Search Results (2,453)

Cyanobacterial harmful algal blooms are an increasing concern for wildlife health, particularly in eutrophic wetlands, yet well-documented avian cases supported by environmental, pathological, and toxicological evidence remain scarce. This study describes a sentinel case of probable microcystin toxicosis in a Red-gartered coot (Fulica armillata) from Laguna Petrel, a protected coastal wetland in central Chile, during a broader wildlife mortality event. Surface-water monitoring included nutrient analyses, in situ physicochemical measurements, phytoplankton assessment, and cyanotoxin quantification. The evaluated bird was documented alive with severe motor impairment, euthanized, and examined by gross necropsy, histopathology, and tissue toxicology. Water analyses showed elevated nutrients, persistently alkaline and highly productive conditions, marked dominance of Microcystis aeruginosa, and high concentrations of microcystin-LR, microcystin-RR, microcystin-YR, and nodularin. The bird showed marked hepatic lesions at necropsy, histopathological changes compatible with acute hepatotoxic injury, and detectable microcystin-LR in lyophilized liver tissue. Taken together, these findings support a diagnosis of probable microcystin toxicosis in this individual. This case highlights the value of waterfowl as sentinels of ecosystem health threats and underscores the importance of integrated monitoring in protected coastal wetlands potentially affected by toxic cyanobacterial blooms. Full article

Cyanidin-3-O-Glucoside (C3G) is the primary anthocyanin-active component in bilberry, exhibiting various pharmacological activities such as antioxidant, anti-inflammatory, and lipid metabolism-regulating effects. To address the clinical need for non-alcoholic fatty liver disease (NAFLD) prevention and treatment, this study aimed to investigate the ameliorative effects of C3G on NAFLD pathology and elucidate its molecular mechanisms of protection via the AMPK pathway. After a one-week acclimatization period, 20 six-week-old SPF mice were randomly divided into four groups: normal diet control (NCD), high-fat diet model (HFD), HFD + L-C3G (100 mg/kg/day), and HFD + H-C3G (200 mg/kg/day). Except for the NCD group, the remaining groups were fed a 60% high-fat diet for four weeks to establish an early-stage NAFLD model, with successful model construction verified by weight and liver weight gain. From the fifth week onward, C3G groups received daily administration for four consecutive weeks, while control groups were given an equal volume of distilled water. Liver function, lipid metabolism, oxidative stress, and inflammatory levels were assessed using ELISA, H&E staining, and other methods. The results showed that C3G restored liver function in NAFLD mice, improved lipid metabolism disorders, reduced oxidative stress and inflammatory responses, and alleviated liver pathological damage. Mechanistic studies revealed that C3G regulated the expression of mRNA and proteins related to the AMPK/SIRT1/NF-κB signaling pathway, activating the pathway by upregulating AMPK and its upstream regulators while inhibiting NF-κB-mediated inflammatory responses. This study confirmed that C3G can ameliorate high-fat diet-induced NAFLD lesions by activating the AMPK/SIRT1/NF-κB pathway, providing a potential intervention strategy for NAFLD prevention and treatment. Full article

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes. Full article

Background: Glucuronidation is a major phase II biotransformation reaction responsible for the inactivation and elimination of endogenous compounds and pharmaceuticals. This process is catalyzed by enzymes belonging to the UDP-glucuronosyltransferase (UGT) family, among which UGT1A1 is the most extensively studied. UGT1A1 plays a critical role in the metabolism of numerous drugs and is essential for bilirubin glucuronidation. Due to this specific function, it has significant clinical relevance, as impaired enzyme activity resulting from genetic polymorphisms or mutations can lead to the accumulation of unconjugated bilirubin in the bloodstream. This study aimed to evaluate the association between the UGT1A1*28 allele and the gene expression and protein levels in human liver tissue, in relation to different liver diseases. Methods: Liver tissues were obtained from patients with various liver pathologies and the control group consisted of tissues showing no pathological symptoms. A total of 143 patients were included in the study. Pyrosequencing was used to analyze PCR products for the UGT1A1*28 polymorphism (variable number of TA repeats in the TATA sequence of the promoter). Results: In both the control and study groups, UGT1A1 gene expression at the mRNA level and protein concentration in liver tissue decreased with the increasing number of UGT1A1*28 alleles. The association between UGT1A1 genotype and mRNA/protein content was most pronounced in HCV and AIH, and slightly weaker in the ALK and PBC groups. The significant association between UGT1A1*28 allele and bilirubin concentration was observed in control group but not in liver pathology. Conclusions: The UGT1A1*28 polymorphism is associated with reduced hepatic mRNA and protein abundance in patients with liver disease. However, the significance of this observation for the metabolism of the enzyme substrates should be further investigated. Full article

Clinical monitoring of chronic liver disease (CLD) is currently hindered by the invasiveness of conventional biopsies. While breath-borne volatile organic compound (VOC) analysis offers a promising non-invasive alternative, the metabolic profiles of sedentary populations often overlap significantly with those of healthy individuals, making latent pathologies difficult to identify. To overcome this high-resolution diagnostic challenge, this study developed an integrated framework that couples high-performance semiconductor sensing technology with a machine learning-based analytical baseline. During the biomarker screening phase, GC-MS was utilized to analyze over 2000 VOCs, identifying 20 markers associated with CLD. These were further optimized into a robust feature panel including ammonia, isoprene, dimethyl sulfide (DMS), and limonene. For several critical metabolic features exhibiting high diagnostic potential, preliminary identifications were conducted by referencing NIST database matches and relevant literature. To maintain analytical rigor and account for the inherent complexity of trace volatile metabolites in biological samples, these signals are treated as putative metabolic features and characterized by their retention times. Regarding hardware, an InN-based sensor with Pt-AlN surface modification was fabricated, achieving a limit of detection (LOD) for ammonia below 0.2 ppm. Crucially, while the InN sensor was validated for specific core markers such as ammonia, the current AI classification model is trained on a refined 7-VOC panel derived from the comprehensive GC-MS data. To resolve diagnostic overlaps, a three-state dynamic sampling protocol (resting, exercise, and recovery) was implemented to isolate biomarkers that remain physiologically stable. By integrating multi-dimensional VOC features (e.g., isoprene and DMS) with sensor-validated data through DBSCAN and Random Forest algorithms, the framework successfully captured non-linear metabolic fingerprints. Machine learning results confirm that the framework effectively distinguished sedentary controls from CLD patients, achieving a macro-average AUC of 0.96. This integration provides a high-precision technical pathway for early-stage liver disease screening. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health concern. Although pharmacotherapies such as Resmetirom and semaglutide have recently gained approval by FDA/EMEA, therapeutic options remain limited, necessitating the exploration of novel natural compounds. Our previous research indicated that lycopene exerts protective effects against MASLD; however, its underlying molecular mechanisms remain incompletely understood. The present study aimed to investigate whether lycopene alleviates MASLD by modulating mitophagy, with a focus on the PINK1/Parkin pathway. C57BL/6J mice were fed with high-fat diet for 12 weeks to induce MASLD and daily gavage of lycopene (10/40 mg/kg). In vitro, AML12 cells were treated with lycopene and Mdivi-1 to assess the role of PINK1/Parkin-mediated mitophagy against lipid accumulation, oxidative stress, and apoptosis. The results found that lycopene supplementation significantly ameliorated HFD-induced weight gain, dyslipidemia, hepatic steatosis, pathological liver injury, and elevated serum liver enzymes. It reduced hepatic reactive oxygen species (ROS) overproduction and suppressed the mitochondrial apoptotic pathway, as evidenced by decreased cytochrome c release and caspase cascade activation. Concurrently, lycopene restored ATP levels and mitochondrial membrane potential, improved ultrastructural integrity, and balanced mitochondrial dynamics by downregulating DRP1 and upregulating MFN2 and OPA1. Crucially, lycopene activated PINK1/Parkin-mediated mitophagy, leading to an increased LC3-II/LC3-I ratio and Beclin1 expression, alongside decreased levels of mitochondrial proteins TOM20 and COX IV. In vitro, the lycopene partially reversed the exacerbating effects of Mdivi-1 on lipid accumulation, ROS generation, apoptosis, and the suppression of the PINK1/Parkin pathway. Collectively, lycopene ameliorates MASLD by activating PINK1/Parkin-mediated mitophagy and improving mitochondrial homeostasis, thereby reducing hepatic lipid accumulation and attenuating hepatocyte apoptosis. Full article

Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7α-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver–intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases. Full article

Alpha-fetoprotein (AFP) is a glycoprotein primarily produced by the fetal liver and yolk sac during development. It is a multifaceted biomarker with significant applications in the prenatal screening of congenital abnormalities, cancer, and other disorders. The level of AFP in maternal blood may indicate several obstetric concerns and complications during pregnancy. Atypical AFP levels are commonly utilized as a biomarker for detecting fetal anomalies, placental complications, and other pregnancy-related issues. These findings raise concerns regarding the effectiveness of screening maternal serum alpha-fetoprotein (MS-AFP) as a primary indicator of pregnancy problems and underscore the need for further investigation into the functional role of AFP throughout pregnancy. The measurement of MS-AFP has been utilized for the past four decades. It is anticipated that MS-AFP measurement will continue to be utilized as a component of integrated or sequential tests for chromosomal abnormalities and may serve as a prognostic indicator for adverse obstetric outcomes. Critically, whether AFP functions solely as a passive marker or plays active biological roles in pregnancy physiology and pathology remains unresolved, necessitating additional mechanistic investigation and discourse. This review consolidates critical data from numerous studies on AFP, focusing specifically on its diagnostic and prognostic applications for congenital abnormalities and problems during pregnancy. This review also identifies key research gaps regarding the functional biology of AFP, particularly whether AFP functions as a passive biomarker or an active participant in the pathophysiology of adverse pregnancy outcomes. Full article

Salmonellosis is a global foodborne pathogen with zoonotic importance that seriously threatens livestock breeding and human health. Due to the implementation of an anti-resistance policy, probiotics as an alternative to antibiotics have attracted widespread attention. In this study, the widely used probiotic Escherichia coli Nissle 1917 (EcN) was selected to study its protective effect on mice infected with Salmonella typhimurium. Two mice groups (n = 15) were treated with either EcN and PBS. Flow cytometry showed that the frequency of mature dendritic cells in the Peyer’s patch was significantly increased compared to the PBS group. Previous administration of EcN protected against challenge with Salmonella typhimurium infection as an increased survival rate of the mice, a decreased degree of pathological changes, and the number of live bacteria in the spleen and liver were recorded compared to the control group. The results of 16S rRNA high-throughput sequencing of fecal microbial flora showed that EcN could reduce the abundance of microorganisms in the intestine and reduce the proportion of Lactobacillus, while Ruminococcaceae sp., Rikenella sp. and Bifidobacterium sp. disappeared. In contrast, the abundance of Bacteroides increased, which reduced the effect of Salmonella typhimurium on the distribution of intestinal microorganisms. Our results demonstrated that EcN has a protective effect against Salmonella typhimurium infection and may act as a candidate probiotic bacterium to apply in the future. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality, with incidence expected to increase. Liver transplantation is the most definitive curative option for early HCC, but many patients present beyond accepted transplant criteria, including the Milan criteria. Downstaging aims to reduce tumor burden and enable transplantation without compromising long-term outcomes. Methods: We reviewed the literature on liver transplantation, immune checkpoint inhibitors, immunotherapy–locoregional therapy combinations, and immune-related adverse events in HCC. Results: Immunotherapy-based strategies are emerging as downstaging approaches in selected patients. In advanced HCC, immune checkpoint inhibitor combinations have improved objective response rates compared with tyrosine kinase inhibitors, reaching approximately 20–36% in pivotal phase III trials. In the downstaging setting, early data suggest that immune checkpoint inhibitors, particularly with locoregional therapies, can achieve sufficient tumor regression to permit transplantation in patients initially beyond criteria. The ImmunoXXL trial reported successful downstaging and transplantation in all 16 patients treated with atezolizumab–bevacizumab, with 62.5% complete pathological responses, 2-year recurrence-free survival of 90%, and overall survival of 94%. The VITALITY study achieved successful downstaging in 75.6% of patients beyond Milan criteria, with 36.7% undergoing transplantation and 3-year post-transplant survival of 85%. However, pre-transplant immune checkpoint inhibitor exposure carries a clinically relevant risk of acute allograft rejection, reported in approximately 16–28% of transplanted patients. Conclusions: Immunotherapy-based downstaging before liver transplantation is promising but remains non-standard. Its use should be restricted to carefully selected patients within multidisciplinary protocols, as evidence remains limited by small cohorts, heterogeneous regimens, uncertain washout intervals, and rejection risk. Full article

The liver circadian clock coordinates hepatic lipid metabolism, bile acid synthesis, and glucose homeostasis through interlocking transcription–translation feedback loops. Disruption of this temporal organization is increasingly recognized as a shared pathological feature across the chronic liver disease spectrum. Transcriptomic profiling alone cannot capture the full scope of circadian dysregulation. Approximately half of rhythmically abundant hepatic proteins lack correspondingly rhythmic mRNAs. Roughly 25% of hepatic phosphosites oscillate with a 24-h period. Integrating transcriptomics, proteomics, post-translational modification profiling, metabolomics, and emerging single-cell and spatial approaches is therefore necessary for an accurate account of how circadian programs are remodeled in disease. This narrative review delineates the multi-omics landscape of circadian clock dysregulation across six chronic liver disease categories. These encompass metabolic dysfunction-associated fatty liver disease (MAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatocellular carcinoma (HCC), liver fibrosis, and cholestatic disease. Four molecular features recur across these contexts. BMAL1 functional downregulation, REV-ERBα oscillatory output attenuation, NAD⁺ oscillatory amplitude reduction, and gut–liver axis circadian desynchronization together constitute an inferential framework for hepatic circadian failure. These features represent recurring disease-associated motifs rather than an established pan-disease mechanism. The upstream mechanisms and evidence depth differ substantially by disease category. Oncogenic kinase-driven CLOCK post-translational modifications in HCC, phosphoproteomic remodeling in MAFLD, and epigenomic clock disruption persisting after HCV clearance represent findings that transcriptomics alone would not resolve. The near-complete absence of temporally resolved human tissue data remains the principal barrier to translational progress. This evidence gap limits the clinical actionability of current mechanistic findings across all disease categories. Circadian phase inference algorithms and prospective temporally designed cohort studies offer a methodologically grounded path toward clinically actionable circadian hepatology. Full article

Recently, a strain of Streptococcus agalactiae serotype Ia sequence type 7 clonal complex 1 (SaIa ST7 CC1) has emerged in Latin American tilapia aquaculture as an international threat. This study evaluated outbreaks of acute streptococcosis occurring between 2021 and 2025 on commercial Nile tilapia (Oreochromis niloticus) farms in six Latin American countries, aiming to integrate molecular, clinical, pathological, and environmental data. In total, 360 moribund or recently dead fish at various production stages (larvae/fry, pre-grow-out, and grow-out) were examined, and 25 S. agalactiae isolates were serotyped and subjected to real-time PCR analysis, multilocus sequence typing (MLST), virulence and antimicrobial resistance gene profiling, and antimicrobial susceptibility testing. All isolates belonged to SaIa and shared the same ST7 CC1 MLST profile, forming a highly homogeneous cluster with reference SaIa ST7 CC1 strains previously isolated from tilapia farms in Asia. These results are consistent with the regional spread of a single clonal line. At the larval and fry stages, SaIa ST7 CC1 was associated with hyperacute septicemia, gastrointestinal hemorrhage, and frequent intestinal intussusception, whereas in pre-grow-out and grow-out fish, neurological signs were more prominent, followed by ocular signs, systemic hemorrhages, and coelomic lesions. Histopathological examination showed profuse colonization of the brain, spleen, liver, and intestine by Gram-positive cocci, accompanied by marked acute circulatory and inflammatory lesions and few chronic granulomatous responses, consistent with a rapidly progressing, highly aggressive infectious process. All outbreaks occurred during extended periods of warm water (>32 °C), with large day–night thermal gradients and reduced dissolved oxygen, suggesting that thermal stress may exacerbate disease expression in affected systems. All SaIa ST7 CC1 strains exhibited phenotypic susceptibility to florfenicol and amoxicillin, whereas 84% (21/25) and 100% (25/25) exhibited intermediate susceptibility to oxytetracycline and enrofloxacin, respectively. In total, 5 of the 21 isolates (23.8%) with intermediate susceptibility to oxytetracycline carried tetracycline resistance genes (tetM, tetO). These findings identify SaIa ST7 CC1 as a clinically significant emerging threat associated with thermally facilitated and geographically expanding streptococcosis in tilapia production in Latin America. Immediate priorities include screening imported broodstock using MLST or whole-genome sequencing (WGS), harmonized regional molecular surveillance, climate-adaptive farm management practices, prudent antimicrobial use, and serotype-matched vaccination and breeding strategies that improve both disease and heat resilience. Full article

Emodin exhibits promising hepatomodulatory potential, yet its precise actions remain poorly characterized across distinct hepatic pathological states. Dose-dependent effects of emodin (40, 80, and 120 mg/kg) were investigated in mice with metabolic dysfunction-associated steatotic liver disease (MASLD), as well as healthy control mice, through integrated histopathological, biochemical, metabolomic, and gut microbiota profiling. The 80 mg/kg dose tended to yield the most favorable hepatoprotective outcomes in MASLD mice, whereas the 120 mg/kg dose was accompanied by apparent adverse hepatic alterations in normal mice. Correlative analyses further suggested that such divergent hepatic responses may be potentially linked to the gut microbiota–short-chain fatty acid (SCFA) axis, as well as the modulation of BAX/Bcl-2 balance and ESR1 expression. The hepatic effects of emodin are state- and dose-dependent. The dose of 80 mg/kg may represent a plausible candidate therapeutic range for MASLD, and the gut–liver axis is proposed as a likely underlying regulatory pathway. Full article

Background/Objectives: Liver diseases cause more than 2 million annual deaths globally, accounting for 4% of the total global mortality rate. Hepatic fibrosis (HF) acts as an indispensable pathological mediator in the progressive deterioration of chronic liver diseases. Thus, the identification of effective anti-fibrotic targets and rational development of corresponding therapeutic agents are expected to deliver profound clinical value for patients suffering from chronic liver disorders. Methods: An in vivo HF model was established to detect Kupffer cell (KC) polarization and periostin (POSTN) protein expression. In vitro, the CCK-8 (Cell Counting Kit-8) assay was applied to evaluate the regulatory effects of Postn-knockdown macrophages on LX-2 cell activity. Conditional knockout mice with Postn were constructed in vivo, and liver tissue samples were used for single-cell sequencing. Functional enrichment and cell differentiation prediction analyses were performed. CellChat was further utilized to characterize alterations in intercellular communication between Postn-deficient KCs and adjacent liver cells. Finally, POSTN-targeted inhibitors were screened and validated via virtual drug screening and experiments. Results: In the HF model, the M2 polarization of KCs was associated with the upregulated expression of POSTN. In contrast, in vitro Postn knockdown correlated with significantly suppressed LX-2 cell activation. Single-cell profiling suggests that Postn deficiency in Kupffer cells is linked to remodeling of the hepatic microenvironment. In drug repurposing, Rhodiosin exhibited binding affinity to POSTN and was observed to inhibit macrophage M2 polarization. Conclusions: POSTN may contribute to KC M2 polarization and be associated with remodeling of the intercellular interaction network among liver cells. Rhodiosin, as a POSTN-binding compound, shows potential for anti-hepatic fibrotic effects. Full article

Background: Cang-ai volatile oil (CAVO) is a traditional Chinese medicine with properties that soothe the liver and alleviate depression. CAVO is widely utilized in the field of antidepressant research and has surfaced as a possible treatment for depression. Depression is a common affective disorder and effective treatment methods are still limited. CAVO is effective in treating depression; however, the exact mechanism is still unclear. This study aimed to explore the likely mechanism by which CAVO reduces symptoms of depression in rats exposed to chronic unpredictable mild stress (CUMS). Methods: We established a CUMS model in Sprague–Dawley rats and administered CAVO via nebulization to evaluate its therapeutic effect. Behavioral and histology tests were conducted to evaluate brain tissue damage. We utilized metabolomics combined with proteomics to analyze the effects of CAVO. We then assessed molecular validation to further clarify the molecular mechanism of its activity. Results: In CUMS model rats, inhaling aerosolized CAVO reduced brain pathology and depression-like behaviors. CAVO changed serum levels of inflammatory cytokines and neurotrophic factors. Biomarkers linked to CAVO’s antidepressant effects were found via metabolomics. Functional analyses highlighted key molecular players such as TrkB, and CREB, and a close association with the antidepressant action of CAVO was confirmed. Conclusions: This study reveals that CAVO reduces depression-like behaviors in CUMS rats by regulating the NT/Trk signaling pathway. These results demonstrate CAVO’s therapeutic potential and lay the groundwork for future studies and the creation of depressive treatments. Full article