To evaluate the efficacy of ultrasound-guided percutaneous microwave ablation (PMA) combined with portal vein embolization (PVE) for planned hepatectomy.
We retrospectively reviewed data of 18 ...patients with multiple right liver tumors or hilar tumor of liver invades the surrounding tissue and insufficient future liver remnant (FLR) for hepatectomy from July 2015 to March 2017. Ultrasound-guided PMA was performed by using PMCT cold circulation microwave treatment apparatus. PVE was performed after PMA. The increase of FLR was evaluated by computed tomography (CT) 6-22 days after PVE. The proportion of FLR, increase in the amplitude of FLR, procedure-related complications, perioperative morbidity and mortality, and overall survival (OS) rates, the median survival time were analyzed.
The median volume of FLR before PMA and PVE was 369.7 ml (range: 239.4-493.1 ml). After a median waiting period of 11.5 days (range: 6-22 days), the median volume of FLR was increased to 523.4 ml (range: 355.4-833.3 ml). The changes in FLR before and after PMA and PVE were statistically significant (
<0.001). No serious perioperative complications or mortality were found. After a median follow-up time of 51.0 months (range: 2-54 months), the 6-month, 1-year, 2-year, 3-year and 4-year survival rates were 88.9%, 72.2%, 44.4%, 33.3%, 22.2%, respectively, and the median survival time was 15.0 ± 7.1 months.
PMA combined with PVE increases FLR rapidly, avoids touching malignant tumors, and produces fewer procedure-related complications. It appears safe and efficacious for planned hepatectomy.
Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two ...sorafenib‐resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC.
What's new?
Sorafenib, a kinase inhibitor, is one of the most effective drugs available for the treatment of hepatocellular carcinoma (HCC). Its use, however, is limited by acquired resistance. The present study shows that the expression of PFKFB3, a gene involved in glycolytic flux that encodes 6‐phosphofructo‐1‐kinase 2 (PFK2), is strongly associated with sorafenib resistance in HCC cells. PFK is a suspected target of aspirin, a drug associated with reduced HCC risk. Experiments in cells and animals reveal the existence of a synergistic antitumor effect between aspirin and sorafenib, suggesting that sorafenib‐resistant HCC patients may benefit from combined treatment with aspirin.
Objective
Hepatocellular carcinima is one of the most common tumors in clinic and also one of the leading causes of death from cancer worldwide. Quercetin shows significant effects on blocking the ...development of various cancers.
Methods
We used the human hepatocellular carcinoma LM3 and nude mice tumor model to assess the effects of quercetin in hepatocellular carcinoma and clarify its mechanism of action. We collected LM3 cell line treated with different doses of quercetin at different time periods and determined the vital indexes. The liver tissues of mice were collected and used for western boltting (WB), Hematoxylin and Eosin (H&E) and TUNEL staining.
Results
Results indicated that quercetin suppressed the Hepatocellular carcinoma (HCC) growth both in vivo and in vitro. Quercetin could disturb LM3 cells proliferation and cell cycle distribution, thus inducing apoptosis. At the same time, quercetin inhibited LM3 cells migration and invasion and promoted HCC autophagy. These effects at least partly depended on the down‐regulation of the activation of JAK2 and STAT3 by quercetin.
Conclusion
Quercetin inhibited hepatocellular carcinoma progression by modulating cell apoptosis, migration, invasion, and autophagy; and its effects were at least partly related with the JAK2/STAT3 signaling pathway.
Hepatocellular carcinima is one of the most common tumors in clinic. Our research showed that quercetin inhibited hepatocellular carcinoma progression by modulating cell apoptosis, metastasis, and autophagy via the JAK2/STAT3 signaling pathway.
Objective
Non-alcoholic fatty liver disease (NAFLD) can be attributed to the dysregulation of hepatic lipid metabolism; however, its cellular and molecular mechanisms remain unclear. This study aims ...to explore the effect of long non-coding RNA growth arrest specific 5 (GAS5) on hepatic lipid metabolism in fatty liver models.
Methods
Obese mice, high fat diet-fed mice and free fatty acid-stimulated cells were used for GAS5 expression detection. GAS5 overexpression or knockdown models were established to elucidate the regulatory function of GAS5 in
de novo
lipogenesis (DNL) and mitochondrial function. Bioinformatic analyses and dual luciferase assays were used to investigate the interaction between GAS5, miR-26a-5p and phosphodiesterase (PDE) 4B. The involvement of the cyclic adenosine monophosphate (cAMP)/cAMP-response element-binding protein (CREB) pathway was evaluated using H89 and forskolin treatment.
Results
GAS5 was activated
in vitro
and
in vivo
fatty liver models. Knockdown of GAS5 reduced lipid droplet accumulation, DNL associated enzymes and preserved mitochondrial function, while GAS5 overexpression exacerbated hepatic lipid accumulation. Mechanistically, GAS5 sponged miR-26a-5p to increase PDE4B expression and subsequently modulated DNL and mitochondrial function
via
the cAMP/CREB pathway.
Conclusion
Downregulation of GAS5 can activate the cAMP/CREB pathway through miR-26a-5p/PDE4B axis to mitigate hepatic lipid accumulation. This study provides evidence that downregulation of GAS5 may be a potential therapeutic option for the treatment of NAFLD.
Ghrelin is a stomach-derived growth hormone secretagogue that promotes various physiological effects, including energy metabolism and amelioration of inflammation. The purpose of this study was to ...investigate the protective mechanism of ghrelin against liver fibrosis. Liver fibrosis was induced in C57BL/6 mice by intraperitoneal injection of CCl₄ (2.0 mL/kg of 10% CCl₄ v/v solution in peanut oil) two times per week for eight weeks. Ghrelin (10 μg/kg) was intraperitoneally injected two times per week for eight weeks. A second murine liver fibrosis model was induced by bile duct ligation (BDL) and concurrent ghrelin administration for four weeks. Hematoxylin eosin (H&E), and Masson's trichrome were used to detect pathological changes to liver tissue. Western blotting was used to detect protein levels of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), I-collage, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, phosphorylated NF-κB (p-NF-κB), and microtubule-associated protein light chain 3 (LC3). In addition, qRT-PCR was used to detect mRNA levels of TGF-β1, I-collage, α-SMA, MMP2, TIMP1 and LC3, while levels of TGF-β1, p-Smad3, I-collage, α-SMA, and LC3 were detected immunohistochemically. Levels of aspartate aminotransferase and alanine aminotransferase were significantly decreased by ghrelin treatment. Ghrelin administration also significantly reduced the extent of pathological changes in both murine liver fibrosis models. Expression levels of I-collage and α-SMA in both models were clearly reduced by ghrelin administration. Furthermore, ghrelin treatment decreased protein expression of TGF-β1 and p-Smad3. The protein levels of NF-κB and LC3 were increased in the CCl₄- and BDL-treatment groups but were significantly reduced following ghrelin treatment. In addition, ghrelin inhibited extracellular matrix formation by decreasing NF-κB expression and maintaining the balance between MMP2 and TIMP1. Our results demonstrated that ghrelin attenuates liver fibrosis via inhibition of the TGF-β1/Smad3 and NF-κB signaling pathways, as well as autophagy suppression.
Abstract Bacground Ghrelin has been shown to exert various biological functions. However, the effect and mechanism of ghrelin on PA- or LPS-induced liver injury remains unknown. Methods Normal human ...hepatocyte lines (LO2 and 7701) were pretreated with ghrelin (10−8 M) for 30 min before stimulation with lipopolysaccharide (LPS) or palmitic acid (PA). The proliferation and apoptosis of cells were detected with CCK8, Hoechst staining and flow cytometric analysis. Levels of NO of cell supernatants were examined by enzyme-linked immunosorbent assay (ELISA). The protein levels and mRNA of target genes of endothelial NOS (eNOS) and inducible NOS (iNOS) were measured by western blotting, immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Bax, Bcl2, caspase 3, p-Akt, p-P38 and p-JNK were detected by western blotting. Results Results of CCK8, Hoechst staining and flow cytometric analysis showed that ghrelin-pretreatment attenuated LPS- or PA- induced cellular proliferation inhibition and apoptosis induction. ELISA results revealed that ghrelin pretreatment reduced levels of NO of cell supernatants (P < 0.05). Results of western blotting and immunofluorescence showed that protein levels of iNOS in ghrelin- pretreated group were significantly reduced compared with LPS- or PA- treated group, while protein levels of eNOS were restored by ghrelin pretreatment. Results of qRT-PCR showed that mRNA levels of Bax, iNOS were reduced by ghrelin pretreatment, while levels of mRNA of Bcl2 and eNOS were increased (P < 0.05). The protein levels of pAkt were significantly increased by ghrelin pretreatment, while the protein levels of p-JNK, p-P38 and caspase 3 were reduced. The restoration of eNOS could be reversed by an Akt inhibitor. Conclusions Ghrelin pretreatment attenuated LPS- or PA-induced hepatocyte apoptosis, which may least partly via inhibition of mitogen-activated protein kinases (MAPKs)/iNOS and restoration of Akt/eNOS pathways.
The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is continuously rising, evolving into a global health challenge. Concurrently, cases of hepatocellular carcinoma ...(HCC) associated with MASLD are also on the increase. Although traditional risk factors such as age, gender, and metabolic factors play significant roles in the development of HCC, it cannot be overlooked that MASLD, triggered by changes in modern lifestyle and dietary habits, may also exacerbate the risk of HCC, and this phenomenon is common even among non-obese individuals. Regrettably, MASLD often fails to receive timely diagnosis, resulting in a limited number of patients receiving HCC surveillance. Moreover, there is currently a lack of clear definition for the target population for surveillance beyond patients with cirrhosis. Consequently, MASLD-related HCC is often detected at a late stage, precluding the optimal timing for curative treatment. However, our understanding of the pathogenesis and progression of HCC remains limited. Therefore, this paper reviews relevant literature from recent years, delving into multiple dimensions such as pathogenesis, surveillance and diagnosis, prevention, and treatment, aiming to provide new ideas and directions for the prevention and treatment of MASLD-related HCC.
Improving catalytic activity and durabilty through the structural and compositional development of bifunctional electrocatalysts with low cost, high activity and stability is a challenging issue in ...electrochemical water splitting. Herein, we report the fabrication of heterostructured P-CoMoO4@NiCoP on a Ni foam substrate through interface engineering, by adjusting its composition and architecture. Benefitting from the tailored electronic structure and exposed active sites, the heterostructured P-CoMoO4@NiCoP/NF arrays can be coordinated to boost the overall water splitting. In addition, the superhydrophilic and superaerophobic properties of P-CoMoO4@NiCoP/NF make it conducive to water dissociation and bubble separation in the electrocatalytic process. The heterostructured P-CoMoO4@NiCoP/NF exhibits excellent bifunctional electrocatalysis activity with a low overpotential of 66 mV at 10 mA cm−2 for HER and 252 mV at 100 mA cm−2 for OER. Only 1.62 V potential is required to deliver 20 mA cm−2 in a two-electrode electrolysis system, providing a decent overall water splitting performance. The rational construction of the heterostructure makes it possible to regulate the electronic structures and active sites of the electrocatalysts to promote their catalytic activity.
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