International Journal of Environmental Research and Public Health
·
2021
·Vol. 18
·期 22
·12051
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IF 3.39
Yifei Duan,Hua Shi,Yongmei Jiang
In order to understand current blood lead levels (BLLs), we investigated the BLLs of children in Sichuan Province from 2011 to 2020. We then monitored the treatment effects of calcium in children with high BLLs to assess their treatment status. Finally, we explored the effects of lead on Ca2+through in-situ experiments. Whole blood samples were used for BLL tests. The BLLs of 76,362 children aged 0–7 years were measured using atomic absorption spectrometry. The median BLL was 35 μg/L (interquartile range: 28–47). The BLLs were significantly higher in boys than in girls (p< 0.001). The BLLs generally decreased annually and increased with age. The overall prevalence of BLLs ≥ 100 μg/L was 1.20%. The children with high BLLs received subsequent check-ups, and the median time required for effective treatment was 18 months. We observed that lead exposure led to a gradual and persistent loss of Ca2+levels in neurons of mice brain slices, and the effect did not subside immediately even after the lead was removed. China has made rapid progress in pediatric healthcare, but the treatment status remains unsatisfactory. Because lead causes an irreversible loss of Ca2+, there is an urgent need to develop new standardized treatments to reduce the treatment duration.Keywords:blood lead levels;treatment status;calcium supplement;Ca2+imaging
研究领域:
公共卫生
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神经生物学
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儿科医学
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DOI
PubMed
高影响因子
NEURON
·
2023
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IF 16.2
Ning Cheng,Qiqi Dong,Zhen Zhang,Li Wang,Xiaojing Chen,Cheng Wang
Egocentric representations of external items are essential for spatial navigation and memory. Here, we explored the neural mechanisms underlying egocentric processing in the retrosplenial cortex (RSC), a pivotal area for memory and navigation. Using one-photon and two-photon calcium imaging, we identified egocentric tuning for environment boundaries in dendrites, spines, and somas of RSC neurons (egocentric boundary cells) in the open-field task. Dendrites with egocentric tuning tended to have similarly tuned spines. We further identified egocentric neurons representing landmarks in a virtual navigation task or remembered cue location in a goal-oriented task, respectively. These neurons formed an independent population with egocentric boundary cells, suggesting that dedicated neurons with microscopic clustering of functional inputs shaped egocentric boundary processing in RSC and that RSC adopted a labeled line code with distinct classes of egocentric neurons responsible for representing different items in specific behavioral contexts, which could lead to efficient and flexible computation.
研究领域:
神经科学
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认知神经生物学
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系统神经科学
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计算神经科学
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行为神经科学
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分子与细胞神经科学
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DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2022
·
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
EUROPEAN JOURNAL OF PAIN
·
2024
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IF 3.5
Hao-Nan Zheng,Yu-Ru Zhi,Yang-Shuai Su,Jin-Yan Jiang,Hao-Zhou Zhang,Feng Cao,Yun Wang,Yan Chi,Ying Zhang
Background Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). Methods Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 μg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout ( Clec7a −/− ) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. Results Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. Conclusions Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. Significance Statement This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.
研究领域:
胃肠病学
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免疫学
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疼痛研究
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神经科学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2016
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IF 2.857
Jing-Bo Liu,Yu-Xin Li,Xiu-Lan Zhang,Xue-Wen Hua,Chang-Chun Wu,Wei Wei,Ying-Ying Wan,Dan-Dan Cheng,Li-Xia Xiong,Na Yang,Hai-Bin Song,Zheng-Ming Li
To discover potent insecticides targeting ryanodine receptors (RyRs), a series of novel anthranilic diamides analogues (12a–12u) containing N-substituted phenylpyrazole were designed and synthesized. These compounds were characterized by 1H NMR, 13C NMR, and HRMS, and the structure of compound 12u was confirmed by X-ray diffraction. Their insecticidal activities indicated that these compounds displayed moderate to excellent activities. In particular, 12i showed 100 and 37% larvicidal activities against oriental armyworm (Mythimna separata) at 0.25 and 0.05 mg L–1, equivalent to that of chlorantraniliprole (100%, 0.25 mg L–1; and 33%, 0.05 mg L–1). The activity of 12i against diamondback moth (Plutella xylostella) was 95% at 0.05 mg L–1, whereas the control was 100% at 0.05 mg L–1. The calcium-imaging technique experiment results showed that the effects of 12i on the intracellular calcium ion concentration ([Ca2+]i) in neurons were concentration-dependent. After the central neurons of Helicoverpa armigera were dyed by loading with fluo-5N and treated with 12i, the free calcium released in endoplasmic reticulum indicated the target of compound 12i is RyRs or IP3Rs. The activation of RyRs by natural ryanodine completely blocked the calcium release induced by 12i, which indicated that RyRs in the central neurons of H. armigera third-instar larvae is the possible target of compound 12i.
研究领域:
农药化学
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昆虫生理学
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药物化学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Lin Niu,Shilong Wang,Yanyan Xu,Xingwang Zu,Xinyu You,Qiuyang Zhang,Pengwei Zhuang,Min Jiang,Jie Gao,Xiaotao Hou,Yanjun Zhang,Gang Bai,Jiagang Deng
Ethnopharmacological relevance As a classic traditional Chinese medicine , Magnolia officinalis ( M . officinalis ) is widely used in digestive diseases . It has rich gastrointestinal activity including inflammatory bowel disease (IBD) treatment, but the mechanism is not clear. Aim of the study In recent years, there has been a growing interest in investigating the regulatory effects of herbal compounds on transient receptor potential (TRP) channel proteins. Transient receptor potential vanilloid 4 (TRPV4), a subtype involved in endothelial permeability regulation, was discussed as the target of M . officinalis in the treatment of IBD in the study. Based on the targeting effect of TRPV4, this study investigated the active ingredients and mechanism of M . officinalis extract in treating IBD. Materials and methods To reveal the connection between the active ingredients in M . officinalis and TRPV4, a bioactivity-guided high performance liquid chromatography system coupled with mass spectrometry identification was utilized to screen for TRPV4 antagonists. TRPV4 siRNA knockdown experiment was employed to validate the significance of TRPV4 as a crucial target in regulating endothelial permeability by honokiol (HON). The interaction of the active ingredient representing HON with TRPV4 was confirmed by molecular docking, fluorescence-based thermal shift and live cell calcium imaging experiments. The potential binding sites and inhibitory mechanisms of HON in TRPV4 were analyzed by molecular dynamics simulation and microscale thermophoresis. The therapeutic effect of HON based on TRPV4 was discussed in DSS-IBD mice. Results Our finding elucidated that the inhibitory activity of M . officinalis against TRPV4 is primarily attributed to HON analogues. The knockdown of TRPV4 expression significantly impaired the calcium regulation and permeability protection in endothelial cells. The mechanism study revealed that HON specifically targets the Q239 residue located in the ankyrin repeat domain of TRPV4, and competitively inhibits channel opening with adenosine triphosphate (ATP) binding. The immunofluorescence assay demonstrated that the administration of HON enhances the expression and location of VE-Cadherin to protect the endothelial barrier and attenuates immune cell infiltration. Conclusions The finding suggested that HON alleviates IBD by improving endothelial permeability through TRPV4. The discovery provides valuable insights into the potential therapeutic strategy of active natural products for alleviating IBD.
研究领域:
药理学
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民族药理学
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胃肠病学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Advanced Materials Interfaces
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2023
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IF 5.4
Fengying Jiang,Yizhu Shan,Junyuan Tian,Lingling Xu,Chaohai Li,Fang Yu,Xi Cui,Chengwei Wang,Zhou Li,Kailiang Ren
Poly( l -lactic acid) (PLLA) films have excellent piezoelectric properties, but the strong hydrophobicity of the surface makes it difficult for cells to attach there. PLLA nanofibers have good biocompatibility, but the weak piezoelectric coefficient limits the ability of the nanofibers to stimulate cell growth. Therefore, the PLLA piezoelectric film is combined with the PLLA nanofibers to make a multilayer film. In our tests, the piezoelectric output of the multilayer film ≈260 mV. In the biological experiments section, without piezoelectric stimulation, the cell length on the nanofibers is approximately twice that of the cells in the blank control group. The length of cells cultured on piezoelectric-based stimulated nanofibers is more than twice that of cells cultured on nanofibers without piezoelectric stimulation. Therefore, it is confirmed that under the dual action of nanofiber guidance and piezoelectric stimulation, the growth rate of cells is four times faster than that in ordinary Petri dishes. Intracellular calcium imaging experiments confirmed that the concentration of Ca 2+ in electrically stimulated cells is approximately twice that of ordinary cells. It is also confirmed that piezoelectric materials can complete electrical stimulation of cells in indirect contact with cells.
研究领域:
生物材料
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组织工程
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神经科学
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细胞生物学
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材料科学
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DOI
高影响因子
STAR Protocols
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2024
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IF 1.3
Siyao Zhou,Shumin Duan,Hongbin Yang
Summary To exclude the influence of motion on in vivo calcium imaging, animals usually need to be fixed. However, the whole-body restraint can cause stress in animals, affecting experimental results. In addition, some brain regions are prone to bleeding during surgery, which lowers the success rate of calcium imaging. Here, we present a protocol for calcium imaging using heparin-treated fiber in head-fixed mice. We describe steps for stereotaxic surgery, including virus injection and optic fiber implantation, fiber photometry, and data analysis. For complete details on the use and execution of this protocol, please refer to Du et al. 1
研究领域:
神经科学
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生物医学工程
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成像技术
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DOI
PubMed
高影响因子
International Journal of Biological Sciences
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2024
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IF 8.2
Zihan Wang,Zhuowei Lei,Quanji Wang,Qian Jiang,Zhuo Zhang,Xiaojin Liu,Biao Xing,Sihan Li,Xiang Guo,Yanchao Liu,Xingbo Li,Yiwei Qi,Kai Shu,Huaqiu Zhang,Yimin Huang,Ting Lei
Somatostatin analogues (SSTA) are first-line pharmacological treatment choice for acromegaly, which received satisfying tumor shrinkage and normalization of growth hormone. However, there are still patients unresponsive to SSTA, and the underline mechanism remains unknown. Besides, there is no evidence regarding the role of endoplasmic reticulum stress (ERS) and its transmission in SSTA resistance, which also require investigation. Primary growth hormone adenoma cells and cell lines were treated with SSTA; autophagy double-labeled LC3 (mRFP-GFP) adenovirus transfection, flow cytometry sorting, western blotting, calcium imaging as well as immunofluorescence staining were used to determine ERS and autophagy signal transmission; xenograft and syngeneic tumor in vivo model were exploited to confirm the ERS signal transmission mediated effect. Our results revealed that SSTA induces ERS in pituitary growth hormone (GH) adenoma cells. The ERS signals can be intercellularly transmitted, leading to less responsible to SSTA treatment. Moreover, SSTA stimulates inositol triphosphate (IP 3 ) elevation, mediating ERS intercellular transfer. In addition, connexin 36 tunnels ERS transmission, and its blocker, Quinine, exhibits a synergistic effect with SSTA treating GH adenoma. Our study provided insight into ERS intercellular transmission mediated SSTA resistance, which could be translated into clinical usage to improve SSTA efficiency in GH adenoma treatment.
研究领域:
内分泌学
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药理学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Yang Xiaohua,Zhang Min,Lu Zhihong,Zhi Linping,Xue Huan,Liu Tao,Liu Mengmeng,Cui Lijuan,Liu Zhihong,He Peifeng,Liu Yunfeng,Zhang Yi
Glucagon-like peptide-1 receptor (GLP-1R) agonist-based therapeutics for type 2 diabetes mellitus have attracted worldwide attention. However, there are challenges in the development of small molecule GLP-1R agonists owing to the complexity of ligand recognition and signal induction mechanisms. Here, we attained S6 using virtual screening and fluorescent imaging plate reader (FLIPR)-based calcium assays. The purpose of this study was to identify and characterize S6, a novel small molecule GLP-1R agonist. Data from cellular thermal shift assay (CETSA) and Bio-Layer Interferometry (BLI) indicated that S6 could bind potently with GLP-1R. Radioimmunoassay data showed that S6 potentiated insulin secretion in a glucose-dependent manner and the insulinotropic effect was mediated by GLP-1R. Calcium imaging techniques suggested that S6 elevated the intracellular calcium concentration [(Ca2+)i] by activating GLP-1R. In patch-clamp experiments, we demonstrated that S6 inhibited voltage-dependent K+ (Kv) channels in a GLP-1R-dependent fashion. Besides, S6 significantly prolonged action potential duration but had no effect on voltage-dependent Ca2+ channels. In summary, these findings indicate that S6 stimulates glucose-dependent insulin secretion mainly by acting on GLP-1R, inhibiting Kv channels, increasing (Ca2+)i. This study will provide direction for the screening and development of novel small-molecule agents targeting GLP-1R in the future.
研究领域:
药理学
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内分泌学
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糖尿病
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分子生物学
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DOI
PubMed
高影响因子
BIOLOGICAL RESEARCH
·
2025
·Vol. 58
·期 1
·1-22
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IF 4.6
Chen Hanbin,Li Guanghong,Deng Lin,Li Shuli,Huang Songqiang,Lee Simon Ming-Yuen,Nie Xiaowei,Bian Jin-Song
Background Pain serves as a vital protective mechanism triggered by tissue damage. While NSAIDs and opioids offer relief, their prolonged usage is hindered by adverse effects. Developing analgesics with fewer side effects is crucial for effective pain treatment. The TRPV1 channel is a key target for pain relief, with its inhibitors effectively reducing hyperalgesia in animals. This research utilized virtual screening to identify TRPV1-selective natural compounds for potent analgesic properties. Results The physcion exhibited the notable affinity for TRPV1 compared to the compounds examined. After conducting molecular dynamics simulations, physcion emerged as the compound demonstrating the highest binding affinity towards TRPV1, a finding corroborated by calcium imaging, which validated its inhibitory impact. Furthermore, physcion mitigated the stretch number in the acetic acid-induced stretching model, prolonged the latency period in the hot water tail-flick and hot plate assays, and heightened the pain withdrawal threshold lowered by complete Freund’s adjuvant (CFA). Notably, physcion exerted a marked effect in ameliorating bone cancer-induced pain in the hot plate and von Frey tests. Additionally, physcion diminished the levels of inflammatory cytokines and the mRNA expression of both inflammatory and calcium-related genes in the CFA-induced murine model. Furthermore, physcion downregulated the expression of inflammatory genes induced by tumor necrosis factor-α (TNF-α) in RAW264.7 cells. The underlying mechanism potentially involves the suppression of the NF-κB and MAPK signaling cascades. Conclusions Our investigation underscores the potential of physcion as a promising candidate for analgesic therapy.
研究领域:
药理学
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疼痛研究
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分子生物学
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计算生物学
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炎症研究
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神经药理学
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肿瘤学
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药物研发
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DOI
PubMed
高影响因子
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