Nanoscale
·
2019
·Vol. 11
·期 29
·13714-13719
·
IF 6.97
Yuhan Wang,Jie Zhan,Yumiao Chen,Sifan Ai,Liantao Li,Ling Wang,Yang Shi,Junnian Zheng,Zhimou Yang
The selective formation of nanomedicines around cancer cells is very important for cancer therapy because it increases the inhibitory capacity and decreases the systemic toxicity. However, successful examples are rare. Taking advantage of the overexpression of both the enzyme alkaline phosphatase (ALP) and the cell membrane receptor (CCK2R), we demonstrated in this study the selective formation of supramolecular nanofibers and hydrogels in the pericellular space of two cancer cell lines (HeLa and HepG2 cells). Both cell lines showed high expression levels of extracellular ALP and membrane-bound CCK2R. ALP efficiently converted Comp. 1 to a self-assembling molecule (Comp. 2). Comp. 2 interacted with CCK2R, thereby facilitating the self-assembly and formation of hydrogels around the cancer cells. The selective pericellular hydrogelations efficiently inhibited cancer cells. Pericellular hydrogelation around cancer cells is a promising strategy to control the formation of nanomedicines spatiotemporally in cellular microenvironments for cancer therapy and diagnostics.
研究领域:
生物医学
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肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2021
·
IF 4.964
Feifei Wang,Wenqian Cai,Wenzhuo Shi,Haiwen Wu,Qian Shen,Yanan He,Song Cui,Lihui An
The molecular mode of action underpinning the response of mollusks exposure to endocrine disrupting chemicals (EDCs) remains unclear due to a lack of available information regarding their genome. Single molecule real-time (SMRT) sequencing makes it possible to reveal molecular mechanisms by direct sequencing of full-length transcripts. In the present study, the transcriptome profile of the freshwater snail Parafossarulus striatulus after exposure to 17β-estradiol (E2) or 17α-methyltestosterone (MT) was evaluated using SMRT sequencing strategy. In total, 216,598 non-redundant and full-length gene isoforms were generated and 106,266 isoforms were predicted with a complete open reading frame (ORF). Moreover, 60.36% of the isoforms were matched to known proteins in at least one of six databases. Differential gene expression analyses showed significantly different patterns in paired samples with different treatments. The expression levels of several membrane receptor isoforms of P. striatulus including dopamine receptor (DR), FMRFamide receptor (FMRFaR), neuropeptide Y receptor (NYR) and neuropeptide FF receptor (NFFR), but not estrogen receptor (ER) or estrogen-related receptor (ERR), were significantly affected by E2 and MT. These findings suggest that activation of membrane receptors, as well as other signaling pathways, might be critical for mediating the effects of endocrine disruption in mollusks. The transcriptome information obtained from the SMRT sequencing provides a significant contribution to the investigation of the molecular mode of action of endocrine disrupting chemicals on P. striatulus.
研究领域:
生态毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2025
·
IF 42.5
Zhao Yang,Yu-Qi Ping,Ming-Wei Wang,Chao Zhang,Shu-Hua Zhou,Yue-Tong Xi,Kong-Kai Zhu,Wei Ding,Qi-Yue Zhang,Zhi-Chen Song,Ru-Jia Zhao,Zi-Lu He,Meng-Xin Wang,Lei Qi,Christian Ullmann,Albert Ricken,Torsten Schöneberg,Zhen-Ji Gan,Xiao Yu,Peng Xiao,Fan Yi,Ines Liebscher,Jin-Peng Sun
Androgens, such as 5α-dihydrotestosterone (5α-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5α-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5α-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition. Notably, the presence of the “Φ(F/L) 2.64 -F 3.40 -W 6.53 ” and the “F 7.42 ××N/D 7.46 ” motifs, which recognize the hydrophobic steroid core and polar groups, respectively, are common in adhesion GPCRs (aGPCRs), suggesting that many aGPCRs may recognize different steroid hormones. Finally, we exploited in silico screening methods to identify a small molecule, AP503, which activates GPR133 and separates the beneficial muscle-strengthening effects from side effects mediated by AR. Thus, GPR133 represents an androgen membrane receptor that contributes to normal androgen physiology and has important therapeutic potentials.
研究领域:
药理学
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分子生物学
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结构生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2016
·
IF 5.218
Dong Yuhao,Liu Jin,Pang Maoda,Du Hechao,Wang Nannan,Awan Furqan,Lu Chengping,Liu Yongjie
The growth-stimulating effects of catecholamine stress hormones have been demonstrated in many pathogens. However, catecholamine-induced growth and its underlying mechanisms remain poorly understood in Aeromonas hydrophila. The present study sought to demonstrate that norepinephrine (NE), epinephrine (Epi), dopamine (Dopa), and L-dopa stimulate the growth of A. hydrophila in iron-restricted media containing serum. NE exhibited the strongest growth stimulation, which could be blocked by adrenergic antagonists. Furthermore, it was demonstrated that NE could sequester iron from transferrin, thereby providing a more accessible iron source for utilization by A. hydrophila. The deletion of the amoA gene associated with amonabactin synthesis revealed that the amonabactin siderophore is not required for NE-stimulated growth. However, the deletion of the TonB2 energy transduction system resulted in the loss of growth promotion by NE, indicating that a specific TonB-dependent outer membrane receptor might be involved in the transport of iron from transferrin. Collectively, our data show that catecholamine sensing promotes the growth of A. hydrophila in a manner that is dependent on the TonB2 energy transduction system.
研究领域:
微生物学
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分子生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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