<sup>13</sup>C<sub>6</sub>&#45;Glucose Labeling Associated with LC&#45;MS&#58; Identification of Plant Primary Organs in Secondary Metabolite Synthesis

This paper presents a novel and efficient method for certifying primary organs involved in secondary metabolite synthesis. As the most important secondary ...

Chengdu University of Traditional Chinese Medicine

Background: Colon adenocarcinoma (COAD) is the most common subtype of colon cancer, and cuproptosis is a recently newly defined form of cell death that plays an important role in the development of several malignant cancers. However, studies of cuproptosis-related lncRNAs (CRLs) involved in regulating colon adenocarcinoma are limited. The purpose of this study is to develop a new prognostic CRLs signature of colon adenocarcinoma and explore its underlying biological mechanism. Methods: In this study, we downloaded RNA-seq profiles, clinical data and tumor mutational burden (TMB) data from the TCGA database, identified cuproptosis-associated lncRNAs using univariate Cox, lasso regression analysis and multivariate Cox analysis, and constructed a prognostic model with risk score based on these lncRNAs. COAD patients were divided into high- and low-risk subgroups based on the risk score. Cox regression was also used to test whether they were independent prognostic factors. The accuracy of this prognostic model was further validated by receiver operating characteristic curve (ROC), C-index and Nomogram. In addition, the lncRNA/miRNA/mRNA competing endogenous RNA (ceRNA) network and protein−protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). Results: We constructed a prognostic model based on 15 cuproptosis-associated lncRNAs. The validation results showed that the risk score of the model (HR = 1.003, 95% CI = 1.001−1.004; p < 0.001) could serve as an independent prognostic factor with accurate and credible predictive power. The risk score had the highest AUC (0.793) among various factors such as risk score, stage, gender and age, also indicating that the model we constructed to predict patient survival was better than other clinical characteristics. Meanwhile, the possible biological mechanisms of colon adenocarcinoma were explored based on the lncRNA/miRNA/mRNA ceRNA network and PPI network constructed by WGCNA. Conclusion: The prognostic model based on 15 cuproptosis-related lncRNAs has accurate and reliable predictive power to effectively predict clinical outcomes in colon adenocarcinoma patients.

In Silico Identification and Validation of Cuproptosis-Related LncRNA Signature as a Novel Prognostic Model and Immune Function Analysis in Colon Adenocarcinoma.

 Lung cancer has the highest mortality rate among cancers worldwide, and non-small cell lung cancer (NSCLC) is the major lethal factor. Saponins in Paris polyphylla smith exhibit antitumor activity against non-small cell lung cancer, but their targets are not fully understood.  In this study, we used differential gene analysis, lasso regression analysis and support vector machine recursive feature elimination (SVM-RFE) to screen potential key genes for NSCLC by using relevant datasets from the GEO database. The accuracy of the signature genes was verified by using ROC curves and gene expression values. Screening of potential active ingredients for the treatment of NSCLC by molecular docking of the reported active ingredients of saponins in  Smith with the screened signature genes. The activity of the screened components and their effects on key genes expression were further validated by CCK-8, flow cytometry (apoptosis and cycling) and qPCR.  204 differential genes and two key genes (RHEBL1, RNPC3) stood out in the bioinformatics analysis. Overall survival (OS), First-progression survival (FP) and post-progression survival (PPS) analysis revealed that low expression of RHEBL1 and high expression of RNPC3 indicated good prognosis. In addition, Polyphyllin VI(PPVI) and Protodioscin (Prot) effectively inhibited the proliferation of non-small cell lung cancer cell line with IC50 of 4.46 μM ± 0.69 μM and 8.09 μM ± 0.67μM, respectively. The number of apoptotic cells increased significantly with increasing concentrations of PPVI and Prot. Prot induces G1/G0 phase cell cycle arrest and PPVI induces G2/M phase cell cycle arrest. After PPVI and Prot acted on this cell line for 48 h, the expression of RHEBL1 and RNPC3 was found to be consistent with the results of bioinformatics analysis.  This study identified two potential key genes (RHEBL1 and RNPC3) in NSCLC. Additionally, PPVI and Prot may act on RHEBL1 and RNPC3 to affect NSCLC. Our findings provide a reference for clinical treatment of NSCLC.

Machine learning and bioinformatics-based insights into the potential targets of saponins in  smith against non-small cell lung cancer.

WW domain binding protein 2 (), considered an emerging breast cancer gene, functions as a binding partner for WW domain proteins. The  gene is involved in mediating the malignant development and clinical drug resistance of breast cancer, but its potential mechanism remains unclear. Therefore, it is necessary to elucidate the mechanism of WBP2 in breast cancer, which will help to provide new methods for clinical diagnosis and treatment of breast cancer.

WW domain binding protein 2 (WBP2) as an oncogene in breast cancer: mechanisms and therapeutic prospects-a narrative review.

Unraveling the specific organs and tissues involved in saponin synthesis, as well as the light regulatory mechanisms, is crucial for improving the quality of artificially cultivated medicinal materials of  plants.  saponin VII (PS VII), a high-value active ingredient, is found in almost all organs of  plant species. In this study, we focused on  var.  (Franch.) Hand. - Mzt. (PPY) and found that PS VII synthesis predominantly occurs in leaves and is increased by high light intensity. This intriguing discovery has unveiled the potential for manipulating non-traditional medicinal organ leaves to improve the quality of medicinal organ rhizomes. The analysis of the impact of organ differences on saponin concentration in  var.  (Franch.) Hara (PPC),  Franch. (PF), and PPY revealed consistency among the three  species and was mainly dominated by PS VII. Notably, the leaves and stems exhibited much higher proportions of PS VII than other organs, accounting for 80-90% of the four main saponins. Among the three  species, PPY had the highest concentration of PS VII and was selected for subsequent experiments. Further investigations on saponin subcellular localization, temporal variation, and stem wound fluid composition demonstrated that PS VII is synthesized in mesophyll cells, released into the intercellular space through exocytosis, and then transported to the rhizome via vascular tissue. These findings confirm the significant role of leaves in PS VII synthesis. Additionally, a C-glucose feeding to trace PS VII biosynthesis revealed that only PS VII in the leaves exhibited incorporation of the labeled carbon, despite conducting C-glucose feeding in leaves, stems, rhizomes, and roots. Thus, the leaves are indeed the primary organ for PS VII synthesis in PPY. Furthermore, compared with plants under 100 μmol m s, plants under 400 μmol m s exhibited a higher PS VII concentration, particularly in the upper epidermal cells of the leaves. We propose that high light intensity promotes PS VII synthesis in leaves through three mechanisms: (1) increased availability of substrates for saponin synthesis; (2) protection of leaves from high light damage through enhanced saponin synthesis; and (3) enhanced compartmentalization of saponins within the leaves, which in turn feedback regulates saponin synthesis.

The synthesis of  saponin VII mainly occurs in leaves and is promoted by light intensity.

Breast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin-proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.

Siyu Chen

State Key Laboratory of Southwestern Chinese Medicine Resources,
College of Pharmacy

Chengdu University of Traditional Chinese Medicine

¹³C₆-Glucose Labeling Associated with LC-MS: Identification of Plant Primary Organs in Secondary Metabolite Synthesis

Siyu Chen

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}State Key Laboratory of Southwestern Chinese Medicine Resources,College of Pharmacy

Chengdu University of Traditional Chinese Medicine

13C6-Glucose Labeling Associated with LC-MS: Identification of Plant Primary Organs in Secondary Metabolite Synthesis

State Key Laboratory of Southwestern Chinese Medicine Resources,
College of Pharmacy

¹³C₆-Glucose Labeling Associated with LC-MS: Identification of Plant Primary Organs in Secondary Metabolite Synthesis