Prediction of potential mechanisms of rhubarb therapy for colorectal cancer based on network pharmacological analysis and molecular docking.

The objective of this study was to investigate the potential targets and mechanism of Rheum palmatum L in the treatment of colorectal cancer based on the network pharmacology and molecular docking, which could provide the theoretical basis for clinical applications. The potential components were screened using TCMSP database and articles. The gene targets of colorectal cancer were screened through the Genecards database and Online Mendelian Inheritance in Man database. Then, the common targets of components and colorectal cancer were used to construct the network diagram of active components and targets in Cytoscape 3.7.0. The protein-protein interaction (PPI) diagram was generated using String database, and the targets were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular docking between gene targets and active components was analyzed via AutoDock, and visualized through PyMol. Among this study, main targets might be TP53, EGF, MYC, CASP3, JUN, PTGS2, HSP90AA1, MMP9, ESR1, PPARG. And 10 key elements might associate with them, such as aloe-emodin, beta-sitosterol, gallic acid, eupatin, emodin, physcion, cis-resveratrol, rhein, crysophanol, catechin. The treatment process was found to involve nitrogen metabolism, p53 signaling pathway, and various cancer related pathway, as well as the AGE-RAGE signaling pathway, estrogen signaling pathway, interleukin-17 signaling pathway and thyroid hormone signaling pathway. The molecular docking was verified the combination between key components and their respective target proteins. Network pharmacological analysis demonstrated that R palmatum was could regulated p53, AGE-RAGE, interleukin-17 and related signaling pathway in colorectal cancer, which might provide a scientific basis of mechanism.

Common mechanisms of Wumei pills in treating ulcerative colitis and type 2 diabetes: Exploring an integrative approach through network pharmacology.

Wumei pills (WMP), a classical Chinese herbal formula, have shown efficacy in the treatment of ulcerative colitis (UC) and type 2 diabetes (T2DM). However, the underlying mechanisms by which WMP simultaneously targets these distinct diseases remain unclear. In this study, a network pharmacology approach was employed to unravel the potential molecular mechanisms of WMP in UC and T2DM treatment. This analysis provides a bioinformatics foundation for the traditional Chinese medicine concept of "treating different diseases with the same treatment." WMP was found to contain 65 active components, including flavonoids, sterols, and alkaloids, that act on 228 shared targets for UC and T2DM. Network analysis identified 5 core compounds (Quercetin, Kaempferol, beta-Sitosterol, Isocorypalmine, Stigmasterol) and 8 core proteins (AKT1, ESR1, TP53, IL6, JUN, MYC, TNF, EGFR) that play pivotal roles in the treatment of UC and T2DM by WMP. WMP exerts its therapeutic effects by modulating signaling pathways, including the NF-κB pathway, PI3K-Akt pathway, and p53 pathway. Molecular docking results indicate a strong binding affinity between core compounds and core genes. This study bridges the understanding of 2 diseases using network pharmacology and provides insights into shared therapeutic mechanisms, opening doors for further research in modern Chinese herbal formulations.

Comprehensive bioinformatics analysis of FXR1 across pan-cancer: Unraveling its diagnostic, prognostic, and immunological significance.

Fragile X-related protein 1 (FXR1) is an RNA-binding protein that belongs to the fragile X-related (FXR) family. Studies have shown that FXR1 plays an important role in cancer cell proliferation, invasion and migration and is differentially expressed in cancers. This study aimed to gain a comprehensive and systematic understanding of the analysis of FXR1's role in cancers. This would lead to a better understanding of how it contributes to the development and progression of various malignancies. this study conducted through The Cancer Genome Atlas (TCGA), GTEx, cBioPortal, TISIDB, GEPIA2 and HPA databases to investigated FXR1's role in cancers. For data analysis, various software platforms and web platforms were used, such as R, Cytoscape, hiplot plateform. A significant difference in FXR1 expression was observed across molecular and immune subtypes and across types of cancer. FXR1 expression correlates with disease-specific survival (DSS), and overall survival (OS) in several cancer pathways, further in progression-free interval (PFI) in most cancers. Additionally, FXR1 showed a correlation with genetic markers of immunomodulators in different cancer types. Our study provides insights into the role of FXR1 in promoting, inhibiting, and treating diverse cancers. FXR1 has the potential to serve as a diagnostic and prognostic biomarker for cancer, with therapeutic value in immune-based, targeted, or cytotoxic treatments. Further clinical validation and exploration of FXR1 in cancer treatment is necessary.

Network pharmacology and molecular docking study on the treatment of polycystic ovary syndrome with angelica sinensis- radix rehmanniae drug pair.

This study aimed to investigate the angelica sinensis - radix rehmanniae (AR) role in polycystic ovary syndrome (PCOS), employing network pharmacology and molecular docking techniques for active ingredient, targets, and pathway prediction. AR active components were obtained through TCMSP platform and literature search. The related targets of AR and PCOS were obtained through the disease and Swiss Target Prediction databases. An "active ingredient-target" network map was constructed using Cytoscape software, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was conducted through Hiplot. Finally, Auto Dock Tools software was used to conduct molecular docking between active ingredients and core targets. The main bioactive ingredients of AR in the treatment of PCOS are acteoside, baicalin, caffeic acid, cistanoside F, geniposide, etc. These ingredients involve 10 core targets, such as SRC, HSP90AA1, STAT3, MAPK1, and JUN. The effect of AR on anti-PCOS mainly involves the AGE-RAGE signaling pathway, Relaxin signaling pathway, TNF signaling pathway, and ErbB signaling pathway. Molecular docking results showed that the main active components and key targets of AR could be stably combined. AR can improve hyperandrogen status, regulate glucose homeostasis, and correct lipid metabolism and other physiological processes through multi-component, multi-target, and multi-pathway. Thus, it could play a significant role in PCOS treatment. The results of our study provide a scientific foundation for basic research and clinical applications of AR for the treatment of PCOS.

Prognostic Value of Inflammatory and Nutritional Markers for Patients With Early-Stage Poorly-to Moderately-Differentiated Cervical Squamous Cell Carcinoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and Onodera's prognostic nutritional index (OPNI) have been reported as prognostic markers for various cancers. We evaluated the prognostic value of the NLR, PLR, MLR, SII, SIRI, and OPNI for poorly-to moderately-differentiated cervical squamous cell carcinoma (CSCC). PATIENTS AND METHODS: We retrospectively analyzed the cases of 109 patients with early-stage poorly-to moderately-differentiated CSCC who underwent radical surgery at our institution in 2014-2017. The optimal cutoff points for the NLR, PLR, MLR, SII, SIRI, and OPNI were determined by receiver operating characteristic curves. Overall survival was analyzed by the Kaplan-Meier method. We performed a multivariate analysis using the Cox proportional hazard regression model to determine the independent prognostic indicators for early-stage poorly-to moderately-differentiated CSCC. RESULTS: The appropriate cutoff points were: NLR, 1.72; PLR, 111.96; MLR, .24; SII, 566.23; SIRI, 1.38; and OPNI, 52.68. The OS of the patients with a high OPNI (P = .04), low SII (P = .03), or low SIRI (P = .01) was significantly better. The uni- and multivariate analyses identified only the OPNI as an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC (P = .04 and P = .02). CONCLUSION: The OPNI is an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC; the NLR, PLR, MLR, SII, and SIRI are not.

NICD3 regulates the expression of MUC5AC and MUC2 by recruiting SMARCA4 and is involved in the differentiation of mucinous colorectal adenocarcinoma.

Adenocarcinoma is the most prevalent histological subtype of colorectal cancer (CRC), with mucinous colorectal adenocarcinoma (MCA) being a unique form. Although the mucinous subtype is known to elicit a worse response to chemotherapy and immunotherapy than the nonmucinous subtype, its pathogenesis remains poorly understood. Neurogenic locus notch homolog protein 3 (NOTCH3), a member of the NOTCH subfamilies, is highly expressed in CRC. In the past three decades, many studies have been performed evaluating the biological role of NOTCH3 in CRC. However, the precise activities of NOTCH3 in MCA, as well as the mechanisms involved in its transcriptional control, are yet to be elucidated. Our finding showed that the critical transcriptional regulatory factor transcription activator BRG1 (SMARCA4) directly binds to the intracellular domain of NOTCH3 to control transcriptional regulation. Moreover, RNA-sequencing results indicated a common targeting effect on the transcriptional activity of mucin-5AC (MUC5AC) and mucin-2 (MUC2) in CRC cells by NOTCH3 and SMARCA4. Furthermore, NOTCH3 was found to control the expressions of MUC5AC and MUC2 in a SMARCA4-dependent manner. MUC5AC and MUC2, which encode two secreted mucins, are located on chromosome 11p15.5, and are linked to the development of MCA. This finding suggests that the interaction between NOTCH3 and SMARCA4 may be involved in MCA differentiation by jointly targeting MUC5AC and MUC2. Patients with MCA are often treated in accordance with CRC guidelines. Determining the relationship between NOTCH3 and SMARCA4 by demonstrating their interactions in the pathophysiology of MCA could provide novel therapeutic targets and help identify potential prognostic markers for MCA.