LIFE SCIENCES
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2025
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IF 5.1
Wenwen Zha,Ziang Wang,Weitao Hu,Chenkai Ge,Wenbin Yuan,Qinyuan Shen,Weirong Li,Wanqing Chen,Jingrong Tang,Zhonghao Xiao,Yunlong Meng,Lirong Huang,Zilin Zhong,Tao-Sheng Li,Jianjun Chen,Zigang Cao
Bexarotene (Bex) is a selective retinoid X receptor (RXR) agonist and is commonly used as an anti-tumor drug in the clinic to treat patients with cutaneous T-cell lymphoma (CTCL). With the widespread use of this drug, people are increasingly concerned about its side effects and safety of use. At present, the effects of bexarotene drugs on the health of organisms remain uncertain, but retinoid drugs are generally biologically active and may pose potential risks to them. Therefore, in this study, we used a zebrafish model to evaluate the effects of Bex on embryonic development. Six hours after fertilization, we exposed zebrafish embryos to 3 μg/L, 6 μg/L, and 9 μg/L bexarotene. At 96 hpf, compared with the control group, zebrafish embryos exposed to bexarotene showed obvious heart and liver development defects, including reduced hatching rate, pericardial enlargement, heart rate disorder, yolk sac edema, small liver area and abnormal photo-optical motor responses. Transcriptome and qPCR results showed abnormal expression of genes related to heart and liver development was induced by Bexarotene. Mechanistically, bexarotene induced a significant upregulation of the transcriptional expression levels of genes related to the Wnt signaling pathway, and IWR-1 was able to effectively rescue the heart and liver developmental defects of zebrafish caused by bexarotene. Therefore, our study showed that bexarotene may cause zebrafish embryonic developmental defects by upregulating the Wnt signaling pathway, revealing the side effects and associated novel mechanisms of bexarotene, and providing a theoretical basis for its safe and effective use in the treatment of clinically related diseases.
研究领域:
发育生物学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Yuanzhao Wu,Ye'anlun Zhu,An Cheng,Weixuan Yao,Binjie Wang,Ruonan Zheng,Jiye Wang
Tefluthrin, a pyrethroid insecticide commonly used in soil, has raised concerns due to its widespread use and residual presence in aquatic environments. Nevertheless, studies on the toxicological mechanisms of tefluthrin at relevant concentrations during the early life stages of aquatic species remain limited. In this study, we assessed the developmental effects of tefluthrin exposure at concentrations of 1, 10, and 100 μg/L over 8 days on zebrafish embryos/larvae. Exposure to 100 μg/L of tefluthrin significantly reduced hatchability and survival rates, leading to cardiac edema and skeletal deformities. Alizarin Red and Alcian Blue staining showed reduced skeletal mineralization and disrupted craniofacial morphology. Importantly, tefluthrin exposure resulted in the dysregulation of important genes involved in heart and skeletal development, including nppa , vmhc , sox9b , gata4 , runx2a , shha , sp7 , and bmp2b . Mechanistically, tefluthrin exposure increased reactive oxygen species (ROS), decreased antioxidant enzyme activities (SOD, CAT), and elevated malondialdehyde (MDA). Furthermore, exposure to tefluthrin caused significant cell apoptosis in larvae, accompanied by dysregulation in the transcriptional expression of apoptotic genes ( bcl2 , bax , p53 , and caspase-3 ). Treatment with the antioxidant astaxanthin alleviated tefluthrin-induced oxidative stress and provided protection against heart and skeletal toxicity. In conclusion, this study demonstrated that tefluthrin's developmental toxicity affected heart and skeletal development, with mechanisms involving changes in gene expression, oxidative stress, and apoptosis, providing valuable insights for assessing environmental and food contamination risks.
研究领域:
毒理学
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环境科学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Oral Science
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2019
·Vol. 11
·期 1
·1-12
·
IF 2.75
Jiang Yuanjing,Zhang Shixian,Mao Chuanqing,Lai Yongzhen,Wu Di,Zhao Hu,Liao Caiyu,Chen Weihui
The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg − 1 or 150 mg•kg − 1 body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg − 1 . Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
研究领域:
发育生物学
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分子生物学
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颅面发育
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Zekun Li,Kun Jia,Xiaomei Chen,Jun Guo,Zhiguo Zheng,Weihua Chen,Yuan Peng,Yuhao Yang,Huiqiang Lu,Jian Yang
Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish ( Danio rerio ) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.
研究领域:
毒理学
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发育生物学
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水生毒理学
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DOI
PubMed
高影响因子
Communications Biology
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2025
·Vol. 8
·期 1
·1-17
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IF 5.1
Wang He,Kang Tianyang,Li Weiwei
Gestational diabetes during pregnancy is associated with an increased risk of developmental abnormalities in offspring, but the underlying mechanisms remain unclear. It is not known how maternal metabolism and gut microbes influence kidney development in the fetus. Here we show that gestational diabetes alters maternal gut microbiota and reduces the production of key fatty acids that normally support kidney development in offspring. We find that these changes impair a molecular pathway involving the receptor GPR43 , which promotes the growth and migration of kidney cells. In a mouse model, restoring short-chain fatty acids or transferring gut bacteria from healthy donors improves kidney development in offspring, while blocking GPR43 reverses this effect. This study reveals a previously unknown link between maternal gut metabolism and fetal kidney formation and may guide future strategies to prevent congenital kidney disorders in children born to mothers with gestational diabetes.
研究领域:
发育生物学
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微生物学
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代谢学
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分子生物学
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肾脏病学
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妇产科学
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DOI
PubMed
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
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2022
·Vol. 40
·期 1
·2200143
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IF 3.467
Mingyue He,Lidong Yu,Xueting Li,Shuang Ma,Ning Gu,Jianbo Jia,Bingsheng Li,Li Li
The possible detrimental effects of nanomaterials on organisms have become a public concern because of the wide applications of nanomaterials in modern society. This study investigates the effects of silica nanoparticles (nano-SiO 2 ) on zebrafish development. Fluorescent nano-SiO 2 (FITC-nano-SiO 2 ) is synthesized with an emission wavelength of 517 nm. Due to similar hydrodynamic size, FITC-nano-SiO 2 is used to simulate the distribution of nano-SiO 2 in zebrafish. Nano-SiO 2 regulated col2a1a , col9a2 , lect1 , and her12 to delay liver development and regulated prox , wnt2bb , mypt1 , and hhex caused spinal curvature. The hand2 , mef2a , nkx2.5 , and atp1a2a are significantly down-regulated. The whole embryo in situ hybridization revealed amhc and flk1 are also down-regulated. This suggests that nano-SiO 2 affected heart and blood vessels development of zebrafish. Furthermore, it is found that cell apoptosis occurred in the heart. The proapoptotic genes ( bax , bid ) are upregulated, and the antiapoptotic genes ( bcl-2 , mcl-1b ) are down-regulated. Nano-SiO 2 increases the endoplasmic reticulum (ER) stress-related genes ( chop , bip , perk, elF2α ), indicating that the ER stress is involved in cell apoptosis. This study provides a toxicological basis for evaluating the possible hazards of nano-SiO 2 to aquatic organisms.
研究领域:
环境毒理学
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分子生物学
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发育生物学
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产品关联
DOI
高影响因子
BIOLOGY OF REPRODUCTION
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2025
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IF 3
Jin Jing,Kou Xinhui,Wang Xinzhe,Yun Xue,Ding Yinyin,Cai Keshu,Zhai Yongning,Zhou Huifang
PurposeTo investigate how steroid receptor RNA activator (SRA) regulates follicular development in mice.MethodsSystemic SRA knockout mice were introduced. SRA expression was reinstated in the anteroventral periventricular nucleus (AVPV) of the hypothalamus using lentiviral vectors. Subsequently, the estrous cycle, serum hormone levels, follicle development, and hypothalamic kisspeptin expression in mice were assessed. Kiss1 promoter activity was tested with a fluorescent reporter system in Neuro-2a cells.ResultsSRA deficiency caused a shift to shorter metestrus and longer diestrus phases, reduced numbers of large antral and preovulatory follicles, increased formation of atretic cyst-like follicles, lowered serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), and decreased expression of hypothalamic AVPV-kisspeptin in mice. The reinstatement of SRA expression in the AVPV nucleus normalized kisspeptin expression, hormone levels, and follicle development. In Neuro-2a cells, SRA increased Kiss1 transcription upon E2 treatment, a response that was nullified by the estrogen receptor alpha (ERα) inhibitor.ConclusionSRA enhances ERα-mediated Kiss1 transcription in the AVPV nucleus to control the kisspeptin-GPR54 system in hypothalamus, essential for regulating ovulation through the hypothalamus-pituitary-ovary axis.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Yiwen Zhou,Lili Chen,Miaomiao Han,Peixiang Zhu,Yanyi Wang,Xuanxuan Yu,Tingyu Reng,Huijuan Wang,Baochao Li,Caixia Zhang,Ziwei Huang,Shuang Lin,Guoyun Wang,Jie Ge,Baosheng Guo,Huang Li
Maxillary underdevelopment is a critical component of skeletal Class III malocclusion, closely linked to altered biomechanical signaling. Mechanical stimulation through early facemask protraction can effectively promote maxillary growth, yet the underlying mechanotransduction mechanisms remain unclear. In this study, fibroblast growth factor 9 (FGF9) is identified as a key biomechanical responder in maxillary development. Secreted predominantly by osteocytes, FGF9 interacts with fibroblast growth factor receptor 2 (FGFR2) on preosteoblasts to inhibit osteogenic differentiation. Mechanical stress reduces FGF9 secretion from osteocytes, thereby relieving its inhibitory effect and enhancing osteogenesis. Mechanistically, FGF9 promotes nuclear translocation of FGFR2 in preosteoblasts, which modulates transcription factors ATF5 and NR2F1 to suppress bone formation. In vivo, targeted overexpression of FGF9 in bone tissue led to significant maxillary growth impairment, underlying the pathological impact of disrupted mechanical signaling. These findings reveal a novel osteocyte–preosteoblast axis regulated by FGF9–FGFR2 signaling in response to mechanical stimulation and provide mechanistic insight into how biomechanical forces shape craniofacial development. This pathway offers new mechanistic insights and potential therapeutic targets for correcting craniofacial skeletal abnormalities.
研究领域:
发育生物学
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分子生物学
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生物力学
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颅面遗传学
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骨生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Min Chen,Tao Liu,Wenqiang Li,Yingting Li,Puxin Zhong,Huanchen Yan,Jingyin Kong,Weixiang Liang
Background Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.Methods A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the “dissolution-regrowth” method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.Results A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.Conclusion The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.
研究领域:
生物医学工程
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纳米技术
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组织工程
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再生医学
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药学
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产品关联
DOI
PubMed
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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2025
·Vol. 122
·期 6
·e2417735122
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IF 9.1
Wangshu Mou,Ria Khare,Joanna K. Polko,Isaiah Taylor,Juan Xu,Dawei Xue,Philip Benfey,Bram Van de Poel,Caren Chang,Joseph J. Kieber
In seed plants, the canonical role of 1-aminocyclopropane-1-carboxylic acid (ACC) is to serve as the precursor in the biosynthesis of the phytohormone ethylene, and indeed, ACC treatment is often used as a proxy for ethylene treatment. Increasing evidence suggests that ACC can also act independently of ethylene to regulate various aspects of plant growth and development. Here, we explore the effects of ACC on Arabidopsis thaliana root growth and the mechanisms by which it acts. ACC inhibits growth of the primary root in Arabidopsis seedlings when ethylene signaling is blocked, which becomes evident after 36 h of treatment with ACC. This reduced root growth is in part the result of suppressed cell proliferation in the root meristem resulting from altered expression of a key regulator of stem cell niche activity, WOX5. ACC also promotes lateral root (LR) development, in contrast to ethylene, which inhibits LR formation. Transcriptomic analysis of roots revealed no significant changes in gene expression after 45 min or 4 h of ACC treatment, but longer treatment times revealed a large number of differentially expressed genes, including the downregulation of the expression of a small group of phylogenetically related CLE peptides. Reduced expression of these group 1 CLEs in response to ACC leads to the activation of a transcription factor, LBD18, which promotes LR development. These results suggest that ACC acts to modulate multiple aspects of Arabidopsis root growth independently of ethylene via distinct transcriptional effects in the root meristem and LR precursor cells.
研究领域:
植物学
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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
Frontiers in Plant Science
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2020
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IF 4.402
Wei Shuai-Jie,Chai Sen,Zhu Rui-Min,Duan Cun-Ying,Zhang Yan,Li Sha
Ovules are female reproductive organs of angiosperms, containing sporophytic integuments and gametophytic embryo sacs. After fertilization, embryo sacs develop into embryos and endosperm whereas integuments into seed coat. Ovule development is regulated by transcription factors (TF) whose expression is often controlled by microRNAs. Mutations of Arabidopsis DICER-LIKE 1 (DCL1), a microRNA processing protein, caused defective ovule development and reduced female fertility. However, it was not clear whether other microRNA processing proteins participate in this process and how defective ovule development influenced female fertility. We report that mutations of HUA ENHANCER1 (HEN1) and HYPONASTIC LEAVES 1 (HYL1) interfered with integument growth. The sporophytic defect caused abnormal embryo sac development and inability of mutant ovules to attract pollen tubes, leading to reduced female fertility. We show that the role of HEN1 in integument growth is cell-autonomous. Although AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8 were ectopically expressed in mutant ovules, consistent with the reduction of microRNA167 in hen1, introducing arf6;arf8 did not suppress ovule defects of hen1, suggesting the involvement of more microRNAs in this process. Results presented indicate that the microRNA processing machinery is critical for ovule development and seed production through multiple microRNAs and their targets.
研究领域:
植物学
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遗传学
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分子生物学
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DOI
PubMed
高影响因子
Animal
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2017
·Vol. 12
·期 3
·491-500
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IF 1.921
Q. Liu,C. Wang,G. Guo,W. J. Huo,Y. L. Zhang,C. X. Pei,S. L. Zhang,H. Wang
Isovalerate supplements could stimulate rumen development by improving morphology and function of rumen mucosa, and then promote the growth of calves. This study was done to evaluate the effects of isovalerate supplements on morphology and functional gene expression of rumen mucosa in dairy calves. In total, 48 Chinese Holstein male calves with 15 days of age and 45.1±0.36 kg of BW were randomly assigned to four groups. The treatments were: control, low-isovalerate, moderate-isovalerate and high-isovalerate with 0, 3, 6 and 9 g isovalerate per calf per day, respectively. Supplementary isovalerate was hand-mixed into milk in pre-weaning calves and into concentrate portion in post-weaning calves. The study consisted of a 15-day-adaptation period and a 60-day-sampling period. Calves were weaned at 60 days of age. Three calves were slaughtered from each of the four treatments at 30, 60 and 90 days of age. The weight of body and stomach were measured, samples of ruminal tissues and blood were analyzed. Total stomach weight, total stomach to BW ratio, rumen wall and keratinized layer thickness, serum growth hormone and IGF-1 for both pre- and post-weaning calves increased linearly with increasing isovalerate supplements. Rumen to total stomach weight ratio, the length and width of rumen papillae, and serum β-hydroxybutyrate increased linearly for post-weaning calves. However, abomasum weight to total stomach weight ratio decreased linearly for both pre- and post-weaning calves. The relative messenger RNA expression for growth hormone receptor, IGF-1 receptor and 3-hydroxy-3-methylglutaryl-CoA synthase 1 in rumen mucosa increased linearly for post-weaning calves. Our results suggested that isovalerate supplements promoted rumen development in a dose-dependent manner. The optimum dose was 6.0 g isovalerate per calf per day.
研究领域:
动物科学
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分子生物学
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DOI
PubMed
高影响因子
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