Wumei San (WMS) is a traditional Chinese medicine that has been widely applied in the treatment of piglet diarrhea (PD). However, the mechanism of WMS in PD has not been investigated. In this study, the main active compounds of WMS and the target proteins were obtained from the Traditional Chinese Medicine Systematic Pharmacology, PubChem, and SwissTargetPrediction databases. The molecular targets of PD were identified using GeneCards, OMIM, and NCBI databases. The common targets of WMS and PD were screened out and converted into UniProt gene symbols. PD-related target genes were constructed into a protein-protein interaction network, which was further analyzed by the STRING online database. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to construct the component-target gene-disease network. Molecular docking was then used to examine the relationship between the core compounds and proteins. As a result, a total of 32 active compounds and 638 target genes of WMS were identified, and a WMS-compound-target network was successfully constructed. Through network pharmacology analysis, 14 core compounds in WMS that showed an effect on PD were identified. The targets revealed by GO and KEGG enrichment analysis were associated with the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, IL-17 signaling pathway, and other pathways and physiological processes. Molecular docking analysis revealed that the active compounds in WMS spontaneously bind to their targets. The results indicated that WMS may regulate the local immune response and inflammatory factors mainly through the TNF signaling pathway, IL-17 signaling pathway, and other pathways. WMS is a promising treatment strategy for PD. This study provides new insights into the potential mechanism of WMS in PD.

Background: Breast carcinoma is well recognized to be having the highest global occurrence rate among all cancers, being the leading cause of cancer mortality in females. The aim of this study was to elucidate breast cancer at the genomic and transcriptomic levels in different subtypes so that we can develop more personalized treatments and precision medicine to obtain better outcomes. Method: In this study, an expression profiling dataset downloaded from the Gene Expression Omnibus database, GSE45827, was re-analyzed to compare the expression profiles of breast cancer samples in the different subtypes. Using the GEO2R tool, different expression genes were identified. Using the STRING online tool, the protein-protein interaction networks were conducted. Using the Cytoscape software, we found modules, seed genes, and hub genes and performed pathway enrichment analysis. The Kaplan-Meier plotter was used to analyze the overall survival. MicroRNAs and transcription factors targeted different expression genes and were predicted by the Enrichr web server. Result: The analysis of these elements implied that the carcinogenesis and development of triple-negative breast cancer were the most important and complicated in breast carcinoma, occupying the most different expression genes, modules, seed genes, hub genes, and the most complex protein-protein interaction network and signal pathway. In addition, the luminal A subtype might occur in a completely different way from the other three subtypes as the pathways enriched in the luminal A subtype did not overlap with the others. We identified 16 hub genes that were related to good prognosis in triple-negative breast cancer. Moreover, SRSF1 was negatively correlated with overall survival in the Her2 subtype, while in the luminal A subtype, it showed the opposite relationship. Also, in the luminal B subtype, CCNB1 and KIF23 were associated with poor prognosis. Furthermore, new transcription factors and microRNAs were introduced to breast cancer which would shed light upon breast cancer in a new way and provide a novel therapeutic strategy. Conclusion: We preliminarily delved into the potentially comprehensive molecular mechanisms of breast cancer by creating a holistic view at the genomic and transcriptomic levels in different subtypes using computational tools. We also introduced new prognosis-related genes and novel therapeutic strategies and cast new light upon breast cancer.

Tri-(2,3-dibromopropyl) isocyanate (TBC), a newly brominated flame retardant, is widely used in the synthesis of flame retardant materials with characteristics of persistent organic pollutants. To obtain environmental exposure risks of TBC, Wistar rats and HepG2 cell were used for in vivo and in vitro studies on the toxicity of TBC and relevant ecotoxicological mechanisms of apoptosis. 80 Wistar rats were randomly selected and divided into four exposure groups (0, 0.313, 0.625, 1.250) g/(kg·bw) TBC, half male and half female, with oral administration for 28 days. Wistar rats exhibited appetite loss, weight loss, and dull hair with increasing period of TBC exposure. The pathological examinations revealed the most severe damage of liver and the ratio of liver/body weight of 35.497 × 10-3 for high-dosed group (1.250 g/kg·bw) was higher than that of 32.792 × 10-3 for control group in female rats with identical trend in male rats. The above indicators was fairly consistent with the serum test results which further confirmed the liver to be the target organ. The exposure dosages of HepG2 cell were (0, 12.5, 25, 50) μg/mL, individually. The HepG2 cells exposed to TBC for 72 h displayed hazy cell contour and decreased density of cell growth. And there was an inhibition detected by MTT assay, where the maximum inhibition rate was 19.93% under the dose of 50 μg/mL TBC. Apoptosis rate detected by flow cytometry which was demonstrated to be positively correlated to exposure dosage of TBC. The apoptosis rates of the low, medium and high dose groups of TBC exposure were (1.082 ± 0.109) %, (3.017 ± 0.09) % and (6.813 ± 0.233) %, individually. Targeted genes and corresponding protein expressions that triggering apoptosis both in vivo and in vitro were significantly altered. Overall, this work discloses the impacts of TBC exposure on hepatotoxicity, which provides new insights for chemical risk assessments of accelerate cell apoptosis via mitochondrial and death receptor pathway.

UNASSIGNED: The aim of this study was to investigate the mechanism of Modified Ginseng-Schisandra Decoction in the treatment of recurrent respiratory tract infection (RRTI) using network pharmacology.
UNASSIGNED: To screen the active ingredients of A Modified Ginseng-Schisandra Decoction, TCMSP, TCMID, Batman-TCM and PubChem database were applied. To predict the targets of active ingredients on RRTI, TCMSP, Pubmed, OMIM, Drug Bank, GAD and TTD database were used. The compounds-therapeutic target network was constructed with Cytoscape 3.7.2 software. The STRING database was used to construct a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify potential signal pathways.
UNASSIGNED: The 3 main active ingredients of Modified Ginseng-Schisandra Decoction obtained by screening were quercetin, kaempferol, and isoflavone; the main therapeutic targets were PTGS2, ESR1, AR, PPARG, NOS2, and others. Based on the PPI network, we found that the targets of Modified Ginseng-Schisandra Decoction were significantly enriched in (FDR <0.01) cancer pathway, tumor necrosis factor (TNF) signaling pathway, hypoxia-inducible factor (HIF-1) signaling pathway, and others.
UNASSIGNED: Modified Ginseng-Schisandra Decoction can treat RRTI primarily through acting in the signal transduction of some key nodes of cancer pathway and TNF pathway. It exerts a direct or indirect influence on multiple signaling pathways, and has the characteristics of multicomponent, multitarget, and multichannel action.

Scrub typhus is a fatal zoonotic disease caused by Orientia tsutsugamushi. This disease is accompanied by systemic vasculitis, lymphadenopathy, headache, myalgia, and eschar. In recent studies, a novel strain that is resistant to current medical treatment was identified in Thailand. Thus, the development of new specific drugs for scrub typhus is needed. However, the exact molecular mechanism governing the progression of scrub typhus has not been fully elucidated. To understand disease-related genetic factors and mechanisms associated with the progression of scrub typhus, we performed a genome-wide association study (GWAS) in scrub typhus-infected patients and found a scrub typhus-related signaling pathway by molecular interaction search tool (MIST) and PANTHER. We identified eight potent scrub typhus-related single nucleotide polymorphisms (SNPs) located on the PRMT6, PLGLB2, DTWD2, BATF, JDP2, ONECUT1, WDR72, KLK, MAP3K7, and TGFBR2 genes using a GWAS. We also identified 224 genes by analyzing protein-protein interactions among candidate genes of scrub typhus and identified 15 signaling pathways associated with over 10 genes by classifying these genes according to signaling pathways. The signaling pathway with the largest number of associated genes was the gonadotropin-releasing hormone receptor pathway, followed by the TGF-beta signaling pathway and the apoptosis signaling pathway. To the best of our knowledge, this report describes the first GWAS in scrub typhus.

The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied.
31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines. Tumor growth measurements, histological and immunohistochemistry analysis, Western blotting, EGFR and K-RAS mutation detection and gefitinib sensitive assay were performed to evaluate the characteristic of established PDX models. Immunofluorescence analysis, anchorage-independent cell growth, Western blotting and gefitinib sensitive assay were performed to assay the characteristic of established primary cell lines. The whole-exome sequencing was used to compare the characteristic of the patient\'s tumor tissue, established PDX and primary cell line.
Twenty-one lung cancer PDX models (67.74%, 21/31) and ten primary cell lines (32.25%, 10/31) were established from patients\' tumor tissues. The histology and pathological immunohistochemistry of PDX xenografts are consistent with the patients\' tumor samples. Various signal pathways were activated in different PDX models (n = 5) and primary cell lines (n = 2). EGFR mutation PDX model and primary cell line (LG1) were sensitive to gefitinib treatment. The expression of CK8/18, TTF1 and NapsinA in LG1 and LG50 primary cells were also positive. And the activated signal pathways were activated in LG1 and LG50 primary cell lines. Furthermore, the gene mutation in PDX tumor tissues and primary cell line (LG50) was consistent with the mutation in LG50 patient\'s tumor tissues.
These data suggested that established lung cancer PDX models and primary cell lines reserved mostly molecular characteristics of primary lung cancer and could provide a new tool to further understand the mechanisms and explore new therapeutic strategies.