Search Results (2,803)

Background/Objectives: The growing threat of antibiotic resistance necessitates the development of novel antimicrobial agents that effectively target pathogenic microorganisms while minimizing toxicity. Methods: Two series DABCO-based cationic homopolymers (D-subs 1kDa, D-subs 5kDa, D-subs 15kDa) and DABCO–pyridinium-based copolymers (PyH-subs 5kDa_Dsubs 5kDa, PyH-subs 7kDa_Dsubs 3kDa, PyH-subs 3kDa_Dsubs 7kDa) were synthesized to mimic to host-defense cationic peptides via ring-opening metathesis polymerization (ROMP). The antimicrobial activities of these polymers were determined by their minimum inhibitory concentrations (MICs) against E. coli (Gram-negative bacteria), P. aeruginosa (Gram-negative bacteria), S. aureus (Gram-positive bacteria), and C. albicans (fungus). In vitro cytotoxicity assays revealed selective toxicity towards bacterial cells, with high selectivity indices for several copolymers. To gain insight into the mechanism of action, morphological changes in S. aureus upon exposure to D-subs 1kDa were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: The D-subs 15kDa homopolymer demonstrated the highest overall antimicrobial activity, particularly against S. aureus (MIC: 8 µg/mL), with all polymers exhibiting minimal hemolytic activity (HC₅₀ ≥ 1024 µg/mL). SEM and TEM results revealed membrane disruption indicative of polymer–bacteria interactions. Additionally, stability studies confirmed polymer integrity under physiological conditions for at least 28 days. Conclusions: These results support the potential of DABCO-based cationic polymers as a promising platform for next-generation antimicrobial therapeutics. Full article

Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common form of cancer worldwide, typically characterized by high mortality and significant morbidity, including pain and speech and swallowing disorders. Complete tumor tissue resection, the common first line of therapy, remains a surgical challenge with room for improvements. Because tumor cells express highly specific surface molecules serving as receptors for ligands, specific targeting ligands can be conjugated to fluorescent molecules in order to better visualize tumor borders. Targeted fluorescence-guided surgery (T-FGS) as well as tumor-targeted and near-infrared (NIR) fluorescence imaging are emerging techniques for real-time intraoperative cancer imaging. Targeting agents include nanodots or fluorophores, which have been conjugated to specific ligands like antibodies, peptides, or other synthetic moieties. This article surveys tumor-targeted ligands in recent and current preclinical studies and clinical trials related to HNSCC, highlighting common NIRF dyes used for molecular imaging and their physical properties, working concentrations, and associated risks. Smaller ligands, nanodots, dual-modality NIR dyes, and activatable agents can enhance tumor-targeting processes, resulting in faster, more penetrable, and clearer imaging, which could lead to improved clinical applications and better tumor removal rates in the future. Full article

Background: Diagnosing and predicting outcomes in elderly patients with heart failure (HF) is challenging due to atypical symptoms and the limited value of natriuretic peptides, highlighting the need to search for new risk stratification biomarkers in this population. Aim: We aimed to analyze factors associated with the composite endpoint (all-cause mortality or decompensated HF-related hospitalization) within six months of follow-up in elderly patients with left ventricular systolic dysfunction and decompensated HF, with particular emphasis on copeptin concentration. Methods: This is a retrospective observational study based on prospectively collected data of 279 consecutive elderly patients hospitalized between 2018 and 2023 due to decompensated HF. Inclusion criteria were age > 65 years, history of HF diagnosed at least two years before the index hospitalization, and left ventricular ejection fraction < 40% on admission echocardiography. Serum copeptin levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) (Human Copeptin ELISA kit, Sunred Biological Technology Co, Shanghai, China). The primary endpoint was all-cause mortality or decompensated HF-related hospitalization during the six-month follow-up. Results: The median age of the study population was 77 years (IQR: 69–79), and 221 (79.2%) were male. The composite endpoint occurred in 110 patients (38.1%). Multivariable analysis showed that serum concentrations of copeptin [hazard ratio (HR) 1.053 (1.042–1.064), p < 0.0001], bilirubin [HR 1.085 (1.057–1.114), p < 0.0001], uric acid [HR 1.005 (1.003–1.006), p < 0.0001], high-sensitivity C-reactive protein (hs-CRP) [HR 1.208 (1.088–1.342), p < 0.0001], and sodium [HR 1.111 (1.025–1.203), p = 0.01], as well as ischemic etiology of HF [HR 3.969 (2.396–6.575), p < 0.0001], were independently associated with worse outcomes. Conclusions: Our study demonstrated that higher concentrations of copeptin, bilirubin, hs-CRP, and uric acid, as well as lower sodium levels and ischemic etiology of HF, were independently associated with all-cause mortality or HF-related hospitalization during a six-month follow-up in elderly patients with decompensated HF. Full article

Background: Most patients with hypertension exhibit elevated and detectable levels of natriuretic peptides, particularly BNP and NT-proBNP, as well as troponin concentrations. However, the prognostic relevance of this finding has not been clearly established in patients who have hypertension without heart failure (HF). In this review, we aimed to evaluate the prognostic utility of BNP/NT-proBNP alongside troponin T/I for risk stratification in hypertensive patients, excluding those with HF. Methods: This systematic review was registered in PROSPERO (CRD42024552031). A systematic literature search was conducted using two online databases, Ovid Medline and Web of Science, to identify studies. Data retrieved from articles were used in line with the PRISMA statement guidelines. Participants were aged ≥ 18 years with hypertension. The primary end point was a major adverse cardiac event (MACE) and its individual components. Descriptive synthesis was performed, and data are presented in tabular form. Results: Seventeen studies (70,021 participants) were retrieved for analysis comprising eight prospective cohort studies, six randomized controlled trials, and three retrospective studies. The review evaluated cardiac biomarkers: BNP (n = 6), NT proBNP (n=9), troponin T (n = 4), and troponin I (n = 7). Studies predicted composite MACE (n = 8), all-cause mortality (n = 7), HF (n = 6), and atrial fibrillation (n = 3) outcomes. Cardiac biomarkers showed a strong association with reported outcomes. However, heterogeneity in biomarker thresholds and methodologies limited comparability. Conclusions: The obtained results suggest that elevated cardiac biomarkers BNP/NT-proBNP and troponin I are associated with significantly higher risk of MACE and are powerful predictors in clinical setting. However, large-scale studies are required to validate the robustness and prognostic utility of these biomarkers Full article

Caenorhabditis elegans, a free-living nematode model, secretes neuropeptides, but the ecological roles of its peptide exudates in regulating rhizosphere microbial activity remain largely unexplored. We identified six short peptides (P1, P9, P19, P20, P25, and P26) from C. elegans exudates that significantly enhanced indole-3-acetic acid (IAA) production by the plant growth-promoting bacterium Arthrobacter pascens ZZ21. These peptides were heat-labile and proteinase K-sensitive but unaffected by DNase I or RNase A, confirming their proteinaceous (peptide) nature rather than nucleic acid origin. The retention of bioactivity in n-butanol extracts further supported their hydrophilic, peptide-like properties. LC-MS/MS identified 30 linear peptides, including the six bioactive ones, which exhibited distinct dose-dependent effects, suggesting diverse regulatory mechanisms. Despite their relatively low abundance, these peptides strongly promoted IAA production in the bacterial culture system across multiple concentrations. These findings reveal an unrecognized mechanism whereby free-living nematodes regulate rhizobacterial metabolism via secreted peptides, offering new insights into nematode-mediated chemical signaling. Therefore, this study advances understanding of plant–microbe–nematode interactions and highlights strategies for manipulating rhizosphere microbiota in sustainable agriculture. Full article

Background/Objectives: Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, typically is asymptomatic in immunocompetent individuals but causes severe complications in immunocompromised subjects and during pregnancy. Current treatments such as pyrimethamine and sulfadiazine are effective for acute infections but cannot eliminate encysted bradyzoites and have significant side effects. The antimicrobial killer peptide (KP) has interesting therapeutic potential, but its intracellular delivery is challenging; hyaluronate-based nanoparticles loaded with KP (KP-NPs) were evaluated to target T. gondii-infected cells that overexpress CD44. Methods: KP-NPs made of chitosan and hyaluronate were produced by microfluidics and were characterized for size, surface charge, encapsulation efficiency, and stability under stress conditions. After excluding their toxicity, their activity was tested in vitro against Candida albicans and T. gondii as free tachyzoite or in infected human foreskin fibroblasts (HFFs). Results: KP was efficiently encapsulated in nanoparticles and protected from harsh acidic conditions at high temperature. Preliminary in vitro testing against C. albicans showed that, at the lowest candidacidal concentration of KP (2.5 μg/mL), KP-NPs killed 90.97% of yeast cells. KP itself proved to be non-toxic for HFFs as host cells and effective against T. gondii. Comparable results were obtained for KP-NPs and blank nanoparticles (BLK-NPs), with no observed toxicity to host cells, confirming that encapsulation did not alter peptide efficacy. The parasiticidal effect of KP alone, as well as KP-NPs at 250 µg/mL and BLK-NPs, was confirmed through tests on free T. gondii tachyzoites. Reduction rates for the number of infected cells ranged from 66% to 90% with respect to control, while the reduction in the number of intracellular tachyzoites ranged from 66% to 80%. Interestingly, KP alone was not effective against intracellular tachyzoite, while KP-NPs maintained an efficacy comparable to the extracellular model, suggesting that particles helped the internalization of the peptide. Conclusions: Encapsulation of KP into hyaluronate/chitosan nanoparticles does not alter its activity and improves its efficacy against the intracellular parasite. Notably, BLK-NPs appeared to exhibit efficacy against the parasite on its own, without the presence of KP. Full article

Despite significant medical advancements, two major health challenges persist: antibiotic resistance in microbial pathogens and drug resistance in cancer cells. To address these issues, research has increasingly focused on discovering novel natural compounds with dual antimicrobial and anticancer activities. Among such candidates, antimicrobial peptides (AMPs) have attracted attention due to their ability to selectively target microbial and cancer cells while exhibiting minimal toxicity toward normal cells. Although Vietnam possesses rich biodiversity, including a wide range of Anura species, studies on AMPs from these organisms remain limited. In this study, a novel AMP, brevinin-1 E8.13, was identified from the skin secretion of Sylvirana guentheri, a frog species native to Vietnam. The brevinin-1 E8.13 peptide was successfully cloned, sequenced, and chemically synthesized. Functional assays revealed that brevinin-1 E8.13 possesses strong antibacterial activity against Staphylococcus aureus and exerts significant antiproliferative effects on various human cancer cell lines, including A549 (lung), AGS (gastric), Jurkat (leukemia), HCT116 (colorectal), HL60 (leukemia), and HepG2 (liver). The peptide demonstrated moderate to potent cytotoxic activity, with IC₅₀ values ranging from 7.5 to 14.8 μM, depending on the cell type. Notably, brevinin-1 E8.13 exhibited low cytotoxicity toward normal human dermal fibroblast (HDF) cells and even promoted cell proliferation at lower concentrations. Furthermore, Chemically Activated Fluorescent Expression (CAFLUX) bioassay results confirmed that the peptide significantly downregulated Cyp1a1 gene expression in HepG2 cells. Collectively, these findings highlight the therapeutic potential of brevinin-1 E8.13 as a dual-function antimicrobial and anticancer agent derived from the skin secretion of Sylvirana guentheri. Full article

The growing population and increasing concerns about food security and sustainability demand innovative solutions to minimize food waste and transform by-products into functional ingredients valuable to the food sector. Brewery by-products, including brewer’s spent grain (BSG) and brewer’s spent yeast (BSY), are underutilized resources despite their high protein contents and potential as sustainable food ingredients. This study aimed to transform BSG and BSY into protein hydrolysates (BSGH and BSYH, respectively) through enzymatic hydrolysis and thus add value to these brewery industry by-products to be used in the food industry. These protein hydrolysates were incorporated into non-alcoholic malt beverages at three different concentrations, and their effects on the physicochemical properties, including color, kinematic viscosity, turbidity, foaming capacity and foam stability, of the non-alcoholic malt beverages were evaluated. Both BSGH and BSYH exhibited higher water solubility (WS) and lower water binding capacity (WBC) values when compared to their native non-hydrolyzed forms, enhancing their suitability as ideal ingredients for protein supplementation of a wide range of food and beverage products. The production of peptides of varying sizes underscored the effectiveness of enzymatic hydrolysis which resulted in an increase in cysteine and methionine levels in BSYH but a decrease in BSGH. The addition of BSGH and BSYH increased the kinematic viscosity and turbidity but reduced the lightness values in color of the non-alcoholic malt beverages. When the properties of the protein hydrolysates were compared, BSYH was more effective than BSGH in forming foams and maintaining their stability for longer periods. These findings highlight the potential of brewery by-products, after enzymatic hydrolysis, as protein-rich ingredients that can support more sustainable food systems and contribute to the nutritional enhancement of various low-protein food and beverage products. Full article

Microbial metabolites offer a multitude of mechanisms for alleviating diabetes, particularly type 2 diabetes (T2D). However, the metabolites of yeasts recognised as safe remain under-explored and are receiving less attention in the treatment of T2D. In addition to the recognised probiotic status of certain yeasts, their genetic feature is responsible for many of the effects observed. Branched and non-branched short-chain fatty acids, bioactive peptides, carotenoids, and polysaccharides (β-glucans, mannans, and peptides derived from them) have vital properties that modulate intestinal permeability, soothe inflammation, and directly influence insulin sensitivity. Their action mechanism ranges from hepatic lipogenesis via the induction of hormone-sensitive lipase and the inhibition of α-glucosidase or DPP-IV to promoting the secretion of GLP-1 (Glucagon-Like Peptide-1) and GIP (Gastric Inhibitory Polypeptide), orchestrating immune modulation, and nourishing the gut microbiota. The richness of the yeast metabolome suggests that a concentrated fermentate could be developed to potentiate the functional effects in vitro in the treatment of T2D. The purpose of this review is to take stock of the current state of knowledge of probiotic yeast metabolites and outline their potential for the treatment of diabetes via the development of food supplements or nutraceuticals. Full article

Background and Objectives: Optimal pharmacological treatment following left ventricular ejection fraction (LVEF) improvement remains largely unknown. This study compared the clinical outcomes of patients with heart failure (HF) with improved EF (HFimpEF) based on the maintenance of sacubitril/valsartan (S/V) or transition to a renin–angiotensin system blocker (RASB). Material and Method: A total of 354 patients with recovered LVEF of at least 40% after S/V treatment from a single center were retrospectively analyzed. Patients were categorized into three groups: those who continued S/V (n = 294), those who switched to RASB (n = 47), and those who discontinued both S/V and RASB (n = 13). The primary endpoint was HF relapse, defined as a two-fold increase in baseline serum N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) concentration exceeding 400 pg/dL. Secondary endpoints included the ratio and difference between baseline and peak NT-proBNP levels. Result: Baseline clinical characteristics were well balanced among groups. Over a median follow-up of 399 (252–589) days, HF relapse occurred more frequently in patients who discontinued both S/V and RASB compared to those who maintained either treatment (53.8% vs. 16.3% vs. 10.6%; p = 0.001). NT-proBNP levels also showed a more pronounced increase in this group. However, there were no significant differences in primary or secondary outcomes between the S/V and RASB groups. Conclusions: Our findings suggest that replacing S/V with another RASB does not worsen outcomes in patients with HFimpEF after S/V treatment, whereas discontinuation of both therapies is associated with a significantly higher risk of HF relapse. A prospective trial is warranted to confirm the safety and effectiveness of this approach in maintaining remission. Full article

Background/Objectives: Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa are steadily increasing, thus the discovery and development of new and effective agents are needed. Antimicrobial peptides (AMPs) are a heterogeneous group of innate defense system peptides with broad antimicrobial activity. In this study, 17 AMPs were tested, identifying CAP-18, a cathelicidin-based compound, as the most active. CAP-18 was optimized by synthesizing structural derivatives, which were selected for further studies based on their activity against a collection of MDR and colistin-resistant P. aeruginosa strains. Methods: AMPs collection was initially tested against different P. aeruginosa strains, identifying CAP-18 as the most active. CAP-18 derivatives were synthetized and assessed by the Minimum Inhibitory Concentration (MIC), time-kill kinetics, cytotoxicity against human cell lines, hemolytic activity, and therapeutic index (IC₅₀/MIC₉₀). The mechanism of action was assessed by Transmission Electron Microscopy (TEM), and in vivo efficacy was determined through a murine skin infection model. Results: CAP-18 and D-CAP-18 had a MIC₉₀ of 4 and 2 μg/mL, respectively, whereas CAP-18₃₁ and D-CAP-18₃₁ presented MIC₉₀ values of 16 mg/L. The shorter derivatives of CAP-18 showed a lower activity. Time-kill curves revealed a fast bactericidal effect. These derivatives showed low toxicity against different human cell lines and low hemolysis, resulting in a wide therapeutic index (IC₅₀/MIC₉₀), with D-CAP-18 having the best therapeutic index (137.4). TEM provided insight into the mechanism of action, revealing bacterial membrane damage. In vivo studies of both CAP-18 and D-CAP-18 showed good activity with a 3 log decrease compared to the infected control group. Conclusions: Among the investigated four peptides, D-CAP-18 is the most promising candidate to treat skin infections caused by MDR P. aeruginosa since it shows potent activity both in vitro and in vivo, and a high therapeutic index. Full article

White muscle disease (WMD) is a degenerative condition of the skeletal and/or cardiac muscle associated with selenium (Se) and/or vitamin E deficiency, which can present in acute, subacute, or chronic forms, and is most commonly observed in young, rapidly growing animals, though it may also occur in older individuals. This study aims to determine the serum concentrations of galectin-3 (Gal-3), cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP), as well as the activity of creatine kinase-myocardial band (CK-MB), in lambs diagnosed with WMD, and to investigate the diagnostic potential of these biomarkers in the evaluation of myocardial injury and skeletal and/or cardiac muscle necrosis associated with WMD. A total of 50 lambs, 20 healthy and 30 with WMD, were included in the study. The diagnosis of WMD was made based on clinical signs, laboratory results, necropsy findings, and blood vitamin E and Se concentrations. The lambs in the WMD group were categorized into two subgroups: confirmed, severe aWMD (acute animals, n = 10) lambs and presumed sWMD (subacute animals, n = 20), based on the clinical progression and severity of the disease. Serum levels of NT-proBNP, Gal-3, and cTnI were assessed using the ELISA technique. Levels of cTnI and CK-MB indicative of myocardial injury were found to be considerably elevated in the aWMD group (p < 0.001) in comparison to both the sWMD and control groups. CK-MB showed a strong positive correlation with cTnI (r = 0.819, p < 0.001). The serum concentrations of Gal-3 and NT-proBNP in healthy lambs were 2.55 ± 0.52 ng/mL and 3.28 ± 0.71 ng/mL, respectively. Serum Gal-3 concentrations were measured as 2.99 ± 0.44 ng/mL in the aWMD group and 3.07 ± 0.42 ng/mL in the sWMD group, while NT-proBNP concentrations were 2.15 ± 0.32 ng/mL and 2.64 ± 0.55 ng/mL in the aWMD and sWMD groups, respectively. No statistically significant differences were found in serum Gal-3 or NT-proBNP levels among the three groups (p > 0.05). In conclusion, this study is the first investigation assessing serum concentrations of Gal-3 and NT-proBNP in lambs afflicted with WMD. The results suggest that Gal-3 and NT-proBNP are ineffective biomarkers for assessing myocardial injury and skeletal and/or cardiac muscle necrosis associated with WMD in lambs. However, cTnI and CK-MB appear to be significant indicators of cardiac involvement in both acute and subacute scenarios. Further research is required to elucidate the molecular function of Gal-3 in muscle and cardiac disease in lambs afflicted with WMD. Full article

Facial aging is a multifactorial process involving changes in bone, fat compartments, ligaments, muscles, and skin. Collagen biostimulators, including synthetic agents and autologous platelet concentrates, have gained attention for facial rejuvenation. Injectable platelet-rich fibrin (i-PRF), a second-generation autologous concentrate, has shown promising regenerative properties due to its natural composition and growth factors. Cosmetic peptides, such as palmitoyl pentapeptide-4 (Matrixyl) and Tetrapeptide-21 (GEKG), are also studied for their ability to stimulate collagen synthesis and remodel the extracellular matrix. This in vitro study examined the potential synergistic effects of i-PRF combined with Matrixyl or GEKG on human dermal fibroblast viability, proliferation, and ECM-related gene expression. Fibroblasts were cultured under six conditions: control, i-PRF alone, Matrixyl alone, GEKG alone, i-PRF + Matrixyl, and i-PRF + GEKG. Viability and proliferation were assessed via MTT, crystal violet, and RealTime-Glo™ assays. Gene expression of COL1A1, FN1, and HAS1 was measured using RT-qPCR. The combinations, especially i-PRF + GEKG, led to increased cell viability and upregulated ECM-related genes at 72 h. These effects were stronger than the individual treatments, suggesting synergistic effects, especially with GEKG. These findings highlight the clinical potential of combining autologous platelet concentrates with bioactive peptides for dermal regeneration. Further preclinical and clinical studies are warranted. Full article

Oxytocin (OT) and vasopressin (AVP) are attracting interest as potential measures for dog welfare and human-dog interactions. The potential for detection and measurement of these two neuropeptides in canine saliva provides a viable alternative to more invasive collection methods. This scoping review aims to analyse the scientific literature measuring salivary OT and AVP in dogs, the methods employed, and the areas of research. A comprehensive search was conducted on the Web of Science, Scopus, and ProQuest platforms, yielding a selection of peer-reviewed, primary research studies that specifically measured dog salivary OT and/or AVP. The final selection comprised 16 articles from 2017 to 2024, offering insights into the methods employed for the collection, processing, and analysis of dog saliva samples. The findings highlighted significant variability in OT and AVP salivary concentrations, which also depended on the methods employed. The research areas of the included articles were primarily linked to the social and maternal behaviour spheres. This study draws from extant research to present an overview of the challenges associated with measuring salivary OT and AVP in dogs. It provides a comprehensive picture of this multifaceted issue, which is crucial for accurately interpreting these peptides as indicators of dog welfare. Full article

Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder that has an approved treatment that can still be improved. Antisense oligonucleotides (AONs) are currently delivered intrathecally for SMA therapy based on SMN2 gene splicing correction, and high concentrations are required to achieve an improvement of the disease symptoms. In this study, AONs were introduced into SMA fibroblast cell cultures by means of an arginine–histidine-rich peptide carrier that had been decorated with iRGD ligands. Due to the protected and receptor-mediated nature of AON delivery within these complexes, low concentrations can be used. We assessed the RNA-binding characteristics, cytotoxicity, size, and zeta potential of AON/carrier complexes as well as the efficiency of SMN2 gene splicing correction following transfections. After testing a variety of AON/carrier formulations, we selected those that produced the best outcomes. The AON/carrier complexes that were found to be the most effective significantly increased the proportion of full-length SMN transcripts and the quantity of nuclear gems. Thus, we demonstrated the potential of delivering therapeutic AONs into SMA cells using a ligand-modified peptide carrier. Full article