Biological Procedures Online最新文献

{"title":"A novel telomere-associated genes signature for the prediction of prognosis and treatment responsiveness of hepatocellular carcinoma.","authors":"Kuo Kang, Hui Nie, Weilu Kuang, Xuanxuan Li, Yangying Zhou","doi":"10.1186/s12575-025-00271-8","DOIUrl":"10.1186/s12575-025-00271-8","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, characterized by its high malignancy and poor prognosis. Telomeres, crucial components of eukaryotic chromosomes, have been increasingly recognized for their involvement in tumorigenesis, development, and impact on the prognosis of cancer patients. However, the precise role of telomere-associated genes in HCC remains incompletely elucidated.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) database was utilized to download data from 374 HCC and 50 normal liver tissue samples. Differential genes were screened and intersected with 2093 telomere-related genes (TRGs) in GeneCards, resulting in the identification of 704 TRGs exhibiting survival differences. Through univariate Cox regression analysis, multivariate Cox regression analysis, and LASSO regression, a prognostic model consisting of 18 TRGs for HCC risk assessment was developed. The single-cell and spatial transcriptomics were utilized to analyze the expression and distribution of 18 TRGs in HCC. Subsequently, Mendelian randomization (MR) analysis confirmed a causal relationship between ASF1A and alcoholic HCC among the identified 18 TRGs. The expression and functional significance of ASF1A in HCC cell lines were investigated through colony formation assays, Transwell migration assays, and wound healing experiments.</p><p><strong>Results: </strong>We developed a prognostic risk model for HCC incorporating 18 TRGs. Kaplan-Meier analysis demonstrated that the overall survival (OS) rate of the high-risk group was significantly inferior to that of the low-risk group. Cox regression analysis identified age (HR = 1.017, 95% CI: 1.002-1.032, P = 0.03), stage (HR = 1.389, 95% CI: 1.111-1.737, P = 0.004), and risk score (HR = 5.097, 95% CI: 3.273-7.936, P < 0.001) as three independent risk factors for HCC patients. The five-year receiver operating characteristic curve (ROC) and multivariate Cox regression analysis further validated the accuracy of our model. Time-dependent ROC results revealed that the 1-year, 3-year, and 5-year AUC values were AUC = 0.801, AUC = 0.734, and AUC = 0.690, respectively. The expression and distribution of 18 TRGs in HCC were further validated through single-cell and spatial transcriptomics data. Additionally, immune subtype analysis indicated a significantly lower proportion of C3 and C4 subtypes in the high-risk TRG group compared to the low-risk group. Meanwhile, tumor immune dysfunction and exclusion (TIDE) were significantly higher in the high-risk group than in the low-risk group. Furthermore, we observed differences in IC50 values among nine chemotherapeutic drugs across different TRG risk subtypes which partially confirmed our model's predictive efficacy for immunotherapy. Amongst these eighteen TRGs analyzed by MR analysis, ASF1A was found to be associated with alcoholic HCC pathogenesis. We further confirmed ASF1A was significant overexpression in HCC","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"8"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and experimental verification in vivo reveal the mechanism of Zhushao Granules against ulcerative colitis.","authors":"Benjiao Gong, Chenglin Zhang, Shaofei Hu, Xueying Zhang, Hui Zou, Jiayao Li, Jiahui Wang, Yanlei Kao, Fujun Liu","doi":"10.1186/s12575-025-00268-3","DOIUrl":"10.1186/s12575-025-00268-3","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"7"},"PeriodicalIF":3.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the Future: A Game Theory to Tumor Therapeutic Strategies.","authors":"Fang-Yuan Liu, Xin Liu, Dan-Ni Ding, Shao-Xuan Liu, Jing Xu, Yu-Xin Zhao, Yan-Hong Wang, Feng-Juan Han","doi":"10.1186/s12575-025-00264-7","DOIUrl":"10.1186/s12575-025-00264-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"6"},"PeriodicalIF":3.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celebrating World Cancer Day: Innovative Biological Approaches to Cancer and their Alignment with Sustainable Development Goals (SDGs).","authors":"Hamed Kioumarsi, Bolin Liu","doi":"10.1186/s12575-025-00263-8","DOIUrl":"10.1186/s12575-025-00263-8","url":null,"abstract":"","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"3"},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of T-cell Depletion in Tumors and Advances in Clinical Research.","authors":"Xiangfei Su, Mi Zhang, Hong Zhu, Jingwen Cai, Zhen Wang, Yuewei Xu, Li Wang, Chen Shen, Ming Cai","doi":"10.1186/s12575-025-00265-6","DOIUrl":"10.1186/s12575-025-00265-6","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"5"},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Mechanism of Canmei Formula in Preventing and Treating Recurrence of Colorectal Adenoma Based on Data Mining and Algorithm Prediction.","authors":"Xiaoling Fu, Yimin Xu, Xinyue Han, Xiangying Lin, Jingnan Wang, Guanhong Li, Xiaochen Fu, Min Zhang","doi":"10.1186/s12575-025-00266-5","DOIUrl":"10.1186/s12575-025-00266-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The high incidence of recurrence and malignant transformation of colorectal adenoma (CRA) are current issues that need to be addressed in clinical practice. Canmei Formula (CMF) has shown promising results in the prevention and treatment, however, it lacks effective clinical data support and its mechanism of action is not fully elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this study is to evaluate the clinical efficacy and safety of CMF in preventing and treating CRA, and to explore its effective chemical components and pharmacological mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;A randomized controlled clinical trial was conducted, with patients diagnosed with CRA within 6 months as the study subjects. After randomization, the patients were divided into a treatment group (receiving CMF granules) or a control group (receiving berberine hydrochloride tablets). The one-year recurrence rate of CRA was used as the key efficacy indicator to assess the effectiveness of CMF in preventing and treating CRA. The chemical components of CMF were identified using the UFLC-Q-TOF-MS/MS combined system. Data mining and the wSDTNBI algorithm were combined to construct a differential expression gene (DEG) - CMF prediction target interaction network for CRA. The core targets of CMF in CRA prevention and treatment were identified through topological analysis, and validated using molecular docking and in vitro experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;During the period from October 1 2021 to December 31 2023, a total of 228 participants were included in the study. After block randomization, 114 patients were assigned to each group. In the treatment group, 98 patients completed follow-up examinations, with 16 patients (14.0%) exhibiting shedding, Adenoma recurrence was identified in 24 (24.5%) patients through colonoscopy. In the control group, 99 cases completed the follow-up examination, while 15 cases (13.2%) were lost to follow-up. There were 45 cases (45.5%) experienced recurrence of adenomas. During the follow-up period, no cases of colorectal cancer or severe adverse reactions were reported. UFLC-QTOF-MS/MS identification was combined with traditional Chinese medicine database mining to obtain 192 active chemical components of Canmei Formula. Using the wSDTNBI algorithm, 1044 prediction targets were predicted, and 3308 differentially expressed genes of CRA were extracted from the TCGA database. Network topology analysis and bioinformatics analysis were performed on 164 intersecting core targets. Molecular docking and qPCR analysis revealed that CMF downregulates angiotensin II type 1 receptor (AT1R) and regulated interleukin-8 (CXCL8) and matrix metalloproteinase 13 (MMP13) within the REN/Ang II/AT1R axis of the renin-angiotensin signaling pathway, thereby preventing and treating CRA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This small-scale randomized controlled clinical trial showed that CMF granules can safely and effect","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"4"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of HER2 Expression on the Prognosis of Muscle-Invasive Bladder Cancer Patients Treated with Bladder-Preservation Comprehensive Therapy.","authors":"Yatong Chen, Fei Luo, Tingji Zhang, Jian Li","doi":"10.1186/s12575-025-00261-w","DOIUrl":"10.1186/s12575-025-00261-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;HER2 expression has been confirmed to be associated with bladder cancer aggressiveness. Anti-HER2 RC48-ADC is approved in China for the treatment of patients with advanced urothelial carcinoma with failed chemotherapy who are HER2 positive (IHC 2 + or 3 +). The discovery of HER2 positivity in urothelial carcinoma and the development of anti-HER2 drugs have brought new hope for bladder preservation treatment in MIBC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate HER2 expression in MIBC patients and its correlations with clinical characteristics, to analyze the impact of HER2 expression on the prognosis of MIBC patients administered bladder-preservation comprehensive therapy, and to explore the efficacy and safety of RC48-ADC in MIBC patients administered bladder-preservation comprehensive therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively collected information on MIBC patients. All 217 patients underwent cTURBT, of whom 175 received GC chemotherapy, while the remaining 42, due to intolerance to GC chemotherapy and HER2 positivity (IHC 2 + or 3 +), received RC48-ADC treatment. Of the 175 patients administered cTURBT combined with GC chemotherapy, 92 and 83 were HER2-negative and HER2-positive, respectively. Recurrence-free survival (RFS) and overall survival (OS) in HER2-negative and HER2-positive patients were compared to analyze the correlation between HER2 expression and prognosis. RFS and OS in the 83 HER2-positive patients administered cTURBT combined with GC chemotherapy and the 42 HER2-positive patients administered cTURBT combined with RC48-ADC were compared to analyze the differences in prognosis between the two treatment methods. The adverse reactions of GC and RC48-ADC were also compared.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 217 included patients, 125 (57.6%) were HER2 positive (IHC 2 + or 3 +). HER2 positivity was significantly associated with tumor size, multifocality, pathological grade, tumor stage, and pelvic lymph node metastasis (P &lt; 0.05). Totally 175 patients underwent cTURBT combined with GC chemotherapy, including 92 HER2-negative and 83 HER2-positive cases. There were no significant differences in gender, age, smoking status, tumor location, and ECOG score between the two groups (P &gt; 0.05), but the proportions of patients with tumors &gt; 3 cm, multifocal tumors, T3 stage, high-grade tumors, and pelvic lymph node metastasis were higher in the HER2-positive group versus the HER2-negative group (P &lt; 0.05). Tumor recurrence rate in the 83 HER2-positive patients was 67.5%, with a median RFS of 19.0 months (95% CI: 10.3-27.7). Totally 22 deaths occurred during the follow-up period, with a median OS of 56.0 months (95% CI: 45.7-66.3). In the 92 HER2-negative patients, the tumor recurrence rate was 56.5%, with a median RFS of 36.0 months (95% CI: 26.1-45.9); 4 deaths occurred during the follow-up period, with the median OS not reached. After cTURBT, of the 125 HER2-positive patients exam","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"2"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved ChIP Sequencing for H3K27ac Profiling and Super-Enhancer Analysis Assisted by Fluorescence-Activated Sorting of Formalin-Fixed Paraffin-Embedded Tissues.","authors":"Nenggang Jiang, Zhihao Wen, Huan Tao, Hongyan Liao","doi":"10.1186/s12575-025-00262-9","DOIUrl":"10.1186/s12575-025-00262-9","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"1"},"PeriodicalIF":3.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology and Molecular Docking Study on the Mechanism of the Therapeutic Effect of Strychni Semen in NSCLC.","authors":"He Geng, Yujie Xue, Binghua Yan, Zhaoxue Lu, Hengjin Yang, Peng Li, Jundong Zhou","doi":"10.1186/s12575-024-00259-w","DOIUrl":"10.1186/s12575-024-00259-w","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"26 1","pages":"33"},"PeriodicalIF":3.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chang-Wei-Qing Combined with PD-1 Inhibitor Alleviates Colitis-Associated Colorectal Tumorigenesis by Modulating the Gut Microbiota and Restoring Intestinal Barrier.","authors":"Junkai Wen, Shunyun Wang, Kexiang Sun, Haoyue Wang, Zeting Yuan, Wanli Deng","doi":"10.1186/s12575-024-00258-x","DOIUrl":"10.1186/s12575-024-00258-x","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"26 1","pages":"32"},"PeriodicalIF":3.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}