1. The global epidemic of metabolic diseases, such as obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated fatty liver disease (MAFLD), has emerged as a major public health challeng...

Metabolic-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease globally, with no effective pharmacological treatments available for early-stage cases. Rutin, a bioactive flavonoid from Sophora japonica L., exhibits diverse pharmacological effects, but its multi-pathway mechanisms in improving MAFLD remain unclear. In this study, we employed a high-fat diet (HFD)-induced MAFLD mouse model to investigate the therapeutic effects of rutin supplementation. Rutin supplementation significantly reduced blood lipid and liver lipid levels and alleviated liver injury in MAFLD model mice. Fecal microbiota transplantation experiments revealed that rutin alleviated MAFLD by modulating the gut microbiota composition. Through 16S rRNA sequencing analysis and non-targeted metabolomics analysis of the normal control (NC), HFD and rutin groups, rutin was found to alter key species (Ruminococcus torques) and associated metabolites (e.g., 7-dehydrocholesterol, short-chain fatty acids), suggesting a mechanism involving the gut microbiota. Antibiotic treatment experiments revealed that rutin alleviates MAFLD via the blood entry pathway. Network pharmacology analysis showed that rutin can directly act on targets closely related to MAFLD development, including tumor protein p53, epidermal growth factor receptor, and prostaglandin-endoperoxide synthase 2, as well as key signaling pathways such as PI3K/AKT and MAPK. Transcriptomics analysis of the NC, HFD and rutin groups revealed that rutin may ameliorate MAFLD through PI3K/AKT and MAPK signaling pathways, which might be enhanced by the gut microbiota and blood entry pathways. In conclusion, rutin can treat MAFLD through both the gut microbiota and blood entry pathways, resulting in a synergistic effect. Our study provides a novel strategy for evaluating functional food components and offers a scientific basis for dietary flavonoid-based interventions against MAFLD.

Multidrug resistance severely limits the therapeutic efficacy of cancer treatment, and carbon-based material-mediated photothermal therapy provides a promising strategy for overcoming tumor drug resistance.

Sphingolipids, a class of lipids, are widely present in the cell membranes of all eukaryotic and some prokaryotic organisms. These lipids play crucial roles in the formation of the lipid bilayer and are categorised into several groups, including sphingomyelins, ceramides, sphingosine-1-phosphate, and glycosphingolipids. In addition to their structural significance, sphingolipids also show bioactivity, regulating various signalling pathways involved in cell growth, differentiation, ageing, and apoptosis, and are closely associated with several chronic diseases, including obesity and type 2 diabetes mellitus. Notably, dysregulated sphingolipid metabolism contributes to obesity-related metabolic dysfunction through altered lipid accumulation, insulin signalling, organelle stress, and inflammation. This review summarises the various mechanisms and recent research advances related to sphingolipids and their association with obesity. It further examines how the metabolic effects of ceramides vary according to their acyl-chain length, enzyme of origin, tissue distribution, and metabolic context, as well as how adipose depot, sex, age, and metabolic phenotype influence the sphingolipid response to obesity. It further considers plant-derived sphingolipids as a compositionally distinct exogenous input to host sphingolipid pools, comparing their structural and enzymatic features with those of mammalian sphingolipids. Pharmacological, dietary, and lifestyle approaches that modify sphingolipid metabolism are also considered. Accordingly, the review summarises our current knowledge regarding the dietary occurrence, intestinal handling, and metabolic effects of sphingolipids and identifies the evidence gaps that currently limit conclusions regarding their relevance to obesity.