Toxics
·
2023
·Vol. 11
·期 4
·328
·
IF 4.6
Xiangqin Zheng,Yuexin Wei,Jiadong Chen,Xia Wang,Dinggang Li,Chengjun Yu,Yifan Hong,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.Keywords:difenoconazole;reproductive toxicity;testis;retinoic acid signaling;GC-2 cell;apoptosis
研究领域:
毒理学
·
生殖生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
SAUDI PHARMACEUTICAL JOURNAL
·
2016
·
IF 2.233
Jinpu Peng,Lianju Shen,Jinjun Chen,Xining Cao,Yue Zhou,Huali Weng,Chunlan Long,Deying Zhang,Shengfen Tu,Yan Zhang,Dawei He,Tao Lin,Guanghui Wei
This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group ( n = 10) and normal control group ( n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder.
研究领域:
生殖生物学
·
内分泌学
·
组织病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 5
·3364-3370
·
IF 3.9
Yuying Jiang,Yifeng E,Pengyan Wei,Jia Wang,Peng Chen,Lei Wang,Thomas F. Krenzel,Kun Qian,Xiyuan Tong
An electrochemical method based on a Linde Type-A zeolite-modified glass carbon electrode (LTA/GCE) was introduced for the determination of retinoic acid (RA). LTA zeolite could be synthesized through a hydrothermal method and served as a commercial electrochemical sensor with high stability and sensitivity in electrochemical progress. The as-synthesized product was characterized by scanning electron microscopy (SEM), differential thermal analysis (DTA), X-ray powder diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Under optimal conditions, a detection limit of 0.8 μM was obtained for RA with a linear range of 0.8–20.1 μM. This electrochemical method for determining RA was simpler and cheaper than previously reported methods. Furthermore, the modified electrode could be applied to the detection of RA in tap water, achieving a linear range of 1.4–15.0 μM with a detection limit of 1.4 μM and good recovery. The modified electrode designed by this method provided good selectivity, stability, and reproducibility for RA determination and reliable application for the analysis of RA in environmental water.
研究领域:
环境科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2013
·Vol. 51
·期 18
·3932-3940
·
IF 3.543
Wei Lu,Meng-Ling Lu,Qing-Peng Zhang,Yong-Qing Tian,Zhi-Xiang Zhang,Han-Hong Xu
Environment-friendly and controlled release formulation is highly promising for reducing environmental pollution and achieving the most effective utilization of pesticides. As a novel “green” nanocarrier of pesticides, amphiphilic self-assembled nanoparticles were prepared by chemical conjugation of octahydrogenated retinoic acid (OR) to the backbone of glycol chitosan (GC). In aqueous media, the synthesized OR-GC conjugates formed nanosized particles with a diameter of 257 nm. Hydrophobic azadirachtin (AZA) was efficiently loaded into the OR-GC nanoparticles at a feed weight ratio of up to 1:4 using a simple dialysis method, the maximum drug-loading efficiency of which was 74%. AZA-OR-GC (25 wt %) nanoparticles also showed sustained release of the incorporated AZA (65% of the loaded dose was released in 7 days at 27 °C in phosphate-buffered saline; pH 7.2). Cytotoxicity tests and cell cycle arrest assays confirmed that OR-GC exhibits good biocompatibility; AZA-OR-GC (25 wt %) nanoparticles also showed favorable inhibition of cell proliferation in Sl-1 cells compared with free AZA in organic solvents. Overall, controlled release AZA-OR-GC may be a promising environment-friendly formulation for integrated pest management. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51 , 3932–3940
研究领域:
农药科学
·
生物材料
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
CELL RESEARCH
·
2017
·Vol. 28
·期 1
·48-68
·
IF 15.606
Xu Xingxing,Li Chuanyin,Gao Xiaobo,Xia Kun,Guo Hui,Li Yali,Hao Zijian,Zhang Lei,Gao Daming,Xu Chenfan,Xu Huatai,Xiong Zhi-Qi,Qiu Zilong,Mei Ling,Xie Xiaoduo,Ruan Kangcheng,Hu Ronggui
The autism spectrum disorders (ASDs) are a collection of human neurological disorders with heterogeneous etiologies. Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner. Excessive UBE3A dosage was found to impair RA-mediated neuronal homeostatic synaptic plasticity. ASD-like symptoms were recapitulated in mice by overexpressing UBE3A in the prefrontal cortex or by administration of an ALDH1A antagonist, whereas RA supplements significantly alleviated excessive UBE3A dosage-induced ASD-like phenotypes. By identifying reduced RA signaling as an underlying mechanism in ASD phenotypes linked to UBE3A hyperactivities, our findings introduce a new vista of ASD etiology and facilitate a mode of therapeutic development against this increasingly prevalent disease.
研究领域:
神经科学
·
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Ying Zou,Chaoxian Chi,Fangling Wu,Chuan-Fan Ding
Retinoic acid (RA) regulates cell proliferation, differentiation, and apoptosis and exists in three primary isomers: all-trans-RA (ATRA), 9-cis-RA (9cRA), and 13-cis-RA (13cRA). RA derivatives, such as bexarotene (BT) and arotinoid acid (TTNPB), are used to treat cutaneous T-cell lymphoma and induce cellular pluripotency. Due to their distinct biological activities, accurate identification and analysis of these isomers are crucial. This study developed a rapid and efficient method for analyzing RA isomers and their derivatives using ion mobility mass spectrometry (IM-MS) and theoretical calculations. RA isomers and derivatives exhibit overlapping mobilities and cannot be separated by direct IM-MS. By forming ternary complexes with β-cyclodextrin (β-CD) and metal ions, baseline separation was achieved with a peak resolution (R p-p ) of up to 3.42. Tandem MS and theoretical calculations revealed distinct differences in interactions, spatial structures, and binding energies, enabling mobility-based separation. Photostability tests showed rapid photoisomerization of 13cRA into 9cRA and ATRA within seconds. Analysis of 13cRA soft capsules from four brands demonstrated good stability, with measured content aligning closely with labeled values. This method offers a new approach for accurate RA isomer analysis, with potential applications in pharmaceuticals and food industries.
研究领域:
生物化学
·
药物化学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
NATURE GENETICS
·
2016
·Vol. 49
·期 1
·119-124
·
IF 31.616
Shao Changwei,Bao Baolong,Xie Zhiyuan,Chen Xinye,Li Bo,Jia Xiaodong,Yao Qiulin,Ortí Guillermo,Li Wenhui,Li Xihong,Hamre Kristin,Xu Juan,Wang Lei,Chen Fangyuan,Tian Yongsheng,Schreiber Alex M,Wang Na,Wei Fen,Zhang Jilin,Dong Zhongdian,Gao Lei,Gai Junwei,Sakamoto Takashi,Mo Sudong,Chen Wenjun,Shi Qiong,Li Hui,Xiu Yunji,Li Yangzhen,Xu Wenteng,Shi Zhiyi,Zhang Guojie,Power Deborah M,Wang Qingyin,Schartl Manfred,Chen Songlin
Flatfish have the most extreme asymmetric body morphology of vertebrates. During metamorphosis, one eye migrates to the contralateral side of the skull, and this migration is accompanied by extensive craniofacial transformations and simultaneous development of lopsided body pigmentation1,2,3,4,5. The evolution of this developmental and physiological innovation remains enigmatic. Comparative genomics of two flatfish and transcriptomic analyses during metamorphosis point to a role for thyroid hormone and retinoic acid signaling, as well as phototransduction pathways. We demonstrate that retinoic acid is critical in establishing asymmetric pigmentation and, via cross-talk with thyroid hormones, in modulating eye migration. The unexpected expression of the visual opsins from the phototransduction pathway in the skin translates illumination differences and generates retinoic acid gradients that underlie the generation of asymmetry. Identifying the genetic underpinning of this unique developmental process answers long-standing questions about the evolutionary origin of asymmetry, but it also provides insight into the mechanisms that control body shape in vertebrates.
研究领域:
遗传学
·
发育生物学
·
比较基因组学
✓ 已验证
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Tingting Luo,Jingtian Han,Feng Zhao,Xiaohong Pan,Baocheng Tian,Xiujuan Ding,Jing Zhang
Novel chitosan-cystamine-retinoic acid conjugate (CS-SS-RA) was synthesized and could self-assemble into redox-sensitive micelles in aqueous environment with low critical micelle concentration value. CS-SS-RA micelles were characterized with spherical shape, desirable particle size, negative zeta potential, high paclitaxel (PTX) loading and encapsulation efficiency and redox-sensitivity. Hemolysis and cytotoxicity studies proved the safety of CS-SS-RA micelles for intravenous administration. Cytotoxicity study against HepG2 cells and the growth inhibition study on three-dimensional multicellular tumor spheroids (MCTSs) revealed that PTX-loaded CS-SS-RA micelles exhibited higher antitumor activity than free PTX. The in vitro cellular uptake profiles of FITC-labeled CS-SS-RA micelles evaluated via confocal laser scanning microscopy and flow cytometry indicated that CS-SS-RA micelles could enhance cellular uptake efficiency of PTX, and their internalization by HepG2 cells were mediated by clathrin-mediated endocytosis and macropinocytosis. These results demonstrated that CS-SS-RA micelles could be developed as a promising platform for intracellular delivery of hydrophobic antitumor agents.
研究领域:
药剂学
·
肿瘤学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2022
·Vol. 29
·期 13
·19890-19897
·
IF 5.19
Zhao Anran,Miao Jingjing,Liu Liru,Pan Luqing
Retinoid X receptor (RXR) has been found to be a major target in various processes of endocrine disruption from the exposure to organotin compounds (OTCs), including imposex in gastropod mollusks. It was also reported in bivalves that OTCs caused intersex and skewed sex ratio. In order to evaluate the effect of these ligand-like OTCs, we constructed a reconstituted yeast system (CfRE system) based on GAL4 yeast two-hybrid principle using scallop Chlamys farreri retinoid X receptor ( Cf RXR a ) and retinoid X response element (RXRE) to investigate the ligand-induced transactivation of Cf RXR a . Responses of Cf RXR a to 9-cis retinoic acid (9cRA) and tested four OTCs showed concentration-dependent response which is comparable with reported RXRa in vitro assay of human and gastropods. The detective limits of the CfRE system were found to be 100 nM for 9cRA and 10–1000 nM for the tested OTCs. While the tested non-Sn endocrine disrupting chemicals, including Benzo[a]pyrene, 2,4-Dichlorophenol, Nonylphenol, and Tetrabromobisphenol A, showed no effect on Cf RXR a response. The present assay system may provide a valuable tool for screening assessments of unidentified environmental ligand chemicals on bivalve mollusks. It is also useful for comparison of sensitivity differences among species exposed to EDCs.
研究领域:
分子生物学
·
环境科学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 9
·2311
·
IF 5.4
Yongjie Bao,Wenni Rong,An Zhu,Yuan Chen,Huiyue Chen,Yirui Hong,Jingyang Le,Qiyao Wang,C. Benjamin Naman,Zhipeng Xu,Lin Liu,Wei Cui,Xiang Wu
Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterizing by cognitive impairments in the elderly after surgery. There is limited effective treatment available or clear pathological mechanisms known for this syndrome. In this study, a Connectivity Map (CMap) bioinformatics model of POCD was established by using differently expressed landmark genes in the serum samples of POCD and non-POCD patients from the only human transcriptome study. The predictability and reliability of this model were further supported by the positive CMap scores of known POCD inducers and the negative CMap scores of anti-POCD drug candidates. Most retinoic acid receptor (RAR) agonists were negatively associated with POCD in this CMap model, suggesting that RAR might be a novel target for POCD. Most importantly, acitretin, a clinically used RAR agonist, significantly inhibited surgery-induced cognitive impairments and prevented the reduction in RARα and RARα-target genes in the hippocampal regions of aged mice. The study denotes a reliable CMap bioinformatics model of POCD for future use and establishes that RAR is a novel therapeutic target for treating this clinical syndrome.Keywords:bioinformatics model;retinoic acid receptor;connectivity map;postoperative cognitive dysfunction;acitretin
研究领域:
神经科学
·
药理学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
·
2022
·
IF 4.772
Liqin Yang,Zhixiong Xia,Jianhua Feng,Menghuan Zhang,Pu Miao,Yingjie Nie,Xiangyan Zhang,Zijian Hao,Ronggui Hu
Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.
研究领域:
神经科学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 6
·2372-2382
·
IF 5.251
Kong-Jun Lu,Wei Wang,Xiao-Ling Xu,Fei-Yang Jin,Jing Qi,Xiao-Juan Wang,Xu-Qi Kang,Meng-Lu Zhu,Qiao-Ling Huang,Chao-Heng Yu,Jian You,Yong-Zhong Du
An ointment containing retinoic acid deformable liposomes (TRA DLs) and epidermal growth factor cationic deformable liposomes (EGF CDLs) was prepared for the treatment of deep partial-thickness burns. The characterization tests confirmed both liposomes featured small particle sizes, high drug entrapment efficiencies and sustained drug release behavior. Compared with the free drug, TRA DLs and EGF CDLs exhibited superior skin permeation and remarkably increased drug deposition by 2.9 and 18.8 folds, respectively. Results on HaCaT cells indicated the combined application of two liposomes exerted a synergistic effect and prominently promoted cell proliferation and migration. Application of the dual liposomal ointment on a deep partial-thickness burn model stimulated wound closure (p < 0.001), promoted skin appendage formation and increased collagen production, thus improving healing quality. Finally, it was demonstrated that TRA significantly up-regulated the expression of EGFR and HB-EGF to enhance the therapeutic effect of EGF. Therefore, the dual liposomal ointment is a promising topical therapeutic for burn treatment.
研究领域:
药剂学
·
伤口愈合
·
药物递送系统
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）