To evaluate local tumor control and determinants of treatment success following magnetic resonance (MR)-guided microwave ablation (MWA) of liver malignancies. This single-center retrospective study evaluated prospectively included patients undergoing MR-guided MWA between September 2021 and February 2025. Procedures were performed under general anesthesia using a 1.5-Tesla MR scanner and two MR-compatible MWA systems. Complications were assessed according to CIRSE. Technical success was defined as total lesion coverage on MR imaging one day post-ablation. Local recurrence and hepatic tumor progression were analyzed using follow-up liver MR imaging every three months. Determinants of treatment success included lesion size, tumor entity, ablation duration, MWA system, lesion and antenna conspicuity (6-point Likert scale), adjacent vascular structures, liver cirrhosis, and antenna position (central/non-central). Forty-eight liver lesions in 40 patients (median age 62.5 years, 70.0% male) were treated. MWA systems 1 and 2 were used in 33/48 (68.8%) and 15/48 lesions (31.3%), respectively. Technical success was achieved in 46/48 lesions (95.8%), with one peri-procedural complication (CIRSE grade 3, 2.5%). Mean follow-up was 21.0 ± 10.9 months, with one patient lost to follow-up. Local recurrence occurred in 4/47 lesions (8.5%), all treated with system 1, while no recurrence was observed with system 2 (p = 0.173). As the only relevant determinant of treatment success, adjacent vascular structures were associated with higher local recurrence rates (p = 0.019). No local recurrence occurred in lesions < 20 mm. MR-guided MWA of liver tumors is safe, achieving high technical success and local tumor control. Adjacent vascular structures increase the risk of local recurrence and may warrant more aggressive treatment. Question Whether MR-guided MWA provides reliable local tumor control for liver malignancies and which procedural or anatomical factors influence treatment success. Findings MR-guided MWA achieved high technical success, low complication rates, and strong local tumor control; local recurrence occurred in lesions ≥ 20 mm and with low-power MWA systems, as well as adjacent vascular structures, significantly increased risk of local recurrence. Clinical relevance Prospectively acquired single-center cohorts of MR-guided MWA with real-time position monitoring in a standardized MR workflow, highlighting the impact of technical factors and the importance of lesion selection based on device-specific ablation characteristics.
In patients with liver-dominant metastatic disease undergoing yttrium-90 (⁹⁰Y) transarterial radioembolization (TARE), response assessment remains challenging, particularly in multifocal disease where manual RECIST-based measurements may not adequately reflect overall hepatic tumor burden. In addition, the prognostic relevance of volumetric changes in tumor, liver, and spleen after TARE remains unclear. This retrospective study evaluated automated CT-based whole-liver tumor volumetry as a quantitative imaging biomarker for response assessment and progression risk stratification following TARE. We retrospectively analyzed imaging and clinical data from 57 adults with liver-dominant metastatic disease (colorectal, neuroendocrine, uveal melanoma, and breast cancer) treated with yttrium-90 (⁹⁰Y) resin TARE between January 2012 and December 2022. Inclusion criteria were age ≥ 18 years, availability of baseline contrast-enhanced CT imaging, and clinical follow-up. Patients undergoing liver resection, transplantation, or additional locoregional therapies during follow-up were excluded. Baseline tumor volume was a strong independent predictor of progression-free survival (PFS), demonstrating excellent discriminatory performance (ROC-AUC 0.91; 95% CI 0.82-1.00). A threshold of 270 mL most accurately identified early progression (< 12 months), with a sensitivity of 0.84 and specificity of 0.92. In contrast, lesion count, embolization strategy, and maximum tumor diameter were not significantly associated with PFS. Automated baseline tumor volumetry demonstrated promising prognostic performance compared with conventional clinical and procedural parameters in patients with liver-dominant metastases treated with ⁹⁰Y TARE. Automated quantification of intrahepatic tumor burden may serve as a useful and readily accessible imaging biomarker for early risk stratification, although external validation is required before clinical implementation.
Nonalcoholic fatty liver disease (NAFLD), also termed metabolic dysfunction‑associated fatty liver disease is a problem across the world. The most important factor of the increase in NAFLD prevalence is the insulin resistance. This study is the first clinical trial with the aim of determining the effect of Pistacia atlantica Sub. Kurdica gum on glycemic indices especially insulin resistance in patients with nonalcoholic fatty liver disease. In this double-blind randomized clinical trial 50 patients with nonalcoholic fatty liver disease were randomized into two groups: those given syrup containing Pistacia atlantica sub. Kurdica gum (Group A), those on placebo (Group B). Over a two-month period, Group A given syrup containing 500 mg of P. atlantica sub. Kurdica gum per each tablespoon and Group B given syrup without P. atlantica sub. Kurdica gum. Anthropometric measures, biochemical indices and physical activity were evaluated at the beginning and end of the intervention. We observed a significant decrease in fatty liver grade in group A (P = 0.03). The mean of fasting serum insulin and the insulin-resistance index (HOMA-IR) decreased significantly (P = 0.002, P < 0.001) and quantitative insulin sensitivity check index (QUICKI) increased from baseline in group A (P = 0.001). Fasting blood sugar (FBS) decreased significantly from baseline in group A (P = 0.019), but the mean changes between group not significant (P = 0.061). Weight had significant decrease in group A (P < 0.001). Pistacia atlantica sub. Kurdica gum can decrease insulin resistance, increase insulin sensitivity and subsequently improvement NAFLD in patient with nonalcoholic fatty liver disease. It is suggested that clinical trials be conducted in the long duration of the intervention, as well as a larger sample size. Registration number of Clinical trial: IRCT20231219060466N1 (https://irct.behdasht.gov.ir/).
Patients with liver disease often experience nutritional insufficiency due to an interplay of metabolic disturbances and dietary alterations leading to decreased muscle mass and the development of protein-calorie malnutrition (PCM). This study aimed to evaluate the prevalence of PCM in patients with steatotic liver disease (alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD)) and their impacts on mortality and healthcare utilization. We identified hospitalizations with ALD, MASLD, and PCM using International Classification of Diseases codes in the National Inpatient Sample from 2016 to 2020. Descriptive analyses compared hospitalizations with and without PCM. Multivariable linear models adjusting for confounders evaluated the association between PCM and inpatient mortality, length of stay (LOS), and total charges. PCM was found to be significantly more prevalent among hospitalizations with ALD or MASLD than those with neither (ALD 175.5 versus 51.8; MASLD 149.0 vs. 50.7; neither: 49.3 per 1000 hospitalizations; p < 0.001). Among hospitalizations with ALD nor MASLD, PCM was significantly associated with higher mortality (ALD adjusted odds ratio [aOR] 1.61; 95% CI 1.55-1.66; MASLD aOR 1.89; 95% CI 1.84-1.93), LOS (ALD 3.78 more days; 95% CI 3.67-3.88; MASLD 5.65 more days; 95% CI 5.53-5.77), and total charges (ALD $45,013; 95% CI $42,549-$47,477; MASLD $74,502; 95% CI $71,214-$77,789). We found a higher prevalence of PCM among individuals with ALD compared to those with MASLD nor neither condition. PCM was associated with increased mortality, LOS, and total charges in those with ALD and MASLD. Our findings underscore the importance of early identification and management of PCM in patients with steatotic liver disease to mitigate adverse outcomes and reduce healthcare utilization.
To explore the protective effect and mechanism of loganin, a iridoid glycoside isolated from Corni Fructus, on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) mice model and L-02 cells. ALI mice model was developed by an intraperitioneal injection of 0.3% CCl4. Thirty 8-week-old male C57BL/6 mice were randomly divided into 5 groups using a random number table, including control, model, loganin (40 and 80 mg/kg), and silybin (100 mg/kg) groups (n=6). After 6 consecutive days of intragastric administration, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using an automatic biochemical analyzer. Hepatic pathological changes were observed by hematoxylineosin (HE) staining. Levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in liver tissue were detected by enzyme-linked immunosorbent assay (ELISA). Superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents were measured using biochemical kits. Mitochondrial ultrastructure and autophagosome formation were observed by transmission electron microscopy (TEM). Co-localization of mitophagy markers LC3 and TOMM20 were assessed by immunofluorescence (IF). Protein expressions of NOD-like receptor protein 3 (NLRP)3, LC3 II/LC3 I, p62, Beclin-1, Atg-7, Parkin, and PINK1 were determined by Western blot. In vitro, an injury model was established in L-02 hepatocytes stimulated with CCl4. Cell viability was assessed by CCK-8 assay, and related mechanisms were evaluated using the aforementioned methods. Besides, CCl4-stimulated L-02 cells were intervened with NLRP3 shRNA or Mdivi-1. Compared with the model group, pre-treatment with loganin (40 and 80 mg/kg) significantly reduced serum AST and ALT levels (P<0.01), alleviated pathological injuries such as swelling, necrosis, inflammatory infiltration, and lipid vacuolation in liver tissue. Loganin also markedly decreased the levels of IL-6 and TNF-α, increased SOD activity, and reduced MDA content in liver tissues (P<0.05 or P<0.01). Mechanistically, loganin up-regulated the ratios of LC3 II/LC3 I and expressions of Beclin-1, Atg-7, Parkin, and PINK1, while down-regulated p62 and NLRP3 protein expressions (P<0.05). In vitro experiments further confirmed that loganin attenuated CCl4-induced injury in L-02 cells by enhancing mitophagy and inhibiting NLRP3 inflammasome activation, which was reversed by the mitophagy inhibitor Mdivi-1. Loganin protected against CCl4-induced ALI both in vivo and in vitro by suppressing the NLRP3 inflammasome and enhancing mitophagy.
Ginkgo biloba is a nutritional supplement known for its antioxidant properties and beneficial effects on different organs. This study aimed to investigate the protective effect of Ginkgo biloba supplementation against acute lead toxicity in rats. Thirty-two male Wistar rats were divided into four groups and treated daily for 7 days. The control group received normal saline (1 mL/day, orally). The model group received lead acetate (50 mg/kg/day, ip) without any treatment, and the model with either ethylenediaminetetraacetic acid (EDTA) (50 mg/kg/day, ip) or Ginkgo biloba (200 mg/kg/day, oral gavage). After 7 days, blood samples were collected, and livers, kidneys, and testes were excised and stored for evaluation of oxidative stress markers and histological assessment. Acute lead acetate administration resulted in significant weight loss, an increase in kidney index, elevated serum creatinine and liver enzyme levels, including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase (AlkP), and extensive histological damage in the liver, kidney, and testicular tissues. Administration of the Ginkgo biloba significantly improved serum creatinine and AlkP, showing greater efficacy than EDTA, and reduced histopathological changes, similar to EDTA, including hepatic vascular congestion and fibrosis, renal dilation of Bowman spaces, and glomerular degeneration. Furthermore, Ginkgo biloba treatment improved Leydig and spermatogonia cell counts. Both Ginkgo biloba and EDTA reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) and catalase activities in these organs. Ginkgo biloba exhibited protective effects against lead-induced hepatic, renal and testicular damage through its ability to reduce oxidative stress damage. These results indicate that Ginkgo biloba may serve as a valuable adjunct therapy for mitigating lead-associated organ damage.
Peroxynitrite (ONOO-) plays a pivotal role in the pathogenesis of Rheumatoid arthritis (RA) and drug-induced liver injury (DILI), with its dynamic accumulation closely associated with disease progression. To effectively monitor the level of ONOO- in biological system, fluorescent probes offer distinct advantages for ONOO-, including high spatiotemporal resolution, non-invasive imaging capability, and exceptional sensitivity for detecting transient ONOO- fluctuations in living systems. These probes enable real-time visualization of ONOO- in inflamed joints or drug-stressed livers, facilitating early diagnosis and therapeutic monitoring. Thus, a novel mitochondria-targeted ratiometric near-infrared (NIR) fluorescent probe, DXD, was designed and synthesized via the condensation reaction of a diphenylamino-substituted xanthene with dicyanoisophorone. The incorporation of a dicyanoisophorone bridging unit enabled emission redshift into the NIR region, while a phenylboronic acid recognition group conferred rapid and selective responsiveness to ONOO-. DXD exhibited a markedly larger Stokes shift and faster response kinetics for ONOO-. Importantly, the original emission peak of DXD at 734 nm gradually decreased, while a new peak at 618 nm progressively emerged and intensified, enabling ratiometric detection of ONOO-. Functionally, DXD enabled selective monitoring of dynamic fluctuations in both endogenous and exogenous ONOO- in live cells. It is noteworthy that ONOO- concentrations were significantly elevated in RA and DILI models compared to normal mice, providing important imaging evidence for the role of ONOO- in disease progression. Detecting ONOO- levels using fluorescent probes is critically important because ONOO- acts as a key pathogenic mediator in both RA and DILI models, driving inflammation, autoimmunity, and tissue damage. Furthermore, its real-time monitoring serves as an early and sensitive biomarker for disease progression, often showing changes before traditional clinical indicators.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic epidemic with no specific effective therapy, characterized by hepatic steatosis and excessive hepatocyte apoptosis. This study explored the protective effects and mechanisms of Ganoderic acid A (GA-A) against MASLD. In high-fat diet (HFD)-fed mice and palmitic acid (PA)-stimulated HepG2 cells, GA-A notably relieved hepatic steatosis, liver injury, lipid metabolic disorders and hepatocyte apoptosis. Acetyl-CoA carboxylase (ACC) was identified as a direct target of GA-A via protein microarray, molecular docking, SPR, CETSA and Co-IP assays. Mechanistically, GA-A activated the AMPK-ACC pathway and suppressed ACC activity. Application of the ACC inhibitor ND646 and ACC silencing partially abrogated GA-A's therapeutic effects, confirming both ACC-dependent and independent actions. Collectively, GA-A directly targets ACC to ameliorate MASLD, indicating its potential as a promising candidate drug for this metabolic liver disease.
Here, we present a non-surgical protocol for modeling murine liver metastasis by disseminating injected cells or compounds into the murine portal vein. We describe steps for identifying the portal vein and other vital structures adjacent to and within the liver by ultrasound, determining an optimal route to avoid vital structures, and injecting into the portal vein. We also report on the findings for reproducibility, adverse effects, and histopathological findings.
Hepatic fibrosis is a progressive pathology driven by hepatic stellate cell (HSC) activation and excessive extracellular matrix deposition. While mesenchymal stem cell (MSC) therapies show promise, their clinical translation is hindered by the inherent safety constraints of live cell transplantation. MSC-derived apoptotic vesicles (MSC-ApoVs), a structurally distinct class of extracellular vesicles, emerge as a compelling cell-free alternative. However, their specific therapeutic efficacy and mechanistic targets in hepatic fibrosis remain elusive. MSC-ApoVs were isolated from human umbilical cord MSCs and stringently characterized to exclude non-vesicular contaminants. Their anti-fibrotic efficacy was evaluated in vitro using TGF-β1-activated LX-2 cells and in vivo within a CCl₄-induced murine fibrosis model. To elucidate and functionally validate the underlying mechanisms, we integrated transcriptomic profiling (RNA-seq), dual-luciferase reporter assays, and dual-directional pharmacological interventions. Furthermore, human clinical liver biopsies were analyzed to determine the clinico-pathological relevance of the identified targets. We demonstrated that MSC-ApoVs were efficiently internalized by HSCs, significantly blunting TGF-β1-induced activation, proliferation, and migration, alongside a marked reduction in fibrotic markers (α-SMA, MMP2, and Collagen-I). Transcriptomic screening identified Insulin-like Growth Factor Binding Protein 3 (IGFBP3) as a crucial pro-fibrotic mediator. Mechanistically, MSC-ApoV-enriched miR-409-3p directly targeted and downregulated IGFBP3, thereby restricting the PI3K-AKT signaling cascade-a dependency unequivocally validated by targeted rescue and blockade assays. In vivo, systemic MSC-ApoV administration robustly ameliorated CCl₄-induced hepatic fibrosis and restored liver function. Crucially, clinical analyses revealed a strong positive correlation between elevated IGFBP3 expression and the severity of human fibrotic progression. This study delineates a novel cell-free therapeutic paradigm, demonstrating that MSC-ApoVs mitigate hepatic fibrosis largely through the miR-409-3p-mediated silencing of the IGFBP3/PI3K-AKT axis. By integrating robust in vitro, in vivo, and clinical evidence, these findings highlight MSC-ApoVs as a highly efficacious and translatable alternative to traditional live stem cell therapies for hepatic fibrosis.
The prognostic effect of concurrent metabolic dysfunction-associated steatotic liver disease (MASLD) on outcomes for hepatocellular carcinoma (HCC) patients remains unclear. The Prognostic Nutritional Index (PNI) reflects nutritional and inflammatory status and is a well-known prognostic factor. We therefore aimed to evaluate and compare the prognostic role of PNI in patients with HCC with and without concurrent MASLD undergoing curative surgical resection. In our retrospective study, 991 patients undergoing curative HCC resection were stratified according to MASLD status and pre-operative PNI (cut-off: 45). Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier methods and Cox proportional hazards models. Further subgroup analysis was performed according to their concurrent viral hepatitis status. High PNI was identified as an independent protective factor against poor OS for the entire cohort (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.49-0.87, p = 0.004). The Kaplan-Meier analysis showed that the high-PNI/MASLD group had the best OS, while the low-PNI/no-MASLD group had the worst. Subgroup analysis indicated that high PNI was an independent protective factor for OS only in the no-MASLD group (HR: 0.59, p = 0.003) but not the MASLD group (HR: 0.94, p = 0.793). Its prognostic effect was more significant in HCC patients without concurrent MASLD or with chronic hepatitis B. To conclude, a better nutritional status, assessed by PNI, is a valuable prognostic marker for patients with HCC. Its protective effect on OS is significantly pronounced in patients without concurrent MASLD, indicating that MASLD status modifies the prognostic utility of PNI.
Reconstruction of segment 5 and/or segment 8 anterior sector veins ≥ 5 mm is widely recommended in adult right lobe living donor liver transplantation (LDLT) to prevent venous congestion. Whether this approach is universally required, or whether selective ligation guided by intraoperative findings is acceptable in lower-risk recipients, remains unresolved. This single-centre retrospective cohort study included adult recipients who underwent right lobe LDLT without inclusion of the middle hepatic vein at a high-volume transplant centre (approximately 150 adult LDLTs per year) between November 2021 and May 2025. Eligible patients had intraoperatively measured segment 5 and/or segment 8 veins ≥ 5 mm. Venous management was determined intraoperatively and was not randomized: reconstruction was preferred in recipients judged at higher risk of congestion, and all recipients with graft-to-recipient weight ratio (GRWR) < 0.8 were managed in the reconstruction group. The primary endpoints were postoperative day 7 (POD7) international normalized ratio (INR), total bilirubin, and ascites volume. Multivariable adjustment was prespecified for postoperative ascites only, adjusting for ligation status, MELD score, and GRWR. Prespecified sensitivity analysis restricted to GRWR ≥ 0.8 was performed. Partial Olthoff early allograft dysfunction (EAD) and approximate ILTS-iLDLT small-for-size syndrome (SFSS) were assessed as secondary analyses. A total of 170 recipients were included (16 selective ligation; 154 reconstruction). Baseline variables did not differ statistically, but all 20 recipients with GRWR < 0.8 were in the reconstruction group. POD7 outcomes were comparable: INR 1.24 vs. 1.27 (p = 0.80), bilirubin 1.46 vs. 1.70 mg/dL (p = 0.35), ascites 1100 vs. 1250 mL (p = 0.89). In multivariable analysis (n = 91), selective ligation was not independently associated with ascites (β = 0.202; 95% CI - 0.359 to + 0.764; p = 0.476); MELD was the only significant predictor (p = 0.024). The GRWR ≥ 0.8 sensitivity analysis confirmed these findings. Partial Olthoff EAD was 25.0% vs. 15.7% (p = 0.42); approximate SFSS was 27.3% vs. 24.7% (p = 1.00). Post-hoc power for the ascites comparison was 80% only for Cohen's d ≥ 0.90, far larger than the observed d = 0.02. In carefully selected recipients with adequate graft volume and favourable intraoperative findings, selective ligation of segment 5 and/or 8 veins ≥ 5 mm was not associated with worse early graft function in this cohort. Given the small ligation group, non-randomized allocation, and substantial missing data, these preliminary results are consistent with the feasibility of selective ligation in a selected lower-risk subgroup but cannot establish its safety, clinical applicability, or equivalence to reconstruction. Prospective, adequately powered, multicentre validation is required before any change in current clinical practice can be considered. not applicable.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a known risk factor for type 2 diabetes (T2D). However, whether MASLD onset age modifies T2D risk remains poorly understood. We aimed to determine the association of MASLD onset age and risk of incident T2D in a large prospective cohort. 58,814 MASLD- and T2D- free participants at the first health examination (2006-2007) in the Kailuan Study were included. By December 31, 2015, 29,016 new-onset MASLD cases were identified. Each MASLD case was randomly matched to a MASLD-free control by age (±1 years) and sex. After excluding participants who developed T2D within first 2 years of follow-up, 19,378 MASLD cases and 19,483 controls were included. All participants were followed for incident T2D until 31 December 2020. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 11.8 years, 2,301 incident T2D cases were documented. Compared with non-MASLD, MASLD patients with onset age < 40 years had the highest risk of T2D (HR=6.18, 95% CI: 4.28, 8.93), followed by gradually attenuated elevated risks in older onset age groups: 40-<50 years (HR = 3.29, 95% CI: 2.70, 4.00), 50-<60 years (HR = 3.14, 95% CI: 2.69, 3.66), 60-<70 years (HR = 2.94, 95% CI: 2.39, 3.62), and ≥ 70 years (HR = 2.17, 95% CI: 1.56, 3.01). MASLD onset at any age is associated with increased risk of T2D, with earlier onset conferring progressively greater risk. This highlights the importance of preventing, or at least delaying MASLD onset, particularly in young adults.
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MicroRNAs (miRNAs) are crucial in animal stress responses. While some studies have investigated miRNA regulatory mechanisms, limited research exists on miRNAs involved specifically in stress caused by high temperatures. To explore the regulatory mechanism of miRNA in tsinling lenok trout under high-temperature stress. MiR-8159-x and miR-200-z were selected as candidates for further investigation. These candidates were identified through bioinformatics analysis of small RNA sequencing data obtained from tsinling lenok trout. Bioinformatics research indicates that miR-8159-x may target IRE1α, BAX, Cytc, and CxⅢ, while miR-200-z may target PERK, ATF4, and BIM. The analysis of RT-qPCR indicated a noteworthy reduction in the expression levels of miRNAs in the high-temperature stress group when compared to the control group. Conversely, the expression of target genes displayed an opposite pattern. Luciferase reporter gene assay demonstrated that the binding of miRNAs to the target genes caused a notable reduction in luciferase activity. The findings presented suggest that miR-8159-x and miR-200-z play a role in the stress reaction experienced by tsinling lenok trout when exposed to elevated temperatures.
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Liver metabolism is under tight control of the circadian system. Disruption of key clock gene expression (desynchronosis) leads to the misalignment of metabolic pathways. However, the relationship between circadian dysregulation and hepatic protein-synthetic function, as well as its sexual dimorphism, remains poorly understood. To evaluate the effect of chronic photoperiod disruption on hepatic protein-synthetic function (total protein, albumin) and to establish its relationship with the expression of key circadian proteins (BMAL1, CLOCK, PER2) in male and female rats, as well as to assess the efficacy of exogenous melatonin in correcting the identified disturbances. The study was performed on 240 adult Wistar rats (120 males, 120 females). Animals were divided into 3 groups: control (light: dark 10:14 h), dark deprivation (LL, constant light for 21 days), and LL + melatonin (12 mg/L drinking water). Plasma levels of total protein and albumin were measured. Immunohistochemistry was used to assess the percentage of positively stained hepatocytes for BMAL1, CLOCK, and PER2. Statistical analysis included two-way ANOVA, Pearson correlation analysis, ANCOVA, and ROC analysis. Dark deprivation reduced albumin levels by 15.7% in males and by 15.9% in females compared to controls. Two-way ANOVA revealed significant effects of "lighting conditions" (F = 145.3, p < 0.0001), "sex" (F = 18.7, p < 0.01), and their interaction (F = 7.2, p < 0.05). BMAL1 and CLOCK expression decreased by more than 70% in both sexes, whereas PER2 expression paradoxically increased by 28.9-35.0%. Strong correlations were found between albumin levels and expression of BMAL1 (r = 0.79-0.81, p < 0.001), CLOCK (r = 0.69-0.74, p < 0.001), and PER2 (r= - 0.68 to - 0.71, p < 0.001). ANCOVA (R²=0.71, p < 0.0001) identified BMAL1 expression as the most significant independent predictor of albumin levels (β = 0.52, p < 0.0001), with sex retaining independent significance (p = 0.02). ROC analysis demonstrated high predictive performance of BMAL1 expression for hypoalbuminemia (AUC = 0.87-0.89, p < 0.0001). Melatonin treatment fully restored the expression of all examined circadian proteins and normalized protein synthetic parameters to control levels in both sexes. Chronic photoperiod disruption induces profound hepatic desynchronosis characterized by suppression of BMAL1/CLOCK and accumulation of PER2, which is associated with decreased protein synthetic function. A pronounced sexual dimorphism in susceptibility to desynchronosis was identified. BMAL1 expression is a highly informative predictor of hypoalbuminemia. Exogenous melatonin fully restores the impaired parameters, supporting its use as an effective chronobiotic. The liver works on a daily (circadian) rhythm. When this rhythm is disrupted—for example, by constant light exposure—it can harm liver function. However, scientists did not know exactly how rhythm disruption affects the liver’s ability to make proteins (like albumin), or whether males and females respond differently. This study tested whether constant light harms liver protein production, and whether the sleep hormone melatonin could fix it. They used 240 adult rats (120 males, 120 females). The rats were split into three groups:1. Normal light-dark cycle (control).2. Constant light for 21 days (to disrupt their body clock).3. Constant light plus melatonin in their drinking water.They measured blood levels of total protein and albumin (a key protein made by the liver). They also measured three key clock proteins (BMAL1, CLOCK, PER2) in the liver cells. Constant light lowered albumin levels by about 16% in both male and female rats. It also caused major changes in the liver’s clock proteins: BMAL1 and CLOCK dropped by over 70%, while PER2 increased. These changes were strongly linked to lower albumin levels. The study also found that sex mattered—males and females responded differently to rhythm disruption. Using a statistical model, BMAL1 was the best predictor of low albumin. Importantly, melatonin treatment fully restored all clock proteins and normalised protein production in both sexes. Disrupting the body’s daily rhythms harms the liver’s ability to make essential proteins. The clock protein BMAL1 may serve as a useful marker for liver problems. Melatonin—a natural hormone already used for sleep disorders—could potentially help protect liver function when circadian rhythms are disturbed (e.g., in shift workers, people with chronic jet lag, or those living under abnormal light cycles).
Many women suffer from symptoms associated with dysfunction of the lower urinary tract, including incontinence and overactive bladder, especially during pregnancy. While causes are likely multifactorial, environmental factors, such as exposure to polychlorinated biphenyls (PCBs), have been shown to alter voiding in adult female mice. However, the distribution of PCBs and their metabolites to the bladder and urine, as well as their effects on bladder drug-metabolizing enzyme expression after dosing with PCB mixtures, remains largely unexplored. Female C57BL/6J mice were exposed to MARBLES PCB mixture (0, 0.1, 1, and 6 mg/kg/d) through gestation and lactation, and post-weaning bladder, urine, blood, adipose, and liver were collected for measurement of PCBs and OH-PCBs, and for abundance of cytochrome P450 (Cyp) transcripts in liver and bladder. PCBs and OH-PCBs were detected in all tissues in a dose-dependent manner. Bladder, adipose, and liver retained parent PCBs while OH-PCBs were predominant in urine and blood. Cyp1a2 mRNA abundance was elevated in the liver of the high dose PCB group versus the vehicle, and the same trend was observed in the bladder. These results define the signatures of PCBs and OH-PCBs in the bladders and urine of post-weaning dams exposed to the MARBLES mixture of PCBs and provide a reference for comparison with accumulation in more commonly studied tissues. Our results also provide new insights into the regulation of Cyp1a2 in the liver and bladder, changes that may play a role in how environmental exposures in adulthood alter voiding function.
Reproducibility and cross-species translation using the domestic pig (Sus scrofa) are limited by the lack of a standardised molecular framework for biological maturation: the pig's developmental tempo differs substantially from the human's, yet no tissue-resolved transcriptomic staging system exists. Synchronising porcine and human maturation is essential to move preclinical research from descriptive to predictive. We built a transcriptomic atlas of porcine development across five tissues (muscle, brain, liver, blood, lung) from 1,924 PigGTEx RNA-seq profiles. A single partial-least-squares (PLS) regressor staged each tissue at its native ordinal resolution and also drove cross-species transfer and biomarker extraction. Our central result: transfer of a pig-trained developmental score to other species is dominated by tissue identity, with phylogenetic distance a weaker secondary effect. Projected onto the seven-species Cardoso-Moreira atlas, transfer was strongest for brain and heart ([Formula: see text]-0.92) and weakest for the labile liver and ovary ([Formula: see text] and 0.42). Brain and heart stayed high even from pig to chicken ([Formula: see text] across ∼320 Myr), whereas liver and ovary collapsed. A variance partition confirmed the ranking (organ Type-II [Formula: see text], [Formula: see text]; phylogeny significant only at the species level, Spearman [Formula: see text], [Formula: see text], [Formula: see text]). The score independently confirmed lung, muscle, and adipose on the human dGTEx resource ([Formula: see text]-0.67) against an ortholog-scramble null and three controls. Because it is fit on pig and projected onto foreign-batch atlases, the transfer cannot arise from a pig-side artefact. A web application is available at https://pigdevstage.streamlit.app. The porcine developmental programme transfers to humans and more distant amniotes in a tissue-dependent manner, so the pig's value as a developmental model is set by how conserved each organ's developmental logic is, not by phylogenetic proximity. Validated on foreign-species atlases, the transfer sidesteps the stage-study confound that bounds within-pig staging to muscle and liver. The atlas is therefore best used organ by organ: strong for conserved organs (brain, heart) and weak for labile ones (liver).
Hepatitis B virus (HBV) infection is a globally prevalent disease and remains a significant public health burden. In Ethiopia, where HBV is endemic, it is a major contributor to chronic liver disease and liver-related mortality. Timely disclosure of serostatus is crucial for preventing intra-family transmission, facilitating contact tracing and vaccination, promoting adherence to follow-up and antiviral therapy, and improving the physical and psychosocial well-being of affected individuals. Therefore, this study aimed to assess the prevalence of HBV serostatus disclosure and identify factors associated with disclosure among adults receiving care at the Gastroenterology clinic of Hawassa University Comprehensive Specialized Hospital. An institution-based analytical cross-sectional study was conducted from July 20 to September 30, 2025, to enroll all eligible participants. Data were collected via interviewer-administered, semi-structured questionnaires supplemented by a data abstraction sheet, and analyzed using STATA version 16.1. Poisson regression with robust variance estimation identified factors associated with HBV serostatus disclosure; results were presented as adjusted prevalence ratios (aPR) with 95% confidence intervals (CI), and statistical significance was set at P < 0.05. Of the 245 participants, 171 (69.8%) were male, and the median age was 34 years (interquartile range: 26-45 years). Overall, 46.5% of participants (95% CI: 40.3-52.8%) disclosed their HBV serostatus to at least one contact. Factors independently associated with HBV serostatus disclosure included being female (aPR = 1.46; 95% CI: 1.07-2.00), being ever married (aPR = 1.80; 95% CI: 1.21-2.68), living with chronic HBV for more than five years (aPR = 1.25; 95% CI: 1.11-1.96), having no comorbidities (aPR = 3.24; 95% CI: 1.43-5.39), having normal liver status (aPR = 1.31; 95% CI: 1.00-1.72), and having a higher HBV knowledge score (aPR = 1.07; 95% CI: 1.03-1.12). The findings indicated that HBV serostatus disclosure was low when compared to other African settings. Disclosure was driven by female gender, being ever married, longer duration of HBV diagnosis, absence of comorbidities, normal liver status and higher HBV knowledge. While the study provided valuable insights into the dynamics of disclosure, its cross-sectional design meant that definitive causal relationships could not be established. Not applicable.