Biological Procedures Online最新文献

Background: Zhushao Granules (ZSG) had exhibited beneficial effects in the treatment of ulcerative colitis (UC) as an effective herbal prescription in Traditional Chinese Medicine. However, the underlying anti-inflammatory mechanism of ZSG remains unclear. This study aimed to decipher the mechanism of ZSG against UC combining network pharmacology and animal-based experiments.

Methods: Network pharmacology was employed to identify active components and therapeutic targets of ZSG against UC. The protein-protein interaction (PPI) network was constructed among the therapeutic targets using the STRING database, and GO and pathway analyses were carried out using DAVID. Then, the "herb-component-target-pathway" network based on therapeutic targets was established and the topological parameters were subsequently calculated to identify hub active components, targets and pathways by Cytoscape. Finally, the therapeutic function and the special pathway of ZSG against UC were validated using a TNBS-induced UC model in BABL/c mice.

Results: Ninety-four active components of ZSG and 460 potential targets were acquired from the Encyclopedia of Traditional Chinese Medicine and Tradition Chinese Medicine Systems Pharmacology Database and Analysis Platform. 884 potential targets of UC were obtained from OMIM and HINT. Sixty-two overlapping potential targets were identified as therapeutic targets of ZSG against UC. PPI network filtered out 61 therapeutic targets. GO and pathway analyses extracted 48, 25, and 98 terms corresponding to biological processes, molecular functions and Reactome pathways, respectively. Enrichment analysis suggested that the therapeutic targets were mainly involved in immune regulation, especially RIP-mediated NF-κB activation via ZBP1. Topological analysis of the "herb-component-target-pathway" network recognized 9 hub components, 20 hub targets and 18 hub pathways. The animal-based experiments revealed that ZSG ameliorated symptoms and histological changes in TNBS-induced colitis by significantly inhibiting the ZBP1/RIP/NF-κB pathway.

Conclusions: ZSG might alleviate the mucosal damage and ameliorate colitis via targeting ZBP1/RIP/NF-κB pathway, which laid the theoretical foundation for the clinical application and further study of ZSG and provided new insights into UC treatment.

Background: Cancer poses significant economic and societal burdens on countries in the coming decades. During chemotherapy, patients frequently encounter adverse reactions. Recent research has revealed that Chinese medicine plays a crucial role in mitigating the side effects of chemotherapy. Therefore, in this article, we propose that the cancer treatment process can be likened to an unequal game. To refine treatment strategies, we suggest employing the Steinberg model to incorporate Chinese medicine into the chemotherapy regimen for tumor treatment.

Results: We found that when malignant tumors exhibit vigorous proliferation, doctors should administer Chinese medicine in conjunction with chemotherapy drugs, continuously optimizing the therapeutic effect of the Chinese medicine. Upon reaching a specific threshold in the treatment effect of the Chinese medicine, doctors may appropriately augment the dosage of chemotherapy drugs, building upon the initial regimen. Conversely, in cases where the proliferation ability of malignant tumors is weak, the dosage of chemotherapy and the adjuvant therapy with Chinese medicine should be kept in a relatively balanced state. Once the effect of the Chinese medicine attains a particular threshold, the dosage of chemotherapy can be concurrently increased to achieve a superior therapeutic result.

Conclusions: From a game theory perspective, doctors can devise strategies to minimize drug toxicity and improve tumor treatment outcomes by coordinating the use of chemotherapy drugs with appropriate adjustments to Chinese medicine therapy methods.

T lymphocytes (T cells) are essential components of the adaptive immune system that play a vital role in identifying and eliminating infected and tumor cells. In tumor immunotherapy, T cells have emerged as a promising therapeutic strategy due to their high specificity, potent cytotoxic capability, long-lasting immune memory, and adaptability within immunotherapeutic approaches. However, tumors can evade the immune system by depleting T cells through various mechanisms, such as inhibitory receptor signaling, metabolic exhaustion, and physical barriers within the tumor microenvironment. This review provided an overview of the mechanisms underlying T-cell depletion in tumors and discussed recent advances in clinical research related to T-cell immunotherapy for tumors. It highlighted the need for in-depth studies on key issues such as indications, dosage, and sequencing of combined therapeutic strategies tailored to different patients and tumor types, providing practical guidance for individualized treatment. Future research on T-cell depletion would be necessary to uncover the fundamental mechanisms and laws of T-cell depletion, offering both theoretical insights and practical guidance for the selection and optimization of tumor immunotherapy. Furthermore, interdisciplinary, cross-disciplinary, and international collaborative innovations are necessary for developing more effective and safer treatments for tumor patients.

Archived clinical formalin-fixed paraffin-embedded tissue (FFPE) is valuable for the study of tumor epigenetics. Although protocol of chromatin immunoprecipitation coupled with next generation sequencing (NGS) (ChIP-seq) using FFPE samples has been established, removal of interference signals from non-target cell components in the samples is still needed. In this study, the protocol of ChIP-seq with purified cells from FFPE lymphoid tissue of nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI) after fluorescence-activated cell sorting (FACS) was established and optimized. Essential steps included single cell preparation, heat treatment enhancing antigen retrieval and labeling, cell sorting, chromatin shearing, ChIP and NGS. Through assistance of FACS, we successfully isolated tumor cells from FFPE lymph node samples of nTFHL-AI and profiled super-enhancers (SEs) mapping by enrichment of H3K27ac signals. The data indicated that the SEs mapping of the sorted cells was different from that of the entire unsorted tissue sample. The H3K27ac signals with cell lineage specificity from background cell components were successfully removed, and the remaining SEs mapping was more similar to T follicular helper cell in an unsupervised clustering analysis, rather than the primary tissue. In addition, we also evaluated the protocol using cultured pure cell lines, and the results indicated that the sequencing data obtained through this protocol had high fidelity and reproducibility. These results show that ChIP-seq for H3K27ac profiling and SEs mapping assisted by FACS with pathological FFPE tissue is available for research of histone modification. Precise epigenetic characteristics of the tumor cell can be described with this protocol.

Strychni Semen, characterized by its bitter taste and warm properties, has been confirmed to possess anti-tumor properties. However, the molecular mechanism of Strychni Semen in treating non-small cell lung cancer (NSCLC) needs further study. This study aimed to explore the molecular mechanism of Strychni Semen in treating NSCLC based on network pharmacology and molecular docking. The active components and targets of Strychni Semen were retrieved from the TCMSP, supplemented by the HERB database and the related literature. NSCLC-related targets were retrieved from the GeneCards, OMIM and DisGenet databases. The intersection targets of Strychni Semen in treating NSCLC were obtained via an online platform. The Protein-Protein Interaction (PPI) network was subsequently constructed to deeply analyse the interrelationship of the intersection targets via the String database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out via the Metascape database. The interactive networks between Strychni Semen and NSCLC were constructed via Cytoscape 3.9.1. Molecular docking detected interactions between the key components and the core targets. The core targets were validated via GEO datasets. 21 active components and 67 targets were identified, with 47 associated with NSCLC. The key active components were Stigmasterol, IcarideA, 2-Hydroxymethylanthraquinone, (+)-catechin, (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, (S)-Stylopine, Brucine and Isobrucine. The core targets were PTGS2, NR3C1, ESR1, CASP3 and PRKACA. Molecular docking revealed that these compounds undergo strong binding affinity with the core genes. GEO database indicated that PTGS2 was the most promising core target. In addition, Strychni Semen's effects on NSCLC involved mainly the Calcium pathway, the Estrogen pathway, and the cGMP-PKG and cAMP pathways. This study visually demonstrated the mechanism of the therapeutic effect of Strychni Semen in NSCLC through multiple components, targets and pathways which provides a basis for clinical treatment and further experimental research.

Chang-Wei-Qing (CWQ) is a widely recognized Traditional Chinese Medicine (TCM) formulation composed of Astragalus, Codonopsis, Atractylodes, Poria, Coix seed, Akebia trifoliata Koidz, Sargentodoxa cuneata, and Vitis quinquangularis Rehd. This formulation has garnered significant interest for its positive effects in mitigating colorectal cancer, and when combined with PD-1, it affects some gut microbiota associated with tumor infiltrating lymphocytes cells. However, the biological rationale underlying the suppression of colitis-associated colorectal cancer (CAC) in AOM/DSS-treated mice by CWQ combined with PD-1 inhibitor remains to be explored. Our aim is to explore the chemopreventive effect of CWQ combined with PD-1 inhibitor on CAC, with a focus on modulating the gut microbiota. A mouse model of CAC was established using azoxymethane (AOM) and dextran sulfate sodium (DSS) treatment. Pathological evaluation of tissue samples included immunohistochemistry and hematoxylin and eosin staining. Intestinal barrier function was assessed by transmission electron microscopy. Fecal microbiota and metabolites were analyzed through 16 S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Mice treated with antibiotics served as models for fecal microbiota transplantation. CWQ combined with PD-1 inhibitor suppressed CAC in AOM/DSS-treated mice. This combined therapy effectively alleviated gut dysbiosis in the CAC model by increasing microbial diversity, enriching probiotic populations such as Limosilactobacillus and Bifidobacterium, and reducing pathogenic bacteria like Desulfovibrio. Additionally, CWQ combined with PD-1 inhibitor downregulated metabolites associated with the NF-kappa B signaling pathway. The combined treatment also significantly improved intestinal barrier function in CAC mice. Transmission electron microscopy of the CWQ combined with PD-1 inhibitor group showed enhanced cellular integrity, a relatively normal mitochondrial structure with intact membranes, and a more abundant, unexpanded endoplasmic reticulum, underscoring the protective effects of this combination on intestinal barrier integrity. Transcriptomic analysis further demonstrated that the combined therapy upregulated genes involved in tight and adherens junctions, while downregulating genes linked to innate immune responses. CWQ combined with PD-1 inhibitor can ameliorate dysbiosis in the AOM/DSS mouse model, with the metabolites of the gut microbiome potentially possessing anti-inflammatory activity. Moreover, CWQ combined with PD-1 inhibitor improves intestinal barrier function, thereby effectively inhibiting the occurrence and development of CAC.