Search Results (5,525)

Piglets weaning is a critical developmental stage marked by significant metabolic and inflammatory challenges. The hepatic responses during this period may differ among pig breeds with distinct genetic backgrounds. To explore the phenotypic and molecular differences in the livers between the Zaozhuang Heigai (HG) pig and Duroc×Landrace×Yorkshire (DLY) piglets and elucidate the regulatory mechanisms of genetic background on liver function, five 35-day-old piglets from each breed were selected. Body weight and liver coefficients were measured; histological features of liver sections were observed, and the transcriptome and metabolome of the liver were determined using mRNA sequencing and non-targeted metabolomics analysis. The results showed that HG piglets had significantly lower body weight (p < 0.01) and slightly higher liver coefficients than DLY piglets. Histological examination revealed that the hepatic lobule structure was intact in both breeds, while mild hepatic congestion was observed in some DLY piglets. Transcriptome analysis identified 429 differentially expressed genes (DEGs) with criteria of FDR adjusted p-values < 0.01 and |log₂(Fold Change)| > 1, and they were significantly enriched in oxidoreductase activity, peroxisome proliferator-activated receptor (PPAR) signaling, and arachidonic acid metabolism pathways. Metabolome analysis identified 169 differentially expressed metabolites (DEMs) with criteria of p < 0.05, VIP > 1, and |log₂(Fold Change)| > 1, and they were significantly enriched in nucleotide metabolism, arginine biosynthesis, and arachidonic acid metabolism pathways. Integrative analysis of DEGs and DEMs showed that arachidonic acid metabolism was the common pathway. Within this pathway, key genes (GPX3, ALOX5, and CBR3) were significantly associated with specific metabolites (15-deoxy-PGJ₂ and phosphatidylcholines) (FDR adjusted p < 0.05), suggesting a gene–metabolite interaction network that coordinates inflammatory regulation and oxidative stress. These findings provide molecular evidence for breed-specific hepatic metabolic regulation during the weaning period and are therefore conducive to the management of weaned piglets and the investigation of local pig characteristics. Full article

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their structure, which enable them to act as stable nanocarriers. Exosomes derived from milk and colostrum stand out in cancer prevention and treatment due to these properties. BMEs can be enriched with bioactive peptides, lipids, and nucleic acids. The targeted drug delivery capacity of BMEs can be made more efficient through these enrichment processes. For example, BME enriched with an iRGD peptide and developed using hypoxia-sensitive lipids selectively transported drugs and reduced the survival rate of triple-negative breast cancer (TNBC) cells. ARV-825-CME formulations increased antitumor activity in some cancer types. The anticancer effects of exosomes are supported by these examples. In addition to their anticancer activities, exosomes also exhibit effects that maintain immune balance. BME and BCE can regulate inflammatory responses with their miRNA and protein loads. These effects of BMEs have been demonstrated in studies on colon, breast, liver, and lung cancers. The findings support the safety and scalability of these effects. However, significant challenges remain in terms of their large-scale isolation, load heterogeneity, and regulatory standardization. Consequently, BMEs represent a new generation of biogenic nanoplatforms at the intersection of nutrition, immunology, and oncology, paving the way for innovative therapeutic approaches. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

Ferulic acid (FA) is a green feed additive. To investigate the molecular mechanisms by which FA attenuates heat stress-induced hepatic and intestinal oxidative stress, as well as cholesterol metabolism disorders in Megalobrama amblycephala (9.75 ± 0.04 g), individuals were fed diets supplemented with 0, 100, or 200 mg/kg FA for eight weeks, followed by exposure to heat stress at 34 °C for 48 h. The results indicated that FA supplementation reduced malondialdehyde levels and downregulation genes involved in inflammatory responses (e.g., interleukin-6), apoptosis (e.g., caspase 8), and endoplasmic reticulum stress (e.g., immunoglobulin binding protein) (p < 0.05), which collectively alleviated heat stress-induced hepatic and intestinal oxidative stress. FA supplementation increased the expression of ATP-binding cassette transporter A1, apolipoprotein A1, and liver X receptor α (p < 0.05), and restored liver and plasma TC levels to pre-stress levels (p < 0.05). Additionally, FA ameliorated the heat stress-induced dysbiosis of the intestinal microbiota and modulated the composition and abundance of metabolites in intestinal contents and plasma, some of which are associated with cholesterol metabolism. In conclusion, dietary FA can alleviate heat stress-induced hepatic and intestinal oxidative stress, maintain the stability of the intestinal microbiota and regulate metabolic profiles, and improve the cholesterol metabolism disorders caused by heat stress. Full article

Microplastics (MPs) are prevalent in freshwater systems; consequently, fish ingest them either accidentally or intentionally. Once ingested, MPs can translocate to various organs and cause physiological effects. Most studies have focused on tropical and marine fishes, and many have used mass-based methods that measure exposure only by the total mass of microplastics, ignoring particle number and size. These studies have also rarely examined MP effects or fate after a depuration period, limiting our understanding of MP impacts on temperate fishes, hindering the harmonisation of toxicological studies, and complicating assessments of food safety for cultured and wild fish. This study investigated the physiological impacts of dietary exposure to polystyrene microplastics (PS-MPs; 1–10 µm) in Salmo trutta fed a diet with ~5.4 × 10⁶ PS-MPs g⁻¹ feed for 21 days, followed by a 90-day depuration period. PS-MPs translocation from the intestine to the liver and muscle was investigated. Enzymatic biomarkers of oxidative stress and metabolism were analysed in the liver, digestive enzyme activity was assessed in the intestine, and inflammatory enzyme responses were evaluated in both liver and intestinal tissues. In addition, malondialdehyde (MDA) concentration, an indicator of lipid peroxidation, was quantified in blood, muscle, and liver samples. Results show that 1–5 µm PS-MPs translocated to the liver and muscle, while 10 µm particles largely remained in the intestine, with a small fraction detected in muscle tissue but not in the liver. Most biochemical markers were unaffected; however, both trypsin and peroxidase activities significantly decreased after 21 days, and lipid peroxidation increased in blood following 90 days of depuration. PS-MPs persisted in muscle following 90 days of depuration. These findings demonstrate that dietary exposure to PS-MPs in the size range 1–10 µm leads to selective physiological alterations in S. trutta and results in persistent accumulation of MPs in organs, especially muscle tissue consumed by humans, highlighting a clear concern for food safety. Full article

Obesity is closely linked to dyslipidemia, hepatic injury, and chronic inflammation through disturbances in the gut–liver axis. Here, we evaluated the anti-obesity effects of L. rhamnosus (Lacticaseibacillus rhamnosus) CU262 in a high-fat diet (HFD) mouse model and elucidated mechanisms using an integrated multi-omics strategy. Male C57BL/6 mice received CU262 during 12 weeks of HFD feeding. Phenotypes, serum/liver biochemistry, gut microbiota (16S rRNA sequencing), fecal short-chain fatty acids (SCFAs), and hepatic transcriptomes (RNA-seq) were assessed. CU262 significantly attenuated weight gain and adiposity; improved serum TC, TG, LDL-C and HDL-C; lowered ALT/AST and FFA; and mitigated oxidative stress and inflammatory imbalance (↓ IL-6/TNF-α, ↑ IL-10). CU262 restored alpha diversity, reduced the Firmicutes/Bacteroidetes ratio, enriched beneficial taxa (e.g., Akkermansia), and increased acetate and butyrate. Liver transcriptomics showed CU262 reversed HFD-induced activation of cholesterol/steroid biosynthesis and endoplasmic reticulum stress, with downregulation of key genes (Mvk, Mvd, Fdps, Nsdhl, and Dhcr7) and Pcsk9, yielding negative enrichment of steroid and terpenoid backbone pathways and enhancement of oxidative phosphorylation and glutathione metabolism. Correlation analyses linked Akkermansia and SCFAs with improved lipid/inflammatory indices and repression of cholesterol-synthetic and stress-response genes. These findings demonstrate that CU262 alleviates HFD-induced metabolic derangements via microbiota-SCFA-hepatic gene network reprogramming along the gut–liver axis, supporting its potential as a functional probiotic for obesity management. Full article

Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins. Full article

The immunosuppressive T regulatory cells (Tregs) regulate immune responses and maintain immune homeostasis, yet their functions in metabolic dysfunction-associated steatotic liver disease (MASLD) remain controversial. Here we report increased accumulation of Tregs and effector T cells within the liver parenchyma of mice fed a Western diet (WD). This pattern was also observed in MASH patients, where an increase in intrahepatic Tregs was noted. In the absence of adaptive immune cells in Rag1 KO mice, WD promoted accumulation of intrahepatic neutrophils and macrophages and exacerbated hepatic inflammation and fibrosis. Similarly, targeted Treg depletion exacerbated WD-induced hepatic inflammation and fibrosis. In Treg-depleted mice, hepatic injury was associated with increased accumulation of neutrophils, macrophages, and activated T cells in the liver. Conversely, induction of Treg numbers using recombinant IL2/αIL2 mAb cocktail reduced hepatic steatosis, inflammation, and fibrosis in WD-fed mice. Analysis of intrahepatic Tregs from WD-fed mice revealed a phenotypic signature of impaired Treg function in MASLD. Ex vivo functional studies showed that glucose and palmitate, but not fructose, impaired the immunosuppressive ability of Treg cells. The findings indicate that the liver microenvironment in MASLD impairs the ability of Tregs to suppress effector immune cell activation, thus perpetuating chronic inflammation and driving MASLD progression. Full article

Zanthoxylum bungeanum leaves (ZBL) are a phytogenic feed resource, but their energy value and functional effects in laying hens are not well defined. Two experiments were conducted. In Exp. 1, 96 healthy 38-week-old Roman Pink laying hens were allotted to either a control diet or a diet containing 5% ZBL (eight replicates, six hens per replicate) to determine apparent metabolizable energy (AME) using an indicator method (7 d adaptation, 3 d collection). The AME and nitrogen-corrected AME of ZBL were 5.46 and 5.33 MJ/kg, respectively. In Exp. 2, 832 healthy 41-week-old hens were randomly assigned to diets supplemented with 0, 1%, 2%, or 3% ZBL (8 replicates, 26 hens per replicate) for 8 weeks after 1 week adaptation. Dietary ZBL at 1% to 3% did not affect production performance (p > 0.05), but increased albumen height linearly (p < 0.05) and improved yolk color at 2% and 3% (p < 0.05). ZBL increased serum albumin (p < 0.05) with a linear tendency (p = 0.065), and elevated serum IgA and IgM linearly (p < 0.05). Serum total antioxidant capacity and total superoxide dismutase were increased (p < 0.05) with significant linear and quadratic responses (p < 0.05), while serum malondialdehyde was reduced (p < 0.05). In the liver, 3% ZBL increased total antioxidant capacity (p < 0.05), hepatic catalase activity was decreased in all ZBL groups (p < 0.05), and hepatic malondialdehyde was reduced (p < 0.05). Cecal acetate increased linearly (p < 0.05), and propionate and butyrate increased with both linear and quadratic dose responses (p < 0.05). ZBL improved small intestinal morphology, especially duodenal villus height (p < 0.05). Gut microbiota was remodeled, with a marked reduction in norank_o__WCHB1-41 and increases in Ruminococcus, Pseudoflavonifractor, and several Coriobacteriales and Erysipelatoclostridiaceae taxa. Overall, ZBL provides usable energy and, at 2–3% inclusion, enhances egg quality, antioxidant status, humoral immunity, short-chain-fatty-acid production, and intestinal health without compromising laying performance. Full article

A multifunctional diagnosis and treatment carrier, ZIF-8@CDs, based on carbon quantum dots (CDs) and the zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework which serves as a core structure for constructing the responsive delivery platform, is developed in this paper. The anticancer drug doxorubicin (DOX) and Survivin oligo (siRNA) are loaded to form a ZIF-8@CDs/DOX@siRNA dual loading platform. CDs of 5–10 nm are synthesized by the solvent method and combined with ZIF-8. Electron microscopy shows that the composites are nearly spherical particles of approximately 200 nm, and the surface potential decreases from +36 mV before loading CDs to +25.7 mV after loading. The composite system shows unique advantages: (1) It has Fenton-like catalytic activity, catalyzes H₂O₂ to generate hydroxyl radicals, and consumes glutathione in the tumor microenvironment. The level of reactive oxygen species (ROS) in the ZIF-8@CDs group is significantly higher than that in the control group. (2) To achieve visual diagnosis and treatment, its fluorescence intensity is superior to that of the traditional Fluorescein isothiocyanate (FITC)-labeled vector; (3) It has a high loading capacity, with the loading amount of small nucleic acids reaching 36.25 μg/mg, and the uptake rate of siRNA by liver cancer cells is relatively ideal. The ZIF-8@CDs/DOX@siRNA dual-loading system is further constructed. Flow cytometry shows that the apoptosis rate of HepG2 cells induced by the ZIF-8@CDs/DOX@siRNA dual-loading system is 49%, which is significantly higher than that of the single-loading system (ZIF-8@CDs/DOX: 34.3%, ZIF-8@CDs@siRNA: 24.2%) and the blank vector (ZIF-8@CDs: 12.6%). The platform provides a new strategy for the integration of tumor diagnosis and treatment through the multi-mechanism synergy of chemical kinetic therapy, gene silencing and chemotherapy. Full article

Background: Large language models (LLMs) are increasingly used in clinical medicine, yet their ability to interpret advanced intraoperative hemodynamic monitoring—particularly in the context of liver transplantation—remains largely unexplored. In this proof-of-concept study, we evaluated ChatGPT’s capacity to interpret multimodal hemodynamic data derived from both standard anesthesia monitoring and the PiCCO system. The study also employed a structured assessment instrument (ARQuAT), adapted through a Delphi-based process to evaluate LLM-generated clinical interpretations. Methods: Ten key surgical–hemodynamic phases of liver transplantation were identified using a modified Delphi approach to capture the major physiological transitions of the procedure. Sequential screenshots representing these phases were obtained from five liver transplant recipients, yielding a total of 50 images. Each screenshot, along with standardized clinical background information, was submitted to ChatGPT. Five expert anesthesiologists independently assessed the model’s responses using the modified ARQuAT tool, which includes six content-quality domains (Accuracy, Up-to-dateness, Contextual Consistency, Clinical Usability, Trustworthiness, Clarity) and a separate catastrophic Risk item. Descriptive statistics were calculated for domain-level performance. Inter-rater reliability (Kendall’s W) and internal consistency (Cronbach’s alpha, McDonald’s omega) were also analyzed. All statistical analyses and visualizations were performed using NumIQO. Results: ChatGPT demonstrated consistently high performance across all content-quality domains, with median scores ranging from 4.6 to 4.8 and more than 90% of all ratings classified as satisfactory. Lower scores appeared only in a small subset of frames associated with abrupt hemodynamic changes and did not indicate a recurring weakness in any specific domain. Catastrophic Risk exhibited a pronounced floor effect, with 86% of ratings scored as 0 and only three isolated high-risk assessments across the dataset. Internal consistency of the six ARQuAT content domains was excellent, while inter-rater agreement was modest, reflecting ceiling effects and tied ratings among evaluators. Conclusions: ChatGPT generated clinically acceptable, contextually aligned interpretations of complex intraoperative hemodynamic data in liver transplant recipients, with minimal evidence of unsafe recommendations. These findings suggest preliminary promise for LLM-assisted interpretation of advanced monitoring, while underscoring the need for future studies involving larger datasets, dynamic physiological inputs, and expanded evaluator groups. The reliability characteristics observed also provide initial support for further refinement and broader validation of the Delphi-derived ARQuAT framework. Full article

Background/Objectives: Previous studies have demonstrated that the cessation of liver damage after HCV cure can improve liver function, histological necroinflammation, and portal hypertension. However, scarce data about fibrosis stage or cirrhosis regression have been reported during follow-up. Methods: A prospective study evaluating hepatic biopsies and liver stiffness measurement by vibration-controlled transient elastography (VCTE-LSM) after the end of treatment (EOT) in patients with compensated advanced chronic liver disease (cACLD). Fibrosis was evaluated according to two semi-quantitative grading systems (METAVIR and Laennec) at 6 years after EOT (LB6) and compared with biopsies at 3 years (LB3). Results: Fifty-four patients with LB6 (34 with paired LB3–LB6) were included. Median (IQR) age was 53.9 (48.5–59.3), 38 (70.4%) were men, and 13 (24.1%) were HIV-coinfected. The VCTE-LSM was >15 kPa in 30 (55.6%). The LB6 (81.4 months after EOT) showed non-advanced fibrosis (F1–F2) in 12 (22.4%) patients, bridging (F3) in 26 (48.2%), and cirrhosis (F4) in 16 (29.6%): F4A in 7 (13.0%), F4B in 4 (7.4%), and F4C in 5 (9.3%). The 1-year post-EOT follow-up VCTE-LSM ≤ 8.6 kPa identifies patients without advanced fibrosis (AUROC = 0.929), with a negative predictive value of 88.9% and a positive predictive value of 95.2%. Paired biopsies showed regression in 9 (47.4%) out of 19 patients with cirrhosis: 8 (61.5%) of 13 with F4A but only 1 (16.7%) of 6 with F4B–F4C. Conclusions: Advanced fibrosis persists in most patients with advanced chronic liver disease after HCV eradication. Regression is possible in mild cirrhosis. However, it is a limited and slow event. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory roles throughout MASLD progression remain insufficiently defined. A 10-week high-fat, choline-deficient (HFCD) mouse model was established, and liver pathology was evaluated at weeks 6, 8, and 10. Time-resolved assessments combined untargeted metabolomics, magnetic resonance imaging–proton density fat fraction (MRI-PDFF), serum biochemistry, histological staining, immunofluorescence, and transmission electron microscopy to characterize dynamic alterations in lipid metabolism, redox status, inflammation, and fibrogenesis. The HFCD diet produced a clear temporal sequence of liver injury. Steatosis, phosphatidylcholine depletion, and early antioxidant loss appeared by week 6. By week 8, mitochondrial structural damage and pronounced cytokine elevation were evident. At week 10, collagen deposition and α-SMA activation signaled fibrotic progression. Metabolomics indicated significant disruptions in pathways related to ATP-binding cassette (ABC) transporters, one-carbon metabolism, and the tricarboxylic acid (TCA) cycle. Using integrated analytical strategies, this study suggests that choline deficiency may be associated with a time-dependent pathological cascade in MASLD, beginning with phospholipid destabilization and extending to altered mitochondria–endoplasmic reticulum crosstalk at mitochondria-associated membranes, alongside amplified oxidative–inflammatory responses, which collectively may contribute to progressive fibrogenesis as the disease advances. Full article

Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed. The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response. Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models. The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC. In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ⁹-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a progressive spectrum of metabolic liver injury in which immune activation, metabolic stress, and stromal remodeling evolve in a tightly interdependent manner. Although early disease stages are dominated by metabolic overload, accumulating evidence indicates that immunometabolic rewiring and fibro-inflammatory amplification critically shape the transition toward metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis. This review synthesizes emerging insights into how hepatocyte stress responses, innate and adaptive immune circuits, and extracellular matrix-producing stromal populations interact to form a dynamic, feed-forward network driving disease progression. Particular emphasis is placed on the deterministic role of immune–fibrotic coupling in shaping clinical phenotypes, disease trajectory, and therapeutic responsiveness. Rather than focusing on individual molecular layers, we highlight how integrated clinical, imaging, and biomarker-informed frameworks can capture immune–fibrotic signatures relevant to risk stratification and precision intervention. Building on this systems-level perspective, we outline next-generation therapeutic strategies targeting immunometabolic circuits, cross-organ communication, and multi-system dysfunction. Finally, we discuss how future precision medicine—supported by integrative biomarker profiling and dynamic physiological assessment—may reshape MASLD management and improve long-term hepatic and cardiometabolic outcomes. Full article