Pathology, research and practice最新文献

{"title":"Single-cell transcriptomic analyses provide insights into the tumor microenvironment heterogeneity and invasion phenotype in retinoblastoma","authors":"Xiaoliang Zhang ,&nbsp;Hong Liu ,&nbsp;Zhida Lan ,&nbsp;Guangping Gao ,&nbsp;Guanyu Li ,&nbsp;Ziwei Dai ,&nbsp;Shangyao Qin ,&nbsp;Wei Shen","doi":"10.1016/j.prp.2025.156009","DOIUrl":"10.1016/j.prp.2025.156009","url":null,"abstract":"<div><h3>Background</h3><div>As the most common intraocular malignant tumor, retinoblastoma (RB) is associated with high mortality during early childhood. The heterogeneous cellular composition of the tumor microenvironment (TME) plays a pivotal role in modulating immune responses, tumor growth and metastasis progression. However, the landscape of TME heterogeneity and cell-cell communication networks in RB remain poorly characterized.</div></div><div><h3>Methods</h3><div>Different phenotypes of RB were characterized by integrated single-cell sequencing data. Cellular subclusters of three principal TME components were systematically identified. CellChat analyzed package was employed to depict intercellular communications across all types of cells in TME. Next, pseudotime trajectory analyses were performed with Monocle package. CIBERSORT algorithms (LM22 signature matrix) and CIBERSORTx platform were employed to characterize immune cell infiltration landscape from microarray data. Finally, functional enrichment profiling elucidated associations between TME subcluster signatures and extraocular invasion phenotypes of RB.</div></div><div><h3>Results</h3><div>Characteristic subclusters of TME components, such as MG1 in tumor-associated macrophages (TAMs) and AC1 in astrocyte-like cells were probably associated with RB extraocular invasion in different ways. And RB invasive progression might be relevant with the cell-cell communications landscape change between TME-related cell populations. Trajectory analysis revealed the potential correlation of RB invasion with the increase of immature TAMs and the decrease of terminally differentiated astrocyte-like cells. Functional enrichment analysis further profiled the distinct molecular feature of characteristic subclusters.</div></div><div><h3>Conclusions</h3><div>This study systematically delineates TME heterogeneity landscapes across non-invasive versus invasive RB, providing mechanistic insights into intercellular communications within TME. Our findings might have the potential to develop microenvironment-targeted therapeutic strategies in RB management.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156009"},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and analysis of diagnostic markers related to lactate metabolism in myocardial infarction","authors":"Haozhen Yu ,&nbsp;Lanxin Gu ,&nbsp;Heng Ma ,&nbsp;Lu Yu","doi":"10.1016/j.prp.2025.156010","DOIUrl":"10.1016/j.prp.2025.156010","url":null,"abstract":"<div><div>Lactate metabolism is implicated in myocardial infarction (MI), yet the underlying mechanisms are not fully understood. Identifying lactate metabolism-related genes (LMRGs) could uncover new diagnostic and therapeutic targets for MI. We conducted a bioinformatics analysis on GeneCards database to identify 498 LMRGs and intersected them with differentially expressed genes (DEGs) from MI samples, yielding 17 key genes. We utilized consensus clustering and weighted gene co-expression network analysis (WGCNA) to refine our gene list to 981 candidate genes. Machine learning algorithms identified three biomarkers: OLIG1, LIN52, and RLBP1, associated with 'ribosome' and 'carbon metabolism' pathways. Enrichment analyses and immune microenvironment assessments were performed, and networks including drug-gene interactions and kinase-transcription factor (TF)-mRNA-miRNA were constructed to explore the functions and potential therapeutic implications of these genes. The three biomarkers showed significant correlations with immune cell types, with OLIG1 having the highest positive correlation with monocytes and the highest negative correlation with neutrophils. The drug-gene network revealed potential interactions such as methapyrilene with LIN52 and 'bisphenol A′ with RLBP1. The kinase-TF-mRNA-miRNA network comprised 209 nodes and 470 edges, indicating complex regulatory mechanisms. Our study identified three key biomarkers, OLIG1, LIN52, and RLBP1, in lactate metabolism associated with MI, providing insights into potential diagnostic markers and therapeutic targets. These findings warrant further investigation into the molecular mechanisms of these biomarkers in MI.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156010"},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting E3 ligases for lung cancer therapy: The promise of DCAF-PROTACs","authors":"Md Sadique Hussain ,&nbsp;Lina Eltaib ,&nbsp;Amita Joshi Rana ,&nbsp;Mudasir Maqbool ,&nbsp;Sumel Ashique ,&nbsp;Mashael N. Alanazi ,&nbsp;Yumna Khan ,&nbsp;Mohit Agrawal","doi":"10.1016/j.prp.2025.156001","DOIUrl":"10.1016/j.prp.2025.156001","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer-related mortality, underscoring the urgent need for novel therapeutic strategies. One emerging approach in drug development targets oncogenic proteins via the ubiquitin-proteasome system (UPS), specifically through proteolysis-targeting chimeras (PROTACs). Among the various E3 ligase complexes, the CRL4 complex—comprising DDB1 and CUL4-associated factors (DCAFs)—has garnered attention for its roles in cellular homeostasis, DNA repair, and oncogenesis. This review explores the therapeutic potential of DCAF-based PROTACs (DCAF-PROTACs) in lung cancer by focusing on the substrate receptors DCAF13, DCAF15, and DCAF16, which mediate CRL4-dependent ubiquitination. We first discuss the dysregulation of DCAF proteins in lung cancer and then elaborate on their mechanistic role in facilitating target-specific protein degradation via DCAF-E3 ligase complexes. Recent studies show that DCAF-PROTACs selectively degrade oncogenic proteins, addressing treatment resistance and tumor heterogeneity. Notably, DCAF13 promotes lung adenocarcinoma by destabilizing p53, while DCAF15-PROTACs target and degrade RBM39 effectively. Additionally, the development of electrophilic PROTACs targeting DCAF16 presents a promising avenue for degrading nuclear proteins. Despite these advancements, several challenges must be addressed prior to clinical translation, including issues related to drug bioavailability, stability, and emerging resistance mechanisms. This review also explores the potential of combination therapies, particularly with immunotherapy, to enhance tumor specificity and therapeutic efficacy. Ultimately, the deployment of DCAF-PROTACs marks a significant advancement in precision oncology, offering a novel and targeted approach to protein degradation-based cancer treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 156001"},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical advantages in providing artificial intelligence-assisted prostate cancer diagnosis: A pilot study","authors":"C. Eloy ,&nbsp;A. Asaturova ,&nbsp;J. Pinto ,&nbsp;I. Rienda ,&nbsp;A. Syrnioti ,&nbsp;R. Prisco ,&nbsp;A. Polónia","doi":"10.1016/j.prp.2025.156007","DOIUrl":"10.1016/j.prp.2025.156007","url":null,"abstract":"<div><div>Prostate cancer is a prevalent male malignancy, with increasing incidence rates placing significant diagnostic burdens on pathology services worldwide. Artificial intelligence (AI) is emerging as a promising aid in enhancing diagnostic efficiency and accuracy. This study evaluates the clinical benefits of AI-assisted prostate biopsy (PB) diagnosis, with Paige Prostate tool, compared to non-AI-assisted PB diagnosis, focusing on its predictive accuracy for features in radical prostatectomy (RP) specimens. A retrospective analysis included 55 patients divided into two cohorts: one with non-AI-assisted PB diagnosis (n = 25) and another with AI-assisted PB diagnosis (n = 30). Pathological assessments recorded tumor size, Gleason score, Grade Group, and perineural invasion. The correlation between PB and RP results was analyzed, with statistical significance set at p &lt; 0.05. AI-assisted PB diagnosis showed faster reporting times by 24 hours, enhancing workflow efficiency. AI assistance improved the correlation of tumor size between PB and RP, showing a substantial agreement (R=0.646, p &lt; 0.001) compared to non-AI (R=0.479, p = 0.015). Gleason Score concordance increased by 13 % in the AI-assisted group, achieving 73.3 % versus 60 % in the non-AI-assisted group. This small pilot study suggests that AI-assisted PB diagnosis appears to enhance efficiency and accuracy in the diagnosis of prostate cancer, a finding to be confirmed with further studies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156007"},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanozymes: A novel approach to upgrade atherosclerosis treatment","authors":"Maryam Mahjoubin-Tehran ,&nbsp;Prashant Kesharwani ,&nbsp;Wael Alamahmeed ,&nbsp;Sercan Karav ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.prp.2025.156005","DOIUrl":"10.1016/j.prp.2025.156005","url":null,"abstract":"<div><div>Atherosclerosis has become a global health concern, contributing to the rise in cardiovascular diseases and causing significant morbidity and disability. The development of atherosclerosis begins with the accumulation of low-density lipoprotein (LDL) in the subendothelial space. As LDL becomes trapped in the arterial walls, reactive oxygen species (ROS) are generated, resulting in oxidative stress, impaired endothelial function, and oxidative modification of the retained LDL, forming oxidized LDL (ox-LDL). The oxidation of LDL to form ox-LDL is considered one of the most important factors in the development of atherosclerosis. Recently, there has been a growing interest in nanomaterials with enzyme-like characteristics called nanozymes in the field of biomedicine. The use of nanozymes has become increasingly popular because they offer solutions to the limitations associated with natural enzymes, including high costs, low stability, and challenging storage requirements. Nanozymes with anti-oxidative activities, such as catalase-, SOD-, and GPx-like nanozymes, have been extensively studied for various disease therapies, including atherosclerosis. Furthermore, nanozymes can be designed to have multiple enzyme-like activities. In this review, we aim to summarize studies that have used nanozymes as a therapeutic approach for the treatment of atherosclerosis. The results of this study have shown that nanozymes have a significant impact in reducing atherosclerotic plaques in <em>ApoE</em>^{<em>−/−</em>} mice. This effect is mainly achieved through ROS scavenging, which leads to the suppression of foam cell formation and inflammation.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156005"},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic re-classification of combined hepatocellular-cholangiocarcinoma and small duct type intrahepatic cholangiocarcinoma","authors":"Motoko Sasaki ,&nbsp;Yasunori Sato ,&nbsp;Yasuni Nakanuma","doi":"10.1016/j.prp.2025.155999","DOIUrl":"10.1016/j.prp.2025.155999","url":null,"abstract":"<div><h3>Background</h3><div>Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) shares various features with small duct type intrahepatic cholangiocarcinoma (SmD-iCCA) and sometimes histological diagnosis may be difficult.</div></div><div><h3>Methods</h3><div>We examined genetic alterations such as hTERT promoter (hTERT), p53, and fibroblast growth factor receptor 2 (FGFR2) in 103 PLCs diagnosed as cHCC-CCA or SmD-iCCA. A cluster analysis was performed on the R software for re-classification of PLCs including cHCC-CCA and SmD-iCCA.</div></div><div><h3>Results</h3><div>The primary liver carcinomas (PLCs) were divided into 5 clusters; 19 tumors (18 %) in Cluster-1 (with alterations in hTERT and/or p53), 24 (23 %) in Cluster-2 (FGFR2 and/or p53), 13 (13 %) in Cluster-3 (IDH2 or null), 19 (18 %) in Cluster-4 (MTAP and/or FGFR2), 28 (27 %) in Cluster-5 (ARID1A and/or PBRM1), being based on genetic alterations. Cluster-1 and Clusters-2 to- 5 formed distinct 2 groups. Cluster-1 was characterized by significantly bigger size, rich and higher histological grade of HCC component, significantly less cholangiolocellular carcinoma (CLC)-component, ductal plate malformation pattern and bile duct adenoma in the background livers. No SmD-iCCA was included in Cluster-1, whereas SmD-iCCA distributed evenly in Clusters 2–5. Cluster-4 was characterized by higher prevalence of hepatitis B and higher histological diversity scores.</div></div><div><h3>Conclusion</h3><div>PLCs diagnosed as cHCC-CCA or SmD-iCCAs could be divided into 5 clusters based on genetic alterations. Cluster-1 was HCC-like cluster characterized by hTERT alteration, rich and higher grade of HCC and bigger size. Clusters-2–5 may be iCCA-like clusters characterized by different genetic alterations. cHCC-CCA in Cluster-1 and Clusters-2–5 may be handled separately for further analysis and treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155999"},"PeriodicalIF":2.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radioprotective and radiosensitizing properties of silymarin/silibinin in response to ionizing radiation","authors":"Faezeh Arghidash ,&nbsp;Fatemeh Gheybi ,&nbsp;Hamid Gholamhosseinian ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.prp.2025.156002","DOIUrl":"10.1016/j.prp.2025.156002","url":null,"abstract":"<div><div>Cancer is a health and treatment challenge that the world is facing, and many efforts are being made to develop treatment solutions for all forms of cancer. Radiotherapy (RT), one of the cancer treatment methods, can cause toxicity in healthy cells, even though it has positive effects on killing cancer cells. It is possible for cancer cells to develop resistance to radiotherapy. To address these issues, it can be beneficial to combine treatments. Combining plants with conventional cancer treatment is a viable option, and their potential can be utilized in this area. The therapeutic properties of silymarin and its active ingredient silibinin have been used in traditional medicine for a long time. The purpose of this review is to investigate the radioprotective and radio-sensitizing properties of silymarin/silibinin in cancer treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 156002"},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin ameliorates RF-EMR-induced reproductive damage by inhibiting ferroptosis through Nrf2 pathway activation","authors":"Jingjing Wang ,&nbsp;Jie Dong ,&nbsp;Qian Xu ,&nbsp;Song Yan ,&nbsp;Haihui Wang ,&nbsp;Hui Lei ,&nbsp;Xuhui Ma ,&nbsp;Tao Yang ,&nbsp;Ke Wang ,&nbsp;Zhen Li ,&nbsp;Xiaohong Wang","doi":"10.1016/j.prp.2025.156003","DOIUrl":"10.1016/j.prp.2025.156003","url":null,"abstract":"<div><div>In recent years, there has been increased attention to the deleterious impacts of radiofrequency electromagnetic radiation (RF-EMR) on male reproductive ability, necessitating the exploration of effective protective measures. Melatonin has antioxidant and anti-apoptotic effects, and there is growing evidence of its benefit to the reproductive process. However, the biochemical mechanisms by which melatonin protects against reproductive damage from RF-EMR exposure are unknown. Here, we found that prolonged (8 weeks) exposure to RF-EMR [2.45 GHz; power density, 2.5 W/m²; whole-body specific absorption rate (SAR), 0.125–0.5 W/kg] induced ferroptosis and oxidative stress in testicular tissue, leading to a decrease of sperm quality in male mice. Notably, the administration of melatonin mitigated the oxidative harm to the testicles and ferroptosis caused by RF-EMR in mice. Mechanistically, melatonin could inhibit ROS production and ferroptosis by stimulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway through its receptors (MT1/MT2). Taken together, these results indicate that melatonin could potentially improve RF-EMR-induced reproductive damage in male mice by blocking ferroptosis through activation of the Nrf2 pathway.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 156003"},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of uterine NK cells in pregnancy complication","authors":"Shahnaz Sabetkam ,&nbsp;Ali Rafat ,&nbsp;Zeinab Mazloumi ,&nbsp;Hossein Kalarestaghi ,&nbsp;Mohammadmahdi Bahramloo ,&nbsp;Elahe Naderali ,&nbsp;Khadijeh Dizaji Asl","doi":"10.1016/j.prp.2025.155998","DOIUrl":"10.1016/j.prp.2025.155998","url":null,"abstract":"<div><div>Remodeling of blood vessels and angiogenesis play a critical role in the pregnancy process, particularly at the implantation site. Both the innate and adaptive immune systems, especially uterine natural killer (uNK) cells, are involved in this process. During the first trimester, uNK cells constitute approximately 70 % of decidual leukocytes and are differentiated from CD34⁺ progenitor cells. In comparison to peripheral blood NK cells, uNK cells secrete specific cytokines that promote tissue remodeling while exhibiting lower cytotoxic activity. Any disturbance in the function of uNK cells or dysregulation of their receptors can lead to reproductive failures. This review focuses on the role of uNK cells in pregnancy disorders such as preeclampsia, recurrent pregnancy loss, and endometriosis. The findings of this research will assist researchers in targeting specific checkpoints to address pregnancy disorders in clinical settings.</div></div><div><h3>Significance statement</h3><div>In this study, we highlight the evidence that NK cells play a pivotal role in pregnancy disorders and appropriate phenotype and normal expression of receptors on uNK cells affected pregnancy outcomes. In summary, arterial remodeling and correct implantation are related to the presence of various cytokines and factors in the uterine microenvironment. Collectively, it seems that the result of this study can be helpful in clinic. In the other word, specialist can use appropriate drugs in infertility.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155998"},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asiaticoside enhances the anti-tumor effect of anti-PDL1 by regulating T cell activity through increasing LCK activity","authors":"Qingyi Ren ,&nbsp;Fang Wang ,&nbsp;Fei Du ,&nbsp;Chenxi He ,&nbsp;Xiaodong Wang ,&nbsp;Jun Wang ,&nbsp;Zhuo Zhang ,&nbsp;Yuhong Sun","doi":"10.1016/j.prp.2025.155995","DOIUrl":"10.1016/j.prp.2025.155995","url":null,"abstract":"<div><div>Anti-PD-L1 antibody confers anti-tumor effects, but its long-term use can provoke resistance and adverse effects. Asiaticoside, a bioactive triterpene glycoside from <em>Centella asiatica</em> L., regulates immune function and induces apoptosis of hepatocellular carcinoma (HCC) cells. T cells play a vital role in killing tumor cells and require lymphocyte-specific protein tyrosine kinase (LCK) for activation. Here, we examined whether a combined asiaticoside and anti-PD-L1 treatment regulates T cells via LCK activation to enhance the anti-tumor effect in vivo. We established a subcutaneous mouse HCC model using Hepa1–6 cells and measured spleen and tumor weight. Morphological changes of tumor tissues were assessed by hematoxylin-eosin staining. Tumor cell apoptosis and proliferation were determined by TUNEL staining and KI67 immunohistochemistry. The proportion of activated T cells in the spleen was detected by flow cytometry, and the levels of phosphorylated p-LCK and p-AKT in the spleen were determined by Western blotting. Changes in the levels of serum inflammatory factors were detected with ELISA. Our results revealed that the combined asiaticoside and anti-PD-L1 treatment inhibited tumor growth by enhancing apoptosis and reducing tumor cell proliferation. The treatment activated T cells to increase the proportion of effector T cells in the spleen, evidenced by upregulated p-LCK and p-AKT levels. It also increased the level of TNF-α in the serum and decreased IL-6, implying an enhanced immune response. In conclusion, the combined asiaticoside and anti-PD-L1 treatment enhances the anti-HCC effect in vivo by promoting LCK activation to regulate T cells.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 155995"},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}