Background: Hepatocellular carcinoma (HCC) poses ongoing difficulties for public health systems due to its high incidence and poor prognosis. Huqi formula (HQF), a well-known prescription in traditional Chinese medicine, has demonstrated notable clinical effectiveness in the treatment of HCC. However, the mechanisms underlying its therapeutic effects have yet to be completely elucidated. Purpose: This study aimed to investigate the anti-HCC effects of HQF and its underlying mechanisms. Methods: Chemical profiling and quantification of HQF were conducted by LC–MS and HPLC. Orthotopic and subcutaneous tumor models were established through hydrodynamic injection of Akt/Nras plasmids and subcutaneous injection of c-Met/sgPten cells, respectively, to evaluate the therapeutic effects of HQF on HCC. Network pharmacology, RNA-Seq, molecular docking, Western blot, and flow cytometry were employed to assess the anti-HCC mechanisms. Results: LC–MS analysis identified 41 components, with HPLC quantification showing salvianolic acid B as the most abundant compound (0.303%). In Akt/Nras and c-Met/sgPten-induced HCC models, HQF significantly reduced tissue damage, improved liver function, and inhibited HCC progression. Mechanistic studies revealed that HQF induced apoptosis in HCC cells by downregulating p-PI3K, p-AKT, and p-mTOR expression, with molecular docking indicating the strongest binding affinity between salvianolic acid B and PI3K. HQF further enhanced CD4+ and CD8+ T cell infiltration within the tumor microenvironment. When combined with PD-1 therapy, HQF improved therapeutic efficacy against HCC. Finally, toxicity assays confirmed the safety profile of HQF. Conclusion: HQF demonstrated significant anti-HCC effects and a synergistic effect with PD-1, could be used as an alternative therapeutic agent for HCC. Graphical
Hepatocellular carcinoma (HCC) is still a public health disease with its high prevalence and morbidity. Short of early diagnosis biomarkers and effective therapy, the treatment of HCC patients hasn’t achieved ideal effect. Hypoxia is a hallmark of HCC, which is mainly induced by imbalance of tumor cell proliferation and insufficient supply of oxygen. Recently, amounting evidence suggested lncRNAs, especially hypoxia-related lncRNAs play a pivotal role in regulating HCC. Hypoxia-related lncRNAs are involved in altering glucose metabolism, maintaining of cancer stem cell-like properties (CSCs), cell apotosis, proliferation and immune escape, which all contribute to the poor prognosis of HCC patients. The novel identified hypoxia-related lncRNAs could be the potential target or biomarkers of HCC, which are beneficial to the clinical treatment. Herein, we summarized currently reported hypoxia-related lncRNAs and their related mechanisms, providing potential application and future perspective of hypoxia-related lncRNAs as a potential therapeutic target.
17 August 2024 in Clinical and Translational Oncology
The objective of this study is to analyze and summarize the characteristics of the clinical data of patients with systemic lupus erythematosus (SLE) complicated with liver failure, and to improve the cognition of the disease. The clinical data of patients with SLE complicated with liver failure hospitalized in Beijing Youan Hospital from January 2015 to December 2021 were collected retrospectively, including general information and laboratory examination data, and the clinical characteristics of the patients were summarized and analyzed. Twenty-one SLE patients with liver failure were analyzed. The diagnosis of liver involvement was earlier in 3 cases than that of SLE, and later in 2 cases. Eight patients were diagnosed with SLE and autoimmune hepatitis at the same time. The medical history is between 1 month and 30 years. This was the first case report of SLE complicated with liver failure. We found that: (1) among the 21 patients, organ cysts (liver and kidney cysts) were more common and the proportion of cholecystolithiasis and cholecystitis was higher than that in previous studies, but the proportion of renal function damage and joint involvement was lower. (2) The inflammatory reaction was more obvious in SLE patients with acute liver failure. The degree of liver function injury in SLE patients with autoimmune hepatitis was less than that in patients with other liver diseases. (3) The use of glucocorticoid in SLE patients with liver failure was worthy of further discussion. Key Points• Patients with SLE complicated with liver failure have a lower proportion of renal impairment and joint involvement.• The study firstly reported SLE patients with liver failure.• Glucocorticoids in the treatment of SLE patients with liver failure are worthy of further discussion.