Search Results (1,540)

The invasive fish Atherina boyeri constitutes an ecologically disruptive yet underexploited biomass with strong potential for transformation into value-added biofunctional ingredients. This study investigates the functional, antioxidant, and antimicrobial properties of protein hydrolysates that were produced from fish collected in the Hirfanlı and Yamula reservoirs using three commercial proteases (alcalase, bromelain, and flavourzyme). Bromelain produced the highest degree of hydrolysis, yielding higher proportions of low-molecular-weight peptides and greater radical-scavenging activity. Flavourzyme hydrolysates exhibited the most favorable emulsifying properties, Alcalase hydrolysates produced the highest foaming capacity and stability. All hydrolysates showed high absolute zeta-potential values across pH 3–9, demonstrating strong colloidal stability. Protein solubility remained above 80% across most pH levels, indicating extensive peptide release and improved compatibility with aqueous media. The Oil-binding capacity (2.78–3.75 mL/g) was consistent with reported values for marine hydrolysates. Antioxidant and antimicrobial evaluations revealed clear enzyme-dependent patterns, with Bromelain exhibiting the strongest DPPH activity and Alcalase and Flavourzyme showing the most pronounced inhibition of major foodborne pathogens. Additionally, all hydrolysates exhibited measurable ACE-inhibitory activity, with flavourzyme-derived peptides showing the highest inhibitory activity, underscoring their potential relevance for antihypertensive applications. These findings highlight the strategic valorization of A. boyeri through enzymatic hydrolysis, demonstrating its potential as a sustainable, clean-label functional ingredient source. Full article

The zoonotic potential of bat coronaviruses, especially HKU5, is a significant issue because of their capacity to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry. This study offers structural insights into the binding kinetics of HKU5 (Bat Merbecovirus HKU5) receptor-binding domain (RBD) spike protein with human ACE2 through a multiscale computational method. This study employed structural modeling, 300-nanosecond (ns) molecular dynamics (MD) simulations, alanine-scanning mutagenesis, and computational peptide design to investigate ACE2 recognition by the HKU5 RBD and its interactions with peptides. The root mean square deviation (RMSD) investigation of HKU5–ACE2 complexes indicated that HKU5 exhibited greater flexibility than SARS-CoV-2, with RMSD values reaching a maximum of 1.2 nm. Free energy analysis, Molecular Mechanics/Generalized Born Surface Area (MM/GBSA), indicated a more robust binding affinity of HKU5 to ACE2 (ΔG_Total = −21.61 kcal/mol) in contrast to SARS-CoV-2 (ΔG_Total = −5.82 kcal/mol), implying that HKU5 binding with ACE2 had higher efficiency. Additionally, a peptide was designed from the ACE2 interface, resulting in the development of 380 single-site mutants by mutational alterations. The four most promising mutant peptides were selected for 300-nanosecond (ns) MD simulations, subsequently undergoing quantum chemical calculations (DFT) to evaluate their electronic characteristics. MM/GBSA of −37.83 kcal/mol indicated that mutant-1 exhibits the most favorable binding with HKU5, hence potentially inhibiting ACE2 interaction. Mutant-1 formed hydrogen bonds involving Glu74, Ser202, Ser204, and Asn152 residues of HKU5. Finally, QM/MM calculations on the peptide–HKU5 complexes showed the most favorable ΔE_interaction of −170.47 (Hartree) for mutant-1 peptide. These findings offer a thorough comprehension of receptor-binding dynamics and are crucial for evaluating the zoonotic risk associated with HKU5-CoV and guiding the design of receptor-targeted antiviral treatments. Full article

The bioactive potential of dairy-derived peptides has attracted increasing interest due to their capacity to exert antioxidant and antihypertensive effects. This study investigated three artisanal cheeses manufactured with animal rennet (CTRL), Onopordum platylepis extract (OP), or a mixture of both coagulants (AR/OP) to compare their peptide profiles and associated bioactivities. Water-soluble extracts were analyzed to identify precursors and released bioactive peptides, and in vitro assays were performed to assess antioxidant activity and angiotensin-converting enzyme (ACE) inhibition. The analysis of precursors suggested a predominance of antioxidant sequences in CTRL and ACE-inhibitory precursors in OP, with AR/OP showing intermediate values. However, direct peptide identification confirmed that the AR/OP mixture produced a wider range of peptides with antioxidant activity, while OP and AR/OP exhibited similarly high levels of ACE-inhibiting peptides. These results were consistent with in vitro assays, which confirmed AR/OP as the most active sample for antioxidant potential and OP, closely followed by AR/OP, as the strongest for ACE inhibitory activity. Overall, the integration of precursor analysis, peptide identification, and experimental validation highlights the influence of the coagulant on the generation of bioactive peptides, suggesting that the use of Onopordum platylepis Murb. (O. platylepis) alone or in combination with animal rennet may enhance the functional properties of cheese. Full article

The preventive effect of leucine (Leu) against colonic damage in piglets infected with porcine epidemic diarrhea virus (PEDV) was examined in this study. Three groups (n = 6) were randomly assigned to eighteen 7-day-old Du-roc × Landrace × Large piglets (body weight [BW] = 2.58 ± 0.05 kg): Control, PEDV-infected (PEDV), and Leu-supplemented + PEDV-infected (Leu + PEDV). Following a three-day period of acclimatization, the Leu + PEDV group was given Leu (400 mg/kg BW) orally every day. On day eight, the PEDV and Leu + PEDV groups were challenged with PEDV, while the Control group was given Dulbecco’s Modified Eagle’s Medium. Colonic tissues were collected on day 11. PEDV infection induced severe colonic damage by an increase in crypt, disrupting intestinal homeostasis, including impaired barrier integrity (matrix metalloproteinase-7 and matrix metalloproteinase-13 upregulation), mucus disorganization (mucin 5AC elevation), oxidative stress (reduced catalase activity and increased malondialdehyde levels), inflammation, electrolyte imbalance and enhanced viral replication. Leu supplementation reversed these injuries by alleviating oxidative stress, suppressing inflammation, inhibiting viral replication and stabilizing ion homeostasis. This study provides a scientific basis for Leu as a nutritional intervention to alleviate PEDV-induced colonic damage in piglets. Full article

Background/Objectives: Oral hygiene is crucial for maintaining overall health, as poor oral care can lead to various systemic diseases. Although xylitol is widely used to inhibit plaque formation, more effective agents are needed to control oral biofilms. Herein, we evaluated the inhibitory effects of sialyllactose (SL), a type of human milk oligosaccharide (HMO), and its partial structure N-acetylneuraminic acid (Neu5Ac) against Streptococcus biofilm. Methods: Under a CO₂ atmosphere, Streptococcus mutans and mixed Streptococcus species were each cultivated in vitro, and the inhibitory effects of HMOs [2′-fucosyllactose, 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL)] and Neu5Ac on biofilm formation were evaluated. Bacterial biofilm formation was quantified using the crystal violet assay. Biofilm architecture and viability were visualized using confocal laser-scanning microscopy (CLSM) with SYTO9/propidium iodide staining. Transcriptomic responses of S. mutans biofilms to the test compounds were analyzed by RNA-Seq. Statistical analysis was performed using one-way analysis of variance followed by Tukey’s test. Results: SLs and Neu5Ac at 100 mM significantly inhibited S. mutans biofilm formation, with stronger effects than those of xylitol. The inhibitory effects varied among HMOs, with 6′-SL being more effective than 3′-SL and Neu5Ac being most effective. These effects were consistent in assays targeting biofilms formed by other S. mutans strains and in a mixed biofilm comprising Streptococcus species. Gene expression analysis suggested that the inhibitory mechanism involves the physical inhibition of surface adhesion and stress-induced regulation of gene expression. Conclusions: This study provides insights into the physiological significance of HMOs in the oral cavities of humans. HMOs exhibited potential as functional foods to control oral biofilm formation and reduce the risk of oral and systemic diseases. Full article

Background/Objectives: Human serum albumin (HSA) is a major endogenous inhibitor of angiotensin-converting enzyme (ACE) and helps fine-tune the activity of the renin–angiotensin–aldosterone system (RAAS), thereby potentially influencing the development of cardiovascular (CV) diseases. As the principal transport protein for free fatty acids (FFAs), HSA may have its ACE-inhibitory capacity modified by its FFA cargo and, through this mechanism, may also affect CV disease risk. We therefore tested the hypothesis that the composition of HSA-bound FFAs determines the magnitude of endogenous ACE inhibition. Methods: We quantified endogenous ACE inhibition and examined the effect of FFA concentration on this inhibition in clinical patients (n = 161 and n = 101, respectively). We measured the effects of HSA treated with saturated, monounsaturated, and polyunsaturated FFAs, as well as FFA-free HSA, on recombinant ACE and on tissue ACE. Results: Endogenous ACE inhibition was stronger in patients with higher serum HSA concentrations (Spearman’s rho = 0.422, 95% CI 0.281–0.544, p < 0.001), whereas total FFA concentration was not associated with endogenous ACE inhibition (Spearman’s rho = 0.088, p = 0.38, n = 101). However, removal of free fatty acids substantially worsened the ACE-inhibitory effect of HSA on recombinant ACE (charcoal-treated HSA: IC₅₀ = 23.24 [19.40–29.78] g/L vs. control HSA: 7.84 [6.58–9.75] g/L, p < 0.001) and on tissue ACE isolated from lung, heart, and lymph node. FFA chain length, degree and position of unsaturation, and cis/trans configuration all differentially modulated endogenous ACE inhibition. Among saturated fatty acids, stearic acid (IC₅₀ = 7.98 [7.04–9.23] g/L), and among omega-3 and omega-6 fatty acids, α-linolenic (IC₅₀ = 5.60 [4.28–6.15] g/L) and γ-linolenic acids (IC₅₀ = 5.09 [4.28–6.15] g/L) produced the greatest enhancement of the ACE-inhibitory capacity of HSA. Conclusions: The present results indicate that HSA concentration relates to endogenous ACE inhibition in serum, and in vitro experiments demonstrate that HSA-bound FFAs can modulate HSA-mediated ACE inhibition, a mechanism that may be relevant to cardiovascular physiology and disease. Full article

Background: Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication with limited therapeutic options. Jaceosidin (JAC), a natural flavonoid from Folium Artemisiae Argyi, shows potential in cardiovascular diseases, but its role and mechanism in SIMD remain unclear. This study aims to investigate the protective effects of JAC against SIMD and explore the underlying molecular mechanisms. Methods: In vitro, AC16 human cardiomyocytes were stimulated with TNF-α and treated with JAC. Cell viability and apoptosis were assessed using CCK−8 and flow cytometry, respectively. Transcriptomic and metabolomic analyses were performed to identify altered pathways. Molecular docking evaluated JAC’s interaction with SIRT2. The SIRT2 inhibitor AGK2 was used to validate its role. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) determined H3K18la enrichment on target gene promoters. In vivo, a murine SIMD model was established via LPS injection, and cardiac function was evaluated by echocardiography. Serum markers (cTnT, CK−MB) and myocardial lactylation levels were measured. Results: JAC significantly attenuated TNF-α−induced injury in AC16 cells by enhancing viability and reducing apoptosis. Multi-omics analyses revealed JAC suppressed glycolysis and lactate production. JAC specifically inhibited histone H3K18 lactylation (H3K18la), and molecular docking indicated strong binding affinity with SIRT2. AGK2 treatment reversed JAC-mediated suppression of H3K18la. ChIP-qPCR confirmed H3K18la directly regulates IL-6, BAX, and BCL-2 expression. In vivo, JAC improved cardiac function (LVEF, LVFS, LVDd, LVDs), reduced serum cTnT and CK−MB levels, and decreased myocardial H3K18la in LPS−treated mice. Conclusions: JAC alleviates SIMD by activating SIRT2, which inhibits H3K18la, thereby modulating inflammatory and apoptotic pathways. This study identifies JAC as a novel metabolic-epigenetic therapeutic agent for SIMD. Full article

Background/Objectives: Hypertension represents a leading contributor to cardiovascular disorders and premature mortality. Given the pervasive nature of adverse effects associated with current angiotensin-converting enzyme inhibitors (ACEIs), there is a significant interest in identifying novel bioactive lead compounds from natural sources. This study identifies, for the first time, three novel angiotensin-converting enzyme (ACE) inhibitory peptides released from Bungarus multicinctus (BM) via simulated gastrointestinal digestion (SGD). Methods: Active fractions were enriched by ultrafiltration and subjected to stability assessment. The peptide sequences were then determined using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and bioinformatics tools, followed by chemical synthesis. Finally, the inhibitory mechanism was investigated using kinetic analysis and molecular docking. Results: The intestinal digest exhibited potent ACE inhibition, with the <5 kDa fraction achieving 79% inhibition at 1 mg/mL and demonstrating favorable stability under varying temperatures, pH, and ionic strengths. Molecular docking revealed strong binding (affinity < −9.9 kcal/mol) of the peptides PPSPPRW, WGFTKF, and PSLFPPRL to key ACE residues—Tyr523, His513, and Arg522—via hydrogen and hydrophobic interactions. Enzyme kinetics characterized PPSPPRW and WGFTKF as competitive inhibitors, and PSLFPPRL as mixed type. The peptides demonstrated acceptable cell viability at lower concentrations, establishing a preliminary safety window for therapeutic application. Conclusions: These findings establish BM as a valuable source of stable, bioactive ACE-inhibitory peptides (ACEIPs) acting as promising lead compounds for antihypertensive therapies. Full article

Background: Emerging immune-evasive viral variants threaten the efficacy of current vaccines, underscoring the need for strategies that elicit broad and durable protection. Heterologous prime–boost regimens combining distinct vaccine platforms can enhance humoral and cellular immunity through complementary mechanisms. Methods: Using an intramuscular immunization scheme aligned with clinical vaccination practice, CD-1 mice received homologous or heterologous prime–boost regimens combining a replication-deficient Orf virus (Parapoxvirus orf, ORFV)-based spike vaccine (ORFV-S) with the licensed adjuvanted recombinant protein vaccine VidPrevtyn Beta. Spike-specific humoral and cellular immune responses were assessed. Results: ORFV-S alone induced potent and broad spike-specific IgG responses and achieved the strongest ACE2-binding inhibition across variants of concern. ORFV-S priming followed by VidPrevtyn Beta boosting markedly enhanced the magnitude and cross-variant breadth of antibody responses compared with homologous protein vaccination. Both homologous ORFV-S and heterologous regimens incorporating ORFV-S elicited strong CD4⁺ and CD8⁺ T-cell responses, whereas VidPrevtyn Beta alone induced only modest T-cell activity, demonstrating that ORFV-S effectively complements protein-based vaccines. Conclusions: The ORFV-S vector represents a potent vaccine platform capable of inducing broad humoral and cellular immunity. Its use in heterologous prime–boost combinations enhances both antibody magnitude and breadth beyond homologous protein vaccination, supporting its application in vaccination strategies against evolving viral pathogens. Full article

Overactivation of the renin–angiotensin–aldosterone system (RAAS) promotes haemodynamic overload, inflammation, and fibrosis in the heart and kidneys. Recently, sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone therapy in cardiorenal protection. Emerging data indicate that adding SGLT2 inhibitors to angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, or angiotensin receptor–neprilysin inhibitors confers additional cardiorenal protection, yet their mechanistic basis and optimal clinical use in cardiovascular (CV) disease remain unclear. This review will integrate pre-clinical and clinical evidence on dual RAAS/SGLT2 modulation in CV disease, providing mechanistic insight into dual therapy. The review will finally outline priorities for future translational and outcome studies. Clinically, adding SGLT2 inhibitors to RAAS-based therapy reduces heart failure hospitalizations and slows kidney disease progression without new safety liabilities in type 2 diabetes, heart failure, and chronic kidney disease. Mechanistically, SGLT2 inhibition restores tubuloglomerular feedback and constricts the afferent arteriole; RAAS blockade dilates the efferent arteriole, and together, they lower intraglomerular pressure. Both classes also reduce oxidative stress, inflammatory signalling, and pro-fibrotic pathways, with SGLT2 inhibitors in several settings shifting RAAS balance toward the protective ACE2/angiotensin-(1–7)/Mas receptor axis. Key gaps include the scarcity of adequately powered trials designed to test combination therapy versus either component alone, limited evidence on timing and sequencing, incomplete characterization in high-risk groups, and mechanistic insight limited by study design in animal and cell models. Collectively, current data support layering SGLT2 inhibitors onto RAAS-based therapy, while definitive evidence from dedicated clinical trials is awaited. Full article

Inflammation plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS), contributing to plaque instability, thrombosis, and myocardial injury. This review aims to comprehensively examine the inflammatory mechanisms underlying ACS and evaluate current and emerging anti-inflammatory therapeutic strategies. We conducted a comprehensive literature review examining the role of inflammatory pathways in ACS pathophysiology, including innate and adaptive immune responses, key inflammatory mediators, and cellular mechanisms. We analyzed current evidence for anti-inflammatory therapies and their clinical outcomes in ACS management. Inflammatory processes in ACS involve complex interactions between innate immune cells (neutrophils, macrophages, monocytes) and adaptive immune cells (T lymphocytes, B cells). Key mechanisms include neutrophil extracellular trap (NET) formation, macrophage polarization, T cell subset imbalances (Th1/Th17 predominance with regulatory T cell dysfunction), and complement activation. Inflammatory biomarkers such as C-reactive protein, interleukin-6, and NET-specific markers demonstrate prognostic value. Anti-inflammatory therapies including colchicine, canakinumab (IL-1β inhibition), and methotrexate have shown cardiovascular benefits in clinical trials. Emerging targets include NET inhibition, T cell modulation, and precision inflammatory profiling approaches. Inflammation represents a critical therapeutic target in ACS beyond traditional risk factor modification. While colchicine and IL-1β inhibition have demonstrated clinical efficacy, future strategies should focus on precision medicine approaches targeting specific inflammatory pathways based on individual patient profiles. Integration of anti-inflammatory therapy with lipid management and antithrombotic strategies offers promise for improving ACS outcomes through comprehensive targeting of the multifactorial pathophysiology underlying coronary artery disease. Full article

Drug-coated balloons (DCBs) have emerged as an alternative to drug-eluting stents (DESs) in percutaneous coronary intervention, delivering antiproliferative drugs without leaving a permanent implant. This review provides a comparative analysis of sirolimus-coated DCBs (DCB-S), paclitaxel-coated DCBs (DCB-P), and DESs across key scenarios: de novo coronary lesions in chronic coronary syndrome (CCS), acute coronary syndromes (ACS), and in-stent restenosis (ISR). We discuss late lumen loss (LLL), target lesion/vessel revascularization (TLR/TVR), vessel patency, and major adverse cardiac events (MACE) outcomes, along with current guidelines and emerging indications for DCB-S. We also examine pharmacological differences between sirolimus and paclitaxel (mechanisms of action, tissue uptake, and healing profiles), trial methodologies, and recent innovations in DCB technology. Across stable de novo lesions (especially small vessels and high bleeding-risk patients), multiple trials show DCB-P can achieve non-inferior clinical outcomes to DES. Early data suggest newer DCB-S may likewise match DES outcomes in broader populations. In ACS, DCB-only strategies have demonstrated feasibility and safety in carefully selected lesions without heavy thrombus, with randomized studies like REVELATION (STEMI) showing non-inferior fractional flow reserve and low revascularization rates compared to DES. For ISR, DCB-P is an established Class I treatment in both BMS-ISR and DES-ISR, yielding similar or lower TLR rates than repeat stenting. DCB-S are now being evaluated as an alternative in ISR, aiming to avoid additional stent layers. Contemporary guidelines endorse DCB use in ISR and small vessels, and experts anticipate expanding indications as evidence grows. Sirolimus and paclitaxel differ in antiproliferative mechanisms and pharmacokinetics—sirolimus (cytostatic, mTOR inhibition) may offer faster endothelial recovery, whereas paclitaxel’s high lipophilicity ensures sustained arterial wall retention. Technological advances (e.g., phospholipid micro-reservoirs for sirolimus) are enhancing drug transfer and addressing prior limitations. In summary, DCB-P and DCB-S now represent viable alternatives to DES in specific scenarios, especially where “leaving nothing behind” could reduce long-term complications. Ongoing large randomized trials, such as SELUTION DeNovo, currently available as conference-presented data, together with longer-term follow-up will further clarify the optimal niches for DCB-S versus DCB-P and DES. Full article

SARS-CoV-2, the causative agent of COVID-19, has led to over seven million deaths worldwide prior to May 2025. Despite widespread vaccination programs, COVID-19 remains a persistent global health challenge, underscoring the urgent need for new therapeutic approaches. Orientin is a flavonoid with reported antiviral activity, though its potential against SARS-CoV-2 remains poorly explored. This study aimed to investigate whether Orientin interacts with the viral Spike protein and impacts viral replication. Molecular docking simulations using DockThor were employed to predict the binding affinity between Orientin and the receptor-binding domain (RBD) of the Spike protein. Fluorescence spectroscopy assays were performed to assess direct interactions between Orientin and the trimeric form of the Spike protein. Additionally, cytotoxicity and viral replication assays were carried out in Vero cells to evaluate Orientin’s antiviral effects. Docking results indicated that Orientin likely binds to key RBD residues involved in ACE2 receptor recognition. Spectroscopic analyses showed a decrease in intrinsic tryptophan fluorescence, suggesting direct interaction. Orientin demonstrated no cytotoxicity in Vero cells and exhibited moderate inhibition of viral replication. These findings suggest that Orientin interacts with critical regions of the Spike protein and may act as a moderate in vitro inhibitor of SARS-CoV-2, warranting further investigation into its therapeutic potential. Full article

The COVID-19 pandemic exposed critical vulnerabilities in single-target antiviral strategies, highlighting the urgent need for multi-mechanism therapeutic approaches against emerging viral threats. Here, we present an integrated computational framework systematically evaluating natural fatty acids as potential dual ACE2 (Angiotension Converting Enzyme 2)-inflammatory modulators; compounds simultaneously disrupting SARS-CoV-2 viral entry through allosteric ACE2 binding while suppressing host inflammatory cascades; through allosteric binding mechanisms rather than conventional competitive inhibition. Using molecular docking across eight ACE2 regions, 100 ns molecular dynamics simulations, MM/PBSA free energy calculations, and multivariate statistical analysis (PCA/LDA), we computationally assessed nine naturally occurring fatty acids representing saturated, monounsaturated, and polyunsaturated classes. Hierarchical dynamics analysis identified three distinct binding regimes spanning fast (τ < 50 ns) to slow (τ > 150 ns) timescales, with unsaturated fatty acids demonstrating superior binding affinities (ΔG = −6.85 ± 0.27 kcal/mol vs. −6.65 ± 0.25 kcal/mol for saturated analogs, p = 0.002). Arachidonic acid achieved optimal SwissDock affinity (−7.28 kcal/mol), while oleic acid exhibited top-ranked predicted binding affinity within the computational hierarchy (ΔG_bind = −24.12 ± 7.42 kcal/mol), establishing relative prioritization for experimental validation rather than absolute affinity quantification. Energetic decomposition identified van der Waals interactions as primary binding drivers (65–80% contribution), complemented by hydrogen bonds as transient directional anchors. Comprehensive ADMET profiling predicted favorable safety profiles compared to synthetic antivirals, with ω-3 fatty acids showing minimal nephrotoxicity risks while maintaining excellent intestinal absorption (>91%). Multi-platform bioactivity analysis identified convergent anti-inflammatory mechanisms through eicosanoid pathway modulation and kinase inhibition. This computational investigation positions natural fatty acids as promising candidates for experimental validation in next-generation pandemic preparedness strategies, integrating potential therapeutic efficacy with sustainable sourcing. The framework is generalizable to fatty acids from diverse biological origins. Full article

This study aimed to evaluate the health-promoting potential of wafers enriched with almond peel as a natural source of bioactive compounds. Wafers were prepared with different concentrations of almond peel (1%, 2%, 5%, and 10%) and analyzed to determine their phenolic content, antioxidant capacity, enzyme inhibition, anticancer properties, and sensory properties. Three types of samples were examined: buffer extracts (PBS), ethanol extracts (EtOH), and samples obtained after in vitro digestion (TRW). Antioxidant properties were assessed using ABTS^+• and DPPH^• assays, as well as Fe²⁺ chelation and reducing power tests. Enzyme inhibitory activities against LOX, COX, ACE, and lipase, and antiproliferative potential of hydrolysates toward AGS and HT-29 cell lines were also determined. The highest levels of total phenolic, flavonoids, and phenolic acids were found in digested samples of wafers with 10% almond peel addition (W10), reaching 2.243 mg/g, 6.153 µg/g, and 0.554 mg/g, respectively, while PBS extracts of control wafers (WK) showed the lowest values (0.159 mg/g, 0.146 µg/g, and 0.316 mg/g, respectively). The digested W10 samples showed the strongest antioxidant and enzyme inhibitory activities. The wafer hydrolysates caused only a modest reduction in HT-29 cell viability, and this effect was observed exclusively at the higher concentrations tested. The results confirm that almond peel enhances the health-promoting properties of wafers. Full article