Hoof abnormalities, liver abscesses, and congestive heart failure (CHF) are animal welfare concerns that have increased in fed cattle. Our objective was to determine whether relationships between these issues exist in fed cattle at slaughter. Each condition was evaluated at a slaughter establishment in the Great Plains region of the United States (1,417 m elevation) on cattle ( Bos taurus , beef-type only) <30 months of age ( N = 398). Statistical analysis was performed to determine relationships between the prevalence of hoof abnormalities, liver abscesses, and CHF between each other and selected carcass characteristics: USDA quality grade (QG), USDA yield grade (YG), hot carcass weight (HCW), ribeye area (REA), and fat thickness (FT). Of the cattle, 85% had at least one hoof abnormality, 13% had a liver abscess, 52% had CHF, and 5% had all three disorders. There were no differences ( p > 0.4955) within the proportion of CHF, liver abscess, and hoof abnormality scores. Cattle with both a wide toe and inward curve (421.62 ± 10.45 kg) had lighter carcasses ( p < 0.034) than cattle with only an inward curve (460.95 ± 2.72 kg) or cattle with a shovel hoof (470.16 ± 6.79 kg). The HCW was heavier ( p = 0.0295) for cattle with mild CHF (463.60 ± 3.24 kg) than those with no CHF (451.51 ± 3.22 kg). The REA for cattle with no CHF was 103.17 ± 0.93 cm 2 , for those with mild CHF was 104.51 ± 0.88 cm 2 , and for those with severe CHF was 98.63 ± 2.46 cm 2 ( p = 0.0711). There was a greater proportion ( p = 0.0099) of heifers with no CHF (70.97 ± 8.17%) than steers (45.78 ± 2.61%). There were no differences ( p > 0.1025) in the REA, FT, and QG across hoof, liver, and CHF scores. Differences were present ( p < 0.034) in the HCW between the hoof and CHF scores. Further research is required to guide actions to address the animal welfare and productivity concerns associated with these issues.

Adeno-associated virus (AAV)-mediated liver injury is the primary off-target toxicity observed with viral gene therapy. Understanding of the underlying mechanisms has been hindered by the fact that murine studies poorly model AAV toxicity. The X-linked myotubular myopathy (XLMTM) gene therapy program epitomizes this therapeutic discordance, because a subset of participants treated with AAV8-driven myotubularin (MTM1) gene replacement developed fatal liver injury that was not predicted by preclinical models. Here, we investigated a multihit hypothesis whereby loss of Mtm1 interacts with the postweaning environment to precipitate liver injury in XLMTM mouse models. Mtm1 knockout (KO) mice fed purified ingredient diets manifested liver dysfunction that mirrored patient clinical presentations, including elevated plasma transaminases, altered bile acid composition, and histological features of cholestasis. We further demonstrated a role for MTM1 in maintaining hepatocyte structure and localization of the bile salt export pump. Liver-specific deletion of Mtm1 recapitulated many of these features, supporting a liver-autonomous role for Mtm1. Treatment of diet-sensitized mice with AAV8-driven gene therapy increased the susceptibility of cholestasis in global KO mice and induced liver injury in wild-type mice. Last, as a proof of concept, we treated global KO mice with lipid nanoparticle MTM1 gene replacement, which prevented development of key histopathological liver abnormalities. These findings provide critical insights into the environmental precipitants and molecular mechanisms of liver dysfunction in XLMTM and the adverse events seen in viral gene therapy studies and more broadly offer a framework to model AAV-associated toxicity and identify potential therapeutic interventions.

Context: With the increasing incidence rate of type II diabetes, it is particularly important to study its potential molecular mechanism and intervention means. Protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in insulin signalling and lipid metabolism. Objective: The purpose of this study was to explore the effect of PTP1B protein macromolecule on lipid metabolism in type II diabetes patients under the intervention of aerobic exercise. Materials and methods: The subjects were type II diabetes patients who had undergone aerobic exercise intervention. There were no significant abnormalities in liver and kidney function, indicating the safety of the intervention method. Therefore, PTP1B plays an important role in the regulation of lipid metabolism in type II diabetes. Conclusion: Aerobic exercise, as an effective intervention, can significantly improve the lipid metabolism in type II diabetes patients by affecting the function of PTP1B, thus providing new ideas and methods for clinical treatment.

Liver health in myotubular and centronuclear myopathies: a patient-driven data collection study to better understand liver health and improve standards of care.

This study leverages machine learning and cytokine profiles to differentiate liver and renal function abnormalities in the aging population, aiming for advancements in early detection techniques. The analysis involved data from 760 participants, employing logistic regression, random forest, lasso regression, extreme gradient boosting, and support vector machines to create diagnostic models. Cytokine levels were measured via ELISA, alongside liver and renal clinical function tests. The data were randomly split 3:1 into training and hold-out validation sets; Synthetic Minority Over-sampling Technique (SMOTE) was applied exclusively to the training set to mitigate class imbalance. Models were assessed on precision, recall, F1 score, specificity, and the area under the curve (AUC). Lasso regression was notably effective in identifying renal function abnormalities, delivering AUCs of 0.895 for males and 0.940 for females, pointing to its robustness in feature selection and model accuracy. For liver function, logistic regression was most accurate, with AUCs of 0.918 for males and 0.794 for females, identifying VCAM-1, REG4, Thrombomodulin, Notch-3 for males, and GDF-15, LDL R, CA125, PON1 for females as key discriminative cytokines. These results illustrate the models' capability in discerning critical biomarkers for early detection, with performance improved by SMOTE through correction of class imbalance in the training data. Integrating machine learning with cytokine profiling emerges as a highly promising method for early detection of liver and renal abnormalities in the aging population, suggesting significant potential for improving preventive healthcare outcomes.

Nandrolone decanoate induces liver damage via TGF-β/Smad3/miR-29 and regulation of FAT/CD36, PTP1B, HNF4A expression in male rats: Rescue effect of N-acetylcysteine.

Background Volumetric evaluation of liver and spleen size is useful, yet pediatric reference values remain limited and lack external validation. Purpose To establish normative liver and spleen volumes from contrast-enhanced CT in children and validate them in external regional and international datasets. Materials and Methods In this retrospective study, contrast-enhanced abdominal CT scans (patient age, 2-18 years) from Asan Medical Center and Pusan National University Yangsan Hospital (January 2005 to June 2021) were collected for the derivation dataset. Patients with chronic diseases, liver and/or spleen imaging abnormalities, or missing height and/or weight measurement within 3 months were excluded. Portal-phase CT images were segmented automatically with manual correction. Data from Seoul National University Children's Hospital (January 2018 to December 2021) and Cincinnati Children's Hospital Medical Center (January 2018 to July 2021) were used for regional and international validation, respectively. Model performance was assessed with the average pinball loss and absolute errors for predicting 50th percentiles. Results A total of 1298 children (median age, 11.3 years [IQR, 8.0-15.0 years]; 660 female) were included (derivation set, n = 1030 [all Asian]; regional validation set, n = 114 [all Asian]; international validation set, n = 154 [racially diverse]). The model including sex, height, and weight had the lowest average pinball loss for predicting 50th percentile liver (54.50 mL) and spleen (18.64 mL) volume and was therefore selected. Compared with previously published formulas, the model showed lower average pinball loss in the regional validation dataset for both liver (5th, 11.55 mL vs 11.93 mL; 50th, 50.88 mL vs 55.47-116.02 mL; 95th, 15.85 mL vs 19.49 mL) and spleen volumes (5th, 3.69 mL vs 3.74 mL; 50th, 15.19 mL vs 16.03 mL; 95th, 5.01 mL vs 5.59 mL). In international external validation, the average pinball loss was lower for the 50th percentiles (liver, 50.28 mL vs 50.30 mL; spleen, 20.97 mL vs 21.42 mL), and absolute errors were comparable (liver, 100.56 mL vs 100.60 mL [P = .53]; spleen, 41.93 mL vs 42.83 mL [P = .69]). Conclusion Normative liver and spleen volumes in children derived using quantile regression models and the respective predictive performance were presented. © RSNA, 2026 Supplemental material is available for this article.

TREM2-expressing macrophages in liver diseases.

Detection and characterisation of focal liver lesions (FLLs) remain challenging. Computed tomography (CT) provides crucial information on lesion number, location, nature and growth dynamics of FLLs over time. The study evaluated the use of contrast-enhanced triple-phase CT (TPCT) amongst patients with suspected FLLs in a tertiary hospital setting. This was a prospective, observational study. Patients with clinically suspected FLL or prior history of FLLs who underwent contrast-enhanced TPCT scans at the tertiary care centre between June 2022 and November 2023 were enrolled. Descriptive statistics were used for presenting study outcomes. Biopsy was performed selectively, particularly for representative lesions (up to 2 in number) in patients with multiple FLLs. Where histopathology was not feasible, diagnoses were confirmed through a composite reference standard. The accuracy and adequacy of TPCT in the diagnosis of FLLs were also evaluated. A P < 0.05 was considered statistically significant. Eighty patients were enrolled, the mean age was 54.1 ± 12.14 years and most were males (61.3%). Of the 299 FLLs, 154 were benign, while 145 were malignant. Metastases and haemangiomas were the most commonly identified malignant and benign lesions, respectively. The FLLs were categorised as hypovascular (59%) and hypervascular (41%). TPCT showed 100% sensitivity and specificity for diagnosing abscesses, cysts, intrahepatic cholangiocarcinoma and focal nodular hyperplasia. The specificity for diagnosing all cases was 100%. This study further validates the significance of TPCT in assessing FLLs and characterising focal liver abnormalities across various pathological scenarios and stages of the disease.

Hepatitis B virus (HBV)-related liver disease is an inflammatory-associated disease, with diverse clinical phenotypes ranging from asymptomatic HBV carriers to hepatocellular carcinoma. Interleukin-37 (IL-37), a cytokine that effectively inhibits innate and adaptive immunity, has powerful anti-inflammatory and anti-tumor effects. Several single nucleotide polymorphisms (SNPs) in the IL37 gene are genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression. However, different ethnic groups may have different allele frequencies and linkage disequilibrium structures. The effect of SNPs in IL37 on HBV infection and its relationship with different clinical outcomes have not been clarified among the Han people in southern China. Based on in silico functional prediction and previously reported in the literature to be potentially associated with diseases, we screened seven potentially functional SNPs (rs3811046, rs3811047, rs2723176, rs2723186, rs4611652, rs4392270, and rs4241122) located in the IL37 genomic region and 3-kb upstream and downstream of the gene body. 1,582 subjects were included in the study, including 747 patients with HBV-related liver disease, 405 patients who cleared HBV, and 430 healthy controls. The seven SNPs were genotyped using the SNaPshot SNP assay, and co-dominant, dominant, and recessive models were used to explore the association of each SNP with HBV infection and clinical outcomes after HBV infection. The rs4241122 demonstrated a significant association with both HBV infection and its clinical outcomes, with the GG genotype identified as an independent protective factor for spontaneous clearance of HBV. The rs2723186 and rs4392270 were also significantly associated with HBV clearance under specific genetic models. Furthermore, rs3811046 and rs3811047 were correlated with the progression of liver abnormalities following HBV infection. Our data suggests that SNPs at the IL37 locus are associated with susceptibility to HBV infection and clinical outcomes after HBV infection.

Effects of melatonin or physical exercise application in rats with hepatopulmonary syndrome.

This study evaluated the toxicity of methanol extracts of Newbouldia laevis in rats. Phytochemical screening was done using standard methods. Twenty five Wistar rats were divided into five groups of five rats each. The control group received 0.9% normal saline. The remaining groups were administered once daily for four days; 125, 250, 500, and 750 mg/kg body weight of the extract and afterwards monitored for 14 days. At the end, blood and organ samples were collected for biochemical, hematological and histopathological evaluation. Appreciable amount of flavonoids, alkaloids, saponins, tannins, oxalate and phytate were present. Significantly increased ALT activity of 65.28±1.55 U/L and 71.05±1.28 U/L were recorded at higher extract treatment doses of 500 and 750 mg/kg respectively compared to 34.71±1.99 U/L for the Control, just as AST and ALP presented similar trend of increased activities. Concentrations of total protein dropped from 74.74±2.25 g/dL (control) to 34.49±4.97 g/dL, while Urea (11.91±0.20 mg/dL) and creatinine (108.88±5.31 mg/dL) increased significantly compared to 5.36±0.41 mg/dL and 68.23±3.33 mg/dL recorded for controls respectively, indicating dose-dependent liver and kidney dysfunction. Other liver, kidney and haematological parameters varied significantly (p ≤ 0.05) compared to the Control. Organ histology revealed pathological abnormalities in liver and kidney of treated rats at higher doses. This evaluation presented significant dose-dependent alterations in biochemical, haematological, histological parameters, indicating potential organ-specific toxicity at higher doses. These findings have shown N. laevis methanol root extract as a potential alternative treatment for malaria and a source for drug development having shown potent antiplasmodial properties, however, proper dose regulation is needed in the use.

To observe the clinical effect and safety of herbal cake-insulated moxibustion in the auxiliary treatment of carotid atherosclerosis (CAS) differentiated as interaction of phlegm and blood stasis. Sixty-three patients with CAS differentiated as interaction of phlegm and blood stasis were randomly divided into an experimental group (33 cases, 4 cases dropped out) and a control group (30 cases, 3 cases dropped out). In the experimental group, herbal cake-insulated moxibustion was delivered in combination with oral administration with atorvastatin. In the control group, atorvastatin was administered orally. The duration of treatment in either group was composed of 12 weeks. Common carotid intima-media thickness (cIMT), the total area of carotid plaque, common carotid blood flow parameters, blood lipids contents (4 items) and traditional Chinese medicine (TCM) syndrome score were compared between the two groups before and after treatment. Blood routine and liver and kidney function were detected before and after treatment, and adverse events were recorded to evaluate safety. Compared with those before treatment, the bilateral cIMT and the contents of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in serum were reduced after treatment (P<0.05, P<0.001), the scores of the primary symptoms and secondary symptoms of TCM, as well as the total score were lower (P<0.001) in the two groups. The left cIMT and the contents of the serum TC, TG and LDL-C in the experimental group were lower than those of the control group (P<0.05, P<0.01), and the scores of the primary symptoms and secondary symptoms of TCM, as well as the total score were lower than those of the control group (P<0.001, P<0.01). After treatment, the bilateral peak systolic velocity (PSV) and end diastolic velocity (EDV) were increased in the experimental group (P<0.001), the right EDV was increased in the control group (P<0.001), and the bilateral PSV and EDV in the experimental group were higher than those of the control group (P<0.05, P<0.01, P<0.001). After treatment, there was no significant difference in the total area of carotid plaque between the two groups. After treatment, there were no significant abnormalities in blood routine and liver and kidney functions in both groups, and the safety was good. On the basis of conventional medication, the herbal cake-insulated moxibustion as an auxiliary treatment, presents its synergistic effect on CAS of interaction of phlegm and blood stasis syndrome in the patients, and this therapy is safe in clinical application.

Abstract Background Anti-inflammatory therapies have shown promise in reducing major adverse cardiovascular events (MACE) in patients with coronary atherosclerosis. AZD5718, a selective 5-lipoxygenase-activating protein (FLAP) inhibitor, has been shown in small and large animal models of atherosclerosis to reduce leukotriene production, decrease neutrophil chemotaxis and attenuate atherosclerosis progression but its efficacy in coronary plaque regression of patients with recent acute myocardial infarction (AMI) has not been evaluated. Purpose The PASSIVATE trial evaluated whether treatment with 125 mg of AZD5718 daily for 12 months, compared with matching placebo, reduces non-calcified plaque volume (NCPV) progression on computed tomography coronary angiography (CTCA) in patients with recent AMI. Methods This randomised, double-blind, placebo-controlled trial was conducted across 8 sites in Singapore and New Zealand. We included participants who were hospitalised for an AMI, defined according to the 4th Universal Definition of MI, underwent invasive coronary angiography showing at least ≥50% stenosis in one epicardial coronary artery and ≥20% in a second artery and a baseline white blood cell count ≥ 7.0 X 103/uL. We excluded patients with eGFR&amp;lt;50 mL/min/1.73 m2, abnormal liver or thyroid function tests, asthma or who were on treatment with other leukotriene antagonists. The primary efficacy endpoint was the absolute change from baseline to 12 months in total non-calcified (&amp;lt;130 HU) coronary plaque volume (mm3) measured on CTCA. Key secondary endpoints included the 12-month change in high-sensitivity C-reactive protein (hs-CRP) and peri-coronary adipose tissue attenuation (PVAT), a marker of peri-coronary inflammation on CTCA. All baseline and 12-month CTCA scans were analysed centrally at a core imaging facilty in Singapore. Results Baseline demographics, NCPV and hs-CRP were not significantly different between groups (Table 1). At 12 months, compared with baseline, mean NCPV increased by 55.46 ± 210.24 mm³ in the placebo group and increased by 48.47 ± 166.53 mm³ in the AZD5718 group (P=0.78) (Figure 1). Compared with the placebo group, the AZD5718 group had a more attenuated increase in neutrophil count (placebo group 0.49 ± 14.41 x10⁹/L vs. AZD5718 group 0.16 ± 6.04 x10⁹/L ; P=0.012) over 12 months. Other secondary efficacy endpoints, including hs-CRP (Figure 1), PVAT (Figure 1), total plaque volume, fibrofatty plaque volume and calcified plaque volume, showed no significant differences in change over 12 months between the placebo and AZD5178 groups. There were no significant differences in adverse or serious adverse events between the placebo and AZD5718 groups. Conclusions Treatment with AZD5718, a FLAP inhibitor, did not reduce NCPV or hs-CRP compared with placebo over 12 months in patients with recent AMI. These findings suggest limited efficacy of AZD5718 in modulating plaque progression or systemic inflammation in this population.Table 1:Baseline characteristics Figure 1:12-month change in endpoints

Novel In Vivo CAR platform for autoimmune disease therapy

Piezo1 is essential for endothelial-to-hematopoietic transition and hematopoietic stem/progenitor cell generation during embryonic development

The overuse of antibiotics in food animals encourages antimicrobial resistance (AMR) and leads to drug residues entering the human food chain. This study examined antibiotic residues in broiler chickens and the biochemical effects of consuming contaminated meat on Wistar rats. Thirty-two broiler chickens received therapeutic doses of fluoroquinolone, sulfonamide, gentamicin, oxytetracycline, neomycin, tylosin, and penicillin over two weeks, while the control group was given distilled water and standard feed. Meat from treated chickens was incorporated into the diets of rats for four weeks. Analysis using High-Performance Thin Layer Chromatography (HPTLC) and UV spectrophotometry revealed notable antibiotic residues in chicken muscle: penicillin (4.88 mg/g), tylosin (1.17 mg/g), gentamicin (0.31 mg/g), oxytetracycline (0.22 mg/g), neomycin (0.20 mg/g), sulfonamide (0.19 mg/g), and fluoroquinolone (0.015 mg/g), all exceeding United States or European maximum residue limits (MRLs). Residues were also detected in rat muscle, with penicillin (0.153 mg/g) and tylosin (0.138 mg/g) being the highest. Rats fed contaminated meat showed significant increases in liver enzymes (ALT up to 92.07 UI/L; AST up to 88.93 UI/L) and kidney markers (Na⁺ up to 183.93 mmol/L; creatinine up to 12.47 mmol/L) compared to controls. Hematological changes included elevated white blood cell counts (16.60 × 10⁹/L) and packed cell volume (53.17%). These findings confirm that consuming meat from antibiotic-treated poultry can transmit residues capable of causing liver, kidney, and blood abnormalities. Regulatory oversight and responsible antibiotic use in animal production are critical to protect public health.

Prevalence and characteristics of hepatotoxicity following asparaginase in adolescent and young adult acute lymphoblastic leukemia

ABSTRACTBackgroundImmune checkpoint inhibitors (ICIs) improve cancer outcomes but cause significant hepatobiliary toxicity (e.g., liver dysfunction, immune‐mediated liver disease). Prior studies were limited to small samples or case reports. This study evaluated hepatobiliary toxicity, risk variations, and temporal trends for six ICIs (PD‐1/PD‐L1 inhibitors) via the FDA Adverse Event Reporting System (FAERS) to guide safer use.MethodsWe analyzed 18 640 061 FAERS reports (2004–2024). Disproportionality analyses (ROR, PRR, EBGM, BCPNN) detected hepatobiliary toxicity signals. A Weibull model analyzed AE timing. Logistic regression assessed effects of age, gender, and weight.ResultsPD‐L1 inhibitors (Durvalumab, Atezolizumab) are associated more strongly with immune‐mediated liver disease/hepatic failure (ROR = 4.28–5.07). PD‐1 inhibitors (Nivolumab, Pembrolizumab) are linked more to hepatitis/liver abnormalities (ROR = 3.42–3.93). AE reports are common in males (53.32%) and patients > 65 years (43.43%), though demographics didn't alter risk (p > 0.05). Median onset: 23 days (Toripalimab liver injury) vs. 84 days (Tislelizumab autoimmune hepatitis), supporting drug‐specific monitoring in the first three months.ConclusionOur FAERS analysis showed PD‐L1 inhibitors were more associated with immune‐mediated liver disease and hepatic failure, whereas PD‐1 inhibitors were linked to hepatitis and liver abnormalities, underscoring the need for drug‐specific monitoring.

BackgroundSystemic lupus erythematosus (SLE) presents myriad challenges to gastroenterologists, although clinically significant liver involvement is uncommon. Literature regarding liver involvement remains variable, and the scope to illuminate this issue is vast, necessitating further study.Aims and objectivesThe purpose of this study was to assess and categorize the liver involvement in SLE and to evaluate treatment response.MethodsOur study was a retrospective observational study. Diagnosed cases of SLE referred to the Department of Gastroenterology were evaluated for liver involvement. Detailed history, clinical examination, and biochemical profile were recorded. Imaging, liver biopsy, and/or endoscopic gastroduodenoscopy were used as adjuncts wherever needed. After proper evaluation, patients were categorized according to liver involvement, and treatment response was assessed.ResultsOut of 96 patients with SLE referred to gastroenterology, 32 had liver abnormalities. Six (12.5%) patients had non-alcoholic fatty liver disease, four (12.5%) had nodular regenerative hyperplasia, two (6.25%) had lupus hepatitis, five (15.62%) had drug-induced liver injury, and one case each (3.12%) had hepatic infarction, hepatitis B, and hepatitis C. Autoimmune hepatitis (AIH) was seen in five (15.62%) patients, primary biliary cholangitis (PBC) was seen in one (3.12%), and AIH-PBC overlap was seen in three (9.375%) patients. Treatment was tailored according to the diagnosis, and response was assessed. One patient with hepatic infarction presenting as ALF died.ConclusionLiver perturbations may arise from basic diseases or side effects during treatment or unrelated factors. It is a multifaceted interplay between autoimmune mechanisms, vascular complications, and drug-related hepatotoxicity. Recognizing diverse presentations and understanding diagnostic intricacies are crucial for clinicians managing SLE patients with hepatic involvement, enabling better treatment outcomes.