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  1. Article ; Online: Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling

    Yuhang Xu / Lingfei Luo / Jingying Chen

    Ecotoxicology and Environmental Safety, Vol 238, Iss , Pp 113620- (2022)

    2022  

    Abstract: Sulfamethoxazole (SMX) is a widespread broad-spectrum bacteriostatic antibiotic. Its residual is frequently detected in the water and may therefore bioaccumulate in the brain of aquatic organisms via blood circulation. Brain capillaries toxicity is very ... ...

    Abstract Sulfamethoxazole (SMX) is a widespread broad-spectrum bacteriostatic antibiotic. Its residual is frequently detected in the water and may therefore bioaccumulate in the brain of aquatic organisms via blood circulation. Brain capillaries toxicity is very important for brain development. However, little information is available in the literature to show the toxicity of SMX to brain development. To study the SMX’s brain toxic effects and the related mechanisms, we exposed zebrafish embryos to SMX at different concentrations (0 ppm, 1 ppm, 25 ppm, 100 ppm and 250 ppm) and found that high concentration (250 ppm) of SMX would not only caused an abnormal in malformation rate, hatching rate, body length and survival rate of zebrafish embryos, but also lead to brain oedema. In addition, SMX also induced cerebral ischaemia, aggravates oxidative stress, and changes genes related to oxidative stress (sod1, cat, gpx4, and nrf2). Furthermore, ischaemia caused by SMX could promote ectopic angiogenesis in brain via activating the angiogenesis-related genes (vegfab, cxcr4a, cxcl12b) from 24 h to 53 h. Inhibition of VEGF signalling by SU5416, or inhibition of chemokine downstream PI3K signalling by LY294002, could rescue the brain capillaries toxicity and brain oedema induced by SMX. Our results provide new evidence for the brain toxicity of SMX and its residual danger in the environment and aquatic organisms.
    Keywords Sulfamethoxazole ; Brain capillaries toxicity ; Brain oedema ; VEGF ; Chemokine ; Environmental pollution ; TD172-193.5 ; Environmental sciences ; GE1-350
    Subject code 616
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Zebrafish as a Model for Germ Cell Regeneration

    Zigang Cao / Qifen Yang / Lingfei Luo

    Frontiers in Cell and Developmental Biology, Vol

    2021  Volume 9

    Abstract: Germ cell acts as a link between transfer of genetic information and process of species evolution. Defects or malformations of germ cells can lead to infertility or tumors. Germ cell regeneration is one of the effective ways to treat the infertility. ... ...

    Abstract Germ cell acts as a link between transfer of genetic information and process of species evolution. Defects or malformations of germ cells can lead to infertility or tumors. Germ cell regeneration is one of the effective ways to treat the infertility. Therefore, it is of great scientific and clinical interests to dissect the cellular and molecular mechanisms underlying germ cell regeneration. Progress have already been achieved in germ cell regeneration using model organisms for decades. However, key open issues regarding the underpinning mechanisms still remain poorly understood. Zebrafish is well known for its powerful regenerative capacity to regenerate various tissues and organs. Recently, advances in genomics, genetics, microscopy, and single cell technologies have made zebrafish an attractive model to study germ cell development and regeneration. Here we review recent technologies for the study of germ cell regeneration in zebrafish, highlight the potential of germline stem cells (GSCs) in the contribution to reproductive system regeneration, and discuss the nanos. Wnt signaling and germ cell-specific factors involved in the regulation of germ cell regeneration.
    Keywords zebrafish ; germ cell ; regeneration ; germline stem cell ; nanos2 ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A noncanonical function of histidyl‐tRNA synthetase

    Rui Ni / Lingfei Luo

    FEBS Open Bio, Vol 8, Iss 5, Pp 722-

    inhibition of vascular hyperbranching during zebrafish development

    2018  Volume 731

    Abstract: Histidyl‐tRNA synthetase (Hars) catalyzes the ligation of histidine residues to cognate tRNA. Here, we demonstrate a noncanonical function of Hars in vascular development in zebrafish. We obtained a novel zebrafish cq34 mutant which exhibited ... ...

    Abstract Histidyl‐tRNA synthetase (Hars) catalyzes the ligation of histidine residues to cognate tRNA. Here, we demonstrate a noncanonical function of Hars in vascular development in zebrafish. We obtained a novel zebrafish cq34 mutant which exhibited hyperbranching of cranial and intersegmental blood vessels 48 h after fertilization. The gene responsible for this phenotype was identified as hars. We found the increased expression of cdh5 and vegfa in the harscq34 mutant. Knockdown of cdh5 in the mutant reduced disordered connections of the hindbrain capillaries. Inhibition of vascular endothelial growth factor signaling suppressed the abnormal vascular branching observed in the mutant. Moreover, the human HARS mRNA rescued the vascular defects in the cq34 mutant. Thus, the noncanonical function of Hars regulates vascular development, mainly by modulating expression of cdh5 and vegfa.
    Keywords angiogenesis ; Cdh5 ; histidyl‐tRNA synthetase ; Vegfa ; zebrafish ; Biology (General) ; QH301-705.5
    Subject code 580
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway

    Jingmei Song / Jianlong Ma / Xing Liu / Zhuofu Huang / Lianghui Li / Linke Li / Lingfei Luo / Rui Ni / Jianbo He

    npj Regenerative Medicine, Vol 8, Iss 1, Pp 1-

    2023  Volume 14

    Abstract: Abstract When the proliferation of residual hepatocytes is prohibited, biliary epithelial cells (BECs) transdifferentiate into nascent hepatocytes to accomplish liver regeneration. Despite significant interest in transdifferentiation, little is known ... ...

    Abstract Abstract When the proliferation of residual hepatocytes is prohibited, biliary epithelial cells (BECs) transdifferentiate into nascent hepatocytes to accomplish liver regeneration. Despite significant interest in transdifferentiation, little is known about the maintenance of nascent hepatocytes in post-injured environments. Here, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a mutant containing a nonsense mutation in the gene nibrin (nbn), which encodes a component of the Mre11-Rad50-Nbn (MRN) complex that activates DNA damage response (DDR). The regenerated hepatocytes cannot be maintained and exhibit apoptosis in the mutant. Mechanistically, the nbn mutation results in the abrogation of ATR-Chk1 signaling and accumulations of DNA damage in nascent hepatocytes, which eventually induces p53-mediated apoptosis. Furthermore, loss of rad50 or mre11a shows similar phenotypes. This study reveals that the activation of DDR by the MRN complex is essential for the survival of BEC-derived hepatocytes, addressing how to maintain nascent hepatocytes in the post-injured environments.
    Keywords Medicine ; R
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Roles of mTOR Signaling in Tissue Regeneration

    Xiangyong Wei / Lingfei Luo / Jinzi Chen

    Cells, Vol 8, Iss 9, p

    2019  Volume 1075

    Abstract: The mammalian target of rapamycin (mTOR), is a serine/threonine protein kinase and belongs to the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family. mTOR interacts with other subunits to form two distinct complexes, mTORC1 and mTORC2. ... ...

    Abstract The mammalian target of rapamycin (mTOR), is a serine/threonine protein kinase and belongs to the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family. mTOR interacts with other subunits to form two distinct complexes, mTORC1 and mTORC2. mTORC1 coordinates cell growth and metabolism in response to environmental input, including growth factors, amino acid, energy and stress. mTORC2 mainly controls cell survival and migration through phosphorylating glucocorticoid-regulated kinase (SGK), protein kinase B (Akt), and protein kinase C (PKC) kinase families. The dysregulation of mTOR is involved in human diseases including cancer, cardiovascular diseases, neurodegenerative diseases, and epilepsy. Tissue damage caused by trauma, diseases or aging disrupt the tissue functions. Tissue regeneration after injuries is of significance for recovering the tissue homeostasis and functions. Mammals have very limited regenerative capacity in multiple tissues and organs, such as the heart and central nervous system (CNS). Thereby, understanding the mechanisms underlying tissue regeneration is crucial for tissue repair and regenerative medicine. mTOR is activated in multiple tissue injuries. In this review, we summarize the roles of mTOR signaling in tissue regeneration such as neurons, muscles, the liver and the intestine.
    Keywords mTOR signaling ; metabolism ; tissue regeneration ; neuron ; muscle ; liver ; intestine ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Germline Stem Cells Drive Ovary Regeneration in Zebrafish

    Zigang Cao / Xiaoyu Mao / Lingfei Luo

    Cell Reports, Vol 26, Iss 7, Pp 1709-1717.e

    2019  Volume 3

    Abstract: Summary: Germline stem cells (GSCs) sustain gametogenesis during the organismal life cycle. Although evidence suggests that GSCs are consistently present in the zebrafish ovary and support oogenesis, whether GSCs are involved in zebrafish ovary ... ...

    Abstract Summary: Germline stem cells (GSCs) sustain gametogenesis during the organismal life cycle. Although evidence suggests that GSCs are consistently present in the zebrafish ovary and support oogenesis, whether GSCs are involved in zebrafish ovary regeneration is poorly understood. Here, we found that nanos2, a conserved vertebrate GSC marker, is required for maintaining GSCs in zebrafish. We applied genetic ablation and tissue resection techniques to delineate the function of GSCs in zebrafish ovary regeneration. After GSC ablation, ovaries fail to regenerate and are converted to sterile testes. Amputated ovarian tissues completely regenerate as a result of the proliferation of residual GSCs, but nanos2 mutant ovaries fail to regenerate after amputation due to a lack of GSCs. The repression of Wnt signaling leads to reduced numbers of GSCs and delayed ovary regeneration. Our results provide insight into the key role of GSCs in driving ovary regeneration. : Germline stem cells maintain ovarian high fecundity throughout the life cycle in zebrafish. Cao et al. demonstrate that the GSC marker nanos2 is required for the maintenance of GSCs and provide evidence that ovary regeneration is a GSC-driven process in zebrafish. Keywords: GSCs, nanos2, zebrafish, ovary regeneration, Wnt
    Keywords Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Contributions of biliary epithelial cells to hepatocyte homeostasis and regeneration in zebrafish

    Wenfeng Zhang / Jingying Chen / Rui Ni / Qifen Yang / Lingfei Luo / Jianbo He

    iScience, Vol 24, Iss 3, Pp 102142- (2021)

    2021  

    Abstract: Summary: Whether transdifferentiation of the biliary epithelial cells (BECs) to hepatocytes occurs under physiological conditions and contributes to liver homeostasis remains under long-term debate. Similar questions have been raised under pathological ... ...

    Abstract Summary: Whether transdifferentiation of the biliary epithelial cells (BECs) to hepatocytes occurs under physiological conditions and contributes to liver homeostasis remains under long-term debate. Similar questions have been raised under pathological circumstances if a fibrotic liver is suffered from severe injuries. To address these questions in zebrafish, we established a sensitive lineage tracing system specific for the detection of BEC-derived hepatocytes. The BEC-to-hepatocyte transdifferentiation occurred and became minor contributors to hepatocyte homeostasis in a portion of adult individuals. The BEC-derived hepatocytes distributed in clusters in the liver. When a fibrotic liver underwent extreme hepatocyte damages, BEC-to-hepatocyte transdifferentiation acted as the major origin of regenerating hepatocytes. In contrast, partial hepatectomy failed to induce the BEC-to-hepatocyte conversion. In conclusion, based on a sensitive lineage tracing system, our results suggest that BECs are able to transdifferentiate into hepatocytes and contribute to both physiological hepatocyte homeostasis and pathological regeneration.
    Keywords cellular physiology ; cellular biology ; developmental biology ; Science ; Q
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Tel2 regulates redifferentiation of bipotential progenitor cells via Hhex during zebrafish liver regeneration

    Junren Zhang / Yang Zhou / Shuang Li / Dashuang Mo / Jianlong Ma / Rui Ni / Qifen Yang / Jianbo He / Lingfei Luo

    Cell Reports, Vol 39, Iss 1, Pp 110596- (2022)

    2022  

    Abstract: Summary: Upon extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via biliary epithelial cell (BEC) transdifferentiation, which includes dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and then ... ...

    Abstract Summary: Upon extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via biliary epithelial cell (BEC) transdifferentiation, which includes dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and then redifferentiation of BP-PCs to nascent hepatocytes and BECs. This BEC-driven liver regeneration involves reactivation of hepatoblast markers, but the underpinning mechanisms and their effects on liver regeneration remain largely unknown. Using a zebrafish extensive hepatocyte ablation model, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a liver regeneration mutant, liver logan (lvl), in which the telomere maintenance 2 (tel2) gene is mutated. During liver regeneration, the tel2 mutation specifically inhibits transcriptional activation of a hepatoblast marker, hematopoietically expressed homeobox (hhex), in BEC-derived cells, which blocks BP-PC redifferentiation. Mechanistic studies show that Tel2 associates with the hhex promoter region and promotes hhex transcription. Our results reveal roles of Tel2 in the BP-PC redifferentiation process of liver regeneration by activating hhex.
    Keywords CP: Cell biology ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration

    Chenglu Xiao / Junjie Hou / Fang Wang / Yabing Song / Jiyuan Zheng / Lingfei Luo / Jianbin Wang / Wanqiu Ding / Xiaojun Zhu / Jing-Wei Xiong

    npj Regenerative Medicine, Vol 8, Iss 1, Pp 1-

    2023  Volume 13

    Abstract: Abstract Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial ... ...

    Abstract Abstract Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial cells after ventricular resection and endothelium-specific overexpression of dominant-negative Xenopus Brg1 (dn-xbrg1) inhibited myocardial proliferation and heart regeneration and increased cardiac fibrosis. RNA-seq and ChIP-seq analysis revealed that endothelium-specific overexpression of dn-xbrg1 changed the levels of H3K4me3 modifications in the promoter regions of the zebrafish genome and induced abnormal activation of Notch family genes upon injury. Mechanistically, Brg1 interacted with lysine demethylase 7aa (Kdm7aa) to fine-tune the level of H3K4me3 within the promoter regions of Notch family genes and thus regulated notch gene transcription. Together, this work demonstrates that the Brg1-Kdm7aa-Notch axis in cardiac endothelial cells, including the endocardium, regulates myocardial proliferation and regeneration via modulating the H3K4me3 of the notch promoters in zebrafish.
    Keywords Medicine ; R
    Subject code 570
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling

    Wei Huang / Yu Zhang / Kang Cao / Lingfei Luo / Sizhou Huang

    BioMed Research International, Vol

    2018  Volume 2018

    Abstract: During somitogenesis, Fgf8 maintains the predifferentiation stage of presomitic mesoderm (PSM) cells and its retraction gives a cue for somite formation. Delta/Notch initiates the expression of oscillation genes in the tail bud and subsequently ... ...

    Abstract During somitogenesis, Fgf8 maintains the predifferentiation stage of presomitic mesoderm (PSM) cells and its retraction gives a cue for somite formation. Delta/Notch initiates the expression of oscillation genes in the tail bud and subsequently contributes to somite formation in a periodic way. Whether there exists a critical factor coordinating Fgf8 and Notch signaling pathways is largely unknown. Here, we demonstrate that the loss of function of geminin gave rise to narrower somites as a result of derepressed Fgf8 gradient in the PSM and tail bud. Furthermore, in geminin morphants, the somite boundary could not form properly but the oscillation of cyclic genes was normal, displaying the blurry somitic boundary and disturbed somite polarity along the AP axis. In mechanism, these manifestations were mediated by the disrupted association of the geminin/Brg1 complex with intron 3 of mib1. The latter interaction was found to positively regulate mib1 transcription, Notch activity, and sequential somite segmentation during somitogenesis. In addition, geminin was also shown to regulate the expression of deltaD in mib1-independent way. Collectively, our data for the first time demonstrate that geminin regulates Fgf8 and Notch signaling to regulate somite segmentation during somitogenesis.
    Keywords Medicine ; R
    Subject code 570
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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