NEUROSCIENCE RESEARCH
·
2011
·
IF 2.096
Haiyan Xu,Ruirui Chen,Xiaoyan Cai,Defu He
Neostriatum plays an important role in the pathophysiology of Parkinson's disease (PD). However, the changes of sensitivity of dopamine receptors of neostriatal neurons in PD have been less addressed in vivo . In the present study, systemic exposure to paraquat and maneb induced Parkinsonian symptoms and neuronal loss of substantia nigra pars compacta. Using single-unit recording methods, three types of neostriatal neurons were recorded including medium spiny-like neurons, large aspiny-like neurons and fast-spiking interneurons. In the exposed rats, increased firing activity of neostriatal neurons was revealed when compared to control rats. Following D1 receptor agonist, SKF38393 and D2 receptor agonist, LY171555 iontophoretically administrated respectively, effects of increase and decrease in firing activity were both observed in neostriatal neurons. However, stronger inhibitory effects of activating D1 receptors and weaker excitatory effects of activating D2 receptors were found in the exposed rats as compared to controls. It indicated that differential changes of sensitivity of D1 and D2 receptors in Parkinson's disease were related to the modulation of the imbalance between D1-receptor-dependent striatonigral direct pathway and D2-receptor-dependent striatopallidal indirect pathway. Our results illustrate the electrophysiological changes of in vivo neostriatal neurons in Parkinson's disease, thereby providing insight into the regulatory mechanisms of dopamine-mediated physiology.
研究领域:
神经科学
·
药理学
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DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2017
·Vol. 19
·期 12
·1-11
·
IF 2.02
Chen Daquan,Song Xiaoyan,Wang Kaili,Guo Chunjing,Yu Yueming,Fan Huaying,Zhao Feng
In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance ( 1 H–NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3 ± 2.12 nm and zeta potential − 30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
Insect Science
·
2015
·Vol. 24
·期 4
·543-558
·
IF 2.144
Qin-Hui Zhang,Zhong-Nan Wu,Jing-Jiang Zhou,Yong-Jun Du
Olfaction is primarily mediated by highly specified olfactory receptors (ORs). Here, we cloned and identified an olfactory receptor, named SlituOR1 (Genbank no. JN835269), from Spodoptera litura and found evidence that it is a candidate pheromone receptor. It exhibited male-biased expression in the antennae, where it was localized at the base of sensilla trichoidea, the antennal sensilla mainly responsive to pheromones in moths. Conserved orthologues of this receptor, found among known pheromone receptors within the Lepidoptera, and SlituOR1 were placed among a clade of candidate pheromone receptors in a phylogeny tree of insect OR gene sequences. SlituOR1 showed differential expression in S. litura populations attracted to traps baited with different ratios of the two sex pheromone components (9 Z ,11 E )-tetradecadienyl acetate ( Z 9 E 11-14:OAc) and (9 Z ,12 E )-tetradecadienyl acetate ( Z 9 E 12-14:OAc). Knocking down of SlituOR1 by RNA interference reduced the electroantennogram (EAG) response to Z 9 E 11-14:OAc, and this result is consistent with the field trapping experiment. We infer that variation in transcription levels of olfactory receptors may modulate sex pheromone perception in male moths and could provide some of the flexibility required to maintain the functionality of communication with females when a population is adapting to a new niche and reproductive isolation becomes an advantage.
研究领域:
昆虫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Zhu Qing,Mao Li-Na,Liu Cheng-Peng,Sun Yue-Hua,Jiang Bo,Zhang Wei,Li Jun-Xu
Vitexin, a C-glycosylated flavone present in several medicinal herbs, has showed various pharmacological activities including antinociception. The present study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain. This model was prepared by making a surgical incision on the right hindpaw and von Frey filament test was used to assess mechanical hyperalgesia. Isobolographical analysis method was used to examine the interaction between vitexin and acetaminophen. A reliable mechanical hyperalgesia was observed at 2 h post-surgery and lasted for 4 days. Acute vitexin administration (3–10 mg/kg, i.p.) dose-dependently relieved this hyperalgesia, which was also observed from 1 to 3 days post-surgery during repeated daily treatment. However, repeated vitexin administration prior to surgery had no preventive value. The 10 mg/kg vitexin-induced antinociception was blocked by the opioid receptor antagonist naltrexone or the GABA A receptor antagonist bicuculline. The doses of vitexin used did not significantly suppress the locomotor activity. In addition, the combination of vitexin and acetaminophen produced an infra-additive effect in postoperative pain. Together, though vitexin-acetaminophen combination may not be useful for treating postoperative pain, vitexin exerts behaviorally-specific antinociception against postoperative pain mediated through opioid receptors and GABA A receptors, suggesting that vitexin may be useful for the control of postoperative pain.
研究领域:
药理学
·
疼痛研究
·
神经科学
✓ 已验证
DOI
高影响因子
METABOLIC BRAIN DISEASE
·
2018
·Vol. 33
·期 5
·1721-1731
·
IF 2.441
Chen Zhao-Di,Chen Wen-Qiang,Wang Zhi-Yuan,Cao Dan-Ni,Wu Ning,Li Jin
Previous studies have shown that agmatine, a potential neuromodulator or co-transmitter, exhibited antidepressant-like action in animal models, yet its mechanism, especially the receptor mechanism, remains unclear. In the present study, using efaroxan, a preferential antagonist of I 1 imidazoline receptor (I 1 R) and yohimbine, an antagonist of α 2 adrenergic receptor (α 2 AR), we investigated the roles of I 1 R and α 2 AR in agmatine’s antidepressant-like effect in acute and sub-acute depression models in mice. We found that in the tail-suspension test (TST) and the forced swimming test (FST), acute administration of agmatine (20 and 40 mg/kg, p.o.) significantly shortened the immobility time. Concurrent administration of efaroxan (1 mg/kg, i.p.) completely abolished the antidepressant-like effects of agmatine (40 mg/kg, p.o.) whereas yohimbine (5 mg/kg, i.p.) failed to exert similar effects, suggesting that the acute antidepressant-like effects of agmatine was mainly mediated by I 1 R but not α 2 AR. Additionally, in the learned helplessness (LH) test, repeated administration of agmatine (20 mg/kg, p.o., q.d.) for 5 days significantly decreased the escape latency and the number of escape failure, and these effects were respectively abolished by concurrent administration of efaroxan (0.5 mg/kg,i.p., q.d.) and yohimbine (3 mg/kg, i.p., q.d.) for 5 days, suggesting that the antidepressant-like action of agmatine in the LH test was achieved via the activation of both I 1 R and α 2 AR. In summary, we found that the antidepressant-like effects of agmatine in the TST and the FST were mediated by activating I 1 R and in the sub-acute LH test were mediated by activating both I 1 R and α 2 AR.
研究领域:
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AIP Advances
·
2024
·Vol. 14
·期 8
·
IF 1.4
Zheng Yu,Song Rujuan,Wei Shengjie,Dong Lei,Chen Yazhou
Long-term potentiation (LTP) in the Schaffer-CA1 region of the hippocampus is closely related to learning and memory. Magnetic stimulation, as an effective physical means of regulating synaptic plasticity, has received widespread attention. However, research on the mechanism of the effect of different frequencies of magnetic fields (MFs) on LTP is relatively scarce. This article focuses on Ca 2+ , Na + , K + , NMDA receptors, and AMPA receptors that play important roles in the process of MF regulation of LTP. A combined electrophysiological and pharmacological approach was used to identify Ca 2+ as a key factor in the modulation of LTP by MFs of different frequencies. Subsequently, further experiments revealed that low levels of intracellular Ca 2+ concentration ([Ca 2+ ] i ) intensified the inhibition of low-frequency MFs on LTP, while high levels of [Ca 2+ ] i enhanced the promotion effect of high-frequency MFs on LTP, indicating a positive correlation between [Ca 2+ ] i levels and MF regulation of LTP levels. The research results of this article may help explore the deeper relationship between different frequencies of MFs and synaptic plasticity, and they also have a certain reference value for magnetic stimulation therapy in the treatment of neurological diseases related to LTP injury or learning and memory deficits.
研究领域:
神经科学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Xiayu Wu,Yongjun Liu,Changhao Zou,Fuqin He,Fang Guo,Sijia Liu,Yi Fan,Xuedong Zhu,Qianyi Zhou,Dan Shu
Introduction: Traditional Miao and Dai Chinese medicines have used nicotine-rich leaf tobacco to treat traumatic injuries by promoting hemostasis. While nicotine is known to enhance platelet aggregation, its effects on other platelet functions and underlying mechanisms remain unclear.Methods and Results: This study aimed to thoroughly investigate nicotine’s effects on human platelets and its pharmacological mechanisms, using thromboelastography to assess nicotine’s impact on platelet function during coagulation. This study aimed to investigate the functional effects of nicotine on human platelets and elucidate its pharmacological mechanisms. The impact of nicotine on platelet function during the coagulation process was assessed using thromboelastography. Further studies showed that nicotine fully activates washed platelets, promoting aggregation, granule release, adhesion, spreading, and plaque retraction. Concurrently, nicotine was found to enhance the intracellular concentration of calcium ions in platelets ([Ca2+]i). To explore the underlying mechanisms, molecular docking software was employed to identify the platelet membrane receptors PAR1 and PAR4, which exhibited the highest docking scores with nicotine. Intervention with two receptor inhibitors demonstrated that only the PAR4 inhibitor could reverse the stimulatory effects of nicotine on platelet granule release. Through the examination of alterations in the downstream signaling pathways of PAR4 receptors, it was determined that nicotine promo-facilitates the phosphorylation of PI3K, AKT, and ERK1/2 proteins, subsequently contributing to the activation of αIIbβ3 receptors in platelets. Conversely, the application of PAR4 inhibitors was found to reverse these effects.Discussion: In conclusion, nicotine activates αIIbβ3 receptors and significantly enhances platelet function by promoting the phosphorylation of the platelet PAR4 receptor signaling pathway. These findings suggest the potential utility of nicotine as a hemostatic agent.
研究领域:
药理学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2015
·Vol. 10
·期 6
·e0131407
·
IF 3.234
Xinda Lin,Qinhui Zhang,Zhongnan Wu,Yongjun Du
Olfaction is primarily mediated by highly specific olfactory receptors (ORs), a subfamily of which are the pheromone receptors that play a key role in sexual communication and can contribute to reproductive isolation. Here we cloned and identified an olfactory receptor, SlituOR3 (Genbank NO. JN835270), from Spodoptera litura , to be the candidate pheromone receptor. It exhibited male-biased expression in the antennae, where they were localized at the base of sensilla trichoidea. Conserved orthologues of these receptors were found amongst known pheromone receptors within the Lepidoptera, and SlituOR3 were placed amongst a clade of candidate pheromone receptors in a phylogeny tree of insect ORs. SlituOR3 is required for the EAG responses to both Z9E11-14:OAc and Z9E12-14:OAc SlituOR3 showed differential expression in S . litura populations attracted to traps baited with a series of sex pheromone blends composed of different ratios of (9Z,11E)-tetradecadienyl acetate (Z9E11-14:OAc) and (9Z,12E)-tetradecadienyl acetate (Z9E12-14:OAc). The changes in the expression level of SlitOR3 and antennal responses after SlitOR3 silencing suggested that SlitOR3 is required for the sex pheromone signaling. We infer that variation in transcription levels of olfactory receptors may modulate sex pheromone perception in male moths and could affect both of pest control and monitoring efficiency by pheromone application after long time mass trapping with one particular ratio of blend in the field.
研究领域:
昆虫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Guo Liu,Shan Huang,Xiaochen Liu,Wanzhen Chen,Xin Ma,Shuang Cao,Liping Wang,Lanlan Chen,Huanghao Yang
Transmembrane signal transduction is of profound significance in many biological processes. The dimerization of cell-surface receptors is one prominent mechanism by which signals are transmitted across the membrane and trigger intracellular cascade amplification reactions. Recreating such processes in artificial systems has potential applications in sensing, drug delivery, bioengineering, and providing a new route for a deep understanding of fundamental biological processes. However, it remains a challenge to design artificial signal transduction systems working by the receptor dimerization mechanism in a predictable and smart manner. Here, benefitting from DNA with features of programmability, controllability, and flexible design, we use DNA as a building material to construct an artificial system mimicking dimerization of receptors for signal transduction and cascade amplification. DNA-based membrane-spanning receptor analogues are designed to recognize external signals, which drives two receptors into close spatial proximity to activate DNAzymes inside the cell-mimicking system. The activation of the DNAzyme initiates the catalyzed cleavage of encapsulated substrates and leads to the release of fluorescent second messengers for signal amplification. Such an artificial signal transduction system extends the range of biomimetic DNA-based signaling systems, providing a new avenue to study natural cell signaling processes and artificially regulate biological processes.
研究领域:
合成生物学
·
分子生物学
·
纳米生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Yaqi Wang,Ping Shu,Mei Lv,Yonghao Xing,Haoran Zhang,Xiaojing Yan,Bo Wang,Tingting Huang,Minfeng Fang
Farfarae Flos and its honey-processed product are used to treat respiratory diseases; yet their active components and therapeutic targets remained unclear. Herein, we developed an integrated strategy combining receptor chromatography and mice models to screen and evaluate active components in both raw and honey-processed Farfarae Flos. We focused on three key receptors,β 2 -AR, CysLT 1 R, and M 3 R, known to be involved in antitussive, anti-inflammatory, and expectorant activities. These receptors were immobilized onto silica gels to construct affinity columns. Using these columns, we identified the bioactive compounds in both forms of Farfarae Flos. The results revealed an identical set of target-specific compounds across raw and honey-processed samples: chlorogenic acid (CGA) and caffeic acid (CA) targeted β 2 -AR; CGA and rutin bound to CysLT 1 R; and CGA along with isochlorogenic acids A, B, and C interacted with M 3 R. Notably, the interactions of rutin with CysLT 1 R and isochlorogenic acids A, B, and C with M 3 R are reported for the first time. These findings indicate that both raw and honey-fired Farfarae Flos share the same material basis for their antitussive, anti-inflammatory, and expectorant effects, with no significant alteration in pharmacological efficacy due to honey processing. Furthermore, the binding affinities of the bioactive compounds for the receptors correlated well with the molecular docking-predicted binding energies of the corresponding compound-receptor complexes. To our knowledge, this study represents the first target-centric comparative analysis of raw and processed Farfarae Flos. It establishes a generalizable framework for investigating processing-induced changes in herbal pharmacology and provides empirical evidence connecting metabolomic profiles to clinical efficacy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ELECTROPHORESIS
·
2015
·Vol. 36
·期 19
·2433-2441
·
IF 3.028
Chunye Liu,Xuejiao Zhang,Hui Jing,Yanqing Miao,Lingzhi Zhao,Yan Han,Cuixia Cui
Oriented covalent immobilized β 2 -adrenergic receptor (β 2 -AR) CE (OIRCE) was developed to determine the interactions between a set of natural extracts of Radix Paeoniae Rubra (NERPR) and β 2 -AR, and to predict the activity of NERPR. The inner capillary surface is chemically bonded with stable β 2 -AR coating via microwave-assisted technical synthesis. The modified capillaries were characterized via infrared spectroscopy and fluorescence microscopy. Furthermore, the bonding amounts of β 2 -AR were first obtained via fluorescence spectroscopy method. In determining the amount of bonded β 2 -AR, the regression equation A = 576 707C + 35.449 and the correlation coefficient 0.9995 were obtained. This result revealed an excellent linear relationship in the range of 2 × 10 −4 mg/mL to 1 × 10 −3 mg/mL. The normalized capacity factor ( K RCE ) was obtained using OIRCE in evaluating drug–receptor interactions. Related theories and equations were used to calculate K RCE values from apparent migration times of a solute and EOF. The order of K RCE and the binding constant ( K b ) values between drugs and β 2 -AR was well consistent. The results confirmed that the OIRCE and K RCE values can be effectually used to investigate drug-receptor interactions, and OIRCE has the potential to predict drug activity and to select leading compounds from natural chemicals.
研究领域:
药学
·
分析化学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2019
·Vol. 44
·期 3
·835-846
·
IF 2.928
Bao‑Wen Liu,Zhi‑Xiao Li,Zhi‑Gang He,Qian Wang,Cheng Liu,Xian‑Wei Zhang,Hui Yang,Hong‑Bing Xiang
In this study, we focused on several itch‑related molecules and receptors in the spinal cord with the goal of clarifying the specific mediators that regulate itch sensation. We investigated the involvement of serotonin receptors, opioid receptors, glia cell markers and chemokines (ligands and receptors) in models of acetone/ether/water (AEW)‑ and diphenylcyclopropenone (DCP)‑induced chronic itch. Using reverse transcription‑quantitative polymerase chain reaction, we examined the expression profiles of these mediators in the lower cervical spinal cord (C5‑8) of two models of chronic itch. We found that the gene expression levels of opioid receptor mu 1 (Oprm1), 5‑hydroxytryptamine receptor 1A (Htr1a) and 5‑hydroxytryptamine receptor 6 (Htr6) were upregulated. Among the chemokines, the expression levels of C‑C motif chemokine ligand (Ccl)21, Cxcl3 and Cxcl16 and their receptors, Ccr7, Cxcr2 and Cxcr6, were simultaneously upregulated in the spinal cords of the mice in both models of chronic itch. By contrast, the expression levels of Ccl2, Ccl3, Ccl4 and Ccl22 were downregulated. These findings indicate that multiple mediators, such as chemokines in the spinal cord, are altered and may be central candidates in further research into the mechanisms involved in the development of chronic itch.
研究领域:
神经生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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