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| 1 | Identification of an endogenous glutamatergic transmitter system controlling excitability and conductivity of atrial cardiomyocytes显示文摘As an excitatory transmitter system,the glutamatergic transmitter system controls excitability and conductivity of neurons.Since both cardiomyocytes and neurons are excitable cells,we hypothesized that cardiomyocytes may also be regulated by a similar system. | Duanyang Xie Ke Xiong Xuling Su Guanghua Wang Qiang Ji Qicheng Zou Lingling Wang Yi Liu Dandan Liang Jinfeng Xue Luxin Wang Xueting Gao Xingdong Gu Hongyu Liu r Xiaoyu He Li Li Jian Yang Youming Lu Luying Peng Yi-Han Chen | 2021 | Cell Research2021，31，9： | 5 |
| 2 | Effects of complement inhibition on the ABC phenomenon in rats显示文摘Researchers reported that intravenously injected PEGylated colloidal drug carriers lose their long-circulating characteristic and accumulated extensively in liver when they are administrated twice in the same animal with certain intervals. This phenomenon was referred to as the 'accelerated blood clearance(ABC) phenomenon'. Some former studies had found that complement-mediated phagocytosis, activated by antigen–antibody complex, was responsible for inducing the phenomenon. According to the theory, we have used cobra venom factor to deplete complement in vivo and to investigate the effect of complement inhibition on the ABC phenomenon. Rats were administered by injection of cobra venom factor solution to build up the model of complement exhaustion/inhibition, and the effect of the inhibition of complement on ABC phenomenon was carried out. It seemed that inhibition of complement didn’t affect the pharmacokinetic of the first infection. By contrast, in rats of which complement had been depleted, the second dose of PEGylated nanoemulsions showed enhanced circulation time compared with normal rats in a complement inhibition-independent manner, but the ABC phenomenon was not completely eliminated. It indicated that complement inhibition could certainly weaken the accelerated clearance;meanwhile, there were other factors causing the ABC effect.These findings provide novel insights into the attenuating of ABC phenomenon and lay foundation for further study of immune mechanism. | Lirong Wang Yuqing Su Xuling Wang Kaifan Liang Mengyang Liu Wenya Tang Yanzhi Song Xinrong Liu Yihui Deng | 2017 | Asian Journal of Pharmaceutical Sciences2017，12，3： | 2 |
| 3 | Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons显示文摘Activation of the heart normally begins in the sinoatrial node(SAN).Electrical impulses spontaneously released by SAN pacemaker cells(SANPCs)trigger the contraction of the heart.However,the cellular nature of SANPCs remains controversial.Here,we report that SANPCs exhibit glutamatergic neuron-like properties.By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse,we found that SANPCs co-clustered with cortical neurons.Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system,expressing genes encoding glutamate synthesis pathway(G/s),ionotropic and metabotropic glutamate receptors(Grina,Gria3,Grm1 and Grm5)t and glutamate transporters(Slc17a7).SANPCs highly expressed cell markers of glutamatergic neurons(Snap25 and S/-c17a7)t whereas Gad1,a marker of GABAergic neurons,was negative.Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca2+transients frequency in single SANPC.Collectively,our work suggests that SANPCs share dominant biological properties with glutamatergic neurons,and the glutamatergic neurotransmitter system may act as an intrinsic regulation module of heart rhythm,which provides a potential intervention target for pacemaker cell-associated arrhythmias. | Dandan Liang Zhigang Xue Jinfeng Xue Duanyang Xie Ke Xiong Huixing Zhou Fulei Zhang Xuling Su Guanghua Wang Qicheng Zou Yi Liu Jian Yang Honghui Ma Luying Peng Chunyu Zeng Gang Li Li Wang Yi-Han Chen | 2021 | Protein & Cell2021，12，7： | 1 |
| 4 | Glutamate drives local Ca^(2+)release'in cardiac pacemaker cells显示文摘The sinoatrial node(SAN)is the origin of the electrical signals for rhythmic heartbeats in mammals.The spontaneous fring of SAN pacemaker cells(SANPCS)triggers cardiac contraction.'Local Ca^(2+)release'(LCR),a unique cellular activity,acts as the'engine'of the spontaneous fring of SANPCs.However,the mechanism of LCR initiation remains unclear.Here,we report that endogenous glutamate drives LCRs in SANPCs.Using a glutamate sensor,we unraveled a tight correlation between glutamate accumulation and LCR occurrence,indicating a potential relationship between glutamate and LCRs.Intracellular application of glutamate significantly enhanced the LCRs in both intact and permeabilized SANPCs.Mechanitically,we revealed that mitochondrial excitatory amino acid transporter 1(EAAT 1)-dependent mitochondrial glutamate import promoted ROS generation,which in turn led to the oxidation of Ca^(2+)-handling proteins,ultimately resulting in enhanced LCRs.Importantly,EAAT1 depletion reduced both the spontaneous fring rates of isolated SANPCs and the heart rate in vitro and in vivo,suggesting the central role of EAAT1 as a glutamate transporter in the regulation of cardiac autonomic rhythm.In conclusion,our results indicate that glutamate serves as an LCR igniter in SANPCs,adding a potentially important element to the coupled clock theory that explains the origin of spontaneous firing.These findings shed new light on the future prevention and treatment of cardiac pacemaker cell-related arrhythmias. | Duanyang Xie Ke Xiong Xuling Su Guanghua Wang Qicheng Zou Luxin Wang Caihong Zhang Yuting Cao Beihua Shao Yixin Zhang Peidong Zhang Dandan Liang Yi Liu Yi-Han Chen | 2022 | Cell Research2022，32，9： | 0 |
| 5 | Using bio-orthogonally catalyzed lethality strategy to generate mitochondria-targeting anti-tumor metallodrugs in vitro and in vivo显示文摘Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anti-cancer therapies.To exploit the synthetic lethality concept in the design of chemical anti-cancer agents,we developed a bio-orthogonally catalyzed lethality(BCL)strategy to generate targeting anti-tumor metallodrugs both in vitro and in vivo.Metallodrug Ru-rhein was generated from two non-toxic species Ru-N_(3)and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition(Cu AAC)reaction without the need of an external copper catalyst.The non-toxic species Ru-arene complex Ru-N_(3)and rhein-alkyne were designed to perform this strategy,and the mitochondrial targeting product Ru-rhein was generated in high yield(>83%)and showed high anti-tumor efficacy in vitro.This BCL strategy achieved a remarkable tumor suppression effect on the tumor-bearing mice models.It is interesting that the combination of metal-arene complexes with rhein via Cu AAC reaction could transform two non-toxic species into a targeting anti-cancer metallodrug both in vitro and in vivo,while the product Ru-rhein was non-toxic towards normal cells.This is the first example that exclusive endogenous copper was used to generate metal-based anti-cancer drugs for cancer treatment.The anti-cancer mechanism of Ru-rhein was studied and autophagy was induced by increased reactive oxygen species and mitochondrial damage.The generality of this BCL strategy was also studied and it could be extended to other metal complexes such as Os-arene and Ir-arene complexes.Compared with the traditional methods for cancer treatment,this work presented a new approach to generating targeting metallodrugs in vivo via the BCL strategy from non-toxic species in metal-based chemotherapy. | Xuling Xue Chenggen Qian Qin Tao Yuanxin Dai Mengdi Lv Jingwen Dong Zhi Su Yong Qian Jing Zhao Hong-Ke Liu Zijian Guo | 2021 | National Science Review2021，8，9： | 0 |
| 6 | Mixed PEGylated surfactant modifying system decrease the accelerated blood clearance phenomenon of nanoemulsions in rats显示文摘The accelerated blood clearance(ABC) phenomenon which is induced by repeated injection of poly(ethylene glycol)(PEG)-coated colloidal carriers gives clinical challenge to the promising drug delivery system. It is necessary to decrease this unexpected immunological response.A novel 4-arm poly(ethylene glycol-5000)4-cholesteryl methyl amide(4-arm PEG5000-CHMA)has been synthesized. The structure of 4-arm PEG5000-CHMA was confirmed by IR and 1H-NMR spectrum. The pharmacokinetics of the tocopheryl nicotinate(TN)-loaded nanoemulsions modified with 4-arm PEG5000-CHMA or/and 1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-n-[methoxy(poly-ethyleneglycol)-2000](mPEG2000-DSPE) have been studied. Furthermore, the ABC phenomenon has been detailed investigated in rats by TN-loaded nanoemulsions modified with 4-arm PEG5000-CHMA and mPEG2000-DSPE(CPNE). The plasma levels of TN and anti-PEG IgM antibody were determined by HPLC and ELISA, respectively.The circulation time of the CPNEs were comparable to the mPEG2000-DSPE coated nanoemulsions. Moreover, the ABC phenomenon can be decreased by CPNEs. This study designs a method to decrease the ABC phenomenon and develops a clinical promising nanoemulsion for therapeutic or imaging purpose. | Yuqing Su Wenya Tang Yanzhi Song Chunling Wang Qingjing Tian Xuling Wang Jingjing Quan Buoqun Li Shaoning Wang Yihui Deng | 2017 | Asian Journal of Pharmaceutical Sciences2017，12，1： | 0 |
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