Development of donkey milk fermented with Lactococcus lactis subsp. lactis CECT 31096 and characterization of the antioxidant and antihypertensive activity.

Aryl-functionalized mono- and diketone curcumin derivatives inhibit SARS-CoV-2 Spike:ACE2 interactions.

The envelope-anchored trimeric spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates the attachment and entry of the virus within human cells by utilizing the angiotensin converting enzyme 2 (ACE2) as a receptor, present in the epithelial cells of the upper respiratory tract and lungs. The ACE2 interaction interface with the SARS-CoV-2 spike protein was utilized to design an ACE2-derived peptide sequence (FD11) that targeted the viral spike protein. It was found to be non-cell penetrating, while invivo studies revealed the non-cytotoxic nature of the peptide molecule. The minimum effective concentration of the peptide was found to be 10 μM with 95% cell viability in Vero E6 cell line. The IC50 of the peptide was found to be around 6.4 μM. Treatment of the peptide in SARS-CoV-2 infected Vero E6 cells was found to decrease the infectivity as compared to control. This presents a simple approach where host-pathogen protein interaction-interface derived peptides can be used for binding with substrate macromolecules to target and modulate pathogen infectivity.

Antiviral potential of galactose-binding lectin from Vatairea macrocarpa seeds against SARS-CoV-2.

Does ACE2 deficiency have a role in Parkinson's disease -exacerbated pulmonary fibrosis?

Patients with difficult to control hypertension (HTN) are often referred by general practitioners to specialized centers to estimate global cardiovascular (CV) risk profile, evaluate hypertension-mediated organ damage (HMOD), and optimize antihypertensive therapy. This referral provides a unique opportunity to analyse patients with high CV risk and HTN in a real-world setting, characterized by the rigorous adoption of uniform and state-of-the-art procedures by expert personnel. To examine (1) global CV risk profile, office and out-of-office blood pressure (BP) levels, and markers of HMOD in adult patients referred to a high-volume European Hypertension center; (2) to evaluate how these clinical parameters impact on the choice of different antihypertensive therapies. An observational, cross-sectional study was conducted in adult patients of both sexes, aged ≥ 18 years, with essential treated hypertension, who were consecutively evaluated at the Excellence Hypertension Center at Sant'Andrea Hospital in Rome, Italy. Office and out-of-office BP levels were measured, and different hypertension phenotypes were set according to European guidelines. CV risk profile was estimated according using SCORE2. Only patients with treated HTN were selected for the analysis and stratified according to antihypertensive therapies: (1) angiotensin receptor blockers (ARBs); (2) angiotensin converting enzyme (ACE) inhibitors; (3) other drugs (including diuretics, beta-blockers, calcium channel blockers, alpha-blockers, mineralocorticoid receptor antagonists). From an overall database of 11,168 outpatients, a total of 5,677 patients with treated HTN were analysed (46.3% females, age 63.6 ± 13.1 years, BMI 27.4 ± 4.8kg/m2, office BP 140.6 ± 17.5/85.5 ± 11.5 mmHg, 24-hour BP 128.7 ± 13.7/77.2 ± 9.7 mmHg, SCORE2 5.4 ± 4.3%). Among these, 52.9% were treated with ARBs, 30.2% with ACE inhibitors and 17.0% with other drugs. Patients treated with ARBs were more frequently males, and significantly older, had more frequently obesity (P < 0.001), dyslipidaemia (p < 0.001), and diabetes (p < 0.001) than those treated with other drug classes. They also had more frequently CV comorbidities (P < 0.001) and resistant HTN (P < 0.001). They received more BP lowering agents (P < 0.001), being more frequently treated with triple (P < 0.001), quadruple (P < 0.001), or more complex (P < 0.001) combination therapies. Comparable office and out-of-office BP control were recorded between patients treated with ARBs and those patients managed with either ACE inhibitors or other drugs. Among adult outpatients referred to an excellence hypertension center, the majority were treated with ARBs, alone or in combination therapies. ARB-treated patients presented more frequently CV risk factors, comorbidities, and difficult-to-treat HTN.

The antihypertensive and cardiovascular effects of lawsone methyl ether in high salt-induced hypertensive rats are mediated through multiple pathways.

Olive (Olea europaea L.) byproducts, such as seeds and leaves, are abundant agro-industrial residues and represent underexplored protein sources with potential health relevance. However, the repertoire of bioactive peptides that may be released from olive proteins during gastrointestinal digestion remains poorly characterized. This study aimed to perform a comprehensive in silico screening to identify and characterize multifunctional bioactive peptides potentially released from olive proteins during gastrointestinal digestion. Five UniProt-reviewed Olea europaea L. proteins (annotation score 5/5) were selected as curated reference sequences and subjected to simulated gastrointestinal digestion using pepsin, trypsin, and chymotrypsin. The resulting peptides were filtered and evaluated using a battery of in silico tools to predict physicochemical properties, bioactivity, and bioavailability-related features. Molecular docking analyses were conducted to explore peptide-target interaction patterns. Simulated digestion generated a diverse peptide pool, from which a reduced set of high-ranking candidates was prioritized based on predicted bioactivity. Correlation analyses suggested that structural features such as amphipathicity and steric accessibility were associated with stronger predicted activities. Molecular docking analyses indicated stable and target-specific interaction patterns with proteins involved in cardiometabolic and inflammatory pathways, supporting the prioritization of selected peptide candidates interacting with angiotensin-converting enzyme, dipeptidyl peptidase IV, and the TLR4/MD2 complex. This study provides an integrated in silico screening and prioritization framework to identify olive-derived peptide candidates with predicted multifunctional bioactivity. The findings offer a rational basis to guide future experimental validation and support the valorization of olive byproducts as sources of functional food ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Benzoylaconitine and ginsenoside Rb1 synergistically attenuate cardiac remodeling through dual enhancement of DLG1-dependent mitochondrial integrity.

Evaluating Kidney Responses to Angiotensin-Converting Enzyme Inhibition at the Single-Cell Level.

Chronic allograft dysfunction (CAD) remains a leading cause of graft loss after kidney transplantation. Dapagliflozin (DAPA) has shown renal and cardiometabolic benefits in nontransplanted patients with chronic kidney disease. However, data on recipients with CAD are lacking. Adult kidney transplant recipients (n = 208), with estimated glomerular filtration rate (eGFR) 25-45 mL/min/1.73 m 2 or 45-60 mL/min/1.73 m 2 with ≥10% annual decline, were randomized to receive DAPA 10 mg/d or placebo for 12 mo. The outcomes were differences in eGFR, in eGFR slopes, proteinuria, blood pressure, body mass index (BMI), and safety. There was no difference in eGFR between groups ( P = 0.611). However, at month 12, eGFR was higher in the PLACEBO group (n = 102; 39.4 ± 0.9 vs 36.5 ± 0.9 mL/min/1.73 m 2 ( P = 0.029). In the DAPA group (n = 106), the least square means (LSM) of eGFR slopes was -0.86 ± 0.65 mL/min/1.73 m 2 at the third month while remaining at -0.75 ± 0.65 mL/min/1.73 m 2 at 12 mo. The PLACEBO group presented an LSM slope of -0.34 ± 067 mL/min/1.73 m 2 at 3 mo and +0.51 ± 66 mL/min/1.73 m 2 at 12 mo. In a per-protocol analysis, patients in the DAPA group (n = 86) under angiotensin-converting enzyme inhibitor/ angiotensin receptor blockers (n = 23) did not present an eGFR dip, but those not under angiotensin-converting enzyme inhibitor/ angiotensin receptor blockers (n = 63) did. DAPA reduced proteinuria from 267 to 84 mg/g ( P < 0.001), body weight by 2 kg ( P = 0.02), BMI by 0.7 kg/m 2 ( P = 0.023), systolic blood pressure by 7 mm Hg ( P = 0.014), diastolic blood pressure from baseline to 9 mo (80.5 ± 1.2 vs 76.8 ± 1.2 mm Hg, P = 0.021), and glycated hemoglobin in patients with diabetes by 0.5% ( P = 0.04). The incidence of serious adverse events did not differ between groups. In kidney transplant recipients with CAD, DAPA did not improve eGFR compared with placebo, but presented reductions in proteinuria, blood pressure, BMI, and glycated hemoglobin, with acceptable safety.

Allosteric Targeting of the ACE2 Dimer Interface by a Medium-sized Compound Inhibits SARS-CoV-2 Entry.

Bladder cancer (BC) is one of the most frequent malignancies of the urinary tract. This study aimed to investigate the association between angiotensin-converting enzyme (ACE) I/D polymorphism (rs1799752) and bladder cancer risk in Egyptian patients. Bladder cancer cases (n = 140) were diagnosed based on cystoscopy and confirmed by histopathological examination of biopsies. Fifty sex- and age-matched healthy individuals served as controls. Peripheral blood was used to extract the genomic DNA, and the ACE I/D (rs1799752) polymorphism was genotyped using polymerase chain reaction (PCR). Genotype frequencies were comparable between groups (II:12% vs. 11.4%, ID: 76% vs. 74%, and DD: 12% vs14.3% in control and BC patients, respectively), with no significant difference in allele or genotype distributions (co-dominant model DD vs. II: OR 1.25, 95%CI 0.34-4.63, p = 0.751). However, within the patient group, the heterozygous genotype (ID) was significantly more prevalent in high grade tumors (P = 0.0177), muscle-invasive BC (MIBC, p = 0.0042), and poor prognosis cases (high grade + MIBC, P < 0.0017). The over-dominant model (ID vs. II + DD) showed a strong association with poor prognosis (OR = 4.8, 95%CI 1.96-11.78, p < 0.001). A trend toward higher ID frequency that did not reach statistical significance was observed in advanced stages (T3/T4, p = 0.058). The ID genotype is strongly linked to the carcinogenesis of BC and with the poor prognosis, indicating its possible role as a predictive biomarker for risk assessment and progression in this population.

Introduction. Acute massive blood loss and hemorrhagic shock remain major challenges for modern military medicine, accounting for over 90% of preventable battlefield deaths. Traditional methods of monitoring vital signs often prove ineffective in compensated conditions, when blood pressure and heart rate remain stable until sudden decompensation and the loss of more than 40% of circulating blood volume (CBV). Aim. This study aimed to systematize data on genetic markers that determine individual tolerance to hypovolemia and to justify their integration into digital predictive monitoring systems to optimize evacuation logistics. Methods. The study methodology included a comprehensive analysis of scientific publications from the PubMed, Scopus, and Google Scholar databases published between 2020 and 2026, as well as a review of current Tactical Combat Casualty Care (TCCC) clinical guidelines. Results. The analysis revealed that the population of soldiers is heterogeneous in terms of compensatory capacity, with groups demonstrating high tolerance (HT) and low tolerance (LT) identified. The genetic determinants of this distribution include polymorphisms in genes of the renin-angiotensin-aldosterone system (RAAS), specifically variations in angiotensin-converting enzyme (ACE) and angiotensin II receptor type 1 (AGTR1). Conclusions. The limitations of using genetic data in field conditions are discussed, and it is argued that the integration of molecular markers into tactical medicine is possible only after large-scale clinical validation and currently represents a promising theoretical direction for the development of long-term care protocols.

Comparative peptidomics of four wasp venoms reveals extensive peptide diversity, proteolytic patterns, and predicted bioactivities.

Antihypertensive treatments, including diuretics and beta/calcium channel blockers, are associated with a range of adverse effects. Naturally sourced ACE inhibitors may serve as viable alternatives to synthetic medications. Various peptides derived from plants have been assessed for their ACE inhibitory properties through both in vivo and in vitro studies. The objective of this research was to evaluate the ACE inhibitory activity of seed-protein (muskmelon, watermelon, and sunflower) hydrolysates generated using different proteases. ACE was extracted from sheep lung tissue, while protein from the mentioned seeds was isolated and hydrolysed using pepsin, trypsin, and crude enzyme from the stem of Wrightia tinctoria. Tricine-SDS PAGE (16%) was conducted to observe the nature of hydrolysis. The method by Cushman and Cheung was used to examine ACE inhibition. The results were compared across different sources and enzymatic treatments. Muskmelon hydrolysate treated with W. tinctoria enzyme exhibited the highest ACE inhibition at 85.17% ± 0.39 after 3 h of incubation (p <0.001), resembling the inhibitory effects observed in the positive control, Lisinopril, at 86.55% ± 1.15. The enhanced ACE inhibitory activity observed in muskmelon seed hydrolysate suggests the generation of potent bioactive peptides through enzymatic hydrolysis. Differences in inhibitory potential among seed-derived hydrolysates may be attributed to variations in protein composition and peptide profiles resulting from the use of different proteases. Muskmelon seed protein hydrolysate generated using W. tinctoria demonstrated strong in vitro ACE inhibitory activity, which was comparable to that of Lisinopril, a standard drug for ACE inhibition. These findings highlight its potential as a natural source of bioactive peptides for the management of hypertension.

Multiple sclerosis (MS) is an immune-mediated and demyelinating disease affecting oligodendrocytes, leading to neurodegeneration. Immunocompromised individuals may have a reduced antibody response after vaccination, and this insufficient immune response in COVID-19 individuals might contribute to the pathophysiology of MS. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds the angiotensin-converting enzyme 2 (ACE2) to entry into the host's cell and infect human cells. Evaluation of the effects of drugs for the treatment of MS, such as fingolimod, cladribine, dimethyl fumarate, and teriflunomide, on the expression of ACE2 in human lung carcinoma cell lines. We used Calu-3 human lung adenocarcinoma cells, physiologically expressing the ACE2 gene, and A549-hACE2-TMPRSS2 human lung carcinoma cells, overexpressing the human ACE2 gene, and challenged them with the pro-inflammatory interleukin-1β (IL-1β) in the presence or absence of MS drugs, and assessed ACE2 mRNA and protein levels. MS drugs affected ACE2 mRNA and protein levels differently in Calu-3 and A549-hACE2-TMPRSS2 cells. Fingolimod (50 nM) significantly reduced ACE2 protein levels under inflammatory conditions in Calu-3 cells. Cladribine reduced ACE2 protein levels in A549-hACE2-TMPRSS2 cells. Dimethyl fumarate increased ACE2 protein levels in Calu-3 cells under both basal and pro-inflammatory conditions. Teriflunomide increased ACE2 protein levels in Calu-3 cells and ACE2 mRNA levels in A549-hACE2-TMPRSS2 cells, both in basal and pro-inflammatory conditions. We incubated cells with drug concentrations similar to those found in the plasma of relapsing-remitting MS patients treated with disease-modifying drugs (DMD), although they act via different mechanisms. Fingolimod acts on sphingosine-1-phosphate receptors and inhibiting class 1 histone deacetylase could suppress ACE2 expression, independently of its immunosuppressive action, or might act at post-transcriptional levels. Fingolimod also stimulates the secretion of neurotrophic factors in the CNS and exerts neuroprotective effects. Data suggest that drugs used in the treatment of MS can modify ACE2 expression; specifically, fingolimod reduces ACE2 expression and may have a protective role against SARS-CoV-2 infection.

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes. Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD-ACE2 complex, play key roles in virus-receptor engagement. Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2. In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

Fabry disease(FD) is a rare X-linked lysosomal storage disorder associated with progressive multiorgan damage. Because perceptual differences between patients and clinicians regarding diagnosis and treatment can contribute to suboptimal management. We aimed to compare the perceptions of patients with FD and nephrologists in South Korea regarding the diagnostic process, treatment decisions, and genetic counseling. We conducted a cross-sectional survey enrolling 25 patients with FD, 33 patients with chronic kidney disease (without a known genetic etiology), and 27 nephrologists. The surveys assessed diagnostic testing considerations, treatment preferences, attitudes toward angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), and genetic counseling priorities. All three groups prioritized diagnostic accuracy, while both patient groups emphasized procedural concerns (e.g., pain from blood draw and blood loss risk) significantly more than clinicians. A perception gap existed regarding ACEi/ARB therapy: 92.3% of clinicians believed in its renoprotective effect, whereas only 26.1% of patients agreed to treatment without strong evidence. Both groups agreed on the importance of genetic counseling for family screening.Regarding treatment, 96% of patients and 81.5% of clinicians preferred oral over injectable enzyme replacement therapy. These significant perception gaps highlight the need for improved patient education and shared decision-making to enhance treatment adherence and clinical outcomes in FD management.

The effect of ARNI and SGLT2i therapies on the inflammasome pathway in myocardial heart transplantation biobank samples