Pathology, research and practice最新文献

{"title":"Indomethacin alleviates acute pancreatitis by restoring autophagic flux via the AMPK signaling pathway","authors":"Lijun Lou ,&nbsp;Jing Li ,&nbsp;Yan Li ,&nbsp;Jiaming Feng ,&nbsp;Jun Yu ,&nbsp;Zeyu Wang ,&nbsp;Chao Zhang ,&nbsp;Liyu Chen ,&nbsp;Yuanhang Zhao ,&nbsp;Yongzhan Nie ,&nbsp;Liyan Li ,&nbsp;Yanglin Pan","doi":"10.1016/j.prp.2026.156377","DOIUrl":"10.1016/j.prp.2026.156377","url":null,"abstract":"<div><div>Acute pancreatitis (AP) remains a significant clinical challenge lacking early, targeted pharmacological interventions to prevent disease progression. Dysfunctional autophagy is a central pathogenic mechanism in AP. While indomethacin (IND), a nonsteroidal anti-inflammatory drug, is known to prevent post-ERCP pancreatitis, its broader therapeutic potential and underlying mechanisms in other forms of AP are unclear. Emerging evidence suggests that IND has the potential to activate autophagy. This study aimed to investigate whether IND protects against AP by regulating autophagy. We established cerulein (CER)-induced AP models both in vivo and in AR42J cells to evaluate the protective effects of IND. Transcriptomic and pathway analyses were conducted to identify underlying signaling mechanisms. Our results demonstrate that IND alleviated CER-induced pancreatic injury, as indicated by improved histopathological scores, reduced serum amylase and lipase levels, diminished inflammatory cell infiltration, and attenuated acinar cell cytotoxicity. Mechanistically, transcriptomic and experimental data revealed that IND restored autophagy via activation of the AMP-activated protein kinase (AMPK) signaling pathway. Critically, the protective effects of IND were abolished by either the autophagy inhibitor chloroquine or the AMPK inhibitor Compound C (CC). In conclusion, our findings suggest that IND may serve as a promising therapeutic candidate for the treatment of AP.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156377"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078735","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":"Renal cell carcinoma with biphasic morphology: A cohort showing similar morphology but distinct clinicopathological and molecular features","authors":"Ye Liao ,&nbsp;Xin Wang ,&nbsp;Zhenhua Zhang ,&nbsp;Xinyi Shen ,&nbsp;Peng Su ,&nbsp;Daochen Chong ,&nbsp;Yanxia Jiang ,&nbsp;Yujun Li ,&nbsp;Wei Zhang ,&nbsp;Wenjuan Yu","doi":"10.1016/j.prp.2026.156360","DOIUrl":"10.1016/j.prp.2026.156360","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Biphasic morphology, characterized by small cells clustered around basement membrane material, is a distinctive feature of &lt;em&gt;TFEB&lt;/em&gt;-rearranged renal cell carcinoma (RCC). However, other RCC subtypes may exhibit similar histological characteristics. Clinicopathological data from 12 cases of RCC with biphasic morphology—including four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC, four cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC, and four cases of chromophobe RCC (ChRCC)—were collected. Most of the 12 patients survived without complications, except for one patient with ChRCC who died accidentally 25 months after surgery. Microscopically, all 12 tumors showed varying proportions of biphasic morphology, comprising clear or eosinophilic large cells arranged in nests, glandular, or papillary structures, and clustered small cells forming pseudorosette structures around basement membrane-like deposits. Large pale cells with clear to foamy cytoplasm were observed in the four ChRCC tumors. IHC revealed consistent nuclear and cytoplasmic expression of TFEB in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and diffuse nuclear positivity of TFE3 in &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC. Cathepsin K and GPNMB were expressed in most &lt;em&gt;TFEB&lt;/em&gt;- and &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCCs, whereas the melanocytic markers Melan A and HMB45 were expressed to varying degrees. Additionally, PD-L1 (22C3) was expressed with a high CPS of approximately 90 in two cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC. CK7, CD117, and Ksp-cad were expressed in both large and small cells in the four cases of ChRCC. FISH identified TFEB rearrangement in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and TFE3 rearrangement in all four cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC. RNA sequencing and whole-exome sequencing revealed &lt;em&gt;TFEB&lt;/em&gt;–&lt;em&gt;MALAT1&lt;/em&gt; fusion in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC. &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;SFPQ&lt;/em&gt; fusion was detected in two cases, and &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;MED15&lt;/em&gt; fusion in the other two &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC cases. PD-L1 (22C3) expression was detected in three cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC, two &lt;em&gt;TFE3&lt;/em&gt;-&lt;em&gt;MED15&lt;/em&gt; fusion subtype showed a CPS of approximately 30 and 20, whereas one &lt;em&gt;TFE3&lt;/em&gt;-&lt;em&gt;SFPQ&lt;/em&gt; fusion subtype showed a CPS of approximately 5. Additionally, in the four ChRCC cases, multiple segments of chromosomes 1, 2, 6, 8, 9, 10, and 17 were either lost or amplified. The biphasic structure with small cell components in RCC is observed in &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and in &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC and ChRCC, which may be prone to misdiagnosis based solely on morphology. Patients with &lt;em&gt;TFEB&lt;/em&gt;- and &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCCs exhibiting small cell components tend to be younger and have more favorable prognoses. The &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;MED15&lt;/em&gt; gene fusion in RCC with a biphasic structure containing small cell components has been reported here for the first time. Genetic alterations in ChRCC with small cell components ","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156360"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980040","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":"UBR5, a potential diagnostic and prognostic biomarker induces osteosarcoma progression","authors":"Mufan Li ,&nbsp;Jie Liang ,&nbsp;Xia Jiang ,&nbsp;Meiling Zheng ,&nbsp;Yao Liu ,&nbsp;Hua Jiang ,&nbsp;Hanan Long ,&nbsp;Vincent Kam Wai Wong ,&nbsp;Junjiang Fu","doi":"10.1016/j.prp.2026.156361","DOIUrl":"10.1016/j.prp.2026.156361","url":null,"abstract":"<div><h3>Background</h3><div>Ubiquitin protein ligase E3 component n-recognin 5 (<em>UBR5</em>) locates on chromosome 8q22, a region that commonly disrupted in a variety of cancers. Emerging evidence suggests UBR5 is involved in cancer progression, yet its oncogenic and prognostic roles, especially in osteosarcoma, remain poorly defined.</div></div><div><h3>Methods</h3><div>TCGA, GTEx, and GEO databases were integrated to analyze the expression level, and prognostic and diagnostic value of <em>UBR5</em> across cancers. <em>UBR5</em> genetic alterations and protein interactions were assessed using cBioPortal and GeneMANIA. UBR5 expression in osteosarcoma samples was validated by immunohistochemistry, Western blotting, and immunofluorescence staining. Functional assays, including gain- and loss-of-function experiments, CCK-8, colony formation, and transwell assays were used to evaluate the role of UBR5 in osteosarcoma cell lines. Additionally, the impact of Ubr5 knockdown on tumor growth was assessed in a mouse syngeneic transplant model.</div></div><div><h3>Results</h3><div>UBR5 expression was significantly elevated in osteosarcoma and various cancers, and its upregulation was strongly associated with poor prognosis. Furthermore, <em>UBR5</em> exhibited high diagnostic accuracy in distinguishing cancer from normal tissues. Genomic analysis revealed frequent <em>UBR5</em> alterations correlated with poor overall survival (OS). Protein interaction analysis showed UBR5’s association with chromatin assembly and histone modification. Knockdown of UBR5 inhibited proliferation, migration, invasion of osteosarcoma cell lines, while its overexpression promoted these malignant phenotypes <em>in vitro</em>. Moreover, knockdown of Ubr5 suppressed tumor growth <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>This study identifies UBR5 as a key driver of osteosarcoma progression and a promising diagnostic and prognostic biomarker across cancers, highlighting its potential as a biomarker and therapeutic target.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156361"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980039","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":"TCN1 knockdown inhibits the progression and glycolysis of non-small cell lung cancer via regulating B3GNT3","authors":"Hui Zhou ,&nbsp;Yayun Cui ,&nbsp;Lailing Li","doi":"10.1016/j.prp.2026.156376","DOIUrl":"10.1016/j.prp.2026.156376","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality globally. Transcobalamin 1 (TCN1) is a driver associated with the progression of various cancers. However, the role of TCN1 in NSCLC remains elusive. The current research aimed to disclose the biological function and regulatory mechanisms of TCN1 in NSCLC. The expression pattern of TCN1 in NSCLC was first identified via qRT-PCR and western blotting. Functional assays including CCK-8, Transwell, Epithelial-mesenchymal transition (EMT), and glycolysis detection were performed to evaluate the effects of TCN1 on the malignant phenotype of NSCLC cells. Then LinkedOmics database and KEGG pathway analysis were employed to explore TCN1-mediated molecular pathways. Finally, the rescue tests were conducted to validated the underlying molecular mechanisms. Here, we observed that TCN1 was apparently overexpressed in NSCLC and predicted poor prognosis. TCN1 knockdown restrained the proliferation, metastasis, EMT, and glycolysis of NSCLC cells. Mechanism studies demonstrated that TCN1 positively regulated B3GNT3 level via activating the EGFR pathway. Knockdown of B3GNT3 also suppressed the malignant progression and glycolysis of NSCLC cells, and its overexpression partially rescued the effects of TCN1 knockdown. In vivo experiments presented that TCN1 knockdown attenuated tumor growth in the xenograft mouse model and downregulated B3GNT3 expression. Collectively, TCN1 overexpression aggravated NSCLC progression by regulating the expression of B3GNT3. The TCN1-B3GNT3 axis served a key part in the growth, migration, invasion, and glycolysis of NSCLC cells, making it a potential therapeutic target for NSCLC treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156376"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023921","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":"HOXC8 derived from cancer-associated fibroblasts regulates lung cancer cell malignant metastasis and ferroptosis by mediating the transcription of GCH1","authors":"Chao Qin ,&nbsp;Xiaolei Shu ,&nbsp;Wei Wang ,&nbsp;Xin Wang ,&nbsp;Yi Li ,&nbsp;Xiaolong Li ,&nbsp;Shu Lai ,&nbsp;Yongpeng He","doi":"10.1016/j.prp.2025.156345","DOIUrl":"10.1016/j.prp.2025.156345","url":null,"abstract":"<div><h3>Background</h3><div>In the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) play a role in aggravating the tumor progression. However, research on its specific mechanisms of action remains insufficient. The aim of this study was to clarify the role of the transcription factor homeobox C8 (HOXC8) in CAFs and GTP cyclohydrolase I (GCH1) in the lung cancer.</div></div><div><h3>Methods</h3><div>MTT, EdU, Transwell, and stemness assays were employed to measure the biological behaviors of lung cancer cells. The ferroptosis-related indicators were determined by corresponding kits. The GEO database and TGCA samples were used to analyze the differentially expressed genes of CAFs after co-culture with lung cancer cells and the expression of HOXC8 in lung adenocarcinoma. Bioinformatics analysis and dual luciferase reporter system were used to detect the interaction between HOXC8 and GCH1. A xenograft tumor model and IHC staining were used to determine the effect of CAFs on tumor growth and GCH1 expression <em>in vivo</em>.</div></div><div><h3>Results</h3><div>CAFs accelerated lung cancer cell viability, proliferation, metastasis, sphere formation efficiency, and blocked ferroptosis-related indicators, but upregulated the HOXC8 level. The si-HOXC8-CAFs restrained the malignant progression of lung cancer cells. Interestingly, it was proved that HOXC8 bound to the promoter of GCH1 and induced its expression. Besides, overexpression of GCH1 rescued the effect of CAFs with knockdown of HOXC8 on lung cancer cells. CAFs with silenced HOXC8 inhibited tumor growth and GCH1 expression <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>Our results indicate that CAFs-derived exosomes are a key source of HOXC8 in lung cancer cells. HOXC8 directly binds to the GCH1 promoter to activate its transcription, which in turn suppresses ferroptosis and promotes lung cancer progression. These findings contribute to the new intervention and treatment options for combating the malignant progression of lung cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156345"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928823","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":"Anisodine hydrobromide inhibits inflammation and metabolic reprogramming to alleviate the inflammatory response in an acute cerebral infarction model","authors":"Chenyan Sui ,&nbsp;Zhixuan Zhang ,&nbsp;Xin Huang ,&nbsp;Likun Han ,&nbsp;Changyan Fan ,&nbsp;Su Peng ,&nbsp;Jun Zhu ,&nbsp;Jialong Sun ,&nbsp;Jianwei Li ,&nbsp;Wang Xiao ,&nbsp;Xiaoyan Wang ,&nbsp;Xiaodong Zhang ,&nbsp;Lingling Hu ,&nbsp;Xin Gu","doi":"10.1016/j.prp.2026.156374","DOIUrl":"10.1016/j.prp.2026.156374","url":null,"abstract":"<div><div>Acute ischemic stroke (AIS), a primary cause of global mortality and disability, involves the sudden interruption of cerebral blood flow, leading to significant neurological impairment. Inflammation plays a critical role in exacerbating brain damage following stroke, making effective anti-inflammatory treatments essential. This study explored the therapeutic potential of anisodine hydrobromide (Ani), a traditional Chinese medicine, in modulating inflammatory responses and glycolysis in the lymphocytes of AIS patients. We evaluated the impact of Ani on peripheral blood mononuclear cells (PBMCs) and purified Treg cells from these patients. Our findings indicated that Ani significantly increased the proportion of Treg cells and upregulated Foxp3 expression, suggesting enhanced anti-inflammatory effects. Ani also reduced the levels of proinflammatory cytokines and inhibited NLRP3 inflammasome activation in T cells. Additionally, Ani influenced glycolysis by downregulating the expression of key glycolytic enzymes, PKM2 and LDHA, through its effects on DNA methylation. Chromatin immunoprecipitation and molecular docking studies revealed that Ani interacts with DNMT1, modifying DNA methylation patterns and increasing 5hmC levels at the promoters of <em>PKM2</em> and <em>LDHA</em>. These results indicate that Ani exerts neuroprotective effects by modulating both inflammatory and metabolic pathways, suggesting a promising avenue for AIS therapy. Further clinical validation and exploration of the therapeutic efficacy of Ani are warranted to confirm its potential as a treatment for AIS.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156374"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023829","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":"Serine/arginine-rich splicing factor 1 inhibits ferroptosis and promotes glycolysis in endometrial cancer via activating mTOR and β-catenin","authors":"Qing Zhu ,&nbsp;Ao Zhang ,&nbsp;Yang Gao ,&nbsp;Zhenzhong Feng ,&nbsp;Nan Li ,&nbsp;Qiang Wu","doi":"10.1016/j.prp.2026.156364","DOIUrl":"10.1016/j.prp.2026.156364","url":null,"abstract":"<div><div>Serine/arginine-rich splicing factor 1 (SRSF1) is a pre-mRNA-splicing factor functioning as an oncogene in multiple cancers. However, the biological roles of SRSF1 in endometrial cancer (EC) have not been explored. Here we demonstrated its pivotal function and the regulatory mechanism in regulating ferroptosis and glycolysis in EC. Results showed that SRSF1 inhibited ferroptosis in EC cells, indicated by decreased cell death rate, lipid peroxidation and Fe^2 + concentration. SRSF1 accelerated glycolysis in EC cells, evidenced by enhanced glucose uptake, lactate production and adenosine triphosphate production. Mechanistically, SRSF1 elevated the levels of phosphorylated mTOR and β-catenin in EC cells. Besides, the regulation of glycolytic enzyme proteins by SRSF1 in EC cells was dependent on mTOR and β-catenin. Furthermore, rescue assays unveiled that mTOR, β-catenin, and glycolysis involved in the regulatory function of SRSF1 on ferroptosis in EC cells. Finally, animal study proved that SRSF1 knockdown restrained <em>in vivo</em> tumor growth and potentiated the antitumor efficacy of ferroptosis inducer through glycolysis inhibition. In conclusion, the present study uncovered that SRSF1 acts as a tumor promoter in EC through activating mTOR and β-catenin to inhibit ferroptosis and facilitate glycolysis, proposing a therapeutic target for EC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156364"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019122","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":"OXPHOS inhibitor IACS010759 suppresses tumor growth by modulating autophagy in esophageal squamous cell carcinoma","authors":"Xiao Han ,&nbsp;Xueyuan Hu ,&nbsp;Guangzhao Zhu ,&nbsp;Yingchao Ma ,&nbsp;Kaige Li ,&nbsp;Hongtao Liu ,&nbsp;Tianli Fan ,&nbsp;Yue Xu ,&nbsp;Wenna Guo ,&nbsp;Yanting Zhang","doi":"10.1016/j.prp.2026.156363","DOIUrl":"10.1016/j.prp.2026.156363","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant digestive tract cancer with poor prognosis. Cancer cells generally exhibit increased glycolytic activity, and it was previously believed that oxidative phosphorylation (OXPHOS) is downregulated in all cancers. However, recent studies have shown increased OXPHOS activity in some tumors, even alongside active glycolysis. This has led to the exploration of targeting elevated OXPHOS as a therapeutic strategy. Despite this, the role of OXPHOS in ESCC tumorigenesis and progression remains unclear. In this study, we found that OXPHOS-related genes are highly expressed in ESCC cell lines and tissues, and this elevated expression correlates with clinical prognosis. The OXPHOS inhibitor IACS-010759 suppressed ESCC cell proliferation, clonogenicity, and migration, while disrupting mitochondrial morphology and function. Furthermore, IACS-010759 inhibited xenograft tumor growth in nude mice. Treatment with IACS-010759 also inhibited autophagy and activated the AKT/mTOR pathway in ESCC cells. The autophagy inducer rapamycin counteracted the inhibitory effects of IACS-010759, indicating that IACS-010759 inhibits ESCC autophagy via AKT/mTOR activation, thereby exerting anti-tumor effects. Interestingly, inhibiting OXPHOS increased glycolytic activity. Combining IACS-010759 with the glycolysis inhibitor 2-DG resulted in a significant synergistic anti-tumor effect in ESCC cells and xenografts. In conclusion, our findings suggest that the OXPHOS pathway may serve as a promising therapeutic target for ESCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156363"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023920","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":"Targeting FOXM1/PSAT1 axis by Brusatol inhibits lung cancer malignant progression","authors":"Siyi Ou ,&nbsp;Xiaobo Wang ,&nbsp;Yulan Sun ,&nbsp;Yongfeng Liang ,&nbsp;Jing Bai ,&nbsp;Chuanchun Han ,&nbsp;Jing Song","doi":"10.1016/j.prp.2026.156365","DOIUrl":"10.1016/j.prp.2026.156365","url":null,"abstract":"<div><div>Brusatol (BRU), an extract from Brucea javanica, has been found to inhibit cancer progression. However, the downstream targets of Brusatol and its underlying mechanisms in lung cancer still not fully elucidate and warrant further investigation. Here, we identified that Brusatol significantly downregulated the mRNA and protein levels of phosphoserine aminotransferase 1 (PSAT1). Notably, overexpression of PAST1 could impair the antitumour effects of Brusatol on lung cancer cells in vitro and in vivo. Further mechanism studies revealed that FOXM1, an important transcription factor, was directly bound to the promoter of PSAT1, facilitating its transcription. Besides, FOXM1 upregulation antagonizes Brusatol’s suppression of PSAT1 and sustains tumor cell viability. Collectively, our data suggested that the FOXM1/PSAT1 axis might play an important role in the antitumour effects of Brusatol and that Brusatol may hold promise as a novel therapeutic strategy for lung cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156365"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980042","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":"Lactylation of HK2 facilitates cisplatin resistance in NSCLC by promoting cell migration, invasion, and glycolysis","authors":"Fanrui Zeng ,&nbsp;Wenyang Wang ,&nbsp;Peng Liu ,&nbsp;Qingsi Zeng","doi":"10.1016/j.prp.2025.156349","DOIUrl":"10.1016/j.prp.2025.156349","url":null,"abstract":"<div><h3>Objective</h3><div>Cisplatin (DDP) resistance has markedly diminished the efficacy of DDP-based chemotherapy in non-small cell lung cancer (NSCLC). Glycolysis represents a key contributor to NSCLC progression. Lactylation, a novel epigenetic modification, directly regulates glycolysis-associated gene expression. This study aimed to investigate whether lactylation-mediated modulation of glycolytic genes contributes to DDP resistance in NSCLC.</div></div><div><h3>Methods</h3><div>Cell viability, migration, and invasion capacities in parental and resistant NSCLC cells were assessed using cell counting kit-8 and Transwell migration/invasion assays. RT-qPCR and Western blot analyses were employed to quantify mRNA and protein levels of glycolytic markers. A xenografted tumor model was established to evaluate in vivo tumor progression.</div></div><div><h3>Results</h3><div>DDP-resistant NSCLC cells exhibited elevated glycolysis activity and increased lactylation levels of hexokinase 2 (HK2). Moreover, HK2 lysine lactylation (Kla) and protein stability were enhanced in resistant cells through suppression of ubiquitination. Functional experiments demonstrated that HK2 downregulation inhibited cell viability, migration, invasion, and glycolytic metabolism in A549/DDP and H1229/DDP cells, with these effects being reversed following sodium lactate treatment. Crucially, the glycolytic inhibitor 2-deoxy-<span>D</span>-glucose (2-DG) abrogated this rescue, and a K873R lactylation-deficient mutant failed to restore the malignant phenotype, confirming the specificity of the mechanism. <em>In vivo</em> studies further confirmed that HK2 inhibition suppressed tumor growth.</div></div><div><h3>Conclusions</h3><div>Lactylation at K873 stabilized HK2 by inhibiting its ubiquitination, which in turn drove glycolytic flux and promoted malignant behaviors in DDP-resistant NSCLC. This HK2 lactylation-stabilization axis represents a novel mechanism underlying chemoresistance and a promising therapeutic target for overcoming DDP resistance in NSCLC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156349"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904013","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}