Search Results (1,035)

This study investigated white wastewater (WW) as a potential source of antimicrobial peptides, employing hydrolysis with Pronase E followed by separation through electrodialysis with ultrafiltration membranes (EDUF) to increase the value of dairy components within a circular economy framework. The WW hydrolysate was divided into two key fractions: the cationic recovery compartment (CRC) and the anionic recovery compartment (ARC). The EDUF process effectively separated peptides, with peptide migration rates reaching 6.83 ± 0.59 g/m²·h for CRC and 6.19 ± 0.66 g/m²·h for ARC. Furthermore, relative energy consumption (REC) increased from 1.15 Wh/g to 2.05 Wh/g over three hours, in line with trends observed in recent studies on electrodialysis energy use. Although 29 peptides were statistically selected from the CRC (20) and ARC (9) compartments, no antibacterial activity was exhibited against Clostridium tyrobutyricum and Pseudomonas aeruginosa; however, antifungal activity was observed in the feed and ARC compartments. Peptides from the ARC demonstrated activity against Mucor racemosus (MIC = 0.156 mg/mL) and showed selective antifungal effects against Penicillium commune (MIC = 0.156 mg/mL). This innovative approach paves the way for improving the recovery of anionic peptides through further optimization of the EDUF process. Future perspectives include synthesizing selected peptides and evaluating their antifungal efficacy against these and other microbial strains, offering exciting potential for applications in food preservation and beyond. Full article

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with increasing prevalence and substantial morbidity and mortality. Recent advances in pharmacotherapy have transformed its management. This review summarizes current evidence supporting the use of sodium–glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, alongside selected use of angiotensin receptor–neprilysin inhibitors. Emphasis is placed on early initiation of disease-modifying therapies, phenotypic tailoring, and comorbidity-targeted strategies, especially in obese and diabetic patients. Together, these approaches define a new era of guideline-directed, personalized care for patients with HFpEF. Full article

Background/Objectives: Real-world evidence shows alarmingly suboptimal utilization of guideline directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). One of the barriers of GDMT implementation appears to be concerns about the potential development of drug-related adverse events (AEs), particularly in high-risk patients. This study aimed to evaluate whether advanced HFrEF (AHF) patients can be up-titrated safely and whether AHF predisposes individuals to the occurrence of putatively drug-related AEs. Methods: A total of 373 HFrEF patients with documented baseline, 2 months, and 12 months visits were analyzed for utilization and target dosages (TDs) of HF drugs. Successful up-titration and AEs were evaluated for different stages of HF reflected by N-terminal pro-B type natriuretic peptide (NT-proBNP) (<1000 pg/mL, 1000–2000 pg/mL, >2000 pg/mL). Results: A stepwise increase in HF medications was observed for all drug classes during follow-up. At 12 months, 73%, 75%, 62%, 86%, and 45% of patients received ≥90% of TDs of beta-blockers (BBs), renin–angiotensin system inhibitors (RASis), mineralocorticoid receptor antagonists (MRAs), sodium–glucose cotransporter-2 inhibitors (SGLT2 i), and triple-therapy, respectively. Predictors of successful up-titration in logistic regression were baseline HF drug TDs, estimated glomerular filtration rate (eGFR), and potassium, but not NT-proBNP or age. The development of AEs was rare, with hyperkalemia as the most common event (34% at 12 months). AEs were comparable in all stages of HF. However, the development of hyperkalemia was more frequent in patients with higher NT-proBNP and also accounted for most cases of incomplete up-titration. Conclusions: This study suggests that with dedicated protocols and frequent visits, GDMT can be successfully implemented across all stages of HFrEF, including patients with AHF. Full article

Medicinal plants and animal-derived proteins represent valuable natural sources of bioactive components with pharmaceutical potential. Whilst some medicinal plants and animal-derived proteins also offer rich sources of anticoagulant bioactive peptides, their development faces multiple challenges: anticoagulant evaluation relies on single-parameter assays with limited reliability, native proteins demonstrate suboptimal activity without enzymatic treatment, and few researchers investigate bioavailable peptides. Our study establishes an innovative framework using the leech as a case study to overcome these barriers. A novel anticoagulant evaluation model was first established with the Critic-G1 weighting method. And we optimized the enzymatically hydrolyzed extracts with high activity using Box–Behnken response surface methodology. Subsequently, the everted gut sac model was implemented to simulate intestinal absorption and screen for absorbable peptide fractions. Furthermore, peptidomics was employed to identify the bioactive peptides. Lastly, we identified the bioactivity using anticoagulation assays. Results indicated that the optimal hydrolysis conditions were achieved with trypsin at 50.48 °C, an enzyme-to-substrate ratio of 6.78%, 7.51 h, and pH of 8.06. The peptide DLRWM was identified through integrated peptidomics and molecular docking approaches, with subsequent activity validation demonstrating its potent anticoagulant effects. This study has successfully identified a novel anticoagulant peptide (DLRWM) with confirmed intestinal absorption properties and provides a template for unlocking the pharmaceutical potential of medicinal animal proteins. Full article

In order to innovatively develop high-activity ACE inhibitory peptides from edible fungi, the conditions for a double-enzymatic hydrolysis preparation of ACE inhibitory peptides from Flammulina velutipes were optimized by response surface methodology. After purification by macroporous resin, gel chromatography, and RP-HPLC, a crude peptide fraction was obtained; its ACE inhibition rate was 85.73 ± 0.95% (IC₅₀ = 0.83 ± 0.09 mg/mL). Based on LC-MS/MS sequencing, the four novel peptides, namely, FAGGP, FDGY, FHPGY, and WADP, were screened by computer analysis and molecular docking technology. The four peptides exhibited a binding energy between −9.4 and −10.3 kcal/mol, and formed hydrogen bonds with Tyr523, Ala354, and Glu384 in the S1 pocket, Tyr520 and His353 in the S2 pocket, and His383 in the HEXXH zinc-coordinating motif of ACE, indicating their good affinity with the ACE active site. The IC₅₀ values of the four ACE inhibitory peptides were 29.17, 91.55, 14.79, and 41.27 μM, respectively, suggesting that these peptides could potentially contribute to the development of new antihypertensive products. Full article

Acinetobacter baumannii is a multidrug-resistant bacterium that has gained significant attention in recent years due to its involvement in a growing number of hospital-acquired infections. The World Health Organization has classified it as a critical priority pathogen, underscoring the urgent need for new therapeutic strategies. Post-translational modifications (PTMs), such as phosphorylation, play essential roles in various bacterial processes, including antibiotic resistance, virulence or biofilm formation. Although proteomics has increasingly enabled their characterization, the identification of phosphorylated peptides remains challenging, primarily due to the enrichment procedures. In this study, we focused on characterizing serine, threonine, and tyrosine phosphorylation in the A. baumannii ATCC 17978 strain. We optimized three parameters for phosphopeptide enrichment using titanium dioxide (TiO₂) beads (number of enrichment fractions between the phosphopeptides and TiO₂ beads, the quantity peptides and type of loading buffer) to determine the most effective conditions for maximizing phosphopeptide identification. Using this optimized protocol, we identified 384 unique phosphorylation sites across 241 proteins, including 260 novel phosphosites previously unreported in A. baumannii. Several of these phosphorylated proteins are involved in critical bacterial processes such as antimicrobial resistance, biofilm formation or pathogenicity. We discuss these proteins, focusing on the potential functional implications of their phosphorylation. Notably, we identified 34 phosphoproteins with phosphosites localized at functional sites, such as active sites, multimer interfaces, or domains important for structural integrity. Our findings significantly expand the current phosphoproteomic landscape of A. baumannii and support the hypothesis that PTMs, particularly phosphorylation, play a central regulatory role in its physiology and pathogenic potential. Full article

Background/Objectives: We aimed to identify the factors associated with clinically important changes in quality of life (QoL) of real-world heart failure (HF) patients. Methods: This is a single-centre, prospective cohort study including 419 patients at an HF clinic between January 2013 and February 2020. QoL was assessed regularly using Minnesota Living with Heart Failure Questionnaire (MLHFQ). We used five nested linear mixed-effects models to account for QoL measurements between patients and within-patient. Models were adjusted for time, sociodemographic factors, comorbidities, self-care adherence, and HF severity factors. Results: Median age was 78 years, 54.4% of patients were female, and 49.6% had left ventricle ejection fraction ≥ 50%. At baseline, 62.5% of patients were New York Heart Association (NYHA) class II. Median N-terminal-pro-B type natriuretic peptide level was 1454 pg/mL. Mean MLHFQ total score at baseline was 25 points (95%CI: 22.97–27.60). Having an implanted cardiac resynchronization therapy-pacemaker (CRT-P) was associated with moderate to large improvement in QoL (−13.55 points, 95%CI: −22.45–−4.65). NYHA class II and estimated glomerular filtration rate < 30 mL/min/1.73 m² were associated with small to moderate QoL deterioration (9.74 points, 95%CI: 6.74–12.75 and 5.82 points, 95%CI: 1.17–10.47, respectively). NYHA classes III or IV and a recent HF hospitalization were associated with large to very large QoL deterioration (28.39 points, 95%CI: 23.82–32.96; 60.59 points, 95%CI: 34.46–86.72; and 26.91 points, 95%CI: 21.80–32.03, respectively). Conclusions: CRT-P implantation, NYHA class and HF hospitalization are associated with the most clinically important QoL changes. Full article

Background: The antimicrobial peptides (AMPs) SET-M33L and SET-M33L-PEG were investigated against 10 clinical isolates of P. aeruginosa. Methods: Their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and minimum biofilm inhibitory concentrations (MBICs) were evaluated against tobramycin, ceftazidime, and polymyxin B. Results: MICs and MBCs were 7- to 100-fold lower than tobramycin, and 10- to 300-fold lower than ceftazidime. Fractional inhibitory concentration (FIC) indices showed an additive effect, while fractional bactericidal concentration (FBC) indices showed synergistic effects (FBC < 0.5) for most isolates. Conclusion: SET-M33L and SET-M33L-PEG are promising antimicrobial agents against strong biofilm-forming P. aeruginosa, including MDR isolates. Full article

Porcine intestinal mucosa hydrolysates (PIMHs) are by-products of heparin production obtained through a specific enzymatic hydrolysis process, which can theoretically generate bioactive peptides (BAPs). This study aimed to identify, characterize, and quantify BAPs in two Palbio products manufactured by Bioiberica S.A.U. (Palafolls, Spain), which are PIMH protein sources used for animal feed: Palbio^® HP (PHP) and Palbio^® 62 SP^® (P62). Using mass spectrometry (MS)-based peptidomics, we analyzed three samples from each product, fractionated based on molecular weight (<3 kDa, 3 to 10 kDa, and >10 kDa). The <3 kDa fraction was analyzed directly, while the other two fractions were enzymatically digested before MS analysis. The workflow identified 961 peptides in PHP and 1134 in P62. Subsequent bioinformatic analysis using public databases (APD2, StraPep, AHTPDB, and BIOPEP-UWM) led to the identification of six significant BAPs in both PHP and P62, with respective quantified amounts (pg peptide/μg sample): DAVEDLESVGK (0.1626, 0.1939), EGIPPDQQRLIFAGK (0.2637, 0.1852), TITLEVEPSDTIENVK (0.3594, 0.4327), TNVPRASVPDGFLS (1.4596, 0.1898), TNVPRASVPDGFLSEL (8.0500, 0.9224), and VHVVPDQLMAF (0.0310, 0.0054). The first three BAPs are related to antimicrobial activity, while the latter three are associated with cytokine/growth factor-like, antioxidant, and immunomodulatory activities. These bioactivities align with previously reported in vivo benefits observed in animal nutrition using Palbio products. Our findings demonstrate that PHP and P62 are valuable sources of BAPs, supporting their potential role in improving animal health and performance. Full article

A novel actinobacterial strain, designated E54^T, was isolated from a hyper-arid desert soil sample collected from the Kumtagh Desert in Dunhuang, Gansu Province, China. Phylogenetic analysis based on 16S rRNA gene sequences placed strain E54^T within the genus Lentzea, showing highest similarity to Lentzea waywayandensis DSM 44232^T (98.9%) and Lentzea flava NBRC 15743^T (98.5%). However, whole-genome comparisons revealed that the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between E54^T and these related strains were below the thresholds for species delineation. Strain E54^T exhibited typical morphological characteristics of the genus Lentzea, forming a branched substrate. It grew optimally at 28–30 °C, pH 7.0–9.0, and tolerated up to 10% NaCl. The cell wall contained meso-diaminopimelic acid, the predominant menaquinone was MK-9(H₄), and major fatty acids included iso-C_16:0. The polar lipid profile comprised diphosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl inositol, hydroxyphosphatidyl ethanolamine, and an unidentified lipid. The characteristic amino acid type of the cell wall was meso-DAP. Whole-cell hydrolysis experiments revealed the characteristic cell wall sugar fractions: ribose and galactose. The genome of strain E54^T is approximately 8.0 Mb with a DNA G+C content of 69.38 mol%. Genome mining revealed 39 biosynthetic gene clusters (BGCs), including non-ribosomal peptide synthetases (NRPS), polyketide synthases (PKS), terpenes, and siderophores. Comparative antiSMASH-based genome analysis across 38 Lentzea strains further demonstrated the genus’ remarkable biosynthetic diversity. NRPS and type I PKS (T1PKS) were the most prevalent BGC types, indicating a capacity to synthesize structurally complex and pharmacologically relevant metabolites. Together, these findings underscore the untapped biosynthetic potential of the genus Lentzea and support the proposal of strain E54^T as a novel species. The strain E54^T (=JCM 34936^T = GDMCC 4.216^T) should represent a novel species, for which the name Lentzea xerophila sp. nov. is proposed. Full article

Low-molecular-weight polypeptides (<3 kDa) were prepared from Periplaneta americana via enzymatic hydrolysis and ultrafiltration, yielding 3.53 ± 0.01 mg/g of peptide-rich extract. The extract was primarily composed of peptides, proteins, polysaccharides, phenolics, and flavonoids. HPLC-MS analysis identified 1402 peptide sequences, 80.51% of which were below 1000 Da, predominantly consisting of tri-, tetra-, and octapeptides. Monosaccharide profiling detected D-(+)-galactose, and quantitative assays determined the contents of total phenolics (12.28 mg/g), flavonoids (15.50 mg/g), proteins (85.84 mg/g), and total sugars (17.62 mg/g). The biological activities of the extract were systematically evaluated. The peptide fraction inhibited hyaluronidase activity by 58% at 5 mg/mL, suggesting protection of extracellular matrix integrity. In HaCaT keratinocytes, it promoted cell proliferation by 62.6%, accelerated scratch wound closure by 54%, upregulated Wnt-10b and β-catenin expression, and reduced intracellular ROS levels under oxidative stress. In LPS-stimulated RAW 264.7 macrophages, the extract decreased TNF-α, IL-6, and IL-1β production by 30%, 25%, and 28%, respectively, reduced MDA levels by 35.2%, and enhanced CAT and SOD activities by 12.3% and 60.3%. In vivo, complete closure of full-thickness skin wounds in mice was achieved by day 14. Safety evaluations using the chick chorioallantoic membrane assay and human patch tests confirmed the extract to be non-irritating and non-toxic. These findings highlight Periplaneta americana extract as a promising multifunctional bioactive ingredient for cosmetic and dermatological applications. Further studies on its active components, mechanisms of action, and clinical efficacy are warranted to support its development in skin health and aesthetic medicine. Full article

In this study, camel milk (CM) and Gir cow milk (GCM) were fermented through cofermentation via yeast–lactic cultures, i.e., Lacticaseibacillus rhamnosus (M9, MTCC 25516) and Saccharomyces cerevisiae (WBS2A, MG101828), and their antioxidant and antidiabetic effectiveness were studied. To optimize the growth conditions, the level of proteolysis was evaluated by exploring various inoculation levels (1.5, 2.0 and 2.5%) as well as incubation durations (0, 12, 24, 36 and 48 h). Peptides were extracted and purified through 2D gel electrophoresis as well as SDS–PAGE. Water-soluble extracts (WSEs) of ultrafiltered (UF) peptide fractions were evaluated via reversed-phase high-performance liquid chromatography (RP-HPLC) to identify the peptide segments. By applying the Peakview tool, peptide sequences obtained from liquid chromatography–mass spectrometry (LC/MS) were reviewed by comparison with those in the BIOPEP database. Furthermore, the elevated levels of TNF-α, IL-6, IL-1β and nitric oxide (NO) in RAW 267.4 cells treated with lipopolysaccharide (LPS) are considerably lower than those in cultured CM and GCM. Protein macromolecules in CMs and GCMs have been captured via confocal laser scanning microscopy (CLSM) and Fourier transform infrared (FTIR) spectroscopy both before and after fermentation. Full article

Dendrobium, a prominent genus in the Orchidaceae family, has generated significant research attention due to its demonstrated biological potential, particularly its notable anti-inflammatory and antioxidant activities. In this study, two fractions of fermented Dendrobium officinale polysaccharides (FDOPs) were successfully isolated through a multi-stage purification strategy including gradient ethanol precipitation, gel column chromatography, and ion exchange chromatography with Lactobacillus reuteri CCFM863. Structural characterization revealed that both Dendrobium officinale polysaccharide fractions consisted of (1→4)-β-D-Manp, (1→4)-β-D-Glcp, and (1→4)-α-D-Glcp residues. The anti-inflammatory efficacy and keratinocyte-protective potential of FDOPs (FDOP-1A and FDOP-2A) were investigated by using lipopolysaccharide (LPS)-induced RAW264.7 and HaCaT cells models, which showed significant inhibitions on the inflammatory factors of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and interleukin-1 beta (IL-1β); recovered levels of filaggrin (FLG), aquaporin 3 (AQP3), transient receptor potential vanilloid 4 (TRPV4), cathelicidin antimicrobial peptide (CAMP)/LL-37, and adiponectin (ADIPOQ); and the reduced protein expression of the TLR4/IκB-α/NF-κB/NLRP3 pathway. Notably, the FDOPs exhibited a remarkable reactive oxygen species (ROS) scavenging capacity, demonstrating superior antioxidant activity. Therefore, FDOPs show dual anti-inflammatory and antioxidant properties, making them suitable as active ingredients for modulating epidermal inflammation and promoting skin barrier repair. Full article

Hermetia illucens, the black soldier fly, is a common and widespread fly of the family Stratiomyidae. Its ability to grow on contaminated substrates suggests the production of antimicrobial peptides that enable its survival. This study aimed to verify the impact of direct and indirect infection with Salmonella enteritidis on the expression of defensins and cecropins in Hermetia illucens larvae. In addition to an infection with a microorganism, it was interesting to verify if the expression of peptides and the relative action of hemolymph changed in larvae subjected to mechanical stress by abdominal puncture. The peptide fraction of the hemolymph of infected larvae was tested using antibiogram and minimum inhibitory concentration tests against Salmonella enteritidis and Salmonella typhimurium. Both molecular and microbiological tests were carried out at three different time points, on larvae not subjected to any treatment (T-0), four hours after treatment (T-1), and 24 h after treatment (T-2). The results of the microbiological tests showed the antimicrobial action of the peptide fraction of the hemolymph against both S. typhimurium and S. enteritidis; for the latter one, the action was more marked. Interesting results were also found for larvae subjected only to mechanical stress by puncture. Molecular tests on the expression of defensins and cecropins were in full agreement with those obtained in the microbiological tests, with expression more pronounced in larvae infected directly with Salmonella enteritidis. Temporal and condition-specific regulation of defensins and cecropins highlights the complexity of the immune response and suggests sophisticated mechanisms by which the host fine-tunes antimicrobial peptide expression to enhance pathogen defense while preventing excessive immune activation. Full article

Introduction: Candidozyma auris (Cz. auris) has emerged globally, and diseases caused by it are associated with a mortality rate of 30–72%. This yeast is often multidrug-resistant and challenging to treat. A synthetic peptide, consisting of 11 amino acids of human lactoferrin (hLF1-11), offers a new therapy that is active against Candida albicans, non-albicans Candida yeasts, as well as Cz. auris. The current study examined the susceptibility of clinically relevant Candida species to hLF(1-11) in vitro and investigated the synergistic interaction of this peptide with fluconazole (FLU) and anidulafungin (ANI). Methods: Susceptibility of the yeasts to hLF(1-11) was tested with a microdilution method to determine minimum inhibitory concentrations (MICs). A total of 59 strains belonging to 16 species of Candida or Candidozyma were tested. The treatment cohort included 20 strains of Cz. auris originating from six different countries. Results: Mean MIC values of all susceptible strains ranged from 16.66 ± 6.46 μg/mL to 45.83 ± 10.21 μg/mL. There were no statistical differences in the susceptibility of hLF(1-11) for Cz. auris across geographic origins. In the combinatory tests, drugs acting together, the fractional inhibitory concentration indexes [FIC] < 1.0, showed a synergistic or additive effect on the efficacy of FLU and ANI when used in combination with hLF(1-11). [FIC] indexes 1–2 were interpreted as intermediate. MIC values in combinatory use were 1–2 titer steps lower than when used alone. Conclusions: hLF(1-11) inhibits the growth of yeasts that belong to the genus Candida, including Cz. auris. The combinatory use may be further investigated to treat infections caused by resistant yeasts. Full article