JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2024
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IF 8
Guangxia Xu,Xiaoyu Long,Junjie Zhai,Yunhao Liu,Chaowei Wang,Jinbu Li,Xing Wang
Widespread use of the pyrethroid insecticide beta-cypermethrin (beta-CYP) has led to adverse effects on nontarget populations within agroecosystems. Despite the efficacy of beta-CYP in pest control, its toxicological and defense mechanisms remain incompletely understood. In the present study, we explored the toxicological effects, antioxidant mechanisms and immune response against beta-CYP using Drosophila melanogaster , a well-established model organism for the study of insect biology, to represent the broader class of nontarget organisms. We exposed Drosophila larvae to 0.667 μg/mL beta-CYP and revealed that delayed development and caused intestinal epithelial damage in larvae. To gain insights into the molecular underpinnings of these effects, RNA sequencing analysis and quantitative polymerase chain reaction validation were performed. These analyses revealed that the messenger RNA levels of glutathione S-transferase were increased, third instar larvae exhibited an increase in reactive oxygen species content and a corresponding increase in antioxidant enzyme activity in response to beta-CYP exposure, indicating an upregulated response to oxidative stress. Beta-CYP also activated Hippo pathway to resist apoptosis and promote cell proliferation. Moreover, beta-CYP induced melanization and Toll immune pathways involved in immune response in Drosophila larvae, specifically the Toll pathway gene Drs . This activation suggests that Drosophila increases antioxidant defenses and promotes mitosis in damaged tissues as compensatory mechanisms to mitigate the cytotoxic effects of beta-CYP. These findings provide new insight into the mechanisms of beta-CYP–induced toxicity and the defense mechanisms in insects; they may also inform strategies for the sustainable use of insecticides and the development of mitigation measures to protect nontarget species in agroecosystems.
研究领域:
毒理学
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昆虫生物学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2015
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IF 2.014
Baoyan Zhang,Zhiping Xu,Yixi Zhang,Xusheng Shao,Xiaoyong Xu,Jiaogao Cheng,Zhong Li
Fipronil is the first phenylpyrazole insecticide widely used in controlling pests, including pyrethroid, organophosphate and carbamate insecticides. It is generally accepted that fipronil elicits neurotoxicity via interactions with GABA and glutamate receptors, although alternative mechanisms have recently been proposed. This study evaluates the genotoxicity of fipronil and its likely mode of action in Drosophila S2 cells, as an in vitro model. Fipronil administrated the concentration- and time-dependent S2 cell proliferation. Intracellular biochemical assays showed that fipronil-induced S2 cell apoptosis coincided with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, a significant decrease of Bcl-2 and DIAP1, and a marked augmentation of Cyt c and caspase-3. Because caspase-3 is the major executioner caspase downstream of caspase-9 in Drosophila , enzyme activity assays were used to determine the activities of caspase-3 and caspase-9. Our results indicated that fipronil effectively induced apoptosis in Drosophila S2 cells through caspase-dependent mitochondrial pathways.
研究领域:
毒理学
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细胞生物学
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昆虫学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Yingxia Hu,Haijie Wu,Chenying Lu,Hanqing Xu,Boyang Li,Wanchun Guan,Mingjiang Wu,Yitian Gao,Haibin Tong
Cadmium (Cd) is a widely distributed toxic heavy metal that enters the environment via anthropogenic mobilization and accumulates in plants and animals, causing metabolic abnormalities even mortality. Although the toxic effects and stress damage of cadmium have been investigated extensively over the past few decades, research on its ability to trigger ferroptosis, growth retardation, and behavioral abnormalities is insufficient. As a result, the effects of CdCl 2 exposure on growth and development, activity and sleep, and ferroptosis in this study were examined in fruit fly ( Drosophila melanogaster ). When exposed to 0.5 mM CdCl 2 , the entire growth period from larvae to adults was prolonged, and the rates of pupation and eclosion were decreased. Additionally, CdCl 2 exposure resulted in a decrease in body weight and individual size of fruit fly and high lethality rate. Moreover, CdCl 2 exposure altered fruit fly behavior, including decreased activity and increased sleep duration, particularly in females. Ferrostatin-1 (Fer-1) is a potent selective ferroptosis inhibitor that effectively slows lipid hydroperoxide accumulation to rescue body size reduction and restore activity and sleep in CdCl 2 -exposed female flies. CdCl 2 exposure could induce ferroptosis in fruit fly mechanistically, as evidenced by inhibition of Nrf2 signaling pathway, accumulation of lipid peroxidation, impairment of GPX4 antioxidant system, and upregulation of iron metabolism. Our findings suggest that Cd exposure triggers ferroptosis, which leads to growth retardation and behavioral disorders in fruit fly.
研究领域:
毒理学
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发育生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Jie Wang,Chunyan Wu,Xing Zhang,Yuanyuan Song,Binquan Wang,Ke Zhang,Mingkuan Sun
As a result of the ban on bisphenol A (BPA), a hormone disruptor with developmental neurotoxicity, several BPA derivatives (BPs) have been widely used in industrial production. However, there are no effective methods for assessing the neurodevelopmental toxic effects of BPs. To address this, a Drosophila exposure model was established, and W 1118 was reared in food containing these BPs. Results showed that each BPs displayed different semi-lethal doses ranging from 1.76 to 19.43 mM. Exposure to BPs delayed larval development and affected axonal growth, resulting in the abnormal crossing of the midline of axons in the β lobules of mushroom bodies, but the damage caused by BPE and BPF was relatively minor. BPC, BPAF, and BPAP have the most significant effects on locomotor behavior, whereas BPC exhibited the most affected social interactions. Furthermore, exposure to high-dose BPA, BPC, BPS, BPAF, and BPAP also significantly increased the expression of Drosophila estrogen-related receptors. These demonstrated that different kinds of BPs had different levels of neurodevelopmental toxicity, and the severity was BPZ > BPC and BPAF > BPB > BPS > BPAP ≈ BPAl ≈ BPF > BPE. Therefore, BPZ, BPC, BPS, BPAF, and BPAP should be evaluated as potential alternatives to BPA.
研究领域:
毒理学
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神经生物学
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产品关联
DOI
PubMed
高影响因子
Nanotoxicology
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2025
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IF 3.4
Junyue Wang,Yang Jiang,Yán Wāng
Silicon dioxide nanoparticles (SiO2 NPs) are widely utilized in industrial and biomedical applications owing to their unique physicochemical properties; however, their potential biological effects require comprehensive evaluation. In this study, the model organism Drosophila melanogaster was employed to investigate the impacts of dietary exposure to SiO2 NPs of different sizes and concentrations on developmental and reproductive outcomes. The assessed parameters included egg-laying rate, pupation time, adult emergence time, pupation rate, adult emergence rate, larval weight, and sex ratio. The results revealed that at concentrations of 0.2% or lower, neither nanoparticle size produced significant effects on development or reproductive capacity. In contrast, exposure to 2% SiO2 NPs (both 15 nm and 30 nm) led to reduced body weight in third instar larvae. Notably, 30 nm SiO2 NPs exposure significantly decreased pupation and adult emergence rates and was associated with delayed pupation and emergence times. Although total egg production remained unchanged, flies exposed to 30 nm SiO2 NPs exhibited an earlier oviposition peak. These findings suggest that exposure to SiO2 NPs at the national standard concentration of 0.2% does not cause notable developmental effects in Drosophila, whereas a tenfold increase in concentration may induce developmental delays. Considering that the 0.2% standard is based on human exposure and accounting for interspecies extrapolation, the 2% concentration may still represent a relevant dose range. Overall, these results indicate that excessive intake of SiO2 NPs could pose toxicological risks and provide a theoretical foundation for further studies on the mechanisms underlying SiO2 NPs-induced toxicity.
研究领域:
毒理学
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纳米毒理学
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发育生物学
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生殖生物学
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环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports
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2024
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IF 7.5
Lihong Sheng,Jianpeng Gao,Qingyuan Wei,Ye Gong,Zhi-Xiang Xu
Lipid droplets (LDs) are dynamic organelles essential for lipid storage and organismal survival. Studies have highlighted the importance of glial function in brain LD formation during aging; however, the genes and mechanisms involved remain elusive. Here, we found that Ugt35b , a member of the uridine diphosphate (UDP)-glycosyltransferases that catalyze the transfer of glycosyl groups to acceptors, is highly expressed in glia and crucial for Drosophila lifespan. By integrating multiomics data, we demonstrated that glial Ugt35b plays key roles in regulating glycerolipid and glycerophospholipid metabolism in the brain. Notably, we found that Ugt35b and Lsd-2 are co-expressed in glia and confirmed their protein interaction in vivo . Knockdown of Ugt35b significantly reduced LD formation by downregulating Lsd-2 expression, while overexpression of Lsd-2 partially rescued the shortened lifespan in glial Ugt35b RNAi flies. Our findings reveal the crucial role of glial Ugt35b in regulating LD formation to maintain brain lipid homeostasis and support Drosophila lifespan.
研究领域:
神经科学
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衰老研究
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
AGING CELL
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2021
·Vol. 20
·期 3
·e13319
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IF 9.304
Gang Du,Zhiming Liu,Zihua Yu,Zhangpeng Zhuo,Yuedan Zhu,Juanyu Zhou,Yang Li,Haiyang Chen
As they age, adult stem cells become more prone to functional decline, which is responsible for aging-associated tissue degeneration and diseases. One goal of aging research is to identify drugs that can repair age-associated tissue degeneration. Multiple organ development-related signaling pathways have recently been demonstrated to have functions in tissue homeostasis and aging process. Therefore, in this study, we tested several chemicals that are essential for organ development to assess their ability to delay intestinal stem cell (ISC) aging and promote gut function in adult Drosophila . We found that taurine, a free amino acid that supports neurological development and tissue metabolism in humans, represses ISC hyperproliferation and restrains the intestinal functional decline seen in aged animals. We found that taurine represses age-associated ISC hyperproliferation through a mechanism that eliminated endoplasmic reticulum (ER) stress by upregulation of the target genes of unfolded protein response in the ER (UPR ER ) and inhibiting the c-Jun N-terminal kinase (JNK) signaling. Our findings show that taurine plays a critical role in delaying the aging process in stem cells and suggest that it may be used as a natural compound for the treatment of age-associated, or damage-induced intestinal dysfunction in humans.
研究领域:
衰老研究
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干细胞生物学
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分子遗传学
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产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
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2019
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IF 0
Cai-Hong Li,Jun-Li Yang
This study is to investigate the potential of wolfberry water extracts for the treatment of Alzheimer’s disease (AD) and the relationship between their anti-AD property and the geographic locations in China. Total extracts of all wolfberry samples showed the potent to decrease self-induced A β 1-42 aggregation and Cu 2+ -induced A β 1-42 aggregation and the antioxidant capacity as well as the bioactivity for binding bio-metal. A transgenic drosophila model assay revealed that TE of S1 and S6 (S1-TE and S6-TE) at 100 μg/mL demonstrated the potent rescue effect on memory loss compared to the positive control memantine at 20 μg/mL. Further study also revealed the polysaccharide extracts could contribute to their anti-AD property, and the anti-AD activity conspicuously depends on growing environment. Wolfberry samples S1 and S6 showed much more potent anti-AD property. Meanwhile this study demonstrated that the Chinese commonly consumed wolfberry in boiling water might have the beneficial function to prevent AD pathology.
研究领域:
神经科学
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植物化学
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药理学
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产品关联
DOI
STAR Protocols
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2022
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IF 0
Yajie Gao,Yuanxiang Zhu,Qinmiao Sun,Dahua Chen
Summary Here, we provide an optimized RNA-induced silencing complex (RISC) assembly and cleavage protocol in vitro without using radiolabeled RNA. The protocol is useful to characterize the biochemical properties of the RISC. We describe the preparation of RNA probes, the target RNA, and Drosophila cell lysates for RISC assembly assay. We then detail AGO1 complexes immunoprecipitation for RISC cleavage assay. This protocol can detect RISC assembly and cleavage products within 5 days. Moreover, it can detect 5′- and 3′-cleavage products simultaneously. For complete details on the use and execution of this protocol, please refer to Gao et al. (2022) .
研究领域:
分子生物学
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生物化学
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细胞生物学
✓ 已验证
DOI
PubMed
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Yuling Dong,Changjian Xie,Beibei Du,Hongliang Liu,Shujing Zhang,Qiuxiang Pang,Desheng Zhang
Sodium benzoate (SB) is a widely used synthetic food preservative with broad-spectrum antimicrobial activity. Although generally recognized as safe at regulated levels, concerns persist regarding its potential toxicity at high concentrations. Our previous study demonstrated that chronic exposure to high-dose SB (2000 ppm) significantly delayed pupation and adult emergence timing while altering gut microbiota composition in Drosophila melanogaster . However, whether these developmental and microbial disruptions will be vertically transmitted to the next generation remains unknown. Therefore, in this study, we investigated the trans-generational effects of SB on F1 offspring development and gut microbiota dynamics. Notably, larval pupation and adult emergence time were significantly delayed in offspring derived from SB-exposed parents (2000 ppm). Strikingly, the gut microbiota dysbiosis observed in parental flies was partially attenuated in the F1 generation. However, F1 offspring exhibited significantly higher Shannon and Simpson diversity indices, suggesting a profound restructuring of the microbial community that may reflect over-compensation or an alternative dysbiotic state rather than complete normalization. Gene expression analysis further revealed that while most SB-induced transcriptional changes were normalized in offspring, four key genes, Yp2 , TOR , E74B and CAT , remained persistently upregulated, indicating sustained trans-generational dysregulation. Collectively, these findings provide novel evidence that SB exposure can induce trans-generational developmental toxicity, potentially mediated by persistent gene dysregulation despite recovery of the gut microbiota. These findings highlight the need for further mechanistic investigations in future work.
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产品关联
DOI
高影响因子
eLife
·
2025
·
IF 0
Pengzhen Dong,Yue Li,Yuying Wang,Qiang Zhao,Tianfeng Lu,Jian Chen,Tianyu Guo,Jun Ma,Bing Yang,Honggang Wu,Hai Huang
Coordinated activation and directional migration of adult stem cells are essential for maintaining tissue homeostasis. Drosophila tracheal progenitors are adult stem cells that migrate posteriorly along the dorsal trunk to replenish degenerating branches that disperse the fibroblast growth factor mitogen. However, it is currently unknown how the overall anterior-to-posterior directionality of such migration is controlled. Here, we show that individual progenitor cells migrate together in a concerted, disciplined manner, a behavior that is dependent on the neighboring fat body. We identify the fat body-derived cytokine, Upd2, in targeting and inducing JAK/STAT signaling in tracheal progenitors to maintain their directional migration. Perturbation of either Upd2 production in fat body or JAK/STAT signaling in trachea causes aberrant bidirectional migration of tracheal progenitors. We show that JAK/STAT signaling promotes the expression of genes involved in planar cell polarity leading to asymmetric localization of Fat in progenitor cells. We provide evidence that Upd2 transport requires Rab5- and Rab7-mediated endocytic sorting and Lbm-dependent vesicle trafficking. Our study thus uncovers an inter-organ communication in the control of disciplined migration of tracheal progenitor cells, a process that requires vesicular trafficking of fat body-derived cytokine Upd2 and JAK/STAT signaling-mediated activation of PCP genes.
✓ 已验证
产品关联
DOI
PubMed
Frontiers in Cell and Developmental Biology
·
2025
·
IF 4.3
Jinhua Yan,Chenxi Feng,Hanmei Zhang,Ting Luo,Haiyang Chen,Haiou Chen
Introduction Intestinal stem cells (ISCs) possess the ability to self-renew and differentiate, which is essential for maintaining intestinal tissue homeostasis. However, their functionality significantly declines with age, leading to diminished tissue regeneration and an increased risk of age-associated diseases. Methods This study investigates the effects of Dapagliflozin (DAPA), a novel insulin sensitizer and SGLT2 inhibitor, on aging ISCs using the Drosophila melanogaster model. Our findings demonstrate that DAPA can inhibit the MAPK signaling pathway, as confirmed by network pharmacology analysis and molecular docking experiments. Results DAPA ameliorates ISC aging, improves intestinal function (including enhanced fecal excretion, restored intestinal barrier integrity and acid-base balance), and enhances healthspan. These results highlight the potential of DAPA as an anti-aging therapeutic agent. Discussion This study provides new evidence for the application of DAPA as an anti-aging treatment.
研究领域:
细胞生物学
·
分子生物学
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药物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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