Search Results (817)

Background/Objectives: To date, few studies have investigated the therapeutic effects of soy versus whey protein supplementation on obesity and insulin resistance (IR), yielding inconsistent findings. The aim of the present study was to compare the therapeutic efficacy of soy versus whey protein on obesity and IR and to elucidate their potential molecular mechanisms. Methods: Forty male C57BL/6J mice were randomly divided into two groups and fed either a normal diet (n = 8) or a high-fat diet (HFD, n = 32) for 16 weeks to induce obesity. After 16 weeks, HFD-induced obese mice were further randomized into three groups: HFD control, HFD + 20% whey protein isolate (WPI), and HFD + 20% soy protein isolate (SPI) for 6 weeks (n = 8). Results: Body weight, weight gain, body mass index, and Lee index showed no significant differences between the WPI and SPI groups. Compared with the WPI group, serum concentrations of insulin and leptin and the homeostasis model assessment of IR (HOMA-IR) were significantly lower, and thymus wet weight, fetal total cholesterol level, and serum glucose-dependent insulinotropic polypeptide concentration were significantly higher in the SPI group. Compared with the WPI group, the protein levels of GLUT4 and p-PI3K/PI3K were significantly higher in the SPI group. Metabolomics analysis showed that hepatic phosphocholine levels were significantly higher in the SPI group than in the WPI group. Moreover, hepatic differentially abundant metabolites of SPI- and WPI-fed mice were primarily enriched in the glycerophospholipid metabolism pathway. Conclusions: Soy protein was more effective than whey protein in ameliorating IR in HFD-induced obese mice, probably by modulating the PI3K-GLUT4 pathway and glycerophospholipid metabolism. Moreover, soy protein and whey protein showed comparable anti-obesity efficacy. Full article

Paroxysmal nocturnal hemoglobinuria (PNH) is associated with bone marrow failure disorders and may arise during the long-term follow-up of aplastic anemia (AA), which is named AA/PNH syndrome. Thrombosis is the most frequent clinical complication and is the main cause of mortality in PNH. However, thromboses tend to originate in hepatic and cerebral venous vessels, but rarely in the hepatic microvascular vein in PNH patients. Here, we report on a young man with hepatic sinusoidal obstruction syndrome (HSOS) secondary to AA/PNH syndrome. His main manifestations were hemolytic anemia, renal injury, ascites, hepatomegaly, and elevated liver enzymes. The diagnosis was confirmed by peripheral blood flow cytometry, enhanced computed tomography (CT), and liver biopsy. Initially, he received symptomatic treatments including diuretics, intermittent abdominal paracentesis, and low-molecular-weight heparin. Meanwhile, due to the occurrence of PNH activity during hospitalization, methylprednisolone 40 mg per day was administered, which was later transitioned to oral prednisolone. Subsequently, the dose of corticosteroids was gradually decreased once his hemoglobin stabilized. The association between HSOS and AA/PNH syndrome is exceptionally rare, as evidenced by the scant literature on the subject. This case underscores the critical need for awareness of HSOS secondary to AA/PNH syndrome, which needs a high index of suspicion and for which prompt treatment is needed to reduce morbidity and mortality. Full article

Background: Sarcopenia is a clinical condition linked to various liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD includes a spectrum from steatosis to steatohepatitis, which may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. The influence of dietary habits and nutrient intake on MASLD and its progression is well-established. However, the association between dietary consumption and sarcopenia in MASLD patients remains underexplored. This study evaluated whether there is an association between sarcopenia and habitual food consumption in MASLD patients. Methods: A cross-sectional study was conducted with outpatients diagnosed with MASLD. Sarcopenia was defined based on the 2019 EWGSOP2 criteria. Dietary intake was assessed using three 24 h recalls per patient, with intrapersonal variance corrected using the Multiple Source Method (MSM) software (Version 1.0.1). Steatosis was diagnosed via upper abdominal ultrasound, and the Fibrosis-4 Index (FIB-4) was used to assess hepatic fibrosis. Results: MASLD patients (n = 76) were evaluated. The mean age was 52.9 (SD, 12.0) years, and 75.0% were female. Two had sarcopenia, and 27.6% (n = 21) had probable sarcopenia (characterized by low muscle strength only). Among probable sarcopenia, F1-F2 were observed in 61.9%, and 23.8% had indeterminate FIB-4 grades. Calcium intake was lower among patients with probable sarcopenia than those no sarcopenia (p = 0.04). Conclusions: In these MASLD patients, only two patients were diagnosed with sarcopenia, and around a third had probable sarcopenia. The majority of MASLD patients with lower calcium, energy, and protein intake, but only lower calcium intake in those with probable sarcopenia. Full article

Objectives: Although angiopoietin-like 4 (ANGPTL4) is highly associated with glucose hemostasis and lipid metabolism, the relationships between the serum ANGPTL4 level, glucose status and hepatic steatosis remain unclear. Therefore, this study aimed to quantify the independent effects of glucose intolerance and hepatic steatosis on circulating ANGPTL4 concentrations. Methods: A total of 348 age- and sex-matched participants with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed diabetes (NDD) with or without hepatic steatosis were recruited for this cross-sectional study. Serum ANGPTL4 levels were measured, and multivariate linear regression analysis was used to evaluate the relationship between ANGPTL4, glycemic status and hepatic steatosis. Results: Compared with NGT, both IGT and NDD were associated with significantly higher serum ANGPTL4 concentrations, irrespective of hepatic steatosis status. Serum ANGPTL4 did not differ by the presence versus absence of hepatic steatosis. In multiple regression analysis, body mass index, homeostasis model assessment of insulin resistance, NGT vs. IGT, and NGT vs. NDD were independently associated with ANGPTL4 levels after adjustment for cardiovascular risk factors and adiponectin, whereas hepatic steatosis was not. Conclusions: Elevated serum ANGPTL4 concentrations were independently associated with prediabetes and diabetes, irrespective of hepatic steatosis. Full article

Background: Adolescents suffering from obesity are at higher risk of bone fragility due to hepatic steatosis, which may lead to an inflammatory microenvironment in the bone marrow. We therefore aimed to assess the reliability of measuring the bone marrow fat fraction (BMFF) and T2* of the lumbar vertebral marrow using the proton density fat fraction (PDFF) sequence for adolescents with obesity and liver steatosis. Method: This was an observational feasibility pilot study on adolescents living with obesity and liver steatosis. Anthropometric measurements were obtained. Participants underwent abdominal MRI, MR elastography and dual-energy X-ray absorptiometry (DXA). Regions of interest were drawn using the radiology interface from the central L1 to L4 vertebrae on fat and T2* maps from the PDFF sequence. ImageJ was used to measure abdominal compartment fat areas. Descriptive analyses, the intraclass correlation coefficient, and correlation results were obtained from anthropometric, adiposity, BMFF, and T2* measurements. Results: We recruited 23 adolescents with a body mass index > 85th percentile and mean age = 14.7 years (interval 12–17 years), and n = 18 (78%) were boys. BMFF and T2* measurements were successful in 100% of cases. The intra-operator reproducibility of the BMFF and T2* measurements was excellent: ICC = 0.99 (95% confidence interval (CI) [0.986; 0.999]) and ICC = 0.99 (95% CI [0.992; 0.999]), respectively. The inter-operator ICC was good for BMFF (ICC = 0.89; 95% CI [0.705; 0.963]) and moderate for T2* (ICC = 0.66; 95% CI [0.239; 0.873]). Only BMFF was inversely correlated with vertebral-bone mineral density (r = −0.67; p = 0.0009). However, T2* measurements showed a positive linear relationship with the total body fat tissue percentage measured by DXA (r = 0.48; p = 0.03) and the total abdominal fat area (r = 0.45; p = 0.04). Conclusions: PDFF could be a reliable imaging biomarker for bone health assessment in adolescents living with obesity. Full article

Psoriasis is a complex inflammatory disease related to cardiometabolic disorders (CMDs). Galectin-4 (gal-4) is involved in biological processes such as lipid raft stabilization, intestinal inflammation and tumorigenesis. Charcot-Leyden crystals (CLCs), inter alia, Charcot-Leyden crystal/galectin-10 (CLC/gal-10), are involved in eosinophil-derived diseases. To date, neither of these galectins has been investigated in the context of psoriasis. The study aimed to evaluate serum galectin-4 and -10 levels in psoriatic patients and explore potential relationships with disease activity, metabolic or inflammatory indices. Blood samples were collected from 60 patients with plaque-type psoriasis and 30 healthy volunteers and evaluated using an Enzyme-Linked Immunosorbent Assay (ELISA). Morphological and biochemical indices were measured using routine laboratory techniques. Plasma gal-4 and gal-10 concentrations were significantly higher in patients with psoriasis than in the control group (p < 0.05). Galectins did not correlate with the Psoriasis Area Severity Index (PASI) nor age (p > 0.5); however, gal-4 showed a significant positive correlation with Body Mass Index (BMI), psoriasis duration (p = 0.03), and transaminase activity. Both proteins were the highest in obese psoriatics (p < 0.05). The results indicate that galectin-4 and galectin-10 may be involved in the pathophysiological mechanisms underlying CMDs in psoriatics. These galectins represent promising candidates for biomarkers of metabolically driven inflammation, with galectin-4, in particular, emerging as a potential indicator of hepatic dysfunction in psoriatic patients. Full article

Background: The increase in obesity rates and related liver diseases has risen in recent years in Mexico. Dietary factors, such as the imbalance between n-6 and n-3 polyunsaturated fatty acids, have been associated with a higher risk of developing conditions such as fatty liver. The objective of this study was to analyse the influence of the dietary n-6/n-3 ratio on fatty liver in Mexican adults. Methods: This analytical cross-sectional study included 213 Mexican adults aged 18 to 65 years, of both genders. The dietary n-6/n-3 ratio was calculated using the Nutritionist Pro software. Participants were divided into two groups according to the median of their dietary n-6/n-3 intake ratio: “low” (<10.2:1) and “high” (≥10.2:1). Anthropometric and biochemical markers were evaluated using standardised methods. The hepatic steatosis index (HSI) was used as a surrogate marker of fatty liver. Multivariate logistic regression analyses were conducted to predict fatty liver based on HSI. Results: Overall, the mean dietary n-6/n-3 ratio was 12.75 in the general population. Higher HSI values were found in participants with a high n-6/n-3 ratio (p = 0.038). In the multivariate model, the n-6/n-3 ratio was positively associated with high HSI (OR = 1.48, 95% CI, 1.02, 1.99). Conclusions: This study concludes that a high n-6/n-3 ratio may contribute to the development of fatty liver in Mexican adults. These results highlight the importance of a balanced intake of fatty acids to prevent metabolic complications and improve public health. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition worldwide, occurring both independently and, more importantly, as the most common extraintestinal complication of inflammatory bowel disease (IBD). The study primarily investigated MASLD prevalence in Crohn’s disease (CD) and ulcerative colitis (UC) to enhance prevention and early detection, especially given the recent approval of the first treatment for this condition. Secondary objectives included identifying risk factors, exploring the uric acid/high-density lipoprotein cholesterol ratio (UHRatio) as a steatosis marker and evaluating correlations between non-invasive fibrosis scores, Fibrosis-4 (FIB-4), AST-to-Platelet Ratio Index (APRI), and histological fibrosis severity. We conducted a prospective study on 58 patients diagnosed with IBD. The type of IBD was not independently associated with liver steatosis or fibrosis. Disease activity correlated significantly with hepatic steatosis in CD patients and with hepatic fibrosis in UC patients. The UHRatio proved useful in assessing steatosis prevalence, whereas FIB-4 and APRI scores did not correlate significantly with fibrosis severity. This study is, to our knowledge, the first to evaluate UHRatio as a potential predictor of MASLD in patients with IBD, expanding on previous findings reported in the general population. Our results suggest that this non-invasive biomarker, previously used to identify MASLD, may improve early prediction and could serve as a useful screening tool for MASLD in IBD patients. Full article

Background/Objectives: Cardiovascular diseases (CVD) remain the leading cause of diet-related mortality, with hepatic overproduction of very-low-density lipoprotein (VLDL) being a central driver of dyslipidemia. The microsomal triglyceride transfer protein (MTP) is essential for this process, and its activity is negatively regulated by cyclic adenosine monophosphate (cAMP). Theophylline, a methylxanthine found in tea, increases intracellular cAMP. This study aimed to evaluate whether physiologically relevant concentrations of theophylline could beneficially modulate lipoprotein secretion in an ex vivo model of diet-induced MTP activation. Methods: Primary hepatocytes were isolated from rats fed a high-fat, high-carbohydrate diet (HFCD). Cells were treated with 100 µM theophylline, and the secretion of triglyceride (TG), total cholesterol (TC), VLDL-cholesterol (VLDL-C), and HDL-cholesterol (HDL-C) was quantified. Hepatocellular MTP activity and atherogenic indices were also assessed. Results: Compared to untreated control cells, theophylline treatment significantly reduced the secretion of TG by 6% and TC by 24%. Specifically, VLDL-C secretion decreased by 6%, while HDL-C secretion increased substantially by 93%. These lipid-modulating effects were correlated with a 6.9% reduction in MTP activity. Consequently, significant improvements were observed in the atherogenic indices TG/HDL-C, TC/HDL-C, and the atherogenic index (AI) (p < 0.01). Conclusions: Our findings demonstrate that physiologically attainable concentrations of theophylline rebalance lipoprotein secretion by suppressing hepatic MTP activity, shifting the lipid profile toward an anti-atherogenic state. These results highlight the potential of theophylline as a functional dietary component for mitigating diet-induced dyslipidemia and reducing cardiovascular risk. Full article

Hepatitis B Virus (HBV) continues to pose a significant global health challenge, with over 254 million chronic infections and current therapies being non-curative, necessitating lifelong treatment. The HBV ribonuclease H (RNase H) is essential during HBV reverse transcription by cleaving the viral pregenomic RNA after it has been copied into the (−) polarity DNA strand, enabling the viral polymerase to synthesize the (+) DNA strand. Although RNase H inhibition terminates viral replication and thus viral infectiveness, its targeting as an HBV treatment is unexploited. Its catalytic site contains four carboxylates that bind to two Mg²⁺ ions essential for RNA hydrolysis. As part of our ongoing research on RNase H inhibitors, we developed 23 novel N-hydroxypyridinedione (HPD) analogues. Specifically, 17 HPD imines, 4 HPD oximes, 1 2,6-diamino-4-((substituted)oxy)pyrimidine 1-oxide derivative, and 1 barbituric acid analogue were designed, synthesized, and tested for their anti-HBV activity. The HPD derivatives could be docked in the RNase H active site to coordinate the two Mg²⁺ ions and effectively inhibited viral replication in cellular assays. The 50% effective concentration (EC₅₀) values of these HPD compounds ranged from 0.5 to 73 μM, while the 50% cytotoxic concentration (CC₅₀) values ranged from 15 to 100 μM, resulting in selectivity indexes (SIs) up to 112. Furthermore, the novel HPD derivatives exhibited favourable pharmacokinetic-relevant characteristics, including high cellular permeability, good aqueous solubility, and overall drug-like properties. These findings indicate that HPD imines and oximes possess substantial antiviral potency and selectivity against HBV, underscoring the potential of the HPD scaffold as a promising framework for the development of next-generation anti-HBV agents. Full article

Metabolic-associated steatotic liver disease is currently one of the most common causes of liver disease in the world, affecting a large portion of the global population; these patients are at risk of developing advanced liver fibrosis and cirrhosis. Noninvasive tests (NITs), including lab tests such as FIB-4, NAFLD Fibrosis Score and the Aspartate Aminotransferase-to-Platelet Ratio Index, are widely used for fibrosis risk stratification, but their accuracy across various racial, ethnic, and age groups remains poorly characterized. This review examines disparities in NIT performance across these populations and the need for tailored screening strategies. A comprehensive, narrative literature review highlighted significant variability in NIT performance, with studies in African American, Hispanic and Asian patients all revealing mixed results when the performance of NITs was used to assess fibrosis levels. Additionally, the age of patients may influence fibrosis testing, as older adults tend to have higher false-positive rates due to age-based biases. Although imaging modalities like VCTE and MRE may offer superior accuracy in the noninvasive assessment of hepatic fibrosis, they face accessibility limitations and have rarely been validated in specific racial groups. This review concludes that current NITs for MASLD risk stratification needs to be recalibrated with population-specific and age-adjusted thresholds, and future research should focus on inclusive validation studies and integrating clinical judgment to improve screening accuracy. Full article

Background/Objectives: Chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with risk of advanced hepatic fibrosis and cirrhosis. Given the increased risk, the presence of insulin resistance, metabolic syndrome, and hepatic fibrosis should be assessed in individuals with chronic hepatitis B. The Lipoprotein Insulin Resistance Index (LP-IR) is a simple method of assessing insulin resistance in the general population, and lipoprotein profiles have been shown to reflect hepatic steatosis and fibrosis in patients with MASLD. However, LP-IR and lipoprotein profiles have not been evaluated in patients with chronic hepatitis B. Methods: Lipoprotein profiles and LP-IR scores were evaluated in a cohort of patients with chronic hepatitis B using NMR spectroscopy. Results: Serum samples from 50 patients with chronic hepatitis B and 44 with chronic hepatitis B and metabolic syndrome were analyzed. A cut-off value was defined that differentiates patients with and without insulin resistance. Increased large VLDL and reduced small VLDL particles were observed, suggesting the presence of hepatic steatosis and fibrosis. Conclusions: In this largely Asian cohort of chronic hepatitis B patients, where BMI and conventional markers are less reliable, LP-IR scores differentiated patients with and without insulin resistance and metabolic syndrome. In addition, distinctive lipoprotein profiles such as increased large VLDL and reduced small VLDL particles were observed in these chronic hepatitis B patients, suggesting the presence of hepatic steatosis and fibrosis. Future studies with larger sample sizes are necessary to confirm the utility of these NMR-measured lipoprotein parameters in predicting metabolic disease and fibrosis among patients with underlying liver disease. Full article

Mitigating stress responses is crucial for maintaining optimal productivity and profitability in modern poultry production. The effects of early feed withdrawal (EFW) and vitamin C (Vit C) supplementation, both individually and in combination, on heat-stressed broilers’ productivity, stress responses, and metabolic markers were investigated. In total, 240 newly hatched Cobb-500 male chicks were randomly distributed to four treatment groups (six replicates × 10 birds per group). A basal diet was offered to the control group; meanwhile, the EFW group underwent a 24 h early feed withdrawal on day four of age. The Vit C group was given 200 mg/kg vitamin C daily, and the EFW + Vit C group received both interventions. The study was executed under hot summer conditions, where the average minimum and maximum temperature-humidity Index (THI) were 29.15 ± 0.78 and 33.34 ± 0.76, respectively. The results demonstrated a superior stress-mitigating effect when EFW was combined with Vit C supplementation, leading to a significant improvement in productive parameters and elevated blood metabolic hormone levels. Additionally, total antioxidant capacity was enhanced, hepatic endogenous antioxidant enzyme expression was upregulated, and stress biomarkers were reduced. Furthermore, the economic efficiency indicators were significantly improved with EFW, and when EFW was combined with Vit C addition. These findings suggest that integrating multiple stress mitigation strategies, such as EFW and Vit C supplementation, may be more effective in relieving the adverse effects of heat stress by restoring homeostasis and optimizing broilers’ productivity and profitability. Full article

Renin–angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), have been associated with improved outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess the differential impact of ACEIs versus ARBs on survival and cardiovascular outcomes in individuals with MASLD. Using data from the UK Biobank, we identified 52,143 participants with exclusive use of either an ACEI or ARB. Individuals with viral, autoimmune, cholestatic, or alcohol-related liver disease were excluded. MASLD was defined as fatty liver index ≥ 60 with ≥1 cardiometabolic risk factor. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders. Outcomes included all-cause mortality, cardiovascular events, hepatic decompensation, and hepatocellular carcinoma (HCC), analyzed using Cox proportional hazards models. Among MASLD participants, ARB use was associated with significantly lower all-cause mortality compared to ACEI use (HR, 0.94; 95% CI, 0.90–1.00; p = 0.031) after IPTW adjustment. Cardiovascular risk was also lower with ARBs (HR, 0.92; 95% CI, 0.89–0.96; p < 0.001), particularly in subgroups with BMI ≥ 25 kg/m², no diabetes, and advanced fibrosis. No differences in hepatic decompensation or HCC incidence were observed. Benefits of ARBs were not significant in participants without steatotic liver disease. ARB use was associated with improved survival and reduced cardiovascular events in individuals with MASLD, whereas ACEIs expressed no comparable benefit. These findings suggest that ARBs might be a more effective RAS inhibitor subclass in MASLD and support their preferential use in patients with steatotic liver disease requiring antihypertensive therapy. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as NAFLD, affects nearly one-third of the global adult population and is a leading cause of chronic liver disease, particularly among individuals with obesity and type 2 diabetes (T2DM). Bariatric surgery, including sleeve gastrectomy (SG), has demonstrated a favorable impact on liver fat reduction. However, the predictive value of early postoperative weight-loss trajectories for long-term hepatic improvement remains uncertain, especially in Asian populations, in which MASLD remains understudied despite its increasing prevalence. Methods: We retrospectively reviewed 198 adults who underwent SG at a tertiary Korean center between January 2019 and April 2024. After excluding 21 who had postoperative complications or missed early follow-up, 177 patients (mean age 37 ± 9 years; 41% male; mean body mass index (BMI) 40 kg/m²) were included in the final analysis. The two-week total weight-loss index (TWL_2W) was calculated, and its association with one-year hepatic steatosis resolution, defined as the normalization of the hepatic steatosis index (HSI < 30) at one year, was assessed using receiver operating characteristic (ROC) analysis to explore the trend toward predictive value. Optimal cut-offs were derived using the Youden Index. Multivariable logistic regression models were adjusted for age, sex, baseline hemoglobin A1c (HbA1c), and BMI. Subgroup analyses were performed according to baseline HSI (35–44, 45–54, ≥55) and type 2 diabetes mellitus (T2DM) status. Results: The mean TWL_2W was 7.9 ± 6.6%. A loss of 7.9% optimally predicted HSI values < 30 at one year (area under the curve [AUC] 0.602; unadjusted odds ratio [OR] 2.34; 95% confidence interval [CI] 1.16–4.73). Predictive accuracy improved in T2DM patients (AUC 0.737, 95% CI 0.54–0.95), in whom TWL_2W ≥ 9.1% conferred an adjusted OR 9.12 (95% CI 1.39–59.82), whereas no association was observed in non-diabetic subjects. Stratified analysis showed a pronounced effect in moderate baseline steatosis (HSI 45–54; OR 3.56), but absolute normalization was rare when the baseline HSI was ≥55. Early weight loss was not significantly linked to one-year HbA1c or triglyceride targets. Conclusions: An 8–9% reduction in body weight within two weeks of SG was independently associated with the resolution of hepatic steatosis at one year, particularly among patients with T2DM or moderate baseline hepatic steatosis. This simple metric may assist in early risk stratification and guide personalized postoperative care. Full article