Search Results (1,811)

Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) responsiveness of nanomaterials, there is tremendous potential for their applications in breast cancer diagnosis and therapy. In the diagnostic arena, nanomaterials serve as core components of novel contrast agents (e.g., gold nanorods, quantum dots, superparamagnetic iron oxide nanoparticles) and biosensing platforms, substantially enhancing the sensitivity and specificity of molecular imaging modalities—such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging (FLI)—and enabling high-sensitivity detection of circulating tumor cells and tumor-derived exosomes, among various liquid biopsy biomarkers. In therapy, nanoscale carriers (e.g., liposomes, polymeric micelles) improve tumor targeting and accumulation efficiency through passive and active targeting strategies, thereby augmenting anticancer efficacy while effectively reducing systemic toxicity. Furthermore, nanotechnology has spurred the rapid advancement of emerging modalities, including photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Notably, the construction of theranostic platforms that integrate diagnostic and therapeutic units within a single nanosystem enables in vivo, real-time visualization of drug delivery, treatment monitoring, and therapeutic response feedback, providing a powerful toolkit for advancing breast cancer toward personalized, precision medicine. Despite challenges that remain before clinical translation—such as biocompatibility, scalable manufacturing, and standardized evaluation—nanomaterials are undoubtedly reshaping the paradigm of breast cancer diagnosis and treatment. Full article

Spectroscopic techniques offer significant potential for investigating ligand–protein interactions, particularly for assessing conformational modifications and binding affinity. In the present study, a complementary approach combining near-UV circular dichroism (CD) and second-derivative fluorescence spectroscopy was applied to evaluate how two representative nonsteroidal anti-inflammatory drugs—phenylbutazone (PHB, a marker of Sudlow’s site I) and ketoprofen (KP, a marker of Sudlow’s site II)—influence the tertiary structure of human serum albumin in its native form (HSA) and after glycation by glucose (gHSA_GLC), fructose (gHSA_FRC), and glucose–fructose syrup (gHSA_syrup). The results demonstrate that glycation substantially modifies the tertiary structure of HSA and decreases its drug-binding capacity at Sudlow’s sites I and II, with the most pronounced conformational changes observed for gHSA_FRC, confirming fructose as the most reactive glycation agent. PHB induced distinct conformational rearrangements, including a characteristic increase in ellipticity near ~290 nm, indicating perturbations in the chiral microenvironment surrounding Trp214 within Sudlow’s site I. By contrast, KP induced weaker, site-specific structural changes, primarily within Phe-rich hydrophobic domains of site II. Glycation consistently increased the polarity and solvent exposure of aromatic residue microenvironments—particularly within Tyr-rich regions—while the local environment of Trp214 remained comparatively stable. These findings suggest that PHB and KP modulate the conformational flexibility of glycated HSA predominantly by reorganizing Tyr-rich regions rather than directly perturbing Trp214. Overall, the study shows that glycation heterogeneity significantly influences protein–drug interactions, with important implications for altered pharmacokinetics in diabetes and metabolic disorders. The combined application of near-UV CD and second-derivative fluorescence spectroscopy offers a sensitive and complementary strategy for distinguishing structural differences between non-glycated and glycated HSA and for characterizing drug–albumin interactions at the tertiary structural level of the macromolecule. Full article

This study synthesizes novel photosensitizer calcination betaine hydrochloride carbon dots (CBCDs) to address the critical challenge of Enterococcus faecalis (E. faecalis) biofilms, a major cause of root canal treatment failure. To this end, this study investigates the effective elimination via reactive oxygen species (ROS) mediated by these CBCDs. CBCDs were prepared by calcining betaine hydrochloride and rigorously characterized for their structural and chemical properties using transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Their optical characteristics were also thoroughly analyzed through UV-Vis and fluorescence spectroscopy. The RNO-ID assay was performed to explicitly confirm ROS production, particularly verifying significant singlet oxygen (¹O₂) generation. Bactericidal efficacy of the CBCDs was comprehensively evaluated against planktonic E. faecalis and its formed biofilms. Live/dead staining was subsequently performed to observe their state after treatment. As a result, TEM confirmed nanosized CBCDs, and FTIR/XPS analyses identified crucial functional groups. Colony Forming Unit (CFU) assays revealed a dose-dependent reduction in E. faecalis viability, achieving complete eradication at 200 mg/L under light irradiation. Complete cell death and inactivation of the formed biofilms with increasing CBCD concentrations were also strongly evidenced by red fluorescence. The obtained results underscore CBCDs as highly effective photodynamic agents for the robust elimination of E. faecalis biofilms, offering a promising new strategy to combat persistent oral infections. Full article

Objectives: Pretargeting strategies enhance the specificity and safety of radiopharmaceuticals by separating tumor targeting from radionuclide delivery. To address the rapid clearance and systemic exposure of directly labeled small-molecule agents, a DZ-1–based pretargeting system was developed, utilizing its broad-spectrum tumor-targeting characteristics. Methods: Three DZ-TCO precursors (DZ-1-TCO, DZ-Lys-TCO, and DZ-Lys-PEG₄-TCO) were synthesized and evaluated by near-infrared fluorescence imaging in HeLa and U87MG tumor-bearing mice. Two tetrazine probes (methyl-tetrazine and mono-substituted tetrazine) were labeled with ⁶⁸Ga to yield ⁶⁸Ga-DOTA-Me-Tz and ⁶⁸Ga-DOTA-H-Tz, whose stability was assessed in PBS and serum. Pretargeted PET imaging was performed using different precursor/probe combinations and pretargeting intervals (24, 48, and 72 h). Results: All precursors exhibited tumor accumulation peaking at 24 h and signal retention up to 96 h. Both ⁶⁸Ga-DOTA-Me-Tz and ⁶⁸Ga-DOTA-H-Tz maintained >85% radiochemical stability after 4 h. PET imaging identified DZ-Lys-TCO as the most effective precursor (1.98 ± 0.72 %ID/g, T/M 3.86 ± 0.91). Using ⁶⁸Ga-DOTA-H-Tz, the 48 h interval achieved optimal uptake (3.24 ± 0.95 %ID/g) with the highest tumor-to-muscle ratio (8.30 ± 3.39). Biodistribution confirmed rapid renal clearance, low off-target accumulation, and peak tumor uptake of 3.53 ± 1.76 %ID/g (T/M 10.9 ± 0.3 at 30 min). Conclusions: The DZ-TCO/⁶⁸Ga-DOTA-Tz pretargeting system enables high-contrast tumor imaging with low background. The combination of DZ-Lys-TCO and ⁶⁸Ga-DOTA-H-Tz at a 48 h interval provides optimal performance, representing a promising platform for precise and safe radiopharmaceutical imaging. Full article

Alzheimer’s disease (AD) is a worldwide problem due to the lack of effective therapy and accurate methods for timely diagnosis. The complexity of AD’s pathophysiology complicates the development of effective therapeutic agents, as most drugs act on only one therapeutic target, bypassing others. The design and development of multifunctional agents capable of altering metal ion-induced abnormalities, oxidative stress, and toxic beta amyloid (Aβ) aggregates is of interest. Herein, we report the first boron dipyrromethene (BODIPY) based bifunctional copper chelator with clioquinol, BDP-CLQ, capable of both optical detection of Aβ fibrils and copper chelation, with multiple anti-AD properties. Foremost, BDP-CLQ demonstrated a 3-fold and 5-fold fluorescence increase at 650 nm and 565 nm in the presence of Aβ and effective copper chelation (pK_d = 16.6 ± 0.3). In addition, BDP-CLQ demonstrated a potent inhibition of Aβ aggregation, reduction in Aβ-induced stiffness of neuronal cells, and antioxidant activity. BDP-CLQ is the first BODIPY-based fluorescent probe with multiple anti-AD activities, as well as the first clioquinol-based probe capable of Aβ optical visualization. This study demonstrates the prospects of the development of clioquinol-based theranostic probes since this allows combining several promising anti-AD actions in a single molecule and developing multi-targeted drugs. Full article

Root knot nematodes (RKNs; Meloidogyne spp.) are among the biotic stressors that reduce growth and yield by 25–100% in solanaceous crops like tomato. The present study screened 35 eggplant accessions against RKNs (inoculum: 1 J2/g soil). Average root galls and egg masses per root ranged from 6.66 to 196.66 and from 4.66 to 192.66, respectively. Of the 35 accessions, BR3 was identified as resistant, exhibiting low galling index (6.66 galls/root) and egg mass count (4.66 egg masses/root), along with the highest total phenolic content (1515.92 μg/g). The shaft grafting of the susceptible tomato variety Hisar Arun (scion) onto resistant eggplant accession BR3 (rootstock) achieved a 90% success rate. Three biocontrol agents, namely, Trichoderma viride, Paecilomyces lilacinus, and Pseudomonas fluorescence were applied @2 g and 4 g per kg of soil to enhance resistance against RKNs in the grafted tomato plants (Hisar Arun variety). Among these, P. lilacinus at 4 g/kg soil reduced root galls, egg masses, and final nematode population by 84.65%, 95.7%, and 82.12%, respectively, compared with positive controls. Grafted plants treated with P. lilacinus at 4 g/kg soil also exhibited superior growth parameters relative to the control plants. Hence, the Integrated Nematode Management (INM) strategy developed in the present study can be used for delivering natural resistance against root knot nematodes in tomato plants and other solanaceous crops. Full article

Fruit and coffee industries are responsible for huge quantities of agro-industrial wastes which is of great environmental and public health concern. Therefore, the aim of this work involves the use of such wastes for the production of β-D-glucan from basidiomycete strains which are powerful biological response modifiers in several clinical disorders. Experimental planning for optimization of several parameters was carried out by a full factorial of two levels of three factors for production of beta-glucans and basidiomycete species, where waste concentration and interaction between species and agro-industrial waste were the most important factors. The best conditions involved a basidiomycete strain of Lentinula edodes in a culture medium containing 400 g/L of waste coffee grounds which revealed the production of extracellular β-glucans (141.16 mg/L) at the 3rd day of fermentation. Intrinsic fluorescence properties of mushroom β-D-glucan were investigated by fluorescence spectroscopy as well as a fluorescence microtiter plate reader exhibiting emission peaks at 492 and 528 nm. Differential chromatographic behavior of β-D-glucan was investigated by immobilized metal affinity chromatography (IMAC) using epoxy-activated Sepharose 6B containing different chelating agents, spacer arms, and metal ions. One-step purification of β-D-glucan was devised using a column of epoxy-activated Sepharose 6B-IDA-Cu (II). FTIR analysis of several β-D-glucans from the chromatographic fractions was carried out to investigate their structural properties. Full article

Minimally invasive treatment is increasingly successful in managing carious lesions in primary teeth, owing to the regenerative capacity of the dental pulp and the possibility to influence the pulp–dentin complex. Chemo-mechanical caries excavation (CME) with Brix 3000, a papain-based enzymatic agent, allows selective removal of infected dentin while preserving affected dentin for potential remineralization. Fluorescence-aided caries excavation (FACE) enables visualization of porphyrins produced by cariogenic microorganisms, guiding selective dentin removal. In this study, 42 children aged 4–7 years with ICDAS II code 05–06 lesions in primary molars were treated, and the correlation between fluorescence intensity and cariogenic microbial load was evaluated. CME was performed using Brix 3000, and residual dentin was categorized by fluorescence as red, red with pale-pink areas, pale-pink, or non-fluorescent. Microbiological samples were collected pre- and post-excavation, cultured under standardized laboratory conditions, and quantitatively analyzed. Results showed that higher fluorescence intensity corresponded to increased presence of S. mutans (ρ = 0.945, p < 0.001), while other species were present in lower quantities. CME with Brix 3000 significantly reduced microbial load, and fluorescence reliably indicated areas requiring removal. These findings demonstrate that combining FACE with Brix 3000 allows precise, minimally invasive caries removal in primary teeth, providing an objective method to guide tissue-preserving excavation while effectively controlling cariogenic microorganisms. Full article

This study aimed to evaluate the antiproliferative, apoptotic, and oxidative stress-inducing effects of the combination of metformin and doxorubicin (adriamycin) in OVCAR3 and SKOV3 ovarian cancer cell lines and to investigate the potential synergistic interactions between the two agents. Cell viability was assessed using the MTT assay. Apoptosis was quantified via Annexin V/PI staining followed by flow cytometry. Caspase-8 and caspase-9 activities were measured using colorimetric assays. Oxidative stress parameters, including reactive oxygen species (ROS) and nitric oxide (NO), were determined using DCFH-DA fluorescence and the Griess assay, respectively. The mRNA expression levels of apoptosis-related genes (Bcl-2, Survivin, Bax, and Caspase-3) were analyzed by qRT-PCR. Drug interaction and synergy were evaluated using the Chou–Talalay combination index (CI) model and the highest single agent (HSA) model. Prognostic relevance of target genes and protein interaction networks was examined through TCGA and STRING databases. The metformin–doxorubicin combination demonstrated strong synergistic antiproliferative effects in both cell lines (CI < 0.7 in OVCAR3). The combination significantly increased apoptosis compared with single-agent treatments, yielding a total apoptotic rate of 62.5 ± 4.2% in OVCAR3. Caspase-8 and caspase-9 activities were elevated by 5.6 ± 0.7-fold and 7.3 ± 0.8-fold, respectively. Combination treatment also induced marked oxidative stress, increasing NO levels to 12.4 ± 1.1 µM and ROS levels to 412 ± 25% in OVCAR3 cells. qRT-PCR analyses revealed downregulation of anti-apoptotic Bcl-2 (0.28 ± 0.04-fold) and Survivin (0.25 ± 0.03-fold), along with upregulation of pro-apoptotic Bax (5.8 ± 0.6-fold) and Caspase-3 (6.5 ± 0.7-fold). Bioinformatic analyses indicated that high Bcl-2 and Survivin expression correlated with poorer overall survival in ovarian cancer patients. Metformin enhances the anticancer efficacy of doxorubicin through synergistic activation of intrinsic and extrinsic apoptotic pathways, induction of oxidative and nitrosative stress, and transcriptional regulation of key apoptotic markers. These findings support the potential use of metformin as an adjuvant agent to strengthen doxorubicin-based chemotherapy in ovarian cancer. Full article

Oxydifficidin is a natural polyketide antibiotic that has long been recognized as a ribosome-targeting agent that inhibits protein synthesis. In this paper, we describe Bacillus velezensis strain EV17 and compare its complete genome sequence with that of the previously characterized B. velezensis strain K-3618 and the difficidin biosynthetic gene cluster (BGC) combined with mass spectrometry to elucidate the production of oxydifficidin by these strains. Toeprinting and small fluorescent peptide assays showed that isolated oxydifficidin induces a generalized inhibition of translation at every step of elongation in protein biosynthesis. In previous studies, it has been demonstrated that oxydifficidin targets bL12 protein. Although spontaneous mutations conferring resistance to oxydifficidin in ribosomal protein bL12 located relatively close to the thiostrepton binding site on uL11, our data show that oxydifficidin binding does not interfere with thiostrepton, thereby refining previous findings about its putative ribosomal target. We are the first to show that this compound does not affect eukaryotic translation and has two orders of magnitude lower effect on eukaryotic cells compared to bacteria. These facts are important to further investigate its potential as a bioprotectant against phytopathogens or even as a therapeutic agent. Full article

This study evaluated the antagonistic activity of the cell-free supernatant of Lacticaseibacillus rhamnosus ATCC 9595 (Lcr-CFS) against Listeria monocytogenes, a major foodborne pathogen, that represents a challenge to food safety, due to its remarkable tolerance to environmental stresses and strong biofilm-forming ability. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Lcr-CFS against L. monocytogenes were defined as 31.25 and 62.5 mg/mL, respectively. Time-kill assays revealed dose- and time-dependent bactericidal effects. At sub-MICs, Lcr-CFS significantly reduced L. monocytogenes biofilm formation, disrupted preformed biofilms and decreased cell viability (80.3–96.7%), effects that were confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and fluorescence microscopy. Transmission electron microscopy showed L. monocytogenes cell wall damage, cytoplasmic leakage, and morphological alterations consistent with bactericidal effects. Additionally, exposure to 1x and 2x MIC of Lcr-CFS induced reactive oxygen species (ROS) accumulation, indicating oxidative stress as part of the mechanism by which Lcr-CFS exerts its antimicrobial activity. Gene expression analysis revealed upregulation of stress and virulence-associated genes (sigB, prfA, degU, flaA, motA, hlyA, pclA, and actA) upon exposure to 0.5x MIC suggesting a complex cross-talk network between adaptive mechanisms and environmental stresses. Although L. monocytogenes initiates a stress response, it appears unable to counteract the damage induced by Lcr-CFS, resulting in cell death. These findings highlight the antimicrobial and anti-biofilm properties of Lcr-CFS against L. monocytogenes. Given its in vitro efficacy, Lcr-CFS emerges as a promising biocontrol agent to improve food safety by mitigating the persistence of L. monocytogenes in food processing settings. Full article

The lysosome is no longer viewed as a simple degradative “trash can” of the cell. The lysosome is not only degradative; its acidic, redox-active lumen also serves as a chemical “microreactor” that can modulate anticancer drug disposition and activation. This review examines how the distinctive chemical features of the lysosome, including its acidic pH (~4.5–5), strong redox gradients, limited thiol-reducing capacity, generation of reactive oxygen (ROS), diverse acid hydrolases, and reservoirs of metal ions, converge to influence the fate and activity of anticancer drugs. The acidic lumen promotes sequestration of weak-base drugs, which can reduce efficacy by trapping agents within a protective “safe house,” yet can also be harnessed for pH-responsive drug release. Lysosomal redox chemistry, driven by intralysosomal iron and copper, catalyzes Fenton-type ROS generation that contributes to oxidative damage and ferroptosis. The lysosome’s broad enzyme repertoire enables selective prodrug activation, such as through protease-cleavable linkers in antibody–drug conjugates, while its membrane transporters, particularly P-glycoprotein (Pgp), can sequester chemotherapies and promote multidrug resistance. Emerging therapeutic strategies exploit these processes by designing lysosomotropic drug conjugates, pH- and redox-sensitive delivery systems, and combinations that trigger lysosomal membrane permeabilization (LMP) to release trapped drugs. Acridine–thiosemicarbazone hybrids exemplify this approach by combining lysosomal accumulation with metal-based redox activity to overcome Pgp-mediated resistance. Advances in chemical biology, including fluorescent probes for pH, redox state, metals, and enzymes, are providing new insights into lysosomal function. Reframing the lysosome as a chemical reactor rather than a passive recycling compartment opens new opportunities to manipulate subcellular pharmacokinetics, improve drug targeting, and overcome therapeutic resistance in cancer. Overall, this review translates the chemical principles of the lysosome into design rules for next-generation, more selective anticancer strategies. Full article

Interrelations between the plasma membrane and cytoskeleton are of crucial importance for essential cellular processes such as endocytosis, formation of intercellular junctions, cell morphology, etc. Many studies validate the beneficial effects of polyphenols as antioxidant and protective agents, but a molecular mechanism of their interaction and transition through the plasma membranes of different cell lines is still missing. In this study, we examined the affinity of fractions enriched in flavonoid glycosides (FGs) and caffeoylquinic acids (CQAs), obtained from the methanol extract of the medicinal plant Inula oculus-christi L., to reorganize the plasma membrane structure and actin cytoskeleton by using confocal microscopy. Assessment of the degree of membrane ordering aiming to distinguish the ordered from disordered regions of the cellular membranes was performed using the fluorescent dye Di-4-ANEPPDHQ, and visualization of F-actin was by TRITC-phalloidin. Two epithelial cell lines with clear differences in their origin and plasma membrane organization were chosen: the non-malignant MDCK II and the cancerous A549. Our results showed that flavonoid glycosides exhibited an ordering effect on plasma membranes of cancerous cells and fluidized one on non-malignant cells. Different patterns of actin reorganization were observed for both cell lines after treatment. Our results indicate the potential of plant-derived polyphenols as modulators of the membrane’s structural organization, offering valuable insights for the development of membrane-targeted therapeutic strategies. Full article

Background: Cancer therapeutics development has been a challenge in medical and scientific areas due to their toxicity, limited biocompatibility, and unfortunate side effects. However, despite advances in early detection and the study of novel treatments, the mortality rate for breast cancer remains high, making it a significant global health concern. Objectives: In this study, poly(methyl methacrylate) (PMMA) nanoparticles functionalized with acrylic acid (AA), fumaramide (FA), and curcumin (CUR) as chelating and inhibitor agents were synthesized by emulsion polymerization techniques. Methods and Results: Comprehensive physiochemical characterization studies based on gravimetry, dynamic light scattering (DLS), electrophoresis, Fourier transform infrared (FT-IR), ultraviolet–visible (UV–Vis) and photoluminescence (PL) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) revealed a pH dependence of nanoparticles that exhibit structural changes upon interaction with calcium (Ca²⁺) and magnesium (Mg²⁺) ions. Calorimetric thermodynamic properties measured by isothermal titration calorimetry (ITC) confirmed chelating coordination and positive cooperativity between the nanoparticles and metal ions. In vitro studies showed the low cytotoxicity of nanoparticles by fibroblast proliferation, and their chelation process was observed by fluorescence microscopy, with the loss of interaction between cells. Conclusions: These results suggest that the functionalized nanoparticles have potential in drug delivery systems (DDS) for targeted breast cancer therapies, providing a promising polymer material for more efficient and less toxic treatments. Full article

With emerging viruses and drug resistance on the rise, the discovery and development of innovative antiviral substances and agents are necessary for the effective treatment and control of viral outbreaks. Surrogate viruses are safer alternatives used in research to mimic dangerous or hard-to-culture viruses. They enable efficient, ethical, and cost-effective screening of antiviral compounds. In this study, we used a recombinant viral hemorrhagic septicemia virus (rVHSV) expressing enhanced green fluorescent protein as a surrogate for RNA viruses for the high-throughput screening of antiviral agents. An optimized mixture of viruses and EPC host cells was distributed in 96-well plates containing chemical compounds or plant extracts for screening. Using this system, 44,642 chemical compounds and 8104 plant and marine organism extracts were tested; 140 candidates were selected from primary screening, and 8 compounds and 5 plant extracts were further selected based on the selectivity index (SI), representing the ratio of the cytotoxic concentration (CC₅₀) to the inhibition concentration (IC₅₀). Among these, compound 3, which had the highest SI value of 1046, was further tested, considering in vitro activity against VHSV and another fish rhabdovirus, snakehead rhabdovirus (SHRV). Full article