Search Results (7,927)

Reprogramming is a hallmark of cancer, enabling tumour cells to sustain rapid proliferation, resist cell death, and adapt to hostile microenvironments. This review explores the expression profiles of key metabolic enzymes and transporters involved in glucose, amino acid, and lipid metabolism across the five most deadly cancers worldwide: lung, breast, colorectal, liver, and gastric cancers. Through a comparative analysis, we identify consistent upregulation of glycolytic enzymes such as LDHA, PKM2, and HK2, as well as nutrient transporters like GLUT1, ASCT2, and LAT1, which contribute to cancer progression, metastasis, and therapy resistance. The role of enzymes involved in glutaminolysis (e.g., GLS1, GDH), one-carbon metabolism (e.g., SHMT2, PHGDH), and fatty acid synthesis (e.g., FASN, ACLY) is also examined, with emphasis on their emerging relevance as diagnostic, prognostic, and predictive biomarkers. While several metabolic proteins show strong potential for clinical translation, only a few, such as tumour M2-pyruvate kinase (TuM2-PK) and serum LDH measurement, have progressed into clinical use or trials. This review addresses some of the challenges in biomarker development. Ultimately, our findings underscore the importance of metabolic proteins not only as functional drivers of malignancy but also as promising candidates for biomarker discovery. Advancing their clinical implementation could significantly enhance early detection, treatment stratification, and personalized oncology. Full article

Cellular plasticity enables cells to dynamically adapt their phenotype in response to environmental cues, a process central to development, tissue repair, and disease. Among the most studied plasticity programs is epithelial–mesenchymal transition (EMT), a transcriptionally controlled process by which epithelial cells acquire mesenchymal traits. Originally described in embryogenesis, EMT is now recognized as a key driver in both tumor progression and fibrotic remodeling. In cancer, EMT and hybrid epithelial/mesenchymal (E/M) states promote invasion, metastasis, stemness, therapy resistance, and immune evasion. In fibrotic diseases, partial EMT (pEMT) contributes to fibroblast activation and excessive extracellular matrix deposition, sustaining organ dysfunction mainly in the kidney, liver, lung, and heart. This review integrates recent findings on the molecular regulation of EMT, including signaling pathways (TGF-β, WNT, NOTCH, HIPPO), transcription factors (SNAIL, ZEB, TWIST), and regulatory layers involving microRNAs and epigenetic modifications. Moreover, we discuss the emergence of pEMT states as drivers of phenotypic plasticity, functional heterogeneity, and poor prognosis. By comparing EMT in cancer and fibrosis, we reveal shared mechanisms and disease-specific features, emphasizing the translational relevance of targeting EMT plasticity. Finally, we explore how cutting-edge technologies, such as single-cell transcriptomics and lineage tracing, are reshaping our understanding of EMT across pathological contexts. Full article

The development of physiologically relevant three-dimensional (3D) culture systems is essential for modeling tumor complexity and improving the translational impact of cancer research. We established a 3D in vitro model of human hepatocellular carcinoma (HCC) using a marine collagen peptide-based (MCP-B) biomimetic hydrogel scaffold optimized for multicellular spheroid growth. Compared with conventional two-dimensional (2D) cultures, the MCP-B hydrogel more accurately recapitulated native tumor biology while offering simplicity, reproducibility, bioactivity, and cost efficiency. HCC cells cultured in MCP-B hydrogel displayed tumor-associated behaviors, including enhanced proliferation, colony formation, migration, invasion, and chemoresistance, and enriched cancer stem cell (CSC) populations. Molecular analyses revealed upregulated expression of genes associated with multidrug resistance; stemness regulation and markers; epithelial–mesenchymal transition (EMT) transcription factors, markers, and effectors; growth factors and their receptors; and cancer progression. The spheroids also retained liver-specific functions, suppressed apoptotic signaling, and exhibited extracellular matrix remodeling signatures. Collectively, these findings demonstrate that the 3D HCC model using MCP-B hydrogel recapitulates key hallmarks of tumor biology and provides a robust, physiologically relevant platform for mechanistic studies of HCC and CSC biology. This model further holds translational value for preclinical drug screening and the development of novel anti-HCC and anti-CSC therapeutics. Full article

A growing interest is focused on the efficient production of deinoxanthin (DEIX) and its use as a bioactive antioxidant. Here, we produced DEIX from Deinococcus radiodurans and examined how DEIX regulates hydrogen peroxide (H₂O₂)-mediated oxidative behaviors in mouse-derived bone marrow (BM) stromal cells and BM monocytes. We also evaluated whether oral supplementation with DEIX has radioprotective potential against total body irradiation (TBI)-mediated impairments in growth, organs, survival, and hematopoietic development using a mouse model. The direct addition of DEIX recovered H₂O₂-mediated oxidative disorders in the proliferation and the balance between osteoblast and osteoclast activity of the BM-derived cells in a dose-dependent manner. We found that recovery was closely associated with the DEIX’s potencies to remove cellular reactive oxygen species and to restore the expression of key molecules that tightly control bone homeostasis. Long-term oral supplementation with DEIX (25 mg/kg body weight, once per day for 42 consecutive days) protected mice against sub-lethal TBI (5 Gy)-mediated decreases in organ and body weights and lifespan. Supplemental DEIX also inhibited TBI-mediated structural damage in organs and restored endogenous antioxidant defense systems in the liver of TBI-exposed mice. Moreover, supplemental DEIX recovered a dysregulated hematopoietic process in TBI-exposed mice. Collectively, our results introduce an efficient method to produce DEIX and demonstrate its potency to recover oxidative cellular complication in H₂O₂-exposed BM-derived cells. Overall, our findings suggest that DEIX is a great antioxidative molecule to prevent or protect TBI-mediated systemic damages. Full article

Kupffer cells (KCs), the predominant resident macrophages in the liver, exhibit an inflammatory activation state that is pathologically linked to various hepatic disorders. Studies have shown that macrophages undergo metabolic reprogramming under inflammatory conditions, and the expressions of glucose and lipid metabolism-related factors change significantly. However, glycerol kinase (GK), as a related factor that links glycolipid metabolism, the role of GK in inflammatory conditions, and its mechanism have not been reported. The aim of the present study was to explore the role of GK in the inflammatory response of KCs. LPS challenge induced marked dysregulation of glucose and lipid metabolic profiles, accompanied by a significant elevation in GK expression in pro-inflammatory KCs. GK significantly decreased the expression of pro-inflammatory factors in LPS-treated KCs. Further studies found that GK can alleviate the level of LPS-stimulated reactive oxygen species (ROS) and the expression of antioxidant factors. Meanwhile, the results showed that GK alleviates LPS-induced KCs inflammation through inhibiting the p38/STAT3 signaling pathway. The results of this study are the first to reveal that GK may alleviate Kupffer cells’ inflammatory responses by inhibiting the p38/STAT3 signaling pathway and mitigating LPS-induced ROS generation. The findings provide a potential reference for future development of drugs targeting GK to prevent KCs inflammation and even liver damage. Full article

Obesity and metabolic syndrome (MetS), growing global health concerns, are closely linked to the development of insulin resistance, type 2 diabetes, steatotic liver disease, and cardiovascular diseases (CVDs). An increase in visceral adipose tissue, the main symptom of MetS, contributes to systemic metabolic dysfunction, resulting in disturbances in glucose and lipid metabolism, mitochondrial dysfunction, and redox imbalance, which creates a vicious cycle of inflammation and oxidative stress, accelerating comorbidities. N-acetylcysteine (NAC), a precursor to glutathione, with antioxidant and anti-inflammatory properties, is described as a potent metabolic modulator that restores metabolic homeostasis. NAC’s ability to modulate oxidative stress and inflammation may be particularly valuable in preventing or mitigating cardiovascular complications of MetS. The aim of this narrative review is to summarize current evidence from cellular, animal, and human studies on NAC’s impact on metabolic health. MetS affects nearly one-third of the global population; therefore, there is a pressing need for accessible therapeutic strategies. NAC appears to offer potential benefits as an adjunctive agent for individuals with metabolic disturbances, but further research is needed to confirm its efficacy and establish its role in clinical practice. Full article

Objectives: This study focuses on the regulatory mechanism of Schisandrin B (Sch B) on the lipid metabolism and apoptosis of AML-12 liver cells, with a particular emphasis on its potential therapeutic effect and mechanism of action in preventing and treating metabolic-associated fatty liver disease (MAFLD) by activating the PPARγ signaling pathway. Methods: An MAFLD cell model was established by inducing AML-12 cells with a mixture of oleic acid (OA) and palmitic acid (PA) (2:1). AML-12 cells were divided into a control group, a model group, and 20 μM and 40 μM Sch B groups. The cells were lysed and prepared into the cell suspension, then the cell suspension was centrifuged to obtain its supernatant, and the levels of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the supernatant were detected according to the instructions of the kits. Effects of Sch B on the pathological changes of AML-12 cells were observed by Oil Red O staining. The key targets were screened through network pharmacology, and relevant targets were verified through molecular docking simulation. The activity of PPARγ was detected using a dual luciferase reporter plasmid, and the level of cell apoptosis was detected using the Annexin V-FITC/PI double staining method. The Western blot method was used to analyze the expression of genes related to lipid metabolism and apoptosis pathways. Results: Sch B could regulate lipid metabolism disorders in OA+PA-induced MAFLD cell model. The activation of PPARγ-PCK1/Aspase is a key step in the action of Sch B, which can effectively block fatty acid synthesis, improve fatty acid oxidation, and reduce lipid droplet aggregation in liver cells, thereby alleviating lipid metabolism abnormalities in the MAFLD cell model and inhibiting cell apoptosis. Conclusions: This finding may lay an important theoretical foundation and open a new research direction for the deep development and application of Schisandra chinensis. Full article

The development of hepatic steatosis in geese is a complex, multistage process involving genes related to lipid synthesis, transport, storage, and metabolism. Key genes activated during this process include ME1 (malic enzyme 1), SCD1 (stearoyl-CoA desaturase), ACSL1 (acyl-CoA synthetase long-chain family member 1), and ELOVL6 (elongation of very-long-chain fatty acids protein 6). The expression of these genes varies depending on the tissue, breed, and metabolic context. Geese possess a unique ability to develop hepatic steatosis (fatty liver) without accompanying inflammation or liver damage. This condition typically arises from overfeeding, either through carbohydrates or fats, leading to significant triglyceride accumulation in hepatocytes. Importantly, this state remains reversible and is considered non-pathological. The physiological and molecular changes observed in overfed geese, particularly regarding liver lipid accumulation and serum enzyme activity, closely resemble those found in human non-alcoholic fatty liver disease (NAFLD). This similarity makes geese an excellent biomedical model for studying NAFLD. Overfeeding initiates a cascade of enzymatic reactions that regulate lipid metabolism at the genetic level. These reactions decrease circulating free fatty acids and glucose while promoting triglyceride storage in the liver. The aim of this study is to synthesize current knowledge on the genetic regulation of fatty acid metabolism in geese, highlighting how these genes coordinate the processes of activation, desaturation, synthesis, and elongation during induced steatosis. Moreover, the summarized effects of different diet supplements will enhance goose feeding strategies for foie gras production. Full article

Background: The aim of this study was to investigate the effects of matcha on lipid metabolism, insulin resistance (IR), inflammation, and gut dysbiosis in non-alcoholic fatty liver disease (NAFLD) induced by a cafeteria diet. Methods: Forty-eight 7-week-old male Wistar rats were divided into six groups (n = 8), including a control group (C), C + 0.2% matcha group (C + 0.2%), C + 1% matcha group (C + 1%), cafeteria group (Caf), Caf + 0.2% matcha group (Caf + 0.2%), and Caf + 1% matcha group (Caf + 1%). All rats were sacrificed at the end of the 12th week of the experiment. A one-way analysis of variance (ANOVA), followed by a Fisher’s post hoc test, was used to determine the significant differences among each of the groups. Results: The results indicated that plasma experiment triglycerides (TGs) significantly increased in the Caf group compared to the C group, and significantly decreased TG levels were found in the Caf + 1% group compared to the Caf group. In addition, the liver total cholesterol and TG had significantly increased in the Caf group, while the 0.2% Matcha intervention can mitigate hepatic lipid accumulation. Blood sugar, serum insulin, the homeostasis model assessment of IR (HOMA-IR), and plasma leptin significantly increased in the Caf group and were significantly lower in the Caf + 0.2% and Caf + 1% groups. Hepatic cytokines significantly increased in the Caf group, while, on the other hand, significantly lower concentrations were found in the Caf + 1% group. In addition, beneficial bacteria including Akkermansia, Faecalibacterium, and Parabacteroides increased after matcha supplementation. Conclusions: These results suggested that 12 weeks of a cafeteria diet can induce abnormal lipid metabolism, IR, liver inflammation, and an altered gut microbiotic composition, while both the 0.2% and 1% matcha interventions might regulate obesity, lipid accumulation, IR, and inflammatory responses, and help maintain a healthier gut microbiota, which may then ameliorate the development of NAFLD. Full article

Background/Objectives: Ethnopharmacological studies indicates that plant-based infusions are usually consumed by some people in advanced stages of diabetes, that is, when poor pancreatic dysfunction coexists with insulin resistance (IR). Current treatments aim to prevent β-cell deterioration by promoting improved insulin function and/or enhancing pancreatic function to avoid the development of hyperglycemia. Therefore, Croton guatemalensis (Cg) and Eryngium cymosum (Ec), two medicinal plants with potential insulin-sensitizing effects described in previous studies, were assessed on parameters related to IR and on the architecture of pancreatic islets in rats exposed to a syrup containing 8.8% glucose and 5.2% fructose in drinking water. Methods: After an 8-week exposure to syrup, plant extracts were orally administered for four weeks at traditional doses (Cg: 30 mg/kg body weight; Ec: 470 mg/kg body weight). Body weight, food intake, and drinking water consumption were monitored. At the end of the study, IR surrogate indices were calculated, metabolic assays were performed, and white adipose tissues, liver, gastrocnemius muscle, and pancreas were extracted in fasting and postprandial state for lipid quantification (liver), measurement of Akt phosphorylation status by western blot (liver and muscle), and determination of insulin content by immunohistochemistry (pancreatic islets). Results: Both species decreased hepatic lipid content without promoting significant changes in visceral adiposity. Although they did not improve surrogate markers of fasting IR, both ameliorated insulin function, glucose tolerance, and restored the glucose-stimulated insulin secretory response in metabolic tests. Cg restored the insulin signaling response in liver and muscle, whereas Ec only did so in muscle. Moreover, both appeared to enhance insulin pancreatic content or restore pancreatic islet population. Conclusions: Cg and Ec can reverse the IR phenotype in a tissue-specific manner and improve pancreatic function. Full article

Background/Objectives: Multiple criteria are used worldwide to select hepatocellular carcinoma (HCC) patients with a low risk of recurrence for liver transplantation (LT). However, it remains unclear which criteria are best for the LT-involved stakeholders, particularly in accurately identifying patients at high risk of recurrence. This work aimed to identify the most accurate criteria for selecting HCC patients for LT. Methods: In June 2023, a systematic literature search was conducted in PubMed and CENTRAL to identify studies including LT selection criteria of HCC patients. Data was extracted from recurrence-free survival curves using a validated algorithm and subsequently used to calculate measures of diagnostic performance routinely used in clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were applied. Results: Of 815 records screened, only 17 met our study inclusion parameters, embodying 14 LT selection criteria. All LT criteria achieved an adjusted positive predictive value (aPPV) over 80%, indicating the correct selection of at least 80% of low-risk HCC patients. However, the adjusted negative predictive value (aNPV) was below 50% in most cases, indicating that these criteria cannot correctly identify patients with a true high risk of recurrence. This raises major ethical concerns regarding the models’ ability to exclude patients from LT. Since a perfect model is nonexistent, we created a ranking to account for the distinct concerns of all stakeholders in LT eligibility in the context of HCC. Conclusions: These results highlight the urgent need for refined or newly developed criteria with improved specificity and NPV to select more patients amenable to LT who are currently excluded. Full article

We review the latest development in non-angiogenic tumours. We focused on the last 3 years except the rarer tumours, for which the papers are older. Following the explanation of the modified hallmark of cancer, inducing angiogenesis and/or accessing vessels, the authors review primary and metastatic tumours growing into lung, liver and brain, plus oral cancer, lymphomas and node metastasis. Also progress in treatment, not many unfortunately, and techniques in non-angiogenic tumours are discussed. Full article

Introduction: Mn is a trace element essential for growth and development in organisms, and adequate Mn levels are crucial for maintaining normal liver function. This study aimed to investigate the effects of Mn deficiency on the liver and elucidate the underlying mechanisms using transcriptomics. Methods: Weanling mice were fed a Mn-deficient diet, and Mn chloride (MnCl₂) was administered intraperitoneally to correct the deficiency. Liver pathological changes were evaluated through histological examination. Liver function and key lipid metabolism markers were assessed using biochemical assays, while hepatic oxidative stress levels were measured via flow cytometry and biochemical kits. Alterations in inflammatory factors were detected using ELISA and qPCR. The mechanisms underlying Mn’s effects on liver function were further explored through Western blot, qPCR, and transcriptome sequencing. Results: Mn deficiency impaired liver morphology and structure. Serum levels of ALT, AST, and ALP were significantly elevated, while ALB decreased, confirming hepatic dysfunction. This dysfunction led to oxidative stress, characterized by increased hepatic ROS and MDA levels, alongside reduced Mn-SOD, GSH-Px, and T-AOC activities. Additionally, Mn deficiency elevated serum TG, TC, and LDL-C levels, indicating abnormal lipid metabolism. Hepatic pro-inflammatory factors (IL-6, IL-1β, and TNF-α) were significantly upregulated. Transcriptomic analysis revealed distinct gene expression patterns under different Mn conditions, with KEGG pathway analysis identifying the PPAR signaling pathway as a key regulatory target. Conclusions: Our findings suggest a potential pathogenic cascade in which manganese deficiency may initially induce hepatic oxidative stress, potentially leading to suppression of the PPAR signaling pathway. This inhibition of PPARα/γ could subsequently orchestrate downstream manifestations of aberrant lipid metabolism and inflammatory responses. Thus, the PPAR signaling pathway is proposed as a plausible central hub for translating oxidative damage into metabolic and inflammatory dysfunction in the manganese-deficient liver. Full article

Background: Childhood obesity has reached epidemic levels in developed countries and is an emerging concern in developing regions. Children with excess weight are more likely to maintain this condition over time into adulthood and face a higher risk of developing metabolic disorders such as type 2 diabetes, hypertension, metabolic dysfunction-associated liver disease, and dyslipidemia. Early identification of obesity risk is, therefore, a key public health challenge. Methods: This is an observational, prospective, single-center cohort pilot study in 66 mother–infant dyads recruited at the Gynecology and Obstetrics Service of the Virgen de la Arrixaca University Hospital (Murcia, Spain). The primary objective is to identify early-life, non-invasive biomarkers associated with increased adiposity by integrating multi-omics approaches and analyzing maternal–infant interactions. Pregnant women will be enrolled during the third trimester and will undergo a baseline visit at 38 weeks of gestation for clinical and anthropometric assessment. Buccal swabs and fecal samples will be collected at baseline and in the peripartum period for epigenetic (DNA methylation), metagenomic, and metabolomic analyses. Infants will be evaluated at birth and followed at 6 months, 1 year, 2 years, and 3 years. Each visit will include detailed anthropometric measurements, along with collection of buccal swabs and fecal samples for multi-omics profiling. Conclusions: This multidisciplinary study aims to assess how maternal factors influence infant epigenetic and microbial patterns, and their relation to adiposity development. Early identification of such biomarkers may guide personalized prevention strategies and reduce the long-term burden of obesity-related comorbidities. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health burden, affecting millions and contributing significantly to liver-related morbidity and mortality. While substantial progress has been made in elucidating the virology and natural history of HBV, the management of chronic hepatitis B (CHB) continues to present clinical challenges. The development of potent nucleos(t)ide analogs and pegylated interferon has improved viral suppression and delayed disease progression, yet a definitive cure remains elusive due to the persistence of covalently closed circular DNA (cccDNA). Recent research has focused on novel antiviral agents, immunomodulatory therapies, and combination strategies aimed at achieving a functional cure. This review summarizes current therapeutic approaches, recent advancements, and emerging directions in CHB management. Full article