Journal of Inflammation Research
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2022
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IF 4.631
Fan Ye,Yucui Jiang,Jian Zhang,Yingxin Zong,Mei Yu,Cuihua Chen,Chan Zhu,Yan Yang,Keke Jia,Gongxi Chen,Zongxiang Tang
Background Senecio scandens Buch.-Ham (S. scandens) belongs to the Compositae family. As a Traditional Chinese medicine, S. scandens has been used in China to treat conjunctivitis, mastitis and vaginitis, it also has the function of antibacterial and relieving itching.Methods Water extract of S. scandens (WSS) was prepared and its quality was controlled by HPLC. The antipruritic effects of WSS were evaluated by itch behavioral experiments. The oxazolone and compound 48/80 were induced to mice scratch behavior, scratch was recorded 30 min after sensitization. The relationship between the antipruritic mechanism and MrgprB2 on mast cell was studied by using mast cell-deficient Kit (W-sh) “Sash” mice and MrgprB2−/− mice. The mast cells were observed by toluidine blue staining. In vitro, the effects of WSS on MrgprB2 were studied by calcium imaging; The whole-cell patch clamp method recorded the MrgprB2 mediate voltage-dependent currents in mast cells.Results The content of rutin (0.012%) and hyperin (0.014%) in the WSS were determined. WSS could ameliorate the pruritus induced by Oxazolone (inhibition was 41.19%, p = 0.004) and compound 48/80 (inhibition was 50.29%, p = 0.001). Meanwhile, WSS could reduce the number of mast cells in mice skin tissue with allergic contact dermatitis (ACD) (p = 0.002) or compound 48/80 (p = 0.013). In addition, WSS could inhibit the calcium influx (1 mg/mL: p = 0.001, 3 mg/mL: p < 0.0001) and the voltage-dependent currents induced by activation of MrgprB2 on mast cell. WSS also attenuated the calcium influx induced by compound 48/80 in HEK293 cells overexpressing MrgprB2/X2.Conclusion These results showed that WSS could ameliorate pruritus by inhibiting MrgprB2 receptor on mast cells.
研究领域:
药理学
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免疫学
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中药学
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细胞生物学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2024
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IF 4.2
Xiaoyi Huo,Yinna Wang,Zheming Liu,Jia Liu,Hang Zhu,Yong Zhou,Yilong Man,Xiaomao Zhou,Haihao Ma
The slowpoke channel responds to the intracellular calcium concentration and the depolarization of the cell membrane. It plays an important role in maintaining the resting potential and regulating the homeostasis of neurons, but it can also regulate circadian rhythm, sperm capacitation, ethanol tolerance, and other physiological processes in insects. This renders it a potentially useful target for the development of pest control strategies. There are relatively few studies on the slowpoke channels in lepidopteran pests, and their pharmacological properties are still unclear. So, in this study, the slowpoke gene of Plutella xylostella ( Pxslo ) was heterologous expressed in HEK293T cells, and the I-V curve of the slowpoke channel was measured by whole cell patch clamp recordings. Results showed that the slowpoke channel could be activated at −20 mV with 150 μM Ca 2+ . The subsequent comparison of the electrophysiological characteristics of the alternative splicing site E and G deletions showed that the deletion of the E site enhances the response of the slowpoke channel to depolarization, while the deletion of the G site weakens the response of the slowpoke channel to depolarization. Meanwhile, the nonspecific inhibitors TEA and 4-AP of the Kv channels, and four pesticides were tested and all showed an inhibition effect on the PxSlo channel at 10 or 100 μM, suggesting that these pesticides also target the slowpoke channel. This study enriches our understanding of the slowpoke channel in Lepidopteran insects and can aid in the development of relevant pest management strategies.
研究领域:
昆虫学
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药理学
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分子生物学
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害虫管理
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DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE BIOLOGY
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2017
·Vol. 250
·期 5
·483-492
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IF 1.696
Chai Ran,Chen Yafei,Yuan Hongbo,Wang Xuzhao,Guo Shuai,Qi Jinlong,Zhang Hailin,Zhan Yong,An Hailong
Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Dysfunction of the CaCCs is implicated in many diseases. Drug discovery targeting at CaCCs has recently become possible with the determination that TMEM16A is the molecular identity of CaCCs. In this study, we demonstrated that resveratrol (RES), a Chinese traditional medicine compound, is a novel activator of TMEM16A. The yellow fluorescence protein quenching assay and measurement of intracellular calcium fluorescence intensity show that RES activates TMEM16A channels in an intracellular Ca 2+ -independent way. The data of inside-out patch clamp revealed that RES dose-dependently activates TMEM16A (EC 50 = 47.92 ± 9.35 μM). Furthermore, RES enhanced the contractions of the ileum of guinea pigs by activating the TMEM16A channel, which indicated that RES might be a promising drug for the treatment of gastrointestinal hypomotility. As RES was able to induce TMEM16A channel activation, TMEM16A can be added to the list of RES drug targets.
研究领域:
药理学
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生理学
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药物发现
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DOI
PubMed
高影响因子
STAR Protocols
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2023
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IF 0
Ya-Wei Ji,Xiang-Ying Xu,Cui Yin,Chunyi Zhou,Cheng Xiao
Summary Analysis of synaptic strength and plasticity provides functional insights of complicated neural circuits. Here, we describe steps for cell- and projection-specific optogenetic manipulation of divergent basal ganglia circuits using anterograde and retrograde viral vectors. We quantitatively analyze synaptic function of these circuits utilizing a patch-clamp technique. This protocol is applicable to probe potential circuit targets for treatment of brain diseases. For complete details on the use and execution of this protocol, please refer to Ji et al. 1
研究领域:
神经科学
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分子生物学
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生物医学工程
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DOI
PubMed
Frontiers in Pharmacology
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2024
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IF 4.4
Li Liang,Wu Xiaorong,Gong Jili,Wang Zhuqiang,Dai Weibo,Qiu Li,Zuo Hongyuan,Yi Mengqin,Yuan Hui,Hu Mei,Gao Zhaobing,Tian Fuyun
Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) prescribed to patients diagnosed with insomnia, which can achieve excellent therapeutic outcomes. As positively modulating the γ-aminobutyric acid (GABA) type A receptors (GABAARs) is the most effective strategy to manage insomnia, this study aimed to investigate whether the activation of GABAARs is involved in the anti-insomnia effect of HWD. We assessed the metabolites of HWD using LC/MS and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and tested the pharmacological activity in vitro and in vivo using whole-cell patch clamp and insomnia zebrafish model. In HEK293 cells expressing α1β3γ2L GABAARs, HWD effectively increased the GABA-induced currents and could induce GABAAR-mediated currents independent of the application of GABA. In the LC-MS (QToF) assay, 31 metabolites were discovered in negative ion modes and 37 metabolites were found in positive ion modes, but neither three selected active metabolites, Danshensu, Coptisine, or Dihydromyricetin, showed potentiating effects on GABA currents. 62 active metabolites of the seven botanical drugs were collected based on the TCMSP database and 19 of them were selected for patch-clamp verification according to the virtual docking simulations and other parameters. At a concentration of 100 μM, GABA-induced currents were increased by (+)-Cuparene (278.80% ± 19.13%), Ethyl glucoside (225.40% ± 21.77%), and β-Caryophyllene (290.11% ± 17.71%). In addition, (+)-Cuparene, Ethyl glucoside, and β-Caryophyllene could also serve as positive allosteric modulators (PAMs) and shifted the GABA dose-response curve (DRC) leftward significantly. In the PCPA-induced zebrafish model, Ethyl glucoside showed anti-insomnia effects at concentrations of 100 μM. In this research, we demonstrated that the activation of GABAARs was involved in the anti-insomnia effect of HWD, and Ethyl glucoside might be a key metabolite in treating insomnia.
研究领域:
中医药学
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神经药理学
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分子生物学
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DOI
PubMed
高影响因子
Small
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2024
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IF 13
Gerile Oudeng,Seema Banerjee,Qin Wang,Ding Jiang,Yadi Fan,Honglian Wu,Feng Pan,Mo Yang
Retinitis pigmentosa is the main cause of inherited human blindness and is associated with dysfunctional photoreceptors (PRs). Compared with traditional methods, optoelectronic stimulation can better preserve the structural integrity and genetic content of the retina. However, enhancing the spatiotemporal accuracy of stimulation is challenging. Quantum dot-doped ZnIn 2 S 4 microflowers (MF) are utilized to construct a biomimetic photoelectric interface with a 0D/3D heterostructure, aiming to restore the light response in PR-degenerative mice. The MF bio interface has dimensions similar to those of natural PRs and can be distributed within the curved spatial region of the retina, mimicking cellular dispersion. The soft 2D nano petals of the MF provide a large specific surface area for photoelectric activation and simulate the flexibility interfacing between cells. This bio interface can selectively restore the light responses of seven types of retina ganglion cells that encode brightness. The distribution of responsive cells forms a pattern similar to that of normal mice, which may reflect the generation of the initial “neural code” in the degenerative retina. Patch-clamp recordings indicate that the bio interface can induce spiking and postsynaptic currents at the single-neuron level. The results will shed light on the development of a potential bionic subretinal prosthetic toolkit for visual function restoration.
研究领域:
神经科学
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生物医学工程
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材料科学
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眼科
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DOI
PubMed
高影响因子
NEUROSCIENCE
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2018
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IF 3.382
Lingqi Gao,Junde Han,Jie Bai,Jing Dong,Sen Zhang,Mazhong Zhang,Jijian Zheng
Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development. All experiments were performed using acutely dissected whole-mount Sprague–Dawley rat retinas (0–14 postnatal days [P0–P14]). Ketamine reversibly blocked spontaneous network activity in the rat retina from P0 to P9 and irreversibly blocked such activity from P10 to P12. The peak of physiological and ketamine-induced neuronal apoptosis mainly occurred from P7 to P9. Blockade of nicotinic acetylcholine receptors (nAChRs) also induced reversible inhibition of spontaneous network activity from P0 to P7 and extensive neuronal apoptosis in the P7 rat retina, while activation of nAChRs or increases in endogenous ACh levels attenuated ketamine-induced apoptotic responses. Furthermore, blockade of α7-nAChR and ß2-nAChR subtypes induced neuronal apoptosis in the developing retina, while activation of the α7-nAChR subtype attenuated ketamine-induced apoptotic responses. These results demonstrate that ketamine may inhibit early synchronized spontaneous network activity by blocking nAChRs, and that such inhibition may contribute to ketamine-induced neuronal apoptosis in the developing rat retina.
研究领域:
神经科学
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药理学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
Stem Cells International
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2015
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IF 2.813
Quanwen Liu,Yi Shen,Jiarong Chen,Jie Ding,Zihua Tang,Cui Zhang,Jianling Chen,Liang Li,Ping Chen,Jinfu Wang
In this paper, we developed a two-step-induction method of generating functional hair cells from inner ear multipotent cells. Multipotent cells from the inner ear were established and induced initially into progenitor cells committed to the inner ear cell lineage on the poly-L-lysine substratum. Subsequently, the committed progenitor cells were cultured on the mitotically inactivated chicken utricle stromal cells and induced into hair-cell-like cells containing characteristic stereocilia bundles. The hair-cell-like cells exhibited rapid permeation of FM1-43FX. The whole-cell patch-clamp technique was used to measure the membrane currents of cells differentiated for 7 days on chicken utricle stromal cells and analyze the biophysical properties of the hair-cell-like cells by recording membrane properties of cells. The results suggested that the hair-cell-like cells derived from inner ear multipotent cells were functional following differentiation in an enabling environment.
研究领域:
发育生物学
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神经科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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