Search Results (1,081)

Phthalates are a class of compounds commonly used as plasticizers in various industrial and consumer products. In line with the increasing environmental and biological exposure concerns regarding these compounds, this study investigated the dose-dependent effects of diethyl phthalate (DEP) on the liver in a subacute rat model. Diethyl phthalate (DEP) was given orally by gavage to female Wistar albino rats at doses of 100, 300, and 600 mg/kg body weight per day for 21 days in order to assess liver tissue and associated function test levels. Liver function was evaluated by analyzing serum biochemical data. Liver tissues were evaluated using histopathological staining (H&E and Masson’s trichrome staining), immunohistochemical analysis of IL-1β and TGF-β, tissue ELISA for IL-6 and TNF-α, and comet assay to determine DNA damage. DEP exposure was found to cause significant, dose-dependent histopathological changes in liver tissue, including hepatocyte necrosis, cytoplasmic vacuolization, sinusoidal dilation, and vascular congestion. AST levels were significantly increased compared to the control group, while no significant changes were observed in other serum biochemical parameters. Compared to the control group, the expression of pro-inflammatory cytokines (IL-6 and TNF-α), IL-1β, and TGF-β was found to be elevated in the DEP-treated groups, and their levels increased with increasing exposure dose. DEP exposure also caused significant DNA damage in liver tissue. These findings indicate that despite an increase in AST levels observed in subacute DEP exposure, there were limited changes in serum biochemical parameters; serum liver enzymes alone may not fully reflect the extent of hepatic damage, and DEP can cause significant inflammatory, histopathological, and genotoxic effects in liver tissue. Full article

Curcumin, a natural polyphenolic compound derived from the curcuma genus, has attracted considerable attention due to its simple chemical structure, favorable safety profile, and broad-spectrum pharmacological activities. This review provides a comprehensive summary of recent advances in curcumin research, with a specific focus on its therapeutic potential in cancer, inflammation, depression, and metabolic disorders, including non-alcoholic fatty liver disease, hypertension, and osteoporosis. It highlights curcumin’s modulation of critical signaling pathways, such as PI3K/Akt, NF-κB, JAK/STAT, MAPK/ERK, mTOR, and Wnt/β-catenin, which regulate essential cellular processes, including proliferation, apoptosis, metabolism, and immune response. In various models of solid tumors and hematologic malignancies, curcumin has exhibited potent anti-cancer effects and shows promise in combination with chemotherapy to overcome drug resistance. Moreover, the mechanisms underlying curcumin’s effects on inflammation-related diseases and chronic conditions are becoming increasingly well-understood. To address its limitations, such as poor water solubility, rapid metabolism, and low bioavailability, several advanced drug delivery systems—such as nanocarriers, microspheres, and solid dispersions—have been developed to enhance its in vivo stability and targeting efficiency. Beyond its pharmacological applications, curcumin is also employed as a functional additive in food science, particularly in active packaging and food safety testing. In conclusion, curcumin not only serves as a valuable pharmacological probe but also functions as a natural molecular template bridging basic research, formulation innovation, and multidisciplinary translational applications. Future research should focus on optimizing its chemical structure, advancing biosynthesis engineering, and conducting rigorous clinical trials to facilitate its widespread adoption in precision medicine and health interventions. Full article

Background: To improve the early recognition of biliary atresia (BA) and timely treatment, this study developed a predictive model integrating combi-elastography, a novel form of elastography, to distinguish biliary atresia from other cholestatic liver diseases (non-BA) in infants. Method: A total of 69 children aged < 60 days with cholestatic hepatitis were retrospectively enrolled. All patients underwent conventional ultrasonography, combi-elastography, and laboratory testing. The variables were selected using logistic regression to construct a nomogram model, and the performance of the model was evaluated. Results: Multifactorial logistic regression analysis indicated that GGT (p = 0.015), the gallbladder morphology (p = 0.017), and the fibrosis index of the combi-elastography (p = 0.017) could be used as independent predictors to differentiate BA from other causes of cholestasis. A nomogram model constructed with these three indexes showed better performance, with an area under the operating characteristic curve (AUC) of 0.887 (0.823, 0.952) (p < 0.001), sensitivity of 86.4%, and specificity of 76.0%. Using 1000 Bootstrap resamples for internal validation of the model, the predictive effect of the nomogram model to identify biliary atresia from other cholestatic liver diseases was in good agreement with the actual situation. Decision-curve analysis showed that the use of the nomogram model to predict biliary atresia gained more clinical value at a risk threshold of 0.10–0.80. Conclusion: The nomogram constructed integrating combi-elastography and liver function indices shows promising value for predicting the risk for developing biliary atresia. Full article

Background/Objectives: Reduced serotonin transporter (SERT) function is associated with increased vulnerability to emotional and metabolic dysregulation, particularly in elderly women. Most preclinical studies relied on young male rodents with complete Sert deficiency; the Western diet (WD) acerbates these abnormalities. However, complete Sert loss does not fully reflect the human condition of partial SERT dysfunction. Here, we examined the effects of WD in aged female Sert^+/− mice on metabolic, biochemical, molecular, and behavioral outcomes. Methods: Wild-type (WT) and Sert^+/− mice were fed WD or a control diet. Emotionality, cognition, glucose tolerance (GT), plasma ¹HNMR spectroscopy metabolome and biochemical parameters were studied. Gene expression analyses of nitric oxide (NO)-related markers were performed in the hypothalamus, dorsal raphe, and liver. Results: WD-exposed WT mice showed impaired GT and reduced plasma lactate and branched-chain amino acid levels; metabolome changes were more pronounced in mutants, while GT was unchanged. Naïve Sert^+/− mice exhibited lower lactate and alanine levels compared with WT controls. WD increased leptin and cholesterol levels in both genotypes, whereas triglyceride concentrations were reduced in Sert^+/− mice. Both WD and Sert deficiency increased Nos expression, while arginase expression was differentially regulated by genotype and diet. Malondialdehyde levels were elevated in the prefrontal cortex of Sert^+/− mice regardless diet. WD also impaired object recognition memory and induced anxiety- and depression-like behaviors, with more pronounced effects in Sert^+/− mice, except marble test behavior. Conclusions: Partial Sert deficiency aggravates some but not all WD-induced metabolic alterations, enhances oxidative stress, dysregulates arginine–NO signaling, and modifies behavior, highlighting the translational relevance of Sert^+/− mice for modeling SERT dysfunction. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic kidney disease (≈4 cases per 10.000 inhabitants) and a major cause of end-stage kidney disease (ESKD). Beyond progressive cystic enlargement of the kidneys and frequent extrarenal involvement, adults with ADPKD often exhibit a distinctive “body phenotype” with central adiposity and marked abdominal distension due to renal and hepatic organomegaly. In this setting, conventional anthropometric indices such as body mass index (BMI) and crude body weight are of limited value, as they cannot distinguish nutritional tissues (muscle, subcutaneous fat) from non-nutritional mass (cyst fluid, fibrotic tissue, or expanded extracellular water). This review summarizes the current evidence on malnutrition and sarcopenia in adult ADPKD, with a focus on the impact of organomegaly and adiposity. Cross-sectional work using the modified Subjective Global Assessment (SGA) has shown that approximately one-third of ambulatory ADPKD patients are at risk of becoming, or have become, malnourished, and that height-adjusted total kidney and liver volume (htTKLV) is the strongest clinical predictor of malnutrition, whereas eGFR plays a secondary role. Bioelectrical impedance analysis (BIA) further demonstrates a disease-specific body composition phenotype, with increased total and extracellular body water, particularly in the trunk, a reduced phase angle and reduced lean mass, consistent with early malnutrition and sarcopenia. These alterations are present even at relatively preserved kidney function and, in matched analyses, distinguish ADPKD from non-ADPKD CKD. Prospective data from a multicenter cohort indicate that the baseline SGA-defined nutritional status independently predicts short-term eGFR decline in typical ADPKD, supporting malnutrition as a potential modifier of renal trajectory rather than a mere correlate of advanced disease. In parallel, narrative syntheses on adiposity highlight that a higher BMI, waist circumference and visceral fat are associated with larger total kidney volume, faster eGFR loss and greater symptom burden, and raise concern for a sarcopenic obesity phenotype in which excess fat and cystic mass coexist with low muscle mass. Collectively, these findings support a pathophysiological model in which organomegaly-driven mechanical effects (early satiety, gastrointestinal discomfort), systemic inflammation, insulin resistance and cyst-related metabolic reprogramming converge to produce “hidden malnutrition” in ADPKD, masked by apparent overweight. From a clinical perspective, malnutrition and sarcopenia should be regarded as central, disease-modifying components of the ADPKD phenotype. Routine nutritional screening (e.g., SGA/PG-SGA) and BIA-based body composition assessment, particularly in patients with severe organomegaly or symptomatic polycystic liver disease, should be integrated into ADPKD care pathways, and individualized, muscle-preserving nutritional strategies should be tested in future prospective studies. Full article

Metabolic Dysfunction-Associated Steato-Hepatitis (MASH) is a multiple-hit disease. Endotoxins, ethanol, and other metabolites of certain gut microbiota can reach the liver and accelerate inflammation and disease progression. Targeting ethanol-producing colonic bacteria with rifaximin could affect the progress of MASH. In the present study, thirty mice were assigned to three groups (n = 10 mice per group). Mice received either a normal diet, a Western diet, or a Western diet with oral rifaximin. After 12 weeks, liver function, serum levels of TNF-α, interleukin (IL)-1β, IL-6, and lipopolysaccharides (LPS) were measured. Liver specimens were assessed for pathological changes, lipid deposition, and fibrosis. Expression of p53, GFAP, CD68, and TLR-4 in the liver was also assessed. Faecal samples were evaluated for ethanol contents. Lactobacillus acidophilus, in addition to ethanol-producing Klebsiella pneumoniae and Escherichia coli, were isolated, quantified, and tested for sensitivity to rifaximin. Rifaximin was able to ameliorate Western diet-induced biochemical changes and elevated TNF-α, IL-1β, IL-6, and LPS levels. Changes in liver histology, fibrosis, and lipid content were attenuated. Expressions of p53, GFAP, CD68, and TLR-4 in the liver were all reduced. The Western diet-induced increases in faecal ethanol or ethanol-producing bacteria were not corrected by rifaximin. After 12 weeks, isolated bacteria from the rifaximin group were rifaximin-resistant. Our findings imply that the protective impact of rifaximin in the MASH model is unlikely to be mediated by alteration of ethanol-producing colonic bacteria because of acquired rifaximin resistance. Rifaximin-induced reduction in endotoxemia and inflammation in the liver appears to be a more relevant explanation. Full article

Biopolymer adhesives are moving toward frontline use in medicine and manufacturing as the limitations in some petrochemical systems, including cytotoxicity, challenges in wet adhesion for specific families of synthetic resins and formaldehyde emissions associated with amino-formaldehyde materials are becoming increasingly difficult to accept. This review integrates mechanisms, material classes and quantitative performance across biopolymer-based adhesives. We focus on architectures that combine permanent covalent anchoring with reversible, energy-dissipating bonds and on how functional group density, crosslink density, microstructure and additives act as design knobs for wet performance, durability and degradation. Across biomedical applications, chitosan, alginate, gelatin and related hydrogels achieve wet lap-shear strengths on the order of tens of kilopascals, cut liver-bleeding times by roughly half, provide strong antibacterial activity and close diabetic wounds by about 92 percent by day 14. Thermoresponsive alginate–gelatin sealants exceed clinically relevant burst pressures and microneedle patches withstand more than 120 mmHg while sealing arteries in under a minute. In industrial settings, dialdehyde-based starch resins deliver 0.83 to 1.05 MPa dry shear and maintain strength after water immersion while meeting stringent emission classes, and silane-modified nanocellulose in urea–formaldehyde markedly reduces free formaldehyde without sacrificing the internal bond. We conclude by identifying priorities for standardized wet testing, and lifetime matching of strength and degradation that can support large-scale clinical and industrial translation. Full article

Deoxynivalenol (DON) is a common mycotoxin in cereal crops such as corn, wheat, and their processed products. It can cause feed refusal and growth retardation in piglets. This study systematically evaluated the effects of dietary exposure to purified DON at low doses of 0.25, 0.5, 1.0, and 2.0 mg/kg on growth performance, blood biochemistry, antioxidant capacity, immune function, intestinal health, and reproductive development in female weaned piglets over a 42-day period. Although dietary exposure to 0.25–2.0 mg/kg of DON did not significantly affect growth performance, it induced subclinical multi-organ toxicity. Notably, decreased platelet count (PLT) at 0.25–2.0 mg/kg and increased serum alanine aminotransferase (ALT) activity at 2.0 mg/kg were observed. DON exposure also impaired antioxidant function with reduced serum total antioxidant capacity (T-AOC) at 0.25–2.0 mg/kg, and elevated malondialdehyde (MDA) content in the jejunum and ileum at 0.5–2.0 mg/kg. Furthermore, at all doses tested (0.25–2.0 mg/kg), DON suppressed anti-inflammatory cytokine interleukin-10 (IL-10) levels in both serum and intestine, reduced duodenal villus height (VH), and decreased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Additionally, histopathological injuries of liver, kidney, duodenum, jejunum, ileum, uterus and ovaries were also observed at doses of 1.0–2.0 mg/kg. In summary, this study confirms the multi-organ toxicity of low-dose DON in piglets. Our findings suggest that DON concentrations in pig feed should be more strictly controlled and highlight the importance of considering subclinical health endpoints, such as oxidative stress markers and immune parameters, in future risk assessments of mycotoxin exposure. Full article

Rheumatoid arthritis remains a major clinical challenge requiring safer and more effective alternatives to conventional non-steroidal anti-inflammatory drugs (NSAIDs). This pioneering study evaluated the anti-inflammatory, analgesic, antioxidant, and safety effects of Artemisia herba alba extract in complete Freund’s adjuvant (CFA)-induced arthritis in rats. Animals received oral Artemisia herba alba (250 or 500 mg/kg), indomethacin (3 mg/kg), or saline for 15 days. CFA induced marked joint inflammation, mechanical allodynia, locomotor impairment, and oxidative stress. Treatment with Artemisia herba alba 500 mg/kg significantly reduced paw swelling, improved mobility in the open-field test, and markedly attenuated pain hypersensitivity. In parallel, biochemical analyses showed restoration of total antioxidant capacity, prevention of lipid peroxidation, and normalization of creatinine levels. Unlike indomethacin, which induced hepatotoxicity (elevated ASAT (Aspartate Aminotransferase)/ALAT (Alanine Aminotransferase)) and pronounced oxidative stress, Artemisia herba alba preserved liver and kidney function and did not produce histopathological alterations. Histological findings further indicated reduced inflammatory infiltrate and cartilage protection, particularly at 500 mg/kg. Taken together, these results suggest that Artemisia herba alba displays a multitarget effect with anti-inflammatory, antioxidant and analgesic activity, along with a superior safety profile compared with indomethacin, consistent with reports from other phenolic-rich natural products. However, findings should be interpreted in light of the small sample size and preclinical study design, and further mechanistic and clinical investigations are warranted. Full article

2-acetylfuran is a product of the Maillard reaction and is widely found, especially in heat-processed foods such as grain products, baked goods, and dairy products. Although 2-acetylfuran contributes to flavor, high concentrations may be toxic. Its target organs and dose–response relationships remain poorly characterized. In this study, transgenic zebrafish with fluorescently labeled immune and neural systems were used to assess the effects of 2-acetylfuran on immune and neural development. Wild-type zebrafish were employed to assess the toxicity of 2-acetylfuran on locomotor ability, gastrointestinal development, and liver function. The maximum non-lethal concentration (MNLC) and the 10% lethal concentration (LC₁₀) for zebrafish embryos were 0.844 and 0.889 μL/mL, respectively. Regarding immunotoxicity, at concentrations of 0.281, 0.844, and 0.889 μL/mL, 2-acetylfuran significantly reduced the numbers of neutrophils, T cells, and macrophages. Regarding locomotor and neurotoxicity, motor speed and total locomotor distance were significantly reduced at 0.844 and 0.889 μL/mL. These findings were consistent with neurodevelopmental assessments, in which 0.844 μL/mL 2-acetylfuran resulted in a significant increase in apoptotic cells in the central nervous system and markedly shortened peripheral motor nerve lengths. Regarding gastrointestinal toxicity, 0.844 and 0.889 μL/mL 2-acetylfuran significantly reduced the gastrointestinal area, while neutrophil counts showed no significant changes, suggesting a relatively mild effect on the gastrointestinal tract. Regarding hepatic toxicity, all tested concentrations of 2-acetylfuran primarily increased the delayed yolk sac absorption area. Furthermore, at 0.844 μL/mL, histological examination revealed hepatic pathological changes characterized by hepatocyte nuclear swelling, vacuolar degeneration, and hepatocyte necrosis. In summary, this study reveals the multi-organ toxicity profile of 2-acetylfuran in the zebrafish model, with particularly high sensitivity in the immune system and liver. This research provides theoretical support for risk assessment and process control of 2-acetylfuran in foods. Full article

Hepatitis C virus (HCV) still lacks a licensed vaccine. The envelope glycoprotein E2 is a key neutralizing target, but its dense N-glycan shield can hinder epitope exposure. In this study, we revisit E2 glycan editing and examine whether single-site deletion preserves antigen integrity while improving immune responses in mice under a DNA immunization setting. Using a secreted E2 ectodomain (sE2384–661), we generated five N to D mutants at conserved sites (N1, N2, N4, N6, and N11) and evaluated them in a unified DNA immunization model with identical CpG content and delivery conditions across groups. The N2 mutant (N423, sE2-N2) maintained expression, secretion, and ER localization; furthermore, in mice, it was associated with higher anti-E2 titers and greater inhibition of H77 (genotype 1a) HCVcc at the tested dilutions, with limited activity against Con1 (1b). Cellular analyses showed increased IFN-γ ELISPOT counts and higher frequencies of granzyme B⁺/perforin⁺ CD8⁺ T cells after N2 immunization, while IL-4 remained low. Functionally, N2 elicited stronger specific lysis of CT26-sE2 targets in vitro and slowed CT26-sE2 tumor growth in vivo. In HCV-infected ICR^4R+ mice, therapeutic vaccination with sE2-N2 reduced blood HCV RNA and hepatic readouts compared with sE2. A monoclonal antibody isolated from sE2-N2-immunized mice (1C1) neutralized HCVcc in vitro and, after passive transfer, lowered viremia and liver signals in infected mice. Collectively, these findings indicate that selective removal of the N2 glycan preserves antigen properties and is associated with improved humoral and cellular immunity and measurable in vivo activity, supporting targeted glycan editing as a practical strategy to refine E2-based HCV vaccines. Full article

Background: Age-related declines in respiratory muscle strength and ventilatory efficiency can impair functional capacity and metabolic health in older adults. Inspiratory muscle training (IMT) has been proposed as a practical intervention to counteract these changes, yet its systemic effects remain unclear. This study aimed to examine the effects of short-term IMT on functional capacity, diaphragm thickness, and liver tissue characteristics in healthy elderly men. Methods: Thirty community-dwelling men aged 60–80 years were randomly assigned to an IMT or control group. The IMT group performed four weeks of breathing exercises using a POWERbreathe^® device at 40% of maximal inspiratory pressure, with a weekly 10% increase in pressure. Pre- and post-intervention assessments included the six-minute walk test (6MWT), diaphragm thickness and liver density via computed tomography, and quality of life (QoL; SF-12). Results: Four weeks of inspiratory muscle training significantly improved diaphragm thickness (11.7%), fatty liver density (FLD) (+16.7%), and six-minute walk performance (+5.3%), with large time × group effects favoring the IMT group. While the physical quality of life showed modest, comparable improvements, mental health outcomes demonstrated a moderate, time-dependent improvement without a significant group-by-time interaction. Conclusions: Short-term IMT improved diaphragmatic function and functional capacity in older men and was associated with favorable changes in a liver-related biomarker; however, given that only a single liver-related metric was assessed, these findings should not be interpreted as evidence of overall improvements in liver health. Full article

Background: Recently, based on HOMA-IR, we estimated empirical optimal cut-off values for SHBG levels of ≤41.5 nmol/L in women with PCOS. Other proposed markers of insulin resistance include triglyceride and glucose levels, and anthropometric measurements. Therefore, our current study aimed to analyze its consistency with the cut-off values that discriminate insulin resistance based on the TyG, TyG-BMI, and TyG-WC indices in women with PCOS. Methods: Age, body weight, height, waist circumference, glucose, insulin, triglyceride, and SHBG levels were retrieved from the medical records of 264 Caucasian women diagnosed with PCOS. The TyG, TyG-BMI, and TyG-WC indices were calculated. The mean meta-cut-off SHBG level was calculated using receiver-operating characteristic (ROC) analysis combined with diagnostic test accuracy meta-analysis. Results: The mean meta-cut-off value for SHBG levels for the assessment of insulin resistance was less than 43.1 (95% CI: 37.0–49.2) nmol/L. The pooled sensitivity and specificity of SHBG levels for the assessment of insulin resistance were 74.7% and 66.9%, respectively. The pooled mean prevalence of insulin resistance based on all indices was 36.1% (95% CI: 33.5–38.7%) with a standard deviation of 18.7% and positive predictive value (PPV) of 52.8% (95% CI: 12.2–87.5%) and the negative predictive value (NPV) of 80.2% (95% CI: 45.1–97.7%). Conclusions: Our study confirms the usefulness of SHBG level as a marker of insulin resistance in Caucasian women with PCOS. A value below 43 nmol/L, with high sensitivity and specificity, enables the detection of insulin resistance and a high risk of prediabetes, prompting close monitoring of liver function. Full article

Background: Metabolic syndrome (MetS) comprises interrelated metabolic abnormalities that collectively confer increased risk of cardiovascular disease and hepatic morbidity. The MAF-5 score is a non-invasive prognostic marker of liver fibrosis and mortality, while Cystatin C (CysC) is a sensitive indicator of renal function that also reflects inflammation, atherosclerosis, and metabolic dysfunction. Although both MetS and CysC have been widely studied, their potential interplay via MAF-5 remains unclear. We aimed to investigate the relationship between MAF-5 scores and CysC levels in MetS patients for the first time. Materials and Methods: Adults (≥18 years) with MetS were included in this study. MAF-5 scores (based on waist circumference, BMI, diabetes status, AST, and platelet count) and CysC levels were recorded. The MAF-5–CysC relationship was assessed via Pearson correlation. Participants were grouped into MAF-5 quartiles, and continuous variables were compared using ANOVA with Bonferroni-corrected pairwise tests. Results: We included 347 MetS patients (54.8% female, median age 54 years). The median MAF-5 score was 1.25, and MAF-5 correlated positively with CysC (r = 0.357, p < 0.001). CysC levels differed significantly across MAF-5 quartiles (Q1 = 0.96, Q2 = 0.99, Q3 = 1.06, Q4 = 1.09; p < 0.001), with Q4 showing higher values than Q1 and Q2. Conclusions: A significant correlation was found between MAF-5 scores and CysC in patients with MetS. CysC levels differed significantly across MAF-5 quartiles, suggesting a potential link between systemic inflammation, liver fibrosis, and CysC. These results highlight shared inflammatory and fibrotic pathways, underlying metabolic dysfunction. Clinically, combined assessment of MAF-5 and CysC may improve risk stratification, identifying patients at higher risk for hepatic fibrosis and adverse outcomes. Full article

Patient-derived organoids (PDOs) have emerged as promising preclinical models for studying tumor biology and testing therapeutic strategies in oncology. These three-dimensional culture systems retain key histological, genetic, and functional characteristics of the original tumors, offering a unique opportunity to advance personalized medicine approaches in liver cancer. In this study, we present the methodological framework and preliminary findings of a prospective study aimed at generating and characterizing PDOs from patients with hepatocellular carcinoma (HCC) undergoing surgical resection. Tumor specimens were processed using an optimized protocol for organoid derivation, expansion, and cryopreservation. We evaluated the success rate of organoid establishment and the histo-molecular fidelity to the parental tumor. These early results demonstrate promising engraftment efficiency and maintenance of tumor-specific markers across passages. Our work highlights the potential of PDOs as a reliable and scalable platform for translational research in HCC, setting the stage for future applications in drug screening and biomarker discovery. Full article