Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway.

Nasopharyngeal carcinoma is one of the common malignant tumors that the pathogenesis has not yet been completely defined. SETD1A (histone lysine methyltransferase SET domain-containing 1A) is related to the occurrence of various cancers. However, the role of SETD1A in nasopharyngeal carcinoma remains unclear. The SETD1A overexpression vector, si-NC, si-SETD1A#1, and si-SETD1A#2 were transfected into nasopharyngeal carcinoma cells to overexpress or knockdown SETD1A expression. The assay of biofunction was used to explore the role of SETD1A in nasopharyngeal carcinoma cells. The assay of glucose uptake, lactate release, ATP level, western blot, cell proliferation, and cellular apoptosis analysis were performed to investigate the potential mechanism of SETD1A regulation in nasopharyngeal carcinoma. This study was the first to show that SETD1A was upregulated in nasopharyngeal carcinoma cells and the overexpression of SETD1A significantly promoted the cell proliferation and glycolysis and suppressed the cellular apoptosis. Moreover, SETD1A enhances aerobic glycolysis and cell biological function of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway. SETD1A induced PI3K/AKT activation and subsequently prevented cellular apoptosis. In conclusion, this study identified overexpressed SETD1A as a positive regulator of proliferation that induced nasopharyngeal carcinoma cells' aerobic glycolysis via PI3K/AKT signaling activation in vitro. This study laid a strong foundation for unveiling the precise anticancer mechanism of SETD1A. The SETD1A may become a novel biomarker for further inhibitor design to obstruct the PI3K/AKT-dependent nasopharyngeal carcinoma progression.

Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides.

Pseudomonads are cosmopolitan microorganisms able to produce a wide array of specialized metabolites. These molecules allow Pseudomonas to scavenge nutrients, sense population density and enhance or inhibit growth of competing microorganisms. However, these valuable metabolites are typically characterized one-molecule-one-microbe at a time, instead of being inventoried in large numbers. To index and map the diversity of molecules detected from these organisms, 260 strains of ecologically diverse origins were subjected to mass-spectrometry-based molecular networking. Molecular networking not only enables dereplication of molecules, but also sheds light on their structural relationships. Moreover, it accelerates the discovery of new molecules. Here, by indexing the Pseudomonas specialized metabolome, we report the molecular-networking-based discovery of four molecules and their evolutionary relationships: a poaeamide analogue and a molecular subfamily of cyclic lipopeptides, bananamides 1, 2 and 3. Analysis of their biosynthetic gene cluster shows that it constitutes a distinct evolutionary branch of the Pseudomonas cyclic lipopeptides. Through analysis of an additional 370 extracts of wheat-associated Pseudomonas, we demonstrate how the detailed knowledge from our reference index can be efficiently propagated to annotate complex metabolomic data from other studies, akin to the way in which newly generated genomic information can be compared to data from public databases.

Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated with Azithromycin.

In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors, and natural products) are measured using phenotypic assays. However, advances in mass spectrometry-based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. Although previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reduce pathogenicity, we observed no clear decrease in specialized metabolite production.

Emerging mass spectrometry techniques for the direct analysis of microbial colonies.

One of the emerging areas in microbiology is detecting specialized metabolites produced by microbial colonies and communities with mass spectrometry. In this review/perspective, we illustrate the emerging mass spectrometry methodologies that enable the interrogation of specialized metabolites directly from microbial colonies. Mass spectrometry techniques such as imaging mass spectrometry and real-time mass spectrometry allow two and three-dimensional visualization of the distribution of metabolites, often with minimal sample pretreatment. The speed in which molecules are captured using these methods requires the development of new molecular visualization tools such as molecular networking. Together, these tools are beginning to provide unprecedented insight into the chemical world that microbes experience.

Real-time metabolomics on living microorganisms using ambient electrospray ionization flow-probe.

Microorganisms such as bacteria and fungi produce a variety of specialized metabolites that are invaluable for agriculture, biological research, and drug discovery. However, the screening of microbial metabolic output is usually a time-intensive task. Here, we utilize a liquid microjunction surface sampling probe for electrospray ionization-mass spectrometry to extract and ionize metabolite mixtures directly from living microbial colonies grown on soft nutrient agar in Petri-dishes without any sample pretreatment. To demonstrate the robustness of the method, this technique was applied to observe the metabolic output of more than 30 microorganisms, including yeast, filamentous fungi, pathogens, and marine-derived bacteria, that were collected worldwide. Diverse natural products produced from different microbes, including Streptomyces coelicolor , Bacillus subtilis , and Pseudomonas aeruginosa are further characterized.