Food & Function
·
2021
·Vol. 12
·期 23
·11926-11937
·
IF 5.396
Yajie Guo,Shengli Gao,Zhongxin Jiang,Jinfang Huang,Xiaoman He,Ruijie Jin,Shanbin Sun,Feifei Guo,Yanling Gong,Xiangrong Sun
Gastrointestinal motility (GI) disorder causes symptoms such as dyspepsia, abdominal distention, and constipation and severely affects quality of life. The calcium (Ca2+)-sensing receptor (CaSR) expressed in the digestive tract can be activated by amino acids and participates in GI motility regulation. This study is designed to explore the effect and underlying mechanism of CaSR agonist R568 on the small intestine motility of mice in vivo and ex vivo. R568 was given to male C57BL/6 mice by gavage or incubated with isolated jejunum and ileum segments to observe its effects on GI motility and the involved neurons, neurotransmitters and hormones were detected by fluorescence immunohistochemistry and enzyme-linked immunosorbent assays. The in vivo results showed that the intestinal propulsive rate reduced in response to oral intake of R568. R568 treatment increased the numbers of nitric oxide synthase-positive neurons and nitric oxide release but decreased the choline acetyl transferase-positive neurons and acetylcholine release in the myenteric plexuses. R568 increased the secretion of cholecystokinin in the intestinal tissues and serum but had no effect on the secretion of glucagon like peptide-1. Ex vivo results showed that R568 inhibited the contractility of intestinal strips from the jejunum and ileum. Nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME), M-receptor antagonist-atropine, and tetrodotoxin (TTX) failed to block the effect of R568. CaSR co-expressed with interstitial cells of Cajal (ICCs) in the myenteric plexus suggests the possibility that ICCs mediated the effect of R568. Our findings demonstrate that CaSR activation inhibited intestinal motility, and both the enteric nervous system and non-neural mechanism are involved in this process.
研究领域:
胃肠病学
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药理学
·
神经科学
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PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2025
·
IF 6.6
Xiaoli Gong,Qiuyan Zhang,Na Zhang,Yuhao Zhang,Yu Fu
Long-term consumption of high-salt diets can lead to an increased risk of cardiovascular diseases. γ-Glutamyl peptides (GGP) display a taste-enhancing effect, which contributes to salt reduction. However, preparation of GGP in a sustainable fashion is challenging. Morchella esculenta stipe is a byproduct abundant in Glu/Gln, serving as a potential precursor of GGP. In this study, Morchella esculenta stipe was employed to prepare GGP by transpeptidation reaction. The reaction conditions were optimized, and their taste-enhancing effects were evaluated by sensory and electronic tongue analyses. Several novel GGP were identified by LC-MS/MS, and their binding modes with CaSR were analyzed by molecular docking. It was found that the optimal conditions were enzymatic hydrolysis for 5 h, transpeptidation time for 2 h, and enzyme of 12 U/g. GGP displayed a significant taste-enhancing effect based on sensory and electronic tongue analyses. Several novel di-, tri-, and oligo-GGPs were found. Molecular docking revealed that GGP can bind to CaSR through hydrogen bonds and hydrophobic interaction to enhance taste perception. Overall, this study highlights the potential of utilizing Morchella esculenta stipes as a sustainable source of γ-glutamyl peptides, which effectively enhance salt and umami taste perception and may contribute to salt reduction without compromising the taste.
研究领域:
食品科学
·
生物化学
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DOI
高影响因子
Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology
·
2014
·Vol. 298
·期 3
·501-512
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IF 1.53
Shuaishuai Huang,Yu Ren,Ping Wang,Yanyuan Li,Xue Wang,Haihui Zhuang,Rong Fang,Yuduo Wang,Ningsheng Liu,Michael Hehir,Jeff X. Zhou
Our previous studies illustrated that a steady increase of intracellular calcium concentration ([Ca 2+ ]i) was important for maintaining microtubules (MTs) rearrangement in apoptotic cells. However, little is known about the effect of calcium sensing receptor (CaSR)-mediated increase in [Ca 2+ ]i on cytoskeleton gene expression. We examined the impact of taxol or CaSR agonist/antagonist on the regulation of [Ca 2+ ]i concentration, cytoskeleton arrangement, phosphorylated CREB and cytoskeleton gene expressions in HeLa cells with dominant negative plasmid of CREB (PM). This study demonstrated that Gdcl3 (a specific CaSR agonist) evoked a rapid increase of [Ca 2+ ]i, formed a rigid bundle of MTs which surrounded the nucleus and decreased the cytoskeleton gene expressions in HeLa cells. These effects were rescued by addition of NPS2390 (a specific CaSR antagonist). Moreover, CaSR activity affected cytoskeleton gene expression through transcription factor CREB. Histoscores of pCREB immunoreactivity in tissues of cervical adenocarcinoma, renal clear cell carcinoma, and diffuse large B-cell lymphoma were markedly increased compared with non malignant tissue. These data demonstrate, for the first time, that CaSR-mediated increase in [Ca 2+ ]i probably modulate cytoskeleton organization and gene expression via transcription factor CREB. Anat Rec, 298:501–512, 2015. © 2014 Wiley Periodicals, Inc.
研究领域:
分子生物学
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细胞生物学
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肿瘤学
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高影响因子
ZEITSCHRIFT FUR NATURFORSCHUNG SECTION A-A JOURNAL OF PHYSICAL SCIENCES
·
2022
·Vol. 77
·期 7
·715-722
·
IF 1.712
Jinghao Zhuang,Wenlin Feng,Bo Zhou,Qili Zhang,Chong Liu,Yao Gong
A series of CaSr(WO 4 ) 2 : Eu 3+ and CaSr(WO 4 ) 2 : Eu 3+ , Li + phosphors with different Eu 3+ or Eu 3+ /Li + molar contents were successfully synthesized by high-temperature solid-state reaction. Through a series of characterization methods, the composition, structure and luminescence characteristics of the sample are obtained. Upon excitation at 393 nm, the strong red light corresponding to the 5 D 0 → 7 F 2 transition of Eu 3+ can be observed. The effect of Li + charge compensation on the photoluminescence of the sample is studied. The strongest red emission is obtained through 1% Eu 3+ and 1% Li + doping. All of the results indicate that Li + charge compensation can effectively enhance the red emissions intensity of Eu 3+ -doped CaSr(WO 4 ) 2 phosphors.
研究领域:
材料科学
·
光学
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DOI
高影响因子
Drug Delivery and Translational Research
·
2026
·
IF 6.9
Feng Chengmin,Liu Yuting,Zhang Chenghua,Niu Lijing,Dong Jun,Wang Bing
Fibroblast-to-myofibroblast transition (FMT) and resistance to apoptosis are central drivers of fibrosis. Here, we report that sustained release of Calcium Sensing Receptor (CaSR) positive allosteric modulators (L-Phe, L-Trp, and cinacalcet) from electrospun p-dioxanone copolymer membranes exerts potent, ligand-specific anti-fibrotic effects. All formulations activated Gq-coupled CaSR, evoking ER-Ca 2 ⁺ release and IP₃ generation. Differential recruitment of Gi yielded distinct cAMP/ROS signatures: cinacalcet (strong Gi bias) lowered cAMP and ROS levels, and suppressed AP-1, collagen-I and α-SMA expression; L-Trp (intermediate Gi) left cAMP unchanged while elevating ROS and inflammatory markers but nonetheless inhibited proliferation; L-Phe (weak Gi) raised cAMP, reduced ROS and fibrotic markers. Molecular docking confirmed Gi-coupling potency: cinacalcet (-125.4 kJ mol⁻ 1 ) > L-Trp (-101.7 kJ mol⁻ 1 ) > L-Phe (-75.5 kJ mol⁻ 1 ). In a rat intestinal-adhesion model, cinacalcet and L-Phe membranes prevented adhesions and collagen deposition, whereas L-Trp only inhibited proliferation. Thus, these findings indicate that CaSR ligands tune fibroblast fate via Gi-biased receptor conformations and that ligand electrospun membranes constitute a versatile materials platform for precision antifibrotic therapy. Graphical
The alternative text for this image may have been generated using AI.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Peng Deng,Yang Chen,Xing Shen,Qiuming Chen,Zhaojun Wang,Zhiyong He,Jie Chen,Maomao Zeng
Abstract CaSR has been recognized as a potential receptor involved in kokumi peptide perception. However, the molecular basis underlying kokumi-peptide-induced cellular responses remains insufficiently understood. Herein, CaSR-associated responses induced by kokumi peptides were investigated in STC-1 cells. Compared with MSG stimulation alone, MSG combined with γ-glutamyl peptides enhanced intracellular Ca2+ mobilization and CCK secretion, with response trends consistent with sensory evaluation. MSG+γEγEV elicited the strongest cellular response, increasing CCK secretion from 31.38 ± 3.18 pg/mL in the MSG group to 60.84 ± 4.45 pg/mL, while Ca2+ fluorescence intensity increased by 133.60% relative to MSG treatment alone (p < 0.05). Pretreatment with the CaSR antagonist NPS-2143 reduced MSG+γEγEV-induced Ca2+ mobilization and CCK secretion by 51.09 and 42.90%, respectively, supporting the involvement of CaSR in these cellular responses. Metabolomic and transcriptomic analyses revealed alterations in signaling-associated metabolites and pathways, including calcium signaling, MAPK signaling, PI3K-Akt signaling, cAMP signaling, phosphoinositide-related metabolism, and glycerophospholipid metabolism. These findings suggest that signaling responses associated with CaSR involvement in STC-1 cells share certain features with taste-related signal transduction processes. Collectively, the results provide insights into kokumi-peptide-induced cellular responses and their potential relevance to umami enhancement.
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高影响因子
EPILEPSY RESEARCH
·
2026
·
IF 2.3
Jiahao Liu,Jiawei Li,Ruting Fu,Liya Fang,Yuanyuan Liu,Ruici Liu,Deming Kong,Zhimei Jiang,Lei Liu,Luchuan Wang,Chao Gong,Pei Zeng,Youdi Fu,Xinru Zhu,Jin Guo,Shaobo Zhou
Upregulation of Casr and Gnb1 was observed in both PTZ- and KA-induced acute epilepsy mouse models. • Twenty-four hours post-seizure, reduced levels of Ras pathway activity markers were observed in association with hippocampal neuronal damage. • Vitamin D 3 mitigated brain injury by downregulating Casr , modulating the Ras pathway, and exerting neuroprotective effects. Objective This study aimed to investigate the neuroprotective effects of vitamin D 3 (cholecalciferol, hereinafter referred to as VitD) in acute epilepsy mouse models by examining its modulation of the calcium-sensing receptor ( Casr ), the Ras signalling pathway, and the potential mediator role of guanine nucleotide-binding protein subunit beta-1 ( Gnb1 ). Methods Acute epilepsy was induced in 135 C57BL/6 J mice via intraperitoneal injection(i.p.) of pentylenetetrazole (PTZ) or kainic acid (KA). Mice were randomly assigned to receive VitD pretreatment, valproate (VPA) emergency treatment, or a combination of VitD and Salirasib, a Ras pathway inhibitor. Seizure behaviours and electroencephalography (EEG) were recorded to confirm successful model establishment and to assess the efficacy of interventions. Hippocampal tissue was analysed for histopathological changes, as well as protein and mRNA expression levels of Casr, Gnb1, and Ras pathway-related molecules ( Kras , Raf-1 , Mek , Erk ) using western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Results Both PTZ and KA models showed successful seizure induction with associated hippocampal neuronal damage. Casr and Gnb1 expression were upregulated in both models, more prominently in the KA group, while Ras pathway activity was suppressed. VitD pretreatment reduced seizure frequency, delayed seizure onset, and alleviated neuronal damage—particularly in the PTZ model. VitD downregulated Casr , upregulated Gnb1 , and partially restored Ras pathway activity. Co-treatment with Salirasib enhanced neuroprotection and reduced Gnb1 expression. VPA similarly increased Gnb1 expression and suppressed Ras pathway activity. Conclusion VitD exerts neuroprotective effects in acute epilepsy, potentially through regulation of Casr and the Ras signalling pathway. In this context, Gnb1 likely acting as a downstream potential mediator linking Casr activation to Ras signalling. These findings highlight VitD’s potential as a neuroprotective agent in epilepsy and provide new insights into the molecular mechanisms underlying its action.
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高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Xiuye Huang,Yuxian Li,Yongan Liao,Xiaotong Lin,Xipan Zhao,Xiaojie Li,Shengliang Yuan,Jiuyao Zhou
Introduction The calcium-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), plays a critical role in kidney injury by promoting inflammation and apoptosis when activated. Whether Wulingsan (WLS), a traditional Chinese herbal formula used for kidney disorders, exerts its protective effects against acute kidney injury (AKI) via modulation of the CaSR pathway remains unclear. Methods WLS’s chemical profile was characterized by ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrometry (UHPLC-QE-MS). C57BL/6J mice were divided into Control, cisplatin (CP)-induced AKI, WLS (2.34/4.68/9.36 g/kg), and CaSR inhibitor NPS2143 (4.5 mg/kg) groups. Mice were pretreated with WLS/NPS2143 before CP injection (20 mg/kg, i. p.). Renal function, histopathology, inflammation, oxidative stress, and apoptosis were evaluated. Cisplatin-induced mouse renal tubular epithelial cells (mRTECs) were treated with WLS-containing serum (5%–10%) for in vitro validation. Molecular docking predicted the binding affinity of WLS components to CaSR. Results UHPLC-QE-MS identified 15 major WLS components, with 13 binding to CaSR (Polyporusterone E: binding energy of −10.4 kcal/mol). WLS pretreatment significantly improved renal function (reduced serum creatinine (SCr)/blood urea nitrogen (BUN)), attenuated tubular injury, suppressed inflammation (downregulated monocyte chemoattractant protein-1 (MCP-1)/tumor necrosis factor-α (TNF-α)/interleukin-1β (IL-1β)), alleviated oxidative stress (restored glutathione (GSH)/superoxide dismutase (SOD), reduced malondialdehyde (MDA)), and inhibited apoptosis (decreased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, modulated Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, downregulated cleaved Caspase 3). Mechanistically, WLS inhibited renal CaSR/calmodulin-dependent protein kinase β (CaMKKβ)/adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) pathway activation (reduced CaSR/CaMKKβ/p-AMPK expression). In vitro , WLS-containing serum reduced cisplatin-induced reactive oxygen species (ROS) production, intracellular Ca 2+ overload, and apoptosis in mRTECs, effects reversed by the CaSR agonist cinacalcet. Conclusion This study demonstrates that WLS protects against CP-induced kidney injury and inhibits apoptosis in renal tubular epithelial cells in association with the CaSR/CaMKKβ/AMPK pathway.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yuge Zhao,Weimin Yin,Zichen Yang,Jiuyuan Sun,Jiao Chang,Li Huang,Liangyi Xue,Xiaoyou Zhang,Hui Zhi,Shiyu Chen,Nana Chen,Yongyong Li
Transforming macrophages into the anti-inflammatory M2 phenotype could markedly strengthen inflammatory bowel disease (IBD) treatment, which is considered as a promising strategy. However, the high ferroptosis sensitivity of M2 macrophages, which decreases their activity, is a major stumbling block to this strategy. Therefore, promoting M2 polarization while simultaneously inhibiting ferroptosis to tackle this challenge is indispensable. Herein, a calcium‑carbonate (CaCO 3 ) mineralized liposome encapsulating a ferroptosis inhibitor (Fer-1) was developed (CaCO 3 @Lipo@Fer-1, CLF). The CaCO 3 mineralized coating shields the liposomes to prevent the release of Fer-1 in circulation, while releasing Ca 2+ in the acidic-inflammatory environment. This released Ca 2+ promotes M2 polarization through the CaSR/AKT/β-catenin pathway. The subsequently released Fer-1 effectively upregulates GSH and GPX4 , scavenges reactive oxygen species , and inhibits ferroptosis in M2 macrophages. In vivo, CLF improved the targeting efficiency of IBD lesions (about 4.17-fold) through the epithelial enhanced permeability and retention (eEPR) effect and enhanced IBD therapy by increasing the M2/M1 macrophage ratio and inhibiting ferroptosis. We demonstrate that the synergistic regulation of macrophage polarization and ferroptosis sensitivity by this mineralized nanoinhibitor is a viable strategy for IBD therapy.
研究领域:
纳米技术
·
药学
·
炎症
·
胃肠病学
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DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
·
2020
·
IF 4.364
Feng Chenxi,Bao Xiaoming,Shan Ling,Ling Yunxiang,Ding Yanfei,Wang Jia,Cao Yanzi,Wang Qinwen,Cui Wei,Xu Shujun
Calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCRs). Soluble β-amyloid peptide (Aβ) is one of the orthosteric modulators of CaSR, while, the role and underlying mechanism of CaSR in cognitive decline in Alzheimer’s disease (AD) is unclear. In this study, molecular technology such as live-cell imaging combined with behavioral tests were used to explore the role and the underlying mechanism of CaSR in the cognitive deficits in AD mice. The expression levels of CaSR were increased both in AD mice and Aβ1–42 (β-amyloid protein)-treated primary cultured neurons. Pharmacological inhibition of CaSR ameliorated recognitive and spatial memory deficits of Aβ1–42-oligomer-treated mice in a dose-dependent manner. Pharmacological inhibition of CaSR or down-regulation of the expression of CaSR by CaSR-shRNA-lentivirus prevented the impairment of filopodia, and the synapse induced by oligomeric Aβ1–42. The contents of cytosolic phospholipase A2 (cPLA2) and prostaglandin E2 (PGE2) in hippocampal neurons and tissue were increased after treatment with Aβ1–42 oligomers. Inhibition or down-regulation of CaSR mediates Aβ-induced synapse formation and cognitive deficits partially, through the activation of the cPLA2/PGE2 pathway. This study provides novel insights on CaSR, which is a promising therapeutic target for AD.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
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DOI
PubMed
高影响因子
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