-
Journal of the American Society For... May 2024This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples...
This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples space- and velocity-focusing to precisely analyze the flight-time distribution of ions and predict optimal experimental parameters for the highest mass resolving power. Experimental validation was conducted using a laboratory-made instrument to analyze CsI and angiotensin I ions in low to medium / range. The results indicate that the predicted optimal extraction voltage and delay were reasonably accurate and effective. In the low / range, the peak width obtained using optimal parameters reached the sub nanosecond range, corresponding to a mass resolving power of 10 000-17 000, or 20 000-34 000 if shot-to-shot random fluctuations were minimized by the dynamic data correction method. The observed optimal mass resolving power in the current experiment is 4.8-7.8 times that of commercial instruments. Practical limitations resulting in the gap between the observed and theoretical ultimate mass resolving power are discussed.
PubMed: 38634762
DOI: 10.1021/jasms.4c00018 -
Heliyon Apr 2024In this research, we unveil the medical potential of pearls by identifying a novel bioactive peptide within them for the first time. The peptide, termed KKCHFWPFPW,...
In this research, we unveil the medical potential of pearls by identifying a novel bioactive peptide within them for the first time. The peptide, termed KKCHFWPFPW, emerges as a pioneering angiotensin I-converting enzyme (ACE) inhibitor, originating from the pearl matrix of . Employing quadrupole time-of-flight mass spectrometry, this peptide was meticulously selected and pinpointed. With a molecular weight of 1417.5 Da and a theoretical isoelectric point of 9.31, its inhibitory potency was demonstrated through a half-maximal inhibitory concentration (IC50) of 4.17 μM, established via high-performance liquid chromatography. The inhibition of ACE by this peptide was found to be competitive, as revealed by Lineweaver-Burk plot analysis, where an increase in peptide concentration correlated with an enhanced rate of ACE inhibition. To delve into the interaction between KKCHFWPFPW and ACE, molecular docking simulations were conducted using the Maestro 2022-1 Glide software, shedding light on the inhibitory mechanism. This investigation suggests that peptides derived from the pearl matrix hold promise as a novel source for antihypertensive agents.
PubMed: 38560194
DOI: 10.1016/j.heliyon.2024.e28060 -
Scientific Reports Mar 2024The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin...
The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway.
Topics: Rats; Male; Animals; Quercetin; Renin; Catalase; Aldosterone; Rats, Sprague-Dawley; Reactive Oxygen Species; Hypoxia; Antioxidants; Oxidative Stress; Angiotensin I; Kidney
PubMed: 38556603
DOI: 10.1038/s41598-024-58134-3 -
International Journal of Food Science 2024Tempe is an Indonesian food product traditionally obtained from soybeans through solid-state fermentation with . A variety of substrates can be processed into tempe in...
Tempe is an Indonesian food product traditionally obtained from soybeans through solid-state fermentation with . A variety of substrates can be processed into tempe in the presence of other microorganisms. In this study, grass pea seeds with the addition of flaxseed oil cake (20% w/w) were either fermented using individual mould strains-, , and -or cofermented with the moulds and . In the obtained products, the content of dietary fibre, B group vitamins, and the level of peptides and antioxidant potential in aqueous extracts were measured. Moreover, peptides, angiotensin I convertase inhibitor, and antioxidant activity were determined after digestion. The effect of digestates on the differentiation of enterocytes was also investigated. Fermentation generally resulted in a decrease in the dietary fibre, especially the insoluble fraction (30-50%). The product obtained with was the best source of riboflavin and thiamine among all tested. The fermentation process promoted the accumulation of water-soluble peptides and antioxidant compounds. After digestion, the largest amount of antioxidant and antiradical compounds was released from tempe obtained with . However, the enrichment of the products with antioxidants resulting from solid-state fermentation did not simply translate into an improvement in antioxidant potential after digestion. Generally, fermentation carried out in the presence of brought positive effects only in the case of DSM 1964. Digestion products obtained from tempe had a positive effect on the viability of Caco-2 cells differentiated into enterocytes. Interestingly, a higher activity of differentiation markers (alkaline phosphatase and sucrase-isomaltase) was observed under the influence of digestate of and tempe.
PubMed: 38549663
DOI: 10.1155/2024/5596798 -
Pharmaceuticals (Basel, Switzerland) Feb 2024Olive leaves are consumed as an extract or as a whole herbal powder with several potential therapeutic benefits attributed to polyphenols, tocopherol's isomers, and...
Olive leaves are consumed as an extract or as a whole herbal powder with several potential therapeutic benefits attributed to polyphenols, tocopherol's isomers, and flavonoids, among others. This study assessed the potential variance in the functional features presented by olive leaves from three different Portuguese cultivars-Cobrançosa, Madural, and Verdeal-randomly mix-cultivated in the geographical area of Vale de Salgueiros. Inorganic analysis determined their mineral profiles while an organic analysis measured their total phenolic and flavonoid content, and scanned their phenolic and tocopherol and fatty acid composition. The extracts' biological activity was tested by determining their antimicrobial and antioxidant power as well as their ability to inhibit acetylcholinesterase, butyrylcholinesterase, MAO-A/B, and angiotensin-I-converting enzyme. The inorganic profiles showed them to be an inexpensive source able to address different mineral deficiencies. All cultivars appear to have potential for use as possible antioxidants and future alternative antibiotics against some multidrug-resistant microorganisms, with caution regarding the arsenic content in the Verdeal cultivar. Madural's extract displayed properties to be considered a natural multitarget treatment for Alzheimer's and Parkinson's diseases, depression, and cardiometabolic and dual activity for blood pressure modulation. This work indicates that randomly cultivating different cultivars significantly modifies the leaves' composition while keeping their multifaceted therapeutic value.
PubMed: 38543060
DOI: 10.3390/ph17030274 -
Foods (Basel, Switzerland) Mar 2024The angiotensin-I converting enzyme (ACE) plays a pivotal role in hypertension, and while ACE inhibitors are conventional in hypertension management, synthetic...
The angiotensin-I converting enzyme (ACE) plays a pivotal role in hypertension, and while ACE inhibitors are conventional in hypertension management, synthetic medications often carry undesirable side effects. This has spurred interest in alternative ACE inhibitors derived from natural sources, such as edible insects. The silkworm, recognized for its bioactive peptides with potent ACE-inhibitory properties, has emerged as a promising candidate. This study aims to evaluate the acute toxicity and assess the antihypertensive efficacy of crude mature silkworm hydrolysate powder (MSHP) obtained from mature Thai silkworms. Utilizing the commercial protease Alcalase2.4L, MSHP was administered at various doses, including 50, 100, and 200 mg kg, to hypertensive rats. The investigation spans a 14-day period to observe any potential acute toxic effects. Results indicate that MSHP exhibits LD50 values equal to or exceeding 2000 mg kg, signifying a low level of acute toxicity. Furthermore, the effective dose for blood pressure reduction in hypertensive rats surpasses 100 mg kg of rat body weight. These findings suggest that MSHP derived from Thai mature silkworms holds promise as a natural antihypertensive food source. The implications of this research extend to the development of functional foods, functional ingredients, and dietary supplements aimed at managing hypertension.
PubMed: 38540933
DOI: 10.3390/foods13060943 -
Molecules (Basel, Switzerland) Mar 2024Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However,...
Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the protein (P) and had low IC values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of .
Topics: Angiotensin-Converting Enzyme Inhibitors; Molecular Docking Simulation; Peptidyl-Dipeptidase A; Chromatography, Liquid; Reproducibility of Results; Tandem Mass Spectrometry; Peptides; Angiotensins
PubMed: 38474646
DOI: 10.3390/molecules29051134 -
Physiological Reports Mar 2024With climate change, selection for water efficiency and heat resilience are vitally important. We undertook this study to determine the effect of chronic cyclic heat...
With climate change, selection for water efficiency and heat resilience are vitally important. We undertook this study to determine the effect of chronic cyclic heat stress (HS) on the hypothalamic expression profile of water homeostasis-associated markers in high (HWE)- and low (LWE)-water efficient chicken lines. HS significantly elevated core body temperatures of both lines. However, the amplitude was higher by 0.5-1°C in HWE compared to their LWE counterparts. HWE line drank significantly less water than LWE during both thermoneutral (TN) and HS conditions, and HS increased water intake in both lines with pronounced magnitude in LWE birds. HWE had better feed conversion ratio (FCR), water conversion ratio (WCR), and water to feed intake ratio. At the molecular level, the overall hypothalamic expression of aquaporins (AQP8 and AQP12), arginine vasopressin (AVP) and its related receptor AVP2R, angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), and calbindin 2 (CALB2) were significantly lower; however, CALB1 mRNA and AQP2 protein levels were higher in HWE compared to LWE line. Compared to TN conditions, HS exposure significantly increased mRNA abundances of AQPs (8, 12), AVPR1a, natriuretic peptide A (NPPA), angiotensin I-converting enzyme (ACE), CALB1 and 2, and transient receptor potential cation channel subfamily V member 1 and 4 (TRPV1 and TRPV4) as well as the protein levels of AQP2, however it decreased that of AQP4 gene expression. A significant line by environment interaction was observed in several hypothalamic genes. Heat stress significantly upregulated AQP2 and SCT at mRNA levels and AQP1 and AQP3 at both mRNA and protein levels, but it downregulated that of AQP4 protein only in LWE birds. In HWE broilers, however, HS upregulated the hypothalamic expression of renin (REN) and AVPR1b genes and AQP5 proteins, but it downregulated that of AQP3 protein. The hypothalamic expression of AQP (5, 7, 10, and 11) genes was increased by HS in both chicken lines. In summary, this is the first report showing improvement of growth performances in HWE birds. The hypothalamic expression of several genes was affected in a line- and/or environment-dependent manner, revealing potential molecular signatures for water efficiency and/or heat tolerance in chickens.
Topics: Animals; Chickens; Aquaporin 2; Water; Hot Temperature; Heat-Shock Response; RNA, Messenger
PubMed: 38467563
DOI: 10.14814/phy2.15972 -
Physiological Research Mar 2024Angiotensin-converting enzyme 2 (ACE2), one of the key enzymes of the renin-angiotensin system (RAS), plays an important role in SARS-CoV-2 infection by functioning as a...
Angiotensin-converting enzyme 2 (ACE2), one of the key enzymes of the renin-angiotensin system (RAS), plays an important role in SARS-CoV-2 infection by functioning as a virus receptor. Angiotensin peptides Ang I and Ang II, the substrates of ACE2, can modulate the binding of SARS-CoV-2 Spike protein to the ACE2 receptor. In the present work, we found that co incubation of HEK-ACE2 and Vero E6 cells with the SARS-CoV-2 Spike pseudovirus (PVP) resulted in stimulation of the virus entry at low and high micromolar concentrations of Ang I and Ang II, respectively. The potency of Ang I and Ang II stimulation of virus entry corresponds to their binding affinity to ACE2 catalytic pocket with 10 times higher efficiency of Ang II. The Ang II induced mild increase of PVP infectivity at 20 microM; while at 100 microM the increase (129.74+/-3.99 %) was highly significant (p<0.001). Since the angiotensin peptides act in HEK ACE2 cells without the involvement of angiotensin type I receptors, we hypothesize that there is a steric interaction between the catalytic pocket of the ACE2 enzyme and the SARS-CoV-2 S1 binding domain. Oversaturation of the ACE2 with their angiotensin substrate might result in increased binding and entry of the SARS-CoV-2. In addition, the analysis of angiotensin peptides metabolism showed decreased ACE2 and increased ACE activity upon SARS-CoV-2 action. These effects should be taken into consideration in COVID-19 patients suffering from comorbidities such as the over-activated renin-angiotensin system as a mechanism potentially influencing the SARS-CoV-2 invasion into recipient cells.
Topics: Humans; Renin-Angiotensin System; SARS-CoV-2; Angiotensin-Converting Enzyme 2; COVID-19; Angiotensin I; Peptidyl-Dipeptidase A; Angiotensin-Converting Enzyme Inhibitors; Angiotensin II; Spike Glycoprotein, Coronavirus
PubMed: 38466002
DOI: 10.33549/physiolres.935198 -
Biochemical Pharmacology Apr 2024Angiotensin (Ang)-(1-7) stimulates vasoprotective functions of diabetic (DB) CD34 hematopoietic stem/progenitor cells partly by decreasing reactive oxygen species (ROS),...
Angiotensin (Ang)-(1-7) stimulates vasoprotective functions of diabetic (DB) CD34 hematopoietic stem/progenitor cells partly by decreasing reactive oxygen species (ROS), increasing nitric oxide (NO) levels and decreasing TGFβ1 secretion. Telomerase reverse transcriptase (TERT) translocates to mitochondria and regulates ROS generation. Alternative splicing of TERT results in variants α-, β- and α-β-TERT, which may oppose functions of full-length (FL) TERT. This study tested if the protective functions of Ang-(1-7) or TGFβ1-silencing are mediated by mitoTERT and that diabetes decreases FL-TERT expression by inducing splicing. CD34 cells were isolated from the peripheral blood mononuclear cells of nondiabetic (ND, n = 68) or DB (n = 74) subjects. NO and mitoROS levels were evaluated by flow cytometry. TERT splice variants and mitoDNA-lesions were characterized by qPCR. TRAP assay was used for telomerase activity. Decoy peptide was used to block mitochondrial translocation (mitoXTERT). TERT inhibitor or mitoXTERT prevented the effects of Ang-(1-7) on NO or mitoROS levels in DB-CD34 cells. FL-TERT expression and telomerase activity were lower and mitoDNA-lesions were higher in DB cells compared to ND and were reversed by Ang-(1-7) or TGFβ1-silencing. The prevalence of TERT splice variants, with predominant β-TERT expression, was higher and the expression of FL-TERT was lower in DB cells (n = 25) compared to ND (n = 30). Ang-(1-7) or TGFβ1-silencing decreased TERT-splicing and increased FL-TERT. Blocking of β-splicing increased FL-TERT and protected mitoDNA in DB-cells. The findings suggest that diabetes induces TERT-splicing in CD34 cells and that β-TERT splice variant largely contributes to the mitoDNA oxidative damage.
Topics: Humans; Telomerase; Reactive Oxygen Species; Leukocytes, Mononuclear; Mitochondria; Diabetes Mellitus; Angiotensin I; Peptide Fragments
PubMed: 38458330
DOI: 10.1016/j.bcp.2024.116109