Search Results (8,829)

Prostaglandin E₂ (PGE₂) plays a critical role in regulating uterine endometrial function and supporting embryonic development during early pregnancy in ruminants. However, its precise roles in shaping the uterine microenvironment remain unclear. Herein, 1 mg PGE₂ was infused daily into the uterus of dairy heifers from days 12 to 14 of the estrus cycle. ULF was subsequently collected for integrated proteomic, metabolomic, and targeted lipidomic analyses. In addition, bovine endometrial epithelial cells were used to evaluate the effects of PGE₂ on epithelial adhesion and responsiveness to interferon tau (IFNT). PGE₂ infusion resulted in 909 differentially abundant proteins (DAPs), which are primarily associated with early embryonic development, immune regulation, and cell adhesion. Untargeted metabolomics analysis identified 587 altered metabolites, which were enriched in sphingolipid, arachidonic acid, phenylalanine, and tryptophan metabolism. Proteomic–metabolomic analyses showed that these alterations were primarily associated with early embryonic development, immune regulation, and cell adhesion. Targeted lipidomic analysis showed a global reduction in lipid accumulation, with glycerophospholipid metabolism and choline metabolism most significantly affected. In vitro, PGE₂ reduced epithelial microvilli density, increased osteopontin (OPN) expression, and decreased the expression of junctional proteins (zona occludens-1 (ZO-1), E-cadherin (CDH1), and fibronectin 1 (FN1)). Moreover, PGE₂ enhanced the responsiveness of bEECs to IFNT by interferon alpha/beta receptor 1 (IFNAR1) and IFNAR2, and prostaglandin E receptor 4 (PTGER4) was identified as the primary receptor mediating this response. Collectively, these findings suggest that PGE₂ may modulate lipid metabolism and adhesion-related processes in the endometrium and influence endometrial responsiveness to IFNT, providing insights into molecular mechanisms associated with pregnancy establishment in dairy cows. Full article

Background: The optimal timing of adjuvant chemotherapy after cytoreductive surgery in epithelial ovarian cancer remains uncertain, and perioperative wound-healing responses may transiently create a pro-tumorigenic and drug-resistant microenvironment. This study aimed to characterize time-dependent wound-induced transcriptomic alterations and to identify pharmacologic agents capable of reversing these responses. Methods: An ID8 murine ovarian cancer model was used to compare no treatment, anesthesia alone, and anesthesia plus surgical wounding mimicking futile laparotomy. Tumors were collected at baseline, 1 day (T1), 1 week (T2), and 2 weeks (T3) after intervention. RNA sequencing was performed, and wound-specific differentially expressed genes (WsDEGs) were defined by excluding anesthesia- and progression-related signatures. Functional enrichment analyses were conducted, followed by transcriptome-based drug repurposing using the REMEDY platform to identify compounds predicted to reverse wound-induced gene expression profiles. Results: Surgical wounding significantly increased tumor burden at T1. Transcriptomic analyses revealed distinct, time-dependent wound-associated programs. At T1, WsDEGs were enriched in inflammatory signaling, coagulation, angiogenesis, and immune cell migration, with Vorinostat and Homoharringtonine identified as top candidates to counteract these signatures. At T2, pathways related to cell survival, adhesion, and morphogenesis predominated, with LY-2090314, Artesunate, and Birinapant emerging as potential modulators. At T3, cell-cycle regulation and lipid metabolic pathways were dominant, and Fulvestrant, Atorvastatin, Imatinib, and ABT-737 were predicted to inhibit these processes. Conclusions: Perioperative surgical wounding induces dynamic, stage-specific transcriptomic programs that may promote ovarian cancer progression and alter drug responsiveness. These findings support time-adapted perioperative pharmacologic strategies to optimize postoperative cancer therapy. Full article

Erlotinib (ER) and gefitinib (GB) are frequently prescribed for patients with advanced lung adenocarcinoma (ADC). Although both ER and GB significantly extend median survival, several patients experience early disease relapse due to treatment resistance. This study aimed to identify common genes associated with acquired resistance to ER or GB. This integrative analysis of transcriptomic data identified differentially expressed genes by comparing sensitive PC-9 cells with ER-resistant (PC-9/ER) or GB-resistant (PC-9/GB) cell lines. A Venn diagram was used to identify common genes. Candidate genes were confirmed in our generated drug-resistant cell lines. After six months, the PC-9/ER and PC-9/GB cell lines exhibited 40.7-fold and 109.2-fold increases in resistance to ER and GB, respectively. Flow cytometric analysis demonstrated that both resistant cell lines were resistant to cell cycle arrest and apoptosis induced by ER or GB. Through integrated analysis, we found that two genes, KRT13 and CEACAM5, were up-regulated in both the PC-9/ER and PC-9/GB cell lines. The expression patterns of these two genes did not align with the transcriptome, with only CEACAM5 exhibiting consistent gene and protein expressions. Our findings indicate that CEACAM5 serves as a biomarker for predicting the response of patients to ER and GB treatments. Full article

Atherosclerosis, the leading global cause of death, is a chronic inflammatory vascular disease with higher prevalence and earlier onset in men than in women. This study aims to investigate sex differences in the atherogenic endothelial phenotype during early atherosclerosis processes by providing the first comprehensive analysis of hormone-independent responses in human umbilical vein endothelial cells (HUVECs) from opposite-sex twins. HUVECs underwent pro-inflammatory stimulation with TNF-α and supernatant from activated pro-inflammatory THP-1 cells, revealing distinct sex-specific patterns: mRNA expression of focal adhesion proteins talin-I, vinculin, FAK, and α1-actinin increased significantly only in male cells, while paxillin showed elevated mRNA and protein levels in both sexes. Male HUVECs exhibited stronger induction of cell adhesion molecule VCAM-1, pro-inflammatory cytokine IL-1β, and proangiogenic factors Flt-3L, G-CSF, and PDGF-AA, whereas IL-22 secretion was exclusively upregulated in female cells. These sex differences in levels of focal adhesion, adhesion molecules, and cytokine profiles uncover the mechanistic backgrounds of the atherogenic endothelial phenotype, independent of systemic hormones. The findings emphasize cellular sex as a critical biological variable in early atherosclerosis and vascular inflammation. Full article

The interface between biomaterials and biological systems is crucial for medical implants and tissue engineering. Surface modifications are a key strategy for controlling interactions. Synthetic glycopolymers offer a versatile toolbox, mimicking the structure and function of natural glycoconjugates like mucins. This review highlights the significance of glycopolymers for targeted surface modifications of established biomaterials, such as silicones and poly(meth)acrylates. Controlled polymerization techniques, like the reversible-addition-fragmentation chain-transfer (RAFT) polymerization, enable the synthesis of well-defined glycopolymer architectures. Glycopolymeric surface functionalization creates tailored interfaces for different biological responses, from preventing protein and cell adhesion to promoting specific cell-type binding. The focus lies on using single, well-characterized polymeric base materials and tuning their surface properties through glycopolymer coatings to achieve various and specific functions. This approach opens new dimensions in the development of advanced biomaterials for applications like contact lenses, drug delivery systems, and biosensors and also possesses potential regulatory advantages by leveraging the safety profiles of existing materials. Full article

Helicobacter pylori (H. pylori) is the primary etiological agent for chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The alarming rise in multidrug-resistant (MDR) strains, particularly against clarithromycin (CLR), metronidazole (MNZ), and levofloxacin (LVX), has severely compromised standard therapies. Thus, there is an urgent clinical need for novel antimicrobial agents that operate through distinct mechanisms to bypass resistance pathways and mitigate gastric cancer risk. We designed and synthesized a series of antimicrobial peptides, focusing on the proteolytically stable all-D-amino acid enantiomer, DT7-3, derived from a probiotic-sourced template. Minimum inhibitory concentrations (MICs) were determined against standard strains and 11 clinical MDR isolates via the broth microdilution method. Antimicrobial mechanisms were elucidated using scanning electron microscopy (SEM) for morphology, fluorescence-based assays for anti-adhesion activity, and real-time qPCR to quantify virulence gene expression (babA, ureA, and vacA). Biocompatibility was assessed using defibrinated sheep erythrocytes, gastric epithelial cells (GES-1), and representative beneficial gut microbiota. Analysis of the clinical isolates revealed resistance rates of 63.6% for CLR/LVX and 81.8% for MNZ, with 54.5% identified as MDR. DT7-3 exhibited superior potency (MIC 1–32 µg/mL) against all strains, significantly outperforming its L-enantiomer counterparts. Mechanistic studies unveiled a “triple-hit” mechanism: (1) rapid membrane disruption; (2) potent inhibition of bacterial adhesion to host cells (~60% reduction at 0.5 × MIC); (3) significant downregulation of critical virulence factors (babA, ureA, and vacA). Furthermore, DT7-3 showed an excellent safety profile, with negligible hemolysis (<5% at 32 µg/mL) and minimal cytotoxicity toward GES-1 cells, yielding a high selectivity index (SI, MHC/MIC) > 32 relative to mammalian cells. Crucially, DT7-3 showed high selectivity for the pathogen over beneficial gut microbiota (MIC > 128 µg/mL, SI > 16). Crucially, DT7-3 maintained potent bactericidal activity (MIC ≤ 16 µg/mL) even under cholesterol-enriched conditions. The engineered D-peptide DT7-3 is a potent candidate for combating MDR H. pylori. Its multifaceted mechanism, targeting bacterial viability while suppressing core virulence factors, positions it as a robust lead compound for next-generation eradication therapies aimed at reducing the burden of H. pylori-associated diseases. Full article

Background/Objectives: Severe and recurrent infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa necessitate alternative antimicrobial strategies. Fermented cacao beans represent a niche microbial ecosystem with the potential to harbor beneficial lactic acid bacteria (LAB). This study aimed to isolate and characterize LAB strains from fermented cacao beans in southern Thailand and to evaluate their probiotic potential and antimicrobial activity against MDR P. aeruginosa. Methods and Results: Five Lactiplantibacillus plantarum isolates were identified via MALDI-TOF MS and whole-genome sequencing (WGS). All strains demonstrated antimicrobial activity against 17 clinical MDR P. aeruginosa isolates and CR14 exhibited the largest inhibition zone. The isolates displayed robust probiotic traits, including survival under simulated gastrointestinal conditions. Acid tolerance (pH 2.0) reached 61.15 ± 7.75%, while resistance to pepsin, pancreatin, and bile salts exceeded 88%, 91%, and 92%, respectively. Strong adhesion was confirmed via auto-aggregation (55.02 ± 1.75%), hydrophobicity (45.58 ± 0.96%) and Caco-2 cell attachment (up to 98.11 ± 3.28%). WGS revealed multiple plantaricin-encoding clusters. Coarse-grained molecular dynamic simulations showed that two-peptide plantaricins (plnJ/K and plnNC8-αβ) self-assembled and formed stable pores in bacterial membrane models, confirming a pore-forming antimicrobial mechanism. The strains lacked acquired resistance genes and virulence factors, confirmed by in silico safety assessments. Conclusions: Thus, these L. plantarum strains are promising probiotics for managing MDR P. aeruginosa via functional foods or adjunct therapies. Full article

Bcakground: Hepatocellular carcinoma (HCC) is a prevalent malignancy with limited therapeutic options. Drug repurposing offers an attractive strategy to accelerate anticancer discovery. The pleuromutilin class of antibiotics, including the human-approved agent lefamulin and the veterinary drug tiamulin, has shown preliminary anticancer potential, but its efficacy and mechanism in HCC remain unexplored. Methods: The anti-tumor effects of lefamulin and tiamulin were evaluated in HCC cell lines, patient-derived organoids, and a C57BL/6 mouse subcutaneous tumor model. Safety was assessed in a human normal hepatocyte cell line and by histopathological examination of major organs in treated mice. Mechanistic investigations were performed using RNA-sequencing, RT-qPCR, immunohistochemistry (IHC), filipin staining, pharmacological rescue assays, and shRNA-mediated gene silencing. Results: In this study, we found that both lefamulin and tiamulin markedly inhibited HCC cell proliferation in vitro and significantly suppressed tumor growth in vivo (lefamulin vs. control, p = 0.014; tiamulin vs. control, p = 0.021), without causing significant toxicity. RNA-sequencing analysis revealed consistent downregulation of the cholesterol transporter Abca1 (ATP-binding cassette transporter A1) and alterations in cell adhesion molecule pathways. Functional studies confirmed that treatment reduced ABCA1 protein levels, leading to intracellular cholesterol accumulation and aberrant distribution. Furthermore, treated tumors exhibited a significant increase in CD8⁺ T-cell infiltration, with CD4⁺ T cells and macrophage infiltration remained unchanged, indicating a specific modulation of the tumor immune microenvironment. Conclusions: These findings suggest that lefamulin and tiamulin are promising therapeutic candidates for HCC. Full article

Background: Avian pathogenic Escherichia coli (APEC) contributes substantially to colibacillosis outbreaks in chickens. Because APEC cells readily attach to surfaces and develop biofilms, they pose a notable hazard to poultry production and food safety. This study investigated the antibiofilm and anti-adhesion activities of deep eutectic solvent-based emulsion containing Piper betle L. extract (DEPE) and hydroxychavicol, a pure compound isolated from P. betle leaves against APEC. Methods: Antibiofilm and anti-adhesion activities of DEPE and hydroxychavicol against APEC were investigated. Molecular docking and dynamics simulation of DEPE and hydroxychavicol was conducted. In addition, anti-adhesion activity of DEPE on chicken meat during storage was evaluated. Results: DEPE and hydroxychavicol significantly inhibited biofilm formation at sub-MIC, with DEPE achieving up to 80% inhibition and hydroxychavicol up to 69%. At 8 × MIC, DEPE and hydroxychavicol diminished the viability of both early and established biofilms. Furthermore, DEPE and hydroxychavicol reduced APEC adhesion on the surface as observed by SEM. In silico analyses demonstrated the stable binding of hydroxychavicol to adhesion-related proteins, particularly EcpA and FimH, suggesting a possible mechanism for its anti-adhesion activity. At day 5, DEPE at 4 × MIC significantly reduced 63% bacterial adhesion to chicken meat surfaces during storage, while maintaining the meat’s color. Conclusions: These findings indicate that DEPE and hydroxychavicol are promising candidates for limiting APEC biofilm formation and surface attachment and may serve as alternative antibacterial agents in poultry-related food safety applications. Full article

Myogenic mechanobiology governs how mechanical cues regulate myocyte organization, alignment, and functional maturation; however, in vitro platforms that enable quantitative control and real-time readout of myogenic mechanical microenvironments remain limited. Here, we engineered a pneumatic-driven organ-on-a-chip platform integrating six parallel culture units and a bead-embedded flexible PDMS membrane to deliver cyclic mechanical strain and enable quantitative stress–strain mapping in cardiomyocytes and skeletal muscle cells. Finite element-guided optimization ensured effective membrane deformation, and the platform generated stable and tunable cyclic strain with a strong linear relationship between applied negative pressure (50–700 mbar) and membrane stress and strain. Plasma treatment combined with type I collagen coating restored myogenic cell adhesion and growth on PDMS to levels comparable to standard culture conditions. Under 13% cyclic strain, both cardiomyocytes and skeletal muscle cells exhibited pronounced and highly uniform alignment, with cellular polarity oriented perpendicular to the stretch axis. Moreover, cyclic loading significantly enhanced the expression of contractile maturation markers, including MYH7 in cardiomyocytes and MYH6 in skeletal muscle cells (all p < 0.05), whereas expression of the differentiation regulator MyoG remained unchanged, indicating that mechanical stimulation preferentially promotes structural organization and contractile maturation rather than lineage commitment. Collectively, this quantitatively programmable organ-on-a-chip represents a bioengineered microdevice for studying myogenic mechanobiology, revealing conserved mechanosensitive alignment and maturation responses across myogenic lineages and providing a versatile framework for biomedical engineering research, disease modeling, and mechanotherapeutic screening. Full article

Biofouling has a detrimental effect on marine infrastructure and poses a severe challenge to the global marine industry. Therefore, developing efficient and environmentally friendly anti-fouling coatings to protect those facilities has become extremely necessary nowadays. To address marine biofouling, a series of photocurable degradable waterborne boron-containing polyurethane acrylate (WPU-PTPBx) anti-fouling coatings were prepared by grafting pyridine-triphenylborane (PTPB) onto polyurethane side chains and UV curing. FTIR and ¹H NMR confirmed the successful grafting of PTPB. The WPU-PTPBx aqueous dispersions had a particle size of 30~75 nm with excellent thermal storage stability. DSC and XRD characterizations revealed the amorphous structure of the coatings, which favored biodegradation. All coatings exhibited adhesion strength over 2 MPa, meeting marine application requirements. Antibacterial and anti-algal tests showed that PTPB content positively correlated with anti-fouling performance: the coating achieved a 99.66% inhibition rate against Escherichia coli and reduced the adhesion density of Nitzschia closterium to only 36.9 cells/mm². With favorable degradability and outstanding anti-fouling performance, WPU-PTPBx coatings are promising green anti-fouling materials for marine applications. Full article

Background/Objectives: Nature-inspired therapeutic strategies that promote biological regenerative mechanisms and replicate the native structural microenvironment conductive to formation of healthy tissue are increasingly recognized as a promising platform for skin tissue regeneration and wound healing. This study proposes an innovative design of novel multifunctional scaffolds composed entirely of natural components—gelatin, L-ascorbic (ASA) acid and allantoin—as a bioinspired approach for skin tissue regeneration through pro-regenerative, antimicrobial, and keratinocyte-supportive properties. Methods: The biocompatible, skin-adhesive scaffolds were prepared via a simple and environmentally friendly heat-induced crosslinking of gelatin with varying ASA contents, and by enriching the system with allantoin. The influence of ASA content on scaffold properties was investigated through characterization of their morphology, porosity, swelling behavior, skin tissue adhesion, and allantoin release potential. Biocompatibility was evaluated in vitro using human keratinocyte (HaCaT) cells, while antibacterial activity was assessed against Escherichia coli and Staphylococcus epidermidis. Results: The scaffolds revealed a highly porous, interconnected structure with tunable porosity (87.37–92.39%) and soft-tissue-matched mechanical properties (0.81–1.47 MPa). Incorporation of allantoin into the scaffolds enhanced their mechanical performance and swelling capacity. All scaffolds demonstrated antibacterial activity against both tested bacteria, supported keratinocyte viability and provided sustained release of allantoin for up to 76 h, confirming their multifunctional pro-regenerative potential. Conclusions: The novel gelatin/ascorbic acid scaffolds enriched with allantoin combine a porous replicated structure of native extracellular matrix, fluid absorption capacity, soft-tissue-like mechanical properties, stable skin tissue adhesion, cytocompatibility and antibacterial functionality with the pro-regenerative properties of allantoin, thereby representing a multifunctional and biologically inspired platform for advanced skin tissue regeneration and wound-healing applications. Full article

This study presents a low-cost, small-scale single-chamber microbial fuel cell (MFC) toxicity biosensor fabricated on a printed circuit board (PCB) and a 3D-printed chamber with a volume of 120 μL. The anode consists of a screen-printed carbon electrode on the PCB, while the air cathode is a carbon paper electrode. To address poor adhesion of microorganisms to the smooth anode surface, femtosecond laser processing was used to fabricate a micropore array with 40 μm pores on the electrode. This method can create micropores on the anode surface without damaging the screen-printed electrodes, the PCB substrate, or the pads. These micropores increase the anode’s surface area and hydrophilicity, allowing more microbial coatings to firmly adhere to its surface. In this study, the MFC utilised Rhizobium rosettiformans W3, extracted from activated sludge at a wastewater treatment plant, as the anode microorganism. Its aerobic nature simplifies the design of MFCs, enabling a single-chamber structure and miniaturisation. Using formaldehyde solution as a toxicity sample to test the biosensor’s performance, a 0.1% concentration significantly reduced the sensor’s output power. Full article

Chronic exposure to benzo[a]pyrene (BaP), a Group 1 IARC carcinogen, is a major driver of lung carcinogenesis; however, how sustained subcytotoxic exposure reprograms bronchial epithelium toward preneoplastic states remains poorly defined. Here, we subjected BEAS-2B human bronchial epithelial cells to 12 weeks of continuous BaP at environmentally relevant concentrations (0.1 and 1.0 µM) and interrogated the resulting phenotypes using an integrated multi-scale framework encompassing functional toxicology, RT-qPCR, RNA-seq, phospho-kinase/NF-κB arrays, and organotypic air–liquid interface (ALI) cultures. Cells maintained metabolic competence throughout, evidenced by sustained CYP1A1 and CYP1B1 induction at both acute (4 h) and chronic (12-week) timepoints, while accumulating genotoxic stress as demonstrated by dose-dependent nuclear γ-H2AX foci formation and ATM phosphorylation (Ser1981). RNA-seq revealed a dose-dependent transcriptional shift: 0.1 µM BaP yielded 119 differentially expressed genes (DEGs; |log2FC| ≥ 1, FDR < 0.05), whereas 1.0 µM generated 255 DEGs. Downregulated transcripts were enriched for extracellular matrix and cell-adhesion programs (COL14A1, ADAMTS2, CSMD3, CADM3), while upregulated genes encompassed inflammatory, calcium-signaling, and vesicle-trafficking modules (NFATC4, CSF2RA, SYT1, PCLO). Phospho-kinase/NF-κB arrays confirmed a p53/NF-κB signaling nexus, with concurrent activation of MAPK/ERK (Thr202/Tyr204) and PI3K/Akt (Ser473) pathways. Despite persistent genotoxic stress, cells did not acquire anchorage-independent growth and remained non-tumorigenic in vivo. Critically, ALI organotypic cultures derived from BaP-exposed cells exhibited histological dysplasia, nuclear pleomorphism, and disrupted apical-basal polarity. These findings mechanistically link chronic BaP exposure to an initiation-like preneoplastic state and establish a validated 2D/3D multi-omics platform for PAH-driven lung carcinogenesis research. Full article

The development of inks with suitable rheological, physicochemical, mechanical, and biological properties is crucial for the successful fabrication of functional scaffolds via extrusion-based 3D printing. In this study, collagen/chitosan hydrogels with varying polymer ratios were developed and characterized to evaluate their printability and suitability for cartilage tissue engineering. Rheological analyses revealed that all samples exhibited shear-thinning behavior and solid-like viscoelasticity, with the formulation of an 80:20 COL/CHI ratio (20CHI) demonstrating optimal filament formation and dimensional stability. Physicochemical analyses confirmed the preservation of the collagen triple helix and the formation of hydrogen bonding between chitosan and collagen. 20CHI scaffolds showed swelling capacity and high cohesiveness. In vitro studies confirmed the cytocompatibility of the scaffolds with murine fibroblasts and the ability of the scaffolds to promote adhesion, proliferation, and extracellular matrix production of both chondrocytes and adipogenic mesenchymal stem cells (aMSCs). Quantification of sulfated glycosaminoglycan (sGAG) indicated sustained matrix deposition over 28 days, particularly by chondrocytes. These findings demonstrate that 20CHI hydrogel is a promising candidate for 3D printing of biomimetic scaffolds for cartilage regeneration. Full article