生物学最新文献

{"title":"Blood transcriptomic associations of epigenetic age in adolescents.","authors":"Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas","doi":"10.1080/15592294.2025.2503824","DOIUrl":"10.1080/15592294.2025.2503824","url":null,"abstract":"<p><p>Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14-15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the <i>limma-voom</i> pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of <i>MYO6</i> and <i>ZBTB38</i> across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40-54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2503824"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Varespladib attenuates <i>Naja atra</i>-induced acute liver injury via reversing Nrf2 signaling-mediated ferroptosis and mitochondrial dysfunction.","authors":"Jiahao Liu, Linfeng Wang, Mengxia Xie, Wenjie Zhao, Jiaqi Sun, Yuji Jin, Meiling Liu, Jianqi Zhao, Lixia Cheng, Cheng Wen, Xiaowen Bi, Chunhong Huang","doi":"10.1080/13510002.2025.2507557","DOIUrl":"10.1080/13510002.2025.2507557","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the protective effects of varespladib against <i>Naja atra</i>-induced acute liver injury (ALI) and to elucidate the toxic mechanism of snake venom phospholipase A₂ (SVPLA₂)-induced hepatic oxidative stress, with a particular focus on the role of Nrf2 signaling and its downstream pathways.<b>Methods:</b> A combination of in vivo and in vitro models of <i>N. atra</i> envenomation was employed to assess liver injury, oxidative stress, and mitochondrial dysfunction. The interaction between SVPLA₂ and Nrf2 was analyzed, and the effects of varespladib treatment on these processes were evaluated using histological analysis, biochemical assays, and molecular techniques targeting oxidative stress, ferroptosis, mitophagy, and apoptosis.<b>Results:</b> Varespladib significantly alleviated <i>N. atra</i>-induced ALI. SVPLA₂ was found to directly bind to Nrf2, leading to severe oxidative stress. This oxidative stress initiated a cascade involving Nrf2-mediated ferroptosis, mitochondrial dysfunction, excessive mitophagy, and mitochondria-dependent apoptosis. Treatment with varespladib effectively reversed these pathological events by inhibiting SVPLA₂ activity.<b>Conclusion:</b> Varespladib shows strong therapeutic potential for <i>N. atra</i> envenomation by targeting SVPLA₂. Nrf2 was identified as a direct toxic target of SVPLA₂, and Nrf2-mediated ferroptosis and mitochondrial dysfunction were key mechanisms underlying SVPLA₂-induced hepatic injury.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2507557"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing chronic wasting disease in Korean farms: topsoil removal and 2N NaOH treatment before cervid restocking.","authors":"Kyung-Je Park, Hoo-Chang Park, Yu-Ran Lee, In-Soon Roh, Gordon Mitchell, Young Pyo Choi, Hyun-Joo Sohn","doi":"10.1080/19336896.2025.2527588","DOIUrl":"10.1080/19336896.2025.2527588","url":null,"abstract":"<p><p>Chronic wasting disease (CWD) is a highly contagious prion disease occurring in free-ranging and farmed cervids. In the Republic of Korea, cases of CWD continue to be detected almost annually, on both new and occasionally previously infected farms. CWD-infected animals contaminate soil and other environmental components by shedding prions through their excreta. Since shed prions remain infectious for years in the environment, they can act as infectivity reservoirs facilitating horizontal transmission of CWD. To prevent the further spread of CWD and allow farms to resume operations, control measures on infected farms, including topsoil removal and thorough environmental treatment with 2N NaOH, have been implemented in the Republic of Korea. Restocking remediated farms with cervids was permitted after confirming the absence of prion seeding activity in soil samples using protein misfolding cyclic amplification (PMCA). A total of 215 samples from 18 remediated farms were collected and analysed using PMCA, with only 3 samples from 3 farms displaying prion seeding activity. While the disease control measures effectively eliminated prion seeding activity in CWD-affected farms, CWD recurred at two of the 18 remediated farms 4 to 5 years after restocking animals. It remains unclear whether the recurrence of CWD at the two farms was due to residual prions in the environment after the control measures, or the introduction of the infected animals from other farms. This uncertainty is heightened by the annual occurrence of CWD at multiple farms and the absence of a traceability system for farmed cervids.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"19 1","pages":"20-27"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in genetic engineering for enhanced Polyhydroxyalkanoates (PHA) production: a comprehensive review of metabolic pathway manipulation and gene deletion strategies.","authors":"Raghavendra Paduvari, Divyashree Mysore Somashekara","doi":"10.1080/21655979.2025.2458363","DOIUrl":"10.1080/21655979.2025.2458363","url":null,"abstract":"<p><p>Polyhydroxyalkanoates (PHA) are bioplastics produced by few bacteria as intracellular lipid inclusions under excess carbon source and nutrient-deprived conditions. These polymers are biodegradable and resemble petroleum-based plastics. The rising environmental concerns have increased the demand for PHA, but the low yield in wild-type bacterial strains limits large-scale production. An improvement in the PHA production can be achieved by genetically engineering the wild-type bacterial strains by removing competitive pathways that divert the metabolites away from PHA biosynthesis, cloning strong promotors to overexpress the genes involved in PHA biosynthesis and constructing non-native metabolic pathways that feed the metabolites for PHA production. The desired monomers in the PHA polymers were obtained by elimination of genes involved in PHA biosynthetic pathway. The chain length degradation specific-gene deletion of β-oxidation pathway resulted in the accumulation of PHA monomers having high carbon chain length. A controlled accumulation of monomers in the PHA polymer was achieved by constructing novel pathways in the bacteria and deleting native genes of competitive pathways from the genome of non-PHA producers. The present review attempts to showcase the novel genetic modification approaches conducted so far to enhance the PHA production with a special focus on metabolic pathway gene deletion in various bacteria.</p>","PeriodicalId":8919,"journal":{"name":"Bioengineered","volume":"16 1","pages":"2458363"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of histone methyltransferases in therapeutic resistance of NSCLC.","authors":"Fuze Zhu, Xudong Yang, Yanlong Yang, Xinghe Tong, Jie Jia, Xingkun Gu, Yunping Zhao, Xiaobo Chen","doi":"10.1080/15592294.2025.2536786","DOIUrl":"10.1080/15592294.2025.2536786","url":null,"abstract":"<p><p>Conventional treatments, including chemotherapy, immunotherapy, targeted therapy and radiotherapy, are effective clinical strategies for non-small cell lung cancer (NSCLC) patients, which can significantly improve life quality and prolong survival time. However, the application of drugs in NSCLC patients inevitably leads to therapeutic resistance. In recent years, many studies have shown that histone methyltransferases (HMTs), including both protein arginine methyltransferases (PRMTs) and lysine methyltransferases (KMTs), play pivotal roles in tumor initiation, progression, and treatment resistance. This review synthesizes current insights into histone methylation dynamics driving therapeutic resistance, with a focus on key HMTs and their mechanisms. Additionally, we discuss the molecular mechanisms underlying histone methylation-mediated therapeutic resistance and potential therapeutic strategies targeting histone methylation for overcoming therapeutic resistance in NSCLC.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2536786"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of virus-mediated bacterial interactions on acute gastroenteritis symptoms: A new scoring system for clinical assessment.","authors":"Zhangkai Xu, Zishu Liu, Yuxiang Zhao, Jiang Chen, Weibo Cui, Wenjing Wan, Zhendi Yu, Qingyi Shao, Youshi Liu, Baolan Hu, Dongqing Cheng","doi":"10.1080/21505594.2025.2529442","DOIUrl":"10.1080/21505594.2025.2529442","url":null,"abstract":"<p><p>Acute gastroenteritis (AGE) exerts a substantial healthcare burden and economic loss annually, mainly due to viral infections. The objective of the study was to elucidate the impact of the interactions between the AGE virus and gut microbiota on patient clinical symptoms, thereby facilitating the early diagnosis and treatment of AGE. Clinical information and fecal samples were collected from 289 AGE patients (exclude fungal, parasitic, and bacterial infections), of whom 23.5% were infected with AGE viruses. A scoring method was developed to assess the severity of virus-induced AGE in patients. The results indicate significant differences (<i>p</i> < 0.05 indicates a significant difference, as determined by Kruskal-Wallis test, <i>p</i> = 0.03) in clinical symptom scores among the None-virus, Single-virus, and Dual-virus group. The Single-virus (14.82) and Dual-virus (15.33) groups exhibited more severe clinical symptom, with scoring values higher than None-virus group (12.40). Although significant differences in microbial community composition were observed between the Single-virus and Dual-virus groups (as determined by Adonis analysis, Variation = 0.11, <i>p</i> = 0.034), the diversity index (e.g. Chao1) did not significantly differ among the None-virus (288.14), Single-virus (345.74), and Dual-virus (282.70) groups. Notably, the patients with a higher <i>Prevotella</i>/<i>Bacteroide</i>s index displayed more severe clinical symptom, as the index in the Single-virus and Dual-virus groups was over 10-times greater than in the None-virus group. In summary, this study shows that clinical symptoms of patients with viral AGE could be exacerbated through promoting bacterial competitions, and this understanding would facilitate the early diagnosis and treatment of viral AGE.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2529442"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic study of the immune defense function of the CRISPR1-Cas system in <i>Enterococcus faecalis</i>.","authors":"Shuan Tao, Yewei Fang, Lin Zheng, He Zhang, Yao Xu, Wei Liang","doi":"10.1080/21505594.2025.2530665","DOIUrl":"10.1080/21505594.2025.2530665","url":null,"abstract":"<p><p>Enterococci are Gram-positive cocci that are considered to be one of the causative agents of hospital-acquired infections. CRISPR-Cas is an adaptive immune system with targeted defense functions against foreign invading nucleic acids and plays an important role in antibiotic resistance. In this study, we aimed to investigate II-A CRISPR-Cas-mediated immunity and the molecular mechanism underlying the horizontal transfer of drug resistance genes in <i>Enterococcus faecalis</i>. The mutant strains were constructed by the homologous recombination strategy. The interference of plasmid transformation by the Enterococcus faecalis CRISPR1/Cas system was confirmed through plasmid transformation efficiency. The different mutation positions in the protospacer sequence S1 and PAM region recombinant plasmids were constructed through enzyme digestion and sequencing verification to assess the impact of the CRISPR-encoded immunity. In the wild-type strain, the transformation efficiency of plasmids pAT28-S1-S9 containing protospacers and PAM sites decreased (<i>p</i> < 0.05). Single-base mutations at positions 25 and 28 of the protospacer region eliminated the ability of the wild-type strain to prevent plasmid transformation containing the protospacer and PAM sites (<i>p</i> > 0.05), whereas a single mismatch at protospacer positions 2,10,18,23 did not affect the ability of CRISPR-Cas system-positive strains to interfere with plasmid transformation (<i>p</i> < 0.05). There was no significant difference between the wild-type strain and the mutant strain in the transformation efficiency of the pS1-pΔPAM plasmid without PAM and plasmids containing single mutations (<i>p</i> > 0.05). In conclusion, the CRISPR-Cas system can block the transformation of matching protospacer sequences, and mutations near or within the protospacer adjacent motif (PAM) allow the plasmid to escape CRISPR-encoded immunity.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2530665"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis is important for <i>Toxoplasma gondii</i> replication and virulence <i>in vitro</i> and <i>in vivo</i>.","authors":"Ling-Yu Li, Chun-Xue Zhou, Bing Han, Hany M Elsheikha, Hui-Jie Qiu, Xu-Dian An, Ting Zeng, Dai-Ang Liu, Qing Yang, Xing-Quan Zhu, Huai-Yu Zhou","doi":"10.1080/21505594.2025.2530164","DOIUrl":"10.1080/21505594.2025.2530164","url":null,"abstract":"<p><p>The protozoan parasite <i>T. gondii</i> employs intricate mechanisms to exploit host cells while sustaining their viability, yet its interaction with ferroptosis - an iron-dependent cell death driven by lipid peroxidation - remains poorly defined. Here, we show <i>T. gondii</i> infection induces ferroptotic hallmarks in RAW264.7 macrophages, including elevated lactate dehydrogenase release, labile Fe^{2 +} accumulation, reactive oxygen species (ROS) generation, and lipid peroxidation. Molecular analyses revealed infection-induced downregulation of ferroptosis suppressor GPX4 and upregulation of pro-ferroptotic ACSL4 in macrophages and mice. Mechanistically, the SLC7A11/GPX4 axis governed parasite growth: knockdown of these genes promoted <i>T. gondii</i> replication, whereas overexpression restricted proliferation. Pharmacological studies showed ferroptosis inhibitor Fer-1 suppressed intracellular parasite proliferation. Notably, GPX4 inhibitor RSL3 exhibited context-dependent effects: pre-infection treatment enhanced replication, while post-infection administration inhibited growth. Direct RSL3 exposure induced time-dependent growth arrest in extracellular tachyzoites, associated with disrupted transcriptomes, increased lipid ROS, and downregulated parasite antioxidant genes (<i>TgPRX2</i>, <i>TgTPX1/2</i>, <i>TgNXN</i>), indicating redox homoeostasis impairment. In vivo murine studies corroborated this biphasic effect: therapeutic RSL3 administration post-infection significantly reduced parasite burdens across multiple organs (spleen, liver, kidney, brain) and improved survival rates, while prophylactic pretreatment exacerbated disease progression. We propose RSL3 exerts direct parasiticidal effects via oxidative damage but also enables early nutrient acquisition from ferroptosis-compromised host cells. These findings establish ferroptosis as a critical node in <i>T. gondii</i> pathogenesis, highlighting the parasite's hijacking of host iron-lipid metabolism. The dual role of ferroptosis regulators underscores the host-pathogen metabolic complexity and positions the SLC7A11/GPX4 axis as a promising therapeutic target.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2530164"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IscR-tmRNA regulatory axis plays a key role in multiple stress response and pathogenicity in <i>Aeromonas veronii</i>.","authors":"Xiang Ma, Yuan Tong, Pingwei Gao, Lingmin Sun, Hong Li, Yanqiong Tang, Juanjuan Li, Xue Chi, Zhu Liu","doi":"10.1080/21505594.2025.2530659","DOIUrl":"10.1080/21505594.2025.2530659","url":null,"abstract":"<p><p>Bacterial pathogens intricately modulate their response to a variety of stress and the virulence, particularly in light of the dynamic conditions both in natural habitat and within host organisms. Transfer-messenger RNA (tmRNA), which plays an important role in pathogenicity due to its major function in the trans-translation system for ribosome rescue, has been proved as a stress response molecule. Herein, our results indicate that the global regulator IscR acts as a crucial activator responsible for the expression of tmRNA in <i>Aeromonas veronii</i>, a bacterial pathogen posing significant challenges to both aquatic industry and public health. Bacterial one-hybrid and electrophoretic mobility shift assays (EMSA) confirm the direct binding of IscR to the promoter region of the <i>ssrA</i> gene which encodes tmRNA. Moreover, our phenotypic characterizations illustrate that the complementation of tmRNA can rescue the defects of <i>iscR</i> deletion in response to adverse stress, including nutrient deprivation, elevated temperatures, β-lactam antibiotics, and oxidative stress, as well as in establishing the pathogenicity characterized by motility, aggregation, adhesion, cytotoxicity, bacterial competition, and colonization in mice. Our findings offer insights into a potential model for strengthening bacterial survival in external environments, and provide an initial glimpse into the intricate interplay between the functional roles of IscR and tmRNA in the pathogenicity through the IscR-tmRNA regulatory axis.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2530659"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases <i>Helicobacter pylori</i> density in the murine stomach.","authors":"Licínia Santos, Sinan Sharba, John Benktander, Stefany Ojaimi Loibman, Macarena P Quintana-Hayashi, Mattias Erhardsson, Sara K Lindén","doi":"10.1080/21505594.2025.2530173","DOIUrl":"10.1080/21505594.2025.2530173","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> is the most common gastric pathogen. <i>H. pylori</i> is prone to develop antibiotic resistance and recurrence after therapy makes treatment problematic. <i>H. pylori</i> can be detected attached to the gastric epithelial cells; however, it is mostly found within the gastric mucus. <i>Helicobacter</i> species infections impair the mucus barrier by decreasing the binding ability of the mucins, decreasing the growth-limiting activity of mucins and decreasing mucin production. The current study aimed to restore mucin production in the male C57BL/6 mouse <i>H. pylori</i> (SS1) infection model and evaluate its effects on <i>H. pylori</i> density. Mice infected with SS1 were treated with (R)-α-methylhistamine (RαMH) or interleukin-4 (IL4). Treatment with RαMH or IL4 restored mucin production and decreased gastric <i>H. pylori</i> density compared to mock-treated infected mice. Treatment with RαMH and IL4 did not affect serum anti-<i>H. pylori</i> IgG levels, expression of antimicrobial peptides or <i>H. pylori</i> virulence factors. Further, RαMH did not have cytotoxic effects on <i>H. pylori</i>. However, the expression of cytokines (<i>Tnf</i> and <i>Il4)</i>, factors related to mucus production (<i>Tff1</i>, <i>Spedf, Stat6,</i> and <i>Ptgs1</i>), and mucin O-glycan sialylation levels differed between mice treated with RαMH and IL4. This suggests that increased mucus production can have similar effects on pathogen density in spite of differences in the local niche. In conclusion, agents that stimulate mucin production in the gastric mucosa have the potential to aid in the removal of pathogens from the gastric niche.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2530173"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}