TOXICOLOGY LETTERS
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2025
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IF 2.9
Xiaoyu Mao,Dashuang Mo,Yuqin Cheng,Mengzhu Lv
N -(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a commonly used antioxidant in tire manufacturing, has been widely detected in the environment and shown to exhibit acute toxicity in several organs. However, the effects of 6PPD on immune responses, particularly following injury, remain poorly understood. In this study, we investigated the impact of 6PPD exposure on immune responses using zebrafish as a model. 6PPD exposure disrupted caudal fin regeneration at various stages of the regenerative process. Further analysis revealed that 6PPD impaired immune responses following fin amputation, as evidenced by the reduced number of lyz + /mpx + neutrophils and the downregulation of key immune-related genes. Besides, the morphology of neutrophils was changed upon 6PPD exposure, indicating the defective migration of immune cells. The incubation of zebrafish larvae with lipopolysaccharide (LPS), which induces global immune responses, also exhibited impaired immune function when combined with 6PPD exposure. Additionally, the injection of LPS into the egg yolk or trunk exacerbated immune responses at the injury site, yet 6PPD exposure significantly reduced neutrophil accumulation and downregulated the expression of immune-related genes, confirming the toxicity of 6PPD in immune responses. These findings provide new insights into the toxic effects of 6PPD on immune responses during injury, highlighting its potential to impair immune function in animals and human.
研究领域:
毒理学
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免疫学
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环境科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Ziru Dai,Baolan He,Saiyi Zhong,Mengyuan Xie,Jianfu Qiao,Qi Wang
With increasing environmental pressures and lifestyle changes, suboptimal skin health-such as impaired barrier function and photoaging-are becoming more prevalent. Functional foods have emerged as promising dietary interventions due to their efficacy, safety, and convenience. Oral liquids are favored for their ambient-temperature preparation, low energy demand, absence of organic solvents, and ability to preserve the bioactivity of natural compounds. In this study, we developed a composite oral solution based on oyster polysaccharides, tangerine peel, and sodium hyaluronate. Scanning electron microscopy (SEM) results demonstrated that the particles in the OP-TP-HA oral solution exhibited a uniform, nearly spherical morphology and good dispersion. ABTS radical scavenging rate of OP-TP-HA oral solution was 93.71 %. Further cell-based assays demonstrated enhanced cell proliferation and adhesion in the oral solution. Notably, it significantly promoted zebrafish tail fin regeneration, demonstrating its potential for skin health promotion. These findings provide a basis for the development of natural functional foods for skin repair.
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PubMed
高影响因子
AQUATIC TOXICOLOGY
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2024
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IF 4.1
Sijie Zhang,Hao Wang,Yunlong Meng,Mijia Li,Yang Li,Xinhao Ye,Shiyi Duan,Shimei Xiao,Huiqiang Lu,Keyuan Zhong
Wound healing and tissue regeneration are influenced by a variety of factors. Adverse lifestyle habits, such as excessive alcohol consumption, delay wound healing and increase the risk of secondary infections. Ethyl butyrate is a common food additive widely used to enhance the aroma of alcoholic beverages. This additive is generally considered harmless to human health in both industrial and domestic settings. However, the ecotoxicity and its effects on wound healing have not been elucidated. In this study, we used zebrafish as the experimental animal, and the caudal fins were amputated to explore the effects of ethyl butyrate on wound healing and tissue regeneration. The effect of ethyl butyrate on blastema and bone regeneration and its impact on the transcriptional levels of regeneration-related genes and inflammation-related genes were evaluated. RNA-seq was conducted to determine the differentially expressed genes (DEGs) between the treatment and the control groups. KEGG and GO analysis was conducted to explore the functions of DEGs. Significantly enriched GO terms and KEGG pathways were identified to explore the molecular mechanism underlying the inhibition of zebrafish caudal fin regeneration by ethyl butyrate. The results demonstrated that ethyl butyrate significantly inhibited the regeneration of zebrafish caudal fins, including blastema and bone regeneration. Ethyl butyrate exposure significantly downregulated the expression of genes associated with bone and blastema regeneration and inflammation response. KEGG and GO functional analyses revealed that the DEGs were associated with significant enrichment of extracellular matrix-receptor interactions. Ethyl butyrate treatment downregulated the expression of most extracellular matrix-related genes. These findings indicate that ethyl butyrate potentially modulates pathways associated with the structure, adhesion, modification, and degradation of the extracellular matrix, thereby disrupting extracellular matrix remodeling, inhibiting wound inflammation, impairing blastema and bone regeneration and ultimately hindering caudal fin regeneration. In summary, the findings demonstrate that ethyl butyrate disrupts extracellular matrix remodeling and inhibits the regeneration of zebrafish caudal fins. These results provide valuable insights into the rational use of ethyl butyrate and further investigation of wound healing mechanisms.
研究领域:
毒理学
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再生生物学
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分子生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Fengyan Chen,Shiming Pu,Li Tian,Huan Zhang,Huixian Zhou,Yijing Yan,Xiaolin Hu,Qiong Wu,Xueping Chen,Shuk Han Cheng,Shisan Xu
Headings ethnopharmacological relevance Rehmanniae Radix Praeparata (RRP), a staple in traditional Chinese medicine, is derived from Rehmannia glutinosa Libosch and is renowned for its wound-healing properties. Despite its clinical prevalence, the molecular mechanisms underlying RRP's wound-healing effects have not been fully elucidated. Aim of the study This research endeavored to delineate the molecular and cellular mechanisms underlying the beneficial effects of RRP on wound healing, utilizing a zebrafish model. Materials and methods Zebrafish larvae at 3 days post-fertilization were amputated at the fin and subsequently treated with RRP. The pro-wound healing and regenerative effects of RRP were evaluated through morphological analysis, assessment of cell proliferation and apoptosis, Additionally, mechanistic insights were gained through a comprehensive approach encompassing network pharmacology analysis, cell tracing, RNA-sequencing, CRISPR/Cas9 gene editing, and pharmacological inhibition. Results Our findings demonstrate that RRP significantly accelerates caudal fin regeneration in zebrafish following injury by suppressing cell apoptosis, promoting cell proliferation, and upregulating the expression of regenerative-related genes. Furthermore, RRP triggers autophagy signals during the regenerative process, which is attenuated by the autophagy inhibitor chloroquine (CQ). Notably, the administration of RRP enhances the expression of ahr1 and ahr2 in the regenerating fin. Genetic knockout of ahr1a , ahr1b , or ahr2 using CRISPR/Cas9, or pharmacological blockade of AHR signals with the antagonist CH-223191, diminishes the regenerative potential of RRP. Remarkably, zebrafish lacking ahr2 completely lose their fin regeneration ability. Additionally, inhibition of AHR signaling suppresses autophagy signaling during fin regeneration. Conclusions This study uncovers that RRP stimulates fin regeneration in zebrafish by inducing AHR signals and, at least partially, activating the autophagy process. These findings provide novel insights into the molecular mechanisms underlying the wound-healing effects of RRP and may pave the way for the development of novel therapeutic strategies.
研究领域:
药理学
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分子生物学
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发育生物学
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中医
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PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2025
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IF 4.3
Qian Li,Wenjing Cheng,Hongyu Wang,Jun Chen,Yueyun Qin,Ruozhu Sheng,Shaohong Peng,Zaitian Li,Tao Lu,Liwei Sun
The hazardous effects of microplastics on aquatic biota have been extensively documented. However, the impact of surface functionalization on the toxicological profiles of microplastics, particularly in fish, requires further investigation. In the present study, the effects of polystyrene microplastics (50–100 nm in diameter), either non-functionalized or functionalized with carboxyl (-COOH) or amino (−NH 2 ) groups, on zebrafish were explored. Exposure to all three types of microplastics (0.1, 1, and 10 mg/L) resulted in developmental toxicity in zebrafish at early life stages. This included increased mortality, reduced larval body length, decreased heart rate, impaired swimming ability, as well as disruptions in redox homeostasis, nervous system development, and immune responses. Moreover, all types of microplastics (1 mg/L) inhibited the regenerative capacity of larval zebrafish after caudal fin amputation, both morphologically and functionally. This inhibition was likely due to alterations in immune response, excessive production of reactive oxygen species, and disruptions in the signaling networks that regulate fin regeneration. Among the tested microplastics, amino-modified particles generally exhibited greater developmental toxicity and stronger inhibitory effects on fin regeneration. Our findings confirm that the functionalization of microplastics plays a crucial role in their interactions with biological systems and highlight concerns regarding the potential effects of functionalization, whether intentional or resulting from natural weathering processes.
研究领域:
生态毒理学
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环境科学
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发育生物学
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水生毒理学
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分子生物学
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免疫学
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神经生物学
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再生医学
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DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
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2024
·Vol. 19
·期 1
·1-15
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IF 2.8
Xiao Gongyi,Li Xiangwei,Yang Huiping,Zhang Ruobin,Huang Junlan,Tian Yu,Nie Mao,Sun Xianding
Background The larval zebrafish tail fin can completely regenerate in 3 days post amputation. mTOR , the main regulator of cell growth and metabolism, plays an essential role in regeneration. Lots of studies have documented the role of mTOR in regeneration. However, the mechanisms involved are still not fully elucidated. Materials and results This study aimed to explore the role and mechanism of mTOR in the regeneration of larval zebrafish tail fins. Initially, the spatial and temporal expression of mTOR signaling in the larval fin was examined, revealing its activation following tail fin amputation. Subsequently, a mTOR knockout ( mTOR -KO) zebrafish line was created using CRISPR/Cas9 gene editing technology. The investigation demonstrated that mTOR depletion diminished the proliferative capacity of epithelial and mesenchymal cells during fin regeneration, with no discernible impact on cell apoptosis. Insight from SMART-seq analysis uncovered alterations in the cell cycle, mitochondrial functions and metabolic pathways when mTOR signaling was suppressed during fin regeneration. Furthermore, mTOR was confirmed to enhance mitochondrial functions and Ca 2 + activation following fin amputation. These findings suggest a potential role for mTOR in promoting mitochondrial fission to facilitate tail fin regeneration. Conclusion In summary, our results demonstrated that mTOR played a key role in larval zebrafish tail fin regeneration, via promoting mitochondrial fission and proliferation of blastema cells.
研究领域:
发育生物学
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分子生物学
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再生医学
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PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2023
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IF 4.7
Ju Wang,Lei Wang,Qi Wang,Changhong Liu,Lei Zheng
Zebrafish possesses robust caudal fin regeneration which depends on multiple factors to maintain body integrity. However, it is uncertain whether the caudal fin regeneration is related to gut microbiota . Here, we investigated the effect of Lacticaseibacillus rhamnosus GG (LGG) on the regeneration of caudal fin under oxytetracycline (OTC) exposure. The results demonstrated that 1000 μg/L OTC exposure for 4 days decreased reactive oxygen species (ROS) production at 1 and 3 h post amputation (hpa), increased neutrophil recruitment at 6 hpa, enhanced the number of apoptotic cells at 1, 3, 6 and 12 hpa and inhibited Wnt signaling pathway at 48 hpa in wound site. Furthermore, OTC exposure caused dysbacteriosis by elevating level of Proteobacteria and decreasing the abundance of Firmicutes , particularly Lacticaseibacillus , thereby negatively impacting wound healing and repair. Additionally, the administration of 10 6 CFU/mL of LGG for 48 h could improve intestinal environment through increasing the colonization rate of LGG in OTC-treated larvae intestines. The regenerative process restored by LGG was accompanied with increased ROS production at 1, 3 and 6 hpa, inhibited neutrophil recruitment at 6 hpa, decreased the number of apoptotic cells at 1 hpa, and activated Wnt signaling pathway at 48 hpa in OTC-treated fish. LGG is a promising bacterium for restoring fin regeneration and provides new insights regarding the correlation among the gut microbiota and fin regeneration.
研究领域:
微生物学
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再生生物学
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水生毒理学
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发育生物学
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PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2020
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IF 6.551
Shaochen Pang,Yue Gao,Fengbang Wang,Yuanyuan Wang,Mengxi Cao,Wenjuan Zhang,Yong Liang,Maoyong Song,Guibin Jiang
Dressings coated with silver nanoparticle (AgNP) are widely used in the management of acute and chronic wounds. However, whether AgNP exerts toxicity on wound healing remains ambiguous. To demonstrate the effects of AgNP on wound healing, we precisely quantified the recovery speed of wound by taking advantage of the fin regeneration of zebrafish. This method also enabled assessment of the adverse effect of AgNP on various steps of wound healing in vivo . We revealed that AgNP treatment at the concentration of 2 μg/ml impaired fin regeneration when exposure was performed at the phases of epithelialization and the beginning of blastema formation. Cell proliferation of regenerative blastema was significantly decreased after AgNP exposure. But the canonical signals including Wingless/Integrated (Wnt), Notch and Fibroblast growth factor (Fgf) which play important roles in cell proliferation during fin regeneration were not modulated at 36 hours post amputation (hpa). Further study showed that AgNP impaired fin regeneration through declining amputation-induced ROS as early as epithelialized phase at 18 hpa, rather than inducing ROS generation. AgNP exposure also promoted recruitment of neutrophils in the early phase of wound healing, which suggests that this event dampened amputation-induced ROS. Overall, this study suggested that application of AgNP-coated dressings should be carefully considered at the beginning stage of wound healing.
研究领域:
纳米技术
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伤口愈合
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斑马鱼生物学
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再生医学
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DOI
PubMed
高影响因子
AQUACULTURE RESEARCH
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2023
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IF 2
Tingting Hou,Zaizhao Wang,Kui Tang,Shuai Zhang,Shilin Liu,Jialiang Liu,Xiaoteng Fan,Xiaolin Liu
This study investigated the capability for fin regeneration in zebrafish larvae with the mechanism of FCS isolated from green and purple sea cucumbers Apostichopus japonicus (G-FCS and P-FCS). HPGPC determined that mean molecular weight of purified G-FCS and P-FCS is 19.5 and 18.8 kDa, and the FT-IR spectrum displayed similar characteristic absorption peaks. AFM images presented that G-FCS was shown as a spherical polysaccharide, while P-FCS molecules exhibited elongated chains. For the regeneration examination, FCS increased the regrowth area of the larval fin at 48 hours postamputation with enhanced locomotor behaviors, and the transcription levels of regeneration-related genes (Wnt10a, msx1b, fgf20a, bmp2a, bmp4, and igf2b) were upregulated. Moreover, FCS promoted the mRNA expression of inflammatory factors (iNOS, TNF-α, IL-6, IL-10, and IFN-γ) and TLR/NF-κB pathway-related genes (TLR3, TLR4a, NF-κb, and MyD88). The Western blot analyses of TNF-α and IL-1β supported that FCS enhanced immune response. ELISA results indicated that FCSs increased the contents of NO, CAT, SOD, and G6PD. Summarily, the present results suggested that FCS was a potential regeneration enhancer by elevating immunomodulatory and antioxidative processes in zebrafish.
研究领域:
海洋生物学
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发育生物学
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免疫学
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生物化学
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DOI
高影响因子
PROCESS BIOCHEMISTRY
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2024
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IF 3.7
Juan Huang,Haiyu Ouyang,Wenjing Zhou,Difan Zhu,Haimei Zhi,Wei Li
A supplemented collagen peptide composition (SCPC) containing microbe-fermented collagen peptide, collagen tripeptide, elastin peptide, and sodium hyaluronate was investigated to determine its effects on skin aging, skin elasticity, and tissue regeneration in zebrafish. β-Galactosidase activity was inhibited, while telomerase activity was elevated, by exposure to 0.977 μL/mL of SCPC in an H 2 O 2 -induced aging zebrafish model, indicating that SCPC can delay cell senescence. Expression of the collagen I gene col1a1a was up-regulated by exposure to 62.5 μL/mL of SCPC, indicating that SCPC can improve skin elasticity. Regrowth of the injured caudal fin was enhanced by exposure to only 0.122 μL/mL of SCPC. These improvements to skin aging, elasticity, and tissue regeneration in zebrafish suggest that this SCPC has potential as a functional food with beneficial effects on skin health and aging resistance in humans.
研究领域:
生物技术
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衰老研究
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水产养殖
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功能性食品
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高影响因子
危险品化学品经营许可证（带存储）