Biological Procedures Online最新文献

{"title":"TSZAF Monomer Combination Inhibits the Progression of Ovarian Cancer Via Regulating the AKT/FOXO3A-mediated Glycolysis Pathway.","authors":"Long Zhang, Jialiang Yao, Ziqi Chen, Pan Yu, Xinyi Lu, Jiajun Liu, Bin Luo, Jiwei Liu, Zujun Que, Yan Wu, Jianhui Tian","doi":"10.1186/s12575-025-00323-z","DOIUrl":"10.1186/s12575-025-00323-z","url":null,"abstract":"<p><strong>Background: </strong>Tiao-Shen-Zhi-Ai Formula (TSZAF) is a compound prescription of traditional Chinese medicine used clinically for the treatment of ovarian cancer. In this study, we selected three main active ingredients from TSZAF and combined them into a new TSZAF monomer combination (TSZAF mc) to investigate its effects and mechanisms on inhibiting ovarian cancer proliferation and inducing apoptosis.</p><p><strong>Methods: </strong>The effects of TSZAF mc on proliferative activity and apoptosis in ovarian cancer HEY and SKOV3.IP1 cells were assessed in vitro using CCK-8 assay, colony formation assay, and apoptosis assay. Micromethods, flow cytometry, and immunofluorescence were employed to evaluate the impact of TSZAF mc on aerobic glycolytic metabolites and mitochondrial membrane potential. The mRNA and protein expression of key glycolytic genes were detected by quantitative real-time PCR (RT-PCR) and Western blot (WB). An ovarian cancer subcutaneous tumor model was established in NOD-SCID mice using SKOV3.IP1 cells. TSZAF mc was administered via continuous intraperitoneal injection, and its antitumor efficacy in vivo was assessed through anatomical observation, hematoxylin and eosin (H&E) staining, and immunohistochemistry (IHC). Further RT-PCR, WB, and IHC were performed to validate the expression of key upstream glycolytic genes at mRNA and protein levels. Drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) were used to confirm binding targets. Molecular docking was performed to predict the binding interactions between the monomers and AKT. Finally, the regulatory relationships within signaling pathways were elucidated based on functional assays.</p><p><strong>Results: </strong>TSZAF mc effectively inhibited ovarian cancer proliferation and induced apoptosis. It reduced lactate and ATP production, downregulated mitochondrial membrane potential, and decreased the mRNA and protein expression of key glycolytic genes, including HK2, PKM2, PFKM, GLUT1, and LDHA. In vivo, TSZAF mc suppressed ovarian cancer growth. Moreover, TSZAF mc downregulated the expression of phosphorylated AKT (p-AKT) and phosphorylated FOXO3A (p-FOXO3A) at both protein and tissue levels. CETSA and DARTS demonstrated that TSZAF mc binds AKT. The AKT activator SC79 reversed the inhibitory effects of TSZAF mc on ovarian cancer proliferation and the downregulation of glycolytic proteins.</p><p><strong>Conclusion: </strong>TSZAF mc inhibits ovarian cancer progression by regulating the AKT/ FOXO3A-mediated glycolysis pathway, which may represent one of the mechanisms underlying the clinical efficacy of TSZAF in ovarian cancer treatment.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206415","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":"Leishmania Infection: A Bioorganic Model Under the Light of Benchtop Low Field Nuclear Magnetic Resonance.","authors":"Jairo Mendoza-Roldan, Paola Albanese, Carmela Di Spiridione, Mirco Vacca, Matteo Spagnuolo, Mario Alves, Mariaelisa Carbonara, Maria De Angelis, Danilo Vona, Domenico Otranto","doi":"10.1186/s12575-026-00328-2","DOIUrl":"10.1186/s12575-026-00328-2","url":null,"abstract":"<p><p>BACKGROUND: Low-field benchtop Nuclear Magnetic Resonance (NMR) spectrometers rely on permanent magnets and do not require deuterated solvents, being increasingly employed for quality control and the profilometric assays of complex matrices from food products to metabolically enriched exudates. In this study, the non-destructive, non-invasive, low-cost and time-effective nature of benchtop NMR investigations was exploited to separate Leishmania infantum -positive and -negative dog (Canis lupus familiaris) sera. Moreover, among the Leishmania-positive samples, sera with either circulating free or complexed antibody molecules displayed distinctive NMR profiles with promising discriminatory potential. METHODS: This approach is made possible by the identification of specific bioorganic 1D and 2D NMR signals, such as protons found in pyranose (PYR), phospholipid (SPC), and acetyl moieties (Glyc), whose distribution in serum samples varies in association with specific parasitic infections. RESULTS: The discrimination among Leishmania Negative (n=5) vs Low positive (n=8) samples was successfully performed using the summed integration areas of 3 main buckets (SPC, Glyc, late PYR), while the analytical speciation of High (Ab+) positive (n=8) samples was reached recurring to a further integrated area, belonging to early PYR signals. CONCLUSION: The characterization of inflammatory states through traces of oxidized lipids, and the study of immunological activation using bioorganic signals of glycoproteins, can be easily exploited on a broad scale even in different pathological contexts with features similar to the Leishmania case report. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194084","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":"Correction: Piperlongumine Inhibits Lung Cancer Growth by Inducing Endoplasmic Reticulum Stress Leading To Suppression of M2 Macrophage Polarization.","authors":"Yixin Zhou, Wenjing Teng, Jianchun Wu, Yingbin Luo, Yuli Wang, Yan Li","doi":"10.1186/s12575-026-00324-6","DOIUrl":"10.1186/s12575-026-00324-6","url":null,"abstract":"","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"28 1","pages":"5"},"PeriodicalIF":4.3,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050049","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":"New Candidate Reference Measurement Procedures for MET CNV Detection and Quantification Using Digital PCR.","authors":"Jessica Petiti, Sabrina Caria, Laura Revel, Marika Fava, Giovanna Carrà, Raffaella Albano, Sara Gilardi, Tiziana Venesio, Carla Divieto","doi":"10.1186/s12575-026-00325-5","DOIUrl":"10.1186/s12575-026-00325-5","url":null,"abstract":"<p><p>BACKGROUND: Copy number variation (CNV) of the MET gene is a clinically relevant alteration associated with tumorigenesis, disease progression, and therapy resistance in several cancers, particularly non-small cell lung cancer and colorectal cancer. Elevated MET copy number has prognostic value and can predict response to MET inhibitors, underscoring the clinical need for accurate quantification of MET CNV. However, current diagnostic platforms, such as FISH, qPCR, and NGS, suffer from limited reproducibility, lack of sensitivity, and poor metrological traceability. All these factors lead to poor standardization (e.g. in the reporting units and reference intervals), creating a barrier to inter-laboratory comparability and clinical harmonization. Digital PCR (dPCR) has emerged as a powerful alternative, offering absolute quantification, high sensitivity, and robustness. These features make dPCR particularly suitable for the development of Reference Measurement Procedures (RMPs), essential to establish SI (units) traceability and support the production of certified reference materials. RESULTS: Here, we report the design, optimization, and validation of a duplex droplet dPCR (ddPCR) assay targeting MET and the diploid reference gene RPPH1. Using synthetic constructs, diploid and MET-amplified cell lines, and reference materials, we systematically optimized assay conditions and evaluated analytical performance. The duplex ddPCR showed excellent linearity (R²=0.988), low intra- and inter-run variability (CV≈3.8–3.9%), and reliable quantification across a dynamic range of copy numbers. Measurement uncertainty was rigorously estimated, aligning with metrological standards. Importantly, baseline measurements in diploid cell lines yielded values consistent with the expected two-copy state, confirming accuracy under physiological conditions. CONCLUSION: This work introduces a rigorously validated candidate RMP for MET CNV quantification. By enabling traceable and reproducible measurements, the method addresses a critical gap in CNV standardization and provides a foundation for certified reference material development. The adoption of this RMP has the potential to harmonize molecular diagnostics across laboratories, improve the comparability of clinical trial results, and strengthen the integration of CNV testing into precision oncology, ultimately enhancing patient outcomes. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":"10"},"PeriodicalIF":4.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002880","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":"A Multi-Center Cohort-Based circRNA Diagnostic Model for Detection of Gastric Cancer.","authors":"Xiaoyu Gu, Shuo Ma, Xun Gao, Chenyan Yuan, Wei Gao, Fengfeng Zhao, Yonghui Liu, Chen Zhang, Guoqiu Wu, Shuang Liu","doi":"10.1186/s12575-026-00326-4","DOIUrl":"10.1186/s12575-026-00326-4","url":null,"abstract":"<p><p>BACKGROUND: Gastric cancer (GC) remains one of the most detrimental diseases to human health. Owing to the subtle nature of early symptoms and the absence of robust and effective screening biomarkers, most patients are diagnosed at an advanced stage. Herein, our objective is to establish a non-invasive diagnostic strategy based on circular RNAs (circRNAs) to facilitate the detection of GC. METHODS: We conducted a comprehensive genome-wide screening to identify key circRNAs, which were subsequently validated via RT-qPCR and translated into a plasma-based liquid biopsy analysis. The Chi-square test was applied to evaluate the relationship between circRNA expression and clinicopathological parameters. Receiver Operating Characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of circRNAs in GC. A logistic regression model was established for the prediction of GC and validated in independent clinical cohorts. RESULTS: In the discovery phase, we identified 2 circRNA candidates, hsa_circ_0001185 and hsa_circ_0005265, which were subsequently found to be significantly upregulated in the serum of GC patients through liquid biopsy analysis. The Chi-square test revealed that elevated expression of these circRNAs was significantly correlated with differentiation grade, lymph node metastasis, and TNM stage. ROC analysis demonstrated that hsa_circ_0001185 and hsa_circ_0005265 effectively discriminated GC patients from non-diseased controls, with AUC values of 0.909 and 0.853, respectively. The Diagnostic Model for GC (GC-DM) we developed exhibited an AUC of 0.915, which was subsequently validated in two independent cohorts. CONCLUSION: We developed a GC diagnostic model based on hsa_circ_0001185 and hsa_circ_0005265, demonstrating robust non-invasive diagnostic potential for the detection of GC patients. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988013","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":"Integrated Bioinformatics and Experimental Validation Reveal Fuzheng Yi'ai Formula Induces Immunogenic Cell Death Via the PERK-eIF2α-ATF4 Pathway for Prostate Cancer Treatment.","authors":"Xiaopeng Yu, Lian Peng, Wen Sheng, Renyi Yang, Qinghu He","doi":"10.1186/s12575-025-00321-1","DOIUrl":"10.1186/s12575-025-00321-1","url":null,"abstract":"<p><p>BACKGROUND: The inherently immune-cold microenvironment of prostate cancer (PCa) is a major barrier to the efficacy of immune checkpoint inhibitors (ICIs). Strategies capable of converting “cold” tumors into “hot” ones are therefore urgently needed. This study investigated how the traditional Chinese medicine prescription Fuzheng Yi’ai Formula (FZYAF) reverses the immunosuppressive state of PCa by inducing immunogenic cell death (ICD) and elucidated the underlying molecular mechanisms. METHODS: A combined strategy integrating bioinformatics, in vitro, and in vivo experiments was applied. Core PCa-related targets were first identified using weighted gene co-expression network analysis (WGCNA) and two-sample Mendelian randomization (MR). Ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) was used to characterize active compounds in FZYAF and predict their potential targets. The effects of FZYAF-medicated serum on PCa cell proliferation, migration, invasion, and ICD hallmarks (cell-surface calreticulin (CRT) exposure and extracellular ATP and high-mobility group box 1 (HMGB1) release) were evaluated in vitro. Immunogenicity was assessed in vivo using a prophylactic tumor vaccine model in C57BL/6 mice. The involvement of key signaling pathways was further examined using the PERK-specific inhibitor GSK2606414, along with systematic analysis of the tumor immune microenvironment. RESULTS: Bioinformatics analysis identified ATF4, HMGB1, CYP1B1, and DLL1 as key causal targets linking FZYAF with PCa. In vitro experiments confirmed that FZYAF significantly inhibited PCa cell proliferation and motility in a dose-dependent manner, upregulated the expression of ATF4 and HMGB1, and effectively induced ICD hallmarks (CRT exposure, extracellular secretion of ATP and HMGB1). In vivo, FZYAF-prepared vaccines elicited protective anti-tumor immunity, an effect significantly attenuated by the PERK inhibitor GSK2606414. Furthermore, FZYAF treatment promoted the maturation of intratumoral dendritic cells and increased the infiltration of IFN-γ-secreting CD8⁺ T cells. Western blot analysis verified that FZYAF activated the PERK-eIF2α-ATF4-CHOP signaling pathway in vivo, and this activation was reversible by the PERK inhibitor. CONCLUSION: FZYAF effectively induces immunogenic cell death in prostate cancer cells by activating the PERK-eIF2α-ATF4-CHOP signaling pathway. This study unveils a novel mechanism of FZYAF’s anti-tumor activity, establishing its potential as an ICD inducer and providing a solid theoretical basis for its future clinical application. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":"9"},"PeriodicalIF":4.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932009","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":"A Clinically Derived TCM Decoction (WD-3) Attenuates Malignant Phenotypes of Gastric Cancer through the PPARγ-AMPK Pathway.","authors":"Hengzhou Zhu, Wenyue Zhao, Jingyi Qian, Xiaodan Zhu, Chencen Zhang, Yuqing Geng, Yun Yuan, Yuetong Xia, Lei Huang, Jiejie Fan, Liang Ma, Valeriy Smirnov, Chunhui Jin","doi":"10.1186/s12575-025-00320-2","DOIUrl":"10.1186/s12575-025-00320-2","url":null,"abstract":"<p><strong>Background & objective: </strong>Weitiao No. 3 decoction (WD-3), a clinically used adjuvant therapy for advanced gastrointestinal tumors, lacks clarified mechanisms in gastric cancer (GC).</p><p><strong>Methods: </strong>We profiled chemical constituents by liquid chromatography-mass spectrometry (LC-MS), predicted putative targets and pathways via network pharmacology, evaluated binding by molecular docking, and validated pharmacological effects in MGC-803 cells and mouse xenograft models.</p><p><strong>Results: </strong>LC-MS identified 344 constituents; network analyses yielded 188 putative targets and highlighted core nodes (e.g., AKT1, EGFR, PIK3CA, PPARG). Pathway enrichment and docking converged on the PPARγ (PPARG)/AMPK axis. Experimentally, WD-3 suppressed proliferation and migration, induced G1-phase arrest, and increased PPARγ and phospho-AMPK; perturbation of PPARγ modulated AMPK activation and anti-tumor effects. In vivo, high-dose WD-3 reduced xenograft tumor growth in a dose-dependent manner without overt hepato-renal histopathologic toxicity.</p><p><strong>Conclusions: </strong>Using LC-MS, network pharmacology, docking, and in vitro/in vivo assays, we found that WD-3 suppresses GC cell proliferation/migration and xenograft growth, accompanied by increased total PPARγ and AMPK Thr172 phosphorylation, supporting involvement of the PPARγ/AMPK axis.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":"8"},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916665","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":"Ribosomal Protein RPL29 Promotes Hepatocellular Carcinoma Progression Through Regulation the Expression of Exosome Component 4.","authors":"Xiaoxue Wang, Zexin Zhu","doi":"10.1186/s12575-025-00322-0","DOIUrl":"10.1186/s12575-025-00322-0","url":null,"abstract":"<p><strong>Background: </strong>There are notable challenges in the development of effective therapeutic interventions for primary liver cancer (PLC). The role of ribosomal protein (RP) RPL29 in cancer has been rarely reported and the underlying mechanisms of RPL29 in the progression of Hepatocellular carcinoma (HCC) remain unclear.</p><p><strong>Methods: </strong>In the present study, the expression level and prognostic value of RPL29 in patients with HCC was evaluated by bioinformatics and immunohistochemistry. Moreover, gene expression was suppressed using targeted siRNAs and enhanced through plasmids containing specific gene cDNA sequences. Subsequently, assessments of cell viability and invasive capacity were conducted. Additionally, Western blot analyses and subcutaneous xenograft models in nude mice were utilized to elucidate the potential function of RPL29 in regulating the malignant phenotype of HCC.</p><p><strong>Results: </strong>The expression of RPL29 was found to be significantly elevated in HCC tissues. Further investigation demonstrated that RPL29 actively promotes the proliferation and metastatic potential of HCC cells. Moreover, RPL29 was shown to enhance the expression of Exosome Component 4 (EXOSC4), thereby contributing to the progression and metastasis of HCC. Both RPL29 and EXOSC4 were markedly overexpressed in HCC tissues and were associated with poorer overall survival and disease-free survival outcomes. Notably, the overexpression of RPL29 was able to restore cell viability and invasive capabilities in HCC cells in EXOSC4 silenced cells. In addition, we conducted a screening of two small molecule drugs that specifically target EXOSC4.</p><p><strong>Conclusion: </strong>The present study demonstrated that RPL29 facilitates HCC progression by regulating the expression of EXOSC4, which provides a novel therapeutic option for patients with HCC.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":"7"},"PeriodicalIF":4.3,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896034","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":"DKK1 Overexpression in Lung Adenocarcinoma: Prognostic Implications, Immune Microenvironment Correlates, and Regulatory Network Characterization.","authors":"Yanhong Wang, Jiaxuan Li, Jianhui Tian, Ze Liu, Wang Yao, Jiajun Liu, Zujun Que, Wenji Shangguan","doi":"10.1186/s12575-025-00319-9","DOIUrl":"10.1186/s12575-025-00319-9","url":null,"abstract":"<p><p>BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent malignancy with poor survival outcomes, underscoring the need for better biomarkers and therapeutic targets. Dickkopf-1 (DKK1), a secreted Wnt pathway inhibitor, is dysregulated in many cancers and can promote tumor progression and immune evasion. This study aimed to investigate DKK1 expression and its clinical, immunological, and molecular significance in LUAD. METHODS: Transcriptomic and clinical data from TCGA and GTEx were analyzed to evaluate DKK1 expression, prognostic relevance, immune infiltration, and associated pathways. Functional enrichment and co-expression networks were constructed in silico. Key findings were validated in vitro using siRNA-mediated DKK1 knockdown in lung cancer cells, followed by assays of proliferation, migration/invasion, apoptosis, cell cycle, and protein expression. RESULTS: DKK1 was significantly overexpressed in LUAD and correlated with advanced stage and poor survival. Enrichment analyses suggested roles in extracellular matrix remodeling and invasion. High DKK1 expression was also associated with increased infiltration of innate immune cells and elevated PD-L1 expression, indicating a potential role in shaping an immunosuppressive microenvironment. Functional experiments further confirmed that DKK1 knockdown reduced proliferation, impaired migration and invasion, induced cell-cycle arrest, and promoted apoptosis in LUAD cells. CONCLUSIONS: DKK1 serves as a strong prognostic biomarker in LUAD, linking high expression to aggressive clinicopathologic features and immunosuppressive microenvironments. Its knockdown reversed malignant phenotypes in vitro, supporting DKK1 as a potential therapeutic target and a predictor of immunotherapy resistance. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":"6"},"PeriodicalIF":4.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861791","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":"Effect of the Addition of Xianglian Granules to PD-1 Monoclonal Antibodies in Pancancer Patients.","authors":"Tingting Wu, Shiying Li, Hui Shuang, Yun Li, Shujuan Fu, Haiyan Jiang, Shiqiang Zhang, Boqian Du, Junqiang Lv, Xiaoting Xia, Shengcheng Cao, Liping Yao, Pingsheng Pan, Siqi Feng, Cunya Li, Zhangjie Zhou, Jian Chen, Yi Zhong","doi":"10.1186/s12575-025-00309-x","DOIUrl":"10.1186/s12575-025-00309-x","url":null,"abstract":"<p><strong>Background: </strong>With the successive listing of immune checkpoint inhibitors in China, a new era of immunotherapy for malignant tumors has opened. However, this study has several limitations. Xianglian granule (XG), a Chinese herbal formula, has been proven to have a therapeutic effect on tumors in animal experiments. Our aim was to evaluate the efficacy and safety of XG combined with programmed death ligand 1 (PD-1) in pancancer patients through a randomized, double-blind, controlled trial.</p><p><strong>Methods: </strong>Patients with cancer who received PD-1 monoclonal antibody therapy were randomized to the XG or control group according to the blinded method for 9 weeks. The primary endpoint was the overall survival (OS) rate, and the secondary endpoint was the incidence rate of immune-related adverse events (irAEs). Related biological markers were observed.</p><p><strong>Results: </strong>A total of 91 patients were included in the study. The 3-year OS rates of the XG group and the control group were 35.56% and 15.22%, respectively (P = 0.0012). The lactate dehydrogenase (LDH) level in the XG group was lower than that in the other groups, especially in the lung cancer patients (P = 0.06, P = 0.03). The two groups showed similar safety. The incidence rate of irAEs was 22.2% in the XG group and 32.6% in the control group (P = 0.27). In addition, XG can reduce D-lactic acid (D-LA) and diamine oxidase (DAO) contents (P = 0.012, P < 0.001). The B lymphocyte count and percentage of the XG group increased (P = 0.04, P = 0.035), and the interleukin-2 level decreased (P = 0.045). The Cox regression results suggested that the potential factors of the prognostic model might be XG treatment, D-LA and B lymphocyte count (P = 0.002, P < 0.001, P = 0.001).</p><p><strong>Conclusion: </strong>XG had efficacy-enhancing and toxicity-reducing effects on pancancer patients when combined with a PD-1 monoclonal antibody. The mechanisms may be related to the participation of the intestinal barrier, B lymphocytes and interleukin-2. D-LA and B lymphocytes may be potential factors in the prognostic model of pancancer patients treated with immunotherapy.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"54"},"PeriodicalIF":4.3,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861864","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}