Fuzheng Xiaojijinzhan (FZXJJZF) decoction is an effective prescription for treating colorectal cancer liver metastasis (LMCRC). To elucidate the pharmacological mechanism of the FZXJJZF decoction therapy on LMCRC. Firstly, a network pharmacological approach was used to characterize the underlying targets of FZXJJZF on LMCRC. Secondly, LMCRC-related genes are obtained from the public database TCGA, and those genes are further screened and clustered through Mfuzz, an R package tool. Then, targets of FZXJJZF predicted by network pharmacology were overlapped with LMCRC related genes screened by Mfuzz. Meanwhile, FZJZXJF intervened in LMCRC model,epithelial-to-mesenchymal transition (EMT), and migration and invasion of HCT-116 cells. Thirdly, the transcriptomics data of FZJZXJF inhibited HCT-116 cells of EMT cells were overlapped with EMT database data to narrow the possible range of targets. Based on this, the potential targets and signal pathways of FZJZXJF were speculated by combining the transcriptomics data with the targets from network pharmacology-TCGA. Finally, the anti-cancer mechanism of FZXJJZF on LMCRC was verified in vitro by Real-Time PCR and Western Blot in vitro. By network pharmacological analysis, 282 ingredients and 429 potential targets of FZXJJZF were predicted. The 9268 LMCRC-related genes in the TCGA database were classified into 10 clusters by the Mfuzz. The two clustering genes with the most similar clustering trends were overlapped with 429 potential targets, and 32 genes were found, such as CD34, TRPV3, PGR, VDR, etc. In vivo experiments, FZJZXJF inhibited the tumor size in LMCRC models, and the EMT, migration, and invasion of HCT-116 also be inhibited. Intersecting transcriptomics dates with 32 target genes, it is speculated that the VDR-TGF-β signaling pathway may be an effective mechanism of FZXJJZF. Additionally, it is shown that FZXJJZF up-regulated the expression levels of VDR and E-cadherin and down-regulated the expression levels of TGF-β and Snail1 in vitro. These results confirmed that FZXJJZF plays an effective role in LMCRC mainly by inhibiting EMT phenotype via the VDR-TGF-β signaling pathway. Collectively, this study reveals the anti-LMCRC effect of FZXJJZF and its potential therapeutic mechanism from the perspective of potential targets and potential pathways.

Citrus folium and its main ingredient nobiletin (NOB) have received widespread attention in recent years due to their antitumor effects. The antitumor effect of Citrus folium is related to the traditional use, mainly in its Chinese medicinal properties of soothing the liver and promoting qi, resolving phlegm, and dispelling stagnation. Some studies have proved that Citrus folium and NOB are more effective for triple-negative breast cancer (TNBC), which is related to the syndrome of stagnation of liver qi. From the perspective of modern biomedical research, NOB has anticancer effects. Its potential molecular mechanisms include inhibition of the cell cycle, induction of apoptosis, and inhibition of angiogenesis, invasion, and migration. Citrus folium and NOB can also reduce the side effects of chemotherapy drugs and reverse multidrug resistance (MDR). However, more research studies are needed to clarify the underlying mechanisms. The modern evidence of Citrus folium and NOB in breast cancer treatment has a strong connection with the traditional concepts and laws of applying Citrus folium in Chinese medicine (CM). As a low-toxic anticancer drug candidate, NOB and its structural changes, Citrus folium, and compound prescriptions will attract scientists to use advanced technologies such as genomics, proteomics, and metabolomics to study its potential anticancer effects and mechanisms. On the contrary, there are relatively few studies on the anticancer effects of Citrus folium and NOB in vivo. The clinical application of Citrus folium and NOB as new cancer treatment drugs requires in vivo verification and further anticancer mechanism research. This review aims to provide reference for the treatment of breast cancer by Chinese medicine.

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4⁺memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

Background: Sepsis-induced acute lung injury (ALI) represents the earliest and most severe complication of sepsis, with extraordinarily high mortality rates. Baihe Gujin decoction (BHGJD), a classical traditional Chinese medicine formula, has demonstrated protective effects against various pulmonary diseases, yet its therapeutic potential in sepsis-induced ALI remains unexplored. Methods: The chemical constituents of BHGJD were characterized by mass spectrometry, and potential protective mechanisms were predicted using network pharmacology. In vivo , a cecal ligation and puncture (CLP) mouse model was established to evaluate BHGJD’s protective effects through histopathological assessment and serum inflammatory cytokine analysis. Lung tissue RNA sequencing and untargeted metabolomics were performed to explore underlying molecular mechanisms, followed by validation of key proteins (HO-1, GPX4, PPARα, CPT1A, mTOR, and p-mTOR) by Western blot, immunohistochemistry, and immunofluorescence. Lung-deposited bioactive components were subsequently identified by mass spectrometry. In vitro , (+)-catechin, a representative lung-exposed constituent detected in lung tissue, was used to treat lipopolysaccharide-induced MLE-12 cells. Cellular levels of adenosine triphosphate, reactive oxygen species, and ferrous iron were measured. Mitochondrial ultrastructure was assessed by transmission electron microscopy, and fatty acid oxidation capacity was evaluated using the Seahorse palmitate oxidation assay, followed by validation of key proteins by Western blot. Results: BHGJD significantly ameliorated CLP-induced ALI, as evidenced by improved histological architecture and reduced inflammatory cytokine levels. Integrated multi-omics analysis and experimental validation revealed three interconnected protective mechanisms: 1) activation of an Nrf2/GPX4-associated antioxidant response, initially suggested by glutathione pathway enrichment, reduced lipid peroxidation-related metabolites, and restoration of redox and mitochondrial homeostasis; 2) PPARα/CPT1A-associated metabolic remodeling toward fatty acid utilization, supported by fatty acid transport/metabolism enrichment, coordinated changes in multiple acylcarnitine species, increased PPARα/CPT1A expression, and improved palmitate-supported mitochondrial respiration in vitro ; and 3) reduction of inflammatory lipid mediators. Altered mTOR signaling accompanied these changes and may represent a convergent regulatory pathway. Conclusion: BHGJD alleviates sepsis-induced ALI through coordinated enhancement of Nrf2/GPX4-associated antioxidant defense, PPARα/CPT1A-linked metabolic reprogramming toward fatty acid utilization, and suppression of inflammatory lipid mediators. These findings provide an integrated mechanistic framework for the protective actions of BHGJD.

The geometric mismatch between rigid planar microelectrode arrays (MEAs) and soft three-dimensional (3D) organoids, alongside high electrode-tissue interface impedance, limits the fidelity of in vitro bioelectronic interrogations. We present a self-folding 3D bioelectronic micro-cage featuring dealloyed nanoporous electrodes to omnidirectionally encapsulate hiPSC-derived cardiac organoids for multimodal electrophysiological and thermal monitoring. Fabricated via a wafer-scale MEMS process, the planar SiO₂/PI bilayer utilizes an intrinsic residual stress gradient to spontaneously self-assemble into a 3D conformal cage upon release. Crucially, a magnetron co-sputtered Au-Cu alloy was employed for the electrode layer. During the selective etching of the Cu sacrificial layer, simultaneous dealloying occurs, generating a high-surface-area nanoporous gold electrode structure. The scaffold achieved a predictable folding radius optimized for ~500 μm organoids. The optimized nanoporous gold electrodes exhibited significantly reduced electrochemical impedance (8.3kΩ at 1 kHz) and a massively enhanced charge storage capacity (53 mC/cm²) compared to standard bare gold. Integrated serpentine resistive sensors exhibited highly linear temperature-dependent resistance changes (R² = 0.9993), enabling on-device temperature monitoring during organoid assays. Functionally, the micro-cage recorded synchronized 3D extracellular field potentials from cardiac organoids and monitored electrophysiological responses to externally applied thermal perturbations and pharmacological agents, including Verapamil and Norepinephrine. These results demonstrate a promising MEMS-compatible platform for organoid-based electrophysiological recording, temperature monitoring, and proof-of-concept drug-response assessment.