Experimental Verification of Erchen Decoction Plus Huiyanzhuyu Decoction in the Treatment of Laryngeal Squamous Cell Carcinoma Based on Network Pharmacology.

BACKGROUND: The prescription of Chinese herbal medicine (CHM) consists of multiple herbs that exhibit synergistic effects due to the presence of multiple components targeting various pathways. In clinical practice, the combination of Erchen decoction and Huiyanzhuyu decoction (EHD) has shown promising outcomes in treating patients with laryngeal squamous cell carcinoma (LSCC). However, the underlying mechanism by which EHD exerts its therapeutic effects in LSCC remains unknown. METHODS: Online databases were utilized for the analysis and prediction of the active constituents, targets, and key pathways associated with EHD in the treatment of LSCC. The protein-protein interaction (PPI) network of common targets was constructed and visualized using Cytoscape 3.8.1 software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functional roles of core targets within the PPI network. Protein clustering was conducted utilizing the MCODE plug-in. The obtained results highlight the principal targets and pathways involved. Subsequently, clinical samples were collected to validate alterations in the levels of these main targets through Western blotting (WB) and immunohistochemistry (IHC). Furthermore, both in vivo and in vitro experiments were conducted to investigate the therapeutic effects of EHD on healing LSCC and elucidate its underlying mechanism. Additionally, to ensure experimental reliability and reproducibility, quality control measures utilizing HPLC were implemented for EHD herbal medicine. RESULTS: The retrieval and analysis of databases in EHD medicine and LSCC disease yielded a total of 116 overlapping targets. The MCODE plug-in methods were utilized to acquire 8 distinct protein clusters through protein clustering. The findings indicated that both the first and second clusters exhibited a size greater than 6 scores, with key genes PI3K and ErbB occupying central positions, while the third and fourth clusters were associated with proteins in the PI3K, STAT3, and Foxo pathways. GO functional analysis reported that these targets had associations mainly with the pathway of p53 mediated DNA damage and negative regulation of cell cycle in terms of biological function; the death-induced signaling complex in terms of cell function; transcription factor binding and protein kinase activity in terms of molecular function. The KEGG enrichment analysis demonstrated that these targets were correlated with several signaling pathways, including PI3K-Akt, FoxO, and ErbB2 signaling pathway. On one hand, we observed higher levels of key genes such as P-STAT3, P-PDK1, P-Akt, PI3K, and ErbB2 in LSCC tumor tissues compared to adjacent tissues. Conversely, FOXO3a expression was lower in LSCC tumor tissues. On the other hand, the key genes mentioned above were also highly expressed in both LSCC xenograft nude mice tumors and LSCC cell lines, while FOXO3a was underexpressed. In LSCC xenograft nude mice models, EHD treatment resulted in downregulation of P-STAT3, P-PDK1, PI3K, P-AKT, and ErbB2 protein levels but upregulated FOXO3a protein level. EHD also affected the levels of P-STAT3, P-PDK1, PI3K, P-AKT, FOXO3a, and ErbB2 proteins in vitro: it inhibited P-STAT3, P-AKT, and ErbB2, while promoting FOXO3a; however, it had no effect on PDK1 protein. In addition, HPLC identified twelve compounds accounting for more than 30% within EHD. The findings from this study can serve as valuable guidance for future experimental investigations. CONCLUSION: The possible mechanism of EHD medicine action on LSCC disease is speculated to be closely associated with the ErbB2/PI3K/AKT/FOXO3a signaling pathway.

Biomarkers prediction and immune landscape in ulcerative colitis: Findings based on bioinformatics and machine learning.

BACKGROUND: Ulcerative colitis (UC) presents diagnostic and therapeutic difficulties. The primary objective of this study is to identify efficacious biomarkers for diagnosis and treatment, as well as acquire a deeper understanding of the immuneological characteristics associated with the disease. METHODS: Datasets relating to UC were obtained from GEO database. Among these, three datasets were merged to create a metadata for bioinformatics analysis and machine learning. Additionally, one dataset specifically utilized for external validation. Least absolute shrinkage and selection operator (LASSO) and random forest (RF) were employed to screen signature genes. The artificial neural network (ANN) model and receiver operating characteristic (ROC) curve were used to assess the diagnostic performance of signature genes. The single sample gene set enrichment analysis (ssGSEA) was applied to reveal the immune landscape. Finally, the relationship between the signature genes, immune infiltration, and clinical characteristics was investigated through correlation analysis. RESULT: By intersecting the result of LASSO, RF and WGCNA, 8 signature genes were identified, including S100A8, IL-1B, CXCL1, TCN1, MMP10, GREM1, DUOX2 and SLC6A14. The biological progress of this gene mostly encompasses acute inflammatory response, aggregation and chemotaxis of leukocyte, and response to lipopolysaccharide by mediating IL-17 signaling pathway, NF-kappa B signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway. Immune infiltration analysis shows 25 immune cells are significantly elevated in UC samples. Moreover, these signature genes exhibit a strong correlation with various immune cells and a mild to moderate correlation with the Mayo score. CONCLUSION: S100A8, IL-1B, CXCL1, TCN1, MMP10, GREM1, DUOX2 and SLC6A14 have been identified as credible potential biomarkers for the diagnosis and therapy of UC. The immune response mediated by these signature biomarkers plays a crucial role in the occurrence and advancement of UC by means of the reciprocal interaction between the signature biomarkers and immune-infiltrated cells.

Self-Reconstructed Two-Dimensional Cluster-Based Co-Organic Layer Heterojunctions for Enhanced Oxygen Evolution Reactions.

When it comes to an efficient catalytic oxygen evolution reaction (OER) in the production of renewable energy and chemicals, the construction of heterogeneous structures is crucial to break the linear scalar relationship of a single catalyst. This heterogeneous structure construction helps creatively achieve high activity and stability. However, the synthesis process of heterogeneous crystalline materials is often complex and challenging to capture and reproduce, which limits their application. Here, the dynamic process of structural changes in Co-MOFs in alkali was captured by in situ powder X-ray diffraction, FT-IR spectroscopy, and Raman spectroscopy, and several self-reconfigured MOF heterogeneous materials with different structures were stably isolated. The created ß-Co(OH)2/Co-MOF heterojunction structure facilitates rapid mass-charge transfer and exposure of active sites, which significantly enhanced OER activity. Experimental results show that this heterogeneous structure achieves a low overpotential of 333 mV at 10 mA cm-2. The findings provide new insights and directions for the search for highly reactive cobalt-based MOFs for sustainable energy technologies.

Therapeutic targets and pharmacological mechanisms of Coptidis Rhizoma against ulcerative colitis: Findings of system pharmacology and bioinformatics analysis.

Evidence of the advantages of Coptidis Rhizoma (CR) for the treatment of ulcerative colitis (UC) is accumulating. However, research revealing the targets and molecular mechanisms of CR against UC is scarce. In this research, a bioinformatics analysis was performed to carry out the physicochemical properties and biological activities of phytochemicals in CR and analyze the binding activities, targets, biological functions and mechanisms of CR against UC. This research shows that the CR's key phytochemicals, which are named Coptisine, Berberrubine, Berlambine, Berberine, Epiberberine, Obacunone, Worenine, Quercetin, (R)-Canadine, Magnograndiolide, Palmatine and Moupinamide, have ideal physicochemical properties and bioactivity. A total of 1,904 potential phytochemical targets and 17,995 UC-related targets are identified, and we finally acquire 233 intersection targets between key phytochemicals and disease. A protein-protein interaction network of 233 common targets was constructed; and six hub targets were acquired with a degree greater than or equal to median, namely TP53, HSP90AA1, STAT3, ESR1, MYC, and RELA. The enrichment analysis suggested that the core targets may exert an impact on anti-inflammatory, immunoregulatory, anti-oxidant and anti-fibrosis functions mainly through the PI3K/ART signaling pathway, Th17 differentiation signaling pathway, inflammatory bowel disease signaling pathway, etcetera. Also, a molecular docking analysis shows that the key phytochemicals have strong affinity for binding to the core targets. Finally, the interaction network of CR, phytochemicals, targets, GO functions, KEGG pathways and UC is constructed. This study indicates that the key phytochemicals in CR have superior drug likeness and bioactivity, and the molecular mechanism of key phytochemicals against UC may be via the signaling pathway mentioned above. The potential and critical pharmacological mechanisms provide a direction for future research.

Highly Stable Two-Dimensional Cluster-Based Ni/Co-Organic Layers for High-Performance Supercapacitors.

Basic requirements for advanced and practical supercapacitors need electrode materials with strong stability, high surface area, well-defined porosity, and enhanced capability of ion insertion and electron transfer. It is worth mentioning that the two-dimensional cluster-based Ni/Co-organic layer (Ni0.7Co0.3-CMOL) inherits high stability from the Kagóme lattice and shows excellent pseudocapacitance behavior. As an optimized atomic composition, this crystalline CMOL exhibits excellent performance and stability both in 1.0 M KOH and All-Solid-State Flexible Asymmetric Supercapacitor (ASCs). The specific capacitance values are 1211 and 394 F g-1 and the energy density is 54.67 Wh kg-1 at 1 A g-1. Good cycling stability is characterized by its capacitance retention, maintained at 92.4% after 5000 cycles in a three-electrode system and 90% after 2000 cycles at 20 A g-1 for assembled All-Solid-State Flexible ASCs. An in situ XRD technique was used in the three-electrode system, which showed that there was no signal of crystalline substance that affected the cyclic stability of the material while charging and discharging. These superior results prove that Ni0.7Co0.3-CMOL is a promising candidate for supercapacitor applications.