Search Results (1,938)

Canine hepatocellular carcinoma (HCC), the most common primary liver malignancy in dogs, shares many clinicopathological and molecular similarities with human HCC. However, its molecular characteristics remain insufficiently defined, and reliable diagnostic biomarkers are lacking. Elucidating dysregulated microRNAs (miRNAs) may aid in both disease characterization and comparative oncology research. Small RNA sequencing datasets from canine HCC were analyzed to identify significantly dysregulated miRNAs with high expression and biomarker potential. The top candidate was validated in clinical tissues, cell lines, patient’s plasma and plasma exosomes using RT-qPCR. Comparative analyses were conducted using human HCC datasets (TCGA and GEO), followed by target prediction and functional enrichment to identify conserved molecular pathways. Among the 59 differentially expressed miRNAs, cfa-miR-10a showed the highest average expression level and yet was significantly downregulated in canine HCC tissues. RT-qPCR confirmed reduced expression of cfa-miR-10a in canine HCC tissues, whereas plasma exosomes showed significant enrichment, demonstrating excellent diagnostic performance (AUC = 0.94). The mature sequence of cfa-miR-10a is highly conserved with hsa-miR-10a-5p. TCGA datasets confirmed downregulation of hsa-miR-10a-5p in HCC tissues, whereas a GEO dataset showed no significant change in serum exosome levels. Target prediction and functional annotation identified 59 overlapping genes, with the Proteoglycans in cancer pathways being conserved in both species, mediated by ACTG1, SDC1, FRS2, and WNT9B. Collectively, these findings demonstrate distinct intra-tumoral and exosomal expression pattern of miR-10a in canine HCC and support its potential as a non-invasive biomarker with translational relevance. Full article

Mitochondrial dysfunction is a pivotal contributor to cardiac disease progression, making it a critical target in regenerative interventions. Extracellular vesicles (EVs) have recently emerged as powerful mediators of mitochondrial transfer and cardiomyocyte repair. This review highlights recent advancements in EV bioengineering and their applications in cardiac mitochondrial rescue, with a particular focus on EVs derived from induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs). Drawing upon a growing body of preclinical evidence, we examine the mechanisms of mitochondrial content delivery, EV uptake dynamics, and comparative bioenergetic restoration outcomes across EV sources. Special emphasis is placed on therapeutic outcomes such as adenosine triphosphate (ATP) restoration, reactive oxygen species (ROS) modulation, and improvements in contractility and infarct size. The convergence of mitochondrial biology, stem cell-derived EV platforms, and engineering innovations positions mitochondria-enriched EVs as a promising non-cellular regenerative modality for cardiovascular disease. Full article

The occurrence of antibiotic residues in the environment is of concern not only because of their contribution to the spread of bacterial resistance, but also due to their possible toxicity to non-target organisms. In this study, the aquatic environmental toxicity of ciprofloxacin (CIP) and sulfamethoxazole (SMX) was assessed in the following model organisms: Daphnia magna and Artemia salina (embryonic and immobilisation test with a 10-d follow-up), Phaeodactylum tricornutum (algal growth inhibition test), and Spirodela polyrhiza (duckweed growth inhibition test). Results showed that among the two saltwater organisms, A. salina was insensitive to both antibiotics, whilst P. tricornutum responded only to SMX with an EC₅₀ of 2.7 mg L⁻¹. In freshwater species, D. magna embryos were more sensitive than juveniles to SMX (EC₅₀ 53.8 and 439.2 mg L⁻¹, respectively), whereas the opposite trend was observed for CIP (EC₅₀ 95.9 and 15 mg L⁻¹, respectively). S. polyrhiza confirmed the remarkable sensitivity of aquatic plants to fluoroquinolones, with EC₅₀ values between 0.28 and 0.34 mg L⁻¹ depending on the endpoint considered. Notably, this species was also more sensitive to SMX than expected, with EC₅₀ values between 1.5 and 2.5 mg L⁻¹, which are an order of magnitude lower than those typically obtained with Lemna spp. exposed to sulphonamides. Considering the high environmental input of these antibiotics from both human and veterinary treatments, adverse effects on aquatic plants cannot be excluded, potentially leading to ecosystem-level consequences. Full article

The Lower Passaic River (LPR), located within the New York/New Jersey Harbor Estuarine System, has experienced long-term industrial activities, resulting in elevated concentrations of trace metals in sediment and water. This study aims to assess the bioaccumulation behavior, potential human health risks, and sources of copper (Cu), lead (Pb), and mercury (Hg) in the LPR. Trace metal concentrations were measured in water, sediment, and seven edible aquatic species. Data were analyzed using statistical approaches, and evaluated by bioaccumulation factors (BAFs) and human health risk assessments based on U.S. Environmental Protection Agency (USEPA) guidelines. Results showed that Hg exhibited the highest bioaccumulation potential among the studied metals, except for Cu in Callinectes sapidus. Non-carcinogenic risks from the consumption of aquatic species followed the order Cu > Hg > Pb, with total target hazard quotient (TTHQ) values below 1, suggesting the non-carcinogenic health risk is negligible for adults and for most species in children, except C. sapidus and Morone americana. Carcinogenic risks for all species were within the acceptable threshold (Target Risk < 1 × 10⁻⁴). Sensitivity analysis indicated that body weight and exposure duration primarily influenced children’s carcinogenic risk, whereas trace metal concentrations were more significant for adults. Overall, this study provides insight into contaminant dynamics and health implications in a legacy-contaminated urban river system. Full article

Transmetalation, the exchange of metal ions between coordination complexes and biomolecules, has emerged as a powerful design lever in cancer metallopharmacology. Using thiosemicarbazones (TSCs) as a unifying case study, we show how redox-inert carrier states such as zinc(II) or gallium(III) can convert in situ into redox-active copper(II) or iron(III/II) complexes within acidic, metal-rich lysosomes. This conditional activation localizes reactive oxygen species (ROS) generation and iron deprivation to tumor cells. We critically compare redox-active and redox-inert states, delineating how steric and electronic tuning, backbone rigidity, and sulfur-to-selenium substitution govern exchange hierarchies and kinetics. We further map downstream consequences for metal trafficking, lysosomal membrane permeabilization, apoptosis, and ferroptosis. Beyond TSCs, iron(III)-targeted transmetalation from titanium(IV)-chelator “chemical transferrin mimetics” illustrates a generalizable Trojan horse paradigm. We conclude with translational lessons, including mitigation of hemoprotein oxidation via steric shielding, stealth zinc(II) prodrugs, and dual-chelator architectures and outline biomarker, formulation, and imaging strategies that de-risk clinical development. Collectively, these insights establish transmetalation as a central therapeutic principle. We also highlight open challenges such as quantifying in-cell exchange kinetics, predicting speciation under non-equilibrium conditions, and rationally combining these agents with existing therapies. Full article

The escalating threat of antibiotic resistance has prompted the search for alternative antibacterial therapies. Antibacterial photodynamic therapy (aPDT), which utilizes light-activated photosensitizers to generate reactive oxygen species (ROS), offers a promising, non-invasive approach. The aim of this review is to analyze recent advances in nanoparticle-mediated aPDT and synthesize crucial design principles necessary to overcome the current translational barriers, thereby establishing a roadmap for future clinically applicable antimicrobial treatments. Emerging nanoparticle platforms, including upconverting nanoparticles (UCNPs), carbon dots (CDs), mesoporous silica nanoparticles (MSNs), liposomes, and metal–organic frameworks (MOFs), have demonstrated improved photosensitizer delivery, enhanced ROS generation, biofilm disruption, and targeted bacterial eradication. Synergistic effects are observed when aPDT is integrated with photothermal, chemodynamic, or immunotherapeutic approaches. The review further examines the mechanisms of action, biocompatibility, and antibacterial performance of these nanoparticle systems, particularly against drug-resistant strains and in challenging environments such as chronic wounds. Overall, nanomaterial-mediated aPDT presents a highly promising and versatile solution to antimicrobial resistance. Future perspectives include the integration of artificial intelligence to personalize aPDT by predicting optimal light dosage and nanoplatform design based on patient-specific data, rigorous clinical validation through trials, and the development of safer, more efficient nanoparticle platforms. Full article

Background: The human microbiome holds promise for identifying biomarkers and therapeutic targets. In obesity, interactions between oral and gut communities are increasingly implicated and end in organ injury. Methods: From the IMAGINE study, we analyzed 418 shotgun metagenomes from three specimen types (dental plaque (n = 143; 65 non-obese, 78 obese), saliva (n = 166; 75 non-obese, 91 obese), and stool (n = 109; 57 non-obese, 52 obese)) to compare site-specific microbial shifts between obese (BMI > 30 kg/m²) and non-obese individuals. Differential abundance was assessed with ANCOM-BC; effect sizes were summarized as Cohen’s d. Results: Across all samples, we detected 240 bacterial species in plaque, 229 in saliva, and 231 in stool, with 46 species present across all three sites. Absolute effect sizes were significantly larger in plaque (mean |d| = 0.26) and saliva (0.25) than in stool (0.21; p = 9 × 10⁻³). Several taxa showed an opposite directionality between oral and gut sites, including Streptococcus salivarius and Bifidobacterium longum, indicating site-specific associations. Notably, Actinomyces sp. and Streptococcus sp. exhibited promising effect sizes as diagnostic markers. Conclusions: The oral and gut microbiomes capture complementary obesity-related signals, with stronger shifts observed in oral sites. We suggest that integrating oral and gut profiling could enhance diagnostic and therapeutic strategies in obesity. Full article

Thinopyrum intermedium (c.n. intermediate wheatgrass), marketed under the trade name Kernza, is a promising species for perennial grain production based on seed size, ease of threshing, resistance to shattering, and grain quality. Although numerous generations of breeding for seed yield have been completed, the impact of selection on non-target traits is unknown. Here, we evaluated structural and functional changes brought about by selection for seed yield over a sequence of nine selection cycles (C0 to C9). In two experiments under semi-controlled environmental conditions, we compared gas exchange (A, E, gs, and A/Ci curves), leaf and root morphology, and the structure of seedlings from 10 generations. We found that the selection for yield throughout cycles indirectly changed the leaf structure (leaf size, leaf thickness, and leaf anatomy) and physiology (carbon acquisition and transpiration per unit area), with later cycles showing larger leaves with higher rates of CO₂ assimilation and transpiration. Changes in root structure followed similar trends: selection resulted in longer, more branched, and finer roots. These changes in non-target traits are linked to resource-use strategies and to ecosystem services provided by Kernza. Understanding how the domestication of perennial grains impacts non-target traits will aid in the design of integrated breeding programs for Kernza and other perennial grain crops. Full article

The emergence of drug-resistant Candida species has created an urgent need for non-toxic molecules that inhibit fungal growth, biofilm development, and hyphal formation. In this study, fifty multi-halogenated indole derivatives were screened against ten Candida species, including azole-resistant C. albicans, C. auris, C. glabrata, and C. parapsilosis. Among them, 4,6-dibromoindole and 5-bromo-4-chloroindole exhibited the strongest antifungal and antibiofilm effects, with minimum inhibitory concentration (MIC) values of 10–50 µg/mL, outperforming ketoconazole and comparable to miconazole. Both di-halogenated indoles markedly inhibited cell aggregation, yeast-to-hyphae transition, and induced reactive oxygen species (ROS) accumulation, contributing to fungicidal activity. Microscopic analyses revealed the disruption of hyphal networks and reduced biofilm biomass. They showed moderate cytotoxicity in human hepatocellular carcinoma (HepG2) cells (median lethal dose, LD₅₀ = 35.5 µg/mL and 75.3 µg/mL) and low phytotoxicity in plant assays. The quantitative structure–activity relationship (QSAR) model identified halogen substitution at C4, C5, and C6 positions as optimal for antifungal activity due to enhanced hydrophobic and electron-withdrawing effects. Together, these findings demonstrate that di-halogenated indoles serve as potent, low-toxicity inhibitors of Candida growth, biofilms, and morphogenesis, providing a promising scaffold for next-generation antifungal agents targeting drug-resistant Candida species. Full article

Herbicide glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA), have raised concerns due to their potential neurotoxicity in non-target aquatic species. This study evaluated neurotoxic effects in common carp (Cyprinus carpio) following a 28-day dietary exposure to glyphosate (325.2 and 3310.0 μg/kg) and AMPA (335.2 and 3441.0 μg/kg) at two concentrations, including control and four treatment groups. Brain acetylcholinesterase activity was significantly (p < 0.05) reduced in all exposed groups, while muscle acetylcholinesterase activity remained unchanged. Brain dopamine was significantly (p < 0.05) decreased only in the highest AMPA group. Plasma butyrylcholinesterase activity increased significantly (p < 0.05) in the low-dose glyphosate group. The level of mRNA expression of ache was significantly (p < 0.05) downregulated in the brain across all treatments and upregulated in the gills only at the highest AMPA concentration. Histological analysis of the brain revealed vascular congestion in both glyphosate-exposed groups, indicating pathological changes. These results suggest that dietary exposure to glyphosate and AMPA can affect cholinergic and dopaminergic pathways in fish, with the brain being a particularly sensitive target tissue. Our findings contribute to understanding the potential neurotoxic risks posed by glyphosate-based compounds in aquatic environments. Full article

The present review offers a comprehensive synthesis of the structural diversity, natural occurrence, and therapeutic promise of key ellagitannins (punicalagin, sanguiin H-6, corilagin, geraniin, oenothein B, chebulagic, and chebulinic acids) within the hydrolyzable ellagitannin pool. Distributed in medicinal and dietary plants long used in traditional medicine, ellagitannin-rich species serve as sources of both complex polyphenolic scaffolds and their bioactive metabolites, urolithins, which mediate many of their health-promoting effects. Special emphasis is placed on the multifaceted mechanisms that contribute to their potent antioxidant, anti-inflammatory, antimicrobial, and anticancer effects, extending to both non-communicable and communicable diseases. Despite their broad therapeutic spectrum, clinical translation is limited by challenges such as poor bioavailability, host-gut microbiota variability, and a lack of robust in vivo evidence. The review highlights future directions aimed at unlocking ellagitannins’ potential, including microbiota-targeted strategies for urolithin production, the design of stable prodrugs and analogs, and innovative delivery platforms. By integrating phytochemical, mechanistic and translational insights, this article positions ellagitannins as promising candidates for the development of novel polyphenol-based interventions. Full article

Pacific pygmy octopus Paroctopus digueti is a promising model for cephalopod research and aquaculture; its feeding and nutritional biology remain poorly understood. The anterior salivary glands (ASG), posterior salivary glands (PSG), and digestive gland (DG) are central to these processes, but molecular comparisons are lacking. To address this gap, we performed a transcriptomic study to explore the enzymatic repertoire and functional specialization of these tissues. Total RNA was extracted from ASG, PSG, and DG of three pre-adult individuals collected in La Paz Bay, Mexico. RNA-Seq libraries were sequenced, and a non-redundant multi-tissue transcriptome was assembled. The ASG displayed high expression of neuropeptides, playing a role in neuroendocrine regulation. The PSG showed elevated protease expression, supporting its function in extracellular digestion, alongside toxins that reinforce its role as a venom gland. The DG was enriched in proteins linked to biomolecule catabolism and antimicrobial peptides, alluding to metabolic specialization and immune defense. These results were validated by qPCR, and target genes were also amplified in Octopus maya and O. hubbsorum, showing some similarities in expression patterns. Overall, our findings suggest strong glandular specialization in P. digueti, providing insights into cephalopod digestive physiology and supporting its value as a model species. Full article

Biopreservation using lactic acid bacteria has gained a growing interest as an alternative to chemical preservatives and/or as a complementary tool to prevent fungal spoilage in dairy products. Among the action mechanisms of antifungal LAB, competitionexclusion for trace elements has recently been highlighted. To further investigate this mechanism, two antifungal LAB strains, Lactiplantibacillus plantarum L244 and Lactobacillus rhamnosus CIRM-BIA1759, were studied in a yogurt model. Firstly, the antifungal activity of these strains against four main dairy spoilage fungi (Penicillium biforme, Mucor racemosus, Galactomyces geotrichum and Yarrowia lipolytica) was evaluated with or without trace element (6 metals and 12 vitamins) supplementation. Only manganese supplementation led to a suppression of the antifungal activity of both L. plantarum L244 and L. rhamnosus CIRM-BIA1759 against P. biforme and/or Y. lipolytica. The scavenging of trace elements was then measured using HR-ICP-MS in both cell-free yogurt whey and fungal biomass. HR-ICP-MS results showed a significant scavenging of Mn in L. plantarum L244 and L. rhamnosus CIRM-BIA1759 whey, as well as Cu for L. rhamnosus CIRM-BIA1759. Moreover, element uptake profiles, including metal and non-metal elements, for each of the target fungi were affected by the use of antifungal cultures. Finally, the role of competitionexclusion for manganese in the inhibition of 25 fungal spoilers was evaluated via oCelloScope growth follow-up. Growth inhibition by antifungal LAB strains was suppressed after Mn supplementation in cell-free whey for the 16 (out of 25) fungi initially inhibited without Mn supplementation. The nine other fungi were not inhibited or were poorly inhibited in the different tested conditions. This study confirmed the role of competitionexclusion for Mn in the antifungal activity of L. plantarum L244 and L. rhamnosus CIRM-BIA1759 strains but also revealed that this mechanism is not generic among fungal species, as the growth behavior of several tested species was not impacted by Mn scavenging. Full article

The human endometrium, previously considered a sterile environment, is now recognized as a low-biomass but biologically active microbial niche critical to reproductive health. Advances in sequencing technologies, particularly shotgun metagenomics, have provided unprecedented insights into the taxonomic and functional complexity of the endometrial microbiome. While 16S rRNA sequencing has delineated the distinction between Lactobacillus-dominant and non-dominant microbial communities, shotgun metagenomics has revealed additional diversity at the species and strain level, uncovering microbial signatures that remain undetected by amplicon-based approaches. Current evidence supports the association of Lactobacillus dominance with endometrial homeostasis and favorable reproductive outcomes. Dysbiosis, characterized by increased microbial diversity and enrichment of anaerobic taxa such as Gardnerella, Atopobium, Prevotella, and Streptococcus, is linked to chronic endometritis, implantation failure, and adverse IVF results. Beyond compositional differences, the endometrial microbiome interacts with the host through immunological, metabolic, and epigenetic mechanisms. These interactions modulate cytokine signaling, epithelial barrier integrity, and receptivity-associated gene expression, ultimately influencing embryo implantation. However, discrepancies between published studies reflect the lack of standardized protocols for sampling, DNA extraction, and bioinformatic analysis, as well as the inherent challenges of studying low-biomass environments. Factors such as geography, ethnicity, hormonal status, and antibiotic exposure further contribute to interindividual variability. Culturomics approaches complement sequencing by enabling the isolation of viable bacterial strains, offering perspectives for microbiome-based biotherapeutics. Emerging 3D endometrial models provide additional tools to dissect microbiome–host interactions under controlled conditions. Taken together, the growing body of data highlights the potential of endometrial microbiome profiling as a biomarker for reproductive success and as a target for personalized interventions. Future research should focus on integrating multi-omics approaches and functional analyses to establish causal relationships and translate findings into clinical practice. This review gives a new insight into current knowledge on the uterine microbiome and its impact on implantation success, analyzed through the lenses of microbiology, immunology, and oxidative stress. Full article

The vascular endothelium serves as a critical barrier preventing the transmigration of monocytes, circulating lipoproteins, and other molecules into the subendothelial space, and plays a vital role in regulating vascular tone. A dysfunctional and inflamed endothelial layer in response to disturbed blood flow or other proatherogenic risk factors is the initiating event in the pathogenesis of atherosclerosis, suggesting the importance of an intact and properly functioning endothelium in preventing the onset and progression of this disease. Accumulated evidence demonstrates the significant role of matricellular proteins, which are non-structural and secretory extracellular matrix (ECM) proteins, in the development of atherosclerosis. These proteins exert multifaceted effects on endothelial cells (ECs) ranging from reactive oxygen species (ROS) production, endoplasmic reticulum stress, and expression of adhesion molecules to autophagy and compromised barrier function via stimulating various molecular mechanisms. Given the critical roles of these processes in EC function and atherosclerosis, a better understanding of signaling pathways governed by matricellular proteins in ECs is required to develop therapeutic strategies for suppressing or preventing atherosclerosis and related cardiovascular diseases (CVDs). This review comprehensively summarizes the existing literature on the diverse roles of matricellular proteins in regulating EC inflammation and function, and highlights their potential as viable therapeutic targets for maintaining vascular health and inhibiting the progression of atherosclerosis. Full article