity of bacteria and fungi. Bioactive pulse peptides can reduce serum cholesterol and triglycerides, and inhibit the formation of adipocyte lipid storage, allergenic factors, inflammatory markers, and arterial thrombus without cytotoxicity. The combination of germination and enzymatic hydrolysis can significantly increase the protein digestibility and bioavailability of essential amino acids. Moreover, the utilization and enrichment of bakery and meat products with functional PPHs ensure quality, safety, and health aspects of food products.
Topics: Antioxidants; Angiotensin-Converting Enzyme Inhibitors; Legumins; Peptides; Hydrolysis; Fabaceae; Lipids; Protein Hydrolysates
PubMed: 36200775
DOI: 10.1080/10408398.2022.2124399 -
Indian Journal of Microbiology Sep 2023The essential oil has been reported to be one of the Angiotensin I-Converting Enzyme (ACE) inhibitor resources. Moreover, it has been proven against bacterial pathogens...
UNLABELLED
The essential oil has been reported to be one of the Angiotensin I-Converting Enzyme (ACE) inhibitor resources. Moreover, it has been proven against bacterial pathogens that cause infectious diseases. is one source of essential oil, known as Javanese cardamom is a spice herb commonly used for flavouring food and traditional medicine in Indonesia. However, ACE inhibition activity of has not been reported. The purposes of this study were to identify the main constituent of volatile compounds, inhibition activity toward bacteria, and antihypertension potency of essential oils. Volatile compounds were investigated using Gas Chromatography-Mass Spectrometry (GC-MS). The antimicrobial activity was observed using the microdilution method toward , , and . The antihypertension effect was studied using an ACE inhibition assay. The result showed that eucalyptol was a primary compound of fruit either in Banjar (BJR) and Bogor (BGR) essential oils with the value of 62.22% and 66.23%, respectively. Both BJR and BGR are more active to inhibit gram-positive bacteria () with MIC values of 1 mg/mL. Meanwhile, the BJR exhibited a higher inhibitory activity effect toward ACE compared to BGR with the value of IC 64.86 ± 0.57 μg/mL. These findings suggest that essential oil can be the potential to lead to the treatment of hypertension as an ACE inhibitor and antibacterial agent.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12088-023-01080-x.
PubMed: 37781022
DOI: 10.1007/s12088-023-01080-x -
International Journal of Molecular... Aug 2023Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood....
Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin-angiotensin-aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.
Topics: Pregnancy; Humans; Female; Renin-Angiotensin System; Aldosterone; Chromatography, Liquid; Renin; Tandem Mass Spectrometry; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Angiotensin II; Peptide Hormones
PubMed: 37628909
DOI: 10.3390/ijms241612728 -
Frontiers in Nutrition 2023Exceeding 50% tuna catches are regarded as byproducts in the production of cans. Given the high amount of tuna byproducts and their environmental effects induced by...
BACKGROUND
Exceeding 50% tuna catches are regarded as byproducts in the production of cans. Given the high amount of tuna byproducts and their environmental effects induced by disposal and elimination, the valorization of nutritional ingredients from these by-products receives increasing attention.
OBJECTIVE
This study was to identify the angiotensin-I-converting enzyme (ACE) inhibitory (ACEi) peptides from roe hydrolysate of Skipjack tuna () and evaluate their protection functions on HO-induced human umbilical vein endothelial cells (HUVECs).
METHODS
Protein hydrolysate of tuna roes with high ACEi activity was prepared using flavourzyme, and ACEi peptides were isolated from the roe hydrolysate using ultrafiltration and chromatography methods and identified by ESI/MS and Procise Protein/Peptide Sequencer for the N-terminal amino acid sequence. The activity and mechanism of action of isolated ACEi peptides were investigated through molecular docking and cellular experiments.
RESULTS
Four ACEi peptides were identified as WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12), respectively. The affinity of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) with ACE was -8.590, -9.703, -9.325, and -8.036 kcal/mol, respectively. The molecular docking experiment elucidated that the significant ACEi ability of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) was mostly owed to their tight bond with ACE's active sites/pockets via hydrophobic interaction, electrostatic force and hydrogen bonding. Additionally, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could dramatically elevate the Nitric Oxide (NO) production and bring down endothelin-1 (ET-1) secretion in HUVECs, but also abolish the opposite impact of norepinephrine (0.5 μM) on the production of NO and ET-1. Moreover, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could lower the oxidative damage and apoptosis rate of HO-induced HUVECs, and the mechanism indicated that they could increase the content of NO and activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to decrease the generation of reactive oxygen species (ROS) and malondialdehyde (MDA).
CONCLUSION
WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) are beneficial ingredients for healthy products ameliorating hypertension and cardiovascular diseases.
PubMed: 37502715
DOI: 10.3389/fnut.2023.1197382 -
ACS Omega Dec 2023Macroalgal proteins were extracted from (URPE) (green), (PPPE) (brown), and (LOPE) (red) using ultrasound-assisted enzymatic extraction, which is one of the green...
Macroalgal proteins were extracted from (URPE) (green), (PPPE) (brown), and (LOPE) (red) using ultrasound-assisted enzymatic extraction, which is one of the green extraction technologies. Techno-functional, characteristic, and digestibility properties, and biological activities including antioxidant (AOA) and angiotensin-I converting enzyme (ACE-I) inhibitory activities were also investigated. According to the results, the extraction yield (EY) (94.74%) was detected in the extraction of , followed by and . PPPE showed the highest ACE-I inhibitory activity before digestion. In contrast to PPPE, LOPE (20.90 ± 0.00%) and URPE (20.20 ± 0.00%) showed higher ACE-I inhibitory activity after digestion. The highest total phenolic content (TPC) (77.86 ± 1.00 mg GAE/g) was determined in LOPE. On the other hand, the highest AOA (74.69 ± 1.78 mg TE/g) and AOA (251.29 ± 5.0 mg TE/g) were detected in PPPE. After digestion, LOPE had the highest TPC (22.11 ± 2.18 mg GAE/g), AOA (8.41 ± 0.06 mg TE/g), and AOA (88.32 ± 0.65 mg TE/g) ( < 0.05). protein digestibility of three macroalgal protein extracts ranged from 84.35 ± 2.01% to 94.09 ± 0.00% ( < 0.05). Three macroalgae showed high oil holding capacity (OHC), especially PPPE (410.13 ± 16.37%) ( < 0.05), but they showed minimum foaming and emulsifying properties. The quality of the extracted macroalgal proteins was assessed using FTIR, SDS-PAGE, and DSC analyses. According to our findings, the method applied for macroalgal protein extraction could have a potential the promise of ultrasonication application as an environmentally friendly technology for food industry. Moreover, URPE, PPPE, and LOPE from sustainable sources may be attractive in terms of nourishment for people because of their digestibility, antioxidant properties, and ACE-I inhibitory activities.
PubMed: 38162757
DOI: 10.1021/acsomega.3c05041 -
FEBS Letters Jan 2024Human somatic angiotensin-1-converting enzyme (sACE) is composed of a catalytic N-(nACE) and C-domain (cACE) of similar size with different substrate specificities. It...
Human somatic angiotensin-1-converting enzyme (sACE) is composed of a catalytic N-(nACE) and C-domain (cACE) of similar size with different substrate specificities. It is involved in the regulation of blood pressure by converting angiotensin I to the vasoconstrictor angiotensin II and has been a major focus in the development of therapeutics for hypertension. Bioactive peptides from various sources, including milk, have been identified as natural ACE inhibitors. We report the structural basis for the role of two lacototripeptides, Val-Pro-Pro and Ile-Pro-Pro, in domain-specific inhibition of ACE using X-ray crystallography and kinetic analysis. The lactotripeptides have preference for nACE due to altered polar interactions distal to the catalytic zinc ion. Elucidating the mechanism of binding and domain selectivity of these peptides also provides important insights into the functional roles of ACE.
Topics: Humans; Peptidyl-Dipeptidase A; Kinetics; Angiotensin-Converting Enzyme Inhibitors; Angiotensins
PubMed: 37904282
DOI: 10.1002/1873-3468.14768