Search Results (14,951)

CD26 (dipeptidyl peptidase-4) is a marker of colorectal cancer stem cells with high metastatic potential and resistance to therapy. Although CD26 expression is known to be associated with tumor progression, its functional involvement in epithelial-mesenchymal transition (EMT) and metastasis remains to be fully elucidated. In this study, we aimed to investigate the effects of a monoclonal anti-CD26 antibody on EMT-related phenotypes and metastatic behavior in colorectal cancer cells. We evaluated changes in EMT markers by quantitative PCR and Western blotting, assessed cell motility and invasion using scratch wound-healing and Transwell assays, and examined metastatic potential in vivo using a splenic injection mouse model. Treatment with the anti-CD26 antibody significantly increased the expression of the epithelial marker E-cadherin and reduced levels of EMT-inducing transcription factors, including ZEB1, Twist1, and Snail1, at the mRNA and protein levels. Functional assays revealed that the antibody markedly inhibited cell migration and invasion in vitro without exerting cytotoxic effects. Furthermore, systemic administration of the anti-CD26 antibody significantly suppressed the formation of liver metastases in vivo. These findings suggest that CD26 may contribute to the regulation of EMT and metastatic behavior in colorectal cancer. Our data highlight the potential therapeutic utility of CD26-targeted antibody therapy for suppressing EMT-associated phenotypes and metastatic progression. 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

Fusarium diseases are among the most dangerous fungal diseases of plants. To date, there are no plant protectants that completely prevent fusariosis. Current breeding trends are therefore focused on increasing genetic resistance. While global modern maize breeding relies on various molecular genetics techniques, they are useless without a precise characterization of genomic regions that determine plant physiological responses to fungi. The aim of this study was thus to characterize the expression of candidate genes that were previously reported by our team as harboring markers linked to fusarium resistance in maize. The plant material included one susceptible and four resistant varieties. Biotic stress was induced in adult plants by inoculation with fungal spores under controlled conditions. qRT-PCR was performed. The analysis focused on four genes that encode for GDSL esterase/lipase (LOC100273960), putrescine hydroxycinnamyltransferase (LOC103649226), peroxidase 72 (LOC100282124), and uncharacterized protein (LOC100501166). Their expression showed differences between analyzed time points and varieties, peaking at 6 hpi. The resistant varieties consistently showed higher levels of expression compared to the susceptible variety, indicating their stronger defense responses. Moreover, to better understand the function of these genes, their expression in various organs and tissues was also evaluated using publicly available transcriptomic data. Our results are consistent with literature reports that clearly indicate the involvement of these genes in the resistance response to fusarium. Thus, they further emphasize the high usefulness of the previously selected markers in breeding programs to select fusarium-resistant maize genotypes. Full article

Gastrodia elata Blume is an important medicinal orchid, yet its large-scale cultivation is increasingly threatened by fungal diseases. The 4-coumarate–CoA ligase (4CL) gene family directs a key step in phenylpropanoid metabolism and plant defence, but its composition and function in G. elata have not been investigated. We mined the G. elata genome for 4CL homologues, mapped their chromosomal locations, and analysed their gene structures, conserved motifs, phylogenetic relationships, promoter cis-elements and codon usage bias. Publicly available transcriptomes were used to examine tissue-specific expression and responses to fungal infection. Subcellular localisation of selected proteins was verified by transient expression in Arabidopsis protoplasts. Fourteen Ge4CL genes were identified and grouped into three clades. Two members, Ge4CL2 and Ge4CL5, were strongly upregulated in tubers challenged with fungal pathogens. Ge4CL2 localised to the nucleus, whereas Ge4CL5 localised to both the nucleus and the cytoplasm. Codon usage analysis suggested that Escherichia coli and Oryza sativa are suitable heterologous hosts for Ge4CL expression. This study provides the first genome-wide catalogue of 4CL genes in G. elata and suggests that Ge4CL2 and Ge4CL5 may participate in antifungal defence, although functional confirmation is still required. The dataset furnishes a foundation for functional characterisation and the molecular breeding of disease-resistant G. elata cultivars. Full article

Reactive oxygen species (ROS) are often seen solely as harmful byproducts of oxidative metabolism, yet evidence reveals their paradoxical roles in both promoting and inhibiting cancer progression. Despite advances, precise context-dependent mechanisms by which ROS modulate oncogenic signaling, therapeutic response, and tumor microenvironment dynamics remain unclear. Specifically, the spatial and temporal aspects of ROS regulation (i.e., the distinct effects of mitochondrial versus cytosolic ROS on the PI3K/Akt and NF-κB pathways, and the differential cellular outcomes driven by acute versus chronic ROS exposure) have been underexplored. Additionally, the specific contributions of ROS-generating enzymes, like NOX isoforms and xanthine oxidase, to tumor microenvironment remodeling and immune modulation remain poorly understood. This review synthesizes current findings with a focus on these critical gaps, offering novel mechanistic insights into the dualistic nature of ROS in cancer biology. By systematically integrating data on ROS source-specific functions and redox-sensitive signaling pathways, the complex interplay between ROS concentration, localization, and persistence is elucidated, revealing how these factors dictate the paradoxical support of tumor progression or induction of cancer cell death. Particular attention is given to antioxidant mechanisms, including NRF2-mediated responses, that may undermine the efficacy of ROS-targeted therapies. Recent breakthroughs in redox biosensors (i.e., redox-sensitive fluorescent proteins, HyPer variants, and peroxiredoxin–FRET constructs) enable precise, real-time ROS imaging across subcellular compartments. Translational advances, including redox-modulating drugs and synthetic lethality strategies targeting glutathione or NADPH dependencies, further highlight actionable vulnerabilities. This refined understanding advances the field by highlighting context-specific vulnerabilities in tumor redox biology and guiding more precise therapeutic strategies. Continued research on redox-regulated signaling and its interplay with inflammation and therapy resistance is essential to unravel ROS dynamics in tumors and develop targeted, context-specific interventions harnessing their dual roles. Full article

The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the food chain, thereby diminishing the efficacy of antibiotics in treating bacterial infections. Current research explores the potential of essential oils from derived medicinal plants as alternative phytobiotics. This review examines modern encapsulation strategies that incorporate essential oils into natural-origin matrices to improve their stability and control their release both in vitro and in vivo. We discuss a range of encapsulation approaches utilizing polysaccharides, gums, proteins, and lipid-based carriers. This review highlights the increasing demand for antibiotic alternatives in animal nutrition driven by regulatory restrictions, and the potential benefits of essential oils in enhancing feed palatability and stabilizing the intestinal microbiome in monogastric animals and ruminants. Additionally, we address the economic viability and encapsulation efficiency of different matrix formulations. Full article

The secondary metabolites of the fungus Penicillium thymicola, fumiquinazolines F and G, have antibacterial and antifungal characteristics; however, their potential anti-tumor action against human cancer cells remains unknown. The goal of our study was to determine the biological efficacy of fumiquinazolines F and G on breast and prostate cancer cells. Cancer cell proliferation and migration were monitored in real time using xCELLigence technology and flow cytometry. Alterations in mRNA and protein expression were assessed by RT-qPCR, ELISA, and Western blotting. Our data indicate that fumiquinazolines F and G are more effective in inhibiting breast cancer cell proliferation than prostate cancer cells. Fumiquinazoline F is active against both hormone-dependent epithelial MCF-7 (IC₅₀ 48 μM) and hormone-resistant triple-negative mesenchymal MDA-MB-231 breast cancer cells (IC₅₀ 54.1 μM). The metabolite has low cytotoxicity but slows cell cycle progression. In fumiquinazoline F-treated MDA-MB-231 cells, the levels of proteins implicated in epithelial–mesenchymal transition (EMT) (such as E-cadherin, vimentin, and CD44) fluctuate, resulting in a decrease in cell migratory rate and adhesion to a hyaluronic acid-coated substrate. Thus, fumiquinazolines F and G exhibit anticancer activity by inhibiting EMT, cell proliferation, and migration, hence reverting malignant cells to a less pathogenic phenotype. The compound’s multi-target anticancer profile underscores its potential for further exploration of novel EMT-regulating pathways. Full article

Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies characterized by a poor prognosis and resistance to conventional therapies. Mounting evidence suggests the pivotal role of epithelial–mesenchymal transition (EMT) in tumor progression, metastasis, and therapeutic resistance in these cancers. Protein induced by vitamin K absence II (PIVKA-II)—a valuable HCC detector—has ultimately emerged as a potentially relevant biomarker in PDAC, serving as both a serum biomarker and a prognostic indicator. This study investigates the putative link between PIVKA-II expression and the EMT process in HCC and PDAC. Using a Western blot analysis and electrochemiluminescence immunoassay (ECLIA), we quantified PIVKA-II serum levels alongside two canonical EMT markers—Vimentin and E-cadherin—in selected cohorts. Emerging data suggest a dual, context-dependent role for PIVKA-II. Beyond its diagnostic value in both malignancies, its co-expression with EMT markers points to a potential mechanistic involvement in tumor invasiveness and phenotypic plasticity. Notably, the selective detection of E-cadherin in HCC implies limited EMT activation and a preservation of the epithelial phenotype, whereas the higher expression of Vimentin in PDAC reflects a more substantial shift toward EMT. We provide a comprehensive analysis of key molecular markers, their involvement in EMT-driven pathophysiological mechanisms, and their potential as novel diagnostic tools. Full article

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable adjuvants for azoles and allylamines remains limited. Studies have demonstrated that the human host environment provides multiple carbon sources, which can influence the susceptibility of C. albicans to antifungal agents. Therefore, a comprehensive investigation into the mechanisms by which carbon sources modulate the susceptibility of C. albicans to azoles may uncover a novel pathway for enhancing the antifungal efficacy of azoles. Methods: This study explored the impact of various carbon sources on the antifungal efficacy of azoles through methodologies including minimum inhibitory concentration (MIC) assessments, super-MIC growth (SMG) assays, disk diffusion tests, and spot assays. Additionally, the mechanism by which galactose augments the antifungal activity of azoles was investigated using a range of experimental approaches, such as gene knockout and overexpression techniques, quantitative real-time PCR (qRT-PCR), Western blot analysis, and cycloheximide (CHX) chase experiments. Results: This study observed that galactose enhances the efficacy of azoles against C. albicans by inhibiting the translation of Erg1. This results in the suppression of Erg1 protein levels and subsequent inhibition of ergosterol biosynthesis in C. albicans. Conclusions: In C. albicans, the translation of Erg1 is inhibited when galactose is utilized as a carbon source instead of glucose. This novel discovery of galactose’s inhibitory effect on Erg1 translation is expected to enhance the antifungal efficacy of azoles. Full article

Legumes are among the most important crops globally, serving as a major food source for protein and oil. In tropical regions, the cultivation of legumes has expanded significantly due to the increasing demand for food, plant-based products, and sustainable agriculture practices. However, tropical environments pose unique challenges, including high temperatures, erratic rainfall, soil infertility, and a high incidence of pests and diseases. Indeed, legumes are vulnerable to infections caused by bacteria, fungi, oomycetes, viruses, and nematodes. This review highlights the importance of legumes in tropical farming and discusses major diseases affecting productivity and their impact on the economy, environment, and lives of smallholder legume farmers. We emphasize the use of legume genetic resources and breeding, and biotechnology innovations to foster resistance and address the challenges posed by pathogens in legumes. However, an integrated approach that includes other cultivation techniques (e.g., crop rotation, rational fertilization, deep plowing) remains important for the prevention and control of diseases in legume crops. Finally, we highlight the contributions of plant genetic resources to smallholder resilience and food security. Full article

The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve satisfactory results. Plants induce defense responses to natural elicitors by interpreting multiple genes that encode proteins, including enzymes, secondary metabolites, and pathogenesis-related (PR) proteins. These responses characterize systemic acquired resistance. Humic substances trigger positive local and systemic physiological responses through a complex network of hormone-like signaling pathways and can be used to induce biotic and abiotic stress resistance. This study aimed to assess the effect of humic substances on the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POX), and β-1,3-glucanase (GLU) used as a resistance marker in various plant species, including orange, coffee, sugarcane, soybeans, maize, and tomato. Seedlings were treated with a dilute aqueous suspension of humic substances (4 mM C L⁻¹) as a foliar spray or left untreated (control). Leaf tissues were collected for enzyme assessment two days later. Humic substances significantly promoted the systemic acquired resistance marker activities compared to the control in all independent assays. Overall, all enzymes studied in this work, PAL, GLUC, and POX, showed an increase in activity by 133%, 181%, and 149%, respectively. Among the crops studied, citrus and coffee achieved the highest activity increase in all enzymes, except for POX in coffee, which showed a decrease of 29% compared to the control. GLUC exhibited the highest response to HS treatment, the enzyme most prominently involved in increasing enzymatic activity in all crops. Plants can improve their resistance to pathogens through the exogenous application of HSs as this promotes the activity of enzymes related to plant resistance. Finally, we consider the potential use of humic substances as a natural chemical priming agent to boost plant resistance in agriculture Full article

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

The escalating global challenges of antimicrobial resistance (AMR) and cancer necessitate innovative therapeutic solutions from natural sources. This study investigated the multifaceted therapeutic potential of pigment-enriched plant extracts. We screened diverse plant extracts for antimicrobial and antibiofilm activity against multidrug-resistant bacteria and fungi. Hibiscus sabdariffa emerged as the most promising, demonstrating potent broad-spectrum antimicrobial and significant antibiofilm activity. Sub-inhibitory concentrations of H. sabdariffa robustly downregulated essential bacterial virulence genes and suppressed aflatoxin gene expression. Comprehensive chemical profiling via HPLC identified major anthocyanin glucosides, while GC-MS revealed diverse non-pigment bioactive compounds, including fatty acids and alcohols. Molecular docking suggested favorable interactions of key identified compounds (Cyanidin-3-O-glucoside and 1-Deoxy-d-arabitol) with E. coli outer membrane protein A (OmpA), indicating potential antiadhesive and antimicrobial mechanisms. Furthermore, H. sabdariffa exhibited selective cytotoxicity against MCF-7 breast cancer cells. These findings establish H. sabdariffa pigment-enriched extract as a highly promising, multi-functional source of novel therapeutics, highlighting its potential for simultaneously addressing drug resistance and cancer challenges through an integrated chemical, biological, and computational approach. Full article