Characterized polyphenols from Prunus cerasifera alleviated HFD-induced intestinal inflammation and barrier dysfunction in obese mice by remodeling the gut microbiota and short-chain fatty acid profile.

Impaired liver function, often caused by disease or anticoagulant therapy, can result in deficiencies of essential coagulation factors, including clotting Factor II. This underscores the importance of developing ultrasonic systems capable of detecting clotting factor deficiencies in plasma sample. This study explored the potential of an impulsive acoustic radiation force (IARF)-based ultrasonic system to assess plasma stiffness and distinguish between normal plasma and plasma deficient in coagulation Factor II. The system employed focused ultrasonic beams on a solid sphere, inducing microdisplacement when immersed in human plasma samples. An electrical signal with a frequency of 2.03406 MHz, amplitude of 118 VPP, and pulse repetition frequency of 1.249 Hz powered the ultrasonic transducer. Microdisplacement was monitored using an SR-9000 board operating in pulse-echo mode at 4.89 MHz. Experimental and theoretical microdisplacement curves were used to determine the shear modulus (μ) and time-to-peak displacement (TPD) of plasma samples during coagulation. For control plasma and plasma deficient in coagulation Factor II, μ values measured between 10 and 35 minutes after coagulation onset were 300.11 ± 14.55 Pa and 75.53 ± 2.91 Pa, respectively. Under the same conditions, TPD ranged from 4.86 ± 0.28 ms to 6.97 ± 0.35 ms. A statistically significant difference in μ and TPD values was observed between normal and Factor II-deficient plasma samples. Furthermore, the μ time-curve of prothrombin-deficient plasma exhibited a distinct pattern. These findings demonstrate the potential of the IARF-based ultrasonic system as a laboratory-scale research tool capable of detecting viscoelastic changes in small plasma volumes. While promising, further validation, particularly with larger sample sizes, standardized activation protocols, and clinical cohorts, is required before its applicability to diagnosing coagulation disorders or monitoring therapies can be established.

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is closely linked to metabolic abnormalities, including central obesity, dyslipidaemia, hypertension, hyperglycaemia, and impaired liver function. Identifying effective lifestyle interventions and reliable noninvasive biomarkers remains a public health priority.ObjectiveThis study aimed to evaluate the effect of dietary modification on metabolic and hepatic parameters in women with MAFLD and to assess the potential role of interleukin-18 (IL-18) and alpha-2-macroglobulin (A2M) as noninvasive biomarkers.MethodsA prospective interventional study was conducted on 54 women with obesity and at least one criterion of metabolic syndrome. Participants were categorized into mild MAFLD, moderate MAFLD, or healthy liver groups based on ultrasonographic findings. All participants followed a calorie-restricted, balanced diet (1000–1200 kcal/day) for eight weeks. Anthropometric measurements, 24-hour dietary recall, and biochemical parameters, including IL-18, A2M, and liver enzymes, were assessed at baseline and post-intervention.ResultsAt baseline, women with moderate MAFLD exhibited significantly higher body mass index (BMI), minimal waist circumference (MWC), low-density lipoprotein cholesterol (LDL-C), and LDL/HDL ratio, along with lower high-density lipoprotein cholesterol (HDL-C), reflecting an adverse metabolic profile. They also reported higher macronutrient intake and lower dietary fiber consumption. A strong positive correlation between IL-18 and A2M (p ≤ 0.01) was observed across all groups and was associated with an unfavorable metabolic status. Following the intervention, significant improvements (p ≤ 0.05) were observed in weight, BMI, MWC, LDL-C, and gamma-glutamyl transferase (GGT), along with increased HDL-C levels. A highly significant reduction (p ≤ 0.01) in IL-18 was observed only among participants with MAFLD, while A2M levels decreased significantly (p ≤ 0.05–0.01) across all groups.ConcluionsA calorie-restricted, balanced diet significantly improves metabolic and hepatic parameters in women with MAFLD. These findings highlight the beneficial impact of dietary intervention on liver enzymes and inflammatory markers, particularly GGT, IL-18, and A2M, and support the potential utility of A2M as a noninvasive biomarker and therapeutic target.

Co-exposure profiles of PAHs and their derivatives in coking plant workers' serum and associations with liver function.

Background and aimsCirrhosis is a disease of impaired liver function and fibrosis caused by long-term liver damage. However, to date, no drugs have been approved to improve liver fibrosis. We report the results of a phase 2 study of S-005151 (generic name: Redasemtide), a partial peptide of High-Mobility Group Box 1 (HMGB1), in patients with chronic liver disease.Approach and resultsThis single-center, non-randomized, single-arm, open-label study was performed in Japan in patients with chronic liver disease (cohort A: 5 patients, cohort B: 5 patients) caused by HCV, HBV, MASH, or alcohol, with MR elastography of ≥ 4 kPa and Child–Pugh score up to 7 points. The primary endpoint was safety; secondary endpoints were efficacy against liver injury, function, and fibrosis.One adverse event (dysphonia) was observed in cohort A and one (fever) in cohort B, both of which were mild drug-related adverse events. S-005151 was well-tolerated. Regarding efficacy, there was a trend toward improvement post-treatment, with a decrease in transaminase and improvement in tissue inflammation scores in some cases; however, there was no significant improvement in hepatic dysfunction. Regarding liver fibrosis, there was a rapid and stable decrease in serum type IV collagen 7S levels, improvement in MR elastography findings, and an increase in platelet counts in some cases; 5 of 10 patients showed a trend toward improvement in liver fibrosis.ConclusionsS-005151 is well-tolerated in patients with chronic liver disease and may have therapeutic effects, in reducing liver damage and improving liver fibrosis.Trial registrationjRCT, jRCT 2031200232, Registered 4 December 2020 (https://jrct.mhlw.go.jp/latest-detail/jRCT2031200232).Supplementary InformationThe online version contains supplementary material available at 10.1186/s41232-026-00421-9.

BACKGROUND: Liver injury is a frequent complication of heatstroke and constitutes a direct cause of death. However, only a few studies examined the mechanism underlying heatstroke-induced liver injury. OBJECTIVE: We aimed to evaluate the role of peroxisome proliferator-activated receptor α (PPARα) in heatstroke-induced liver injury and to explore the potential mechanisms. METHODS: Male C57BL/6N mice were subjected to a control (22 ± 1 °C) or extreme heat temperature (39.5 ± 0.5 °C) to induce a heatstroke-associated liver injury animal model. PPARα agonist, ferroptosis inhibitor, and AAV8-mediated PPARα overexpression were administered to the mice to investigate the role of PPARα and ferroptosis in the heatstroke-induced liver injury. Serum was collected for liver function evaluation. Liver tissues were applied for morphological observation, staining detection, ferroptosis examination, and mechanistic exploration. RESULTS: Compared with the control group, extreme heat exposure-induced temperature dysregulation, impaired liver function, and morphological damage in mice. Proteomics screened PPARα as a protein of interest, with its level being significantly decreased in response to extreme heat exposure. Both PPARα activation and overexpression attenuated extreme heat-induced heatstroke and liver injury. Hmox1 was next screened and higher Hmox1 expression was identified, accompanied by elevated markers of ferroptosis including prostaglandin-endoperoxide synthase 2 (Ptgs2), malondialdehyde (MDA), lipid peroxidation (LPO) and Fe2+ levels. Ferroptosis inhibition mitigated heatstroke and liver injury induced by heat exposure. In the setting of extreme heat exposure, PPARα activation suppressed Hmox1 expression and the levels of ferroptosis markers. It not only induced differences in the expression of members of iron generation, efflux and uptake process and reduced hepatic intracellular Fe2+ accumulation, but also stimulated expression of molecules for countering lipid peroxidation including Nrf2-SLC7A11-GPX4 axis and FSP1 signaling. DISCUSSION: PPARα played an essential role in extreme heat exposure-induced heatstroke and liver injury, and PPARα intervention conferred protection against it via inhibition of ferroptosis.

Microplastics (MP) pollution is widespread in livestock farming environments. Exposure to MP can impair the gastrointestinal barrier, alter the structure and metabolism of the microbiota, and subsequently lead to organ damage. MP not only hinder cattle farming but also enter the food chain, posing a potential risk. Polyethylene (PE), a type of MP commonly detected in ruminant feed, has not yet been studied for its specific effects on cattle. Using calves as an animal model, this study investigates how exposure to MP induces toxicity via the rumen microbiota-gut-liver axis. Exposure to MP impaired weight gain and liver development in cattle, altered liver tissue pathology, increased blood lipopolysaccharide (LPS) levels, and triggered a systemic inflammatory response, identifying the liver as the primary target organ. Inflammation was closely associated with the dysbiosis of rumen microbiota and metabolites. MP exposure also damages the barrier integrity of the rumen, jejunum, and colon. The underlying mechanism involves MP altering the rumen microbial composition, which in turn triggers metabolic disorders, activates LPS synthesis pathways, and inhibits tight junction protein expression in the jejunum and colon. Although MP do not cause significant architectural damage to muscle tissue, they disrupt lipid homeostasis and nutrient composition, thereby promoting the deposition of pro-inflammatory LPS within muscle tissue. Rumen fluid metabolomics analysis revealed that differential metabolites were mainly enriched in the ATP-binding cassette transporter (ABC) pathway, with 4-fluoro-3-phenoxybenzoic acid and isovalerylglutamic acid being significantly correlated with levels of LPS, IL-6, TNF-α, and IL-1β. Notably, the concurrent increase in TNF-α and LPS in both the bloodstream and liver, alongside altered blood metabolomics, indicates that MP induce hepatic damage by disrupting the rumen microbiota-gut-liver axis. Transcriptomic analysis revealed that liver inflammatory injury was closely associated with NF-κB activation. Further mechanistic analysis supported the central role of the TLR4/MyD88/NF-κB signaling pathway. MP impair liver function in cattle by disrupting the rumen microbiota-gut-liver axis. This process involves the perturbation of rumen flora and intestinal barriers, triggering LPS translocation into the bloodstream, and ultimately causing liver damage. Video Abstract.

Evaluating the potential risk of ketamine-induced hepatotoxicity in the treatment of mood and anxiety disorders: A systematic review.

A two-wave panel biomonitoring study of changes in urinary pesticide metabolites and their associations with liver function and inflammatory markers.

Elevated liver stiffness is closely associated with morbidity and mortality in metabolic dysfunction-associated steatotic liver disease (MASLD). However, the contribution of increased stiffness to impaired liver function is poorly understood. Here, we demonstrate that hepatic cholesterol levels are determined by the stiffness of the liver. In the human MASLD cohort and a mouse model, intrahepatic cholesterol levels strongly correlated with liver stiffness. We show that a stiff matrix promotes spontaneous accumulation of cholesterol in isolated hepatocytes. As the underlying mechanism, we found that Liver X receptor alpha (LXRα) is mechanosensitively repressed. Activation of Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ) by exposure to stiff substrate, serum stimulation, low-density culture, or deletion of Large tumor suppressor kinase 1 and 2 (LATS1/2) robustly repressed LXRα activity. In the nucleus, YAP disrupted heterodimerization of LXRα with Retinoid X receptor alpha (RXRα) independently of their transcriptional activity. Consistently, hepatocyte-specific ablation of Yap/Taz facilitated hepatic cholesterol efflux and delayed cholesterol-induced fibrosis progression in mice. Transcriptomic analysis of MASLD patient livers confirmed a strong inverse correlation between LXRα target gene expression and liver stiffness as well as YAP/TAZ activity. These findings reveal the mechanosensitive regulation of hepatic cholesterol levels in MASLD, suggesting liver stiffness as a causal factor for hepatocyte dysfunction.

Cirrhosis of the liver is a chronic condition characterised by scar tissue replacing healthy liver tissue, leading to impaired liver function and endocrine disturbances. Hyperprolactinemia in cirrhosis results from reduced dopamine inhibition due to elevated circulating oestrogens. This study assessed the relationship between serum prolactin levels and the Child-Pugh scoring system in predicting complications in liver cirrhosis. A cross-sectional study was conducted on 70 cirrhotic patients over 12 months at a tertiary care center. Inclusion criteria included patients aged ≥18 years with diagnosed cirrhosis. Serum prolactin levels were measured using radioimmunoassay. Disease severity was evaluated using the Child-Pugh scoring system. Statistical analysis was performed to assess correlations between prolactin levels, Child-Pugh scores and clinical complications. Serum prolactin levels showed a strong positive correlation with the Child-Pugh score ( r = 0.641, P < 0.001). Elevated prolactin levels were associated with complications such as ascites, portal hypertension, hepatic encephalopathy and oesophageal varices ( P < 0.001). Patients with higher prolactin levels demonstrated significantly increased 6-month mortality ( P < 0.0001). Receiver operating characteristic curve analysis (area under the curve = 0.98) highlighted prolactin's predictive value for mortality. Serum prolactin is a reliable biomarker for assessing cirrhosis severity and predicting complications. It complements the Child-Pugh scoring system and may guide early interventions in high-risk patients.

Cancer-related pain remains undertreated despite established guidelines. In hepatocellular carcinoma (HCC), underlying chronic liver disease may amplify concerns regarding analgesic safety. We aimed to evaluate pain prevalence, analgesic use, pain-related perceptions, and educational needs among patients with HCC. We conducted a cross-sectional survey of 200 adult patients with HCC receiving systemic therapy at a tertiary referral center. A 30-item questionnaire assessed pain presence and intensity using a numeric rating scale (NRS), analgesic use patterns, liver-related safety concerns, opioid-related stigma, and educational needs. Clinical characteristics, including tumor burden and liver function, were analyzed in relation to pain and perception domains. Fifty-five patients (27.5%) reported current pain (mean NRS, 3.6 ± 2.5; mean worst pain 5.2 ± 2.8). Among them, 31 (56.3%) were using analgesics; however, 51.6% reported using them only when pain became unbearable. Misconceptions regarding analgesic safety were prevalent: 70.0% believed long-term analgesic use damages the liver, 56.0% believed analgesics are unsafe with impaired liver function, 46.5% associated opioids with addiction, and 30.0% hesitated due to the term "narcotic". These beliefs were not associated with Child-Pugh class or serum albumin level. Extrahepatic metastasis was associated with higher liver-related concern scores and a trend toward increased pain prevalence. Patients with elementary school education or less had poorer pain scale knowledge and no prior counseling. Pain undertreatment and safety-related misconceptions are common in HCC and appear independent of objective liver function. Structured, proactive education-particularly for patients with untreated pain and low educational attainment-may improve pain control in this population.

The CCR4-NOT complex is a central regulator of post-transcriptional gene expression that controls mRNA deadenylation and decay. Although the catalytic subunits have been well characterized, the physiological roles of several non-catalytic subunits including CNOT11 in mammalian tissues remain incompletely understood. Here, we investigate the physiological role of CNOT11 using genetic mouse models. No homozygous global Cnot11 knockout mice are obtained from heterozygous intercrosses, indicating that CNOT11 is required for early development. We generate hepatocyte-specific Cnot11 knockout mice (Cnot11-LKO) and find that Cnot11-LKO mice exhibit growth retardation and alterations in serum biochemical parameters during early postnatal stages, which are largely resolved by adulthood. Histological analysis does not reveal overt liver injury, while morphological differences in hepatocytes are observed. A marked increase in Ki67-positive cells was observed in the liver of Cnot11-LKO mice relative to control mice. Most Ki67-positive cells express HNF4A, suggesting that hepatocyte maturation is still in progress in the absence of CNOT11. Transcriptomic analyses of early postnatal livers reveal increased expression of cell cycle-related genes and reduced expression of metabolic genes, further supporting delayed liver maturation. These findings suggest that CNOT11 contributes to proper postnatal liver maturation and is required for the timely establishment of metabolically mature hepatocyte functions.

Frequent fried food intake fuels incidence of metabolic associated fatty liver disease attributed to acrylamide-induced hepatic lipid disorders through arachidonic acid-PGE2-PPARα axis.

Background/Objectives: Malignant distal biliary obstruction (MDBO) is a frequent complication of pancreatic cancer and often leads to obstructive jaundice, impaired liver function, and delayed oncologic treatment. Endoscopic biliary drainage using endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the standard minimally invasive approach for restoring biliary flow. However, clinical outcomes and complication rates vary across studies depending on stent design, placement technique, and patient characteristics. The aim of this systematic review was to evaluate the clinical outcomes and complications associated with endoscopic biliary stenting in pancreatic cancer-related MDBO. Methods: A systematic literature search was performed in PubMed/MEDLINE, ScienceDirect, Web of Science, and the Cochrane Library for studies published between January 2016 and January 2026. Studies evaluating ERCP-guided biliary stenting in adult patients with pancreatic cancer-related malignant distal biliary obstruction were included. Study selection followed PRISMA 2020 guidelines, and methodological quality was assessed using the Newcastle-Ottawa Scale. Clinical outcomes including technical success, clinical success, stent patency, recurrent biliary obstruction, and procedure-related complications were analyzed. Results: Eighteen studies involving a total of 3291 patients were included in the qualitative synthesis. Technical success rates were consistently high, reaching up to 100% in several studies, while clinical success rates generally exceeded 90%. Median time to recurrent biliary obstruction ranged from approximately 102 to 541 days depending on stent type and placement technique. Recurrent biliary obstruction was the most frequently reported complication, occurring in 30.7% of patients. Stent migration occurred in 14.9% of cases, while post-ERCP pancreatitis was reported in approximately 4.2% of patients. Several studies demonstrated longer patency with self-expandable metal stents compared with plastic stents. Conclusions: Endoscopic biliary stenting performed during ERCP is an effective and safe strategy for the management of malignant distal biliary obstruction in pancreatic cancer. Self-expandable metal stents provide more durable biliary drainage and reduce the need for repeat interventions. Nevertheless, recurrent biliary obstruction remains a common limitation, highlighting the need for further improvements in stent technology and optimized placement strategies.

Acute liver failure (ALF) is a critical syndrome characterized by sudden deterioration of liver function, coagulopathy, and hepatic encephalopathy, with a very high mortality rate. However, the global ALF diagnostic criteria exhibit significant heterogeneity, with remarkable differences among countries in terms of disease course duration, grading requirements for hepatic encephalopathy, exclusion principles for basic liver disease, and accompanied symptoms. This inconsistency hinders accurate determination of liver transplantation timing, epidemiological comparisons, prognostic assessments, and cross-border research. This article systematically analyzes the core differences in ALF definitions among liver disease-related associations in China, Japan, Europe, and America; explores their impact on clinical practice and scientific research; and proposes strategies such as multicenter collaboration and molecular typing to promote global integration and research advancement for ALF definitions.

Unraveling hepatotoxicity: mechanistic insights into food chain-transferred nanoplastics disrupting PPAR signaling and liver metabolism.

Abstract Liver abscesses (LA) cause economic losses due to carcass trimming and liver condemnations. Additional feedlot performance losses associated with LA may be caused by impaired liver function and metabolism. This study aimed to identify differentially expressed genes (DEG) in abscessed livers (AL) and non-abscessed livers (NL). Beef × Holstein steers (n = 60) were fed finishing diets containing 20 or 40% corn silage (20CS or 40CS) on a DM basis. Steers were allocated to five pens per diet and harvested after reaching 31% empty body fat, predicted by ultrasound, after 286 (20CS) and 293 (40CS) d on feed. Six representative AL were selected from steers fed 20CS (LA incidence = 40%) and six representative NL were selected from steers fed 40CS (LA incidence = 3%). Liver samples were collected at harvest from the left lobe, a minimum of 15 cm from any abscess. Total RNA from samples were sequenced in 2x150 bp format on an AVITI instrument. Reads were mapped to the Bos taurus reference genome (ARS-UCD2.0), and gene counts were obtained using HTSeq. Differential expression between AL and NL was analyzed using DESeq2. The DEGs were defined as genes with an adjusted-P &amp;lt; 0.10 and underwent gene set enrichment analysis via the g:GOSt function of g:Profiler. A total of 92 DEGs were identified, with 51 upregulated and 41 downregulated in NL compared with AL. Selection of DEGs of interest (5 upregulated, 5 downregulated) was based on their direct relationship to liver function and metabolism. Although DEGs of interest were not correlated with average daily gain, there were correlations with dry matter intake (DMI) and gain to feed (G:F). Genes associated with metabolic and energetic functions, such as MPC1, APOA4, GK5, CPOX, and ADIPOR2 were upregulated in NL. These upregulated genes were positively correlated with dry matter intake (DMI; R &amp;gt; 0.60, FDR &amp;lt; 0.10) and negatively correlated with G:F (R &amp;gt; -0.45, FDR &amp;lt; 0.22). These findings suggest that upregulation of genes associated with metabolic function may increase energy demand. Upregulated genes, specifically MPC1 and GK5, have been associated with less efficient nutrient utilization, consistent with a negative correlation with G:F. Genes associated with liver stress, inflammation, and tissue remodeling, such as TNC, IRF6, HPX,CMKLR2, and ERBB2, were downregulated in NL. Downregulated genes were negatively correlated with DMI (R &amp;gt; -0.50, FDR &amp;lt; 0.33), but positively correlated with G:F (R &amp;gt; 0.38, FDR &amp;lt; 0.78). Downregulated genes such as IRF6 and CMKLR2 are associated with enhanced feed efficiency. This suggests that the downregulated genes may be associated with healthier liver function and reduced immune activation. Overall, these data support that LA may have negative impacts on feedlot performance by altering liver health and metabolism.

BackgroundFrailty is characterized by an age-related decline in physiological reserve and is closely linked to postoperative outcomes. Early identification of preoperative frailty is therefore essential. This study aims to examine the associations between preoperative frailty and postoperative complications and cognitive impairment in patients with liver cancer, and to identify potential contributing factors.MethodsThis observational cohort study was conducted at the Affiliated Hospital of Jiangnan University from February to June 2025 and included 115 patients with liver cancer who underwent surgery. Frailty status was assessed using the Fried Phenotype criteria on 1 day before surgery, and cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) on postoperative day 3. Postoperative complications occurring before discharge were also recorded.ResultsA total of 43 patients (37.4%) developed postoperative complications, which may have been associated with preoperative frailty and its components, including exhaustion, grip strength, and low physical activity. Moreover, significantly higher prevalences of postoperative hypoproteinemia and liver function impairment, as well as markedly lower MoCA scores in unadjusted comparisons on postoperative day 3 (continuous outcome) were observed in patients with preoperative frailty. Receiver operating characteristic (ROC) analysis indicated that the frailty score may serve as a predictor of postoperative complications.ConclusionPreoperative frailty in patients with liver cancer may be associated with postoperative complications, and the frailty score may potentially serve as a predictor of these complications.

Biallelic pathogenic variants in YARS1 cause tyrosyl-tRNA synthase (TyrRS) deficiency that compromises the loading of tyrosine to its tRNA. YARS1 deficiency is characterized by impairment of neurological development, growth, liver function, and hematopoiesis. For other aminoacyl-tRNA synthetase deficiencies, supplementation of the respective amino acid and high-protein diet improved outcome. Whether tyrosine supplementation is effective in YARS1 deficiency is not known. Nine individuals with YARS1 deficiency received tyrosine (7 with and 2 without a high-protein diet). Aminoacylation was measured in patient-derived fibroblasts. Since supplementation, cooperation, endurance, and motor skills improved in 8 of 9 children. Two children demonstrated significant progress in active language skills. Weight gain improved in 6 of 9, and vomiting stopped in all cases. In 4 of 9 children, hematological parameters improved. In vitro, the TyrRS activity determined in 3 fibroblast cell lines homozygous for p.(Arg367Trp) was significantly reduced (0%, 6%, and 24%) at 100 μM tyrosine (physiological blood concentration). At 500 μM tyrosine, TyrRS activity increased to almost normal activity relative to controls at 100 μM. Given the positive cost/risk-benefit ratio, we advocate therapeutic trials with tyrosine supplementation and high-protein diet for YARS1 deficiency. Further studies should aim to determine variant-specific differences and long-term outcomes in comparison with natural history.