Search Results (1,497)

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on oxidative stress in RNASEH2-mutant AGS cells. Methods and Results: By means of flow cytometry, we found that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of Forkhead Box O3 (FOXO3), cytochrome C somatic (CYCS), and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. Conclusions: In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin treatment as a valid approach to ameliorate oxidative stress-related inflammation in AGS patients. Full article

Oxidative stress is a biological imbalance that contributes to cellular damage and is a major driver of aging and age-related disorders, prompting the search for natural antioxidant agents. Our study is a phytochemical, electrochemical, and biological characterization of the antioxidant potential of aqueous extracts from aerial parts of A. occidentale—leaves, bark, fruit, and cashew nuts—traditionally used in folklore medicine. Extracts were analyzed using FT-IR spectroscopy, GC × GC-TOFMS, polyphenol quantification, and antioxidant capacity assays (ABTS, FRAP, DPPH). Biological activity was tested in different mice and human cell lines (SH-SY5Y, MEF, ARPE-19, and HLECs). Aqueous extracts from the leaves and bark of A. occidentale exhibited significantly higher antioxidant activity compared to those from the fruit and cashew nut. These extracts showed elevated polyphenol content and strong performance in antioxidant capacity assays. In vitro, leaf and bark extracts enhanced cell viability under H₂O₂-induced oxidative stress, preserved mitochondrial membrane potential, and upregulated cytoprotective genes (HMOX1, NQO1, GCLC, and GCLM) in multiple cell lines. In contrast, fruit and nut extracts showed minimal antioxidant activity and no significant gene modulation. Our findings underscore the therapeutic potential of A. occidentale leaf and bark extracts as effective natural antioxidants and support their further development as candidates for phytotherapeutic interventions. Full article

The integration of nanotechnology and green synthesis strategies provides innovative solutions in biomedicine. This study focuses on the biofabrication of silver nanoparticles (AgNPs) using Corynespora smithii, an endophytic fungus isolated from Bergenia ciliata. The eco-friendly synthesis process employed fungal extracts as reducing and stabilizing agents thereby minimizing the need for hazardous chemicals. The AgNPs demonstrated strong potent biological activities, showcasing significant antioxidant, antibacterial, and anticancer properties. The antibacterial efficacy was demonstrated against various Gram-positive and Gram-negative bacteria, while cytotoxicity on the A549 lung cancer cell line revealed an IC₅₀ value of 10.46 µg/mL. A molecular docking analysis revealed interactions between the major bioactive compound, dimethylsulfoxonium formylmethylide, and the pathogenic proteins, Staphylococcus aureus and Salmonella typhi, displaying moderate binding affinities. Furthermore, the ADME analysis of dimethylsulfoxonium formylmethylide indicated favourable pharmacokinetic properties, including high gastrointestinal absorption, minimal lipophilicity, and low potential for drug–drug interactions, making it a promising candidate for oral drug formulations. These findings further support the compound’s suitability for biomedical applications. This research emphasizes the potential of C. smithii as a sustainable source for synthesizing bioactive nanoparticles, paving the way for their application in developing novel therapeutic agents. This study highlights the significance of harnessing endophytic fungi from medicinal plants for sustainable nanotechnology advancements. Full article

Most patients with non-small-cell lung cancer (NSCLC) present with advanced/metastatic disease at diagnosis, and molecular profiling is critical in guiding treatment decisions. This retrospective cohort study aimed to characterize EGFR mutations (EGFRm) in advanced/metastatic NSCLC patients, treatment patterns, and real-world outcomes. Adults diagnosed between 2018 and 2021 and treated at a Comprehensive Care Center were included. Time-to-event outcomes were analyzed using the Kaplan–Meier method. A total of 110 patients were included, with a median age of 69.0 years (range, 37–93), 76.4% female, and 83.2% non-smokers. About 97.3% had adenocarcinomas, with 93.6% at stage IV, 40.9% with ≥ three metastatic sites (brain metastases in 24.5%), 33.6% ECOG 2–4, and 58.2% with an EGFR exon-19 deletion. A minority started supportive care or curative-intent treatment, and 81.8% underwent first-line palliative systemic therapy (TKIs, 91.1%; chemotherapy, 8.9%). Median real-world overall survival (rwOS) was 18.9 months (95% CI, 13.8–28.1). Worse rwOS was observed in patients with ECOG 2–4 versus ECOG 0–1 (10.3 vs. 22.8 months; HR 1.82, 95% CI 1.17–2.85; p = 0.008) and in patients with exon-21 L858R versus exon 19 deletions (15.8 vs. 24.2 months; HR 1.59, 95% CI 1.00–2.54; p = 0.048). In patients treated with palliative systemic treatment, median progression-free survival was 10.9 months (95% CI, 8.8–13.6). This study provides important insights regarding real-world characteristics, treatment patterns, and outcomes from a cohort of EGFRm advanced/metastatic NSCLC patients. Full article

Unconventional food plants (UFPs) are increasingly valued for their nutritional composition and bioactive potential. This study proposes a comprehensive characterization of the chemical and bioactive properties of Pereskia aculeata Miller (Cactaceae) (PA); Xanthosoma sagittifolium (L.) Schott (Araceae) (XS); Stachys byzantina K. Koch (Lamiaceae) (SB); and inflorescences from three cultivars of Musa acuminata (Musaceae) var. Dwarf Cavendish, var. BRS Platina, and var. BRS Conquista (MAD, MAP, and MAC), including the assessment of physical, nutritional, phytochemical, and biological parameters. Notably, detailed phenolic profiles were established for these species, many of which are poorly documented in the literature. XS was characterized by a unique abundance of C-glycosylated flavones, especially apigenin and luteolin derivatives, rarely described for this species. SB exhibited high levels of phenylethanoid glycosides, particularly verbascoside and its isomers (up to 21.32 mg/g extract), while PA was rich in O-glycosylated flavonols such as quercetin, kaempferol, and isorhamnetin derivatives. Nutritionally, XS had the highest protein content (16.3 g/100 g dw), while SB showed remarkable dietary fiber content (59.8 g/100 g). Banana inflorescences presented high fiber (up to 66.5 g/100 g) and lipid levels (up to 7.35 g/100 g). Regarding bioactivity, PA showed the highest DPPH radical scavenging activity (95.21%) and SB the highest reducing power in the FRAP assay (4085.90 µM TE/g). Cellular antioxidant activity exceeded 2000% in most samples, except for SB. Cytotoxic and anti-inflammatory activities were generally low, with only SB showing moderate effects against Caco-2 and AGS cell lines. SB and PA demonstrated the strongest antimicrobial activity, particularly against Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus faecalis, with minimum inhibitory concentrations ranging from 0.156 to 0.625 mg/mL. Linear discriminant analysis revealed distinctive chemical patterns among the species, with organic acids (e.g., oxalic up to 7.53 g/100 g) and fatty acids (e.g., linolenic acid up to 52.38%) as key discriminant variables. Overall, the study underscores the nutritional and functional relevance of these underutilized plants and contributes rare quantitative data to the scientific literature regarding their phenolic signatures. Full article

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article

This study reports the impact of a silver nanoparticles/reduced graphene oxide@titanium dioxide nanocomposite (Ag/rGO@TiO₂) on the mechanical and biocompatibility properties of poly(styrene-co-methylmethacrylate)/poly methyl methacrylate (PS-PMMA/PMMA)-based bone cement. The chemical, structural, mechanical, and thermal characteristics of Ag/rGO@TiO₂ nanocomposite-reinforced PS-PMMA bone cement ((Ag/rGO@TiO₂)/(PS-PMMA)/PMMA) were evaluated using Fourier Transform Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), nano-indentation, and electron microscopy. FT-IR, XRD, and transmission electron microscopy results confirmed the successful synthesis of the nanocomposite and the nanocomposite-incorporated bone cement. The elastic modulus (E) and hardness (H) of the ((Ag/rGO@TiO₂)/(PS-PMMA)/PMMA) bone cement were measured to be 5.09 GPa and 0.202 GPa, respectively, compared to the commercial counterparts, which exhibited E and H values of 1.7 GPa to 3.7 GPa and 0.174 GPa, respectively. Incorporating Ag/rGO@TiO₂ nanocomposites significantly enhanced the thermal properties of the bone cement. Additionally, in vitro studies demonstrated that the bone cement was non-toxic to the MG63 cell line. Full article

Background: Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer that accounts for 1–5% of BC patients and regularly affects women under 40 years of age. Approximately 50% of IBC cases are HER2+ and can be treated with the monoclonal antibody-based therapy Herceptin (trastuzumab). However, resistance to Herceptin develops within a year, and effective second-line targeted therapies are currently unavailable for IBC patients. Lipocalin-2 (LCN2) is a promising therapeutic target for IBC due to its role in promoting tumor invasiveness, angiogenesis, and the inflammatory tumor microenvironment characteristic of IBC. Objective: We developed Herceptin-conjugated liposomes loaded with LCN2-targeted small-interference RNA (siRNA) for HER2+ IBCs. Methods: We synthesized DSPE-PEG(2000)-maleimide-Herceptin in a three-step process and formulated the liposomes together with DOPC, PEG(2000)-PE, cholesterol, and siRNA. Results: Dynamic light scattering confirmed the liposome size distribution, which was 66.7 nm for the Herceptin-conjugated liposome versus 43.0 nm in a non-functionalized liposome. Here, we report efficient internalization of this formulation into HER2+ IBC cells, reducing LCN2 levels by 30% and disrupting tumor emboli formation. RNA sequencing revealed 139 genes that were differentially expressed upon LCN2 knockdown, with 25 canonical pathways identified through Ingenuity Pathway Analysis. Conclusions: These findings suggest that LCN2-targeted siRNA within Herceptin-targeted liposomes represents a promising therapeutic strategy for IBC. Full article

Background: Modern viral vector production needs to consider process intensification for higher yields from smaller production volumes. However, innate antiviral immunity triggered in the producer cell may limit virus replication. While commonly used cell lines (e.g., Vero or E1A-immortalised cells) are already compromised in antiviral pathways, the redundancy of innate signaling complicates host cell optimization by genetic engineering. Small molecules that are hypothesized to target antiviral pathways (Viral Sensitizers, VSEs) added to the culture media offer a versatile alternative to genetic modifications to increase permissiveness and, thus, viral yields across multiple cell lines. Methods: To explore how the yield for a chimeric Zika vaccine candidate (YF-ZIK) could be further be increased in an intensified bioprocess, we used spin tubes or an Ambr15 high-throughput microbioreactor system as scale-down models to optimize the dosing for eight VSEs in three host cell lines (AGE1.CR.pIX, BHK-21, and HEK293-F) based on their tolerability. Results: Addition of VSEs to an already optimized infection process significantly increased infectious titers by up to sevenfold for all three cell lines tested. The development of multi-component VSE formulations using a design of experiments approach allowed further synergistic titer increases in AGE1.CR.pIX cells. Scale-up to 1 L stirred-tank bioreactors and 3D-printed mimics of 200 or 2000 L reactors resulted in up to threefold and eightfold increases, respectively. Conclusions: Addition of single VSEs or combinations thereof allowed a further increase in YF-ZIK titers beyond the yield of an already optimized, highly intensified process. The described approach validates the use of VSEs and can be instructive for optimizing other virus production processes. Full article

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that affects motor neurons of people, leading to death. This pathology can be caused by mutations in different genes, including superoxide dismutase 1 (SOD1). Previous studies have pointed out the presence of two transcripts of SOD1, a short one and a long one. The aim of this study was the investigation of these two transcripts both in the SH-SY5Y cell line and in patients’ peripheral blood mononuclear cells. We found that the shortest SOD1 transcript is upregulated under stress conditions in both the cellular model and the patients’ cells. Moreover, we found a potential correlation between the short SOD1 transcript and the severity of the pathology, which also correlates with the age of patients. No correlation was found between SOD1 transcripts and the progression of the disease. These data suggest a toxic effect of short SOD1 transcripts in ALS patients, by affecting the severity of the pathology making it a possible biomarker for this disease. Interestingly, our data suggest that a short SOD1 transcript does not influence and drive disease progression. The finding of a biomarker will have suitable implications as indicators of disease severity and from the perspective of drug development. Full article

Platelet-rich plasma (PRP) has become an increasingly valuable biologic approach for personalized regenerative medicine because of its potent anti-inflammatory/healing effects. It is thought to be an excellent source of growth factors that can promote tissue healing and lessen fibrosis. Although this treatment has demonstrated effectiveness in numerous disease areas, its impact on pulmonary fibrosis (PF) caused by silver nanoparticles (AgNPs) via its antiapoptotic effects remains to be explored. AgNPs were synthesized biologically by Bacillus megaterium ATCC 55000. AgNP characterization was carried out via UV–Vis spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) imaging to reveal monodispersed spheres with a mean diameter of 45.17 nm. A total of 48 male Wistar rats divided into six groups, with 8 rats per group, were used in the current study on the basis of sample size and power. The groups used were the PRP donor, control, AgNP, AgNP + PRP, AgNP + dexamethasone (Dexa) rat groups, and a recovery group. Body weights, hydroxyproline (HP) levels, and CASP3 and TWIST1 gene expression levels were assessed. H&E and Sirius Red staining were performed. Immunohistochemical studies for inducible nitric oxide synthase (iNOS) and cluster of differentiation 68 (CD68) with histomorphometry were conducted. A significant reduction in body weight (BWt) was noted in the AgNP group compared with the AgNP + PRP group (p < 0.001). HP, CASP3, and TWIST1 expression levels were significantly increased by AgNPs but decreased upon PRP (p < 0.001) treatment. Compared with those in the control group, the adverse effects of AgNPs included PF, lung alveolar collapse, thickening of the interalveolar septa, widespread lymphocytic infiltration, increased alveolar macrophage CD68 expression, and iNOS positivity in the cells lining the alveoli. This work revealed that PRP treatment markedly improved the histopathological and immunohistochemical findings observed in the AgNP group in a manner comparable to that of the Dexa. In conclusion, these results demonstrated the therapeutic potential of PRP in a PF rat model induced via AgNPs. This study revealed that PRP treatment significantly improved the histopathological and immunohistochemical alterations observed in the AgNP-induced group, with effects comparable to those of the Dexa. In conclusion, these findings highlight the therapeutic potential of PRP in a rat model of AgNP-induced PF. Full article

Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. The bacterium leverages several unique virulence factors to its advantage in order to colonize the human host. Among these, T4SS-delivered cytotoxin-associated gene A (CagA) has the most well-established links to severe forms of disease. To explore the effect of lactobacilli in disrupting CagA functions within host cells, we expressed HA-tagged humanized cagA in the human gastric epithelial AGS cell line and studied both the phosphorylation levels of CagA and its downstream binding partners. We found that gastric-specific Lactobacillus gasseri Kx110 A1 suppressed the phosphorylation of CagA and inhibited phosphorylation-dependent downstream signaling, resulting in the suppression of CagA-induced cell elongation of AGS cells, commonly known as the hummingbird phenotype. Surprisingly, phosphorylation-independent signaling was unaffected by L. gasseri. Furthermore, our confocal microscopy analysis revealed that CagA was mislocalized to the cytoplasm, suggesting that L. gasseri interferes with its membrane localization and thereby hinders its phosphorylation. Live L. gasseri that had direct contact with host cells was found to be necessary to suppress the hummingbird phenotype. In summary, the data suggest that a L. gasseri strain can inhibit CagA phosphorylation and suppress cell elongation. Full article

Age-related neurodegeneration is characterized by oxidative stress and iron-dependent cell death, yet the neuroprotective mechanisms of folic acid in modulating ferroptosis remain unclear. This study systematically investigated the role of folic acid in inhibiting ferroptosis and attenuating neuronal damage in aging, with a focus on the solute carrier family 7 member 11 (SLC7A11)-glutathione (GSH)-glutathione peroxidase 4 (GPX₄) antioxidant pathway, using aged rats supplemented with folic acid (<0.1, 2.0, and 4.0 mg/kg·diet) for 22 months, with young adult rats as controls. Brain iron accumulation and ferroptosis-related proteins (SLC7A11, GPX₄, Ferritin heavy chain 1 (FTH1)) were evaluated. In vitro, HT-22 hippocampal neuronal cells were pre-treated with folic acid (0, 10, 20 μmol/L) for 72 h before combining with Erastin (10 μmol/L)-induced ferroptosis for an additional 24 h. Intracellular Fe²⁺, lipid peroxidation (LPO), malondialdehyde (MDA), reactive oxygen species (ROS), along with cystine, GSH, and ferroptosis-related protein levels were quantified. Stable sh-SLC7A11 knockdown and control (sh-NC) cell lines were used to validate the dependency of folic acid’s protective effects on SLC7A11 expression. Folic acid supplementation in aged rats dose-dependently reduced aging-related brain iron accumulation and enhanced the expression of SLC7A11, GPX₄, and FTH1. In Erastin-induced HT-22 cells, folic acid significantly mitigated ferroptosis hallmarks. Mechanistically, folic acid increased extracellular cystine uptake and intracellular GSH synthesis, thereby activating the SLC7A11-GSH-GPX₄ antioxidant pathway. Notably, molecular docking technique suggested that compared to GPX₄, folic acid stabilized SLC7A11’s active conformation. sh-SLC7A11 knockdown completely abolished folic acid-mediated protection against ferroptosis, as evidenced by restored loss of cystine, GSH and GPX₄ production. This study innovatively emphasized the critical role of folic acid supplementation in inhibiting ferroptosis by up-regulating the SLC7A11-GSH-GPX₄ antioxidant pathway, primarily through enhancing cystine availability and SLC7A11 expression. These findings established folic acid as a potential dietary intervention for aging-related neurodegenerative diseases characterized by neuronal ferroptosis, providing preclinical evidence for folic acid based neuroprotection. Full article

Background: Alcohol-associated liver disease (ALD) is a primary global health concern, exacerbated by oxidative stress, inflammation, and gut barrier dysfunction. Conventional phytocompounds exhibit hepatoprotective potential but are hindered by low bioavailability. This study aimed to evaluate the hepatoprotective and gut-barrier-restorative effects of green-synthesized silver nanoparticles (AgNPs) derived from Enicostemma littorale, a medicinal plant known for its antioxidant and anti-inflammatory properties. Methods: AgNPs were synthesized using aqueous leaf extract of E. littorale and characterized using UV-Vis, XRD, FTIR, DLS, and SEM. HepG2 (liver) and Caco-2 (colon) cells were exposed to 0.2 M ethanol, AgNPs (1–100 µg/mL), or both, to simulate ethanol-induced toxicity. A range of in vitro assays was performed to assess cell viability, oxidative stress (H₂DCFDA), nuclear and morphological integrity (DAPI and AO/EtBr staining), lipid accumulation (Oil Red O), and gene expression of pro- and anti-inflammatory, antioxidant, and tight-junction markers using RT-qPCR. Results: Ethanol exposure significantly increased ROS, lipid accumulation, and the expression of inflammatory genes, while decreasing antioxidant enzymes and tight-junction proteins. Green AgNPs at lower concentrations (1 and 10 µg/mL) restored cell viability, reduced ROS levels, preserved nuclear morphology, and downregulated CYP2E1 and SREBP expression. Notably, AgNPs improved the expression of Nrf2, HO-1, ZO-1, and IL-10, and reduced TNF-α and IL-6 expression in both cell lines, indicating protective effects on both liver and intestinal cells. Conclusions: Green-synthesized AgNPs from E. littorale exhibit potent hepatoprotective and gut-barrier-restoring effects through antioxidant, anti-inflammatory, and antilipidemic mechanisms. These findings support the therapeutic potential of plant-based nanoparticles in mitigating ethanol-induced gut–liver axis dysfunction. Full article