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Clinical and Molecular Hepatology May 2024
PubMed: 38768960
DOI: 10.3350/cmh.2024.0372 -
Molecular Nutrition & Food Research May 2024Hepatocellular carcinoma (HCC) results from various etiologies, such as Hepatitis B and C, Alcoholic and Non-alcoholic fatty liver disorders, fibrosis, and cirrhosis.... (Review)
Review
SCOPE
Hepatocellular carcinoma (HCC) results from various etiologies, such as Hepatitis B and C, Alcoholic and Non-alcoholic fatty liver disorders, fibrosis, and cirrhosis. About 80 to 90% of HCC cases possess cirrhosis, which is brought on by persistent liver inflammation. TGF-β is a multifunctional polypeptide molecule that acts as a pro-fibrogenic marker, inflammatory cytokine, immunosuppressive agent, and pro-carcinogenic growth factor during the progression of HCC. The preclinical and clinical evidence illustrates that TGF-β can induce epithelial-to-mesenchymal transition, promoting progression and hepatocyte immune evasion. Therefore, targeting the TGF-β pathway can be a promising therapeutic option against HCC.
METHODS AND RESULTS
We carry out a systemic analysis of eight potentially selected culinary Indian spices: Turmeric, Black pepper, Ginger, Garlic, Fenugreek, Red pepper, Clove, Cinnamon, and their bioactives in regulation of the TGF-β pathway against liver cancer.
CONCLUSION
Turmeric and its active constituent, curcumin, possess the highest therapeutic potential in treating inflammation-induced HCC and they also have the maximum number of ongoing in-vivo and in-vitro studies.
PubMed: 38766929
DOI: 10.1002/mnfr.202300793 -
World Journal of Clinical Cases May 2024Hepatic epithelioid angiomyolipoma (HEA) has a low incidence and both clinical manifestations and imaging lack specificity. Thus, it is easy to misdiagnose HEA as other...
BACKGROUND
Hepatic epithelioid angiomyolipoma (HEA) has a low incidence and both clinical manifestations and imaging lack specificity. Thus, it is easy to misdiagnose HEA as other tumors of the liver, especially in the presence of liver diseases such as hepatitis cirrhosis. This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis, and analyzed the literature, in order to improve the understanding of this disease.
CASE SUMMARY
A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver. Based on the patient's history, laboratory examinations, and imaging examinations, a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed. Postoperative pathology showed HEA. During outpatient follow-up, the patient showed no sign of recurrence.
CONCLUSION
HEA is difficult to make a definite diagnosis before surgery. HEA has the potential for malignant degeneration. If conditions permit, surgical treatment is recommended.
PubMed: 38765741
DOI: 10.12998/wjcc.v12.i14.2382 -
Phytomedicine : International Journal... Jul 2024Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic...
BACKGROUND
Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer.
PURPOSE
We aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR).
METHODS
Autodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets.
RESULTS
BA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro.
CONCLUSION
BA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.
Topics: Animals; Receptors, Cytoplasmic and Nuclear; Liver Diseases, Alcoholic; Inflammasomes; Male; Mice; Mice, Inbred C57BL; Disease Models, Animal; Liver; DNA-Binding Proteins; Ethanol
PubMed: 38763006
DOI: 10.1016/j.phymed.2024.155693 -
Oncogene Jun 2024Non-alcoholic steatohepatitis (NASH) is rapidly surpassing viral hepatitis as the primary cause of hepatocellular carcinoma (HCC). However, understanding of...
Non-alcoholic steatohepatitis (NASH) is rapidly surpassing viral hepatitis as the primary cause of hepatocellular carcinoma (HCC). However, understanding of NASH-progressed HCC remains poor, which might impede HCC diagnosis and therapy. In this study, we aim to identify shared transcriptional changes between NASH and HCC, of which we focused on E3 ligase TRIM45. We found TRIM45 exacerbates HCC cells proliferation and metastasis in vitro and in vivo. Further transcriptome analysis revealed TRIM45 predominantly affects fatty acid metabolism and oleic acid restored impaired proliferation and metastasis of TRIM45-deficient HCC cells. IP-tandem mass spectrum and FABP5 depriving experiment indicated that TRIM45 enhance fatty acid synthesis depending on FABP5 presence. Interestingly, we found TRIM45 directly added K33-type and K63-type poly-ubiquitin chains to FABP5 NLS domain, which ultimately promoted FABP5 nuclear translocation. Nuclear FABP5 interacted with PPARγ to facilitate downstream lipid synthesis gene expression. We observed TRIM45 accelerated NASH-to-HCC transition and exacerbated both NASH and NASH-HCC with the enhanced fatty acid production in vivo. Moreover, high concentration of fatty acid increased TRIM45 expression. The established mechanism was substantiated by gene expression correlation in TCGA-LIHC. Collectively, our research revealed a common lipid reprograming process in NASH and HCC and identified the cyclical amplification of the TRIM45-FABP5-PPARγ-fatty acid axis. This signaling pathway offers potential therapeutic targets for therapeutic intervention in NASH and NASH-progressed HCC.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Fatty Acid-Binding Proteins; Non-alcoholic Fatty Liver Disease; Animals; Fatty Acids; Mice; Ubiquitination; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Ubiquitin-Protein Ligases; Disease Progression
PubMed: 38755308
DOI: 10.1038/s41388-024-03056-7 -
Drug Metabolism and Disposition: the... May 2024
PubMed: 38754961
DOI: 10.1124/dmd.118.080523err -
Journal of Translational Medicine May 2024Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma.... (Comparative Study)
Comparative Study
BACKGROUND
Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases.
METHODS
In this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases.
RESULTS
Glycan traits bisection (OR: 3.78 [1.88-9.35], p-value: 5.88 × 10), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75-5.16], p-value: 1.63 × 10), IgG1 galactosylation (OR: 0.35 [0.2-0.58], p-value: 3.47 × 10) and hybrid type glycans (OR: 2.73 [1.67-4.89], p-value: 2.31 × 10) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity.
CONCLUSIONS
Compared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.
Topics: Humans; Hepatitis, Autoimmune; Female; Male; Polysaccharides; Middle Aged; Glycosylation; Case-Control Studies; Immunoglobulin G; Liver Diseases; Adult; Cross-Sectional Studies; Aged
PubMed: 38745252
DOI: 10.1186/s12967-024-05173-z -
Cureus Apr 2024This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation...
This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation excluded alternative etiologies, pinpointing sinusoidal non-cirrhotic portal hypertension. Present therapeutic modalities for AH, including steroids and pentoxifylline, offer limited efficacy, necessitating ongoing investigation. Liver transplantation may be contemplated in refractory cases. This case underscores the intricate nature of AH presentations and the challenges in their management, emphasizing the imperative need for continued research to delineate optimal therapeutic strategies. Early intervention remains pivotal in addressing AH complications, underscoring the need for heightened clinical vigilance and proactive treatment approaches in such cases.
PubMed: 38741864
DOI: 10.7759/cureus.58187 -
Biochemistry and Biophysics Reports Jul 2024The purpose of this study was to examine the effect of pemafibrate in a murine model of non-alcoholic steatohepatitis (NASH).
AIM
The purpose of this study was to examine the effect of pemafibrate in a murine model of non-alcoholic steatohepatitis (NASH).
METHODS
Forty-two, 19-week-old, male, C57BL/6J mice were divided into three groups: a Control group (n = 14), a dextran sulfate sodium (DSS) group (n = 14), and a DSS + PEM group (n = 14). All mice were given a standard rodent diet for the first week, followed by a choline-deficient, high-fat diet (CDHF) for the next 12 weeks. The 22nd day after the animals arrived was taken as Day 1 of the experiment. The Control group continued the CDHF diet and MilliQ water. The DSS group continued the CDHF diet, but starting on Day 1, the group received 0.8 % DSS to drink for 7 consecutive days, followed by MilliQ water for 10 days; this was taken as one course, and it was repeated on the same schedule until autopsy. The DSS + PEM group received the CDHF diet with PEM 0.1 mg/kg/day. Their drinking water was the same as that of the DSS group. On Seven animals from each group were autopsied on each of Day 50 and Day 120, and histopathological and immunohistochemical examinations, as well as quantitative RNA and cytokine measurements, of autopsied mice were performed.
RESULTS
Pemafibrate improved hepatic steatosis (decreased steatosis area), improved liver inflammation enhanced by DSS (decreased aspartate transaminase and alanine aminotransferase), improved hepatic fibrosis promoted by DSS (decreased fibrotic areas and a marker of fibrosis), inhibited tumorigenesis, and decreased intestinal inflammation in the NASH model mice.
CONCLUSIONS
In a murine model of NASH, mixing PEM 0.1 mg/kg/day into the diet inhibited disease progression and tumor formation.
PubMed: 38737727
DOI: 10.1016/j.bbrep.2024.101724 -
Food Science & Nutrition May 2024Liver diseases, encompassing conditions such as cirrhosis, present a substantial global health challenge with diverse etiologies, including viral infections, alcohol... (Review)
Review
Liver diseases, encompassing conditions such as cirrhosis, present a substantial global health challenge with diverse etiologies, including viral infections, alcohol consumption, and non-alcoholic fatty liver disease (NAFLD). The exploration of natural compounds as therapeutic agents has gained traction, notably the herbal remedy milk thistle (), with its active extract, silymarin, demonstrating remarkable antioxidant and hepatoprotective properties in extensive preclinical investigations. It can protect healthy liver cells or those that have not yet sustained permanent damage by reducing oxidative stress and mitigating cytotoxicity. Silymarin, a natural compound with antioxidant properties, anti-inflammatory effects, and antifibrotic activity, has shown potential in treating liver damage caused by alcohol, NAFLD, drug-induced toxicity, and viral hepatitis. Legalon® is a top-rated medication with excellent oral bioavailability, effective absorption, and therapeutic effectiveness. Its active component, silymarin, has antioxidant and hepatoprotective properties, Eurosil 85® also, a commercial product, has lipophilic properties enhanced by special formulation processes. Silymarin, during clinical trials, shows potential improvements in liver function, reduced mortality rates, and alleviation of symptoms across various liver disorders, with safety assessments showing low adverse effects. Overall, silymarin emerges as a promising natural compound with multifaceted hepatoprotective properties and therapeutic potential in liver diseases.
PubMed: 38726410
DOI: 10.1002/fsn3.4010