Copper is an essential trace element that acts as a cofactor in various enzyme active sites in the human body. It participates in numerous life activities, including lipid metabolism, energy metabolism, and neurotransmitter synthesis. The proposal of “Cuproptosis” has made copper metabolism-related pathways a research hotspot in the field of tumor therapy, which has attracted great attention. This review discusses the biological processes of copper uptake, transport, and storage in human cells. It highlights the mechanisms by which copper metabolism affects hepatocellular carcinogenesis and metastasis, including autophagy, apoptosis, vascular invasion, cuproptosis, and ferroptosis. Additionally, it summarizes the current clinical applications of copper metabolism-related drugs in antitumor therapy.

Background: The incidence of Non-alcoholic fatty liver disease (NAFLD) is increasing year by year. Researches showed that Chinese patent medicines (CPMs) had achieved good efficacy in the treatment of Non-alcoholic fatty liver disease. However, the debate on optimum Chinese patent medicine (CPM) persists. Therefore, we conducted a network meta-analysis to objectively compare the efficacy of different Chinese patent medicines in the treatment of Non-alcoholic fatty liver disease.Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, and Chinese Biomedical Literature Database were used as databases for RCT researches retrieval. The retrieval time was from establishment of the database to July 2022. After effective data was extracted, Review Manager 5.4 and Cochrane Collaboration System Evaluator’s Manual were used to assess bias risk. STATA 16.0 based on frequency theory was used for the network meta-analysis.Results: Totally 39 studies were included, involving 13 Chinese patent medicines, including 4049 patients, of which 42 patients were lost. In terms of improving clinical efficiency rate, Zhibitai capsule was most likely the best choice of Chinese patent medicine for Non-alcoholic fatty liver disease. Liuwei Wuling tablet had the best effect in reducing serum ALT and AST; Gandan Shukang capsule had the best effect in reducing serum GGT; Qianggan capsule had the best effect in reducing serum TG; Dangfei Liganning capsule had the best effect in reducing serum TC. None of the included studies had serious adverse reactions.Conclusion: For patients with Non-alcoholic fatty liver disease in this NMA, Zhibitai capsule, Liuwei Wuling tablet, Gandan Shukang capsule, Qianggan capsule, Dangfei Liganning capsule might be noteworthy. Due to the uclear risk bias, better designed double-blind, multi center and large sample RCTs are needed which resolve the problems of blinding, selective reporting and allocation concealment.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42022341240.

Non-alcoholic fatty liver disease (NAFLD) is a progressive metabolic disease characterized by hepatic steatosis, inflammation, and fibrosis that seriously endangers global public health. Epidemiological studies have shown that the incidence of non-alcoholic fatty liver disease in postmenopausal women has significantly increased. Studies have shown that estrogen deficiency is the main reason for this situation, and supplementing estrogen has become a new direction for preventing the occurrence of postmenopausal fatty liver. However, although classical estrogen replacement therapy can reduce the incidence of postmenopausal NAFLD, it has the risk of increasing stroke and cardiovascular diseases, so it is not suitable for the treatment of postmenopausal NAFLD. More and more recent studies have provided evidence that phytoestrogens are a promising method for the treatment of postmenopausal NAFLD. However, the mechanism of phytoestrogens in preventing and treating postmenopausal NAFLD is still unclear. This paper summarizes the clinical and basic research evidence of phytoestrogens and reviews the potential therapeutic effects of phytoestrogens in postmenopausal NAFLD from six angles: enhancing lipid metabolism in liver and adipose tissue, enhancing glucose metabolism, reducing oxidative stress, reducing the inflammatory response, regulating intestinal flora, and blocking liver fibrosis (Graphical Abstract).

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is closely associated with metabolic abnormalities. The causes of NAFLD are exceedingly complicated, and it is known that a variety of signaling pathways, endoplasmic reticulum stress, and mitochondrial dysfunction play a role in the pathogenesis of NAFLD. Recent studies have shown that ubiquitination and deubiquitination are involved in the regulation of the NAFLD pathophysiology. Protein ubiquitination is a dynamic and diverse post-translational alteration that affects various cellular biological processes. Numerous disorders, including NAFLD, exhibit imbalances in ubiquitination and deubiquitination. To highlight the significance of this post-translational modification in the pathogenesis of NAFLD and to aid in the development of new therapeutic approaches for the disease, we will discuss the role of enzymes involved in the processes of ubiquitination and deubiquitination, specifically E3 ubiquitin ligases and deubiquitinating enzymes that are important in the regulation of NAFLD.

Pyroptosis is a distinct form of cell death that plays a critical role in intensifying inflammatory responses. It primarily occurs via the classical pathway, non-classical pathway, caspase-3/6/7/8/9-mediated pathways, and granzyme-mediated pathways. Key effector proteins involved in the pyroptosis process include gasdermin family proteins and pannexin-1 protein. Pyroptosis is intricately linked to the onset and progression of non-alcoholic steatohepatitis (NASH). During the development of NASH, factors such as pyroptosis, innate immunity, lipotoxicity, endoplasmic reticulum stress, and gut microbiota imbalance interact and interweave, collectively driving disease progression. This review analyzes the molecular mechanisms of pyroptosis and its role in the pathogenesis of NASH. Furthermore, it explores potential diagnostic and therapeutic strategies targeting pyroptosis, offering new avenues for improving the diagnosis and treatment of NASH.