Mulberry leaf extract inhibits obesity and protects against diethylnitrosamine-induced hepatocellular carcinoma in rats DOI Creative Commons

Yun‐Ching Chang,

Meng-Hsun Yu,

Hui‐Pei Huang

et al.

Journal of Traditional and Complementary Medicine, Journal Year: 2024, Volume and Issue: 14(3), P. 266 - 275

Published: Jan. 22, 2024

Mulberry leaf has been recognized as a traditional Chinese medicinal plant, which was distributed throughout the Asia. The aqueous extract of mulberry (MLE) various biologically active components such polyphenols and flavonoids. However, inhibitory effect MLE in hepatocarcinogenesis is poorly understood. In this study, we determined role supplementation preventing carcinogen-initiated high-fat diet (HFD)-promoted Sprague-Dawley (SD) rat model. rats were fed an HFD to induce obesity spontaneous hepatomas by administering 0.01% diethylnitrosamine (DEN) their drinking water for 12 weeks (HD group), also through oral ingestion at daily doses 0.5%, 1%, or 2%. At end 12-week experimental period, liver tumors analyzed identify markers oxidative stress antioxidant enzyme activities, serum determine nutritional status function. Histopathological analysis revealed that significantly suppressed severity incidence hepatic tumors. Furthermore, compared with + DEN groups, expression protein kinase C (PKC)-α Rac family small GTPase 1 (Rac1) lower groups. These findings suggest prevents obesity-enhanced, carcinogen-induced hepatocellular carcinoma development, potentially (PKC)α/Rac1 signaling pathway. might be effective chemoprevention modality nonalcoholic fatty disease (NAFLD)/nonalcoholic steatohepatitis (NASH)-related hepatocarcinogenesis.

Language: Английский

Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients DOI Open Access
Mona A. Eldosoky, Reham Hammad, Asmaa A. Elmadbouly

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3157 - 3157

Published: Feb. 5, 2023

Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens-(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p-expression levels a panel of biomarkers in chronic hepatitis C virus (CHCV) liver cirrhosis (LC), especially AFP-negative cases, step toward non-protein coding (nc) RNA precision medicine.79 enrolled CHCV infection LC, subclassified into an LC group without (n = 40) 39). Real-time quantitative PCR was used measure hsa-miR-21-5p, hsa-miR-199a-5p.Plasma hsa-miR-21-5p hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p downregulation the 39) when compared 40). expression positively correlated serum AFP, insulin, insulin resistance (r 0.5, p < 0.001, r 0.334, 0.01, 0.303, 0.02, respectively). According ROC curves, differentiating from combining AFP each miR199a-5p improved diagnostic sensitivity 87%, 82%, 84%, respectively, vs. 69% alone, acceptable specificities 77.5%, 80%, AUC 0.89, 0.85, 0.90, respectively 0.85 alone. hsa-miR-21-5p/hsa-miR-199a-5p hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated at 0.76 0.71, sensitivities 94% 92% 48% 53%, respectively. Upregulation considered independent risk factor development [OR 1.198(1.063-1.329), 0.002].Combining made it possible identify patients' cohort higher than using are markers patients. linked, clinically via silico proof, metabolism, inflammation, dyslipidemia, tumorigenesis well upregulated emergence

Language: Английский

Citations

55

Clinical Applications of Artificial Intelligence (AI) in Human Cancer: Is It Time to Update the Diagnostic and Predictive Models in Managing Hepatocellular Carcinoma (HCC)? DOI Creative Commons
Mario Romeo, Marcello Dallio, Carmine Napolitano

et al.

Diagnostics, Journal Year: 2025, Volume and Issue: 15(3), P. 252 - 252

Published: Jan. 22, 2025

In recent years, novel findings have progressively and promisingly supported the potential role of Artificial intelligence (AI) in transforming management various neoplasms, including hepatocellular carcinoma (HCC). HCC represents most common primary liver cancer. Alarmingly, incidence is dramatically increasing worldwide due to simultaneous “pandemic” spreading metabolic dysfunction-associated steatotic disease (MASLD). MASLD currently constitutes leading cause chronic hepatic damage (steatosis steatohepatitis), fibrosis, cirrhosis, configuring a scenario where an onset has been reported even early stage. On other hand, serious plague, significantly burdening outcomes hepatitis B (HBV) C (HCV) virus-infected patients. Despite progress this cancer, overall prognosis for advanced-stage patients continues be poor, suggesting absolute need develop personalized healthcare strategies further. “cold war”, machine learning techniques neural networks are emerging as weapons, able identify patterns biomarkers that would normally escaped human observation. Using advanced algorithms, AI can analyze large volumes clinical data medical images (including routinely obtained ultrasound data) with elevated accuracy, facilitating diagnosis, improving performance predictive models, supporting multidisciplinary (oncologist, gastroenterologist, surgeon, radiologist) team opting best “tailored” individual treatment. Additionally, contribute enhancing effectiveness metabolomics–radiomics-based promoting identification specific HCC-pathogenetic molecules new targets realizing therapeutic regimens. era precision medicine, integrating into routine practice appears promising frontier, opening avenues cancer research

Language: Английский

Citations

2

Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD) DOI Creative Commons
Paria Zarghamravanbakhsh,

Michael Frenkel,

Leonid Poretsky

et al.

Metabolism Open, Journal Year: 2021, Volume and Issue: 12, P. 100149 - 100149

Published: Nov. 16, 2021

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that was first described in 1980. It has been prevalent and on the rise for many years associated with other disorders such as obesity type 2 diabetes mellitus (T2DM). NAFLD can be best dysfunction stems from insulin resistance-induced hepatic lipogenesis. This lipogenesis increases oxidative stress inflammation often potentiated by genetic gut microbiome dysfunction. As progresses simple steatosis to non-alcoholic steatohepatitis (NASH) cirrhosis hepatocellular carcinoma (HCC), odds of complications including cardiovascular (CVD), chronic kidney (CKD), overall mortality increase. The aim this review describe causes consequences while examining risks each stage poses. In review, etiology "lean" NAFLD, impact obesity, T2DM, genetics, dysbiosis progression are all explored. will also discuss core issue behind NAFLD: resistance (IR). Upon describing effectiveness diet modification, lifestyle changes, glucagon-like peptide 1 receptor (GLP-1) agonists retard stem rate examined.

Language: Английский

Citations

87

MAFLD enhances clinical practice for liver disease in the Asia-Pacific region DOI Creative Commons
Takumi Kawaguchi, Tsubasa Tsutsumi, Dan Nakano

et al.

Clinical and Molecular Hepatology, Journal Year: 2021, Volume and Issue: 28(2), P. 150 - 163

Published: Nov. 10, 2021

Fatty liver is now a major cause of disease in the Asia-Pacific region. Liver diseases this region have distinctive characteristics. First, fatty frequently observed lean/normal-weight individuals. However, there no standard definition unique phenotype. Second, often patients with concomitant viral hepatitis. The exclusion hepatitis from non-alcoholic limits its value and detracts investigation holistic management coexisting Third, liver-associated hepatocellular carcinoma (HCC) generally categorized as non-B non-C HCC. Fourth, population aging rapidly, it imperative to develop practicable, low-intensity exercise program for elderly patients. Fifth, most nonspecialized healthcare professionals still lack an awareness significance both terms intrahepatic extrahepatic cancer. Recently, international expert panel proposed new liver: metabolic dysfunction-associated (MAFLD). One feature MAFLD that dysfunction prerequisite diagnosis. Pertinent regional issues, also provides diagnostic criteria Furthermore, independent any disease, including Therefore, may be more suitable In review, we introduce characteristics discuss advantages improving clinical practice

Language: Английский

Citations

76

Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets DOI Creative Commons

Yinshuang Chen,

Weipeng Wang, Maria P. Morgan

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 8, 2023

Obesity is a global epidemic and overwhelming evidence indicates that it risk factor for numerous cancers, including hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. Obesity-associated hepatic tumorigenesis develops from nonalcoholic fatty liver disease (NAFLD), progressing to steatohepatitis (NASH), cirrhosis ultimately HCC. The rising incidence obesity resulting in an increased prevalence NAFLD NASH, subsequently represents increasingly important underlying etiology HCC, particular as other causes HCC such hepatitis infection, are declining due effective treatments vaccines. In this review, we provide comprehensive overview molecular mechanisms cellular signaling pathways involved pathogenesis obesity-associated We summarize preclinical experimental animal models available study features NAFLD/NASH/HCC, non-invasive methods diagnose NAFLD, NASH early-stage Finally, since aggressive tumor with 5-year survival less than 20%, will also discuss novel therapeutic targets ongoing clinical trials.

Language: Английский

Citations

31

Metabolomics in hepatocellular carcinoma: From biomarker discovery to precision medicine DOI Creative Commons

Xingyun Wu,

Zihao Wang,

Li Luo

et al.

Frontiers in Medical Technology, Journal Year: 2023, Volume and Issue: 4

Published: Jan. 4, 2023

Hepatocellular carcinoma (HCC) remains a global health burden, and is mostly diagnosed at late advanced stages. Currently, limited insensitive diagnostic modalities continue to be the bottleneck of effective tailored therapy for HCC patients. Moreover, complex reprogramming metabolic patterns during initiation progression has been obstructing precision medicine in clinical practice. As noninvasive screening approach, metabolomics serves as powerful tool dynamically monitor identify promising metabolite biomarkers, therefore holds great potential development In this review, we summarize recent advances studies, including alterations associated with progression, well novel biomarkers diagnosis, monitor, prognostic evaluation. highlight application multi-omics strategies containing biomarker discovery HCC. Notably, also discuss opportunities challenges nowadays medicine. technologies improving discovering, made major step toward more timely

Language: Английский

Citations

24

Complement 3a receptor 1 on macrophages and Kupffer cells is not required for the pathogenesis of metabolic dysfunction-associated steatotic liver disease DOI Creative Commons
Edwin A. Homan, Ankit Gilani, Alfonso Rubio‐Navarro

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 8, 2025

Together with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system infiltration macrophages has been linked to progression disease. The role receptors in macrophage activation recruitment MASLD remains poorly understood. In human mouse, C3AR1 expressed primarily Kupffer cells, but downregulated humans compared obese controls. To test 3a receptor (C3aR1) on resident MASLD, we generated mice deficient C3aR1 all (C3aR1-MφKO) or specifically cells (C3aR1-KpKO) subjected them model We show that account for vast majority C3ar1 expression liver. Overall, C3aR1-MφKO C3aR1-KpKO have similar body weight gain without significant alterations glucose homeostasis, hepatic steatosis fibrosis, controls MASLD-inducing diet. This study demonstrates deletion predominant cell expressing , no effect steatosis, inflammation fibrosis dietary model.

Language: Английский

Citations

1

Arctiin attenuated NASH by inhibiting glycolysis and inflammation via FGFR2/CSF1R signaling DOI

Yeliu Fu,

Xiaolin Li,

Yuanyuan Zeng

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177424 - 177424

Published: Feb. 1, 2025

Language: Английский

Citations

1

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future DOI Open Access

João Paulo Margiotti dos Santos,

Mariana Canevari de Maio,

Monike Alves Lemes

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(1), P. 498 - 498

Published: Jan. 2, 2022

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% patients non-alcoholic fatty liver disease (NAFLD). Due to dysfunction numerous metabolic changes that commonly accompany condition (obesity, insulin resistance, type 2 diabetes, syndrome), secretion organokines modified, which may contribute pathogenesis progression disease. In this sense, study aimed perform a review role in NASH. Thus, combining descriptors such as NASH, organokines, oxidative stress, dyslipidemia, search was carried out EMBASE, MEDLINE-PubMed, Cochrane databases articles published last ten years. Insulin inflammation mitochondrial dysfunction, fructose, intestinal microbiota were factors identified participating genesis Changes pattern (adipokines, myokines, hepatokines, osteokines) directly indirectly aggravating compromise homeostasis. further studies involving skeletal muscle, adipose, bone, tissue endocrine organs are essential better understand modulation involved NASH advance treatment

Language: Английский

Citations

38

Terpenoids: Natural Compounds for Non-Alcoholic Fatty Liver Disease (NAFLD) Therapy DOI Creative Commons

Pengyu Yao,

Yajuan Liu

Molecules, Journal Year: 2022, Volume and Issue: 28(1), P. 272 - 272

Published: Dec. 29, 2022

Natural products have been the most productive source for development of drugs. Terpenoids are a class natural active with wide range pharmacological activities and therapeutic effects, which can be used to treat variety diseases. Non-alcoholic fatty liver disease (NAFLD), common metabolic disorder worldwide, results in health burden economic problems. A literature search was conducted obtain information relevant treatment NAFLD terpenoids using electronic databases, namely PubMed, Web Science, Science Direct, Springer, period 2011-2021. In total, we found 43 NAFLD. Over dozen terpenoid compounds origin were classified into five categories according their structure: monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, tetraterpenoids. We that play role NAFLD, mainly by regulating lipid metabolism disorder, insulin resistance, oxidative stress, inflammation. The AMPK, PPARs, Nrf-2, SIRT 1 pathways main targets treatment. promising drugs will potentially create more opportunities However, current studies restricted animal cell experiments, lack clinical research systematic structure-activity relationship (SAR) studies. future, should further enrich on mechanism terpenoids, carry out SAR research, increase likelihood breakthrough insights field.

Language: Английский

Citations

36