Fat mass and obesity-associated protein (FTO) has been linked to various cancers, though its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate FTO expression, its clinical relevance, functional role in HCC progression, and the underlying molecular mechanisms.

Quantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis were used to assess FTO expression in HCC. Functional assays, including proliferation, invasion, and epithelial-mesenchymal transition studies, were conducted using HCC cell lines with FTO knockdown. N6-methyladenosine (m6A) RNA immunoprecipitation and RNA stability assays further elucidated the role of FTO in BUB1 mRNA methylation and stability. Co-immunoprecipitation studies were employed to confirm the interaction between BUB1 and TGF-βR1. In vivo studies in nude mice were conducted to evaluate tumor growth following FTO knockdown.

FTO was significantly upregulated in HCC tissues compared to normal liver tissues, with higher expression observed in advanced tumor-node-metastasis stages and metastatic HCC. Elevated FTO correlated with poor overall survival in patients. Silencing FTO decreased HCC cell proliferation, colony formation, invasion, epithelial-mesenchymal transition, and tumor growth in nude mice. Mechanistically, FTO downregulation led to increased m6A modification of BUB1 mRNA, thereby promoting its degradation via the YTH domain family 2-dependent pathway and reducing BUB1 protein levels. Additionally, BUB1 physically interacted with TGF-βR1, activating downstream TGF-β signaling.

FTO is overexpressed in HCC and is associated with poor clinical outcomes. Mechanistically, FTO promotes HCC progression by stabilizing BUB1 mRNA through an m6A-YTH domain family 2–dependent pathway, which activates TGF-β signaling. Targeting the FTO–BUB1–TGF-βR1 regulatory network may offer a promising therapeutic strategy for HCC.

Patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) are at high risk of bleeding with traditional artificial liver support systems. To address the bleeding risk in liver failure patients, the safety of regional mesylate anticoagulation (RMA) in centrifugation artificial liver support systems (cALSS) is proposed for study.

In this prospective single-arm study, ALF and ACLF patients were treated with cALSS using RMA. Coagulation function was monitored, and the predictors of mesylate dose were analyzed using the area under the curve (AUC). Blood ammonia, model for end-stage liver disease scores, and survival rates at 28 and 90 days were assessed.

All 57 patients showed no new bleeding within 24 h post-cALSS. Most disseminated intravascular coagulation indicators improved at 0.5 h and 24 h post-cALSS. Thromboelastography showed hypocoagulability at 0.5 h post-cALSS. Univariate and multivariate analyses identified pre-R and pre-MA as key factors for R exceeding 10 m at 0.5 h post-cALSS, with odds ratios of 0.91 (95% confidence interval (CI): 0.84–0.98) and 2.03 (95% CI: 1.05–3.90), respectively, P < 0.05. The predictive values were pre-MA ≤ 38 mm (AUC = 0.817, 95% CI [0.690–0.907], P < 0.001) and pre-R > 6.3 m (AUC = 0.790, 95% CI [0.661–0.888], P < 0.001). Patients showed improvements in blood ammonia and model for end-stage liver disease scores after the last session, especially those with high initial levels (>80 µmol/L and >30). The 28-day and 90-day survival rates of ALF patients were similar to those of ACLF patients.

cALSS with RMA is safe for liver failure patients with a high risk of bleeding. Adjusting the mesylate dose based on pre-R and pre-MA enhances safety.

Inherited metabolic liver diseases (IMLDs) have complex etiologies and vary widely in clinical presentation, with a significant overall incidence. With the advancements in diagnostic and treatment technologies, an increasing number of children with inherited metabolic diseases are surviving into adolescence and adulthood. These advancements have improved our understanding of the IMLD disease spectrum and clinical outcomes. This study aimed to analyze changes in the disease spectrum and epidemiological characteristics of inherited metabolic liver diseases (IMLD) over the past 20 years in two specialized liver disease hospitals in northern China.

A retrospective analysis was conducted on IMLD cases diagnosed between January 1, 2002, and December 31, 2023, at two liver disease specialty hospitals in Beijing. Data were obtained from inpatient and outpatient hospital information systems, with diagnoses based on national and international IMLD diagnosis and treatment guidelines.

A total of 2,103 IMLD patients were analyzed, including 1,213 adults and 890 children. IMLD accounted for 4.58‰ of hospitalized liver disease patients during this period. The most common IMLD was Wilson’s disease, comprising 68% of all IMLD cases. The number of diagnosed IMLD types increased from 15 to 32 across two 11-year periods (2002–2012 and 2013–2023). Among pediatric patients, glycogen storage disease and Alagille syndrome were more prevalent in those under one year of age, while Wilson’s disease was prevalent across all age groups. In adult IMLD patients, Wilson’s disease, polycystic liver disease, and hereditary hyperbilirubinemia were more frequently observed.

Over the past 20 years, both the number of diagnosed IMLD cases and disease diversity have significantly increased, with Wilson’s disease remaining the most prevalent IMLD. These findings provide valuable insights for the long-term management of IMLD patients and the allocation of healthcare resources.

Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs.

We report a case of a 45-year-old male with human immunodeficiency virus infection who presented with abdominal pain and vomiting. Imaging studies revealed minimal bilateral ground-glass opacities in the lungs, hepatosplenomegaly, and diffuse lymphadenopathy. A bronchoscopy with bronchoalveolar lavage cytology evaluation showed abundant macrophages containing numerous intracellular organisms with characteristic dot-like kinetoplasts, confirming the diagnosis of Leishmaniasis. Special stains for other infections were negative.

This case highlights the value of bronchoalveolar lavage cytology in diagnosing non-neoplastic lung pathologies, including parasitic infections like Leishmaniasis, thereby enabling prompt and targeted treatment.

Actively identifying the risk factors and predictive indicators associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) can enable early diagnosis and treatment, which is of great significance for prolonging the survival of patients with LC. Hemodynamic disturbances, advanced LC, vascular endothelial injury, and mutations in thrombophilic genetic factors are established risk factors for PVT-LC. Venous dilatation and decreased blood flow velocity contribute to hemodynamic disturbances. The severity of LC can be assessed by the degree of portal hypertension, liver metabolic function biomarkers, and validated liver scoring systems. Iatrogenic interventions, endotoxemia, and metabolic syndrome may induce vascular endothelial injury and hypercoagulability, the latter of which can be quantified via coagulation-anticoagulation-fibrinolysis biomarkers. Mutations in thrombophilic genetic factors, such as Factor V Leiden, MTHFR C667T, and JAK2 V617F, disrupt coagulation-anticoagulation homeostasis and predispose patients to PVT-LC. This review specifically focuses on comprehensively delineating established risk factors and predictive indicators for PVT-LC, thereby providing a theoretical foundation for the construction of clinically applicable PVT predictive models to guide early interventions and improve the prognosis. Future research should further validate the associations between recently proposed risk factors and PVT-LC, while simultaneously establishing cutoff values for indicators with robust predictive value to construct a clinically applicable PVT prediction framework.

Glioblastoma is the most common primary tumor of the central nervous system, characterized by an infiltrative growth pattern, which results in the most unfavorable prognosis. The average survival time of patients after diagnosis of this tumor is typically several months, with complete recovery from glioma being very rare. In recent years, significant involvement of exosomes in the development of cancer, including malignant brain tumors, has been discovered. Exosomes are extracellular vesicles that carry signaling molecules and participate in communication between cells. They influence cell survival, proliferation, migration, and increased neoangiogenesis, all of which significantly contribute to tumor recurrence. Molecules carried by exosomes are considered potential diagnostic markers, enabling early diagnosis of cancer and prompt implementation of appropriate treatment. Of particular diagnostic importance are microRNA molecules, which promote increased cell proliferation and inhibition of apoptosis. Equally important exosomal transmitters include proteins such as PSMD2 and EGFR, which enhance tumor invasiveness and resistance to chemotherapeutic agents. Recent studies suggest the possibility of using exosomes as carriers for new anticancer drugs, potentially improving the therapeutic treatment of cancers resistant to standard treatment methods. This review aimed to provide a comprehensive analysis of recent research on glioblastoma, the role of exosomes in its progression, the potential of exosomes as diagnostic biomarkers, and their use as therapeutic targets for patients who have not responded to conventional treatments.

This study investigates upper gastrointestinal tract (UGIT) involvement in patients with ulcerative colitis (UC), a condition traditionally considered limited to the colon. Although extra-colonic manifestations of UC are well recognized, UGIT issues have received less attention. This research aimed to document the clinical, endoscopic, and histopathological UGIT findings in adults with UC and assess their association with disease severity and extent.

This descriptive cross-sectional study was conducted at Ain Shams University over one year. A total of 78 UC patients underwent comprehensive clinical evaluations, including assessments of gastrointestinal complaints, medication history, disease progression, surgeries, and physical examinations. Endoscopic assessments of both the UGIT and colon were performed, accompanied by biopsies for histopathological analysis.

The study population had a mean age of 35.26 years, with a nearly equal gender distribution. Endoscopic findings revealed significant UGIT involvement: 64% of patients had esophagitis and/or gastroesophageal reflux disease, 93% had gastritis, and 80% had duodenitis. Histopathological findings showed notable inflammation, basal cell hyperplasia, and ulcerations in the esophagus, with 51.3% of patients exhibiting chronic gastritis and 38.5% testing positive for Helicobacter pylori infection. Statistical analysis demonstrated a strong association between colonic disease severity and UGIT endoscopic (p < 0.0001 and p < 0.001 in the esophagus and stomach, respectively) and histopathological (p < 0.004, p < 0.001, and p <0.005 in the esophagus, stomach, and duodenum, respectively) findings, particularly in patients with UGIT symptoms.

This study concludes that UGIT endoscopic and histopathological changes are prevalent among Egyptian UC patients, suggesting a significant link between UC and these UGIT findings.

Hepatic biliary adenofibroma is an exceedingly rare biliary neoplasm that primarily affects adults. It typically presents as a solitary mass composed of low-grade microcystic and tubuloglandular bile duct structures, which are lined by low columnar to cuboidal non-mucin-producing biliary epithelium and supported by abundant fibrous stroma. Histologically, it resembles the Von Meyenburg complex but is much larger in size and often shows cytologic atypia. Although considered benign, emerging case studies and analyses suggest that biliary adenofibroma may serve as a precursor lesion to intrahepatic cholangiocarcinoma. However, its extreme rarity, coupled with an incompletely understood histogenesis, perpetuates diagnostic uncertainty and may lead to misclassification with other similar entities. This review consolidates the current understanding of the histopathological and molecular characteristics of biliary adenofibroma, highlights its differential diagnosis, explores its potential progression to cholangiocarcinoma, and discusses unresolved questions while proposing future research directions.

Neurodegenerative diseases (NDs) represent a major global health challenge in aging populations, with their incidence continuing to rise worldwide. Although substantial progress has been made in elucidating the clinical features and molecular underpinnings of these disorders, the precise mechanisms driving neurodegeneration remain incompletely understood. This review examines the increasing significance of the gut–brain–immune triad in the pathogenesis of NDs, with particular attention to Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. It explores how disruptions in gut microbiota composition and function influence neuroinflammation, blood–brain barrier integrity, and immune modulation through microbial-derived metabolites, including short-chain fatty acids, lipopolysaccharides, and bacterial amyloids. In both Alzheimer’s and Parkinson’s diseases, a reduced abundance of short-chain fatty acid-producing bacterial taxa has been consistently associated with heightened pro-inflammatory signaling, thereby facilitating disease progression. Although detailed mechanistic understanding remains limited, experimental evidence—primarily from rodent models—indicates that microbial metabolites derived from a dysbiotic gut may initiate or aggravate central nervous system dysfunctions, such as neuroinflammation, synaptic dysregulation, neuronal degeneration, and disruptions in neurotransmitter signaling via vagal, humoral, and immune-mediated pathways. The review further highlights how gut microbiota alterations in amyotrophic lateral sclerosis and multiple sclerosis contribute to dysregulated T cell polarization, glial cell activation, and central nervous system inflammation, implicating microbial factors in disease pathophysiology. In addition to identifying critical knowledge gaps, the review emphasizes the need for sustained, multifactorial research efforts, including the development of physiologically relevant brain–gut organoid models and the implementation of standardized experimental protocols. A major limitation in the field remains the difficulty of establishing causality, as clinical manifestations often arise after extended preclinical phases—lasting years or decades—during which aging, dietary patterns, pharmacological exposures, environmental factors, and comorbidities collectively modulate the gut microbiome. Finally, the review discusses how microbial influences on host epigenetic regulation may offer innovative avenues for modulating neuroimmune dynamics, underscoring the therapeutic potential of targeted microbiome-based interventions in neurodegenerative diseases.

The importance of putative folate-biopterin metabolic interactions lies in the role they may play in the expression of several clinically relevant phenotypes. However, to date, clinical studies on folate-biopterin interactions have been limited. The purpose of this article was to highlight the close relationship between these two cofactors, which share structural similarities and exhibit overlapping metabolic pathways. This folate-biopterin crosstalk has generated several ideas and hypotheses that are critical to advancing the biochemical understanding of several important and seemingly disparate clinical and/or biologically important phenotypes. These phenotypes include melanization/pigmentation, phenylketonuria, autism, neural tube defects, affective disorders, and vascular disease. This review provides a timely, integrated overview of this important area of biochemistry, which is under-represented in the literature and would benefit from further scientific and clinical investigation using improved metabolite-specific analytical methodologies applied to clinically relevant questions.