Search Results (274)

Background: Post-hepatectomy liver failure (PHLF) is the most worrisome complication after a major hepatectomy and is the leading cause of postoperative mortality. The most important predictor of PHLF is the future liver remnant (FLR), the volume of the liver that will remain after the hepatectomy, representing a major concern for hepatobiliary surgeons, radiologists, and patients. Therefore, an accurate preoperative assessment of the FLR and the prediction of PHLF are crucial to minimize risks and enhance patient outcomes. Recent radiomics and deep learning models show potential in predicting PHLF and the FLR by integrating imaging and clinical data. However, most studies lack external validation and methodological homogeneity and rely on small, single-center cohorts. This review outlines current CT-based approaches for surgical risk stratification and key limitations hindering clinical translation. Methods: A literature analysis was performed on the PubMed Dataset. We reviewed original articles using the subsequent keywords: [(Artificial intelligence OR radiomics OR machine learning OR deep learning OR neural network OR texture analysis) AND liver resection AND CT]. Results: Of 153 pertinent papers found, we underlined papers about the prediction of PHLF and about the FLR. Models were built according to machine learning (ML) and deep learning (DL) automatic algorithms. Conclusions: Radiomics models seem reliable and applicable to clinical practice in the preoperative prediction of PHLF and the FLR in patients undergoing major liver surgery. Further studies are required to achieve larger validation cohorts. Full article

Background/Objectives: Paclitaxel (PTX) is widely used in the treatment of a variety of solid tumours due to its broad-spectrum anti-tumour activity, but its use in brain gliomas is limited by insufficient blood–brain tumour barrier (BBTB) penetration and systemic toxicity. The aim of this study was to develop a Solutol HS-15-based micellar nanoparticle (PSM) to enhance the brain glioma targeting of PTX and reduce toxicity. Methods: PSMs were prepared by solvent injection and characterised for particle size, encapsulation rate, haemolysis rate and in vitro release properties. A C6 in situ glioma mouse model was used to assess the brain targeting and anti-tumour effects of the PSM by in vivo imaging, tissue homogenate fluorescence analysis and bioluminescence monitoring. Meanwhile, its safety was evaluated by weight monitoring, serum biochemical indexes and histopathological analysis. Results: The particle size of PSMs was 13.45 ± 0.70 nm, with an encapsulation rate of 96.39%, and it demonstrated excellent cellular uptake. In tumour-bearing mice, PSMs significantly enhanced brain tumour targeting with a brain drug concentration 5.94 times higher than that of free PTX. Compared with Taxol, PSMs significantly inhibited tumour growth (terminal luminescence intensity <1 × 10⁶ p/s/cm²/Sr) and did not cause significant liver or kidney toxicity or body weight loss. Conclusions: PSMs achieve an efficient accumulation of brain gliomas through passive targeting and EPR effects while significantly reducing the systemic toxicity of PTX. Its simple preparation process and excellent therapeutic efficacy support its use as a potential clinically translational candidate for glioma treatment. Full article

In this research, the proteomic landscape of 100 kDa protein extract sourced from rabbit brain was compared to extracts from liver and from organ mixture (OM). Our aim was to compare the efficacy of Nanomised Organo Peptides (NOP) ultrafiltrates from two different tissues and a tissue mixture for inducing neurite outgrowth, and subsequently to identify the molecular networks and proteins that could explain such effects. Proteins were isolated by gentle homogenization followed by crossflow ultrafiltration. Proteomic evaluation involved gel electrophoresis, complemented by mass spectrometry and bioinformatics. GO (Gene Ontology) and protein analysis of the mass spectrometry results identified a diverse array of proteins involved in critical specific biological functions, including neuronal development, regulation of growth, immune response, and lipid and metal binding. Data from this study are accessible from the ProteomeXchange repository (identifier PXD051701). Our findings highlight the presence of small proteins that play key roles in metabolic processes and biosynthetic modulation. In vitro outgrowth experiments with neural stem cells (NSCs) showed that 100 kDa protein extracts from the brain resulted in a greater increase in neurite length compared to the liver and organ mixture extracts. The protein networks identified in the NOP ultrafiltrates may significantly improve biological therapeutic strategies related to neural differentiation and outgrowth. This comprehensive proteomic analysis of 100 kDa ultrafiltrates revealed a diverse array of proteins involved in key biological processes, such as neuronal development, metabolic regulation, and immune response. Brain-specific extracts demonstrated the capacity to promote neurite outgrowth in NSCs, suggesting potential application for neuroregenerative therapies. Our findings highlight the potential of small proteins and organ-specific proteins in the development of novel targeted treatments for various diseases, particularly those related to neurodegeneration and aging. Full article

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, but its molecular drivers remain underexplored in Latin American populations. This study investigated the prevalence, co-occurrence, and tissue distribution of somatic mutations in the TERT promoter (C228T/C250T) and CTNNB1 exon 3, as well as TERT gene expression, in liver tissues from Brazilian patients. A total of 85 samples (42 HCC, 21 cirrhosis, and 22 hepatitis) were analysed using Sanger sequencing and RT-qPCR. TERT promoter mutations were detected in 47.6% of HCC tissues, including C228T (45.2%) and C250T (2.4%), and were also present in 19% of cirrhotic tissues but absent in hepatitis samples, supporting their emergence in early hepatocarcinogenesis. CTNNB1 exon 3 mutations occurred in 17.2% of HCCs and significantly co-occurred with TERTp mutations (66.7%, p = 0.0485), although the number of CTNNB1-mutated cases was limited. TERT expression was significantly upregulated in HCC tissues regardless of mutation status (p < 0.001). This is the first study to characterise these mutations in Brazilian HCC patients, highlighting the C228T mutation as a promising biomarker for early detection and molecular surveillance in cirrhotic individuals. Despite the genetic admixture of the studied population, the mutational patterns were comparable to those reported in more homogeneous populations, reinforcing the global relevance of these molecular alterations. Full article

The objective of this study was to formulate a compound suspension comprising paeoniflorin and curcumin, assess its quality characteristics, and investigate its protective efficacy against acute liver injury in mice. The prescriptions were screened using a single-factor test, and nine groups of suspensions were prepared using the dispersion method. Fifty KM mice (four weeks old) were selected and randomly divided into five groups: the CON, LD, PF, CUR, and PC groups. The doses of both paeoniflorin and curcumin were 100 mg/kg BW, and different suspensions were given to different groups by gavage for 14 days. All the groups except the CON group were injected intraperitoneally with 20 μg/kg LPS and 700 mg/kg D-GalN on the last day. According to the results, the suspension prepared using the optimal prescriptions was orange-yellow in color, with homogeneous turbidity and good re-dispersibility. The combination treatment could reduce the severity of pathological injuries of liver, improve the ultrastructure of hepatocytes, increase the activities of T-SOD, GSH-Px, and CAT, decrease the levels of IFN-γ, TNF-α, and IL-1, and down-regulate the expression of genes such as TLR4, MyD88, IκBα, and NLRP3. The underlying mechanism might be associated with the enhancement of antioxidant enzyme activities, inhibition of the TLR4/NF-κB/NLRP3 signaling pathway, and suppression of inflammasome assembly and release in hepatic tissues. Full article

In recent years, bifunctional ingredients extracted and utilized from waste by-products as raw materials have received significant attention in the food production process. Previous studies have found that bovine livers possess both antioxidant and emulsifying potential; therefore, enhancing these dual properties is a current research focus. In this study, three different types of polyphenols (epigallocatechin gallate [EGCG], gallic acid [GA] and tannin [TA]) provide a reference on how to achieve better complexation of polyphenols with bovine liver hydrolysates (BLHs). Based on the molecular weight results, it was shown that the bovine liver peptides bind to polyphenols to form complexes with higher molecular weights. Furthermore, the binding affinities among the three complexes were as follows: TA > EGCG > GA. The emulsions stabilized by the coupling compounds contained more homogeneous and dense droplets (optical microscopy). Both the antioxidant properties and the emulsifying activity of all complexes were superior to those of bovine liver hydrolysates (BLHs) (p < 0.05), confirming synergistic effects that either flavonoids, phenolic acids or tannins possess with bovine liver hydrolysates. This combination provides an effective strategy for developing novel foods with specific functions. Full article

The effects of soy protein and whey protein supplementation on glycemic control show inconsistency, and the mechanisms underlying the impact of a high-protein diet on blood glucose regulation remain unclear. This study aimed to explore the impact of a dual-protein (DP) blend comprising soy protein isolate (SPI) and whey protein concentrate (WPC), processed through high-pressure homogenization, on mice with Type 2 diabetes mellitus (T2DM) and its potential mechanisms. In the in vitro experiments, an insulin-resistant (IR) HepG2 cell model was treated with DP, resulting in a significant enhancement of glucose uptake and upregulation of IRS1 and GLUT4 expression. For the in vivo experiments, male C57BL/6J mice were randomly assigned into four groups (n = 6) based on body weight: normal control, T2DM model group, Metformin-treated group, and DP-treated group. Following a 5-week feeding period, Metformin and DP significantly reduced levels of blood sugar, AUC, TC, TG, and LDL-C in T2DM mice. Additionally, TP and ALB levels in the DP group were notably higher in the model group. In the liver and pancreas, DP alleviated histopathological changes and promoted liver glycogen synthesis in T2DM mice. Moreover, the levels of IRS1 and PI3K in the livers of mice in the DP group were significantly higher than those in the model group. Compared with the model groups, DP significantly reduced the expression of CD45 and increased the expression of CD206 in the pancreas of mice. Furthermore, 16S rRNA analysis revealed that DP altered the composition of the gut microbiota in diabetic mice, increasing the relative abundance of Lactobacillus, Parvibacter, and Lactobacillaceae. This suggested that DP could alleviate functional metabolic disorders in the gut and potentially reverse the risk of related complications. In conclusion, soy whey dual-protein may have an effective nutritional therapeutic effect on T2DM mice by regulating lipid metabolism, the INS/IRS1/PI3K signaling pathway, and gut microbiota. Full article

Background/Objectives: While the presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon aortic valve stenosis (AS) has been performed yet. The hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods: Murine wire injury (WI) to induce AS, or sham surgery, were performed prior to the 4-week assessment of AS severity, left ventricular (LV) function and hypertrophy with echocardiography (echo). Organ weights, levels of leukocytes, cytokines and costimulatory molecules in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes), and immune cell uptake of Cy5-labelled perfluorocarbon nanoemulsions were measured. Results: Trends towards correlation were found between organ weights, myocardial immune cells and echo. Cytokine mRNA levels trended mainly towards an increase in heart and regional lymph nodes and a reduction in spleen and liver, and correlation with echo was more homogeneous after WI. Unchanged cytokine protein levels in myocardium and plasma trended to correlate with echo. A homogeneous pattern was found for echo and costimulatory molecule correlation, while PFC uptake by lymphatic cells was reduced upon AS. Conclusions: The results suggest a link between number and activation state of leukocytes in peripheral organs and cardiac processes in AS. Considering the pathological value of inflammation, it is crucial that future studies investigate if a modulation of the systemic inflammatory reaction relieves severity of AS and opposes development of heart failure. Full article

Background: There is limited data on somatostatin receptor (SSTR) expression of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using modern imaging techniques and stratifying by primary site and tumor grade (G). Understanding patterns of SSTR expression and tumor heterogeneity is essential when determining the relevance of cold and radiolabeled somatostatin analog treatments. Methods: A single-institutional retrospective analysis of metastatic well-differentiated G1-3 GEP-NET patients who underwent Gallium-68 ([⁶⁸Ga])-DOTATATE or Copper-64 ([⁶⁴Cu])-DOTATATE positron emission tomography (PET) imaging from September 2016 to June 2024 was performed. Results: A total of 1192 patients were considered eligible for this study. Among them, 26 (2.2%) were completely negative on SSTR PET/computed tomography (CT), and 27 (2.3%) had weak uptake (less or equal to the normal liver). Up to 40 (3.4%) had heterogeneous SSTR expression on PET/CT: 26 (2.2%) displayed the coexistence of strongly avid lesions with the absence or near absence of SSTR uptake in measurable tumors (heterogeneous strong), while 14 (1.2%) had a combination of absent and weakly expressing SSTR tumors (heterogeneous low). An additional nine cases with prior homogeneous expression (0.8%) developed new SSTR-negative tumors along with disease progression, potentially indicating dedifferentiation. The absent or heterogeneous SSTR expression rates were greater in NET G3 than G1/G2 and in tumors originating outside the small bowel (midgut). Most NETs with absent or heterogeneous SSTR expression were fluorodeoxyglucose-F-18 ([¹⁸F]FDG)-avid. Conclusions: The large majority of metastatic GEP-NETs demonstrate strong and relatively uniform SSTR expression, but approximately 8% are SSTR-negative, weak or heterogeneous on PET/CT. Higher than average rates of absent/heterogeneous/weak SSTR expression occur in G3 NETs and lower rates among small intestine primaries. Full article

Background: Liver transplantation has become the standard of care for patients with end-stage liver disease. Despite advances in surgical techniques, immunosuppression, and perioperative care, disparities in access and outcomes persist across demographic and socioeconomic lines. Objective: To assess trends and disparities in liver transplant admissions in the United States from 2016 to 2021, examining demographic patterns, in-hospital mortality, hospital charges, length of stay, and socioeconomic factors. Methods: Using the National Inpatient Sample (NIS) from 2016 to 2021, we identified liver transplant admissions using ICD-10 PCS codes 0FY00Z1 and 0FY00Z2. Demographic characteristics (age, sex, race, insurance status, and income quartile), clinical outcomes, and resource utilization metrics were analyzed. One-way ANOVA and Hensel’s test were used to assess variance and distribution homogeneity, with a significance threshold of p < 0.05. Results: A total of 9677 liver transplant admissions were analyzed. The mean recipient age remained stable (51–52 years), with males comprising ~62% of transplants. White patients constituted the largest group of recipients (~66–68%), followed by Hispanic (~14–17%) and Black patients (~7–10%). The proportion of transplants relative to liver failure admissions remained stable across racial groups, indicating no widening racial gap during the study period. In-hospital mortality post-transplant remained low (2.37–3.52%) and did not differ significantly by race (p = 0.23), sex (p = 0.24), or income quartile (p = 0.13). Similarly, Charlson Comorbidity Index > 5 did not predict inpatient mortality (p = 0.154). Hospital charges ranged from $578,000 to $766,000, with an average stay of ~21 days. Conclusions: Liver transplantation outcomes, including in-hospital mortality, appear consistent across demographic and socioeconomic groups once patients are admitted for transplant. However, broader disparities in access persist, necessitating further research into pre-transplant barriers and long-term outcomes. These findings support the need for equitable healthcare strategies aimed at optimizing transplant candidacy and survival across all populations. Full article

Definitive endoderm (DE) differentiation leads to the development of the major internal organs including the liver, intestines, pancreas, gall bladder, prostate, bladder, thyroid, and lungs. The two primary methods utilized for in vitro differentiation of induced pluripotent stem cells (iPSCs) into DE cells are the growth factor (GF) and the small molecule (SM) approaches. The GSK-3 inhibitor (CHIR99021) is a key factor for the SM approach. Activin A and Wnt3a are utilized in the GF approach. In this study, both the GF and SM protocols were compared to each other. The results show that both the GF and SM protocol produce DE with a similar morphological phenotype, gene and protein expression, and a similar level of homogeneity and functionality. However, on both the gene expression and proteomic level, there is a divergence between the two protocols during hepatic specification. Proteomic analysis shows that hepatoblasts from the GF protocol have significantly differentially expressed proteins (DEPs) involved in liver metabolic pathways compared to the SM protocol. Well-validated DE differentiation protocols are needed to fully unlock the clinical potential of iPSCs. In the first step of generating DE-derived tissue, either protocol can be utilized. However, for hepatic specification, the GF protocol is more effective. Full article

Majority of commercial L-asparaginase (L-ASNase) activity assays are based on coupled enzymatic reaction, which converts aspartate into pyruvate, subsequently reacting with the probe to form a stable chromophore, which can be detected spectrophotometrically. However, in complex biological samples this method can be inaccurate due to poor optical transparency or presence of compounds interfering with the coupled enzyme reaction–for this kind of cases alternative methods have been suggested. Here we suggest a strategy to rationally pick a method of choice in a variety of situations, taking into consideration the upsides and downsides of each method. A high-throughput fluorometric assay employing the substrate Asp-AMC was rigorously validated for L-ASPNase activity screening. Aassay performance is evaluated in complex biological matrices, including bovine serum, whole and diluted human blood, and finally the mouse blood and liver homogenates samples obtained from pharmacokinetic studies. This comprehensive validation process ensures the reliability and applicability of the assay for assessing L-asparaginase activity in diverse and physiologically relevant environments. Potential interfering factors and matrix effects were addressed, and assay conditions were optimized for each matrix. The optimized assay was employed to screen various L-asparaginase types (intracellular L-ASNases type I RrA, periplasmic L-ASNases type II EcA and EwA) and ASPNase formulations (conjugates with polyamines or polyelectrolyte complexes), comparing their kinetic parameters and stability. Fourier-transform infrared (FTIR) spectroscopy was further employed to investigate the fine features of molecular mechanisms of L-asparaginase catalysis. FTIR spectra of Asn during hydrolysis were analyzed in buffer solutions and in complex biological matrices, such as blood sample or liver homogenates which is crucial in the context of pharmacokinetic research. This combined fluorometric and FTIR approach provides a powerful platform for optimizing L-ASNase formulations and therapeutic strategies for ALL. Based on the results obtained we have developed a strategy to choose an approach for L-Asparaginase activity assessment for a variety of difficult situations when dealing with complex biological samples. Full article

Liver fluke infections, especially those induced by Opisthorchis viverrini, pose considerable health and economic difficulties in aquaculture, particularly in Southeast Asia. Traditional approaches for parasite elimination, including chemical treatments and freezing, exhibit constraints regarding efficacy, environmental sustainability, and practicality. This research investigates an improved dielectric heating system utilizing a 2.45 GHz horn antenna for the selective thermal targeting of parasite-associated regions in Cirrhinus microlepis (small-scale mud carp). The dielectric characteristics of fish tissues, encompassing scales, skin, and muscle, were analyzed utilizing an open-ended coaxial probe technique. Simulation and experimental evaluations were performed to improve energy absorption, heating uniformity, and a particular absorption rate to enable precise thermal localization while preserving the integrity of fish tissue. The findings demonstrate that dielectric heating can specifically elevate the temperature of fish scales, where parasites predominantly inhabit, to levels beyond 70 degrees Celsius, while reducing thermal impact on the underlying muscle tissue. The application of a salt coating on fish scales markedly increased their dielectric loss, exceeding that of muscle tissue, thus enhancing selective heating efficiency and supporting targeted thermal treatment. The ideal distance from the antenna to the sample was established as ranging from 6 to 9 cm, ensuring a balance between energy efficiency and homogeneous heating. This work illustrates the efficacy of dielectric heating as a novel and non-chemical approach for thermal management of parasite-prone tissues in aquaculture, providing a sustainable and viable substitute for traditional treatments. Full article

Abroma augustum (L.) L. f. is characterized by its fibrous structure, spiny trichomes, and distinctive leaf formations, which collectively contribute to its unique morphology and potential medicinal applications. This study aims to investigate the phytochemical constituents and elucidate the pharmacognostic and physicochemical characteristics of the stem bark powder, including evaluation of its antioxidant capacity and hepatoprotective effects against carbon tetrachloride (CCl₄)-induced hepatotoxicity in both in vitro and ex vivo experimental models. Comprehensive phytochemical screening identified 50 distinct phytochemicals, including a range of alkaloids, flavonoids, terpenes, phenolics, and coumarins, among others. The extract displayed substantial solubility, with total phenolic and flavonoid content quantified as 12.32 ± 0.01 mg/g and 42.14 ± 3.5 mg/g, respectively. The antioxidant activity revealed IC₅₀ values obtained from 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), measured at 214.007 µg/mL, 132.307 µg/mL, and 45.455 µg/mL, respectively. Additionally, the methanolic extract exhibited significant hepatoprotective properties, with observable reductions in lipid peroxidation and decreased concentrations of liver damage biomarkers (ALT, AST, and LDH) in both HepG2 cells and goat liver homogenate. Future investigations are warranted to elucidate the underlying mechanisms of these effects, including histopathological examinations and biochemical assays, followed by the administration of plant methanolic extracts. Full article

Cili (Rosa roxburghii Tratt) fruit is a nutrient-rich edible plant known for its antioxidant and hepatoprotective properties. However, conventional extraction methods often lead to the degradation of its bioactive compounds. In this study, we developed a low-temperature homogenate-assisted high-pressure disruption extraction (HHPD) method to obtain a phytochemically enriched cili fruit extract (HHPD-CFE). The chemical characterization of the HHPD-CFE showed that it contained higher levels of polyphenols, polysaccharides, and superoxide dismutase (SOD) than those in conventional squeeze extraction. The hepatoprotective effects of the HHPD-CFE were evaluated in oxidative stress-induced liver injury and hepatic fibrosis models. The HHPD-CFE mitigated oxidative damage by reducing malondialdehyde while enhancing SOD and glutathione activity. Additionally, the HHPD-CFE inhibited the activation of hepatic stellate cells (HSC-T6) and reduced collagen deposition, suggesting a protective role against liver fibrosis. These findings support that the HHPD-CFE is a promising botanical extract with enriched bioactive compounds and liver-protective properties. This study supports the potential application of optimized extraction techniques to preserve thermosensitive compounds and improve the efficacy of functional foods for liver health. Full article