Search Results (1,461)

Hypertension is one major risk factor of cardiovascular diseases, and RAS plays vital role during the development of hypertension. To obtain a novel antihypertensive peptide, Coix glutelin was hydrolyzed by trypsin and further separated by Sephadex G10. Based on 751 identified sequences, pharmacophore mapping, molecular docking, and in silico proteolysis were applied to screen and optimize the candidate sequence. Finally, a novel peptide, ENWAAL, was generated with IC₅₀ of 210.57 μM, which acted with ACE in a competitively inhibitory pattern. The in vivo antihypertensive effect was evaluated in SHRs. Significant improvements were observed in hypertension-related characteristics, including blood pressure, cardiac structure and function, and serum angiotensin II (Ang II) level. In the brain, quantitative real-time PCR analysis revealed significant downregulation of angiotensin II type 1 receptor (AT1R) mRNA expression, concomitant with upregulation of angiotensin-converting enzyme 2 (ACE2) and MAS receptor. The protein expression of ACE and AT1R in the ENWAAL group also significantly decreased. This study can provide a candidate antihypertensive drug targeting RAS. Full article

Plant-based symbiotic systems are often limited by poor storage stability and inconsistent biofunctional performance. This study evaluated the stability and functionality of a fermented blend based on sacha inchi (Plukenetia volubilis) oil press cake (SIC) and yacon (Smallanthus sonchifolius) flour (YF) as sources of protein and fructooligosaccharides (FOS), respectively, using two processing strategies: fermentation with Lactobacillus rhamnosus (T1) and combined enzymatic hydrolysis with Alcalase and fermentation with Lactobacillus plantarum (T2). Both treatments maintained viable cell counts (VCC) above probiotic thresholds (>10⁶ CFU mL⁻¹) during 28 days of storage at 4 °C, confirming their suitability as probiotic carriers. Notably, T2 significantly enhanced metabolic activity, as evidenced by higher organic acid production and increased soluble protein content due to Alcalase-mediated hydrolysis, which promoted the generation of bioactive peptides associated with improved antioxidant and antihypertensive activities. Biofunctional properties, including total phenolic content, antioxidant capacity (AC), and angiotensin-converting enzyme (ACE) inhibitory activity, remained stable throughout storage, while FOS degradation was minimal, confirming preservation of prebiotic functionality. LC–MS/MS Q-TOF analysis revealed a complex phenolic profile that was differentially modulated by lactic acid fermentation, with L. plantarum (T2) promoting extensive phenolic biotransformation and increased metabolite diversity, whereas L. rhamnosus (T1) largely preserved the original phenolic profile. These findings demonstrate that the synergistic interaction between enzymatic hydrolysis and L. plantarum fermentation promoted peptide release, intensified microbial metabolism, and enhanced phenolic biotransformation, thereby contributing to the superior functional properties observed in T2, while maintaining stable biofunctional characteristics throughout refrigerated storage in both treatments. Full article

Adolescence is a developmental stage marked by dynamic interactions between diet, the gut microbiome and endocrine maturation, creating a physiological environment in which early metabolic disturbances can rapidly translate into long-term cardiovascular vulnerability. This narrative review summarises the latest research on the diet–microbiome–hormone axis in adolescents, focusing on the metabolic pathways through which microbial metabolites influence host physiology. Short-chain fatty acids (SCFAs), microbially transformed bile acids and postbiotic signalling molecules regulate enteroendocrine communication, insulin sensitivity, vascular function and inflammatory tone, thereby linking dietary exposures to early cardiometabolic alterations. Dysbiosis, driven by ultra-processed dietary patterns, low fibre intake and reduced microbial diversity, promotes metabolic endotoxemia, neuroendocrine imbalance and endothelial impairment, all of which are recognised as early indicators of cardiovascular disease. A distinctive contribution of this review is the integration of PF into the adolescent cardiometabolic framework. This emerging biotechnological process enables the controlled production of structurally defined bioactive compounds, including angiotensin-converting enzyme (ACE) inhibitory peptides, targeted prebiotic oligosaccharides, fermentable substrates that promote SCFA formation, microbially derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), phytosterols and purified postbiotics. These compounds modulate several regulatory pathways, such as the renin–angiotensin–aldosterone system, lipid and bile acid metabolism, gut barrier stability, inflammatory signalling and endocrine axes involving glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin, insulin sensitivity and growth hormone/insulin-like growth factor-1 (GH/IGF-1) dynamics. By situating precision fermentation within the broader context of adolescent metabolic susceptibility, this review highlights its potential to support microbiome resilience, stabilise hormonal regulation and mitigate early cardiovascular risk. However, further adolescent-specific clinical trials and long-term safety assessments are required to translate these advances into effective public health strategies. Full article

Background: Although prolonged inflammatory symptoms are an infrequent and problematic adverse effect of vaccination that can occur in some people, the transient activation of acute phase reactants (APRs) is expected with adjuvanted vaccines and helps to potentiate immune responses. Methods: This experiment examined the association between vaccine reactogenicity and immunogenicity in monkeys immunized with an adjuvanted recombinant protein including a receptor binding domain–human IgG1-Fc fusion protein (RBD-Fc) sequenced from the ancestral Wuhan strain of SARS-CoV-2. The acute inflammatory reaction to immunization was assessed by determining the decline in serum iron levels at 24 h and the increase in the neutrophil-to-lymphocyte ratio (NLR) as the adherent neutrophil pool trafficked into circulation. Results: Robust primary and secondary antibody responses were elicited. Larger decreases in serum iron and higher NLRs were associated with a stronger inhibition of RBD binding with angiotensin-converting enzyme (ACE2) when five early viral variants of SARS-CoV-2 were tested, including Wuhan, Alpha, Beta, Gamma and Delta. Inhibition of ACE2-RBD binding was less evident when the Omicron variant was tested. Individual variation in the APR was also predictive of the persistence of cell-mediated immunity based on the number of interferon-expressing mononuclear cells activated by viral antigen in ELISpot assays. Conclusions: Rapid antibody responses to primary immunization and large secondary responses to booster immunizations were elicited by this adjuvanted recombinant RBD-Fc vaccine, and our analysis affirmed the view that a transient APR can enhance antibody binding with antigen proteins. Full article

Research on oxazolones, particularly 4-alkynyloxazolones, has garnered increasing interest due to the presence of an alkynyl group, which facilitates molecular conjugation and enables diverse chemical modifications. In this study, three representative 4-alkynyloxazolone derivatives (L1–L3) were synthesized and structurally characterized through single-crystal X-ray diffraction and computational analysis to obtain a reliable structure of L1–L3 to subsequently predict in silico interactions with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein. The crystallographic results revealed high molecular planarity and multifurcated hydrogen bonding. Considering the obtained crystallographic structure, theoretical descriptors such as HOMO–LUMO energy gaps and electrostatic potential maps indicated that these compounds exhibit favorable electronic reactivity, particularly for L3, with favorable drug-like predictions. The lack of methoxy groups in L2 and L3 makes these compounds have lower predicted toxicity parameters than L1. Molecular docking calculations targeting SARS-CoV-2 spike glycoprotein in three different feasible conformations in a biological matrix, i.e., three receptor-binding domains (RBD) in down conformation, two RBD in down and one in up conformation, as well as RBD bound to the human receptor angiotensin-converting enzyme 2 (ACE2), suggested strong binding affinities and specific interactions with the RBD moiety, mainly in the up conformation. Overall, this work integrates crystallographic and computational approaches to establish the structural and in silico evaluation of spike-binding properties of early substituted 4-alkynyloxazolones, suggesting L3 as a candidate for future in vitro antiviral assays. Full article

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally among older adults. Similar to humans, age-related declines in cardiac function are observed in C57BL/6 mice. Angiotensin-converting enzyme 2 (ACE2), a key component of the renin–angiotensin system (RAS), counteracts detrimental RAS effects by converting angiotensin II (Ang II) to angiotensin-(1-7) (Ang-(1-7)), thereby playing a critical role in mitigating CVD pathogenesis. Here, we utilized transgenic K18-hACE2 mice to investigate the protective effects of ACE2 against cardiac aging. Histological and morphometric analyses revealed significant reductions in heart weight and improvements in cardiac structure in K18-hACE2 mice compared to wild-type controls. Furthermore, aged C57BL/6 mice exhibited progressive cardiac aging phenotypes, including mitochondrial dysfunction, telomere shortening, and immune dysregulation—all of which were significantly attenuated in K18-hACE2 mice. These findings demonstrate the protective role of ACE2 in cardiac aging and highlight its potential as a therapeutic target for anti-aging interventions. Full article

Particularly in regions experiencing rapid industrial and healthcare development, the presence of pharmaceutical residues in wastewater is becoming an increasingly pressing environmental concern. In this study, an analytical method was developed to quantify lisinopril (LIS), ramipril (RAM), and enalapril (ENA) in wastewater while being both sensitive and inexpensive. To improve the precision and accuracy of the measurements, propranolol (PRO) was used as an internal standard. To achieve dual preconcentration and enhanced sensitivity, the method integrates filed amplified sample stacking (FASS) with solid-phase extraction (SPE) before capillary electrophoresis (CE) in a synergistic way. Important experimental factors such the composition of the background electrolyte (BGE), pH, injection settings, stacking efficiency, and selection of the SPE sorbent were meticulously calibrated. Under ideal circumstances, the SPE-CE-FASS method demonstrated remarkable linearity within the concentration range of 10–1000 ng L⁻¹ (R² > 0.999), an outstanding level of accuracy (intra- and inter-day RSD < 6%), and satisfactory recovery percents (90–97%) in real wastewater samples. This method offers an eco-friendly and cost-effective alternative to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) by reducing waste, using less solvent, and providing enough sensitivity for trace-level analysis. Hence, it is very suitable for the regular monitoring of angiotensin converting enzyme (ACE) inhibitors in complex wastewater matrices. Full article

Background: In patients with type 2 diabetes mellitus (T2DM), angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are first-line antihypertensive treatments with important cardiovascular benefits, but their impacts on coronary-specific inflammation are unknown. Pericoronary adipose tissue (PCAT) attenuation, as assessed by coronary computed tomography angiography (CCTA), serves as a specific biomarker for coronary inflammation. Here, we aim to assess whether treatment with ACE-I or ARB is correlated with lower PCAT attenuation. Methods: In this retrospective observational study, we analyzed 223 patients with T2DM and coronary atherosclerosis who underwent CCTA from 1 January 2017 to 1 September 2024 at our institution. PCAT attenuation was measured in the proximal right coronary artery. Propensity score matching and multivariate linear regression analyses were performed for comparisons. Results: Of the 223 patients (mean age of 64.9 ± 8.8 years, 69.1% male), 122 patients were on ACE-I or ARB (ACE-I/ARB). ACE-I/ARB users had similar PCAT attenuation as their counterparts after propensity score matching (−72.1 ± 7.5 and −71.7 ± 8.1 HU, respectively; p = 0.722). Subgroup analysis in patients with glomerular filtration rate (GFR) < 90 mL/min revealed lower PCAT attenuation in ACE-I/ARB users (−74.8 ± 6.6 vs. −71.4 ± 7.1 HU; p = 0.038), with a significant interaction between these two factors in the multivariate analysis (p = 0.047). Other antihypertensive treatments (beta blockers, dihydropyridine calcium channel blockers, and thiazides) were not linked with lower coronary inflammation. Conclusions: In T2DM patients with coronary atherosclerosis, we did not find an association between ACE-I/ARB treatment and lower coronary inflammation as defined by PCAT attenuation, although such a relationship may exist in those with reduced GFRs. Full article

The renin–angiotensin system (RAS) regulates inflammation, tissue homeostasis, and barrier integrity in lung and colon epithelial cells. Beyond classical pathways, non-canonical components including angiotensin-converting enzyme 2 (ACE2), epidermal growth factor receptor (EGFR), insulin-like growth factor 2 receptor (IGF2R) and aminopeptidase N (ANPEP) are implicated in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and bacterial sepsis due to their roles in tissue repair and signaling. Despite their similar inflammatory and coagulopathic features, their impact on RAS-associated non-immune gene expression in epithelial tissues remains unclear. This study investigates the regulation of these targets in lung (BEAS-2B) and colon (CRL-1831) cells following exposure to recombinant SARS-CoV-2 spike protein N-terminal domain fragment (S1-NTD) and Pseudomonas aeruginosa-derived lipopolysaccharide (LPS). Cells were treated with 100 ng/mL of S1-NTD or LPS for 12–72 h. Viability was assessed via XTT assays, and molecular changes were analyzed through qRT-PCR and Western blotting. Both stimuli induced a time and dose-dependent decrease in metabolic activity. ACE2 was significantly downregulated in lung cells, while transient upregulation occurred in colon cells at 24 h. EGFR expression increased in colon cells following LPS exposure but decreased in lung cells after S1-NTD treatment. Both IGF2R and ANPEP were upregulated by S1-NTD in lung cells at 72 h, whereas colon cells showed earlier upregulation at 24–48 h. Our findings reveal that viral and bacterial stimuli elicit distinct, tissue-specific regulatory patterns in RAS-associated pathways. These alterations may contribute to epithelial barrier dysfunction and inflammation, highlighting these proteins as potential targets for managing secondary bacterial infections and inflammatory lung–gut complications in COVID-19. Full article

Periodontitis (P) and Type 2 Diabetes Mellitus (T2DM) are chronic inflammatory diseases that share pathophysiological pathways involving immune dysregulation and oxidative stress. Both conditions have been associated with increased susceptibility to viral infections, including SARS-CoV-2. In this regard, molecules associated with viral infection include angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). This study aimed to evaluate the clinical periodontal status, oral microbiota composition, and the expression of ACE2 and TMPRSS2 in the oral epithelium and gingival tissue of patients with and without T2DM and P. Methods: This cross-sectional study enrolled 120 participants allocated into four groups based on periodontal and glycemic status: periodontally healthy non-diabetic individuals (PH non-T2DM), periodontitis without diabetes (P non-T2DM), periodontally healthy individuals with type 2 diabetes mellitus (PH T2DM), and periodontitis with T2DM (P T2DM), with 30 participants per group. Full-mouth clinical periodontal parameters were recorded by a calibrated examiner. Oral microbiota was assessed from unstimulated whole saliva, labial swab samples, and subgingival biofilm by selective culture and checkerboard DNA-DNA hybridization. Gingival exfoliative cytology and full-thickness gingival biopsies were obtained for immunohistochemical evaluation of ACE2 and TMPRSS2 expression. Cytomorphometric analysis and polymorphonuclear cell counts were performed on epithelial smears. Additionally, primary human gingival fibroblasts (HGFs) isolated from each group were stimulated with bacterial ligands (LPS, LTA, and PGN) to assess ACE2 and TMPRSS2 modulation by Western blot. Intergroup comparisons were performed using one-way ANOVA with Bonferroni post hoc correction and the Mann–Whitney U test, with statistical significance set at p < 0.05. Results: Diabetic patients exhibited higher plaque accumulation, clinical attachment loss, and bleeding on probing compared with non-diabetic individuals (p < 0.05). The diabetic groups showed significantly higher levels of Actinomyces, Fusobacterium, and Streptococcus spp., with decreased Staphylococcus counts. ACE2 and TMPRSS2 expression were markedly elevated in gingival epithelial cells of P T2DM patients, predominantly in basal and suprabasal layers. The nuclear-to-cytoplasmic ratio and polymorphonuclear cell counts were also increased in diabetic subjects. Conclusions: T2DM and P synergistically upregulate ACE2 and TMPRSS2 expression and alter the oral microbiota. Full article

Hierarchical functionalisation of the UiO-66(Zr)-NH₂ metal–organic framework with cysteine, poly(ethylene glycol) (PEG), and the SARS-CoV-2 spike receptor-binding domain (RBD) was developed to enable receptor-specific interaction with the angiotensin-converting enzyme 2 receptor (ACE2) in model cells. Post-synthetic modification using cysteine and heterobifunctional PEG linkers allowed controlled bioconjugation of SpyTag-labelled RBD via SpyTag/SpyCatcher chemistry, while preserving the crystallinity, microporosity, and intrinsic optical properties of the UiO-66(Zr)-NH₂ framework. Comprehensive physicochemical characterisation confirmed successful surface functionalisation, tunable aggregation behaviour, and retention of multimodal optical characteristics. Cellular studies in HEK293T and HeLa cells overexpressing EGFP-tagged ACE2 demonstrated enhanced and selective association and uptake of RBD-functionalised nanoparticles compared with non-targeted analogues. Multimodal fluorescence imaging, fluorescence lifetime imaging microscopy, flow-cytometry, and electron microscopy indicated ACE2-dependent endocytic internalisation, with predominant localisation in endosomal and autophagosomal compartments, while both amine- and cysteine-modified formulations exhibited good biocompatibility. Overall, this study establishes a virus-mimetic, ACE2-targeted UiO-66(Zr)-based nanosystem as a proof-of-concept biointerface platform for receptor-specific cellular delivery and imaging, providing a foundation for future MOF-based nanocarriers exploiting ligand–receptor interactions. Full article

The aqueous extract of Diaphragma Juglandis Fructus (AED), a by-product of Juglans regia L., represents a promising food-derived functional ingredient with potential benefits for intestinal health. This study evaluated the anti-colitis effects of AED and explored its underlying mechanisms using LPS-stimulated RAW264.7 macrophages and a DSS-induced colitis mouse model. In DSS-induced colitis in mice, AED at 10 μg/mL suppressed pro-inflammatory cytokine production and inhibited JAK1/STAT3 signaling. In DSS-induced colitis in mice, AED at 600 mg/kg for 7 days mitigated DSS-induced colonic injury, restored tight junction proteins, and improved epithelial barrier integrity. Integrated transcriptomic and metabolomic analyses identified AED-associated alterations in arginine-polyamine and taurine-hypotaurine metabolism, while network pharmacology and molecular docking suggested angiotensin-converting enzyme (ACE) and von Willebrand factor (VWF) as candidate functional targets for further investigation. Collectively, these findings indicate that AED exerts anti-colitis effects in association with coordinated changes in inflammatory signaling, metabolic pathways, and barrier-related markers, supporting its potential as a food-derived functional ingredient candidate for ulcerative colitis management. Full article

Hypertension remains a leading cause of global morbidity and mortality, and angiotensin-converting enzyme (ACE) represents a central therapeutic target within the renin–angiotensin–aldosterone system. Marine microalgae, particularly Phaeodactylum tricornutum, provide an underexplored reservoir of structurally diverse metabolites with potential cardiovascular relevance. In this in silico study, we characterized metabolites putatively annotated by UPLC-ESI-HRMS and evaluated their predicted ACE inhibitory potential. We performed molecular docking with AutoDock 4 and assessed pharmacokinetic and toxicological properties using the SwissADME, PASS, and ProTox platforms. Several metabolites showed favorable binding orientations within the ACE catalytic pocket, including interactions with key residues and proximity to the zinc-binding motif. Lehualide G, Val–Asn–Pro, tanariflavanone B, hydroxyterbinafine, and anhydro-vitamin A exhibited the most favorable docking profiles. PASS predictions indicated vascular-related bioactivity signals for selected compounds, whereas ADMET modeling revealed heterogeneous but classifiable pharmacokinetic and safety characteristics. The convergence of predicted binding compatibility, bioactivity signals, and stratified safety margins supports P. tricornutum as a promising source of candidate molecules for further experimental validation in antihypertensive research. Full article

Background: COVID-19 severity shows marked interindividual variability, suggesting a role for host genetic factors. Polymorphisms in genes involved in the renin–angiotensin system and inflammatory response, such as the angiotensin-converting enzyme (ACE) and the tumor necrosis factor-alpha (TNF-α), have been proposed as potential modulators of disease severity. Objectives: To evaluate the association between the ACE I/D (rs4646994) and TNF-α-308 G/A (rs1800629) polymorphisms and COVID-19 severity in a Mexican population. Methods: A total of 235 individuals with RT-PCR–confirmed SARS-CoV-2 infection were included. Patients were classified as hospitalized (severe, n = 155) or non-hospitalized (asymptomatic–mild, n = 80). Genotyping was performed by PCR–RFLP. Genotype distributions were analyzed using χ² tests under dominant and recessive genetic models, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: The ACE I/D polymorphism showed a significant association with COVID-19 severity. Carriers of the I allele (ID + II) had a higher risk of hospitalization compared with DD homozygotes (OR = 2.78, 95% CI: 1.53–5.06, p = 0.001). After adjustment for sex, the association remained significant (adjusted OR = 2.55, 95% CI: 1.38–4.70, p = 0.003). Sex-stratified analysis revealed that this association was significant only in male patients. The DD genotype was more frequent among non-hospitalized individuals, suggesting a potential protective effect in this population. No significant association was observed between the TNF-α-308 G/A polymorphism. Conclusions: The ACE I/D polymorphism is associated with COVID-19 severity in a Mexican population, with a stronger association observed in males. These findings highlight the potential role of host genetic background and sex-specific effects in COVID-19 outcomes. Full article

Goat blood, a major slaughterhouse by-product, was systematically valorized into dual-function bioactive peptides through an optimized four-step process. Four blood preparations—whole blood (HB), anticoagulant-treated blood (HBS), red blood corpuscles (BC), and plasma (PM)—were subjected to heat pretreatment (90 °C, 15 min) and enzymatic hydrolysis. Neutrase hydrolysis of heat-pretreated whole blood at 8% substrate concentration for 4 h (HBN-8) yielded optimal protein recovery (44.38%) with dual ACE (88.24%) and DPP-IV (81.13%) inhibition. Ultrafiltration enriched bioactive peptides in the ≤3 kDa fraction (DPP-IV: 87.8%; ACE: 65.5%). LC-MS/MS de novo sequencing identified 14 novel peptide sequences (4–9 amino acids), with the most potent SEC fraction showing IC₅₀ values of 0.89 and 0.45 mg Leu eq./mL for DPP-IV and ACE inhibition, respectively. Critically, simulated gastrointestinal digestion enhanced rather than diminished bioactivity, with ACE inhibition increasing progressively to 60.91% at the intestinal phase, supported by predicted generation of bioactive fragments from parent sequences. Caco-2 assays confirmed peptide safety (100–1000 µg/mL) and demonstrated 10.47% transepithelial transport with retained dual inhibitory activities. This study establishes goat blood as a sustainable source of orally bioavailable, GI-stable peptides for the development of functional foods targeting hypertension and type 2 diabetes. Full article