Search Results (6,919)

Background: LUAD, the most common subtype of lung cancer, particularly in non-smokers, is significantly influenced by air pollution from fine particulate matter (PM). One suspected method by which PM contributes to cancer progression is through angiogenesis, which promotes tumor growth and metastasis. This study was conducted to explore the impact of long-term PM exposure on the progression of LUAD, focusing on angiogenesis promotion. Methods: We conducted an integrative bioinformatics analysis incorporating epidemiological and transcriptomic datasets from public repositories (TCGA and GEO) to evaluate differential VEGFA expression in LUAD tissues and its relationship to regional PM exposure. In vitro and in vivo assays using PM-adapted NSCLC cell lines and murine xenograft models served as secondary confirmatory experiments supporting the computational results. Results: Epidemiological analysis revealed a strong positive correlation between long-term PM exposure and lung adenocarcinoma mortality across U.S. states (r = 0.7638, p < 0.0001), underscoring a population-level impact. Bioinformatics analysis identified a significant upregulation of VEGFA in NSCLC tumors from regions with high PM levels, with VEGFA overexpression also associated with poorer patient survival. Gene ontology and pathway enrichment analyses implicated angiogenesis-related processes. These findings were supported by experimental models, in which long-term PM exposure on human and murine LUAD cell lines (A549, H1299, and LLC) induced VEGFA and p-ERK overexpression. Furthermore, PM-exposed cells enhanced angiogenesis processes, as evidenced by increased endothelial cell tube formation and migration in vitro, and promoted tumor vascularization in a xenograft model. These pro-angiogenesis effects were abrogated following inhibition of the MAPK signaling pathway or blockade of VEGFA. Conclusions: Our findings reveal a compelling molecular link between PM exposure and NSCLC progression, centered on VEGFA-driven angiogenesis and urging the need to reduce ambient PM exposure to mitigate its oncogenic impact. Full article

Acute inflammation is frequently triggered by pathogen infections and contributes to host mortality. In this study, a new exopolysaccharide (ObEPS) was isolated from the moss endophyte Ovatospora brasiliensis and characterized for its structure and biological activity. Monosaccharide composition analysis revealed that ObEPS was mainly composed of galactose, glucose, mannose, and glucuronic acid. Multi-angle light scattering and conformation analysis showed a molar mass of 10⁵–10⁶ Da and a compact chain conformation. In vitro experiments showed that ObEPS markedly inhibited nitric oxide production and reduced pro-inflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In a systemic Candida albicans infection model, ObEPS combined with fluconazole significantly reduced fungal colony-forming units (CFUs)/g kidney from 3.8 × 10⁵ to 0.1 × 10⁵, with the reduction of pro-inflammatory cytokine levels and tissue damage compared with the EPS-free groups suffering from C. albicans infection. Overall, these findings indicate that ObEPS has potent anti-inflammatory activity and may serve as a promising natural adjunct for mitigating infection-associated inflammatory damage. Full article

The aim of this study was to elucidate the reproductive strategy of Camellia luteoflora, an endangered evergreen endemic to karst ecosystems. We observed and recorded its flowering phenology and flower-visiting insects, observed pollen morphology, determined pollen viability, and assessed stigma receptivity. The results showed that the flowering period of C. luteoflora started from early September to late December, with the average flowering period of individual flowers being 10–12 days. The pollen morphology of C. luteoflora was subprolate and prolate, with three germinal apertures and the fossulate exine ornamentation. Pollen viability was the highest at the initial opening stage (80.30%). In the process of pollen in vitro, the order of influence on the germination rate and pollen tube length was temperature > sucrose > calcium chloride (CaCl₂) > boric acid (H₃BO₃). The best combination for the germination rate was 24 °C, 75 g/L sucrose, 0.2 g/L CaCl₂, 0.15 g/L H₃BO₃, while that for the pollen tube length was 24 °C, 100 g/L sucrose, 0.2 g/L CaCl₂, 0.25 g/L H₃BO₃. Stigma receptivity was the strongest at the full blooming stage. The pollen/ovule ratio (P/O) was 2240, suggesting a facultative outcrossing breeding system. The outcrossing index (OCI) was 4, suggesting that the exogamous breeding system is the cross-pollination type, partially self-compatible and insect pollinator-dependent. The flower-visiting insects included bees, weevils, and ants. In summary, C. luteoflora exhibits an extended flowering period, with a prolonged overlap of stable pollen viability and stigma receptivity, suggesting a potential strategy to cope with pollination uncertainty. However, field observations recorded only a few species of potential pollinators, while the occurrence frequency of non-pollinating insects was relatively high. It is thus hypothesized that this apparent lack of effective pollinators may act as a potential barrier to successful fertilization and natural regeneration, which might also be one of the factors contributing to its endangered status. Future studies, particularly pollinator exclusion and hand-pollination experiments, are critically needed to verify whether pollinator limitation is indeed a key factor. Full article

In this study, oyster fermentation broth (OFB) was prepared by fermenting oysters with yeast, and its effects on oxidative stress and reproductive damage induced by tripterygium glycosides (TG) in male rats were investigated. Component analysis revealed that OFB contained bioactive substances including proteins (1.19 g/L), taurine (0.76 g/L), organic acids (2.30 mg/mL), polyphenols (123.00 mg GAE/L), flavonoids (1.97 mg RE/L), and zinc (1.10 mg/L). In vitro study revealed that OFB exhibited notable antioxidant activity, with a total antioxidant capacity of 1.28 U/mL, and DPPH, ABTS, and hydroxyl radical scavenging rates of 55.80%, 69.54%, and 48.36%, respectively. Animal experiments showed that, compared with the TG-induced model group, rats administered both low-dose (5 mL/kg) and high-dose (10 mL/kg) OFB showed significantly increased testis and seminal vesicle + prostate indices, sperm count, and serum testosterone (T) levels and decreased sperm malformation rate (p < 0.01 for all). Histological analysis of the testis revealed an increased number of spermatogenic cells and sperm within the seminiferous tubules, along with ameliorated pathological conditions compared to the model group. Potential mechanisms might be related to OFB increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) enzymes and reducing levels of malondialdehyde (MDA) in testis (p < 0.01). The findings demonstrated that OFB successfully alleviated TG-induced reproductive damage in male rats, which might be attributed to its excellent antioxidant effect. The study offers valuable insights for producing functional foods from oysters and further validates OFB’s efficacy in promoting reproductive function. Full article

Background/Objectives: To improve the therapeutic efficacy of albendazole (ABZ) for ileocolonic diseases, its low solubility at higher pH levels should be enhanced. Organic acids have been widely used as pH modifiers to improve the solubility of weakly basic drugs. To achieve an adequate effect of the acidic microenvironmental pH during the drug release, pH modifiers should not leach out from the formulation. In the present work, we aimed to demonstrate that 100% tartaric acid pellets (TAP) can be used as pH-modifier cores, providing an acidic microenvironmental pH to enhance the solubility of albendazole at a higher pH. Methods: This study develops multilayer-coated pellets using TAP as starter cores in a bottom-spray-configured fluidized bed apparatus. The drug-layered TAP were coated with time-dependent and pH-dependent layers. Results: The release of ABZ from tartaric acid-based coated pellets was enhanced compared to that from pellets with the same layering structure but with an inert core of sugar or microcrystalline cellulose (MCC). In vitro experiments showed that tartaric acid remained in the pellet core during the dissolution test at a pH 6.8 medium, which resulted in an enhanced release of albendazole at a higher pH. The application of a combination of time-dependent and pH-dependent polymers aimed not only to prevent the release of albendazole at lower pH levels but also to protect TAP from premature release from the formulation. Conclusions: The application of 100% ready-to-use tartaric acid pellets (TAP) with the applied combination of coatings enhanced the solubility of the weakly basic drug albendazole at higher intestinal pH. Full article

Background/Objectives: Diet and obesity contribute to approximately 50% of tumor development. Therefore, nutrition plays a key role not only in cancer prevention but also in determining prognosis. Notably, between 30% and 90% of cancer patients experience malnutrition. Furthermore, the hypercatabolic state induced by tumors leads to widespread protein degradation, clinically manifesting as sarcopenia or cachexia, and ultimately accelerating mortality. This narrative review examines the potential role of amino acids (AAs) in inhibiting tumor growth and counteracting protein–energy malnutrition—aiming to preserve muscle mass and nourish healthy cells while placing neoplastic cells in a state of metabolic stress. Methods: The analysis was conducted following the Standards for Reporting Qualitative Research guidelines. Results: Administration of targeted mixtures of essential amino acids (EAAs) has been shown to improve muscle mass, strength, and quality of life in patients with hypercatabolic conditions. Experimental in vitro and in vivo studies also suggest a potential inhibitory effect on tumor proliferation. However, increased availability of certain AAs may, in some cases, stimulate tumor growth, one reason why EAAs supplementation in cancer patients remains controversial. Conclusions: Despite prevailing concerns, emerging evidence indicates that supplementation with a complete, well-balanced EAAs formulation may be a valuable adjunct to standard cancer therapies. This approach could help correct cancer-associated protein imbalances, enhance patients’ quality of life, and create a metabolic environment unfavorable to tumor progression. Full article

Egg yolk immunoglobulin Y (IgY) has significant application potential in aquaculture as passive immunotherapy against various bacterial infections owing to its capacity for large-scale and cost-effective production. In this study, IgY antibodies of live or inactivated Aeromonas veronii were generated by laying hens immunization. Subsequently, passive immune protection experiments of the two IgY antibodies were conducted on goldfish (Carassius auratus) infected with A. veronii and Aeromonas hydrophila. The results indicated that both live and inactivated bacteria IgY antibodies provided significant passive protection rates (p < 0.05). Furthermore, ELISA tests demonstrated that the two IgY antibodies, as well as the serum of C. auratus, interacted with A. veronii or A. hydrophila (p < 0.05) in vitro. The bacterial loads in the kidneys of C. auratus immunized with the two IgY antibodies were decreased (p < 0.05), and C. auratus phagocytes had enhanced phagocytic activity. The expression levels of antioxidant factors (SOD, CAT, GSH-Px) and inflammatory factors mRNA (TNF-α, IL-1β, IL-6, IL-8) were down-regulated (p < 0.05). Additionally, histopathological analysis indicated that the renal, splenic, and intestinal tissue structures remained intact, and the immunofluorescence confirmed that apoptosis and DNA damage factors of p53 and γH2A.X reduced (p < 0.05), respectively. Thus, the IgY antibodies of live and inactivated A. veronii exhibit passive immune-protective effects against different pathogenic bacteria in C. auratus. Further, inactivated A. veronii immunization causes less damage to laying hens than that of live bacteria, which aligns more closely with welfare standards for laying hens, and the IgY of inactivated A. veronii is anticipated as a cross-protection against A. veronii and A. hydrophila infections in aquaculture. Full article

This study evaluated the effectiveness of individual clean-in-place (CIP) steps in removing biofilms from reverse osmosis (RO) membranes under dynamic flow conditions using the Centers for Disease Control (CDC) biofilm reactor. Biofilms were developed in the laboratory under continuous flow, using mixed-species bacterial isolates obtained from 10-month-old RO membrane biofilms from a commercial facility. Individual CIP chemicals, representative of those used in commercial protocols, were tested against 24 h-old biofilms. Additionally, a complete six-step sequential CIP process was conducted under dynamic conditions, consisting of treatments with alkali, surfactant, acid, enzyme, a secondary surfactant, and sanitizer. All experiments were performed in quadruplicate, and data were subjected to statistical analysis. Among individual treatments, the acid step was the most effective, significantly outperforming the other CIP cleaning steps by reducing bacterial counts from 5.62 to 4.10 log units, a 96.98% reduction. The full six-step CIP protocol reduced counts to 2.24 log units, indicating the persistence of resistant cells. The presence of viable cells post-treatment highlights the limited efficacy of the tested CIP chemicals in fully eradicating mature biofilms. Additionally, skipping any step in the membrane cleaning can significantly compromise the efficiency and performance during production. These findings suggest that biofilms grown in vitro under dynamic conditions using the CDC reactor exhibit a more robust assessment of the CIP treatments in accomplishing the biofilm control. This study highlights the need for optimized, scientifically validated CIP protocols targeting biofilms to improve cleaning efficacy and food safety. Full article

Background: Post-myocardial infarction (MI) heart failure (HF) is characterized by myocardial energy metabolism disorder, with excessive glycolysis playing a key role in its progression. Silybin (SIL), a flavonoid derived from Silybum marianum, has demonstrated hepatoprotective and metabolic regulatory effects. However, the role of this flavonoid in ameliorating post-myocardial infarction heart failure (post-MI HF) by modulating energy metabolism remains unclear. Methods: This study employed an oxygen–glucose deprivation (OGD) model to induce myocardial cell injury in vitro, with YC-1 treatment used to inhibit hypoxia-inducible factor-1α (HIF-1α) for mechanistic validation. A myocardial infarction-induced HF mouse model was used for in vivo experiments. Results: In vitro, SIL enhanced cell viability, increased ATP levels, and decreased lactate production and reactive oxygen species (ROS) accumulation in OGD-treated myocardial cells. SIL downregulated the mRNA and protein expression of HIF-1α, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA) while inhibiting HIF-1α nuclear translocation. Furthermore, SIL suppressed glycolytic proteins (PFKFB3, GLUT1, and LDHA) in a manner comparable to the HIF-1α inhibitor YC-1. This confirms that SIL’s inhibition of glycolysis is HIF-1α-dependent. In vivo, SIL treatment improved cardiac function parameters (LVEF and LVFS) and attenuated left ventricular remodeling (LVID;d and LVID;s) in post-MI HF mice. Additionally, myocardial fibrosis markers were significantly reduced, accompanied by a decrease in the myocardial mRNA and protein expression of glycolytic proteins, including HIF-1α, PFKFB3, GLUT1, and LDHA. Conclusions: Silybin effectively ameliorates post-myocardial infarction heart failure through the HIF-1α-mediated regulation of glycolysis, leading to improved myocardial energy metabolism and enhanced cardiac function. Full article

Compounds, which rely on metabolism to exhibit toxicity, pose a challenge for next-generation risk assessment (NGRA). Since many of the currently available non-animal new approach methods (NAMs) lack metabolic activity, their use may lead to an underestimation of the true hazard to humans (false negative predictions). We explored here strategies to deal with metabolite-mediated toxicity in assays for developmental neurotoxicity. First, we present an overview of substances that may serve as potential positive controls for metabolite-related neurotoxicity. Then, we demonstrate, using the MitoMet (UKN4b) assay, which assesses the adverse effects of chemicals on neurites of human neurons, that some metabolites have a higher toxic potency than their parent compound. Next, we designed a strategy to integrate elements of xenobiotic metabolism into assays used for (developmental) neurotoxicity testing. In the first step of this approach, hepatic post-mitochondrial fractions (S9) were used to generate metabolite mixtures (“metabolisation module”). In the second step, these were applied to a NAM (exemplified by the UKN4b assay) to identify metabolite-mediated toxicity. We demonstrate the applicability and transferability of these approaches to other assays, by an exemplary study on the basis of the cMINC (UKN2) assay, another NAM of the developmental neurotoxicity in vitro battery. Based on the experience gained from these experiments, we discuss key issues to be addressed if this approach is to be used more broadly for NAM in the NGRA context. Full article

Pseudomonas aeruginosa, a member of the “ESKAPE” group of bacterial pathogens, exhibits biofilm-forming capacity, a key factor contributing to its resistance to conventional antibiotics and posing significant challenges in clinical treatment. To develop more effective therapeutics against such infections, identifying potential drug targets through bioinformatics analysis is essential. Consequently, we utilized data from the GEO database to investigate differentially expressed genes between planktonic and biofilm groups, and identified drug targets through the construction of a protein–protein interaction (PPI) network and the cytoHubba algorithm. Inhibitors targeting this protein were identified through molecular docking screening of the FDA-approved drug library, and their anti-biofilm activity was validated in vitro. Through bioinformatics analysis, we identified GacS as the drug target in this study for treating biofilm-related infections. Virtual screening revealed that oxidized glutathione (GSSG) and arformoterol tartrate (ARF) are both capable of tightly binding to GacS and demonstrating good stability. In vitro experiments further confirmed that both GSSG and ARF demonstrated anti-biofilm activity, particularly when combined with azithromycin (AZM) or clarithromycin (CAM), significantly enhancing the biofilm inhibition effects of these antibiotics. This combination therapy offers a new and innovative strategy to combat biofilm-associated infections, showcasing the potential of GacS inhibitors in clinical applications. In conclusion, GSSG and ARF may serve as effective GacS inhibitors, and their combination with AZM or CAM could provide a novel approach for treating biofilm-related infections, paving the way for more effective treatment options. Full article

Objectives: Atherosclerosis is a chronic inflammatory disease characterized by complex pathological mechanisms. Early detection of vulnerable plaques is critical for assessing rupture risk and preventing acute cardiovascular events. Conventional ultrasound contrast agents (UCAs) are limited in their ability to penetrate the vascular wall and unable to provide detailed information on plaque composition and stability. In this study, we developed biosynthetic gas vesicles (GVs) derived from Halobacterium NRC-1 as UCAs for imaging of vulnerable plaques. Methods: These GVs were functionalized with the VHPKQHR peptide (VHP), enabling specific binding to vascular cell adhesion molecule-1 (VCAM-1), a key biomarker of inflammation in atherosclerosis. In vitro evaluation of VHP-GVs was performed through contrast-enhanced ultrasound imaging using agarose gel phantoms and adhesion assays with inflammatory cell models to assess their targeting capability toward VCAM-1. In vivo ultrasound molecular imaging was performed using the Sprague Dawley (SD) rat model of early-stage atherosclerosis in the left common carotid artery to evaluate imaging efficacy. Results: Both in vitro and in vivo experiments demonstrated that VHP-GVs could effectively penetrate the vascular wall into plaques and generate robust ultrasound contrast signals for precise identification of vulnerable regions. Conclusions: This study establishes a promising tool for the early diagnosis and targeted treatment of atherosclerosis, underscoring the translational potential of biosynthetic nanobubbles in clinical practice. Full article

Background/Objectives: Circulating cell-free DNA (cfDNA) consists of genomic DNA (cf-nDNA) and mitochondrial DNA (cf-mtDNA) fragments released from cells primarily through apoptosis and necrosis. In healthy individuals, the main source of cfDNA is apoptosis, whereas in cancer patients, necrosis predominates. Considering that in vitro cfDNA models are valuable research tools, this study presents an in vitro characterization of cf-mtDNA patterns released into the culture medium by four human cell lines: normal dermal fibroblasts (Hs27), induced pluripotent stem cells (iPSCs), melanoma cells (BMel), and prostate cancer cells (PC3). Furthermore, as fetal bovine serum (FBS)—a widely used supplement in cell culture media—has been shown to contain bovine cfDNA, species-specific primers were employed to eliminate potential artifacts arising from this contamination in in vitro experiments. Methods: Fragmentation analysis of cf-mtDNA was conducted by amplifying the human MT-CYB gene and the D-loop region in four cell lines using species-specific primers. Two indices, Q and λ, were employed to quantify fragmentation. Results: These indices reveal that cancer cells exhibit the highest degree of fragmentation compared to fibroblasts, whereas stem cells show the lowest degree of fragmentation. This study identified species-specific primers for the human and bovine MT-CYB gene, confirming the presence of bovine cf-mtDNA in cell culture media supplemented with FBS. Conclusions: in vitro cellular models are useful for studying the mechanisms of cfDNA release and fragmentation; designed primers provide a reliable tool for assessing contamination across different growth time points minimizing interference errors and non-specific amplifications. Full article

Noni juice polysaccharides demonstrate promising hypoglycemic activity, but their high molecular weight restricts bioavailability. This study established a controlled degradation approach to optimize the functional properties of Noni juice polysaccharides. Molecular characterization demonstrated that the degraded Noni juice polysaccharides (DNJPs, Mw 191.8 kDa) retained the core monosaccharide composition, while exhibiting enhanced solubility. In vitro experiments with insulin-resistant HepG2 cells showed that DNJPs (0.5–2 mg/mL) significantly enhanced glucose consumption (p < 0.01) and mitigated oxidative stress by upregulating antioxidant enzymes (SOD, CAT, and GSH-Px) and decreasing malondialdehyde (MDA) levels. DNJPs activated the PI3K/AKT-Nrf2-GSK3β signaling axis through a multifaceted mechanism involving the following: upregulating the phosphorylation levels of PI3K and AKT; enhancing Nrf2 nuclear translocation, which in turn promotes the expression of downstream targets such as HO-1 and NQO1; inhibiting GSK3β activity; and suppressing FOXO1-mediated gluconeogenesis. These findings underscore DNJPs as promising functional food ingredients that modulate two key pathways to improve glucose metabolism. Full article

Background/Objectives: The conventional treatment of glioblastoma (GBM) with alkylating agents is not curative. The protein O6-methylguanine DNA methyltransferase (MGMT) is a significant limitation, being able to repair drug-induced DNA damage. Thus, exploring non-alkylating agents already approved by the FDA is imperative. The antidepressant fluoxetine (FL) has been explored due to its anti-cancer properties. However, its first-pass effect and its non-targeted distribution to brain tissue are major limitations of FL’s administration, which is conventionally orally administered. Thus, the primary objective of this work was the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) tailored with folic acid (FA) for FL delivery to GBM cells. Methods: A Central Composite Design (CCD) was applied to optimize the NPs. Results: The developed FA-functionalized PLGA NPs exhibited physicochemical properties suitable for brain-targeted delivery. The final formulation presented an average diameter of 167 ± 8 nm, a polydispersity index (PdI) of 0.23 ± 0.07, and a zeta potential of −22.2 ± 0.3 mV. The encapsulation efficiency (EE) and loading capacity (LC) values were 44.4 ± 3.8% and 3.1 ± 0.3%, respectively. In vitro studies demonstrated that the NPs are stable in storage and simulated physiological conditions and can maintain a controlled and slow-release profile of FL for 17 days. In vitro cell uptake experiments demonstrated that conjugation with FA enhances the NPs’ internalization in GBM cells overexpressing folate receptors through endocytosis mediated by this receptor. Furthermore, in vitro cytotoxicity experiments demonstrated that the FL encapsulation in the developed NPs maintains drug efficacy, as well as it was able to increase cell sensitivity to treatment with an alkylating agent. Conclusions: These results suggest that the developed NPs are effective nanocarriers, either as a standalone therapy or as a chemosensitizer in combination with the standard GBM treatment. Full article