Search Results (1,280)

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Based on the limited hepatic hydroxylation efficiency of dietary VD3 in teleosts and the superior bioavailability of its metabolite, 25(OH)D3, this study investigated the regulatory mechanisms of dietary 25(OH)D3 supplementation in yellow catfish—an economically significant species lacking prior nutritional data on this metabolite. A total of 360 fish were divided into three groups—control (basal diet), VD3 (2500 IU/kg VD3), and 25(OH)D3 (2500 IU/kg 25(OH)D3)—and fed for 8 weeks. Compared to the control, both supplemented groups showed elevated superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), and transforming growth factor-β (TGF-β) activities, alongside reduced malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels. The 25(OH)D3 group exhibited higher T-AOC and CAT activities and lower TNF-α than the VD3 group. Metabolomic and transcriptomic analyses identified 65 differentially expressed metabolites (DEMs) and 3515 differentially expressed genes (DEGs). Enrichment analysis indicated that the DEMs (e.g., indole compounds, organic acids, aldosterone, L-kynurenine) and DEGs (pgd, mthfr, nsdhl, nox5, prdx2, mpx, itih2, itih3, eprs1) that were highly and significantly expressed in the 25(OH)D3 group were primarily associated with antioxidant defense and inflammatory responses. Dietary 25(OH)D3 was more effective than VD3 in promoting antioxidant capacity and modulating inflammation in yellow catfish. Full article

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Liver transplantation (LT) for hepatic malignancies is becoming increasingly common, largely because it offers superior survival relative to other treatment approaches. LT is well-accepted for primary liver cancers such as hepatocellular carcinoma and perihilar cholangiocarcinoma and is being increasingly accepted for intrahepatic cholangiocarcinoma and metastases of colorectal cancer or neuroendocrine tumors to the liver. Over time, indications for transplant oncology have broadened, as has the acceptable disease burden for transplantation, particularly with the advent of new neoadjuvant therapies. Other current frontiers in the field include expanding the donor pool through living donors, extended criteria donors, machine perfusion and increasing access to LT for people from disadvantaged socioeconomic backgrounds. Expanding access to LT can offer renewed hope for long-term survival to patients with primary and secondary liver cancer. Full article

Fagonia cretica, a medicinal herb from the Zygophyllaceae family, is traditionally utilized to treat various conditions such as hepatitis, gynecological disorders, tumors, urinary tract issues, and diabetes. The present study aimed to evaluate the therapeutic potential of Fagonia cretica in treating polycystic ovarian syndrome (PCOS) induced in female rats. PCOS, a complex hormonal disorder, was experimentally induced by administering Letrozole (1 mg/kg) in combination with a high-fat diet for 21 days. The affected rats were then treated with hydro-alcoholic extracts of Fagonia cretica at doses of 100 mg/kg, 200 mg/kg, and 300 mg/kg for 20 days. Key biochemical parameters—including serum testosterone, insulin, fasting blood glucose, insulin resistance (HOMA-IR), cholesterol, triglycerides, and lipoprotein levels—were measured. Ultrasound imaging and histopathological analysis of ovarian tissues were also performed. The data were analyzed using computer-based statistical tools, including one-way ANOVA, Cohen’s d effect size, and Tukey’s HSD test, with graphical representations generated using Python 3.10 on the Kaggle platform. Results demonstrated a significant reduction in serum testosterone, insulin, cholesterol, and triglyceride levels (p < 0.05) in treated groups, along with improved ovarian morphology. These findings support the therapeutic potential of Fagonia cretica as a natural treatment for PCOS. Full article

Introduction: Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) is now widely regarded as a valuable aid in decision-making for complex hepatobiliary procedures, with increasing support from recent studies. Methods: We performed a systematic review following PRISMA guidelines, utilizing PubMed, CINAHL, and EMBASE databases to locate studies on the perioperative use ICG in pediatric hepatobiliary surgeries. Two independent reviewers assessed all articles for eligibility based on predefined inclusion criteria. We collected data on study design, patient demographics, surgical indications, ICG dosing, timing of ICG injection, and perioperative outcomes. Results: Forty-three articles, including 930 pediatric patients, from 1989 to 2025 met the inclusion criteria for narrative synthesis in our systematic review, of which 22/43 (51.2%) were retrospective studies, 15/43 were case reports (34.9%), 3/43 (7.0%) were experimental studies, and the other three were prospective comparative studies (7.0%). The current clinical applications of ICG in hepatobiliary pediatric surgery include bile duct surgery (cholecystectomy, choledochal cyst, biliary atresia), reported in 17 articles (39.5%), liver tumor resection, reported in 15 articles (34.9%), liver transplantation, reported in 6 articles (14.6%), and liver function determination, reported in 5 articles (12.2%). Conclusions: ICG fluorescence navigation in pediatric hepatobiliary surgery is a highly promising and safe technology that allows for the intraoperative localization of anatomic biliary structures, aids in the identification and resection of liver tumors, and can accurately determine hepatic function. The lack of comparative and prospective studies, and the variability of the dose and timing of administration are the main limitations. Full article

A young adult patient presented to the gastrointestinal outpatient department with a suspected hepatic tumor. The patient was in a traffic accident ten years ago and underwent splenectomy and distal pancreatectomy at another medical institution. The physical examination was unremarkable. The liver function tests and tumor markers were within normal limits, with the alpha-fetoprotein level at 1.38 ng/mL. Both hepatitis B surface antigen and anti-HCV were negative. Based on the clinical history, intrahepatic splenosis was suspected first. Dynamic computed tomography revealed a 2.3 cm lesion exhibiting suspicious early wash-in and early wash-out enhancement patterns. As previous studies have reported, this finding makes hepatocellular carcinoma and metastatic lesions the major differential diagnoses. For further evaluation, dynamic magnetic resonance imaging was performed, and similar enhancing features were observed, along with restricted diffusion. As hepatocellular carcinoma still could not be confidently ruled out, the patient underwent an ultrasound-guided biopsy. The diagnosis of intrahepatic splenosis was confirmed by the pathologic examination. Intrahepatic splenosis is a rare condition defined as an acquired autoimplantation of splenic tissue within the hepatic parenchyma. Diagnosis can be challenging due to its ability to mimic liver tumors in imaging studies. Therefore, in patients with a history of splenic trauma and/or splenectomy, a high index of suspicion and awareness is crucial for accurate diagnosis and for prevention of unnecessary surgeries or interventions. Full article

The HepACAGA (Hepatic Arteriography and C-arm CT-Guided Ablation) technique, which integrates C-arm CT guidance with transcatheter C-arm CT hepatic arteriography (C-arm CTHA), significantly improves liver tumor ablation outcomes by enhancing tumor visualization, navigation, and the intraprocedural assessment of ablation margins. The two key advantages of using C-arm CT over conventional CT for image guidance are firstly that the entire procedure can be performed in the angiography suite, eliminating the need for patient transfer between the angiography suite (catheterization) and CT-room (ablation), and secondly, that integrated C-arm needle guidance software can greatly reduce the difficulty of needle placement. Beyond these advantages, the HepACAGA technique offers additional benefits across four domains: (1) the direct conversion of ablation to intra-arterial liver-directed therapies (e.g., radioembolization or chemoembolization) upon the intraprocedural detection of disease progression; (2) the direct combination of ablation with intra-arterial treatments or portal vein embolization in one session; (3) the enhanced ablation effect through heat sink effect reduction with adjunct bland embolization or balloon occlusion; and (4) the immediate hemorrhage control through direct embolization. This pictorial essay demonstrates the advantages of combining C-arm CT guidance with real-time C-arm CTHA in the percutaneous thermal ablation of liver tumors, with clinical cases illustrating each of the aforementioned four key domains. Full article

Purpose: Previous studies have reported that blood-based inflammatory markers are associated with prognosis in patients with various solid tumors, including colorectal cancer (CRC). The pan-immune inflammation value (PIV) is a novel prognostic biomarker based on blood count. Here, we aimed to study the association between PIV and survival following transarterial radioembolization (TARE) in patients with liver-dominant metastatic colorectal cancer (CLM). Methods: A total of 49 patients with CLM who underwent TARE at the Ankara University Department of Medical Oncology were retrospectively analyzed. The relationship between clinical and laboratory parameters with post-TARE overall survival (OS) was analyzed by multivariate analyses. Results: The median age was 60 years and 71.4% of patients had received at least two lines of chemotherapy. The objective response rate (ORR) was 59.1% following TARE. Patients with hepatic response after TARE treatment demonstrated significantly longer survival compared to non-responders (p: 0.033). The optimal PIV threshold value was calculated as 629 in ROC analyses. This PIV value had 81% sensitivity and 80% specificity for OS prediction (AUC 0.86; 95% CI: 0.75–0.98, p = 0.008). Patients with elevated PIV > 629 had significantly shorter OS (p = 0.002). In the multivariate analysis, adjusted for ECOG PS, TARE response, presence of extrahepatic disease, number of chemotherapy lines, CEA levels and post-TARE NLR and PIV, only low PIV level was associated with longer OS (>629 vs. ≤629; HR: 4.87; 95% CI: 1.32–17.92; p = 0.017). Conclusions: PIV, a blood-based inflammatory score, may reflect the host’s immune response following TARE and serve as a novel predictor of survival. Full article

Background: Liver cancer is a major health concern worldwide. Radiofrequency ablation is a safe treatment option that can be guided by either ultrasound, computer tomography (CT), or fluoroscopy. Although ultrasound-guided radiofrequency ablation is commonly used in clinical practice, radiofrequency ablation guided by CT is more precise but requires more time and does not offer real-time monitoring, which may result in complications such as pneumothorax or organ damage. Objectives: In this study, we investigated the effect of ultrasound, CT, and combined ultrasound/CT guidance on patient survival and complication development. Methods: A total of 982 radiofrequency ablation sessions conducted on 553 patients were analyzed. Clinical outcomes were assessed during follow-up to determine the survival and recurrence rates of malignant tumors. Results: Overall, the three guidance approaches exhibited significant differences in terms of tumor size, number, complication development, and treatment duration. However, no significant differences were observed in survival rate. A comparison of the effect of CT guidance and ultrasound guidance on complication development revealed a higher odds ratio for CT guidance in some cases. A comparison of combined ultrasound/CT guidance and ultrasound guidance revealed nonsignificant differences in complication development. A comparison of CT guidance and combined ultrasound/CT guidance revealed a higher odds ratio for CT guidance in some cases. Radiofrequency ablation is a safe and effective treatment for liver tumors. However, CT has an increased incidence of complications. Conclusions: Combined ultrasound/computer tomography guidance is recommended for patients with multiple or large tumors or tumors near the hepatic dome or diaphragm. Full article

Background/Objectives: This study aimed to evaluate adipose tissue dysfunction, assessed through adipocytokines and proinflammatory cytokines, in relation to hepatic steatosis (HS) in patients with newly diagnosed type 2 diabetes (T2D). Methods: An observational study evaluated 155 consecutive patients with new-onset T2D; 118 (76.1%) were found to have HS, while the remaining 37 served as the control group without steatosis. Anthropometric status and body mass index (BMI) were evaluated. The biochemical assessment encompassed the measurements of fasting serum lipids, fasting plasma glucose (FPG), liver function tests, adiponectin, leptin, resistin, tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Insulin resistance (IR) was determined using the homeostasis model assessment (HOMA). HS was evaluated using ultrasonographic criteria. Quantitative evaluation of HS was performed by calculating the hepatic steatosis index (HSI). Results: There were statistically significant differences between the groups for age, BMI, weight, waist circumference (WC) and hip circumference, HSI, glucose profile (fasting plasma glucose (FPG), HOMA-IR), liver function tests, adiponectin, leptin, resistin, TNF-α, and IL-6. In multivariate logistic regression analysis, age, smoking, BMI, WC, HOMA-IR, and hypoadiponectinemia were the only independent factors associated with HS. Conclusions: The adipose tissue dysfunction assessed through adipocytokines and proinflammatory cytokines is part of the associated disorders in HS and new-onset T2D. In patients with newly diagnosed T2D, age, smoking, and hypoadiponectinemia consistently emerged as independent predictors of hepatic steatosis. More prospective trials are needed to clarify the “the temporal onset” of adipose tissue dysfunction. Full article

Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of mesenchymal neoplasms with distinctive histological and immunohistochemical features. This systematic review aims to characterize the clinical presentation, diagnostic approach, treatment, and outcomes of adult patients with hepatic PEComa. Methods: We performed a systematic literature search for English-language articles regarding hepatic PEComas using the terms (perivascular epithelioid cell tumor) OR (PEComa) AND (liver) OR (hepatic), up to 25 May 2025. Results: A total of 145 studies encompassing 281 patients were included in the analysis. Most studies originated from Asia. The mean age at diagnosis was 46 years (IQR: 35.25–53.75) with a female predominance. The underlying comorbidities were uncommon among the reported cases, and more than half were asymptomatic at presentation. The tumor presented as a single liver lesion in almost 9 out of 10 patients. Surgical excision was the primary treatment, and diagnosis in 74% of patients was made with positive immunohistochemistry for markers such as HMB-45 and smooth muscle actin. A malignant phenotype was reported in 30 cases. The median follow-up duration was 24 months (IQR: 12–48); recurrence occurred in 17 patients, and disease-related mortality occurred in 8 patients. Conclusions: Primary hepatic PEComa is a rare liver tumor with mostly benign clinical behavior and non-specific presentation. Future studies are needed to support clinician decisions regarding this entity and improve patient care. Full article

Aberrant activation of Wnt/β-catenin signaling, frequently caused by oncogenic mutations, plays a crucial role in the development, progression, and therapy resistance of gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Concurrently, circular RNAs (circRNAs), produced by back-splicing of precursor mRNAs (pre-mRNAs), have emerged as critical modulators of this pathway. Accumulating evidence indicates that specific circRNAs regulate Wnt/β-catenin signaling by sponging microRNAs, interacting with RNA-binding proteins, modulating protein function, and altering the expression of pathway components. Some circRNAs are also subject to feedback regulation by Wnt signaling itself. Clinically, tumor-associated circRNAs are present in body fluids and correlate with disease stage, metastatic burden, and patient survival, underscoring their potential as early and minimally invasive biomarkers. Moreover, targeting oncogenic circRNAs has shown promise in preclinical models of Wnt-driven gastrointestinal malignancies. In this review, we summarize the current understanding of the interplay between circRNAs and Wnt/β-catenin signaling in gastric and esophageal cancers. We discuss the translational challenges and emerging opportunities for biomarker development and targeted therapy. Full article

Background: Congenital hepatic hemangiomas (CHHs) are typically considered rapidly involuting tumors, similar to their cutaneous counterparts (RICHs). However, non-involuting tumors remain poorly characterized. This study examines the evolutionary patterns and management strategies for non-involuting congenital hepatic hemangiomas (NICHHs). Methods: We conducted a retrospective review of clinical, imaging, histological, and genetic data of children diagnosed with NICHH—defined as showing no signs of involution for at least 18 months—between 1991 and 2022. Results: Seven patients (five females, two males) were identified. The median age at diagnosis was 42 days (range: 0–1440). Five patients had asymptomatic lesions, predominantly located in the right hepatic lobe. Histologic confirmation was available in three cases, and a GNAQ gene mutation was identified in one. The median follow-up period was 75 months (range: 35–191). Three patients with giant NICHH were treated with sirolimus, resulting in partial response in two cases and lesion stabilization in one. The four untreated patients showed diverse evolutionary patterns, including delayed involution and tardive growth. Conclusions: NICHH lesions demonstrate distinct long-term evolution. Accurate diagnosis and regular monitoring are essential to avoid unnecessary interventions. Sirolimus may offer a promising non-surgical treatment for select patients, particularly those with giant lesions. Full article