AQUACULTURE
·
2018
·
IF 2.71
Li Wang,Xuezhen Zhang,Lei Wu,Qi Liu,Dianfu Zhang,Jiaojiao Yin
Selenium (Se) is an essential trace element for fish growth and performs its physiological functions mainly through incorporating into selenoproteins . It is well known that dietary Se regulates fish growth by controlling the synthesis of deiodinase , a kind of selenoproteins. However, recently, as many as 41 selenoproteins have been characterized in teleost fish. We propose a hypothesis if other selenoproteins, besides deiodinase, could also involve in the regulation of fish growth. In the present study, rainbow trout ( Oncorhynchus mykiss ) were fed diets supplemented with or without graded levels of Se (2, 4 or 6 mg/kg, from selenium yeast, Se-yeast) for 10 weeks. At the end of the feeding trial, fish growth and the expressions of a total of 28 selenoprotein genes in tissues have been evaluated. Results showed that dietary Se-yeast supplementation significantly increased fish growth ( P < 0.05) without causing oxidative stress in fish tissues. In addition, dietary Se supplementation caused a general up-regulation of selenoprotein gene expressions either in liver (10 genes) or in muscle (11 genes) ( P < 0.05). Correlation analysis showed that rainbow trout growth was significantly and positively correlated to only 4 selenoprotein genes in liver but all the 11 differentially expressed selenoprotein genes in muscle ( P < 0.05), and it presented the strongest correlation with the mRNA levels of muscle selenoprotein W-like gene ( P < 0.05). These results indicate that dietary Se-yeast supplementation is beneficial for rainbow trout growth, and the enhanced growth performance is closely correlated to the expressions of muscle selenoprotein genes, particularly the selenoprotein W-like gene. This study reveals the importance of muscle selenoprotein gene expressions, and provides a new concept for the regulatory mechanism of dietary Se on fish growth.
研究领域:
水产养殖学
·
分子生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
PLoS Pathogens
·
2023
·Vol. 19
·期 4
·e1011314
·
IF 6.7
Lin Lv,Li Chai,Jie Wang,Mengge Wang,Danhui Qin,Hui Song,Yue Fu,Chunyuan Zhao,Jihui Jia,Wei Zhao,Mutian Jia
Stimulator-of-interferon gene (STING) is a vital element of the innate immune system against DNA viruses. Optimal activation of STING is crucial for maintaining immune homeostasis and eliminating invading viruses, and the oligomerization of STING is an essential prerequisite for STING activation. However, the mechanism of cGAMP-induced STING oligomerization in ER remains unclear. Selenoproteins are crucial for various physiological processes. Here, we identified that the endoplasmic reticulum (ER)-located transmembrane selenoprotein K (SELENOK) was induced during virus infection and facilitated innate immune responses against herpes simplex virus-1 (HSV-1). Mechanistically, SELENOK interacts with STING in the ER and promotes STING oligomerization, which in turn promotes its translocation from the ER to the Golgi. Consequently, Selenok deficiency suppresses STING-dependent innate responses and facilitates viral replication in vivo . Thus, the control of STING activation by selenium-mediated SELENOK expression will be a priming therapeutic strategy for the treatment of STING-associated diseases.
Selenoproteins are crucial for various physiological processes. Most selenoproteins locate in the cytoplasm and regulate redox pathways to protect cells from oxidative stress. However, the potential roles of transmembrane selenoproteins are largely unknown. Here, we identified Selenoprotein K (SELENOK), an ER-located transmembrane selenoprotein, as a physiological enhancer of STING-dependent antiviral innate immunity. SELENOK is upregulated during viral infection and enhances STING oligomerization to facilitate the activation of the cGAS-STING pathway and suppress viral replication. These results will be valuable for understanding the physiological roles of transmembrane selenoproteins in immunity. Furthermore, as aberrant STING activation has been linked to various pathological conditions, control of STING activity by SELENOK may be a prime therapeutic strategy.
研究领域:
免疫学
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病毒学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Weiming You,Zhengjun Zhou,Zhanfeng Li,Jin Yan,Yang Wang
Reprogramming oncogenic signaling pathways to generate anti-tumor effects is a promising strategy for targeted cancer intervention, without significant off-target effects. Although reprogramming multi-oncoprotein interactions in a single signaling pathway axis has been shown to achieve sustained efficacy, there are several challenges that limit its clinical application. Herein, we transformed the mouse double minute 2 homolog (MDM2)-heat shock cognate protein 70 (HSC70) axis, a tumor-promoting pathway, into an activator of anti-tumor immunity using the Path-editor, an artificial selenoprotein. Once it enters the cell, Path-editor decomposes into PMI and PPI peptides: PMI inhibits MDM2-mediated p53 degradation and promotes HSC70 expression, while PPI binds to HSC70, enabling its ability to selectively degrade the programmed cell death ligand 1 (PD-L1). As a proof of concept, we tested its performance in microsatellite-stable (MSS) colorectal cancer, which typically displays limited responsiveness to immunotherapy. The results indicated that Path-editor effectively attenuated PD-L1 expression and reversed immune evasion in both CT26 allografts and humanized patient-derived tumor xenograft (PDX) models, thereby inhibiting tumor progression with high biosafety. Therefore, this paper introduces Path-editor as a paradigm for reprogramming oncogenic multi-protein pathways, utilizing selenium-assisted approach to achieve the rapid design of tumor-specific pathway editors. This strategy is expected to reverse immune escape in MSS colorectal cancer and treat difficult malignancies.
研究领域:
肿瘤学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Huang Haoyang,Liu Shaowei,Xu Ligeng,Liang Hengrui,Wu Zihao,Chen Tianfeng,Wang Jinlin,Liu Jun
Though prescribed as first-line drugs for esophageal squamous cell cancer (ESCC) therapy, the antitumor efficacy of Nab-Paclitaxel (Nab-PTX) is still unsatisfactory owing to the limitation on the dosage and therapy duration of Nab-PTX caused by adverse effects. Inspired by the very essential role of Selenoprotein N (SelN) in mediating the calcium homeostasis and the associated redox homeostasis in cells, herein, in this essay, we screened the inhibition effect of selenium-containing drugs in different forms on ESCC cell line. Investigation on KYSE-150 cells demonstrated that Nab-PTX in combination with low dosage of LNT-SeNPs may synergistically improve its antitumor efficacy on ESCC cells through promoting the cellular apoptosis. Proteomics analysis uncovered the core synergistic mechanism of LNT-SeNPs on Nab-PTX was significantly dependent on the endoplasmic reticulum (ER) stress induced by SelN-mediated Ca 2+ -IRE1α, IRE1α(S724)-CHOP-BCL2 axis. SelN knockdown KYSE-150 cell model further confirmed the very indispensable role of SelN in mediating the synergistic effect on Nab-PTX. Moreover, in vivo evaluation on KYSE-150 tumor-bearing mice models also demonstrated the supplementation of LNT-SeNPs with low dosage during the Nab-PTX treatment may synergize the antitumor efficacy and significantly mitigate the adverse reactions or toxicity resulting from a substantial dose of Nab-PTX. Overall, along with the facile accessibility of raw materials, this study reports LNT-SeNPs as a synergistic agent to promote the antitumor efficacy of Nab-PTX, which may be translated as a wide-applicable, efficient and highly safe strategy for clinical treatment of ESCC. Graphical abstract
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Zhejiang University-SCIENCE B
·
2023
·
IF 5.1
Xintong ZHANG,Xiaoxue GAI,Lihua XU,Wenxue MA,Qiaohan LIU,Bendong SHI,Cheng FANG,Jingzeng CAI,Ziwei ZHANG
The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl 2 ) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl 2 was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl 2 in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.
研究领域:
毒理学
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心脏病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Binhua Zou,Zushuang Xiong,Yanzi Yu,Sujiang Shi,Xiaoling Li,Tianfeng Chen
Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species emerges as a viable approach to addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys 2 ) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly lentinan-Se (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys 2 , the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of osteoclastogenesis. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys 2 , potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over osteoclastogenesis inhibition, and the prevention of osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders.
研究领域:
生物材料
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生物医学工程
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药理学
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骨骼生物学
✓ 已验证
DOI
高影响因子
MedComm
·
2024
·Vol. 5
·期 12
·e70033
·
IF 10.7
Jing Li,Mimi Chen,Dingwen Huang,Ziyin Li,Yu Chen,Jinhua Huang,Yuanqun Chen,Zhili Zhou,Zhiying Yu
Ovarian cancer (OV) ranks among the deadliest gynecological cancer, known for its high risk of relapse and metastasis, and a general resistance to conventional platinum‐based chemotherapy. Selenoprotein I (SELENOI) is a crucial mediator implicated in human hereditary spastic paraplegia. However, its role in human tumors remains poorly elucidated. Here, we comprehensively analyzed SELENOI expression patterns, functions, and clinical implications across various malignancies through the integration of bulk transcriptomics, cancer databases, and in vitro and in vivo experiments. Pan‐cancer analysis indicated upregulated SELENOI expression across various cancers, correlating with augmented malignancy, suppressed tumor immunity and poor prognosis. Knockdown of SELENOI caused G0/G1‐phase cell cycle arrest and diminished aggressive cancer phenotypes in OV cells. Moreover, SELENOI inhibition augments ferroptosis and reverses the cisplatin resistance in OV cells by modulating Akt phosphorylation. Conversely, overexpression of SELENOI in OV cells enhanced therapeutic sensitivity to cisplatin by upregulating Akt phosphorylation. Importantly, in vivo studies demonstrated that SELENOI inhibition suppressed ovarian tumor growth and enhanced cisplatin's anticancer effects. These findings highlight the significant role of SELENOI in OV by modulating ferroptosis and chemotherapy resistance. Targeting SELENOI represents a promising therapeutic approach to promote the efficacy of platinum‐based chemotherapy in OV, particularly in cases of resistance. Graphic summary of targeting SELENOI for promoting ferroptosis and reversing chemoresistance in ovarian cancer. Inhibition of SELENOI activated unsaturated fatty acid synthesis and impaired Akt phosphorylation, resulting in the upregulation of ACSL4 expression and induction of ferroptosis. Reduced Akt phosphorylation also led to the downregulation of ALDH3A1 expression, a key gene associated with cisplatin‐resistance, thereby enhancing cisplatin cytotoxicity in SELENOI‐silenced ovarian cancer cells.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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转化医学
✓ 已验证
DOI
PubMed
高影响因子
IMMUNITY
·
2021
·
IF 31.745
Ling-jie Huang,Xin-tao Mao,Yi-yuan Li,Dan-dan Liu,Ke-qi Fan,Rong-bei Liu,Ting-ting Wu,Hao-li Wang,Yu Zhang,Bing Yang,Cun-qi Ye,Jiang-yan Zhong,Ren-jie Chai,Qian Cao,Jin Jin
Summary Inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
研究领域:
免疫学
·
胃肠病学
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代谢组学
·
系统生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Xueling Liu,Weidi Wang,Yali Wang,Wenyuan Duan,Chao Liu,Peng Quan,Jiali Xiao,Yunning Zhang,Yu Hao,Liang Fang,Yilin Song,Wenzhou Zhang
Chronic consequences of diabetes that are most commonly encountered are diabetic foot ulcers (DFUs), driven by microbiota-immune system dyshomeostasis, eventually leading to delayed wound healing. Available therapies, such as systemic or topical administration of anti-inflammatory or antimicrobial agents, are limited due to antibiotic resistance and immune dysfunction. Herein, a hybrid hydrogel dressing is developed as the artificial bioadhesive barrier at wound sites to maintain microbial and immunological homeostasis locally and have potent anti-inflammatory effects. Specifically, Zero-valent selenium nanoparticles are synthesized and encapsulated into the alginate-polyacrylamide interpenetrating hydrogel networks, during which trehalose is adopted to modify the network defects. Besides, as an anti-adhesion agent, trehalose has shown the ability to prevent immune degradation by reducing bacteria binding to HUVECs. The obtained hybrid hydrogel dressing serves as a physical barrier against microbiome invasion, further regulates the composition of the wound microbiome to restore microbial immune homeostasis at the wound site, and cooperatively relieves DFU-associated symptoms. Meanwhile, the hydrogel dressing can synthesize selenoproteins in situ based on biochemical strategies and significantly reduce the secretion of proinflammatory cytokines. The proposed biochemical strategy based on the hybrid hydrogel dressings can efficiently restore microbiota-immune homeostasis in the wounds, presenting a promising approach for DFU therapy in clinics.
研究领域:
生物医学工程
·
材料科学
·
伤口愈合
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2023
·
IF 29
Qianmin Ou,Xinhua Qiao,Zhengshi Li,Luhan Niu,Fangcao Lei,Ruifeng Cheng,Ting Xie,Ning Yang,Yao Liu,Ling Fu,Jing Yang,Xueli Mao,Xiaoxing Kou,Chang Chen,Songtao Shi
Summary Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H 2 S) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates H 2 S production. Here, we show that apoptosis-deficient MRL/ lpr (B6.MRL-Faslpr/J) and Bim −/− (B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced H 2 S levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional H 2 S. Moreover, apoptotic cells and vesicles (apoVs) express key H 2 S-generating enzymes and generate a significant amount of H 2 S, indicating that apoptotic metabolism is an important source of H 2 S. Mechanistically, H 2 S sulfhydrates selenoprotein F (Sep15) to promote signal transducer and activator of transcription 1 (STAT1) phosphorylation and suppress STAT3 phosphorylation, leading to the inhibition of Th17 cell differentiation. Taken together, this study reveals a previously unknown role of apoptosis in maintaining H 2 S homeostasis and the unique role of H 2 S in regulating Th17 cell differentiation via sulfhydration of Sep15 C38 .
研究领域:
免疫学
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Animal Nutrition
·
2024
·
IF 6.1
Xiao Li,Jing Li,Kangle Lu,Xueshan Li,Kai Song,Ling Wang,Chunxiao Zhang
A 10-week feeding trial, followed by 24-h nitrite stress, was performed to evaluate the effects of dietary selenium-L-methionine (Se-Met) on growth, Se accumulation, antioxidant capacity, transcripts of selenoproteins and histological changes of muscle as well as resistance to nitrite stress in spotted seabass ( Lateolabrax maculatus ) reared at optimal (27 °C) and high (33 °C) temperatures. Five experimental diets were formulated to contain 0, 0.9, 1.8, 3.5, and 7.0 mg Se-Met/kg. Each diet was fed to fish (2.60 ± 0.2 g) in two parallel treatments at 27 or 33 °C. The results showed that elevated temperature (33 °C) induced thermal stress in fish, and fish under thermal stress exhibited lower weight gain (WG) and hepatosomatic index (HSI) but a higher condition factor (CF) compared to those reared at 27 °C. However, the growth and feed utilisation were promoted in L. maculatus with 0.9 to 3.5 mg/kg Se-Met treatments. The protein and lipid content in the muscle increased with the dietary Se-Met level, and the total Se level in the whole body and muscle showed a linear increase with dietary Se-Met supplementation. Thermal stress changed the histology of the muscle, leading to raised levels of malondialdehyde (MDA), reduced antioxidant parameters in the serum and liver, and a decrease in the transcripts of selenoprotein genes in the muscle. Meanwhile, increased antioxidant capacity of serum and liver and up-regulated transcripts of selenoprotein of muscle were observed in L. maculatus reaching a maximum with 3.5 mg Se-Met/kg treatment. After 24 h of nitrite stress, thermal stress exacerbated oxidative damage caused by nitrite stress in L. maculatus . In contrast, dietary Se-Met enhanced the resistance to nitrite stress of L . maculatus fed with Se-Met enriched diets containing 0.9 to 1.8 mg Se-Met/kg. Based on the effects of dietary Se-Met on the growth, antioxidant capacity and resistance to nitrite stress of L. maculatus , this study suggests that the optimal range of Se-Met supplementation in L. maculatus diets is 1.80 to 2.39 mg Se-Met/kg of diet at 27 °C and 1.80 to 4.46 mg Se-Met/kg of diet at 33 °C.
研究领域:
水产养殖
·
营养学
·
生理学
·
应激生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2020
·
IF 3.365
Chen Xujun,Li Shuyi,Cong Xin,Yu Tian,Zhu Zhenzhou,Barba Francisco J.,Marszalek Krystian,Puchalski Czesław,Cheng Shuiyuan
Selenium is an essential trace element and micronutrient for human health. Application of organic selenium in plants and microorganisms as trace element supplement is attracting more and more attention. In this study, Bacillus cereus, an important probiotic, was used for selenium enrichment with sodium selenite as selenium source. The growth curve of B. cereus was investigated, and 150 μg/ml was selected as the concentration of selenium for B. cereus fermentation. With application of response surface methodology, the optimal fermentation conditions were obtained as follows: inoculation quantity of 7%, culture temperature of 33°C, and shaking speed of 170 rpm, leading to the maximal selenium conversion ratio of 94.3 ± 0.2%. Field emission scanning electron microscope and energy dispersive spectrometry evidenced that inorganic selenium had been successfully transformed. This study may contribute to get a strain with high Se conversion ratio, so as to extract organic selenium in the form of selenoprotein to be used for further application.
研究领域:
微生物学
·
营养科学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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