Frontiers in Physiology
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2022
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IF 4.755
Jiang Xuan,Zhang Ying,Zhang Huaxing,Zhang Xiaoguang,Yin Xiaopeng,Yuan Fang,Wang Sheng,Tian Yanming
The heart has high energy requirements, with an estimated 40%–60% of myocardial ATP production derived from the oxidation of fatty acids under physiological conditions. However, the effect of short-chain fatty acids on myocardial contraction remains controversial, warranting further research. The present study sought to investigate the effects and mechanisms of acetate, a short-chain fatty acid, on myocardial contraction in rat ventricular myocytes. Echocardiography and Langendorff heart perfusion were used to evaluate cardiac function. Cell shortening and calcium transient were measured in isolated cardiomyocytes. The patch-clamp method determined the action potential and L-type Ca2+ current in cardiomyocytes. Moreover, the expression of GPR43, a type of short-chain fatty acid receptors in cardiomyocytes was examined by immunofluorescent staining and Western blot. We demonstrated that acetate transiently reduced left ventricular developmental pressure in isolated Langendorff heart perfusion model, with no effect on stroke volume and cardiac output in vivo. In addition, acetate transiently and reversibly inhibited cardiomyocyte contraction and calcium transient. Acetate did not affect the action potential and L-type Ca2+ currents in cardiomyocytes. As a short-chain fatty acid receptor, GPR43 was expressed in rat cardiomyocytes. Furthermore, the GPR43 antagonist GLPG0974 prevented the acetate-induced inhibitory effect on myocardial contraction. We conclude that acetate transiently inhibits contraction via the short-chain fatty acid receptor GPR43 in cardiomyocytes.
研究领域:
心脏病学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Cardiovascular Translational Research
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2022
·Vol. 16
·期 1
·127-140
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IF 3.216
Hao Jiameng,Chang Liping,Wang Dandong,Ji Chuanyuan,Zhang Shaolan,Hou Yunlong,Wu Yiling
Heart failure with preserved ejection fraction (HFpEF) is a common public health problem associated with increased morbidity and long-term mortality. However, effective treatment for HFpEF was not discovered yet. In the present study, we aimed to decipher the effects of Periplocin on DOCA-induced heart failure rats and explore the possible underlying mechanisms. We demonstrated that Periplocin could significantly attenuate cardiac structural remodeling and improve cardiac diastolic function. Of note, Periplocin significantly inhibited the recruitment of inflammatory and immune cells and decreased the expression of serum inflammatory cytokines. Meanwhile, Periplocin had the effect of cardiac glycosides to improve cardiomyocyte contractility and calcium transient amplitude. These findings indicate that Periplocin might be a potential medicine to treat HFpEF in patients. Graphical abstract
研究领域:
心脏病学
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药理学
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEUROBIOLOGY OF DISEASE
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2025
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IF 5.6
Teng Teng,Shaofan Yang,Jin Li,Haoyu Wang,Fengjuan Wu,Yong He,Jihua Fan,Hongwei Shi,Mingzhu Huang,Xiang Zhou,Ying Liu,Mingyue Gong,Chuanyan Yang,Huiquan Wang,Zhenlu Cai,Hongli Li,Kuan Zhang
The astrocyte–neuron network in the primary somatosensory cortex (S1) responds dynamically to pain stimuli and plays a pivotal role in pain processing. These stimuli activate astrocytic α7-nicotinic acetylcholine receptors (α7-nAChRs), yet their contribution to pain perception remains largely unclear. This study investigates the role of astrocytic α7-nAChRs in pain information processing and perception. Astrocytic α7-nAChRs were selectively deleted by injecting rAAV5-GfaABC 1 D-NLS-Cre-P2A-mCherry into the S1 region of LoxP-Chrna7 transgenic mice or by tamoxifen administration in ALDH1-CreERT2:Chrna7 loxP/loxP mice. Immunohistochemistry was used to assess the expression of α7-nAChR and gliotransmitter d -serine. Astrocytic Ca 2+ transients were monitored in vivo using two-photon Ca 2+ imaging following AAV5-GfaABC 1 D-cytoGCaMP6f-SV40 labeling. Neuronal Ca 2+ transients in S1 evoked by plantar electric shock were recorded via fiber photometry in freely moving mice. Nociceptive and sensory behaviors were evaluated using hot plate and von Frey tests. Statistical analyses included Welch's t -tests for normally distributed data, Mann–Whitney U tests for non-normal data, and two-way ANOVA. Results showed that conditional deletion of α7-nAChRs in astrocytes markedly reduced d -serine levels within astrocytic territories. Two-photon Ca 2+ imaging and fiber photometry revealed that α7-nAChR deletion attenuated both astrocytic Ca 2+ transients and footshock-evoked neuronal Ca 2+ activity in S1. Behaviorally, thermal pain responses were significantly impaired, whereas tactile thresholds and open-field behaviors were unaffected. These findings identify astrocytic α7-nAChRs in S1 facilitate d -serine levels and enhance astrocytic activity. Their physiological function is essential for pain-related information processing within astrocyte–neuron networks and plays a critical role in regulating pain perception.
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DOI
PubMed
高影响因子
CANCER CELL
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2025
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IF 44.5
Yang Yang,Chuanyan Yang,Xuezhu Chen,Yibin Jiang,Xuejiao Lei,Kang Ma,Yulian Quan,Tianran Li,Chenfu Guo,Yijing Meng,Lin Kang,Xinyu Zhang,Long Jin,Jiafeng Huang,Ning Mu,Zexuan Yan,Qinghua Ma,Shuai Wang,Yanxia Wang,Yong-Ning Shang,Cong Chen,Yu Shi,Shukun Hu,Likun Yang,Chuan Lan,Rong Hu,Ying Zhang,Xia Li,Yunqing Li,Chong Liu,Yu-Hai Wang,Fei Li,Hua Feng,Xiu-Wu Bian,Tunan Chen
Glioblastoma (GBM), the most aggressive primary brain tumor, is shaped by its integration into neural networks. While glutamatergic input is linked to tumor progression, the broader architecture and function of neuron-glioma connectomes remain unclear. Using monosynaptic rabies tracing, we map brain-wide neural input to patient-derived xenografts and reveal a consistent organizational logic: local inputs are primarily glutamatergic, while long-range connections exhibit diverse neurotransmitter profiles, with basal forebrain cholinergic projections emerging as a conserved input across sites. Functionally, presynaptic acetylcholine release promotes GBM progression through muscarinic receptor CHRM3 in a circuit-specific manner. Mechanistically, glutamatergic and cholinergic signals converge to enhance glioma calcium transients but diverge in temporal transcriptional control, with their dual blockade producing additive anti-tumor effects. Therapeutically, the anticholinergic drug scopolamine attenuates glioma growth, whereas the acetylcholinesterase inhibitor donepezil exacerbates disease. These findings reveal the complexity of neuron-glioma connectivity, highlighting long-range neuromodulatory pathways as promising therapeutic targets in GBM.
研究领域:
神经肿瘤学
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神经科学
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癌症生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
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