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World Journal of Hepatology May 2024Non-alcoholic fatty liver disease (NAFLD) poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits. Its complexity stems... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits. Its complexity stems from genetic predisposition, environmental influences, and metabolic factors. Epigenetic processes govern various cellular functions such as transcription, chromatin structure, and cell division. In NAFLD, these epigenetic tendencies, especially the process of histone methylation, are intricately intertwined with fat accumulation in the liver. Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis. While early-stage NAFLD is reversible, its progression to severe stages becomes almost irreversible. Therefore, early detection and intervention in NAFLD are crucial, and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.
PubMed: 38818286
DOI: 10.4254/wjh.v16.i5.703 -
World Journal of Hepatology May 2024The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease...
The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease (MASLD). Insulin resistance, subclinical inflammation, dyslipidemia, obesity, and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD, which includes hepatocellular carcinoma, advanced fibrosis/cirrhosis, and non-alcoholic steatohepatitis (NASH). A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus (GDM). Women with a history of GDM had a higher chance of developing NASH, according to a recent study that used a large-scale database. Although the precise etiology is yet unknown, temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation, affecting distant organs including the liver. Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.
PubMed: 38818285
DOI: 10.4254/wjh.v16.i5.860 -
World Journal of Hepatology May 2024Wilson disease (WD) is a progressive, potentially fatal degenerative disease affecting the liver and central nervous system. Given its low prevalence, collecting data on...
BACKGROUND
Wilson disease (WD) is a progressive, potentially fatal degenerative disease affecting the liver and central nervous system. Given its low prevalence, collecting data on large cohorts of patients with WD is challenging. Comprehensive insurance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases.
AIM
To describe patients with WD in the United States, their treatment and clinical outcome, using a large insurance claims database.
METHODS
This retrospective, longitudinal study was performed in the Clarivate Real-World Data Product database All patients with ≥ 2 claims associated with an International Classification of Diseases 10 (ICD-10) diagnostic code for WD (E83.01) between 2016 and 2021 were included and followed until death or study end. Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD. Clinical manifestations, hospitalisations, liver transplantation and death were documented.
RESULTS
Overall, 5376 patients with an ICD-10 diagnostic code for WD were identified. The mean age at inclusion was 41.2 years and 52.0% were men. A specific WD treatment was documented for 885 patients (15.1%), although the number of patients taking zinc salts may be underestimated due to over the counter purchase. At inclusion, the mean age of patients with a documented treatment was 36.6 ± 17.8 years 42.2 ± 19.6 years in those without a documented treatment. During follow-up, 273 patients (5.1%) died. Compared with the American general population, the standardised mortality ratio was 2.19. The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0% and the mean age at death 52.7 years.
CONCLUSION
Patients treated for WD in the United States had an excess early mortality compared with the American population. These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.
PubMed: 38818282
DOI: 10.4254/wjh.v16.i5.791 -
Journal of Cancer 2024Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate...
Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate in the pathogenesis and development of multiple cancers and are aberrantly overexpressed in various types of cancer. This study aimed to develop a CTA-related gene signature (CTARSig) to predict prognosis in STAD patients and explore its underlying mechanisms. We performed differential and prognostic analyses of CTA-related genes and constructed a CTA-related signature (CTARSig) along with a novel nomogram to predict the prognosis of patients with STAD based on the Cox and The Least Absolute Shrinkage and Selection Operator. CTARSig was further validated in an external cohort (GSE84437). Additionally, univariate and multivariate Cox regression, as well as receiver operating characteristic (ROC) analyses, were performed to assess the CTARSig systematically. Single-sample gene set enrichment analysis and ESTIMATE were used to characterise the Tumor Immune Microenvironment (TIME) in patients with STAD. Furthermore, Gene Set Variation Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses revealed the biological functions and signalling pathways associated with CTARSig. Finally, the human gastric cancer cell lines, HCG-27 and AGS, were used for and experiments, respectively, to further validate the role of ELOVL4. Eleven CTA-related genes were identified to construct the CTARSig. Kaplan-Meier curves, independent prognostic analysis, and ROC curves revealed that CTARSig could better predict survival in patients with STAD. Moreover, in our study, we demonstrated that ELOVL4 is upregulated in gastric cancer tissues and that its high expression is associated with poor survival. Additionally, and experiments demonstrated that ELOVL4 promotes the metastatic and invasive potential of STAD cells, suggesting it may be a potential therapeutic target for STAD. In this study, a novel signature associated with CTAs was constructed for STAD, which may be a good predictor of patient prognosis. Thus, ELOVL4 may be a potential therapeutic target for gastric cancer. This study provides new insights into the potential roles of CTAs in gastric cancer.
PubMed: 38817874
DOI: 10.7150/jca.91842 -
Journal of Cancer 2024Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are primary liver cancers with different therapeutic methods and prognoses. This study aims to...
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are primary liver cancers with different therapeutic methods and prognoses. This study aims to investigate the ultrasonography and enhanced computed tomography (CT) features of these cancers and improve the early diagnosis rate. We retrospectively analyzed the clinical and imaging data of 319 patients diagnosed with HCC and 124 patients diagnosed with ICC, confirmed by pathology. A total of 443 patients were eligible in this study. From the perspective of clinical data, between HCC and ICC patients existed significant differences in age, gender, hepatic background, serum tumor markers of AFP and CA19.9, chronic hepatitis B/C and lymph node infiltration (p<0.05), but not in tumor size, microvascular invasion, serum tumor markers of CEA and CA125 (P>0.05). With respect to ultrasonography features, HCC patients had a higher proportion than ICC patients in splenomegaly (p=0.001), while ICC patients had a higher proportion than HCC patients in absence/not rich vascularity and intrahepatic bile duct dilatation (p<0.05). With respect to CT features, HCC patients were significantly different from ICC patients in the three-phase enhanced CT value mean, enhanced intensity and homogeneity of nodules (P<0.05). A multivariate logistic regression analysis was performed to further clarify the correlation of these indices. However, only age≤60 years (OR=1.861, P=0.045), male (OR=3.850, P<0.001), AFP>7ng/ml (OR=0.119, P<0.001), lymph node infiltration (OR=5.968, P<0.001), intrahepatic bile duct dilatation (OR=2.414, P=0.04), splenomegaly (OR=0.081, P<0.001), rim APHE (OR=3.109, P=0.002), and iso- or hyper enhancement (OR=0.188, P<0.001) were independent risk factors. While there are overlapping ultrasonography and CT features between HCC and ICC, the integration of tumor markers and specific imaging characteristics can be beneficial in distinguishing between the two.
PubMed: 38817871
DOI: 10.7150/jca.94550 -
World Journal of Gastroenterology May 2024Hepatocellular carcinoma (HCC) is a high mortality neoplasm which usually appears on a cirrhotic liver. The therapeutic arsenal and subsequent prognostic outlook are... (Review)
Review
Hepatocellular carcinoma (HCC) is a high mortality neoplasm which usually appears on a cirrhotic liver. The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis. Notwithstanding the current deployment of treatments with curative intent (liver resection/local ablation and liver transplantation) in early and intermediate stages, a high rate of HCC recurrence persists, underscoring a pivotal clinical challenge. Emergent systemic therapies (ST), particularly immunotherapy, have demonstrate promising outcomes in terms of increase overall survival, but they are currently bound to the advanced stage of HCC. This review provides a comprehensive analysis of the literature, encompassing studies up to March 10, 2024, evaluating the impact of novel ST in the early and intermediate HCC stages, specially focusing on the findings of neoadjuvant and adjuvant regimens, aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent. We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent. Finally, we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Neoplasm Staging; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Immunotherapy; Hepatectomy; Liver Transplantation; Treatment Outcome; Chemotherapy, Adjuvant; Prognosis
PubMed: 38817666
DOI: 10.3748/wjg.v30.i19.2512 -
World Journal of Gastroenterology May 2024Cell division cyclin 25C () is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research...
BACKGROUND
Cell division cyclin 25C () is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research has shown that could be a potential therapeutic target for cancers, particularly for hepatocellular carcinoma (HCC). However, the specific regulatory mechanisms underlying the role of in HCC tumorigenesis and development remain incompletely understood.
AIM
To explore the impact of on cell proliferation and apoptosis, as well as its regulatory mechanisms in HCC development.
METHODS
Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences (LV- shRNA) to knock down . Subsequently, a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into mice to assess the effects of knockdown on HCC development . Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays, respectively. The expression of endoplasmic reticulum (ER) stress-related molecules (glucose-regulated protein 78, X-box binding protein-1, and C/EBP homologous protein) was measured in both cells and subcutaneous xenografts using quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, apoptosis was investigated using flow cytometry, qRT-PCR, and western blotting.
RESULTS
was stably suppressed in Hepa1-6 and B16 cells through LV- shRNA transduction. A xenograft model with knockdown was successfully established and that downregulation of expression significantly inhibited HCC growth in mice. knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response, ultimately promoting ER stress-induced apoptosis in HCC cells.
CONCLUSION
The regulatory mechanism of in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.
Topics: Animals; Endoplasmic Reticulum Stress; Carcinoma, Hepatocellular; Cell Proliferation; cdc25 Phosphatases; Apoptosis; Liver Neoplasms; Cell Line, Tumor; Mice; Gene Knockdown Techniques; Cell Movement; Mice, Inbred C57BL; Humans; RNA, Small Interfering; Male; Gene Expression Regulation, Neoplastic; Xenograft Model Antitumor Assays; Carcinogenesis
PubMed: 38817663
DOI: 10.3748/wjg.v30.i19.2564 -
World Journal of Gastroenterology May 2024Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality. This particular type of cancer has the distinctive characteristic of mostly... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality. This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease. This makes the management of patients more challenging, since physicians must take into consideration two different conditions, the chronic liver disease and the tumor. The underlying liver disease has several implications in clinical practice, because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC, obstacles in surveillance, and differences in the efficacy of the treatment against HCC. A shift in the prevalence of liver diseases has been evident over the last few years, with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance. Therefore, in an era of personalized medicine, it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Risk Factors; Prevalence; Precision Medicine; Liver Diseases; Liver
PubMed: 38817660
DOI: 10.3748/wjg.v30.i19.2488 -
World Journal of Gastroenterology May 2024Variceal bleed represents an important complication of cirrhosis, with its presence reflecting the severity of liver disease. Gastric varices, though less frequently...
Variceal bleed represents an important complication of cirrhosis, with its presence reflecting the severity of liver disease. Gastric varices, though less frequently seen than esophageal varices, present a distinct clinical challenge due to its higher intensity of bleeding and associated mortality. Based upon the Sarin classification, GOV1 is the most common subtype of gastric varices seen in clinical practice.
Topics: Esophageal and Gastric Varices; Humans; Gastrointestinal Hemorrhage; Liver Cirrhosis; Treatment Outcome; Severity of Illness Index
PubMed: 38817659
DOI: 10.3748/wjg.v30.i19.2615 -
World Journal of Gastroenterology May 2024The role of exosomes derived from HepG2.2.15 cells, which express hepatitis B virus (HBV)-related proteins, in triggering the activation of LX2 liver stellate cells and...
BACKGROUND
The role of exosomes derived from HepG2.2.15 cells, which express hepatitis B virus (HBV)-related proteins, in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell proliferation remains elusive. The focus was on comprehending the relationship and influence of differentially expressed microRNAs (DE-miRNAs) within these exosomes.
AIM
To elucidate the effect of exosomes derived from HepG2.2.15 cells on the activation of hepatic stellate cell (HSC) LX2 and the progression of liver fibrosis.
METHODS
Exosomes from HepG2.2.15 cells, which express HBV-related proteins, were isolated from parental HepG2 and WRL68 cells. Western blotting was used to confirm the presence of the exosomal marker protein CD9. The activation of HSCs was assessed using oil red staining, whereas DiI staining facilitated the observation of exosomal uptake by LX2 cells. Additionally, we evaluated LX2 cell proliferation and fibrosis marker expression using 5-ethynyl-2'-deoxyuracil staining and western blotting, respectively. DE-miRNAs were analyzed using DESeq2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to annotate the target genes of DE-miRNAs.
RESULTS
Exosomes from HepG2.2.15 cells were found to induced activation and enhanced proliferation and fibrosis in LX2 cells. A total of 27 miRNAs were differentially expressed in exosomes from HepG2.2.15 cells. GO analysis indicated that these DE-miRNA target genes were associated with cell differentiation, intracellular signal transduction, negative regulation of apoptosis, extracellular exosomes, and RNA binding. KEGG pathway analysis highlighted ubiquitin-mediated proteolysis, the MAPK signaling pathway, viral carcinogenesis, and the toll-like receptor signaling pathway, among others, as enriched in these targets.
CONCLUSION
These findings suggest that exosomes from HepG2.2.15 cells play a substantial role in the activation, proliferation, and fibrosis of LX2 cells and that DE-miRNAs within these exosomes contribute to the underlying mechanisms.
Topics: Humans; Exosomes; Hepatic Stellate Cells; Cell Proliferation; Hep G2 Cells; Liver Cirrhosis; MicroRNAs; Hepatitis B virus; Signal Transduction; Liver
PubMed: 38817658
DOI: 10.3748/wjg.v30.i19.2553