Molecular immunology最新文献

{"title":"Liquiritigenin regulates JAK/STAT3 and NF-κB signaling pathways to reduce colonic damage and barrier dysfunction caused by a high-salt diet","authors":"Weiping Yan ,&nbsp;Lei Wang ,&nbsp;Wenting Zhu ,&nbsp;Xiao Liu ,&nbsp;Zihan Xu ,&nbsp;Juntong Liu ,&nbsp;Jie Ding ,&nbsp;Mengling Zhu ,&nbsp;Fenfen Ma ,&nbsp;Zibo Dong","doi":"10.1016/j.molimm.2026.01.005","DOIUrl":"10.1016/j.molimm.2026.01.005","url":null,"abstract":"<div><div>It has been shown that a high-salt diet (HSD) significantly damages the colonic epithelial barrier, resulting in increased intestinal permeability, upset gut microbial balance, and generalized inflammation. Despite this, effective therapeutic strategies to prevent HSD-induced intestinal damage remain limited. This study aims to explore the preventive properties and basic mechanisms of liquiritigenin (LG)，a natural flavonoid, against chronic colonic injury induced by prolonged HSD exposure. A murine model of chronic colitis was established by administering an 8 % NaCl diet, and LG therapy was used to evaluate how it affected the function of the intestinal barrier and allergic reactions. The development of pro- and anti-inflammatory cytokines (<em>il-β</em>, <em>il-6</em>, <em>tnf-α, il-10</em>, and <em>inos</em>) as well as important tight junction proteins (ZO-1, Claudin-3, and Occludin) was assessed. Furthermore, we investigated the molecular processes <em>in vitro</em> using normal colonic epithelial cell line NCM-460, with particular focus on the NF-κB and JAK/STAT3 signaling pathways. LG increased the expression of junction-binding proteins, greatly enhanced the intestinal wall integrity, and mitigated histopathological damage. Furthermore, it markedly attenuated excessive inflammatory responses both <em>in vivo</em> and <em>in vitro</em>. Mechanistically, LG suppressed the phosphorylation of key components within the pathways of JAK/STAT3 and NF-κB, thereby inhibiting downstream inflammatory signaling and epithelial cell injury. Collectively, these results demonstrate that liquiritigenin exerts protective effects against HSD-induced colonic damage by concurrently modulating the NF-κB and JAK/STAT3 pathways, highlighting its therapeutic potential for high salt-related intestinal disorders.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"190 ","pages":"Pages 86-100"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalpol enhances mTORC1/HIF-1α/PDHK1-mediated oxidative metabolism that leads to promote the differentiation of Treg cells in RA","authors":"Qiaoyu Zhang ,&nbsp;Furong Wang ,&nbsp;Peng Ding ,&nbsp;Yu Ge,&nbsp;Yujie Bao,&nbsp;Baoping Jiang,&nbsp;Lingling Zhou","doi":"10.1016/j.molimm.2025.11.016","DOIUrl":"10.1016/j.molimm.2025.11.016","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease in which regulatory T (Treg) cell dysfunction contributes to its pathogenesis, although the mechanisms regulating Treg differentiation remain unclear. In this study, the effects of Catalpol (CAT) on Treg differentiation and its underlying mechanisms were investigated using a CIA mouse model, with animals randomly allocated to CIA, CIA+CAT, and No CIA groups. Synovial pathology was assessed by HE staining, while naive CD4⁺ T cells were differentiated into Tregs in vitro, and treated with CAT. Molecular docking predicted CAT-target interactions, and the mTORC1 activator NV5138 was used alongside CAT for intervention. Treg proportions and mitochondrial membrane potential were analyzed by flow cytometry, IL-10 levels were measured by ELISA, NAD⁺/NADH was detected by assay kit, and mRNA expression of FOXP3, mTOR, Raptor, HIF-1α, and PDHK1 were determined by RT-qPCR, while protein expression was assessed by Western blotting. The results demonstrated that CAT alleviated joint symptoms in CIA mice, promoted Treg differentiation both in vivo and in vitro, and increased mitochondrial membrane potential, NAD⁺/NADH and acetyl-CoA levels in Tregs. CAT also downregulated HIF-1α and PDHK1 mRNA and inhibited p-P70S6K/P70S6K, p-4EBP1/4EBP1, HIF-1α, and PDHK1 protein expression. Treatment with NV5138 was observed to reduce Treg differentiation and oxidative metabolism, effects which were reversed by CAT. These findings demonstrate that CAT promotes Treg differentiation and exerts anti-RA effects through inhibition of the mTORC1/HIF-1α/PDHK1 signaling pathway and enhancement of pyruvate aerobic oxidation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 1-12"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genetic characteristics of Pahepcidin1 and Pahepcidin2 in silver pomfret (Pampus argenteus) and their antibacterial functions in innate immunity","authors":"Qian Fang ,&nbsp;Ruoxin Wang ,&nbsp;Xiumei Liu ,&nbsp;Yajun Wang ,&nbsp;Qingping Xie ,&nbsp;Chunyang Guo ,&nbsp;Mingzhe Yuan ,&nbsp;Xubo Wang","doi":"10.1016/j.molimm.2025.12.004","DOIUrl":"10.1016/j.molimm.2025.12.004","url":null,"abstract":"<div><div>Hepcidins are a class of cysteine-rich antimicrobial peptides that exert significant impacts in response to a variety of pathogens. In this study, two hepcidins were identified from silver pomfret (<em>Pampus argenteus</em>), namely <em>Pahepcidin1</em> and <em>Pahepcidin2</em>. Our findings revealed that <em>Pahepcidin1</em> consists of a 267 open reading frame (ORF) encoding 91 amino acids, while <em>Pahepcidin2</em> consists of 246 bp ORF encoding 81 amino acids. Sequence comparison between <em>Pahepcidins</em> and other homologous genes demonstrated the presence of eight conserved cysteines in the C-terminus region of Pahepcidin1 and six cysteine residues in the C-terminus region of Pahepcidin2. Phylogenetic analysis indicated that both Pahepcidin1 and Pahepcidin2 clustered with other fish homologues, respectively. The results of tissue-specific expression analysis showed that <em>Pahepcidins</em> exhibited the highest expression level in the liver; moreover, the expression level of <em>Pahepcidin1</em> in silver pomfret liver cells (PaL cells) was also significantly increased after stimulation with lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (poly I:C), and <em>Staphylococcus aureus</em> (<em>S. aureus</em>). Meanwhile, this study verified the antibacterial function of recombinant Pahepcidin1, and the results indicated that it possessed broad antibacterial activity against both Gram-positive bacteria (<em>S. aureus</em>) and Gram-negative bacteria (<em>Edwardsiella tarda</em>). In addition, the overexpression of Pahepcidin1 could significantly alter the transcriptional levels of key genes in the NF-κB pathway and downstream immune-related genes. In vivo validation via <em>Vibrio parahaemolyticus</em> challenge showed that <em>Pahepcidin1</em> expression in silver pomfret liver was significantly upregulated at 3 h and peaked at 6 h, then downregulated to below the baseline from 12 h to 48 h. These results suggested that <em>Pahepcidin1</em> might play an essential role in the innate immune system modulation of silver pomfret, providing valuable insights into understanding the antimicrobial immune mechanism of this species.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 163-173"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria in pyroptosis: Mechanisms and implications","authors":"Basmah M. Eldakhakhny ,&nbsp;Wesam h. Abdulaal ,&nbsp;Johra Khan ,&nbsp;Amir Ajoolabady ,&nbsp;Domenico Pratico ,&nbsp;Suhad Bahijri ,&nbsp;Jaakko Tuomilehto ,&nbsp;Anwar Borai ,&nbsp;Bonglee Kim ,&nbsp;Jun Ren","doi":"10.1016/j.molimm.2025.12.002","DOIUrl":"10.1016/j.molimm.2025.12.002","url":null,"abstract":"<div><div>Pyroptosis is an inflammatory, necrotic, and lytic form of programmed cell death, involving activation of inflammasome complexes, inflammatory caspases, and the cleavage of gasdermins. Gasdermins are a large family of pore-forming proteins with critical implications in key cellular processes and inflammatory disease contexts. These gasdermins subsequently oligomerize to form pores in the plasma membrane, releasing cellular contents and inflammatory mediators. Mechanistically, pyroptosis can occur via either caspase-1-dependent canonical pathway or the caspase-1-independent non-canonical pathway, both ultimately resulting in similar forms of pyroptotic cell death. While the underlying mechanisms of pyroptosis are broad and complex, certain key processes simplify the understanding of these mechanisms. One such critical process is the role of mitochondria and mitochondrial dysfunction in mediating pre-pyroptotic signaling. This review aims to provide a brief overview of the general mechanisms of pyroptosis, followed by a discussion of the latest findings on the functional and regulatory roles of mitochondria in pyroptosis. Moreover, we aimed to discuss and decipher emerging concepts such as the interaction between gasdermin D and cardiolipin, the role of mitochondrial DNA and its associated signaling pathways, as well as perspectives on the clinical relevance of these findings in conditions like sepsis, cardiotoxicity, and other diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 98-105"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL2-TLR4 axis activates NETs by accelerating autophagy through ATG7 to promote the progression of idiopathic interstitial pneumonia","authors":"Jianlin He,&nbsp;Jue Li,&nbsp;Min Bai,&nbsp;Jie Yang","doi":"10.1016/j.molimm.2025.12.005","DOIUrl":"10.1016/j.molimm.2025.12.005","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to elucidate the molecular mechanisms through which CXCL2 contributes to the pathogenesis of idiopathic interstitial pneumonia (IIP).</div></div><div><h3>Methods</h3><div>Neutrophils were isolated, and the formation of neutrophil extracellular traps (NETs) was assessed after CXCL2 treatment. Cellular concentrations of cell-free DNA (cf-DNA) were quantified via a cf-DNA/NET kit. Additionally, an enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of IL-6, TNF-α, and LL-37. Western blot analysis was used to measure the levels of LC3-II, LC3-I, citrullinated histone H3 (citH3), myeloperoxidase (MPO), and elastase. Immunohistochemistry was conducted to measure cit H3 levels. Pathological alterations in the lung tissue were examined via microscopic hemosiderin and eosin staining.</div></div><div><h3>Results</h3><div>CXCL2 treatment significantly increased the cellular expression levels of cf-DNA, IL-6, TNF-α, and LL-37, as well as cit H3 and MPO, which are markers of NETs. Furthermore, CXCL2 treatment induced a substantial increase in cellular autophagy. Additionally, CXCL2 treatment led to marked upregulation of TLR4 expression and further elevation of autophagy levels, accompanied by increases in cf-DNA, IL-6, TNF-α, and LL-37 expression. Inhibition of TLR4 expression significantly reduced the levels of these factors. Moreover, the CXCL2-induced upregulation of cf-DNA, IL-6, TNF-α, LL-37, cit H3, and MPO was notably suppressed following the knockdown of ATG7. In IIP murine models, there was a significant upregulation of cf-DNA, IL-6, TNF-α, and LL-37, as well as an increase in cit H3 and MPO expression. Lung tissue analysis revealed inflammatory cell infiltration, alveolar wall thickening, tissue congestion, and edema. Inhibition of CXCL2 and TLR4 expression significantly ameliorated these pathological changes.</div></div><div><h3>Conclusions</h3><div>The CXCL2<img>TLR4 axis may facilitate NET activation by promoting autophagy via ATG7, thereby contributing to IIP progression.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 226-234"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations, challenges, and gaps in the development of an effective vaccine against Neisseria gonorrhoeae, a narrative review","authors":"Narjes Noori Goodarzi ,&nbsp;Mohammad Reza Pourmand","doi":"10.1016/j.molimm.2025.11.019","DOIUrl":"10.1016/j.molimm.2025.11.019","url":null,"abstract":"<div><div><em>Neisseria gonorrhoeae</em>, the causative agent of gonorrhea, accounts for over 87 million new cases annually. It poses a serious threat to global health due to its high antimicrobial resistance. The development of an effective gonorrhea vaccine has been severely hampered by unique characteristics of this pathogen, particularly antigenic and phase variation of surface antigens. Additionally, the difficulty of eliciting effective mucosal immune responses and the inability of natural infection to produce long-lasting immunity further complicate vaccine development. In this review, the main obstacles to gonococcal vaccine development are discussed. Clinical trials evaluating the cross-protective effects (approximately 31–46 %) of 4CMenB vaccine against <em>N. gonorrhoeae</em> have been explored, along with recent advances such as recombinant proteins, multivalent and epitope-based approaches, and emerging mRNA platforms. Promising findings from preclinical studies are highlighted, together with growing role of artificial intelligence and machine learning in antigen discovery and vaccine optimization. Despite these innovations, translating theoretical approaches into safe, immunogenic, and broadly protective vaccines remains a major challenge. This review underscores the urgent need for continued interdisciplinary research to close existing gaps and develop a feasible efficient vaccine to combat drug-resistant gonorrhea.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 13-30"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the role of SMOX in rheumatoid arthritis","authors":"Zuning Jiang ,&nbsp;Ruojia Zhang ,&nbsp;Ya Han ,&nbsp;Ruiyao Sun ,&nbsp;Mingze Kong ,&nbsp;Yuang Zhang ,&nbsp;Junling Li ,&nbsp;Guanhua Song ,&nbsp;Li Qiao ,&nbsp;Lin Wang","doi":"10.1016/j.molimm.2025.11.018","DOIUrl":"10.1016/j.molimm.2025.11.018","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is pathologically marked by joint inflammation and damage. Although the association between spermidine and RA has been recognized, the precise contribution of spermine oxidase (SMOX)-the enzyme catalyzing spermidine synthesis-to RA pathogenesis remains undefined. It’s observed in this study that SMOX was responsible for inflammatory stimuli that its expression increased obviously when RA-associated fibroblast-like synoviocytes (FLSs) were challenged by inflammatory factors. Functionally, silencing SMOX could inhibit migration, invasion, and cytokine production, but induced apoptosis of RA-FLS. Moreover, inhibition of SMOX using JNJ-9350 yielded anti-inflammatory effects comparable to those achieved by gene silencing in RA-FLS. In vivo experiments demonstrated that JNJ-9350 could effectively reduce the severity of arthritis, minimize histopathological damage, and prevent bone erosion in collagen antibody-induced arthritis (CAIA) mice. The present results indicate that SMOX is implicated in the development of RA and suggest that targeting SMOX could be a novel treatment strategy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 235-246"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coxsackievirus B3 regulates macrophage polarization through ANXA3 to promote the development of myocarditis","authors":"Yanfei Chen ,&nbsp;Xingzhu Liu ,&nbsp;Lijuan Meng ,&nbsp;Bin Li ,&nbsp;Zhongjian Su ,&nbsp;Li Jiang ,&nbsp;Yuqin Wu ,&nbsp;Xing Zhang","doi":"10.1016/j.molimm.2025.11.015","DOIUrl":"10.1016/j.molimm.2025.11.015","url":null,"abstract":"<div><h3>Background</h3><div>Viral myocarditis (VMC) is a common inflammatory disease in children that is caused mainly by Coxsackievirus B3 (CVB3) infection. M1 macrophage polarization is a key pathological event in the progression of CVB3-induced myocarditis, and annexin 3 (ANXA3) plays an important role in the process of macrophage activation. Therefore, this study aimed to investigate the function of ANXA3 in CVB3-induced myocarditis and macrophage polarization.</div></div><div><h3>Methods</h3><div>CVB3-challenged mice were used to establish a CVB3-induced myocarditis model, and the polarization of RAW264.7 cells was induced by CVB3 infection. The expression of genes and proteins was detected by RT–qPCR, western blotting, immunohistochemistry, immunofluorescence, and ELISA. The pathological lesions in the cardiac tissue were detected by HE staining. Serum levels of myocardial injury markers were detected using kits.</div></div><div><h3>Results</h3><div>We found that ANXA3 expression was increased in VMC. ANXA3 knockdown hindered the progression of CVB3-induced VMC, as manifested by increased body weight, reduced inflammatory cell infiltration in the heart, and decreased serum levels of myocardial injury markers (LDH, CK, CK-MB and cTnI). ANXA3 knockdown also inhibited the M1 polarization of CVB3-infected mouse heart tissue macrophages and RAW264.7 cells <em>in vitro</em> and reduced the levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α. In addition, CVB3 infection promoted the expression of TLR4, MyD88, and p-IκB-α in mouse heart tissues and RAW264.7 cells and the nuclear transfer of NF-κB p65 and inhibited the expression of IκB-α. Mechanistic studies revealed that CVB3 increased ANXA3 expression by activating the TLR4/MyD88 pathway, thereby promoting NF-κB p65 nuclear translocation and the subsequent M1 polarization of macrophages, eventually leading to the development of CVB3-induced myocarditis.</div></div><div><h3>Conclusion</h3><div>Our study elucidated the role of ANXA3 in promoting CVB3-induced myocarditis, providing a potential intervention target for the treatment of VMC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 68-81"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verticinone inhibits cell growth and induces pyroptosis via regulating AKT pathway in papillary thyroid cancer","authors":"Xincheng Liu,&nbsp;Yang Liu","doi":"10.1016/j.molimm.2025.11.014","DOIUrl":"10.1016/j.molimm.2025.11.014","url":null,"abstract":"<div><h3>Background</h3><div>Verticinone, an alkaloid isolated from <em>Fritillaria</em>, exhibits a range of biological activities. This study aims to investigate the effects of verticinone on papillary thyroid carcinoma (PTC), the most prevalent histological type of thyroid cancer, as well as the potential mechanisms underlying these effects.</div></div><div><h3>Methods</h3><div>Cell counting kit-8, colony formation assay, and 5-ethynyl-2′-deoxyuridine staining were employed to evaluate the impact of verticinone on the proliferation capacity of PTC cells. Wound healing and Transwell assays were conducted to assess the effects of verticinone on the migration and invasion abilities of PTC cells. Flow cytometry was utilized to detect apoptosis in PTC cells. Western blot analysis was performed to measure the expression levels of relevant proteins. Additionally, network pharmacology analysis was conducted to identify potential targets of verticinone and thyroid carcinoma, and molecular docking was used to elucidate the targeting relationship. Finally, the effect of verticinone on tumor growth was evaluated using a xenograft tumor model.</div></div><div><h3>Results</h3><div>Verticinone inhibited the proliferation, migration, and invasion, and induced apoptosis and pyroptosis of PTC cells in a dose-dependent manner. Mechanically, verticinone targeted and inhibited protein kinase B (AKT), facilitating its degradation. AKT overexpression significantly eliminated the effect of verticinone on biological behavior of PTC cells. The results of xenograft tumor experiments demonstrated the inhibitory effect of verticinone on PTC tumor growth.</div></div><div><h3>Conclusion</h3><div>Verticinone inhibited the growth of PTC cells and induced pyroptosis by regulating the AKT pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 41-52"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoimperatorin inhibits cell proliferation and induces apoptosis via regulating PI3K/AKT pathway in acute lymphoblastic leukemia","authors":"Jing Xiao ,&nbsp;Yan Wang","doi":"10.1016/j.molimm.2025.12.009","DOIUrl":"10.1016/j.molimm.2025.12.009","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to explore whether isoimperatorin (ISOIM) regulates the malignant phenotype of T‑cell acute lymphoblastic leukemia (T-ALL) cells through the PI3K/AKT pathway and programmed cell death ligand-1 (PD-L1).</div></div><div><h3>Methods</h3><div>Through <em>in vitro</em> experiments, ISOIM on T-ALL cell proliferation and apoptosis was evaluated using the cell counting kit-8 and EdU assays, flow cytometry, and TUNEL staining. Network pharmacology, molecular docking, and functional enrichment analyses were conducted to analyze the underlying mechanisms of ISOIM. Changes in apoptosis-related proteins, PD-L1 protein, and PI3K/AKT pathway-related proteins were assessed by western blotting.</div></div><div><h3>Results</h3><div>ISOIM inhibited T-ALL cell proliferation, promoted apoptosis, decreased Bcl-2 levels, and increased C-caspase-3 and Bax levels. KEGG and GO enrichment analyses indicated that the overlapping targets between ISOIM and ALL were related to the PD-1 checkpoint and PI3K/AKT pathway. Molecular docking analysis showed good binding between ISOIM and PIK3CA (also known as PI3K). ISOIM reduced PD-L1, p-PI3K, p-AKT, and p-mTOR levels. Moreover, the PI3K/AKT pathway activator 740 Y-P reversed the inhibitory effect of ISOIM on PD-L1 expression and the malignant behavior of T-ALL cells.</div></div><div><h3>Conclusions</h3><div>ISOIM inhibited the malignant behavior of T-ALL cells and reduced PD-L1 levels by suppressing the PI3K/AKT pathway. This study provides a theoretical basis for developing novel treatment strategies for ALL.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 181-191"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}