COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2022
·
IF 4.52
Long Zhu,Mingrong Wang,Shuo Fu,Kaiqi Li,Jialin Liu,Zaizhao Wang
Bisphenol A (BPA) is a widely used endocrine disruptor , which has attracted much attention due to its harmful effects on male reproduction. To investigate the interference of BPA on steroid synthesis in males, male rare minnows ( Gobiocypris rarus ) were exposed to 15 μg L −1 BPA for 7, 14 and 21 d. Meanwhile, a positive control group was performed with 25 ng L −1 17α-ethynyl estradiol (EE2). Results showed that BPA exposure induced lower testosterone (T) levels, while affecting the transcripts of steroidogenic gene StAR . Moreover, BPA induced abnormal germ cells proliferation in the testis in rare minnow. Transcriptome analysis showed that 354 transcripts significantly differentially expressed after BPA exposure for 14 d, several of them were enriched in the signaling pathways of cell cycle process, PPAR signaling pathway, the steroid synthesis pathway and estrogen signaling pathway. BPA significantly increased estrogen receptor (ER) levels and induced abnormal protein levels of PPARγ. BPA disrupted the StAR expression by interfering ER enrichments within StAR 5′ flanking region . Additionally, our study also revealed that BPA and EE2 might have different mechanisms for interfering with steroid hormone levels and germ cells proliferation in the testis.
研究领域:
环境科学
·
内分泌学
·
分子生物学
·
生殖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xue Yang,Fang Gao,Wenan Zhang,Huipeng Li,Xinzhi Huang,Jiajia Wei,Jiayi Bian,Ying Yang,Chenggen Qian,Minjie Sun
Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer. Here, we proposed to achieve migration chain-treatment for metastatic tumors by introducing a cell adhesion molecules CD44 inhibitor (Star miR-34a) to deprive of cell migration capability on the basis of CXCR4 antagonism (cyclam monomer , CM). Dextrin modified 1.8 k PEI with CM-end was prepared to deliver therapeutic miR-34a (named DPC/miR-34a) for efficient anti-metastasis by downregulating adhesion protein CD44 and targeting the CXCR4/SDF-1 axis. Additionally, reduced expression of the anti-apoptotic protein Bcl2 caused by miR-34a could enhance the anti-tumor efficacy of DPC/miR-34a nanoplex administration. Compared with inhibition of the CXCR4/SDF-1 axis or CD44 expression, the multidimensional therapy (DPC/miR-34a) exhibited considerable suppression of cancer cell invasion as assessed by an in vitro cell invasion assay and in vivo anti-metastasis model. Moreover, DPC/miR-34a demonstrated a superior antitumor and anti-metastatic efficacy both in lung metastatic model and orthotopic MDA-MB-231 tumor models, thus providing an efficient approach for combating metastatic tumors.
研究领域:
肿瘤学
·
分子生物学
·
药学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Veterinary Sciences
·
2025
·Vol. 12
·期 5
·428
·
IF 2.3
Yanbing Lou,Tingting Yang,Chenglong Xia,Shijun Yang,Huidan Deng,Yanqiu Zhu,Jing Fang,Zhicai Zuo,Hongrui Guo
Simple SummaryYak, as a unique species of plateau cattle, is highly susceptible to Cu deficiency, which is further exacerbated by poor soil conditions and low nutrient content in yak feed, which is associated with the decline of yak performance. Hormones synthesized by granulosa cells of yak follicles play an indispensable role in reproductive function. In this study, we investigated the effects of different concentrations of copper on the hormone secretion of cultured granulosa cells of yak follicles and the related molecular mechanisms. The above results showed that copper could positively promote the hormone secretion of female yaks, which provided a strategy direction with potential value for improving the fertility of yaks under the condition of copper deficiency.Yak (Bos grunniens) is the main economic animal growing in the Qinghai–Tibet Plateau. Because of its poor growing environment, copper deficiency is common. Studies have shown that appropriate copper supplementation can improve the reproductive performance of heifers. In this study, the primary granulosa cells of yak were isolated, and different copper levels were established by adding copper chelator and copper sulfate. Biochemical, Western blot and transcriptome methods were used to reveal the mechanism of copper on the hormone secretion function of granulosa cells. The results showed that copper promoted hormone secretion by regulating the expression of steroid synthase such as StAR, CYP19A1 and CYP11A1. Transcriptome analysis showed that copper ion levels significantly affected the function of cells, and changes in copper ion level affected genes related to protein phosphorylation, lipid metabolism, lipid biosynthesis, steroid hormone synthesis and the MAPK pathway. In conclusion, copper can promote steroid hormone synthesis in the granulosa cells of yak follicles, and the MAPK signaling pathway may be involved.
研究领域:
动物科学
·
生殖生物学
·
分子生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2022
·
IF 4.46
Xiu Xin,Haiqiong Chen,Fuhong Tian,Jingjing Li,Haoni Yan,Yige Yu,Feifei Ma,Huitao Li,Yiyan Wang,Xiaoheng Li,Yang Zhu,Ren-shan Ge
Perfluoroundecanoic acid (PFUnA), a perfluorinated compound , has environmental persistence, bioaccumulation , and potential toxicity. However, its effect on Leydig cell function remains unclear. Rats (age of 56 days) were gavaged with 0 (corn oil), 0.1, 0.5, 1, or 5 mg/kg/day PFUnA for 28 days. PFUnA significantly reduced serum testosterone levels as low as 0.5 mg/kg. PFUnA markedly decreased Leydig cell number as low as 0.1 mg/kg. PFUnA markedly reduced transcript levels of Star and Insl3 in the testes at 1 mg/kg after adjusting to Leydig cell number. It also reduced their protein levels. PFUnA significantly decreased the phosphorylation of AKT1 and mTOR as low as 0.1 mg/kg and the phosphorylation of ERK1/2 at 1 mg/kg and the phosphorylation of AKT1, AKT2, ERK1/2, and mTOR in Leydig cells at various concentrations (0.01–10 μM) after 24 h of in vitro treatment. In conclusion, PFUnA inhibits Leydig cell function possibly via AKT/ERK1/2/mTOR signaling pathways.
研究领域:
毒理学
·
内分泌学
·
生殖生物学
✓ 已验证
DOI
PubMed
高影响因子
PROGRESS IN ORGANIC COATINGS
·
2016
·
IF 2.632
Qiang Ren,Jun Chen,Fuqiang Chu,Jian Li,Qiang Yu,Dun Wu,Jianbo Fang
A kind of novel nanocoating based on star polymers and graphene was developed. The hydroxyl functionalized star polymers were synthesized by Activators Regenerated by Electron Transfer Atom Transfer Radical Polymerization (ARGET ATRP) using core-first approach. The branching behavior, copolymer composition and glass transition temperature was characterized clearly. Graphene/star polymer coating shows lower conductive percolation threshold values relative to linear analog. Transmission electronic microscopy verified the better dispersion of graphene sheet in star polymer matrix than linear polymer matrix. Rheological tests revealed that the increase of viscosity of star polymer solution aroused by addition of graphene was much weaker compared to that of linear counterpart. Star polymer based coating exhibit very short tack-free time and superior impact resistance. All the results demonstrate that star polymer is a good candidate to fabricate graphene filled nanocoating with advantages in performance as well as processing.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOLOGY OF REPRODUCTION
·
2025
·
IF 3
Liao Shiying,Cheng Jinhua,Zhao Weimin,Dai Chaohui,Fu Yanfeng,Li Bixia,Deng Yanfei,Li Hui
Kynurenine (KYN) is a primary tryptophan derivative found in the human body and fermented foods. Previous studies have shown that KYN is an Aryl hydrocarbon receptor (AHR) agonist and is important in regulating various physiological activities, including female reproduction. Progesterone is a vital steroid hormone that facilitates embryo implantation and maintains pregnancy. However, whether KYN affects its biosynthesis remains unclear. To gain understanding, in vitro luteinized porcine granulosa luteal (pGL) cells were treated with KYN. The results showed that KYN disrupted progesterone biosynthesis by decreasing the expression of STAR and HSD3B in pGL cells. In addition, the expression of three transcription factors of STAR and HSD3B (GATA4, GATA6, and CEBPB) decreased after KYN treatment. Furthermore, the AHR blockade results showed comparable to those of KYN treatment, and subsequent knockdown experiments confirmed these results. These findings suggest that KYN inhibits progesterone biosynthesis in pGL cells by downregulating GATA4, GATA6, and CEBPB expression through AHR. Thus, our results showed for the first time, a previously unknown connection between KYN and progesterone biosynthesis.
研究领域:
生殖生物学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANIMAL REPRODUCTION SCIENCE
·
2023
·
IF 2.2
Wenjiao Liu,Ting Gong,Yongjian Xu
Testosterone is a key crucial hormone synthesized by steroidogenic enzymes that initiate and maintain spermatogenesis and secondary sexual characteristics in adult males. The taste receptor family 1 subunit 3 (T1R3) is reported to be associated with male reproduction. T1R3 can regulate the expressions of steroidogenic enzymes and affect testosterone synthesis . In this study, we addressed the question of whether the expression of steroid synthase was associated with T1R3 and its downstream-tasting molecules during testicular development . The results showed an overall upward trend in testosterone and morphological development in testes from Congjiang Xiang pigs from pre-puberty to sexual maturity. Gene expression levels of testicular steroidogenic acute regulatory protein ( StAR ), 3β-hydroxysteroid dehydrogenase ( 3β-HSD ), cytochrome P450c17 ( CYP17A1 ) and 17β-hydroxysteroid dehydrogenase ( 17β-HSD ) were increased from pre-puberty to sexual maturity. Protein expression changes of CYP17A1 and 3β-HSD were consistent with mRNA. The relative abundance of tasting molecules ( TAS1R3 , phospholipase Cβ2, PLCβ2 ) was increased from pre-puberty to puberty ( P < 0.05), with no further significant changes in expression from puberty to sexual maturity. Steroidogenic enzymes (3β-HSD and CYP17A1) were strongly detected in Leydig cells from pre-puberty to sexual maturity, while tasting molecules were localized in Leydig cells and spermatogenic cells. Correlation analysis showed that the genes mentioned above (except for PLCβ2 ) were positively correlated with testosterone levels and morphological characteristics of the testes at different developmental stages of Congjiang Xiang pigs. These results suggest that steroidogenic enzymes regulate testosterone synthesis and testicular development, and that taste receptor T1R3, but not PLCβ2, may associate with this process.
研究领域:
生殖生物学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 3
·440-448
·
IF 0
Weifeng Lin,Guanglong Ma,Fangqin Ji,Juan Zhang,Longgang Wang,Haotian Sun,Shengfu Chen
Polyethylene glycol (PEG) is considered to be the most effective material to prolong the circulation time of nanoparticles by reducing non-specific protein adsorption in blood. However, it is recognized that PEG decomposes in most physiological solutions, and an anti-PEG antibody has been detected in some normal blood donors as a response to injection with PEGylated polymer particles. Zwitterionic polymers are potential alternatives to PEG for biomedical applications because of their super resistance to non-specific protein adsorption. Thus, finding one polymer with a long circulation time and resistance to the immune response is of significant importance. Here, we prepared four star carboxybetaine polymers of different molecular weights via atom transfer radical polymerization (ATRP) from a β-cyclodextrin (β-CD) initiator for investigating the biocompatibility of carboxybetaine polymer, a typical zwitterionic polymer. The circulation half-life of the largest star polymer (123 kDa) in mice was prolonged to 40 h in vivo, with no appreciable damage or inflammation observed in the major organ tissues. Furthermore, the circulation time of repeat injections showed similar results to the first injection, with no obvious increase in the amount of antibody in blood. The internalization of the star carboxybetaine polymers by macrophage cells was a relatively slow process. The high cell viability in the presence of star carboxybetaine polymers up to 2 mg mL−1 was maintained. The hemolytic activity of the star carboxybetaine polymers at 5 mg mL−1 was almost undetectable. In vitro results prove a key prediction of excellent biocompatibility in vivo. All the results suggest that the carboxybetaine polymer, perhaps even most of the zwitterionic ones, might be a good alternative to PEG in the development of a drug delivery system.
研究领域:
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
Polymer Chemistry
·
2018
·Vol. 9
·期 24
·3347-3354
·
IF 4.927
Xinzhi Liu,Hui Niu,Yang Li,Jin-Yong Dong
This study demonstrates an efficient arm-first approach for the synthesis of star isotactic polypropylene (iPP) via two steps. In the first step iPP “arm” containing a methoxysilane-terminal end was prepared via a designed chain-capping reaction in propylene polymerization, and in the second step an acid-catalyzed intermolecular elimination reaction was carried out between methoxysilane groups at these “arm-ends”, finally giving star polymers with iPP as the arm and Si–O–Si cross-linking structure as the core. Moreover, the arm number could be tailored from 3 to 8 by adjusting the star-forming (cross-linking) reaction time. The chemical structures of “arm” and star polymers were monitored by 1H-NMR, and the star-topological structure evolution was investigated via gel permeation chromatography incorporating a light scattering detector (GPC-LS). The star polymers’ absolute molecular weights as well as their dilute solution properties including the intrinsic viscosity ([η]) and the Mark–Houwink exponent (α) were determined by GPC-LS, confirming the successful synthesis of star iPPs.
研究领域:
高分子化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2015
·Vol. 6
·期 8
·6368-6377
·
IF 3.84
Wenlong Wang,Liang Zhang,Mengtao Liu,Yuan Le,Shanshan Lv,Jiexin Wang,Jian-Feng Chen
Core cross-linked star-shaped polypeptides based on poly(L-glutamic acid)-poly(L-phenylalanine-co-L-cystine) copolymer have been successfully synthesized and thoroughly characterized. The star polypeptides can self-assemble to form 50 nm micelles in aqueous medium, which respond rapidly to both pH change within the physiologically relevant pH range and a reduction environment mimicking the intracellular space. Water-soluble doxorubicin hydrochloride and hydrophobic resveratrol are loaded into the star polypeptides micelles through electrostatic and hydrophobic interactions respectively. The drug loading content can be controlled by tuning the composition of the star polypeptides. The in vitro release studies indicate dual sensitivity enabled rapid drug release at pH 5.5 and 10 mM dithiothreitol (DTT), mimicking the intracellular environment. Furthermore, the star polypeptides are biocompatible and interact well with cells in vitro. Confocal fluorescence microscopy and flow cytometry assays show these star polypeptides can be quickly internalized and effectively deliver the drugs into HeLa cells to inhibit cell growth.
研究领域:
生物材料
·
药物递送系统
·
高分子化学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Ling-Zi Xia,Li-Lan Liu,Jun-Zhe Yue,Zhen-Yu Lu,Jie Zheng,Ming-Zhe Jiang,Min Lin,Jiaming Liu,Hai-Tao Gao
Phthalates (PEs) are widely used plasticizers in polymer products, and humans are increasingly exposed to them. This study was designed to investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by the mixture of three commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty-eight male SD rats were randomly and evenly divided into control group, Que group, MPEs group and MPEs+Que group ( n = 12); The oral exposure doses of MPEs and Que were 450 mg/kg/d and 50 mg/kg/d, respectively. After 91 days of continuous intervention, compared with control group, the testes weight, epididymis weight, serum sex hormones, and anogenital distance were significantly decreased in MPEs group ( P < 0.05); Testicular histopathological observation showed that all seminiferous tubules were atrophy, leydig cells were hyperplasia, spermatogenic cells growth were arrested in MPEs group. Ultrastructural observation of testicular germ cells showed that the edges of the nuclear membranes were indistinct, and the mitochondria were severely damaged with the cristae disrupted, decreased or even disappeared in MPEs group. Immunohistochemistry and Western blot analysis showed that testicular CYP11A1, CYP17A1 and 17β-HSD were up-regulated, while StAR, PIWIL1 and PIWIL2 were down-regulated in MPEs group ( P < 0.05); However, the alterations of these parameters were restored in MPEs+Que group. The results indicated MPEs disturbed steroid hormone metabolism, and caused male reproductive injuries; whereas, Que could inhibit MPEs’ male reproductive toxicity, which might relate to the restored regulation of steroid hormone metabolism.
研究领域:
毒理学
·
药理学
·
生殖生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2024
·
IF 27.7
Rui Li,Yan Li,Kun Jiang,Lijuan Zhang,Ting Li,Aihua Zhao,Zhuo Zhang,Yale Xia,Kun Ge,Yaqiong Chen,Chengnuo Wang,Weitao Tang,Shuning Liu,Xiaoxi Lin,Yuqin Song,Jie Mei,Chun Xiao,Aoxue Wang,Yejun Zou,Xie Li,Xianjun Chen,Zhenyu Ju,Wei Jia,Joseph Loscalzo,Yu Sun,Wei Fang,Yi Yang,Yuzheng Zhao
Arginine is one of the most metabolically versatile amino acids and plays pivotal roles in diverse biological and pathological processes; however, sensitive tracking of arginine dynamics in situ remains technically challenging. Here, we engineer high-performance fluorescent biosensors, denoted sensitive to arginine (STAR), to illuminate arginine metabolism in cells, mice, and clinical samples. Utilizing STAR, we demonstrate the effects of different amino acids in regulating intra- and extracellular arginine levels. STAR enabled live-cell monitoring of arginine fluctuations during macrophage activation, phagocytosis, efferocytosis, and senescence and revealed cellular senescence depending on arginine availability. Moreover, a simple and fast assay based on STAR revealed that serum arginine levels tended to increase with age, and the elevated serum arginine level is a potential indicator for discriminating the progression and severity of vitiligo. Collectively, our study provides important insights into the metabolic and functional roles of arginine, as well as its potential in diagnostic and therapeutic applications.
研究领域:
细胞生物学
·
分子生物学
·
病理学
·
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）