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The RNA sensor MDA5 contributes to the antiviral immune response in Crassostrea gigas by modulating the MAVS-mediated signaling pathway RNA传感器MDA5通过调节mavs介导的信号通路参与长牡蛎的抗病毒免疫应答。
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-01-26 DOI: 10.1016/j.fsi.2026.111160
Yingmei Xu , Yuhao Jin , Mengjia Chen , Yuqing Zeng , Yiqing Wang , Xiaoyu Gu , Xue Qiao , Lingling Wang , Linsheng Song
Melanoma differentiation–associated gene 5 (MDA5) is a key member of the RIG-I-like receptor (RLR) family that detects viral RNA in the cytoplasm and triggers antiviral innate immunity mainly via the MAVS-dependent signaling cascade. In the present study, a MDA5-like homologue (CgMDA5) containing two N-terminal CARD domains, a central DExD/H-box helicase domain and a C-terminal domain (CTD) was identified from Pacific oyster (Crassostrea gigas). CgMDA5 mRNA transcripts were detected in all examined oyster tissues, with the highest level in haemocytes. The mRNA expression of CgMDA5 in haemocytes was significantly upregulated by poly (I:C) and 5′-ppp dsRNA stimulation. CgMDA5 protein exhibited strong in vitro binding activity toward poly (I:C) and dsRNA of 100 bp and 1000 bp in length, with a marked preference for longer dsRNA. The interaction of CgMDA5 and CgMAVS was detected and affirmed by Co-IP after transfection into HEK293T cells. In CgMDA5-RNAi oyster, the mRNA expression level of CgMAVS was down-regulated post poly (I:C) stimulation. Moreover, both RNAi of CgMDA5 and CgMAVS down-regulated the mRNA expression of CgIRF1, CgIRF8 and CgIFNLP. These findings collectively suggest that CgMDA5 is capable of interacting with CgMAVS, thereby activating the CgIRF-CgIFNLP signaling pathway to mediate antiviral immune responses in oyster.
黑色素瘤分化相关基因5 (MDA5)是rig - i样受体(RLR)家族的关键成员,主要通过mavs依赖性信号级联检测细胞质中的病毒RNA并触发抗病毒先天免疫。本研究从太平洋牡蛎(Crassostrea gigas)中鉴定出一个mda5样同源物(CgMDA5),该同源物包含两个n端CARD结构域、一个中央DExD/H-box解旋酶结构域和一个c端结构域(CTD)。在所有牡蛎组织中均检测到CgMDA5 mRNA转录本,其中血细胞中表达量最高。poly (I:C)和5'-ppp dsRNA刺激后,血细胞中CgMDA5 mRNA表达显著上调。CgMDA5蛋白对长度为100 bp和1000 bp的poly (I:C)和dsRNA具有较强的体外结合活性,对长度较长的dsRNA具有明显的亲和性。转染HEK293T细胞后,通过Co-IP检测CgMDA5与CgMAVS的相互作用,并进行了确认。在CgMDA5-RNAi牡蛎中,poly (I:C)刺激后CgMAVS mRNA表达水平下调。此外,CgMDA5和CgMAVS的RNAi均下调CgIRF1、CgIRF8和CgIFNLP的mRNA表达。这些结果共同表明,CgMDA5能够与CgMAVS相互作用,从而激活CgIRF-CgIFNLP信号通路,介导牡蛎的抗病毒免疫反应。
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引用次数: 0
Mechanisms underlying differential utilization of carbohydrates from diverse structures and sources in Nile tilapia (Oreochromis niloticus): Insights from glycolipid metabolism, protein deposition and liver health 尼罗罗非鱼(Oreochromis niloticus)对不同结构和来源的碳水化合物的差异利用机制:来自糖脂代谢、蛋白质沉积和肝脏健康的见解。
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.fsi.2026.111187
Meng-Ting Liu , Chen-Chen Wu , Si-Miao Pan , Samwel Mchele Limbu , Yu-Yang Liang , Ying-Man Yu , Fang Qiao , Mei-Ling Zhang , Zhen-Yu Du , Yuan Luo
The proper structure and source of dietary carbohydrates are vital for farmed fish health, yet their metabolic responses to varied carbohydrates are not clear. To explore fish metabolic responses to varied carbohydrates, Nile tilapia was fed with five different carbohydrate diets for eight weeks. The results showed that polysaccharides significantly enhanced the growth performance of fish (P < 0.05). The fish fed with polysaccharides showed lower serum glucose, pyruvate and lactate, while their liver glucose uptake and catabolic capacity were significantly enhanced (P < 0.05). Furthermore, the PDK4-PDHE1α axis, which linked glycolysis to the TCA cycle, exhibited a stronger response to polysaccharides, particularly in the corn starch group. The total lipid of the whole fish, as well as the TG in the liver and serum, were significantly elevated in the fish fed with wheat and tapioca starch (P < 0.05). Additionally, the fish fed with wheat and tapioca starch exhibited a significant higher expression of PPARγ, DGAT and FAS (P < 0.05). The serum levels of AST and ALT, as well as the liver MDA content, significantly decreased in the fish fed with polysaccharides (P < 0.05). Meanwhile, the expression levels of pro-inflammatory (TNFα and IL12) and apoptosis (caspase8 and caspase9) -related genes in the liver were significantly downregulated, while the antioxidant capacity markedly increased (P < 0.05). The total protein of the whole fish, muscle protein content, and muscle fiber diameter of fish fed polysaccharides were significantly increased, particularly in the corn starch group (P < 0.05). Furthermore, the fish fed with polysaccharides exhibited stronger mTOR signaling response and higher protein synthesis capacity in the muscle, particularly in the corn starch group (P < 0.05). This study demonstrated that the PDK4-PDHE1α axis and mTOR exhibit a stronger response to polysaccharides, boosting carbohydrate breakdown and protein synthesis for growth. PPARγ responds more robustly to wheat and tapioca starch, facilitating the esterification of free fatty acids into TG, which reduced lipid toxicity and maintained liver health.
膳食碳水化合物的适当结构和来源对养殖鱼类的健康至关重要,但它们对不同碳水化合物的代谢反应尚不清楚。为了探索鱼类对不同碳水化合物的代谢反应,研究人员用5种不同的碳水化合物饲料喂养尼罗罗非鱼8周。结果表明,多糖显著提高了鱼的生长性能(P < 0.05)。饲粮中添加多糖显著降低了血清葡萄糖、丙酮酸和乳酸含量,显著提高了肝脏葡萄糖摄取和分解代谢能力(P < 0.05)。此外,连接糖酵解与TCA循环的PDK4-PDHE1α轴对多糖表现出更强的响应,特别是在玉米淀粉组。小麦淀粉和木薯淀粉显著提高了全鱼的总脂质、肝脏和血清中的TG (P < 0.05)。此外,小麦和木薯淀粉饲料显著提高了PPARγ、DGAT和FAS的表达量(P < 0.05)。添加多糖显著降低了血清AST、ALT水平和肝脏MDA含量(P < 0.05)。肝脏促炎基因(TNFα、il - 12)和凋亡基因(caspase8、caspase9)表达水平显著下调,抗氧化能力显著增强(P < 0.05)。全鱼总蛋白、肌肉蛋白含量和肌纤维直径均显著提高,以玉米淀粉组显著提高(P < 0.05)。此外,以玉米淀粉组的mTOR信号响应更强,肌肉蛋白质合成能力更高(P < 0.05)。该研究表明,PDK4-PDHE1α轴和mTOR对多糖的反应更强,促进了碳水化合物的分解和蛋白质的合成。PPARγ对小麦和木薯淀粉反应更强,促进游离脂肪酸酯化成TG,从而减少脂质毒性并维持肝脏健康。
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引用次数: 0
Chronic perfluorobutanoic acid (PFBA) exposure induces apoptosis and inflammation of gill in zebrafish (Danio rerio) 慢性全氟丁酸(PFBA)暴露诱导斑马鱼鳃细胞凋亡和炎症
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-01-28 DOI: 10.1016/j.fsi.2026.111164
Dianyang Zhou , Jianming Chen , Tianyu Zheng , Tianwei Hao , Ping Han , Yadong Xue , Mingzhe Yuan , Xubo Wang
Perfluorobutanoic acid (PFBA), a short-chain perfluoroalkyl substance (PFAS), has been widely adopted as an alternative to regulated long-chain PFAS; however, its chronic ecotoxicological effects remain poorly understood. Herein, an integrated analysis combining transcriptomic, histopathological, and molecular approaches was performed to investigate the impacts of environmentally relevant PFBA exposure (1000 ng/L) on the gill tissue of zebrafish (Danio rerio) over a 63 days post-exposure (dpe). A total of 120 zebrafish were randomly assigned to 4 groups (control, 7 dpe, 35 dpe, and 63 dpe groups), with 3 biological replicates (10 fish per tank) per group. The 1000 ng/L exposure concentration was selected based on published environmental PFBA monitoring data and preliminary dose-response trial results. Histopathological observations revealed progressive gill impairment, characterized by epithelial hyperplasia and tissue disintegration, with prolonged PFBA exposure. Transcriptomic analysis demonstrated sustained dysregulation of genes associated with the nucleotide excision repair pathway, p53 signaling pathway, and apoptotic pathway throughout the exposure period. Molecular assays indicated that PFBA exposure significantly inhibited the expression of key DNA repair proteins (tyms, fen1, and rad51b); in silico molecular docking analyses predicted that PFBA may bind to the active sites of these proteins. Meanwhile, PFBA exposure coordinately upregulated the expression of atm, p53, bax, and casp3 genes, while suppressing bcl-2 expression, thereby activating the mitochondrial apoptotic pathway. Additionally, PFBA exposure induced the activation of inflammatory factors, which further exacerbated gill tissue damage. TUNEL assays confirmed a time-dependent increase in apoptotic signals, which were strongly correlated with cumulative DNA damage. Collectively, our findings suggest a potential mechanistic link between chronic PFBA exposure and gill injury in zebrafish, mediated through the DNA damage-p53-apoptosis cascade. These results underscore the previously underestimated ecological risks posed by short-chain PFAS in aquatic ecosystems.
全氟丁酸(PFBA)是一种短链全氟烷基物质(PFAS),已被广泛采用作为受监管的长链全氟烷基物质的替代品;然而,其慢性生态毒理学效应仍然知之甚少。本文采用转录组学、组织病理学和分子方法进行综合分析,研究环境相关PFBA暴露(1000 ng/L)对斑马鱼(Danio rerio)暴露后63天(dpe)的鳃组织的影响。试验选用120尾斑马鱼,随机分为4组(对照组、7尾组、35尾组和63尾组),每组设3个生物重复(每个鱼缸10尾)。1000ng /L的暴露浓度是根据公开的环境PFBA监测数据和初步剂量-反应试验结果选择的。组织病理学观察显示进行性鳃损伤,以上皮增生和组织解体为特征,长期暴露于PFBA。转录组学分析表明,在整个暴露期间,与核苷酸切除修复途径、p53信号通路和凋亡途径相关的基因持续失调。分子分析表明,PFBA暴露显著抑制关键DNA修复蛋白(tyms、fen1和rad51b)的表达;硅分子对接分析预测PFBA可能与这些蛋白的活性位点结合。同时,PFBA暴露协同上调atm、p53、bax和casp3基因的表达,同时抑制bcl-2的表达,从而激活线粒体凋亡通路。此外,PFBA暴露诱导炎症因子的激活,进一步加剧了鳃组织损伤。TUNEL实验证实了凋亡信号的时间依赖性增加,这与累积DNA损伤密切相关。总的来说,我们的研究结果表明,慢性PFBA暴露与斑马鱼鳃损伤之间存在潜在的机制联系,这种联系是通过DNA损伤-p53-凋亡级联介导的。这些结果强调了以前被低估的短链PFAS在水生生态系统中造成的生态风险。
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引用次数: 0
Two interleukin-1β types reinforce innate immune response modulation in Japanese medaka, Oryzias latipes 两种类型的白细胞介素1β增强了日本稻科植物的先天免疫反应调节
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-01-26 DOI: 10.1016/j.fsi.2026.111157
Mizanur Rahman Washim , Natsuki Morimoto , Takechiyo Sumiyoshi , Aki Nishihara , Siva Nallaperumal , Tomoya Kono , Jun-ichi Hikima
Interleukin-1β is a pro-inflammatory cytokine with pluripotent roles in mediating immune response. In fish, IL-1β plays a major role in inflammatory responses to pathogenic infections, though its immunological functions through direct stimulation have not been studied in detail. In this study, two IL-1β genes (il1b1 and il1b2) from the Japanese medaka (Oryzias latipes) were identified and characterized. The broad immunostimulatory effects of recombinant IL-1β (OlrIL-1β) from Japanese medaka were explored using embryonic fibroblast-like cell line (OLHdrR-e3) and primary cultured kidney cells. Recombinant proteins were produced via prokaryotic expression based on predicted mature isoforms IL-1β1_Asp95 (type II) and IL-1β2_Asp121 (type I) to investigate their distinct functional characteristics. Then, their immune-related gene expression, phagocytosis, and reactive oxygen species (ROS) production ability were evaluated in vitro and ex vivo. rIL-1β triggers the expression of not only pro-inflammatory cytokines such as il1b, tnfa, il6, il8, mcp1b, and csf1b, but also the antimicrobial peptide, def1b. Additionally, they upregulate the expression of cell specific markers, including macrophage- and granulocyte-specific genes mpeg1.1, mpx2, and epx, and nitric oxide synthase (NO) gene nos1. Moreover, medaka OlrIL-1β proteins exhibited robust phagocytosis and superoxide anion production ability than those in unstimulated control. In all evaluations, the OlrIL-1β proteins corresponding to the predicted cleavage sites exhibited strong immune activation, with type I OlIL-1β2_Asp121 demonstrating more potent response than type II. To our knowledge, this is the study to reveal the immunomodulatory functions of Japanese medaka IL-1β, highlighting its potential in immunotherapy for disease prevention and control in aquaculture.
白细胞介素-1β是一种促炎细胞因子,在介导免疫反应中具有多能性作用。在鱼类中,IL-1β在致病性感染的炎症反应中起主要作用,尽管其通过直接刺激的免疫功能尚未得到详细研究。本研究从日本稻(Oryzias latipes)中鉴定了两个IL-1β基因il1b1和il1b2。利用胚胎成纤维细胞样细胞系(OLHdrR-e3)和原代培养的肾细胞,研究了重组日本medaka IL-1β (OlrIL-1β)的广泛免疫刺激作用。以预测成熟亚型IL-1β1_Asp95 (II型)和IL-1β2_Asp121 (I型)为基础,通过原核表达制备重组蛋白,研究其不同的功能特征。然后,在体外和离体实验中评估它们的免疫相关基因表达、吞噬能力和活性氧(ROS)产生能力。il -1β不仅能触发il - 1b、tnfa、il - 6、il - 8、mcp1b和csf1b等促炎细胞因子的表达,还能触发抗菌肽def1b的表达。此外,它们上调细胞特异性标记物的表达,包括巨噬细胞和粒细胞特异性基因mpeg1.1、mpx2和epx,以及一氧化氮合酶(NO)基因nos1。此外,与未受刺激的对照组相比,medaka OlrIL-1β蛋白具有较强的吞噬能力和超氧阴离子产生能力。在所有的评估中,预测切割位点对应的OlrIL-1β蛋白表现出很强的免疫激活,I型oil -1β 2_asp121比II型表现出更强的应答。据我们所知,本研究揭示了日本medaka IL-1β的免疫调节功能,突出了其在水产养殖疾病预防和控制中的免疫治疗潜力。
{"title":"Two interleukin-1β types reinforce innate immune response modulation in Japanese medaka, Oryzias latipes","authors":"Mizanur Rahman Washim ,&nbsp;Natsuki Morimoto ,&nbsp;Takechiyo Sumiyoshi ,&nbsp;Aki Nishihara ,&nbsp;Siva Nallaperumal ,&nbsp;Tomoya Kono ,&nbsp;Jun-ichi Hikima","doi":"10.1016/j.fsi.2026.111157","DOIUrl":"10.1016/j.fsi.2026.111157","url":null,"abstract":"<div><div>Interleukin-1β is a pro-inflammatory cytokine with pluripotent roles in mediating immune response. In fish, IL-1β plays a major role in inflammatory responses to pathogenic infections, though its immunological functions through direct stimulation have not been studied in detail. In this study, two IL-1β genes (<em>il1b1</em> and <em>il1b2</em>) from the Japanese medaka (<em>Oryzias latipes</em>) were identified and characterized. The broad immunostimulatory effects of recombinant IL-1β (OlrIL-1β) from Japanese medaka were explored using embryonic fibroblast-like cell line (OLHdrR-e3) and primary cultured kidney cells. Recombinant proteins were produced via prokaryotic expression based on predicted mature isoforms IL-1β1_Asp<sup>95</sup> (type II) and IL-1β2_Asp<sup>121</sup> (type I) to investigate their distinct functional characteristics. Then, their immune-related gene expression, phagocytosis, and reactive oxygen species (ROS) production ability were evaluated <em>in vitro</em> and <em>ex vivo</em>. rIL-1β triggers the expression of not only pro-inflammatory cytokines such as <em>il1b</em>, <em>tnfa</em>, <em>il6</em>, <em>il8</em>, <em>mcp1b</em>, and <em>csf1b</em><em>,</em> but also the antimicrobial peptide, <em>def1b</em>. Additionally, they upregulate the expression of cell specific markers, including macrophage- and granulocyte-specific genes <em>mpeg1.1</em>, <em>mpx2</em>, and <em>epx</em>, and nitric oxide synthase (NO) gene <em>nos1</em>. Moreover, medaka OlrIL-1β proteins exhibited robust phagocytosis and superoxide anion production ability than those in unstimulated control. In all evaluations, the OlrIL-1β proteins corresponding to the predicted cleavage sites exhibited strong immune activation, with type I OlIL-1β2_Asp<sup>121</sup> demonstrating more potent response than type II. To our knowledge, this is the study to reveal the immunomodulatory functions of Japanese medaka IL-1β, highlighting its potential in immunotherapy for disease prevention and control in aquaculture.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"171 ","pages":"Article 111157"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and efficacy of autogenous multivalent vaccine to prevent Motile Aeromonas Septicemia (MAS) and Bacillary Necrosis of Pangasius (BNP) in striped catfish (Pangasianodon hypophthalmus) 自体多价疫苗预防条纹鲶鱼运动性气单胞菌败血症(MAS)和巴沙鱼细菌性坏死(BNP)的研制及其疗效。
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 10.1016/j.fsi.2026.111177
Le Minh Khoi , Thea Aldiano , Nguyen Bao Trung , Tran Thi Tuyet Hoa , Tu Thanh Dung
Vaccines are central to disease prevention in farmed fish and help reduce antimicrobial use in aquaculture. Autogenous vaccines represent a practical solution for managing pathogens with high genetic variability, particularly in urgent outbreaks. In this study, 28 bacterial strains were isolated from striped catfish (P. hypophthalmus) suffering from Motile Aeromonas Septicaemia (MAS) and Bacillary Necrosis of Pangasius (BNP). Strains were identified using specific primers, 16S rRNA gene sequencing, and DNA fingerprinting, followed by virulence gene screening and pathogenicity testing. Two strains of Aeromonas VH31, VH74, and two strains of Edwardsiella ictaluri VH83, VH116 were selected to formulate injectable autogenous oil-emulsion vaccines. Experimental trials included four groups of bivalent vaccines (VC-VH31/83, VC-VH31/116, VC-VH74/83, VC-VH74/116), one multivalent vaccine (VC-VHMix), and a PBS control, evaluated over 60 days. The multivalent vaccine conferred the highest relative percent survival (91.7%), while VC-VH31/83 and VC-VH31/116 showed moderate protection (66.7% and 70.8%, respectively). In contrast, VC-VH74/83 and VC-VH74/116 yielded minimal protection (12.5%). Serum IgM antibody analysis showed that the fish had an immune response to Aeromonas and Edwardsiella antigens after 15–30 days of vaccination in the vaccine injection treatments. The concentration of total WBCs, lymphocytes, and granulocytes in the blood of the fish increased and peaked after 45 days. Overall growth performance in the most effective vaccine groups (VC-VHMix, VC-VH31/83, VC-VH31/116) was not significantly affected compared to the control. These results demonstrate that autogenous vaccines are a promising approach to control dual infections of MAS and BNP in striped catfish and highlight their potential role in sustainable aquaculture disease management.
疫苗是养殖鱼类疾病预防的核心,并有助于减少水产养殖中抗菌素的使用。自体疫苗是管理具有高度遗传变异的病原体的一种实际解决办法,特别是在紧急暴发时。本研究从患有脓毒血症(MAS)和巴沙鱼杆菌性坏死(BNP)的条纹鲶鱼(P. hypophthalmus)中分离出28株细菌。采用特异引物、16S rRNA基因测序、DNA指纹图谱鉴定菌株,进行毒力基因筛选和致病性检测。选择2株气单胞菌VH31、VH74和2株爱德华氏菌VH83、VH116制备可注射性自油乳剂疫苗。实验试验包括四组二价疫苗(VC-VH31/83、VC-VH31/116、VC-VH74/83、VC-VH74/116)、一组多价疫苗(VC-VHMix)和一组PBS对照,在60天内进行评估。多价疫苗的相对存活率最高(91.7%),而VC-VH31/83和VC-VH31/116的保护作用中等(分别为66.7%和70.8%)。相比之下,VC-VH74/83和VC-VH74/116产生最小的保护(12.5%)。血清IgM抗体分析表明,接种15 ~ 30 d后,鱼对气单胞菌和爱德华氏菌抗原有免疫应答。鱼的血液中白细胞、淋巴细胞和粒细胞的浓度升高,在45天后达到峰值。与对照组相比,最有效的疫苗组(VC-VHMix、VC-VH31/83、VC-VH31/116)的整体生长性能没有显著影响。这些结果表明,自体疫苗是控制条纹鲶鱼MAS和BNP双重感染的一种有希望的方法,并突出了其在可持续水产养殖疾病管理中的潜在作用。
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引用次数: 0
Evaluation of the immunoprotective effects of two Infectious Spleen and Kidney Necrosis Virus (ISKNV) oral vaccines on largemouth bass 两种传染性脾肾坏死病毒(ISKNV)口服疫苗对大口黑鲈免疫保护作用的评价。
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 10.1016/j.fsi.2026.111189
Xuan Zhang , Yunshang Ning , Zengjian Liang , Jinqiao Cao , Tao Xu , Jiayi Luo , Zemiao Zhang , Yingjing Chen , Jingguang Wei , Qiwei Qin , Sumei Xiao , Sheng Zhou
The high pathogenicity and mortality rate of infectious spleen and kidney necrosis virus (ISKNV) have significantly threatened the development of largemouth bass aquaculture in China. Oral vaccines are urgently needed in the aquaculture industry. This study successfully constructed recombinant strains EBY100/pYD1-ISKNV and WB600/pEB03-CotC-ISKNV that can express ISKNV MCP using surface display platforms of Saccharomyces cerevisiae and Bacillus subtilis. Oral immunization of largemouth bass was conducted to evaluate the protective efficacy of both oral vaccines. Following oral immunization, the relative expression levels of IFN-γ, TNF-α, IL-1, CD8α, MHC-Ⅰ, IgM, and IgT in the spleen and head kidney tissues of largemouth bass and serum-specific antibody levels in the E-I and W-I groups were significantly higher compared to the PBS group. Following ISKNV challenge, the survival rate of the E-I group and W-I group were 53.3 % and 50.0 %, respectively, with the relative percent survival (RPS) of 30.0 % and 25.0 %. Viral load detection revealed significantly lower viral loads in the E-I and W-I groups compared to the PBS group. Histopathological examination of tissue sections revealed that no obvious lesions were observed in the liver, spleen, and head kidney of largemouth bass immunized with either oral vaccine compared to the PBS group that exhibited severe lesions in the liver, spleen, and head kidney. In summary, oral administration of EBY100/pYD1-ISKNV and WB600/pEB03-CotC-ISKNV activated both innate and adaptive immune responses in largemouth bass, demonstrating efficacy in preventing ISKNV infection. The two oral vaccines developed in this study provide novel strategies for controlling ISKNV.
传染性脾肾坏死病毒(ISKNV)的高致病性和高致死率严重威胁着中国大口黑鲈养殖业的发展。水产养殖业迫切需要口服疫苗。本研究利用酿酒酵母和枯草芽孢杆菌的表面展示平台,成功构建了表达ISKNV MCP的重组菌株EBY100/pYD1-ISKNV和WB600/pEB03-CotC-ISKNV。对大口黑鲈进行口服免疫,评价两种口服疫苗的保护效果。口服免疫后,E-I组和W-I组大口黑鲈脾脏和头肾组织中IFN-γ、TNF-α、IL-1、CD8α、MHC-Ⅰ、IgM、IgT的相对表达量和血清特异性抗体水平均显著高于PBS组。ISKNV攻毒后,E-I组和W-I组的存活率分别为53.3%和50.0%,相对存活率(RPS)分别为30.0%和25.0%。病毒载量检测显示,与PBS组相比,E-I组和W-I组的病毒载量显著降低。组织切片的组织病理学检查显示,与PBS组相比,口服疫苗免疫的大口黑鲈的肝脏、脾脏和头部肾脏均未见明显病变,而PBS组的肝脏、脾脏和头部肾脏均出现严重病变。综上所述,口服EBY100/pYD1-ISKNV和WB600/pEB03-CotC-ISKNV激活了大口黑鲈的先天和适应性免疫反应,显示出预防ISKNV感染的效果。本研究开发的两种口服疫苗为控制ISKNV提供了新的策略。
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引用次数: 0
Umifenovir protects Procambarus clarkii against white spot syndrome virus by suppressing viral replication and modulating innate immunity 乌米诺韦通过抑制病毒复制和调节先天免疫来保护克氏原螯虾免受白斑综合征病毒的侵害
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-02-11 DOI: 10.1016/j.fsi.2026.111206
Cheng Chen , Bo-Han Li , Chao-Yu Wang , Er-Long Wang , Tian-Qiang Liu , Zhe Zhao
White spot syndrome virus (WSSV) remains one of the most destructive viral pathogens in crustacean aquaculture, yet effective antiviral agents are still lacking. Umifenovir is a clinically approved broad-spectrum antiviral drug with a favorable safety profile and immunomodulatory properties; however, its antiviral potential in aquatic invertebrates has not been explored. In this study, we systematically evaluated the antiviral efficacy and immunological mechanisms of umifenovir against WSSV infection in the crayfish Procambarus clarkii. Toxicity assessment and ADMET predictive analysis confirmed a wide safety window of umifenovir in crayfish. In vivo infection experiments demonstrated that umifenovir significantly suppressed WSSV replication in a dose-, tissue-, and time-dependent manner, achieving up to 97.26% inhibition at 30 mg/kg after 24 h. The treatment also reduced the transcription of viral genes from immediate-early to late stages and improved the survival rate of infected hosts. Both preventive and therapeutic administration conferred robust antiviral protection. Mechanistically, umifenovir inhibited the transcription of key viral genes required for WSSV replication and disrupted the virus-mediated manipulation of innate immune signaling pathways. Umifenovir further enhanced antioxidant capacity, alleviated oxidative stress and inflammatory responses, and attenuated virus-induced apoptosis. In addition, umifenovir reduced abnormal protein accumulation associated with viral replication while increasing lysosomal enzyme activity, indicating restoration of protein homeostasis and strengthened innate immune function. Collectively, these findings provide the first evidence that umifenovir exerts potent anti-WSSV activity in crustaceans by coordinately suppressing viral replication and modulating host immune responses, offering new mechanistic insights into its immunomodulatory effects. Given its favorable safety profile and feasibility for industrial synthesis, umifenovir represents a promising antiviral candidate for immunological intervention and provides a potential translational basis for future disease control strategies in aquaculture.
白斑综合征病毒(White spot syndrome virus, WSSV)是甲壳类水产养殖中最具破坏性的病毒病原体之一,但目前还缺乏有效的抗病毒药物。乌米诺韦是一种临床批准的广谱抗病毒药物,具有良好的安全性和免疫调节特性;然而,其在水生无脊椎动物中的抗病毒潜力尚未被探索。在本研究中,我们系统地评估了乌米诺韦对克氏原螯虾感染WSSV的抗病毒效果和免疫机制。毒性评价和ADMET预测分析证实了乌米诺韦对小龙虾具有较宽的安全窗口。体内感染实验表明,乌米诺韦显著抑制WSSV复制,呈剂量依赖性、组织依赖性和时间依赖性,在30 mg/kg剂量下,24 h抑制率高达97.26%。该处理还降低了病毒基因从早期到晚期的转录,提高了感染宿主的存活率。预防性和治疗性用药均具有强大的抗病毒保护作用。在机制上,乌米诺韦抑制了WSSV复制所需的关键病毒基因的转录,并破坏了病毒介导的先天免疫信号通路的操纵。乌米诺韦进一步增强抗氧化能力,减轻氧化应激和炎症反应,并减轻病毒诱导的细胞凋亡。此外,乌米诺韦减少了与病毒复制相关的异常蛋白质积累,同时增加了溶酶体酶活性,表明蛋白质稳态的恢复和先天免疫功能的增强。总的来说,这些发现首次证明了乌米诺韦通过协同抑制病毒复制和调节宿主免疫反应在甲壳类动物中发挥有效的抗wssv活性,为其免疫调节作用提供了新的机制见解。鉴于其良好的安全性和工业合成的可行性,乌米诺韦代表了一种有前途的免疫干预抗病毒候选药物,并为未来水产养殖疾病控制策略提供了潜在的转化基础。
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引用次数: 0
Zebrafish as a translational model for Bitis arietans envenomation: Integrative proteomic and histopathological insights 斑马鱼作为变异bittis毒化的翻译模型:综合蛋白质组学和组织病理学见解。
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 10.1016/j.fsi.2026.111141
Dayanne Carla Fernandes , Silas Fernandes Eto , Leo Kei Iwai , Monica Lopes-Ferreira , Isabela de Oliveira Cavalcante Pimentel , Luiz Roberto Sardinha , Ismael Feitosa Lima , Denise V. Tambourgi
The genus Bitis, especially the species Bitis arietans, significantly contributes to snakebite incidents in Africa, causing a range of serious medical conditions. This study aimed to explore the pathological mechanisms underlying envenomations by B. arietans using zebrafish (Danio rerio) as a model organism. Blood samples were collected at 3- and 6-h post-envenomation, followed by plasma analysis through mass spectrometry. Key findings indicated that B. arietans venom caused a hemolytic effect leading to acute severe anemia by 6 h post-envenomation. A hematopoietic response was also observed, characterized by an increase in precursor blood cells and leukocytosis with elevated myelomonocytic cell counts. Mass spectrometry analysis identified 558 plasma proteins with differential abundance between the experimental groups, many of which play crucial roles in biological processes such as immune response, hemostasis, coagulation cascade, complement system activation, neutrophil degranulation, and oxidative stress regulation. Additionally, proteins associated with cellular extravasation and regulatory functions were detected, correlating with histopathological lesions observed locally and indicating systemic effects of envenomation affecting vital organs such as the kidneys, heart, liver, and gills. Our results suggest that the plasma protein profile identified may serve as potential biomarkers for assessing lesions resulting from B. arietans envenomation. Overall, these findings enhance our understanding of the toxic impacts of B. arietans venom and underscore the utility of zebrafish as a model for further research into snakebite pathophysiology.
叮咬属,特别是变种叮咬属,是非洲蛇咬伤事件的重要原因,造成一系列严重的医疗状况。本研究以斑马鱼(Danio rerio)为模式生物,探讨变异双歧杆菌中毒的病理机制。在中毒后3小时和6小时采集血样,然后通过质谱法进行血浆分析。主要研究结果表明,异角牛耳毒液在中毒6小时后可引起急性严重贫血的溶血作用。造血反应也被观察到,其特征是前体血细胞和白细胞增多,骨髓单核细胞计数升高。质谱分析鉴定出558种血浆蛋白在实验组之间具有不同的丰度,其中许多蛋白在免疫反应、止血、凝血级联、补体系统激活、中性粒细胞脱粒和氧化应激调节等生物过程中起着至关重要的作用。此外,检测到与细胞外渗和调节功能相关的蛋白质,这些蛋白质与局部观察到的组织病理学病变相关,表明中毒对重要器官(如肾脏、心脏、肝脏和鳃)的全身影响。我们的研究结果表明,鉴定出的血浆蛋白谱可能作为评估变异双歧杆菌中毒引起的病变的潜在生物标志物。总的来说,这些发现增强了我们对变异b.a rietans毒液毒性影响的理解,并强调了斑马鱼作为蛇咬伤病理生理学进一步研究的模型的实用性。
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引用次数: 0
Therapeutic potential of intraperitoneal miconazole nitrate against Saprolegnia parasitica in Labeo rohita under feeding refusal conditions 硝酸咪康唑腹腔注射对拒食条件下黑腹小鲵寄生病的治疗作用。
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.fsi.2026.111167
Mukta Singh , Ratan Kumar Saha , Himadri Saha
Fungal infections caused by Saprolegnia parasitica are a major concern in freshwater aquaculture, particularly during advanced stages of disease when affected fish often exhibit feeding refusal, rendering oral medication ineffective. This study investigates the therapeutic potential of intraperitoneally administered miconazole nitrate (MCZ) in Labeo rohita fingerlings under such critical conditions. The 96-h LD50 of MCZ was determined to be 0.20 ± 0.13 mg kg−1 body weight (BW). Three sub-lethal doses (0.01, 0.02, and 0.04 mg MCZ kg−1 BW) were evaluated alongside a DMSO control over eight time points (0–240 h), analyzing haematological and immuno-biochemical parameters including erythrocyte and leukocyte counts, hemoglobin, hematocrit, Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), glucose, plasma ion concentrations, lysozyme activity, total protein, and respiratory burst activity. A dose-dependent physiological response was observed, with lower doses (especially 0.01 mg MCZ kg−1 BW) exhibiting minimal adverse effects while enhancing immune indicators such as lysozyme and respiratory burst activity. Challenge trials with S. parasitica zoospores further confirmed higher survival and recovery in the low-dose group. These findings highlight the efficacy of injectable MCZ as a vital therapeutic alternative during feeding suppression, offering a targeted strategy for managing saprolegniasis in aquaculture.
由寄生腐殖菌引起的真菌感染是淡水水产养殖的一个主要问题,特别是在疾病晚期,受感染的鱼往往表现出拒食,使口服药物无效。本研究探讨了在这种危急情况下腹腔注射硝酸咪康唑(MCZ)对罗氏Labeo rohita鱼种的治疗潜力。测定MCZ的96 h-LD50为0.20±0.13 mg kg-1体重。三个亚致死剂量(0.01、0.02和0.04 mg kg-1)与DMSO对照在8个时间点(0-240 h)进行评估,分析血液学和免疫生化参数,包括红细胞和白细胞计数、血红蛋白、血细胞比容、MCV、MCH、ALT、AST、葡萄糖、血浆离子浓度、溶菌酶活性、总蛋白和呼吸爆发活性。观察到剂量依赖性生理反应,较低剂量(特别是0.01 mg kg-1)表现出最小的不良反应,同时增强免疫指标,如溶菌酶和呼吸爆发活性。寄生S. zoospore的攻毒试验进一步证实了低剂量组较高的存活率和恢复率。这些发现强调了可注射MCZ作为饲养抑制期间重要的治疗替代方案的有效性,为水产养殖中管理腐殖瘤提供了有针对性的策略。
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引用次数: 0
Fish Meteorin-like factor promotes migration, proliferation and phagocytic activity of monocytes/macrophages 鱼流星蛋白样因子促进单核/巨噬细胞的迁移、增殖和吞噬活性。
IF 3.9 2区 农林科学 Q1 FISHERIES Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 10.1016/j.fsi.2026.111193
Yueshuang Ji , Yinghao Huang , Shengbin Lu , Weihua Zhao , Liwen Zhu , Wa Gao , Jianhua Feng , Gaoliang Yuan , Jun Zou , Junya Wang
Meteorin-like (Metrnl) is a cytokine known to play multifunctional roles in mammalian immunity, yet its immunoregulatory role in teleost remains largely unexplored. In the present study, we systematically investigate the effects of Metrnl on primary monocytes/macrophages (Mo/Mφ) in grass carp (Ctenopharyngodon idella). In vitro, Metrnl significantly increased the viability of primary Mo/Mφ, with increases of 12.7% on day 3 and 7.9% on day 6, as determined by flow cytometric quantification of MCSFR+ cells across multiple biological replicates. Furthermore, Metrnl stimulation promoted Mo/Mφ proliferation and phagocytic activity, resulting in absolute increases of 12.43% and 16.86%, respectively, calculated as the proportion of EdU+MCSFR+ or Beads+MCSFR+ cells within the total MCSFR+ population. Consistent with these findings, in vivo experiments using a Metrnl-expressing plasmid demonstrated enhanced Mo/Mφ proliferation and phagocytosis. Moreover, Metrnl also significantly upregulated the mRNA levels of the chemokines Cxcl8 and Cxcl11.1b, indicating its ability to recruit Mo/Mφ to target sites by activating chemokine-mediated chemotactic signaling. Importantly, neutralization of Metrnl with a specific antibody markedly impaired the enhanced Mo/Mφ recruitment, proliferation and phagocytosis, confirming that the effect is specifically mediated by Metrnl. Our results demonstrate that Metrnl acts as an important regulatory factor that activates and enhances Mo/Mφ-mediated innate immune response.
Meteorin-like (Metrnl)是一种已知在哺乳动物免疫中发挥多功能作用的细胞因子,但其在硬骨鱼中的免疫调节作用仍未被充分研究。在本研究中,我们系统地研究了Metrnl对草鱼原代单核/巨噬细胞(Mo/Mφ)的影响。在体外,通过对MCSFR+细胞进行多个生物重复的流式细胞术定量检测,Metrnl显著提高了原代Mo/Mφ的活力,第3天提高了12.7%,第6天提高了7.9%。此外,以EdU+MCSFR+或Beads+MCSFR+细胞占MCSFR+总细胞群的比例计算,Metrnl刺激可促进Mo/Mφ增殖和吞噬活性,绝对增幅分别为12.43%和16.86%。与这些发现一致,使用表达metrnl的质粒进行的体内实验表明,Mo/Mφ的增殖和吞噬作用增强。此外,Metrnl还显著上调趋化因子Cxcl8和Cxcl11.1b的mRNA水平,表明其能够通过激活趋化因子介导的趋化信号通路将Mo/Mφ募集到靶点。重要的是,用一种特异性抗体中和Metrnl可显著削弱增强的Mo/Mφ募集、增殖和吞噬作用,证实了这种作用是由Metrnl特异性介导的。我们的研究结果表明,Metrnl是激活和增强Mo/ m φ介导的先天免疫应答的重要调控因子。
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引用次数: 0
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Fish & shellfish immunology
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