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PubMed2026

Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of ≥200 subjects, and had ≥1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans↗

PubMed2026

Early hepatic protein responses to dietary restriction-refeeding in Japanese quail: A proteomic investigation.

Feed intake and refeeding after nutrient scarcity induce rapid metabolic adaptations in the poultry liver; however, hepatic proteomic recovery pathways in the early hours post-refeeding remain poorly defined. This study aimed to characterize early liver protein signatures in Japanese quail (Coturnix japonica) recovering from nutritional stress under two refeeding conditions. Eighteen 12-week-old male quails (245.20 ± 0.213 g) were assigned to three groups (n = 6): control fed ad libitum (12.13 MJ/kg), 24 h feed deprivation followed by 6 h refeeding, and 24 h low metabolizable energy (6.30 MJ/kg) diet followed by 6 h refeeding. In total, 854 proteins were identified, of which 515 met the filtering criteria. The low metabolizable energy refeeding showed higher abundance of proteins linked to ATP binding and carbohydrate/carboxylic acid metabolism, alongside detoxification-related proteins, while suppressing translation/RNA-binding machinery and antioxidant pathways. Feed-deprived refeeding enriched in oxidative phosphorylation and mitochondrial complex I assembly with reduced cytoplasmic translation, NMD-related components, and sulfur compound metabolism. A direct comparison indicated divergent recovery strategies: low metabolizable energy refeeding mainly reflected oxidoreductase activity and translation initiation, whereas feed-deprived refeeding potentially enriched mitochondrial ATP production and glutathione-based defenses. Our analysis indicate that 6 h of refeeding initiates an early, incomplete recovery toward hepatic homeostasis, with the severity of prior nutritional restriction dictating distinct liver metabolic priorities. Collectively, these findings might provide a preliminary understanding of the hepatic mechanisms involved in recovery from nutrient deprivation and may help in the development of feeding strategies for managing metabolic recovery in poultry. However, these findings should be considered hypothesis-generating pending further validation.

Animals↗

PubMed2026

In Vivo Genome Editing Approach to Disrupt Hydroxyacid Oxidase 1 for the Treatment of Primary Hyperoxaluria Type 1.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that leads to kidney and liver failure. PH1 is caused by a mutation in the alanine glyoxylate aminotransferase (AGXT) gene, which encodes a key metabolic enzyme that converts glyoxylate to glycine in the liver. Inability to metabolize glyoxylate leads to oxalate overproduction, yielding insoluble calcium oxalate crystals; accumulation of these crystals leads to progressive organ failure. Here, we used a novel, minimally disruptive genome-editing approach to disrupt the mechanism of action of hydroxyacid oxidase 1 (HAO1), an upstream enzyme in the glyoxylate metabolic pathway. Successful gene editing and disruption of the HAO1 gene is expected to increase levels of glycolate, a harmless intermediate of the glycine metabolic pathway, thereby preventing the formation of calcium oxalate crystals. We intravenously administered an adeno-associated virus (AAV) vector expressing the M1HAO1 meganuclease to both wild-type and Agxt-/- mice, a mouse model of PH1. We observed >30% editing of HAO1 in Agxt-/- mice, correlating with a dose-dependent increase in serum glycolate levels. At the highest dose tested, urine glycolate levels increased by 79%, with a concomitant 75% decrease in urine oxalate levels. We also evaluated in vivo targeting in rhesus macaques injected with AAV expressing two different versions of the HAO1 meganuclease. Dose-dependent editing of hepatic DNA and RNA was achieved, and serum glycolate levels changed in a manner consistent with successful liver editing; additionally, the treatment was well tolerated. Our results indicate that AAV-delivered meganucleases can effectively target HAO1 in mice and nonhuman primates to achieve high levels of HAO1 gene editing. Moreover, increased glycolate levels in serum indicate that this intervention significantly impacts the HAO1-mediated glycolate-to-glyoxylate pathway. These data suggest that this approach may represent an effective treatment for PH1.

Hyperoxaluria, Primary↗

PubMed2026

Effects of phytosterols supplementation on hepatic lipid metabolism and metabolic outcomes in obese rodent models: a systematic review and meta-analysis.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and nonalcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPARα, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPARα expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.

Animals↗

PubMed2026

Excess iodine induces lipid metabolic disorders by the gut microbiota SCFAs/H2S-p-AMPKα/PPARγ/SREBP-1c pathway in female rats.

With the development of living standards, the problem of excess iodine has long been overlooked. This study aimed to investigate the detrimental effects of long-term excess iodine exposure on lipid metabolism in female Sprague-Dawley rats from the gut-liver axis perspective, and to elucidate the underlying molecular mechanisms by which the gut microbiota and its metabolites mediate iodine-induced lipid metabolic disorders. The results indicated that abnormal iodine nutrition has a negative effect on the health of rats. Specifically, excess iodine not only causes thyroid disorders but also leads to liver lipid metabolism disorders, including elevated serum and hepatic total cholesterol/triglyceride levels and lipid accumulation in the liver. Further investigation revealed that excess iodine causes liver lipid metabolism disorders by altering the gut microbiota, which resulted in an increase in the relative abundance of Desulfovibrio and Lachnospiraceae NK4A136_group, and a decrease in the relative abundance of Akkermansia and Blautia in excess iodine groups. A decrease in the relative abundance of Blautia and an increase in Lachnospiraceae NK4A136_group were strongly correlated with reductions in short-chain fatty acids (acetic, propionic, and valeric acids), whereas an increase in Desulfovibrio was strongly correlated with an increase in H2S. Additionally, acetic acid was negatively correlated with H2S in serum and liver. Excess iodine reduced hepatic p-AMPKα expression while upregulating key regulators of lipid metabolism, including SREBP-1c, PPARγ and ACC1. These changes may represent one of the key mechanisms by which excess iodine induces lipid metabolism disorders through the microbiota-metabolite axis. Overall, these findings suggest that excess iodine influences lipid metabolism through the gut-liver axis. The results of this study provide scientific references and guidance for the appropriate intake of iodine and offer novel insights for early nutritional interventions targeting lipid metabolism disorders.

Journal Article↗

PubMed2026

Genomic characterization and pathogenicity of ruminant Listeria monocytogenes isolates in a murine oral infection model.

Listeria monocytogenes is a major foodborne pathogen; its ruminant isolates display zoonotic characteristics, causing similar clinical signs in humans, including abortion and encephalitis. However, data on whole genome sequencing and pathogenicity of ruminant L. monocytogenes isolates remain sparse. This study aimed to analyze the genotypic characteristics of L. monocytogenes isolates from ruminants with listeriosis. Furthermore, we assessed the in vivo pathogenicity of four ruminant L. monocytogenes isolates, characterized via whole-genome sequencing-based genetic clustering, in orogastrically inoculated mice. The isolate LM18 (serotype 1/2b, ST224, SL6178) had the lowest lethal dose compared to the other three isolates including previous hypervirulence type (serotype 4b, ST1, SL1) and caused secondary bacteremia in lungs, with sustained bacterial loads in the spleen and liver. Genomic (listeria pathogenicity island -1 and -3) and virulence gene (actA and llsX) mutation analyses associated with virulence suggested from well-recognized studies could not elucidate the virulence of the isolates. SSI-1, which only exists in the isolate LM18 (serotype 1/2b, ST224, SL6178), may help L. monocytogenes survive in the gastrointestinal environment, thereby affecting its virulence. Further research should investigate the role of SSI-1 in the pathogenicity of L. monocytogenes. Moreover, additional studies utilizing larger datasets of ruminant isolates are required to validate our genotypic characterization and to obtain a comprehensive picture of further genotypic differences crucial for L. monocytogenes pathogenicity.

Animals↗

PubMed2026

Genetic evidence for a causal relationship between melatonin metabolism and depression.

To investigate the causal relevance of melatonin metabolism, which provides the biological basis for circulating melatonin levels, to specific depression symptom subtypes, we performed a targeted systematic review of melatonin metabolism pathways in the human brain and liver. Using two-sample Mendelian randomization (MR), we assessed the causal effects of metabolism pathways and/or individual genes on major depressive disorder (MDD) and nine symptom subtypes derived from Patient Health Questionnaire-9 (PHQ-9). Instrumental variables (IVs) were expression quantitative trait loci (eQTL) for eight individual genes, one synthesis route, and three degradation routes. Results were assessed using Bayesian colocalization and phenome-wide association analyses. At the pathway-level, the genetically proxied synthesis-route signal was associated with PHQ-9 Assessment 5 (PHQ9A5, OR: 0.89, 95% CI: 0.85-0.93), but sensitivity analyses suggested this association was primarily driven by TPH1 and may reflect serotonin-related biology. In contrast, higher brain melatonin degradation raised the risk of both PHQ9A1 (OR: 1.03, 95% CI: 1.02-1.04) and PHQ9A7 (OR: 1.03, 95% CI: 1.02-1.03). Within degradation, up-regulation of the kynurenine sub-pathway increased the odds of PHQ9A3 (OR: 1.05, 95% CI: 1.02-1.07), PHQ9A4 (OR = 1.04, 95% CI: 1.02-1.06) and PHQ9A7 (OR: 1.05, 95% CI: 1.02-1.07). Gene-level analyses were largely concordant, except for SULT1A1, whose higher expression was genetically protective for PHQ9A3 but risk-increased for PHQ9A1 and PHQ9A4. Overall, these results demonstrate that melatonin metabolism exerts symptom-specific and pathway-specific causal effects on depression. A stratified view of melatonin's role may help optimize the application of exogenous melatonin supplementation.

Melatonin↗

PubMed2026

Integrated transcriptomic and metabolomic analyses provide new insights into the response of black rockfish (Sebastes schlegelii) larvae to temperature fluctuations.

Sebastes schlegelii usually encounter elevated and fluctuating water temperatures near its upper thermal limit in summer, yet the hepatic responses of larvae to repeated temperature fluctuation regimes remain unclear. To address this question, S. schlegelii larvae were exposed for 8 days to four thermal regimes: constant 18 °C (CT), constant 28 °C (HT), intermittent cooling from 18 to 8 °C followed by recovery to 18 °C (FL), and intermittent warming from 18 to 28 °C followed by recovery to 18 °C (FH). Survival rate was evaluated, and integrated liver transcriptomic and metabolomic analyses were performed. Final survival rates were 96.67% in the CT group, 97.78% in the FL group, and 77.78% in the FH group. Survival rate in the HT group (38.89%) was significantly lower than that in the other three groups (P < 0.05). HTvsCT, FLvsCT, FHvsCT, and FHvsHT comparisons identified 2598, 1207, 622, and 2404 differentially expressed genes and 627, 606, 690, and 610 differential metabolites, respectively. KEGG enrichment analyses of DEGs and SDMs in HTvsCT highlighted HSP-mediated proteostasis, endoplasmic-reticulum protein processing, branched-chain and sulfur amino acid metabolism, glutathione metabolism, and central carbon metabolism, with upregulated hsp90aa1, bckdha, gclc, and pfkp and reduced levels of branched-chain amino acids and methionine. Compared with HT, FH showed attenuated disturbances in proteostasis, amino acid and redox regulation, and central carbon metabolism, together with recovery-associated glycerophospholipid turnover. FL primarily induced polyunsaturated fatty acid (PUFA)-related membrane lipid remodeling. These findings indicate that hepatic responses differed between continuous high-temperature exposure and temperature fluctuations and between fluctuation regimes.

Animals↗

PubMed2026

Structural and tissue-specific organisation of endocrine Fgf19 and Fgf21 signalling in rainbow trout.

Endocrine fibroblast growth factors (FGF19 subfamily) play a key role in regulating metabolic homeostasis in vertebrates. However, their functional diversification in salmonids remains poorly understood. In this study, we conducted an integrative characterisation of Fgf19 and Fgf21 signalling in rainbow trout (Oncorhynchus mykiss) by combining phylogenetic, structural and expression analyses. Phylogenetic analyses revealed the conservation of single fgf19 and fgf21 genes, despite the extensive expansion of receptors post-Ss4R (salmonid-specific fourth-round whole genome duplication). Structural modelling and molecular dynamics simulations demonstrated the stable interactions of both ligands to multiple Fgfr isoforms, with receptor-specific energetic profiles and conserved core interaction residues. Tissue expression profiling revealed clear differences from mammalian models, such as predominant hepatic fgf19 expression and the absence of hepatic fgf21 under basal conditions. In addition, there were complex and tissue-dependent distributions of fgfr and klotho transcripts. These findings support a receptor-driven diversification model of endocrine Fgf signalling in salmonids, suggesting enhanced endocrine plasticity associated with the retention of receptors following post-genomic duplication. Taken together, our findings provide new insights into the structural and regulatory organisation of endocrine Fgf signalling, as well as its potential role in metabolic regulation in rainbow trout.

Animals↗

PubMed2026

Plasticity of hepatic metabolism in Arctic char (Salvelinus alpinus) in response to cyclic hypoxia.

The emergence of cyclic hypoxia puts aquatic organisms' homeostasis under significant strain. Energetic metabolism as well as protein synthesis and folding are particularly altered during hypoxia, while reoxygenation imposes an oxidative challenge. Currently, little is known about how hypoxia-sensitive organisms respond to large oxygen fluctuations. Our previous work on Arctic char revealed that this salmonid, despite being strongly affected by acute hypoxia and reoxygenation (H/R), can successfully reestablish homeostasis, notably through adjustments to hepatic mitochondrial metabolism. However, the mechanisms underlying this acclimation remain poorly understood. We hypothesized that Arctic char remodel their hepatic proteome to optimize energy metabolism, reorganize oxygen-demanding pathways, and maintain cellular homeostasis during repeated H/R cycles. By exposing Arctic char to two or fifteen days of diel cyclic hypoxia, we confirmed this species' limited capacity to respond to acute H/R. Nevertheless, after fifteen cycles, fish adjusted their energetic metabolism through coordinated regulation of carbohydrate and lipid pathways and upregulation of amino acid metabolism. Mitochondrial metabolism was strongly reorganized, particularly at the ubiquinone-Complex III interaction level, alongside adjustments in proline utilization and protein processing. Moreover, protein processing and folding pathways were stimulated in both mitochondria and the endoplasmic reticulum. However, chronic cyclic hypoxia may still promote non-mitochondrial ROS production, DNA replication stress, and impaired immune function. This study highlights how a hypoxia-sensitive fish progressively reorganizes its metabolism and oxygen-demanding pathways to establish a phenotype adapted to chronic cyclic hypoxia, while also revealing the physiological costs associated with this acclimation.

Animals↗

PubMed2026

Uncovering molecular regulatory networks of low-temperature stress response in Trachinotus ovatus via integrated transcriptome and metabolome analyses.

Golden pompano (Trachinotus ovatus) is one of the most economically important marine fish species in China. It is susceptible to low-temperature stress, which significantly challenges its production and supply. Nevertheless, study on the regulatory mechanisms underlying low-temperature stress responses in golden pompano remains limited. Here, we firstly performed a time-series transcriptome analysis to reconstruct dynamic response patterns under low-temperature stress in golden pompano. Transcriptome profiling identified common differentially expressed genes (DEGs), including fos, hlf, and hmgb1, as well as condition-specific DEGs across distinct low-temperature stress groups. Based on cluster analysis, all DEGs were classified into five distinct expression patterns, reflecting diversified regulation of expression in golden pompano during low-temperature stress. Furthermore, condition-specific regulatory modules were explored via weighted gene co-expression network analysis (WGCNA), highlighting that the two module hub genes, serbf2 and lipc, might respond to low-temperature stress by regulating the lipid catabolic process. Subsequently, untargeted metabolomic analysis revealed that glycerophospholipid metabolism was a significantly enriched common pathway, highlighting its crucial role in mediating the response to low-temperature stress. Finally, by integrating transcriptomic and metabolomic analyses, a gene-metabolite interaction network associated with glycerophospholipid metabolism under low-temperature stress was established. These findings underscore the significance of multiple candidate genes and glycerophospholipid metabolism in golden pompano's response to low-temperature stress, thereby laying a solid molecular foundation for the development of low-temperature-tolerant fish strains.

Animals↗

PubMed2026

Robotic Needle Insertion for CT-guided Percutaneous Biopsy of Thoracoabdominal Lesions: A Prospective Multicenter Randomized Trial.

Purpose To compare safety and feasibility between a novel CT-guided robotic system and the conventional freehand technique for puncture biopsy of thoracoabdominal lesions. Materials and Methods In this prospective multicenter randomized trial, individuals with suspected lesions were enrolled between July 2023 and April 2024 across three university teaching hospitals and randomized to the robot-assisted group (n = 82) or the freehand group (n = 83). Procedure outcomes included the technical success rate, targeting error, number of CT scans and needle adjustments, puncture time, and complications. Descriptive and inferential statistics were calculated. Results A total of 165 participants (mean age, 60 years ± 10 [SD]; 83 male) were included. Compared with the freehand group, the robot-assisted group demonstrated a higher technical success rate (97.56% [80 of 82] vs 62.65% [52 of 83], P < .001), lower targeting error (mean Euclidean deviation: 1.7 mm ± 1.1 vs 4.5 mm ± 3.9, P < .001), and fewer CT scans (mean, 4.3 ± 1.9 vs 5.2 ± 2.3; P = .002) and needle adjustments (mean, 0.7 ± 0.7 vs 1.6 ± 1.6; P = .003). Despite differences in geometric precision, both groups achieved 100% (82 of 82 and 83 of 83) diagnostic yield. The median puncture time was comparable between groups (5.5 minutes ± 4.3 vs 4.8 minutes ± 7.0, P = .50). During lung biopsies, the robot-assisted approach yielded fewer complications compared with the freehand approach (4.88% [four of 82] vs 16.87% [14 of 83], P = .014). Conclusion Compared with the freehand approach, robot-assisted biopsy yielded greater precision and reduced adjustments and complications while demonstrating noninferior diagnostic efficacy and comparable duration. Keywords: Robotic Needle Insertion, Biopsy, Thoracoabdominal Lesions, Robot-assisted Biopsy, CT-guided Intervention, Percutaneous Needle Biopsy, Randomized Controlled Trial, Algorithm Development, CT, Clinical Testing, Interventional-Body, Biopsy/Needle Aspiration, Percutaneous, Thorax, Abdomen/GI, Liver, Lung, Kidney ©RSNA, 2026.

Humans↗

PubMed2026

Multi-omics insights into the physiological mechanisms of bile acid accumulation in the gallbladder in brumation-like snakes.

Hibernation/brumation represents an important physiological adaptation for animals to cope with seasonal environmental changes. Field observations suggested increased gallbladder weight in the Five-pacer viper (Deinagkistrodon acutus) during brumation, and our quantitative measurements confirmed this increase together with bile acid accumulation. By integrating a multi-omic approach, this study elucidates the regulatory mechanisms of bile acid accumulation in the gallbladder during brumation. Results showed that taurocholic acid (TCA) and taurodeoxycholic acid (TDCA) were the major components in the gallbladder of the brumation-like group, with significantly elevated concentrations of bile acids, whereas bile acid concentrations in serum and intestinal contents were markedly reduced, indicating suppression of the enterohepatic circulation and consequent accumulation of bile acids in the gallbladder. Hepatic transcriptomic analysis revealed significant downregulation of bile acid synthesis and regulatory genes in brumation-like snakes. In contrast, the alternative synthesis pathway gene sterol 27-hydroxylase (CYP27A1) and some transporter genes were slightly upregulated. Further, some modification genes and regulatory genes showed no significant differences between active and brumation-like states. Gut microbiota analysis demonstrated Akkermansia muciniphila, Bacteroides fragilis, and Citrobacter freundii were more enriched in the active group, which were common microbes related to bile acid metabolism, and the correlation analysis confirmed this relationship. Taken together, these findings indicate that the "physiological bile acid accumulation" observed in snakes during brumation-like state is jointly driven by suppressed hepatic synthesis, reduced enterohepatic circulation, and remodeled microbial community structure. The study provides novel comparative physiological insights into extreme metabolic homeostasis in animals.

Animals↗

PubMed2026

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans↗

PubMed2026

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged↗

PubMed2026

Pre-clinical immunogenicity and safety evaluation of H2 strain Hepatitis A Inactivated Vaccine in rhesus macaques.

BACKGROUND: Hepatitis A is a viral infection of the liver that can cause mild to severe illness. Currently, two types of HAV vaccines are used worldwide, inactivated hepatitis A vaccines, which are used in most countries, and live attenuated vaccines (H2 and L-A-1 strain), which are mainly used in China. The major disadvantage of live attenuated virus to cause secondary infections among contacts and mutation shifts of the live vaccine strain. The H2 strain was selected for the development of an inactivated hepatitis A vaccine to further reduce biosafety risks. Rhesus macaques high genomic homology with humans and the incubation period after hepatitis A vaccination and human natural infections are similar. We use rhesus macaques to assess immunogenicity and safety of the H2 strain Hepatitis A Inactivated Vaccine. METHODS: The vaccine was assessed in rhesus macaques, divided into four groups (n = 10 per group): the control group (adjuvant buffer; aluminum content 0.35 mg/mL; 2 mL per dose), the low-dose group (320EU, 0.5 mL of 640EU/mL with aluminum content 0.35 mg/mL), the medium-dose group (640EU, 1 mL of 640EU/mL with aluminum content 0.35 mg/mL), and the high-dose group (1280EU, 2 mL of 640EU/mL with aluminum content 0.35 mg/mL). Animals were injected intramuscularly at multiple sites in the hind limbs and received four inoculations at 4-week intervals. Test items including Clinical indicators, immunogenicity indicators and Histopathological examination. RESULTS: No abnormalities were observed in any group in terms of general clinical condition throughout the study period except for slight decreases in body temperature after immunization. Hematological parameters, serum biochemistry indices, and histopathological findings showed fluctuated to different degrees of fluctuation after immunization across all groups. Immunogenicity assessments showed that the inactivated hepatitis A vaccine (H2) induced both humoral and cellular immune responses effectively, and the levels of antibodies increased with certain dose- and time-response trends. CONCLUSION: The inactivated hepatitis A vaccine (H2 strain, human diploid cell) was safe and immunogenic in non-human primates. The results provide strong preclinical support for the further clinical development of this vaccine candidate.

Animals↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗

PubMed2026

Proteomic insights into hepatic responses to high soybean meal inclusion with citric acid supplementation in hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles.

This study evaluated the growth performance and hepatic proteomic responses of juvenile hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles fed diets containing 30% or 40% soybean meal (SBM), with or without 3% citric acid supplementation, and compared with a fishmeal (FM) control diet over a 10-week feeding trial. Fish fed 30% SBM (LSBM) showed a final body weight comparable to the FM group, whereas fish fed 40% SBM (HSBM) recorded significantly reduced growth and net protein utilization (NPU) (p < 0.05). Supplementation of citric acid in the 40% SBM diet (HSBM + CA) significantly improved NPU and partially restored growth relative to HSBM. LC-MS/MS based quantitative proteomics identified 1544 hepatic proteins and showed clear dietary segregation. Differentially expressed proteins were predominantly associated with reduced abundance of proteins involved in lipid metabolism, amino acid metabolism, pyruvate metabolism, and the tricarboxylic cycle across all SBM diets, suggesting a shift in oxidative metabolic capacity. In contrast, LSBM induced upregulation of spliceosome-associated proteins and RNA processing components, suggesting adaptive post-transcriptional regulation under moderate SBM inclusion. In contrast, HSBM exhibited greater reduction in metabolic protein abundance without comparable upregulation of adaptive regulatory components, coinciding with reduced nutrient retention. Protein-protein interaction analysis further confirms the correlation between the regulation of spliceosomal clusters and mitochondrial lipid-catabolic modules. Citric acid supplementation did not markedly reverse hepatic metabolic protein changes but improved protein retention. Data are available via ProteomeXchange with identifier PXD081994. These findings suggest a tolerance limit between 30% and 40% SBM inclusion, with 30% inducing adaptive hepatic proteomic responses compatible with maintained growth performance.

Animals↗