The Na⁺/K⁺-ATPase α1 subunit (ATP1A1) is a potential target for hepatic carcinoma (HCC) treatment, which plays a key role in Na⁺/K⁺ exchange, metabolism, signal transduction, etc. In vivo, we found that Panax notoginseng saponins (PNS) could inhibit tumor growth and significantly downregulate the expression and phosphorylation of ATP1A1/AKT/ERK in tumor-bearing mice. Our study aims to explore the potential effects of PNS on the regulation of ATP1A1 and the possible mechanisms of antitumor activity. The effects of PNS on HepG2 cell viability, migration, and apoptosis were examined in vitro. Fluorescence, Western blot, and RT-PCR analyses were used to examine the protein and gene expression. Further analysis was assessed with a Na⁺/K⁺-ATPase inhibitor (digitonin) and sorafenib in vitro. We found that the ATP1A1 expression was markedly higher in HepG2 cells than in L02 cells and PNS exhibited a dose-dependent effect on the expression of ATP1A and the regulation of AKT/ERK signaling pathways. Digitonin did not affect the expression of ATP1A1 but attenuated the effects of PNS on the regulation of ATP1A1/AKT/ERK signaling pathways and enhanced the antitumor effect of PNS by promoting nuclear fragmentation. Taken together, PNS inhibited the proliferation of HepG2 cells via downregulation of ATP1A1 and signal transduction. Our findings will aid a data basis for the clinical use of PNS.

In this study, a pH-responsive controlled-release mesoporous silica nanoparticle (MSN) formulation was developed. The MSNs were functionalized with a histidine (His)-tagged targeting peptide (B3int) through an amide bond, and loaded with an anticancer drug (cisplatin (CP)) and a lysosomal destabilization mediator (chloroquine (CQ)). Cu²⁺ was then used to seal the pores of the MSNs via chelation with the His-tag. The resultant nanoparticles showed pH-responsive drug release, and could effectively target tumor cells via the targeting effect of B3int. The presence of CP and Cu²⁺ permits reactive oxygen species to be generated inside cells; thus, the chemotherapeutic effect of CP is augmented by chemodynamic therapy. In vitro and in vivo experiments showed that the nanoparticles are able to effectively kill tumor cells. An in vivo cancer model revealed that the nanoparticles increase apoptosis in tumor cells, and thereby diminish the tumor volume. No off-target toxicity was noted. It thus appears that the functionalized MSNs developed in this work have great potential for targeted, synergistic anticancer therapies.

Xuefu Zhuyu Capsule (XFZYC) plays a pivotal role in treating coronary heart disease (CHD) because of its potent clinical effects and fewer side effects. However, the possible pharmacological effect on CHD is limited. Thus, this research systematically analyzes XFZYC and CHD through network pharmacology technology. We identified 139 active compounds and 127 overlapped target genes in 11 herbs of XFZYC by using network pharmacology, and these 127 genes regulated the major signaling pathways related to CHD. The analysis of protein–protein interaction networks demonstrated that 30 important gene targets, such as interleukin-6, signal transducer and activator of transcription 3, protein kinase B1, mitogen activated protein kinases 3, cellular tumor antigen p53, vascular endothelial growth factor A, transcription factor p65, and proto-oncogene c-Fos, participated in the regulation of 79 major signaling pathways related to CHD. On this basis, we found that protein kinase B1, cellular tumor antigen p53, and transcription factor p65, which played a role in multiple regulatory pathways of the network, were also regulated by more than 3 compounds and expressed in at least 4 herbs. Molecular docking showed that XFZYC had a good binding potential with the overlapped protein targets. Gene Ontology enrichment analysis revealed that the active targets involved a various of biological process, cellular component, and molecular function, which included the key ones such as positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and protein binding. T cell receptor signaling pathway, programmed death-ligand 1 expression and programmed death cell receptor-1 checkpoint pathway in cancer, FOXO signaling pathway, Ras signaling pathway, interleukin-17 signaling pathway, and VEGF signaling pathway, which were selected from Kyoto Encyclopedia of Genes and Genomes, were closely related to XFZYC in the treatment of CHD. XFZYC has a potential pharmacological effect on CHD, which provides the value for further study of XFZYC’s therapeutic effect on CHD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading chronic liver disorder worldwide. Its pathological progression typically begins with hepatic steatosis, advances to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, and in some cases culminates in hepatocellular carcinoma (HCC). This continuum is influenced not only by metabolic disturbances but also by coordinated local and systemic inflammatory and immune responses. This article systematically summarizes the inflammatory mechanisms underlying MASLD/MASH progression, highlighting their origin in the dynamic crosstalk between innate and adaptive immune compartments. Such interactions involve multiple immune cell subsets, including macrophages, T lymphocytes, and B lymphocytes, and are governed by intricate molecular regulatory pathways. Furthermore, this review explores how these interconnected processes amplify hepatic inflammation and fibrogenesis and discusses potential therapeutic approaches to modulate key nodes within immune signaling networks.

Here, we report the draft genome sequence of a potential novel strain Devosia sp. WQ 349k1, isolated from the feces of Bos taurus. Devosia sp. WQ 349k1 is a deoxynivalenol-degrading bacterial species. This genome information will help further study its molecular mechanism of detoxification.

Epidemiological evidence demonstrates that metabolic dysfunction-associated steatotic liver disease (MASLD) has evolved into one of the most widespread chronic liver disorders globally, posing a serious public health challenge. From a mechanistic perspective, the initiation of MASLD is predominantly fueled by multiple factors. Multiple pathological processes, including insulin resistance, oxidative stress, and inflammatory response, are all closely associated with the core issue of mitochondrial dysfunction. Mitochondria, serving as the hub for cellular energy metabolism, exhibit dysfunction that is widely recognized as the key nexus underlying the initiation and progression of MASLD. Maintaining mitochondrial homeostasis is the core mission of the mitochondrial quality control (MQC) system. The MQC system maintains mitochondrial homeostasis by the precise modulation of pathways including mitochondrial biogenesis (MB), mitochondrial dynamics (fusion and fission), and mitophagy. Hence, dysregulation of the MQC system may promote the pathological progression of MASLD. During the MASLD process, continuous metabolic stress disrupts the balance of MQC, and the dysregulation of MQC further exacerbates hepatocyte lipotoxicity damage, forming a vicious cycle. This review elucidates the mechanisms of MQC in MASLD as well as the latest findings. At the same time, we analyze in depth the regulatory mechanisms of each component of MQC and further explored therapeutic strategies of targeting mitochondria.