Search Results (44,611)

The global rise in antimicrobial resistance poses a major threat to public health, with multidrug-resistant bacterial infections expected to surpass cancer in mortality by 2050. As traditional antibiotic pipelines stagnate, novel therapeutic alternatives are critically needed. Antimicrobial peptides (AMPs), particularly those derived from marine organisms, have emerged as promising antimicrobial candidates due to their broad-spectrum activity, structural diversity, and distinctive mechanisms of action. Unlike conventional antibiotics, AMPs can disrupt microbial membranes, inhibit biofilm formation, and even modulate immune responses, making them highly effective against resistant bacteria. This review highlights the potential of marine AMPs as next-generation therapeutics, emphasizing their efficacy against multidrug-resistant pathogens and biofilm-associated infections. Furthermore, marine AMPs show promise in combating persister cells and disrupting quorum sensing pathways, offering new strategies for tackling chronic infections. Despite their potential, challenges such as production scalability and limited clinical validation remain; nevertheless, the use of new technologies and bioinformatic tools is accelerating the discovery and optimization of these peptides, paving the way for bypassing these challenges. This review consolidates current findings on marine AMPs, advocating for their continued exploration as viable tools in the fight against antimicrobial resistance. Full article

In this study, a series of novel alkoxylated resorcinarenes were synthesized using secondary and tertiary alcohols under mild catalytic conditions involving iminodiacetic acid. Structural characterization, including single-crystal X-ray diffraction, confirmed the successful incorporation of branched alkyl chains and highlighted the influence of substitution patterns on molecular packing. Notably, detailed mass spectrometric analysis revealed that, under specific conditions, the reaction pathway may shift toward the formation of defined oligomeric species with supramolecular characteristics—an observation that adds a new dimension to the synthetic potential of this system. To complement the chemical analysis, selected derivatives were evaluated for biological activity, focusing on bacterial growth and biofilm formation. Using four clinically relevant strains (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis), we assessed both planktonic proliferation (OD₆₀₀) and biofilm biomass (crystal violet assay). Compound 2c (2-pentanol derivative) consistently promoted biofilm formation, particularly in S. aureus and B. subtilis, while having limited cytotoxic effects. In contrast, compound 2e and the DMSO control exhibited minimal impact on biofilm development. The results suggest that specific structural features of the alkoxy chains may modulate microbial responses, potentially via membrane stress or quorum sensing interference. This work highlights the dual relevance of alkoxylated resorcinarenes as both supramolecular building blocks and modulators of microbial behavior. Full article

Regenerative endodontics seeks to restore the vascularized pulp–dentin complex following conventional root canal therapy, yet reliable neovascularization within the constrained root canal remains a key challenge. This study investigates the development of an injectable, dual-curing hydrogel based on methacrylated decellularized amniotic membrane (dAM-MA) and compares its performance to a conventional gelatin methacryloyl (GelMA). The dAM-MA platform was designed for biphasic release, incorporating both free vascular endothelial growth factor (VEGF) for an initial burst and matrix-metalloproteinase-cleavable VEGF conjugates for sustained delivery. The dAM-MA hydrogel achieved shape-fidelity via thermal gelation at 37 °C and possessed tunable stiffness (0.5–7.8 kPa) after visible-light irradiation. While showing high cytocompatibility comparable to GelMA (>125% hDPSC viability), the dAM-MA platform markedly outperformed the control in promoting endothelial tube formation (up to 800 µm total length; 42 branch points at 96 h). The biphasic VEGF release from dAM-MA matched physiological injury kinetics, driving both early chemotaxis and late vessel maturation. These results demonstrate that dAM-MA hydrogels combine native extracellular matrix complexity with practical, dual-curing injectability and programmable VEGF kinetics, offering a promising scaffold for minimally invasive pulp–dentin regeneration. Full article

Traditional brain emulation approaches often rely on classical computational models that inadequately capture the stochastic, nonlinear, and potentially coherent features of biological neural systems. In this position paper, we introduce NeuroQ a quantum-inspired framework grounded in stochastic mechanics, particularly Nelson’s formulation. By reformulating the FitzHugh–Nagumo neuron model with structured noise, we derive a Schrödinger-like equation that encodes membrane dynamics in a quantum-like formalism. This formulation enables the use of quantum simulation strategies—including Hamiltonian encoding, variational eigensolvers, and continuous-variable models—for neural emulation. We outline a conceptual roadmap for implementing NeuroQ on near-term quantum platforms and discuss its broader implications for neuromorphic quantum hardware, artificial consciousness, and time-symmetric cognitive architectures. Rather than demonstrating a working prototype, this work aims to establish a coherent theoretical foundation for future research in quantum brain emulation. Full article

Salinity is a major abiotic stress limiting black gram (Vigna mungo) productivity, particularly in arid and semi-arid regions. Saline soils negatively impact plant growth, nodulation, nitrogen fixation, and yield. This study evaluated the efficacy of co-inoculating salt-tolerant plant growth-promoting bacteria Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 on black gram performance under saline field conditions (EC: 8.87 dS m⁻¹; pH: 8.37) with low organic carbon (0.6%) and nutrient deficiencies. In vitro assays demonstrated the biocontrol potential of SPR11, inhibiting Fusarium oxysporum and Macrophomina phaseolina by 76% and 62%, respectively. Germination assays and net house experiments under 300 mM NaCl stress showed that co-inoculation significantly improved physiological traits, including germination rate, root length (61.39%), shoot biomass (59.95%), and nitrogen fixation (52.4%) in nitrogen-free media. Field trials further revealed enhanced stress tolerance markers: chlorophyll content increased by 54.74%, proline by 50.89%, and antioxidant enzyme activities (SOD, CAT, PAL) were significantly upregulated. Electrolyte leakage was reduced by 55.77%, indicating improved membrane stability. Agronomic performance also improved, with co-inoculated plants showing increased root length (7.19%), grain yield (15.55 q ha⁻¹; 77.04% over control), total biomass (26.73 q ha⁻¹; 57.06%), and straw yield (8.18 q ha⁻¹). Pod number, seed count, and seed weight were also enhanced. Nutrient analysis showed elevated uptake of nitrogen, phosphorus, potassium, and key micronutrients (Zn, Fe) in both grain and straw. To the best of our knowledge, this is the very first field-based report demonstrating the synergistic benefits of co-inoculating Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 in black gram under saline, nutrient-poor conditions without external nitrogen inputs. The results highlight a sustainable strategy to enhance legume productivity and resilience in salt-affected soils. Full article

Exosomes are membranous vesicles that play a crucial role as intercellular messengers. Cells secrete exosomes, which can be found in a variety of bodily fluids such as amniotic fluid, semen, breast milk, tears, saliva, urine, blood, bile, ascites, and cerebrospinal fluid. Exosomes have a distinct bilipid protein structure and can be as small as 30–150 nm in diameter. They may transport and exchange multiple cellular messenger cargoes across cells and are used as a non-invasive biomarker for various illnesses. Due to their unique features, exosomes are recognized as the most effective biomarkers for cancer and other disease detection. We give a review of the most current applications of exosomes derived from various sources in the prognosis and diagnosis of multiple diseases. This review also briefly examines the significance of exosomes and their applications in biomedical research, including the use of aptamers and antibody–antigen functionalized biosensors. Full article

Electrospun nanofibrous membranes have gained considerable attention in bone tissue engineering due to their ability to mimic the extracellular matrix and provide a suitable environment for cell attachment and proliferation. This study investigates the fabrication, characterization, and biocompatibility of poly(L-lactic acid) (PLA)-based membranes enhanced with periclase (MgO) and gold nanoparticles (AuNPs). The membranes were fabricated using an optimized electrospinning process and subsequently characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FT-IR), and contact angle measurements. Additionally, in vitro biodegradation studies in simulated body fluid (SBF) and cytocompatibility tests with osteoblast-like cells were conducted. The results demonstrated that the incorporation of MgO and AuNPs significantly influenced the structural and chemical properties of the membranes, improving their wettability and bioactivity. SEM imaging confirmed uniform fiber morphology with well-distributed nanoparticles. FT-IR spectroscopy indicated successful integration of bioactive components into the PLA matrix. Cytocompatibility assays showed that modified membranes promoted higher osteoblast adhesion and proliferation compared to pristine PLA membranes. Furthermore, biodegradation studies revealed a controlled degradation rate suitable for guided bone regeneration applications. These findings suggest that electrospun PLA membranes enriched with MgO and AuNPs present a promising biomaterial for GBR applications, offering improved bioactivity, mechanical stability, and biocompatibility. Full article

Municipal wastewaters pose a severe risk to the environment and human health when discharged untreated. This is due to their high content of pathogens, such as viruses and bacteria, which can cause diseases like cholera. Herein, the research and development of porphyrin-modified polyethersulfone (PES) ultrafiltration (UF) membranes was conducted to improve bacterial inactivation in complex municipal wastewater and enhance the fouling resistance and filtration performance. The synthesis and fabrication of porphyrin nanofillers and the resultant membrane characteristics were studied. The incorporation of porphyrin-based nanofillers improved the membrane’s hydrophilicity, morphology, and flux (247 Lm⁻² h⁻¹), with the membrane contact angle (CA) decreasing from 90° to ranging between 58° and 50°. The membrane performance was monitored for its flux, antifouling properties, reusability potential, municipal wastewater, and humic acid. The modified membranes demonstrated an effective application in wastewater treatment, achieving notable antibacterial activity, particularly under light exposure. The In-BP@SW/PES membrane demonstrated effective antimicrobial photodynamic effects against both Gram-positive S. aureus and Gram-negative E. coli. It achieved at least a 3-log reduction in bacterial viability, meeting Food and Drug Administration (FDA) standards for efficient antimicrobial materials. Among the variants tested, membranes modified with In-PB@SW nanofillers exhibited superior antifouling properties with flux recovery ratios (FRRs) of 78.9% for the humic acid (HA) solution and 85% for the municipal wastewater (MWW), suggesting a strong potential for long-term filtration use. These results highlight the promise of porphyrin-functionalized membranes as multifunctional tools in advanced water treatment technologies. Full article

Objective: Visceral leishmaniasis (VL), a Neglected Tropical Disease caused by Leishmania donovani, remains insufficiently addressed by current therapies due to high toxicity, poor efficacy, and immunosuppressive complications. This study aimed to identify and characterize repurposed drugs that simultaneously target parasite-encoded and host-associated mechanisms essential for VL pathogenesis. Methods: Two complementary in silico drug repurposing strategies were employed. The first method utilized electron–ion interaction potential (EIIP) screening followed by molecular docking and molecular dynamics (MD) simulations targeting two L. donovani proteins: Rab5a and pteridine reductase 1 (PTR1). The second approach employed network-based drug repurposing using the Drugst.One platform, prioritizing candidates via STAT3-associated gene networks. Predicted drug–target complexes were validated by 100 ns MD simulations, and pharmacokinetic parameters were assessed via ADMET profiling using QikProp v7.0 and SwissADME web server. Results: Entecavir and valganciclovir showed strong binding to Rab5a and PTR1, respectively, with Glide Scores of −9.36 and −9.10 kcal/mol, and corresponding MM-GBSA ΔG_bind values of −14.00 and −13.25 kcal/mol, confirming their stable interactions and repurposing potential. Network-based analysis identified nifuroxazide as the top candidate targeting the host JAK2/TYK2–STAT3 axis, with high stability confirmed in MD simulations. Nifuroxazide also displayed the most favorable ADMET profile, including oral bioavailability, membrane permeability, and absence of PAINS alerts. Conclusions: This study highlights the potential of guanine analogs such as entecavir and valganciclovir, and the nitrofuran derivative nifuroxazide, as promising multi-target drug repurposing candidates for VL. Their mechanisms support a dual strategy targeting both parasite biology and host immunoregulation, warranting further preclinical investigation. Full article

Skin aging is closely related to mitochondrial dysfunction and cell cycle abnormalities, and developing intervention strategies targeting mitochondrial quality control is an important direction for anti-aging research. In this study, we investigated the anti-aging mechanism of Camellia japonica flower (CJF) extract and its active ingredient hyperoside based on a doxorubicin (DOX)-induced endogenous senescence model in human skin fibroblasts (HSFs). LC-MS proteomics analysis revealed that CJF extract and hyperoside specifically activated the FUNDC1-mediated mitochondrial autophagy pathway, significantly ameliorated the DOX-induced decrease in mitochondrial membrane potential and the accumulation of reactive oxygen species (ROS), and alleviated the cellular S-phase blockade and reversed the high expression of senescence-associated β-galactosidase (SA-β-gal). Further studies showed that the two cleared damaged mitochondria by enhancing mitochondrial autophagy and restoring cellular energy metabolism homeostasis while promoting type III collagen and elastin synthesis and repairing the expression of Claudin 1 related to skin barrier function. For the first time, the present study reveals the molecular mechanism of CJF extract in delaying skin aging by regulating the FUNDC1-dependent mitochondrial autophagy pathway, which provides a theoretical basis and a candidate strategy for developing novel anti-aging agents targeting mitochondrial quality control. Full article

Antibiotic misuse accelerates resistance dissemination via plasmid conjugation, but quorum sensing (QS) regulatory mechanisms remain undefined. Using Escherichia coli (E. coli) MG1655 conjugation models (RP4-7/EC600 plasmids), we demonstrate that long-chain acyl-homoserine lactones (C10/C12-HSL) enhance transfer frequency by up to 7.7-fold (200 μM C12-HSL; p < 0.001), while quorum-quenching by sub-inhibitory vanillin suppressed this effect by 95% (p < 0.0001). C12-HSL compromised membrane integrity via ompF upregulation (4-fold; p < 0.01) and conjugative pore assembly (trbBp upregulated by 1.38-fold; p < 0.05), coinciding with ROS accumulation (1.5-fold; p < 0.0001) and SOS response activation (recA upregulated by 1.68-fold; p < 0.001). Crucially, rpoS and rmf deletion mutants reduced conjugation by 65.5% and 55.8%, respectively (p < 0.001), exhibiting attenuated membrane permeability (≤65.5% reduced NPN influx; p < 0.0001), suppressed ROS (≤54% downregulated; p < 0.0001), and abolished transcriptional induction of conjugation/stress genes. Reciprocal RpoS–RMF (ribosomal hibernation factor) crosstalk was essential for AHL responsiveness, with deletions mutually suppressing expression (≤65.9% downregulated; p < 0.05). We establish a hierarchical mechanism wherein long-chain AHLs drive resistance dissemination through integrated membrane restructuring, stress adaptation, and RpoS–RMF-mediated genetic plasticity, positioning QS signaling as a viable target for curbing resistance spread. Full article

Background/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus seed extract in gastric cancer cells. Antioxidant capacity (DPPH, ABTS) and total phenolic and flavonoid contents were analyzed. Cytotoxicity was assessed using the MTT assay in HGC27, MKN45, and AGS gastric cancer cell lines and CCD-1072Sk fibroblasts. Apoptosis, mitochondrial membrane potential (MMP), and cell cycle changes were evaluated via Annexin V-FITC/PI, Rhodamine 123, and PI staining, respectively. RT-qPCR and gene enrichment analyses were conducted to investigate the molecular mechanisms. Apoptosis-related protein expression was analyzed through enzyme-linked immunosorbent assay (ELISA). Results: The extract exhibited high antioxidant activity and a significant phenolic content. It reduced cell viability in a dose-dependent manner in gastric cancer cells, while exerting low toxicity in fibroblasts. It significantly increased apoptosis, induced G0/G1-phase cell cycle arrest, upregulated pro-apoptotic genes (CASP3, CASP7, TP53, BCL2L11), and downregulated anti-apoptotic genes (XIAP, NOL3). Gene enrichment analysis highlighted pathways like apoptosis, necrosis, and cysteine endopeptidase activity. The extract also disrupted MMP, inhibited migration and spheroid formation, suppressed EMT markers (SNAIL, SLUG, TWIST1, N-CADHERIN), and upregulated E-CADHERIN. The expression of Caspase 3 and Bax proteins increased and Bcl2 protein decreased. Conclusions: These findings suggest that Vitex agnus-castus seed extract exerts strong anticancer effects in gastric cancer cells by promoting apoptosis, reducing proliferation, and inhibiting migration. Further studies are warranted to explore its clinical relevance. Full article

Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article

Candidiasis arises from the proliferation of Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have previously identified the N-[(4-sulfamoylphenyl)methyl][1,1′-biphenyl]-4-carboxamide to have fungistatic and fungicidal properties, likely due to the hydrophobic biphenyl–chemical features affecting the structural organization of Candida spp. cell membrane. Here, we designed and synthesized a novel series of twelve 5-arylfuran-2-carboxamide derivatives bearing a new hydrophobic tail as bioisosteric replacement of the diphenyl fragment. Its antifungal effectiveness against C. albicans, C. glabrata, and C. parapsilosis, including ATCC and clinically isolated strains, was assessed for all compounds. The most active compound was N-benzyl-5-(3,4-dichlorophenyl)furan-2-carboxamide (6), with fungistatic and fungicidal effects against C. glabrata and C. parapsilosis strains (MIC = 0.062–0.125 and 0.125–0.250 mg/mL, respectively). No synergistic effects were observed when combined with fluconazole. Interestingly, fluorescent microscopy analysis after staining with SYTO 9 and propidium iodide revealed that compound 6 affected the cell membrane integrity in C. albicans strain 16. Finally, carboxamide 6 exhibited a dose-dependent cytotoxicity on erythrocytes, based on assessing the LDH release. Full article

Background/Objectives: Antimicrobial resistance (AMR) contributes to millions of deaths globally each year, creating an urgent need for new therapeutic agents. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their potential to combat AMR pathogens. This study aimed to evaluate the antimicrobial activity of an AMP from a soil-derived bacterial isolate against Gram-negative bacteria. Method: Soil bacteria were isolated and screened for antimicrobial activity. The bioactive peptide was purified and determined its structure and antimicrobial efficacy. Genomic analysis was conducted to predict the biosynthetic gene clusters (BGCs) responsible for AMP production. Results: Genomic analysis identified the isolate as Paenibacillus sp. Na14, which exhibited low genomic similarity (61.0%) to other known Paenibacillus species, suggesting it may represent a novel species. The AMP from the Na14 strain exhibited heat stability up to 90 °C for 3 h and retained its activity across a broad pH range from 3 to 11. Structural analysis revealed that the Na14 peptide consisted of 14 amino acid residues, adopting an α-helical structure. This peptide exhibited bactericidal activity at concentrations of 2–4 µg/mL within 6–12 h, and its killing rate was concentration-dependent. The peptide was found to disrupt the bacterial membranes. The Na14 peptide shared 64.29% sequence similarity with brevibacillin 2V, an AMP from Brevibacillus sp., which also belongs to the Paenibacillaceae family. Genomic annotation identified BGCs associated with secondary metabolism, with a particular focus on non-ribosomal peptide synthetase (NRPS) gene clusters. Structural modeling of the predicted NRPS enzymes showed high similarity to known NRPS modules in Brevibacillus species. These genomic findings provide evidence supporting the similarity between the Na14 peptide and brevibacillin 2V. Conclusions: This study highlights the discovery of a novel AMP with potent activity against Gram-negative pathogens and provides new insight into conserved AMP biosynthetic enzymes within the Paenibacillaceae family. Full article