BACKGROUND Ribonucleotide reductase (RR) is a key enzyme in tumor proliferation, especially its subunit-RRM2. Although there are multiple therapeutics for tumors, they all have certain limitations. Given their advantages, traditional Chinese medicine (TCM) monomers have become an important source of anti-tumor drugs. Therefore, screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development. AIM To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2. METHODS The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients. TCM monomers that potentially act on RRM2 were screened via literature mining. Using AutoDock software, the screened monomers were docked with the RRM2 protein. RESULTS The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues, and it was negatively correlated with the overall survival rate of patients with the majority of tumor types. Through literature mining, we discovered that berberine, ursolic acid, gambogic acid, cinobufagin, quercetin, daphnetin, and osalmide have inhibitory effects on RRM2. The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein, which mainly interacted through hydrogen bonds and hydrophobic force. The main binding sites were Arg330, Tyr323, Ser263, and Met350. CONCLUSION RRM2 is an important tumor therapeutic target. The TCM monomers screened have a good binding capacity with the RRM2 protein.

https://doi.org/10.12998/wjcc.v10.i31.11299

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8 

GALNT6 promotes bladder cancer malignancy and immune escape by epithelial-mesenchymal transition and CD8+ T cells

Single-cell transcriptomic reveals a cell atlas and diversity of chicken amygdala responded to social hierarchy

To explore the anti-tumor and anti-virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms. 

Study on the mechanism of quercetin in <scp>Sini Decoction Plus Ginseng Soup</scp> to inhibit liver cancer and <scp>HBV</scp> virus replication through <scp>CDK1</scp>

Abstract Dominance hierarchy, is described as the priority to feed, resting and territory in term of aggressive interactions. Increased studies have revealed the underpinned mechanism mediating social hierarchy in mammal, vertebrate and fishes, however, there is rare studies conducting on how brain amydala on social hierarchy in poultry. We performed cross-species analysis with mammalian amygdala, and find that cell types of human and rhesus monkeys were more closely related and that of chickens were more distant. We identified 26 clusters and divided it into 10 main clusters. Of which, GABAnic and glutamatergic neurons are associated with social behaviors, and their sub-neurons GABA_LEG and Glu3, and hub genes RHOB and CDK14 , are considered mediating the social hierarchy of chickens. Additionally, high-rank chickens may have better immune functions and stress tolerance than low-rank chickens. Our results provide to serve the developmental studies of amygdala neuron system, and new insights into the underpinned mechanism of social hierarchy in poultry. 

/pdf/single-cell-transcriptomic-landscape-reveals-a-cell-atlas-of-2iqseatp.pdf

Single-cell transcriptomic landscape reveals a cell atlas of chicken amygdala and key genes in response to social hierarchy

Background: Hepatocellular carcinoma is one kind of clinical common malignant tumor with a poor prognosis, and its pathogenesis remains to be clarified urgently. This study was performed to elucidate key genes involving HCC by bioinformatics analysis and experimental evaluation. Methods: We identified common differentially expressed genes (DEGs) based on gene expression profile data of GSE60502 and GSE84402 from the Gene Expression Omnibus (GEO) database. Gene Ontology enrichment analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, REACTOME pathway enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were used to analyze functions of these genes. The protein-protein interaction (PPI) network was constructed using Cytoscape software based on the STRING database, and Molecular Complex Detection (MCODE) was used to pick out two significant modules. Hub genes, screened by the CytoHubba plug-in, were validated by Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas (HPA) database. Then, the correlation between hub genes expression and immune cell infiltration was evaluated by Tumor IMmune Estimation Resource (TIMER) database, and the prognostic values were analyzed by Kaplan-Meier plotter. Finally, biological experiments were performed to illustrate the functions of RRM2. Results: Through integrated bioinformatics analysis, we found that the upregulated DEGs were related to cell cycle and cell division, while the downregulated DEGs were associated with various metabolic processes and complement cascade. RRM2, MAD2L1, MELK, NCAPG, and ASPM, selected as hub genes, were all correlated with poor overall prognosis in HCC. The novel RRM2 inhibitor osalmid had anti-tumor activity, including inhibiting proliferation and migration, promoting cell apoptosis, blocking cell cycle, and inducing DNA damage of HCC cells. Conclusion: The critical pathways and hub genes in HCC progression were screened out, and targeting RRM2 contributed to developing new therapeutic strategies for HCC.

/pdf/identifying-potential-prognosis-markers-in-hepatocellular-27c635po.pdf

Identifying potential prognosis markers in hepatocellular carcinoma via integrated bioinformatics analysis and biological experiments

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Identifying potential prognosis markers in hepatocellular carcinoma via integrated bioinformatics analysis and biological experiments