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The response to desiccation in Acinetobacter baumannii. 鲍曼不动杆菌对干燥的反应。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-04-12 DOI: 10.1080/21505594.2025.2490209
Massimiliano Lucidi, Giulia Capecchi, Cinzia Spagnoli, Arianna Basile, Irene Artuso, Luca Persichetti, Elisa Fardelli, Giovanni Capellini, Daniela Visaggio, Francesco Imperi, Giordano Rampioni, Livia Leoni, Paolo Visca
{"title":"The response to desiccation in <i>Acinetobacter baumannii</i>.","authors":"Massimiliano Lucidi, Giulia Capecchi, Cinzia Spagnoli, Arianna Basile, Irene Artuso, Luca Persichetti, Elisa Fardelli, Giovanni Capellini, Daniela Visaggio, Francesco Imperi, Giordano Rampioni, Livia Leoni, Paolo Visca","doi":"10.1080/21505594.2025.2490209","DOIUrl":"https://doi.org/10.1080/21505594.2025.2490209","url":null,"abstract":"<p><p>The long-term resistance to desiccation on abiotic surfaces is a key determinant of the adaptive success of <i>Acinetobacter baumannii</i> as a healthcare-associated bacterial pathogen. Here, the cellular and molecular mechanisms enabling <i>A. baumannii</i> to resist desiccation and persist on abiotic surfaces were investigated. Experiments were set up to mimic the <i>A. baumannii</i> response to air-drying that would occur when bacterial cells contaminate fomites in hospitals. Resistance to desiccation and transition to the \"viable but nonculturable\" (VBNC) state were determined in the laboratory-adapted strain ATCC 19606<sup>T</sup> and the epidemic strain ACICU. Culturability, membrane integrity, metabolic activity, virulence, and gene expression profile were compared between the two strains at different stages of desiccation. Upon desiccation, ATCC 19606<sup>T</sup> and ACICU cells lose culturability and membrane integrity, lower their metabolism, and enter the VBNC state. However, desiccated <i>A. baumannii</i> cells fully recover culturability and virulence in an insect infection model following rehydration in physiological buffers or human biological fluids. Transcriptome and chemical analyses of <i>A. baumannii</i> cells during desiccation unveiled the production of protective metabolites (L-cysteine and L-glutamate) and decreased energetic metabolism consequent to activation of the glyoxylate shunt (GS) pathway, as confirmed by reduced resuscitation efficiency of <i>aceA</i> mutants, lacking the key enzyme of the GS pathway. VBNC cell formation and extensive metabolic reprogramming provide a biological basis for the response of <i>A. baumannii</i> to desiccation, with implications on environmental control measures aimed at preventing the transmission of <i>A. baumannii</i> infection in hospitals.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2490209"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049534","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}
引用次数: 0
Staphylococcus aureus β-hemolysin impairs oxygen transport without causing hemolysis. 金黄色葡萄球菌β-溶血素损害氧运输而不引起溶血。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-04-09 DOI: 10.1080/21505594.2025.2490208
Qi Li, Nan Chen, Chenghua Liu, Zhen Zhao, Minjun Huang, Jingjing Li, Guang Yang
{"title":"<i>Staphylococcus aureus</i> β-hemolysin impairs oxygen transport without causing hemolysis.","authors":"Qi Li, Nan Chen, Chenghua Liu, Zhen Zhao, Minjun Huang, Jingjing Li, Guang Yang","doi":"10.1080/21505594.2025.2490208","DOIUrl":"https://doi.org/10.1080/21505594.2025.2490208","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> (<i>S. aureus</i>) infection can lead to the occurrence of hypoxia, however, the underlying mechanisms have not been fully elucidated. β-hemolysin (Hlb) induced hemolysis of red blood cells (RBCs) requires a temperature transition from \"hot\" to \"cold,\" a phenomenon not observed under physiological conditions. In this study, we discovered that RBCs treated with Hlb exhibited a high level of intracellular Ca<sup>2+</sup> and underwent a shape transformation from biconcave discoid to spherical, which was contingent upon the degradation of sphingomyelin of the cell membrane and led to impaired oxygen transport. The increase in intracellular Ca<sup>2+</sup> levels induced by Hlb was dependent on the activation of the ion channel N-methyl-D-aspartate receptor. Furthermore, we found that Hlb-induced Ca<sup>2+</sup> influx increased the cytoplasmic pH and subsequently attenuated the oxygen release from RBCs, which were also observed in both <i>hlb</i> transgenic mice and a murine model with <i>S. aureus</i> challenge. Our findings reveal a novel role for Hlb as sphingomyelinase in impairing RBC function under non-lytic conditions, shedding light on the mechanism behind hypoxia associated with <i>S. aureus</i> infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2490208"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999183","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}
引用次数: 0
miR-6402 targets Bmpr2 and negatively regulates mouse adipogenesis. miR-6402靶向Bmpr2,负调控小鼠脂肪生成。
IF 3.5 4区 生物学
Adipocyte Pub Date : 2025-12-01 Epub Date: 2025-03-03 DOI: 10.1080/21623945.2025.2474114
Malaz Elsheikh, Tomomi Sano, Akiko Mizokami, Yusuke Nakatsu, Tomoichiro Asano, Takashi Kanematsu
{"title":"miR-6402 targets <i>Bmpr2</i> and negatively regulates mouse adipogenesis.","authors":"Malaz Elsheikh, Tomomi Sano, Akiko Mizokami, Yusuke Nakatsu, Tomoichiro Asano, Takashi Kanematsu","doi":"10.1080/21623945.2025.2474114","DOIUrl":"10.1080/21623945.2025.2474114","url":null,"abstract":"<p><p>Obesity is characterized by macrophage infiltration into adipose tissue. White adipose tissue remodelling under inflammatory conditions involves both hypertrophy and adipogenesis and is regulated by transcription factors, which are influenced by bone morphogenetic protein (BMP) signalling. MicroRNAs (miRNAs) regulate gene expression and are involved in obesity-related processes such as adipogenesis. Therefore, we identified differentially expressed miRNAs in the epididymal white adipose tissue (eWAT) of mice fed a normal diet (ND) and those fed a high-fat diet (HFD). The expression of miR-6402 was significantly suppressed in the inflamed eWAT of HFD-fed mice than in ND-fed mice. Furthermore, <i>Bmpr2</i>, the receptor for BMP4, was identified as a target gene of miR-6402. Consistently, miR-6402 was downregulated in the inflamed eWAT of HFD-fed mice and in 3T3-L1 cells (preadipocytes) and differentiated 3T3-L1 cells (mature adipocytes) , and BMPR2 expression in these cells was upregulated. Adipogenesis was induced in WAT by BMP4 injection (<i>in vivo</i>) and in 3T3-L1 cells by BMP4 stimulation (<i>in vitro</i>), both of which were inhibited by miR-6402 transfection. Inflamed eWAT showed higher expression of BMPR2 and the adipogenesis markers C/EBPβ and PPARγ, which was suppressed by miR-6402 transfection. Our findings suggest that miR-6402 is a novel anti-adipogenic miRNA that combats obesity by inhibiting the BMP4/BMPR2 signalling pathway and subsequently reducing adipose tissue expansion.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2474114"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539782","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}
引用次数: 0
Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines. α -亚麻酸介导的宫颈癌细胞系表观遗传重编程。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-02 DOI: 10.1080/15592294.2025.2451551
Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar
{"title":"Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines.","authors":"Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar","doi":"10.1080/15592294.2025.2451551","DOIUrl":"10.1080/15592294.2025.2451551","url":null,"abstract":"<p><p>Cervical cancer, the fourth most common cancer globally and the second most prevalent cancer among women in India, is primarily caused by Human Papilloma Virus (HPV). The association of diet with cancer etiology and prevention has been well established and nutrition has been shown to regulate cancer through modulation of epigenetic markers. Dietary fatty acids, especially omega-3, reduce the risk of cancer by preventing or reversing the progression through a variety of cellular targets, including epigenetic regulation. In this work, we have evaluated the potential of ALA (α linolenic acid), an ω-3 fatty acid, to regulate cervical cancer through epigenetic mechanisms. The effect of ALA was evaluated on the regulation of histone deacetylases1, DNA methyltransferases 1, and 3b, and global DNA methylation by ELISA. RT-PCR was utilized to assess the expression of tumor regulatory genes (hTERT, DAPK, RARβ, and CDH1) and their promoter methylation in HeLa (HPV18-positive), SiHa (HPV16-positive) and C33a (HPV-negative) cervical cancer cell lines. ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines. ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines. ALA reduced methylation in the 5' CpG island of CDH1, RARβ, and DAPK1 promoters and reduced global DNA methylation in cervical cancer cell lines. These results suggest that ALA regulates the growth of cervical cancer cells by targeting epigenetic markers, shedding light on its potential therapeutic role in cervical cancer management.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2451551"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078943","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}
引用次数: 0
Circular RNA Circ_0002762 promotes cell migration and invasion in cervical squamous cell carcinoma via activating RelA/nuclear factor kappa B (Nf-kB) signalling pathway. 环状RNA Circ_0002762通过激活RelA/核因子κ B (nf-kB)信号通路促进宫颈鳞状细胞癌的细胞迁移和侵袭。
IF 3.6 3区 生物学
RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-03-24 DOI: 10.1080/15476286.2025.2478539
Lei Ji, Youguo Chen, Xiaoping Chen
{"title":"Circular RNA Circ_0002762 promotes cell migration and invasion in cervical squamous cell carcinoma via activating RelA/nuclear factor kappa B (Nf-kB) signalling pathway.","authors":"Lei Ji, Youguo Chen, Xiaoping Chen","doi":"10.1080/15476286.2025.2478539","DOIUrl":"10.1080/15476286.2025.2478539","url":null,"abstract":"<p><p>Cervical cancer is a leading cause of cancer-related deaths, with cervical squamous cell carcinoma (CSCC) accounting for a majority of cases. Circular RNAs (circRNAs) have been repeatedly suggested as crucial effectors in modulating the development of multiple malignancies. The expression of circ_0002762 was predicted to be high in CSCC tissues in GEO dataset, but the functional role and underlying regulatory mechanism of circ_0002762 in CSCC was unclear. By series of functional assays and mechanism assays, supported by bioinformatics analysis, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis and western blot assays, we identified that circ_0002762 aberrantly up-regulated in CSCC, promoting CSCC cell migration and invasion. Mechanically, circ_0002762 was transcriptionally activated by Fork head box A1 (FOXA1). Moreover, the involvement of nuclear factor kappa B (NF-kB) signalling in circ_0002762 regulation mechanism in CSCC cells was ascertained. Additionally, circ_0002762, predominantly accumulated in cell cytoplasm, was proved to recruit Mov10 RISC complex RNA helicase (MOV10) to enhance RelA mRNA stability, thus affecting CSCC cell migration and invasion. In summary, FOXA1-mediated circ_0002762 up-regulation could enhance the migratory and invasive abilities of CSCC cells via the MOV10/RelA/NF-kB pathway.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625775","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}
引用次数: 0
A lineage 1 branch porcine reproductive and respiratory syndrome virus live vaccine candidate provides broad cross-protection against HP-like PRRSV in piglets. 一种1系分支猪繁殖与呼吸综合征病毒候选活疫苗对仔猪hp样PRRSV具有广泛的交叉保护作用。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-01-12 DOI: 10.1080/21505594.2025.2451754
Chao Li, Jinhao Li, Bangjun Gong, Hu Xu, Zhenyang Guo, Lirun Xiang, Siyu Zhang, Qi Sun, Jing Zhao, Menglin Zhang, Yan-Dong Tang, Chaoliang Leng, Jianan Wu, Qian Wang, Jinmei Peng, Guohui Zhou, Huairan Liu, Tongqing An, Xuehui Cai, Zhi-Jun Tian, Hongliang Zhang
{"title":"A lineage 1 branch porcine reproductive and respiratory syndrome virus live vaccine candidate provides broad cross-protection against HP-like PRRSV in piglets.","authors":"Chao Li, Jinhao Li, Bangjun Gong, Hu Xu, Zhenyang Guo, Lirun Xiang, Siyu Zhang, Qi Sun, Jing Zhao, Menglin Zhang, Yan-Dong Tang, Chaoliang Leng, Jianan Wu, Qian Wang, Jinmei Peng, Guohui Zhou, Huairan Liu, Tongqing An, Xuehui Cai, Zhi-Jun Tian, Hongliang Zhang","doi":"10.1080/21505594.2025.2451754","DOIUrl":"10.1080/21505594.2025.2451754","url":null,"abstract":"<p><p>Multiple porcine reproductive and respiratory syndrome virus (PRRSV) subtypes coinfect numerous pig farms in China, and commercial PRRSV vaccines offer limited cross-protection against heterologous strains. Our previous research confirmed that a PRRSV lineage 1 branch attenuated live vaccine (SD-R) provides cross-protection against HP-PRRSV, NADC30-like PRRSV and NADC34-like PRRSV. HP-PRRSV has undergone significant genetic variation following nearly two decades of evolution and has transformed into a subtype referred to as HP-like PRRSV, which also exhibits high pathogenicity. The effectiveness of immunising piglets with the SD-R strain to provide protection against infection with HP-like PRRSV remains uncertain. In the present study, we evaluated the protective effects of SD-R vaccine strains on DLF-challenged piglets. The results revealed that piglets challenged with DLF presented clinical symptoms such as continuous high fever and an obvious decrease in daily weight gain. Importantly, the piglets immunised with SD-R exhibited notable reductions in pathological damage, especially of decreases in DLF-induced thymic atrophy. Moreover, the serum of SD-R-immunised piglets strongly neutralised DLF, and the number of SD-R-vaccinated piglets demonstrating viraemia was greatly reduced. These results suggest that the PRRSV lineage 1 branch live vaccine candidate provides broad cross-protection against HP-like PRRSV in piglets.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2451754"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972375","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}
引用次数: 0
Comparative pathogenicity of goose parvovirus across different epidemic lineages in ducklings and goslings. 鹅细小病毒不同流行谱系在雏鸭和雏鹅中的比较致病性。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-05-12 DOI: 10.1080/21505594.2025.2497904
Xiaolong Lu, Qianqian Xu, Miao Cai, Meiqi Li, Xiaoquan Wang, Yanhong Wang, Wenhao Yang, Kaituo Liu, Ruyi Gao, Yu Chen, Jiao Hu, Min Gu, Shunlin Hu, Xiufan Liu, Xiaowen Liu
{"title":"Comparative pathogenicity of goose parvovirus across different epidemic lineages in ducklings and goslings.","authors":"Xiaolong Lu, Qianqian Xu, Miao Cai, Meiqi Li, Xiaoquan Wang, Yanhong Wang, Wenhao Yang, Kaituo Liu, Ruyi Gao, Yu Chen, Jiao Hu, Min Gu, Shunlin Hu, Xiufan Liu, Xiaowen Liu","doi":"10.1080/21505594.2025.2497904","DOIUrl":"10.1080/21505594.2025.2497904","url":null,"abstract":"<p><p>The endemic status of goose parvovirus (GPV) continues to devastate the poultry industry in China. Novel GPV (NGPV) and Mutated GPV (MGPV) represent the predominant lineages. However, the comparative pathogenicity between these viruses remains poorly understood. Herein, we selected representative NGPV and MGPV strains as model viruses to assess their pathogenic potential both <i>in vitro</i> and <i>in vivo</i>. <i>In vitro</i> cellular and embryo assays demonstrated that both NGPV and MGPV were capable of replicating in DEF and GEF cells, leading to pronounced cytopathic effects. However, these viruses exhibited distinct levels of intra-embryonic replication capabilities. Furthermore, we conducted <i>in vivo</i> infection experiments and systematically evaluated the pathogenic differences between NGPV and MGPV by examining various indicators, including growth, clinical signs, gross pathology, skeletal development, viral load, and humoral response in the infected animals. The results showed that both NGPV and MGPV inhibited weight gain in goslings and ducklings, with NGPV exerting a more significant suppressive impact. MGPV induced classical gosling plague pathology in goslings, while NGPV led to short beak and dwarfism syndrome in ducklings, notably disrupting skeletal development. Moreover, MGPV and NGPV exhibited diverse host tropisms, with MGPV being more pathogenic to goslings and NGPV to ducklings. Both viruses elicited specific antibody responses, with MGPV being more effective in goslings and NGPV in ducklings. Additionally, MGPV exhibited stronger humoral response compared to NGPV. These findings enhance our understanding of the pathogenicity of prevalent GPV strains in waterfowl, offering a critical theoretical foundation for devising strategies to prevent GPV infections.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2497904"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037360","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}
引用次数: 0
Ponatinib and other clinically approved inhibitors of Src and Rho-A kinases abrogate dengue virus serotype 2- induced endothelial permeability. Ponatinib和其他临床批准的Src和Rho-A激酶抑制剂可消除血清2型登革热病毒诱导的内皮通透性。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-04-06 DOI: 10.1080/21505594.2025.2489751
Srishti Rajkumar Mishra, Ayan Modak, Mansi Awasthi, Archana Sobha, Easwaran Sreekumar
{"title":"Ponatinib and other clinically approved inhibitors of Src and Rho-A kinases abrogate dengue virus serotype 2- induced endothelial permeability.","authors":"Srishti Rajkumar Mishra, Ayan Modak, Mansi Awasthi, Archana Sobha, Easwaran Sreekumar","doi":"10.1080/21505594.2025.2489751","DOIUrl":"10.1080/21505594.2025.2489751","url":null,"abstract":"<p><p>Severe dengue often presents as shock syndrome with enhanced vascular permeability and plasma leakage into tissue spaces. <i>In vitro</i> studies have documented the role of Src family kinases (SFKs) and RhoA-kinases (ROCK) in dengue virus serotype 2 (DENV2)-induced endothelial permeability. Here, we show that the FDA-approved SFK inhibitors Bosutinib, Vandetanib and Ponatinib, as well as the ROCK inhibitors, Netarsudil and Ripasudil significantly inhibit DENV2-induced endothelial permeability. In cultured telomerase immortalized human microvascular endothelial cells (HMEC-1), treatment with these inhibitors reduced the phosphorylation of VE-Cadherin, Src and myosin light chain 2 (MLC2) proteins that were upregulated during DENV2 infection. It also prevented the loss of VE-Cadherin from the inter-endothelial cell junctions induced by viral infection. In <i>in-vivo</i> studies using DENV2-infected AG129 IFN receptor-α/β/γ deficient mice, ponatinib, when administered 24 h post-infection onwards, demonstrated significant benefits in improving body weight, clinical outcomes, and survival rates. While all virus-infected, untreated mice died by day-10 post-infection, 80% of the ponatinib-treated mice survived, and approximately 60% were still alive at the end of the 15-day observation period. The treatment also significantly reduced disease severity factors such as vascular leakage, thrombocytopenia; mRNA transcript levels of proinflammatory cytokines such as IL-1β and TNF-α; and restored liver function. Comparable effects were observed even when ponatinib treatment was initiated after symptom onset. The results highlight ponatinib as an effective therapeutic option in severe dengue; and also a similar potential for other FDA- approved SFK and ROCK inhibitors.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2489751"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796489","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}
引用次数: 0
The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies. rna结合蛋白在胃肠道恶性肿瘤肿瘤免疫微环境中的调控作用。
IF 3.6 3区 生物学
RNA Biology Pub Date : 2025-12-01 Epub Date: 2024-12-24 DOI: 10.1080/15476286.2024.2440683
Dongqi Li, Xiangyu Chu, Weikang Liu, Yongsu Ma, Xiaodong Tian, Yinmo Yang
{"title":"The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies.","authors":"Dongqi Li, Xiangyu Chu, Weikang Liu, Yongsu Ma, Xiaodong Tian, Yinmo Yang","doi":"10.1080/15476286.2024.2440683","DOIUrl":"10.1080/15476286.2024.2440683","url":null,"abstract":"<p><p>The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (m<sup>6</sup>A). Aberrant regulation of RBPs, such as HuR and YBX1, typically enhances tumour immune escape and impacts prognosis of GI tumour patients. Further, while targeting RBPs offers a promising strategy for improving immunotherapy in GI cancers, the mechanisms by which RBPs regulate the TIME in these tumours remain poorly understood, and the therapeutic application is still in its early stages. This review summarizes current advances in exploring the roles of RBPs in regulating genes expression and their effect on the TIME of GI tumours, then providing theoretical insights for RBP-targeted cancer therapies.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blood transcriptomic associations of epigenetic age in adolescents. 青少年表观遗传年龄的血液转录组学关联。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-16 DOI: 10.1080/15592294.2025.2503824
Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas
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