Molecular immunology最新文献

{"title":"GDF15 activates the PI3K/AKT pathway to mediate macrophage M2 polarization to promote prostate cancer resistance to docetaxel","authors":"Ruiqian Li ,&nbsp;Hongyi Wu ,&nbsp;Fengming Ran ,&nbsp;Yixuan He ,&nbsp;Hong Sun ,&nbsp;Wenjun Peng ,&nbsp;Qilin Wang ,&nbsp;Jun Li","doi":"10.1016/j.molimm.2025.07.006","DOIUrl":"10.1016/j.molimm.2025.07.006","url":null,"abstract":"<div><div>Drug resistance in cancer treatment is a major challenge, and macrophage polarization plays a key role in the development of prostate cancer (PCa). Growth differentiation factor 15 (GDF15) is highly expressed in most cancers and is induced during anticancer treatment. The aim of this study was to investigate the regulatory mechanism of GDF15 in macrophage polarization and resistance to docetaxel (DTX) in PCa patients. We collected clinical samples from PCa patients to evaluate the expression level of GDF15 and its correlation with M2-type macrophage polarization. In this study, CCK-8, RT<img>qPCR, flow cytometry and western blotting were used to investigate the mechanisms by which GDF15 regulates macrophage M2 polarization and PCa chemotherapy resistance. The results showed that GDF15 was significantly upregulated in PCa samples and was closely related to the level of M2 macrophage polarization. Further experiments revealed that M2 macrophages synthesize GDF15, which is involved in the regulation of DTX resistance in PCa cells. Following knockdown of GDF15 expression in M2-type macrophages, we observed that the resistance of PCa cells to DTX was significantly attenuated. This regulatory mechanism was achieved mainly through the inhibition of the PI3K/AKT signaling pathway, preventing the M2 polarization of macrophages. In conclusion, the upregulation of GDF15 in M2 macrophages can activate the PI3K/AKT signaling pathway, enhancing the DTX resistance of PCa cells. These findings provide new insights and potential targets for treatment strategies against PCa chemotherapy resistance.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"185 ","pages":"Pages 27-38"},"PeriodicalIF":3.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655298","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":"Preparation of African swine fever virus (ASFV) p30 monoclonal antibodies and identification of novel antigenic epitopes","authors":"Jiajia Zhang ,&nbsp;Kaili Zhang ,&nbsp;Shaohua Sun ,&nbsp;Dafu Deng ,&nbsp;Ping He ,&nbsp;Hanrong Lv ,&nbsp;Sen Jiang ,&nbsp;Wanglong Zheng ,&nbsp;Nanhua Chen ,&nbsp;Jinguo Gu ,&nbsp;Jianfa Bai ,&nbsp;Jianzhong Zhu","doi":"10.1016/j.molimm.2025.07.009","DOIUrl":"10.1016/j.molimm.2025.07.009","url":null,"abstract":"<div><div>African swine fever (ASF) is a highly infectious disease caused by African swine fever virus (ASFV), with a mortality rate of up to 100 % for highly virulent strains. The ASFV p30 protein is encoded by the early transcriptional gene CP204L. As one of the structural proteins of ASFV, p30 is an ideal diagnostic antigen for ASF. Here, we first generated three monoclonal antibodies (mAbs) specific for p30 from immunized BALB/c mice via cell fusion, which were successfully applied in ELISA, Western blotting, and immunofluorescence assay. Second, two novel antigenic epitopes, ¹⁶⁹TIYGTPLKE¹⁷⁷ and ¹¹¹ETNECTSSFET¹²¹ of p30 were identified using Western blotting with the three p30 mAbs. The two epitopes identified were highly conserved across genotypes I and/or II ASFVs. Third, an indirect ELISA based on epitope peptides of p30 was established to effectively detect antibodies during ASFV infection.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"185 ","pages":"Pages 18-26"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632165","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":"MSC-EVs alleviate sepsis-induced acute lung injury through inhibiting NET-triggered damage to adherens junctions of endothelial cells","authors":"Yuwen Shao ,&nbsp;Dan Wu ,&nbsp;Changhong Miao ,&nbsp;Hao Zhang","doi":"10.1016/j.molimm.2025.07.004","DOIUrl":"10.1016/j.molimm.2025.07.004","url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs) play a crucial role in the progression of sepsis-induced acute lung injury (SI-ALI). Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) are considered to have potential therapeutic effects on SI-ALI. Nevertheless, a comprehensive understanding of the precise mechanism is currently lacking. This study intends to illustrate the therapeutic mechanisms of MSC-EVs against NET-mediated SI-ALI. In vivo and in vitro experiments demonstrate that NETs reduced the expression of VE-cadherin through calpain 1/2 activation, thereby impairing endothelial barrier function and exacerbating the pathogenesis of SI-ALI. MSC-EVs were found to alleviate SI-ALI by reducing the formation of NETs. Additionally, MSC-EVs inhibited NET generation by shifting NETosis to apoptosis through the ROS/AKT pathway. This study delineates the pathogenic role of NET-induced endothelial injury in SI-ALI and promotes MSC-EVs as a novel therapeutic approach for this disease.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"185 ","pages":"Pages 6-17"},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614656","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":"CFH nonsense mutation-mediated pregnancy-associated atypical hemolytic uremic syndrome: Case report","authors":"Chengjun Hu ,&nbsp;Ping Zhang ,&nbsp;Qi Xu ,&nbsp;Rujuan Qin ,&nbsp;Weifeng Chen ,&nbsp;Zhen Shi ,&nbsp;Ping Chen ,&nbsp;Maozhong Xu","doi":"10.1016/j.molimm.2025.07.002","DOIUrl":"10.1016/j.molimm.2025.07.002","url":null,"abstract":"<div><div>Pregnancy-associated hemolytic uremic syndrome (P-aHUS) is characterized by microvascular hemolytic anemia, thrombocytopenia, and acute organ damage, particularly acute kidney injury, occurring during pregnancy or in the postpartum period. This rare disease has been associated with mutations in genes that regulate the complement system in most reported cases. This article introduces a 38-year-old maternal, who gave birth again after 13 years. Approximately four days post-cesarean section, she developed severe anemia, thrombocytopenia, renal impairment, and abnormal liver function, prompting urgent symptomatic treatment by the doctor. Subsequent detections revealed decreased complement C3 levels, a negative result for the ADAMTS13 inhibitory antibody, and a negative stool culture for bacterial fungi. The diagnosis of P-aHUS was confirmed, and the condition was successfully managed with complement blockade therapy using Eculizumab. Genetic sequencing of the complement factor H (<em>CFH</em>) gene revealed the c.3643 C &gt; T mutation (p.Arg1215*), indicating the presence of rare <em>CFH</em> gene variants that may contribute to the patient's condition. These findings elucidate the clinical manifestations and treatment responses associated with the rare disease P-aHUS in relation to specific gene mutations. We underscore the significance of genetic testing for accurate diagnosis and personalized treatment, offering new insights and evidence for the future clinical management and research of similar cases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"185 ","pages":"Pages 1-5"},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597107","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":"Knockdown of FSTL1 attenuates sepsis-induced acute lung injury by inhibiting inflammation and ferroptosis","authors":"Xin Zhou ,&nbsp;Bin Gao ,&nbsp;Kaili Li ,&nbsp;Hongxue Fu ,&nbsp;Yingting Hao ,&nbsp;Ailing Lan ,&nbsp;Fachun Zhou","doi":"10.1016/j.molimm.2025.06.010","DOIUrl":"10.1016/j.molimm.2025.06.010","url":null,"abstract":"<div><div>Sepsis is a life-threatening condition characterized by high morbidity and mortality, with acute lung injury being the earliest and most severe complication. The damage to pulmonary microvascular endothelial cells (HPMECs) resulting from excessive inflammation plays a critical role in sepsis-induced acute lung injury (si-ALI). This study aimed to elucidate the role of Follistatin-like protein 1 (FSTL1) in si-ALI and its underlying pathophysiological mechanisms. We established an in vitro model of HPMECs stimulated by lipopolysaccharide (LPS), revealing a significant upregulation of FSTL1 at both mRNA and protein levels. Knockdown of FSTL1 mitigated inflammation by inhibiting the secretion of interleukin-1β (IL-1β) and interleukin-6 (IL-6), reducing reactive oxygen species (ROS) production, malondialdehyde (MDA) and ferrous ion (Fe^2 +) levels, while simultaneously increasing glutathione (GSH) levels. Moreover, western blot showed that the knockdown of FSTL1 effectively suppresses cellular ferroptosis through the upregulation of SLC7A11, GPX4, and FTH. Conversely, FSTL1 overexpression exacerbated inflammation and ferroptosis, an effect reversible partly by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Furthermore, utilizing cecal ligation and puncture (CLP) method to establish sepsis mice model demonstrated that silencing of FSTL1 alleviated lung tissue damage associated with sepsis-induced pulmonary injury while inhibiting IL-1β and IL-6, ROS production, and ferroptosis. In conclusion, our findings indicated that knockdown of FSTL1 significantly improved si-ALI both in vitro and in vivo, suggesting it as a potential therapeutic target for managing sepsis-induced acute lung injury.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 213-223"},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563566","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":"Gut microbiota-derived Proline-Leucine dipeptide aggravated sepsis-induced acute lung injury via activating Nod2/NF-κB signaling pathway","authors":"Lei Yang ,&nbsp;Siqi He ,&nbsp;Ao Wei ,&nbsp;Xiangyu Wang ,&nbsp;Liangyong He ,&nbsp;Lingzhi Cui ,&nbsp;Sijia Zhang ,&nbsp;Chengliang Zhong ,&nbsp;Yuzhen Zhuo ,&nbsp;Ximo Wang","doi":"10.1016/j.molimm.2025.05.024","DOIUrl":"10.1016/j.molimm.2025.05.024","url":null,"abstract":"<div><h3>Objective</h3><div>Gut microbiota-derived metabolites can modulate lung tissue damage via the gut-lung axis. This study aimed to delineate the alterations in gut microbiota and metabolites associated with sepsis and elucidate their role in potentiating lung tissue damage.</div></div><div><h3>Methods</h3><div>We employed 16S rDNA sequencing and non-targeted metabolomics to assess the changes in gut microbiota and metabolites, utilizing a rat model of sepsis. Furthermore, we investigated the contributions of the gut microbiota-derived Proline-Leucine (Pro-Leu) dipeptide and lipopolysaccharide (LPS) in driving lung inflammation, utilizing both mouse models and MH-S cells.</div></div><div><h3>Results</h3><div>Our findings indicate that sepsis significantly diminished gut microbiota diversity and markedly increased the relative abundance of <em>Bacteroidetes and Escherichia-Shigella</em>, as well as the metabolite Pro-Leu. Notably, Pro-Leu levels correlated with changes in bacterial communities. Additionally, Pro-Leu effectively exacerbated sepsis-induced lung damage. Both Pro-Leu and LPS notably enhanced pro-inflammatory cytokine production (TNF-α, IL-6, and IL-1β) by up-regulating C/EBP-β, p-NF-κB, and NOD2 in lung tissues and MH-S cells.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that Pro-Leu and LPS can synergistically intensify lung inflammation by activating the C/EBP-β/NOD2/NF-κB signaling pathways.</div></div><div><h3>Importance</h3><div>Our findings indicate that sepsis can lead to a disruption of the gut microbiota, an increase in pathogenic bacteria such as Escherichia-Shigella and Bacteroides, and that metabolites derived from the gut microbiota can modulate the lung inflammatory response through the gut-lung axis. Notably, Pro-Leu, a metabolite produced by the gut microbiota, was found to aggravate sepsis-induced ALI by activating the C/EBP-β/NOD2/NF-κB signaling pathways.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 199-212"},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549209","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":"Genetics and humoral responses of the immune system to Aspergillus fumigatus","authors":"Daniel Ruben Akiola Sanya ,&nbsp;Krish Jayachandran ,&nbsp;Djamila Onésime","doi":"10.1016/j.molimm.2025.06.007","DOIUrl":"10.1016/j.molimm.2025.06.007","url":null,"abstract":"<div><div>Due to the increasing incidence of invasive aspergillosis (IA) caused by the opportunistic fungal pathogen <em>Aspergillus fumigatus</em>, coupled with rising antifungal resistance and high mortality rates globally, novel antifungal development is a critical priority for reducing disease burden. The opportunistic fungus <em>Aspergillus fumigatus,</em> prevalent in the environment alongside other fungi, infects immunocompromised individuals with weakened immune systems. The pathogen can cause severe diseases with fatal outcomes. Risk factors contributing to the severity of <em>A. fumigatus</em>-associated diseases have been identified, and the efficacy and molecular targets of antifungal drugs have been documented. Here, we describe specific interactions between the human immune system and the airborne pathogen <em>A. fumigatus</em>, emphasizing how co-infections influence virulence and disease progression. We reported <em>A. fumigatus</em> cell wall components, such as β-glucans, that mediate interactions with the host immune system, acting as virulence factors driving significant morbidity and mortality. We also discovered compounds, biomarkers, and non-coding RNAs with potential for immunotherapy, suitable for applications in targeted antifungal therapy, vaccine development, and diagnostics..</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 164-198"},"PeriodicalIF":3.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535454","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":"NME4: A novel metabolic-associated biomarker for prognosis prediction and immunotherapy response evaluation in clear cell renal cell carcinoma","authors":"Shilong Cheng ,&nbsp;Qisheng Lin ,&nbsp;Kai Chen ,&nbsp;Jiaxing Wang ,&nbsp;Hangyang Peng ,&nbsp;Yaqiang Huang ,&nbsp;Xiangming Mao ,&nbsp;Jianming Lu ,&nbsp;Chuanfan Zhong","doi":"10.1016/j.molimm.2025.06.011","DOIUrl":"10.1016/j.molimm.2025.06.011","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of renal cell carcinoma (RCC) remains high and continues to rise annually, with the clear cell subtype accounting for the majority of cases histologically. While immunotherapy has partially improved the 5-year relative survival rate, response rates vary due to individual heterogeneity, and the overall prognosis remains poor, particularly for high-stage patients. There is an urgent need to identify novel biomarkers for predicting patient prognosis and immunotherapy efficacy to enable personalized treatment.</div></div><div><h3>Methods</h3><div>Univariate and multivariate Cox regression analysis were employed to validate the prognostic value of NME4 in clear cell renal cell carcinoma (ccRCC) across four cohorts, followed by functional enrichment analysis to elucidate its biological functions. Cellular experiments were conducted to verify NME4's role in ccRCC proliferation and migration. Furthermore, the TIDE (Tumor Immune Dysfunction and Exclusion) algorithm and external datasets were utilized to investigate NME4's predictive capacity for immunotherapy response, while using the 'IOBR' package to analyze the relationship between NME4 and ccRCC immune microenvironment. Finally, somatic mutation and copy number variation analysis provided multi-omics insights into NME4's molecular mechanisms in ccRCC.</div></div><div><h3>Results</h3><div>Our study determined the predictive ability of NME4 for ccRCC patient prognosis, and patients with high NME4 expression had worse OS and PFI. Functional enrichment analysis revealed the biological functions of NME4, indicating its involvement in the reprogramming of multiple metabolic pathways. Cellular experiments showed that NME4 promoted the proliferation and migration of ccRCC. The TIDE algorithm and external datasets indicated that low NME4 expression predicts better responses to immunotherapy. Additionally, significant differences were observed between NME4 expression subgroups in multi-omics data analysis based on somatic mutation and copy number variation.</div></div><div><h3>Conclusion</h3><div>In this study, we validated NME4's prognostic predictive capacity for ccRCC patients. Meanwhile, NME4 is expected to be a molecular marker to guide the precise application of immunotherapy in clinical practice.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 149-163"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518318","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":"Linker histone H1.3 promotes IFN-β production targeting MDA5 signaling to inhibit EMCV infection","authors":"Huixia Li ,&nbsp;Xueer Dou ,&nbsp;Na Wang ,&nbsp;Ruiya Lian ,&nbsp;Shasha Li ,&nbsp;Jingying Xie ,&nbsp;Xiangrong Li ,&nbsp;Yanmei Yang ,&nbsp;Yanqiao Wen ,&nbsp;Ruofei Feng","doi":"10.1016/j.molimm.2025.06.005","DOIUrl":"10.1016/j.molimm.2025.06.005","url":null,"abstract":"<div><div>Multiple core histones play pivotal roles in viral infection process, as evidenced in influenza virus and other viruses. Recent findings indicate that linker histone H1.2 regulates the interferon signaling pathway to modulate influenza and EMCV infections, while H1.3 may also play a role in EMCV infection. In this study, we initially demonstrated that overexpression of H1.3 markedly suppressed the EMCV replication and proliferation. Conversely, knockdown of H1.3 expression led to an upregulation of EMCV replication and proliferation. Additionally, we observed a significant enhancement of EMCV-induced type I IFN production in Myc-H1.3 expressing cells. Our further exploration revealed that H1.3 upregulated the expression of MDA5 and enhanced the phosphorylation of TBK1 and IRF3 during EMCV infection, with opposite effects observed in H1.3 knockdown cells. Subsequently, we confirmed the interaction between H1.3 and MAVS, as well as IRF3, using both endogenous and exogenous Co-IP assays. Furthermore, we demonstrated that H1.3 promoted IRF3 phosphorylation and its nuclear translocation in EMCV-infected A549 cells. Notably, the N-terminal domain of H1.3 may play a crucial role in regulating the IFN-β signaling pathway to inhibit EMCV replication. Finally, we observed that EMCV infection upregulated the phosphorylation of H1.3, which may correlate with increased transcriptional expression of genes such as IFN-β. In summary, our findings address the gap in understanding the involvement of H1.3 in viral infection and elucidate the mechanism by which H1.3 negatively regulates EMCV replication. These findings may provide new insights into potential antiviral targets.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 137-148"},"PeriodicalIF":3.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491271","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":"Network pharmacology and in vivo investigation of the growth and immunity-enhancing mechanisms of Tetramethylpyrazine (TMP) in Litopenaeus vannamei","authors":"Renzhi Liu ,&nbsp;Futao Jing ,&nbsp;Zhengxu Chen ,&nbsp;Mingxiang Lu ,&nbsp;Xin Yu ,&nbsp;Yaobing Li ,&nbsp;Luqing Pan","doi":"10.1016/j.molimm.2025.06.009","DOIUrl":"10.1016/j.molimm.2025.06.009","url":null,"abstract":"<div><div>In this study, the shrimp (<em>L. vannamei</em>, 0.89 ± 0.04 g) were fed formulated diets supplemented with Tetramethylpyrazine for six weeks under routine aquaculture conditions, followed by a three-day challenge with White Spot Syndrome Virus (WSSV). The results showed that dietary TMP supplementation significantly improved the specific growth rate and weight gain rate, while reducing the feed conversion ratio. During the viral challenge, the immune protection rate of shrimp was significantly enhanced (<em>P</em> &lt; 0.05). Further analysis using network pharmacology, molecular docking, and quantitative real-time PCR demonstrated that TMP exhibited strong binding affinities with hypoxia-inducible factor 1-alpha (<em>HIF1A</em>), prostaglandin synthase (<em>PTGSH2</em>), and nuclear transcription factors (<em>Relish</em> and <em>Dorsal</em>). At the transcriptional level, TMP significantly inhibited the expression of <em>HIF1A</em> and sterol regulatory element-binding protein (<em>SREBP</em>), while upregulating adiponectin receptor (<em>AdipoR</em>) expression. TMP also promoted lipid catabolismand cholesterol efflux-related genes, while downregulating lipid synthesis genes. Moreover, TMP enhanced the expression of arachidonic acid pathway-related genes and antioxidant enzymes, leading to reduced levels of malondialdehyde (MDA) and blood lipids. Regarding immune stimulation, TMP activated the NF-κB (<em>Dorsal</em>, <em>Relish</em>) signaling pathway, upregulated the expression of antimicrobial peptides, and reduced inflammatory cytokine levels. Under WSSV infection, TMP suppressed viral replication by downregulating <em>HIF1A</em> and <em>VEGF</em> expression (<em>P</em> &lt; 0.05), suggesting that TMP exerts its antiviral effect. High-throughput sequencing of the intestinal microbiota indicated that TMP supplementation increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria, thereby improving intestinal mucosal barrier function. In conclusion, considering both growth performance and physiological health, we recommend an optimal TMP supplementation level of 150 mg/kg in shrimp feed.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 123-136"},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491270","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}