Search Results (9,847)

Palindromic antimicrobial peptides (PAMs) constitute versatile scaffolds for the design and optimization of anticancer agents with applications in therapy, diagnosis, and/or monitoring. In the present study, fluorolabeled peptides derived from the palindromic sequence RWQWRWQWR containing fluorescent probes, such as 2-Aminobenzoyl, 5(6)-Carboxyfluorescein, and Rhodamine B, were obtained. RP-HPLC analysis revealed that the palindromic peptide conjugated to Rhodamine B (RhB-RWQWRWQWR) exhibited the presence of isomers, likely corresponding to the open-ring and spiro-lactam forms of the fluorescent probe. This equilibrium is dependent on the peptide sequence, as the RP-HPLC analysis of dimeric peptide (RhB-RRWQWR-hF-KKLG)₂K-Ahx did not reveal the presence of isomers. The antibacterial activity of the fluorescent peptides depends on the probe attached to the sequence and the bacterial strain tested. Notably, some fluorescent peptides showed activity against reference strains as well as sensitive, resistant, and multidrug-resistant clinical isolates of E. coli, S. aureus, and E. faecalis. Fluorolabeled peptides 1-Abz (MIC = 62 µM), RhB-1 (MIC = 62 µM), and Abz-1 (MIC = 31 µM) exhibited significant activity against clinical isolates of E. coli, S. aureus, and E. faecalis, respectively. The RhB-1 (IC₅₀ = 61 µM), Abz-1 (IC₅₀ = 87 µM), and RhB-2 (IC₅₀ = 35 µM) peptides exhibited a rapid, significant, and concentration-dependent cytotoxic effect on HeLa cells, accompanied by morphological changes characteristic of apoptosis. RhB-1 (IC₅₀ = 18 µM) peptide also exhibited significant cytotoxic activity against breast cancer cells MCF-7. These conjugates remain valuable for elucidating the possible mechanisms of action of these novel anticancer peptides. Rhodamine-labeled peptides displayed cytotoxicity comparable to that of their unlabeled analogues, suggesting that cellular internalization constitutes a critical early step in their mechanism of action. These findings suggest that cell death induced by both unlabeled and fluorolabeled peptides proceeds predominantly via apoptosis and is likely contingent upon peptide internalization. Functionalization at the N-terminal end of the palindromic sequence can be evaluated to develop systems for transporting non-protein molecules into cancer cells. Full article

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article

Perennial wall rocket (Diplotaxis tenuifolia L.—DC.) exhibits genotype-dependent responses to biostimulant applications, which have not yet been deeply investigated. A two-year greenhouse factorial experiment was carried out to assess the interactions between five cultivars (Mars, Naples, Tricia, Venice, and Olivetta), three biostimulant formulations (Cystoseira tamariscifolia L. extract; a commercial legume-derived protein hydrolysate, “Dynamic”; and Spirulina platensis extract) plus an untreated control, and three crop cycles (autumn, autumn–winter, and winter) on leaf yield and dry matter, organic acids, colorimetric parameters, hydrophilic and lipophilic antioxidant activities, nitrate concentration, nitrogen use efficiency, and mineral composition, using a split plot design with three replicates. Protein hydrolysate significantly enhanced yield and nitrogen use efficiency in Mars (+26%), Naples (+25.6%), Tricia (+25%), and Olivetta (+26%) compared to the control, while Spirulina platensis increased the mentioned parameters only in Venice (+36.2%). Nitrate accumulation was reduced by biostimulant application just in Venice, indicating genotype-dependent nitrogen metabolism responses. The findings of the present research demonstrate that the biostimulant efficacy in perennial wall rocket is mainly ruled by genotypic factors, and the appropriate combinations between the two mentioned experimental factors allow for optimization of leaf yield and quality while maintaining nitrate concentration under the regulation thresholds. Full article

Cervical cancer affects 661,000 women worldwide; as a result, new treatment alternatives are still being sought, with steroid oximes being the most prominent. However, the molecular targets where steroid oximes exert their anticancer activity remain unknown. In this study, reports of the activity in cell lines were obtained, and the targets associated with cervical cancer were identified using bioinformatics tools, based on two- and three-dimensional structural similarity analysis. Subsequently, molecular targets were analyzed via molecular docking using Schrödinger software v.2022-4 to determine their effects compared with reference drugs. Interrelated proteins and isolated proteins were observed, suggesting both the multi-target and single-target activity of steroid oximes. The analysis revealed that 60% of the 42 identified proteins had previously been reported in the literature and were associated with cervical cancer in processes related to cell proliferation, invasion, migration, and apoptosis. Among them, SRC, IGF1R, and MDM2 showed feasibility for multi-target interaction, which is consistent with the lower IC₅₀ values reported for oximes in cervical cancer cell lines (HeLa and CaSki). This finding suggests that steroid oximes are multi-target molecules that can inhibit the proteins associated with cervical cancer, particularly through the IGF1R, MDM2, and SRC pathways related to cell proliferation and apoptosis, serving as a guideline for the future design of new steroidal oximes. Full article

Cultured meat is emerging as a sustainable alternative to conventional animal agriculture, with scaffolds playing a central role in supporting cellular attachment, growth, and tissue maturation. This review focuses on the development of gel-based hybrid biomaterials that meet the dual requirements of biocompatibility and food safety. We explore recent advances in the use of naturally derived gel-forming polymers such as gelatin, chitosan, cellulose, alginate, and plant-based proteins as the structural backbone for edible scaffolds. Particular attention is given to the integration of food-grade functional additives into hydrogel-based scaffolds. These include nanocellulose, dietary fibers, modified starches, polyphenols, and enzymatic crosslinkers such as transglutaminase, which enhance mechanical stability, rheological properties, and cell-guidance capabilities. Rather than focusing on fabrication methods or individual case studies, this review emphasizes the material-centric design strategies for building scalable, printable, and digestible gel scaffolds suitable for cultured meat production. By systemically evaluating the role of each component in structural reinforcement and biological interaction, this work provides a comprehensive frame work for designing next-generation edible scaffold systems. Nonetheless, the field continues to face challenges, including structural optimization, regulatory validation, and scale-up, which are critical for future implementation. Ultimately, hybrid gel-based scaffolds are positioned as a foundational technology for advancing the functionality, manufacturability, and consumer readiness of cultured meat products, distinguishing this work from previous reviews. Unlike previous reviews that have focused primarily on fabrication techniques or tissue engineering applications, this review provides a uniquely food-centric perspective by systematically evaluating the compositional design of hybrid hydrogel-based scaffolds with edibility, scalability, and consumer acceptance in mind. Through a comparative analysis of food-safe additives and naturally derived biopolymers, this review establishes a framework that bridges biomaterials science and food engineering to advance the practical realization of cultured meat products. Full article

Background: Antibacterial resistance (ABR) poses a major challenge to global health, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the prominent multidrug-resistant strains. MRSA has developed resistance through the expression of Penicillin-Binding Protein 2a (PBP2a), a key transpeptidase enzyme involved in bacterial cell wall biosynthesis. Objectives: The objective was to design and characterize a novel small-molecule inhibitor targeting PBP2a as a strategy to combat MRSA. Methods: We synthesized a new indole triazole conjugate (ITC) using eco-friendly and click chemistry approaches. In vitro antibacterial tests were performed against a panel of strains to evaluate the ITC antibacterial potential. Further, a series of in silico evaluations like molecular docking, MD simulations, free energy landscape (FEL), and principal component analysis (PCA) using the crystal structure of PBP2a (PDB ID: 4CJN), in order to predict the mechanism of action, binding mode, structural stability, and energetic profile of the 4CJN-ITC complex. Results: The compound ITC exhibited noteworthy antibacterial activity, which effectively inhibited the selected strains. Binding score and energy calculations demonstrated high affinity of ITC for the allosteric site of PBP2a and significant interactions responsible for complex stability during MD simulations. Further, FEL and PCA provided insights into the conformational behavior of ITC. These results gave the structural clues for the inhibitory action of ITC on the PBP2a. Conclusions: The integrated in vitro and in silico studies corroborate the potential of ITC as a promising developmental lead targeting PBP2a in MRSA. This study demonstrates the potential usage of rational drug design approaches in addressing therapeutic needs related to ABR. Full article

The biological effects of nanoparticles are closely related to their intracellular content and location, both of which are influenced by various factors. This study investigates the effects of surface charge on the uptake, intracellular distribution, and exocytosis of CdSe/ZnS quantum dots (QDs) in Raw264.7 macrophages. Negatively charged 3-mercaptopropanoic acid functionalized QDs (QDs-MPA) show higher cellular uptake than positively charged 2-mercaptoethylamine functionalized QDs (QDs-MEA), and serum enhances the uptake of both types of QDs via protein corona-mediated receptor endocytosis. QDs-MEA primarily enter the cells through clathrin/caveolae-mediated pathways and predominantly accumulate in lysosomes, while QDs-MPA are mainly internalized through clathrin-mediated endocytosis and localize to both lysosomes and mitochondria. Exocytosis of QDs-MPA is faster and more efficient than that of QDs-MEA, though both exhibit limited excretion. In addition to endocytosis and exocytosis, cell division influences intracellular QD content over time. These results reveal the charge-dependent interactions between QDs and macrophages, providing a basis for designing biocompatible nanomaterials. Full article

The expression of recombinant proteins in heterologous hosts is a common strategy to obtain larger quantities of the “protein of interest” (POI) for scientific, therapeutic or commercial purposes. However, the experimental success of such an approach critically depends on the choice of an appropriate host system to obtain biologically active forms of the POI. The correct folding of the molecule, mediated by disulfide bond formation, is one of the most critical steps in that process. Here we describe the recombinant expression of hirudin, a leech-derived anticoagulant and thrombin inhibitor, in the yeast Komagataella phaffii (formerly known and mentioned throughout this publication as Pichia pastoris) and in two different strains of Escherichia coli, one of them being especially designed for improved disulfide bond formation through expression of a protein disulfide isomerase. Cultivation of the heterologous hosts and expression of hirudin were performed at different temperatures, ranging from 22 to 42 °C for the bacterial strains and from 20 to 30 °C for the yeast strain, respectively. The thrombin-inhibitory potencies of all hirudin preparations were determined using the thrombin time coagulation assay. To our surprise, the hirudin preparations of P. pastoris were considerably less potent as thrombin inhibitors than the respective preparations of both E. coli strains, indicating that a eukaryotic background is not per se a better choice for the expression of a biologically active eukaryotic protein. The hirudin preparations of both E. coli strains exhibited comparable high thrombin-inhibitory potencies when the strains were cultivated at their respective optimal temperatures, whereas lower or higher cultivation temperatures reduced the inhibitory potencies. Full article

Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between glucose at the C6 position and FA at the C4 position, was designed and synthesized. The hydrophilicity and chemical stability of FA-Glu were tested. FA-Glu’s protection against DNA oxidative cleavage was tested using pBR322 plasmid DNA under the Fenton reaction. The cytotoxicity of FA-Glu was examined via the PC12 cell and bEnd.3 cell tests. Antioxidative neuroprotection was evaluated, in vitro, via a H₂O₂-induced PC12 cell test, measuring cell viability and ROS levels. Antioxidative alleviation of cerebral ischemia–reperfusion injury (CIRI), in vivo, was evaluated using a rat middle cerebral artery occlusion (MCAO) model. The results indicated that FA-Glu was water-soluble (LogP −1.16 ± 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via •OH radicals (SC% 88.00%). It was a non-toxic agent based on PC12 cell and bEnd.3 cell tests results. FA-Glu significantly protected against H₂O₂-induced oxidative damage in the PC12 cell (cell viability 88.12%, 100 μM) and inhibited excessive cell ROS generation (45.67% at 100 μM). FA-Glu significantly reduced the infarcted brain areas measured using TTC stain observation, quantification (FA-Glu 21.79%, FA 28.49%, I/R model 43.42%), and H&E stain histological observation. It sharply reduced the MDA level (3.26 nmol/mg protein) and significantly increased the GSH level (139.6 nmol/mg protein) and SOD level (265.19 U/mg protein). With superior performance to FA, FA-Glu is a safe agent with effective antioxidative DNA and neuronal protective actions and an ability to alleviate CIRI, which should help in the prevention of IS. Full article

Cell-free biosensors harness the selectivity of cellular machinery without living cells’ constraints, offering advantages in environmental monitoring, medical diagnostics, and biotechnological applications. This review examines recent advances in cell-free biosensor development, highlighting their ability to detect diverse analytes including heavy metals, organic pollutants, pathogens, and clinical biomarkers with high sensitivity and specificity. We analyze technological innovations in cell-free protein synthesis optimization, preservation strategies, and field deployment methods that have enhanced sensitivity, and practical applicability. The integration of synthetic biology approaches has enabled complex signal processing, multiplexed detection, and novel sensor designs including riboswitches, split reporter systems, and metabolic sensing modules. Emerging materials such as supported lipid bilayers, hydrogels, and artificial cells are expanding biosensor capabilities through microcompartmentalization and electronic integration. Despite significant progress, challenges remain in standardization, sample interference mitigation, and cost reduction. Future opportunities include smartphone integration, enhanced preservation methods, and hybrid sensing platforms. Cell-free biosensors hold particular promise for point-of-care diagnostics in resource-limited settings, environmental monitoring applications, and food safety testing, representing essential tools for addressing global challenges in healthcare, environmental protection, and biosecurity. Full article

Community detection in complex networks plays a pivotal role in modern scientific research, including in social network analysis and protein structure analysis. Traditional community detection methods face challenges in integrating heterogeneous multi-source information, capturing global semantic relationships, and adapting to dynamic network evolution. This paper proposes a novel unsupervised multimodal community detection algorithm (UMM) based on fractal iteration. The core idea is to design a dual-channel encoder that comprehensively considers node semantic features and network topological structures. Initially, node representation vectors are derived from structural information (using feature vectors when available, or singular value decomposition to obtain feature vectors for nodes without attributes). Subsequently, a parameter-free graph convolutional encoder (PFGC) is developed based on fractal iteration principles to extract high-order semantic representations from structural encodings without requiring any training process. Furthermore, a semantic–structural dual-channel encoder (DC-SSE) is designed, which integrates semantic encodings—reduced in dimensionality via UMAP—with structural features extracted by PFGC to obtain the final node embeddings. These embeddings are then clustered using the K-means algorithm to achieve community partitioning. Experimental results demonstrate that the UMM outperforms existing methods on multiple real-world network datasets. Full article

Plant-sourced Dietary Fibers (PDFs) have garnered significant attention due to their multifaceted health benefits, particularly in glycemic control, lipid metabolism regulation, and gut microbiota modulation. This review systematically investigates advanced modification strategies, including physical, chemical, bioengineering, and hybrid approaches, to improve the physicochemical properties and bioactivity of PDFs from legumes, cereals, and other sources. Key modifications such as steam explosion, enzymatic hydrolysis, and carboxymethylation significantly improve solubility, porosity, and functional group exposure, thereby optimizing the health-promoting effects of legume-sourced dietary fiber. The review further elucidates critical structure–function relationships, highlighting PDF’s prebiotic potential, synergistic interactions with polyphenols and proteins, and responsive designs for targeted nutrient delivery. In functional food applications, cereal-sourced dietary fibers serve as a versatile functional ingredient in engineered foods including 3D-printed gels and low-glycemic energy bars, addressing specific metabolic disorders and personalized dietary requirements. By integrating state-of-the-art modification techniques with innovative applications, this review provides comprehensive insights into PDF’s transformative role in advancing functional foods and personalized nutrition solutions. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Enhancing the nutritional content of crops is crucial for safeguarding human health and mitigating global hunger. A viable method for attaining this goal is the planned implementation of various agronomic practices, including tillage and nutrient provision. A field experiment was executed at the Hungarian University of Agriculture and Life Sciences in Gödöllő in the 2023 and 2024 growing seasons. The study aimed to assess the effects of foliar nutrient supply and soil tillage methods on the grain nutritional composition and mineral content of winter barley. Employing a split-plot design with three replications, the experiment included four nutrient treatments (control, bio-cereal, bio-algae, and MgSMnZn blend) and two soil tillage types (i.e., plowing and cultivator). The results indicated that while protein content was not influenced by the main effects of nutrients and tillage, the levels of β-glucan, starch, crude ash, and moisture content were significantly (p < 0.05) affected by the nutrient treatments and by growing year, treated as a random factor. Notably, bio-algae and bio-cereal nutrients, combined with cultivator tillage, enhanced β-glucan content. All applied nutrient treatments increased the level of starch compared to the control. With regard to grain mineral content, the iron and zinc content responded to the nutrient supply, tillage, and growing year. However, applying a multiple-nutrient composition-based treatment did not increase iron and zinc levels, suggesting that individual applications may be more effective for increasing the content of these minerals in grains. Cultivator tillage improved iron and zinc levels. Moreover, manganese (Mn) and copper (Cu) were predominantly affected by nutrient availability and by growing seasons as a random factor. Therefore, to improve grain quality, this study emphasizes the significance of proper nutrient and tillage methods by focusing on the intricate relationships between agronomic techniques and environmental factors that shape barley’s nutritional profile. Full article

This study aimed to optimize the inoculation dosage and fermentation duration to enhance the protein content and reduce soluble oligosaccharides in soybean meal using Aspergillus oryzae and assessed its performance in dog food extrusion. A 3 × 5 factorial design was used to determine the optimal fermentation conditions. These conditions were applied to ferment soybean meal in bulk for nutritional analysis. Finally, the impact of fermentation on extrusion processing was assessed by formulating and extruding four diets: SBM (30% soybean meal), AMF (30% soybean meal with 1% Amaferm^®—A. oryzae biomass), FSBM (30% fermented soybean meal), and SPI (18% soy protein isolate). Diets were extruded with a single-screw extruder, and physical characteristics of kibbles, particle size distribution, and viscosity of raw mixes were analyzed. The optimal fermentation conditions were 1 × 10⁴ spore/g substrate for 36 h, which increased the crude protein content by 4.63% DM, methionine and cysteine total content by 0.15% DM, and eliminated sucrose, while significantly reducing stachyose, raffinose, and verbascose (95.22, 87.37, and 41.82%, respectively). The extrusion results showed that FSBM had intermediate specific mechanical energy (SME), in-barrel moisture requirements, and sectional expansion index (198.7 kJ/kg, 28.2%, and 1.80, respectively) compared with SBM (83.7 kJ/kg, 34.5%, and 1.30, respectively) and SPI (305.3 kJ/kg, 33.5%, and 2.55, respectively). The FSBM also exhibited intermediate particle size distribution and the least raw mix viscosity. These findings demonstrate that A. oryzae fermentation enhances the nutrient profile of soybean meal while improving extrusion efficiency and kibble quality, supporting its potential use as a sustainable pet food ingredient. Full article