Search Results (54,309)

As life expectancy continues to increase, age-related disorders are becoming more prevalent. Among these, vascular complications resulting from chronic inflammation are particularly concerning, as they impair angiogenesis and hinder tissue repair, both processes that heavily rely on a well-structured extracellular matrix (ECM). In this context, MicroMatrix^® UBM Particulate, a skin substitute composed of collagen, laminin, and proteoglycans, appears to offer properties conducive to tissue regeneration. The aim of this study was to evaluate the regenerative potential of MicroMatrix^® combined with the Secretome of human Dental Pulp Stem Cells (hDPSC-S), using the medicinal leech Hirudo verbana, a well-established model for studying wound healing, angiogenesis, and tissue regeneration. Adult leeches were injected with MicroMatrix^® either suspended in FBS-free medium (CTRL) or supplemented with hDPSC-S. 1-week post-treatment, the animals were sacrificed and subjected to morphological and immunohistochemical analyses. Our findings revealed that MicroMatrix^® successfully integrated into the leech body wall. Notably, when supplemented with hDPSC-S, there was a marked increase in cell infiltration, including telocytes and Hematopoietic Precursor Stem Cells, along with a significantly higher vessel density compared to CTRL. These results support the effectiveness of the cell-free device composed of MicroMatrix^® and hDPSC-S, highlighting its potential as a promising strategy for regenerative therapies aimed at treating complex wounds with poor vascularization. Full article

The increased presence of harmful algal blooms (HABs) is a concern for many aquatic environments, especially with the increasing effects of climate change. Members of the dinoflagellate genus Dinophysis have been shown to produce toxins that can cause Diarrheic Shellfish Poisoning (DSP) in humans who consume infected shellfish. The advancing oyster aquaculture industry in Delaware will require the development of management practices and monitoring HAB species to protect environmental and human health. Temperature, nutrients, and prey abundance can be drivers of Dinophysis blooms. D. acuminata has been historically identified at high concentrations (>200,000 cells L⁻¹) in water samples from Rehoboth Bay, DE, USA. However, the reach of spring blooms and how far they extend to aquaculture sites have not been determined. This study monitored an emergent HABs threat of a toxin-producing dinoflagellate, Dinophysis acuminata, by assessing a transect during the first recorded winter bloom in Torquay Canal and analyzing concentrations of chemical nutrients of combined nitrate and nitrite, and orthophosphate. Pearson correlation coefficient analysis between cell density (cells L⁻¹) and environmental variables across all sites was conducted to determine significant relationships between water temperature, Chl-a concentration, conductivity, dissolved oxygen (DO), combined nitrate and nitrite concentrations (NO_x), and orthophosphate concentrations (PO₄³⁻). Genetic techniques and PCR were utilized to determine the presence of Dinophysis using genus-specific primers to monitor cell density or abundance within the sediments during winter months. There were no significant correlations between environmental variables, and nutrient concentrations did not exceed EPA regulations. Molecular analyses of benthic sediments detected Dinophysis spp., offering insight into potential bloom origins. Overall, there is limited ecological data on Dinophysis acuminata in Rehoboth Bay, DE, USA. The results of this study will help strengthen resources for monitoring HAB species and understanding potential risks to oyster aquaculture in Delaware. Full article

This study investigates T cell subsets in pericardial fluid samples obtained from heart transplantation donors, heart transplantation recipients, and coronary artery bypass graft patients. Using flow cytometry, we characterized regulatory T cells (Tregs), tissue-resident memory T cells (Trm), and exhausted T cells based on specific markers. Our results showed significant alterations in the CD4⁺ and CD8⁺ T cell subsets, migration (CXCR3, CCR5), and exhaustion markers (PD-1, TIM3) across the groups. Notably, Tregs and Trm cells were enriched in recipients, while markers of T cell exhaustion showed a complex regulation. These findings provide novel insights into the local immune regulation in cardiac disease and transplantation. Full article

Cacipacoré virus (CPCV) is an understudied orthoflavivirus with significant gaps in research that hinders our understanding of its ecology, host range, and potential public health impact. A notable barrier to filling this gap is the absence of standardized methodologies for viral quantification, such as plaque-forming and focus-forming assays. This short communication outlines the development of optimized protocols for CPCV titration in two cell lines, Vero CCL-81 and BHK CCL-10, using several overlay and time point conditions. These methodologies address the need for robust quantitative tools to advance research on CPCV and its implications for human and animal health, fostering progress in the surveillance and understanding of this underexplored arbovirus. Full article

Respiratory viral infections are a major cause of morbidity and mortality worldwide. The COVID-19 pandemic has evidenced the need for broad-spectrum antivirals and improved preclinical models that more accurately recapitulate human respiratory disease. These new strategies should also involve the search for drug targets in the infected cell that hamper the development of resistance and of potential efficacy against diverse viruses. Since many viruses reprogram cellular metabolism to support viral replication, we performed a comparative analysis of inhibitors targeting the PI3K/AKT/mTOR pathway, central to virus-induced metabolic adaptations, using MRC5 lung fibroblasts and Huh7 hepatoma cells. HCoV-229E infection in MRC5 cells caused the expected shift in the energy metabolism but the inhibitors had markedly different effects on the metabolic profile and antiviral activity in these two cell lines. Dichloroacetate (DCA), a clinically approved inhibitor of aerobic glycolysis, showed antiviral activity against HCoV-229E in MRC5 cells, but not in Huh7 cells, underscoring that the screening model is more critical than previously assumed. We further tested DCA in polarized human small airway epithelial cells cultured in air–liquid interface, a 3D model that mimics the human respiratory tract. DCA reduced the viral progeny of HCoV-229E, SARS-CoV-2, and respiratory syncytial virus by 2–3 orders of magnitude, even when administered after infection was established. Our work reinforces the need for advanced human preclinical screening models to identify antivirals that target host metabolic pathways frequently hijacked by respiratory viruses, and establishes DCA as a proof-of-concept candidate. Full article

The human endometrium is unique in that it has a high potential for regeneration after menstruation without scarring. Although growth factors are thought to be responsible for scar formation, it has recently been shown for foetal skin that CD26-negative fibroblasts are essential. Thus, we investigated whether CD26 might be involved in scar formation. Primary human endometrial stromal cells (HPESCs) were stimulated with interleukin-1 alpha (IL1α) to induce CD26 protein expression, and secretion of the scar-associated proteins collagen 1 alpha 1 (COL1A1) and TGF-β3 was measured using ELISAs. The contribution of CD26 to wound closure was analysed using a wound healing assay. The CD26 inhibitor diprotin A (DPA) was used to attenuate CD26 activity. Immunohistochemistry of human uterine samples showed negligible stromal staining of CD26, but CD26 was abundant in the endometrial glands. Treatment of CD26-negative HPESCs with IL1α induced CD26 protein expression, strongly stimulated wound healing in vitro, and increased secretion of COL1A1, but decreased TGF-β3 secretion. DPA effectively attenuated all IL1α-induced effects. We suggest that the stromal non-expression of the scar-associated protein CD26 might contribute to non-scarring during endometrial wound healing. Full article

Autism Spectrum Disorder (ASD) is a complex and multifactorial neurodevelopmental condition whose pathogenesis remains only partially elucidated. Earlier accounts of oxidative stress in ASD often relied on the reductive paradigm of an imbalance between oxidants and antioxidants. In contrast, this narrative review, based on a systematic examination of 1102 publications indexed in scientific databases from 2002 to July 2025, reframes the discussion in terms of redox system dysfunction, a broader and more integrative construct. Here, reactive oxidant species, molecular targets, and reducing/antioxidant counterparts are considered elements of a dynamic circuitry whose maladaptation progressively undermines homeostasis. The sequence of events unfolds in three stages. The first is primary redox dysfunction, manifesting as alterations in metabolic, signaling, and defense pathways. From this disturbance, a second stage arises, marked by functional derailment of cellular compartments—from membranes and cytosol to organelles and nuclei—including mitochondrial and peroxisomal deficits. Ultimately, a third stage emerges, defined by neurodevelopmental alterations such as impaired neurotransmission, synaptic dysfunction, abnormal plasticity, morphogenetic defects, neuroinflammation, and gut–brain–microbiota disarrangements. This progression situates the redox system as a central hub at the interface between human cells and the microbiota, resonating with the ecological and evolutionary principles of the holobiont and the One Health framework. By weaving dispersed evidence into a coherent perspective, this review advances beyond previous analyses, offering a unifying paradigm that connects biochemical dysfunction to clinical heterogeneity in ASD and opens new directions for interdisciplinary research. Full article

The human gut microbiota helps maintain metabolic balance, supports immune function, and defends against opportunistic pathogens that can disrupt the microbiota ecosystem. An imbalance or dysbiosis in microbial composition is linked to various diseases, including inflammatory bowel disease, metabolic syndromes, and neurodegenerative disorders. Using microbiota modulation with prebiotics and postbiotics is a practical approach to address these imbalances. Prebiotic compounds are defined as substrates that promote metabolic activity and restore microbial patterns. Postbiotics include short-chain fatty acids (SCFAs), microbial cell lysates, and extracellular compounds. This research aims to investigate how the gut microbiota can be modulated in vitro using the prebiotic ColonX and a postbiotic derived from Kombucha fermentation within a controlled GIS1 in vitro system. These products demonstrate potential for modulation, as they support selective bacterial growth and enhance microbial diversity. Prebiotics help stabilize gut pH, while postbiotics play a crucial role in biofilm formation. Together, they provide an innovative approach to treating dysbiosis and enhancing overall gut health. The findings highlight the importance of utilizing prebiotics and postbiotics to modulate gut microbiota in chronic diseases characterized by dysbiosis. This paper is especially relevant for elderly populations, as gut dysbiosis is common, and microbiota modulation supports healthy aging. Full article

Background/Objectives: Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach and causes various gastrointestinal diseases. Although antibiotic therapy is the most effective method for its eradication, the increasing prevalence of antibiotic resistance has made treatment increasingly challenging in recent years. In this study, the antimicrobial activity, synergistic effects with antibiotics, and mechanisms of action of Bicarinalin, an antimicrobial peptide (AMP) derived from the venom of Tetramorium bicarinatum, were investigated against H. pylori. Methods: To determine the antibacterial activity of Bicarinalin, a well diffusion assay was performed, yielding an inhibition zone of 18.3 mm at a concentration of 32 µg/mL for ATCC strain. MIC₉₉ values were determined by microdilution tests as 4.8 μg/mL for the reference strain. The enhancement of the antimicrobial potential of levofloxacin and clarithromycin when administered together with Bicarinalin has been demonstrated using the well diffusion method. Results: Inhibition zones increased from 14.2 mm to 20 mm for levofloxacin and from 7.3 mm to 16 mm for clarithromycin. This study is the first to identify DNA and protein leakage caused by Bicarinalin in H. pylori. Intracellular protein and DNA leakage were measured, with protein and DNA levels released into the extracellular environment determined as 33.25% and 55.10%, respectively, following Bicarinalin treatment. Furthermore, to investigate its effect on membrane damage, scanning electron microscopy (SEM) was performed, revealing disrupted cell membrane structures, penetration between cells, and severe deterioration of morphological integrity. Conclusions: This study has demonstrated for the first time that, when administered concomitantly, Bicarinalin enhances the antimicrobial activities of levofloxacin and clarithromycin. This highlights its potential as an adjunctive treatment for H. pylori alongside existing drugs. Full article

The design of innovative compounds displaying anti-inflammatory activity in oncological context is a subject of great interest in drug development. It has been proved that a pro-inflammatory microenvironment which accelerates cancer growth and cellular differentiation is often present in malignant bladder tumor. In earlier work, we reported the synthesis of p-aminobenzoic acid derivatives that act as anti-inflammatory compounds able to inhibit the pro-inflammatory markers present in bladder cancer microenvironment. DAB-1 rapidly emerged as an effective lead candidate in this investigation, with its ability to shrink by 90% in 25 days the size of human bladder cancer tumors in an ectopic mouse model. This manuscript discloses the synthesis of 23 new hydrazide derivatives of DAB-1 and reports their in vitro and in vivo biological evaluation. It was discovered that most of the new compounds are essentially nontoxic against RAW 264.7 cells, as evaluated by an MTT assay. Anti-inflammatory activity of the new derivatives was investigated by evaluation of their impact on cellular nitric oxide production, measured by a Griess assay. Some compounds did significatively inhibit nitric oxide production much more effectively than the original DAB-1. Striking activity of 14, which is around four times more potent than DAB-1, promotes this derivative as new lead compound in this study. The study of these analogs reveals that a phenolic/anisole core is a key component to achieve high biological activity. Furthermore, mice models of acute inflammation and invasive BCa tumors were used to assess the in vivo impact of derivative 14, and it was found that this compound does reduce inflammation in these mice, possess similar anti-inflammatory activity but higher anti-tumoral activity compared to DAB-1 with no apparent signs of toxicity. Full article

The objective of this study was to evaluate the antiviral activity of glucosyl hesperidin (GH), a water-soluble derivative of hesperidin with known antioxidant and anti-inflammatory properties, in order to explore its potential applications. Antiviral activity was assessed using feline calicivirus (FCV), a surrogate model for human norovirus, a major foodborne pathogen. Cytotoxicity testing in Crandell–Rees feline kidney (CRFK) cells demonstrated that GH exhibited high biocompatibility, maintaining 100% cell viability at concentrations up to 8000 μM. Antiviral efficacy assays revealed that GH inhibited FCV replication in a concentration-dependent manner across the range of 250~8000 μM, with a half-maximal inhibitory concentration (IC₅₀) of 3281 μM. Complete viral inhibition, however, was not achieved at the maximum concentration tested. In conclusion, GH was shown to inhibit FCV while maintaining low cytotoxicity, indicating its potential as a natural, water-soluble candidate for the suppression of norovirus. Full article

The nourishment of the human population depends on a handful of staple crops, such as maize, rice, wheat, soybeans, potatoes, tomatoes, and cassava. However, all crop plants are affected by at least one virus causing diseases that reduce yield, and in some parts of the world, this leads to food insecurity. Conventional management practices need to be improved to incorporate recent scientific and technological developments such as antiviral gene silencing, the use of double-stranded RNA (dsRNA) to activate an antiviral response, and nanobiotechnology. dsRNA with antiviral activity disrupt viral replication, limit infection, and its use represents a promising option for virus management. However, currently, the biggest limitation for viral diseases management is that dsRNA is unstable in the environment. This review is focused on the potential of nanoparticles and nanocarriers to deliver dsRNA, enhance stability, and activate antiviral gene silencing. Effective carriers include metal-based nanoparticles, including silver, zinc oxide, and copper oxide. The stability of dsRNA and the efficiency of gene-silencing activation are enhanced by nanocarriers, including layered double hydroxides, chitosan, and carbon nanotubes, which protect and transport dsRNA to plant cells. The integration of nanocarriers and gene silencing represents a sustainable, precise, and scalable option for the management of viral diseases in crops. It is essential to continue interdisciplinary research to optimize delivery systems and ensure biosafety in large-scale agricultural applications. Full article

Cadherin 17 (CDH17) is a cell adhesion glycoprotein essential for epithelial integrity. It is frequently overexpressed in various cancers, where it is associated with aggressive behaviour. While evidence indicates that CDH17 functions as an upstream regulator of Wnt/β-catenin signalling, findings are inconsistent across tumour types, limiting the assessment of CDH17 as a biomarker or therapeutic target for Wnt pathway in cancer. In this study, we systematically review and meta-analyse the relationship between CDH17 and Wnt/β-catenin signalling in human cancers and evaluate whether CDH17 modulation affects tumour behaviour through Wnt-related mechanisms. Our search of Medline, Web of Science and Scopus identified five studies examining CDH17 expression in the Wnt/β-catenin pathway in vitro and in vivo. All five studies identified CDH17 as a key driver of canonical Wnt signalling, directly influencing cancer progression in hepatocellular carcinoma (HCC), gastric cancer (GC), and colorectal cancer (CRC). Meta-analysis (MA) showed that CDH17 inhibition consistently reduced Wnt/β-catenin downstream T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) transcriptional activity (MD = −1.32, 95% CI: −1.64 to −0.99, p < 0.00001). Narrative synthesis found that CDH17 suppression decreased total and nuclear β-catenin, phosphorylated glycogen synthase kinase-3 beta (GSK-3β), and cyclin D1 while increasing tumour suppressors, retinoblastoma (Rb) and p53/p21. These changes were associated with reduced proliferation, colony formation, migration, invasion and cell cycle arrest. In vivo, CDH17 suppression resulted in 80–95% tumour growth suppression (Mean Difference (MD) = −96.67, 95% CI: [−144.35, −48.98], p < 0.0001), with immunohistochemistry confirming cytoplasmic β-catenin sequestration and lower cyclin D1 levels. Collectively, these findings show CDH17 as a critical upstream effector sustaining Wnt/β-catenin signalling, cancer progression, tumour proliferation, stem cell properties, and metastasis, and support CDH17 inhibition as a promising therapeutic target across multiple cancer types. Full article

Melanoma is an aggressive malignancy with poor prognosis in advanced stages, and current therapeutic options provide only limited benefits, highlighting the need for novel treatments. Chetomin, a fungal metabolite isolated from Chaetomium cochliodes, has been reported to exhibit diverse biological activities, yet its effects on melanoma cells remain poorly understood. In this study, we evaluated the antitumor potential of chetomin using the human A375 melanoma cell line. Cell viability was assessed with MTT and CellTiter-Glo^® assays, which revealed a significant dose- and time-dependent reduction in proliferation following chetomin exposure. Apoptotic effects were confirmed through Annexin V staining, and immunocytochemical analysis demonstrated a concentration-dependent increase in cleaved PARP1, indicating activation of programmed cell death pathways. Collectively, these findings demonstrate that chetomin effectively inhibits melanoma cell growth and promotes apoptosis. The results suggest that chetomin represents a promising lead compound for melanoma therapy, warranting further investigation into its precise molecular mechanisms. Full article

Background: Most immunologically “cold” tumors do not respond durably to checkpoint blockade because tumor antigen (TA) release and presentation are insufficient to prime effective T-cell immunity. While prior work demonstrated synergy between cisplatin and a TLR7/8/9 agonist (CR108) in 4T1 tumors, the underlying mechanism—particularly whether chemotherapy functions as a broad antigen-releasing agent enabling TLR-driven immune amplification—remained undefined. Methods: Using murine models of breast (4T1), melanoma (B16-F10), and colorectal cancer (CT26), we tested multiple chemotherapeutic classes combined with CR108. We quantified intratumoral and systemic soluble TAs, antigen presentation and cross-priming by antigen-presenting cells, tumor-infiltrating lymphocytes, and cytokine production by flow cytometry/ICS. T-cell receptor β (TCRβ) repertoire dynamics in tumor-draining lymph nodes were profiled to assess amplitude and breadth. Tumor microenvironment remodeling was analyzed, and public datasets (e.g., TCGA basal-like breast cancer) were interrogated for expression of genes linked to TA generation/processing and peptide loading. Results: Using cisplatin + CR108 in 4T1 as a benchmark, we demonstrate that diverse chemotherapies—especially platinum agents—broadly increase the repertoire of soluble tumor antigens available for immune recognition. Across regimens, chemotherapy combined with CR108 increased T-cell recognition of candidate TAs and enhanced IFN-γ⁺ CD8⁺ responses, with platinum agents producing the largest expansions in soluble TAs. TCRβ sequencing revealed increased clonal amplitude without loss of repertoire breadth, indicating focused yet diverse antitumor T-cell expansion. Notably, therapeutic efficacy was not predicted by canonical damage-associated molecular pattern (DAMP) signatures but instead correlated with antigen availability and processing capacity. In human basal-like breast cancer, higher expression of genes involved in TA generation and antigen processing/presentation correlated with improved survival. Conclusions: Our findings establish an antigen-centric mechanism underlying chemo–TLR agonist synergy: chemotherapy liberates a broadened repertoire of tumor antigens, which CR108 then leverages via innate immune activation to drive potent, T-cell-mediated antitumor immunity. This framework for rational selection of chemotherapy partners for TLR7/8/9 agonism and support clinical evaluation to convert “cold” tumors into immunologically responsive disease. Full article