ACS Applied Bio Materials
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2024
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IF 4.6
Yuxiang Zheng,Yongxu Ju,Yang Liu,Fang Yang
Piezoelectric materials, renowned for their ability to convert mechanical energy into electrical energy, have gained attention for their potential in biomedical applications. In particular, piezoelectric nanoparticles, such as barium titanate nanoparticles, hold great promise for treating neurologically related diseases. In this study, barium titanate piezoelectric nanoparticles are used as stimulators to directly treat epileptic neurons. After being modified by polyethylene glycol, barium titanate nanoparticles have shown excellent biocompatibility and dispersibility. Furthermore, such nanoparticles offer wireless piezoelectric stimulation to neurons in response to low-intensity pulsed ultrasound. More importantly, our experiments reveal that piezoelectric stimulation immediately reduces neuronal intracellular calcium concentration and restores cell viability. These effects are attributed to the opening of voltage-gated calcium channels and the release of active substances. These findings offer insights into the potential of piezoelectric stimulation as an approach for epilepsy treatment and enhance our understanding of the mechanisms underlying electrical stimulation in epileptic neurons.
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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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2119
·
IF 4.9
Chengwei Wang,Chunjie Wu,Linjiang Song
Saiga antelope horn (SAH), a rare traditional Chinese medicine, exhibits activities of anti-feverish convulsions and anti-inflammation, whereas its underlying mechanism and specific pharmacological components are still unclear. In the present study, transient receptor potential ankyrin 1 (TRPA1), a major transient receptor potential cation channel was used as a target protein to identified TRPA1 high-affinity peptides (THPs) from SAH digests. Firstly, the SAH was digested under in vitro gastrointestinal conditions. With the method of affinity ultrafiltration and liquid chromatography–mass spectrometry (AUF-LC/MS), about 200 peptides that have a high-affinity interaction with the TRPA1 protein were screened from SAH digests. Subsequently, bioactivity databases and molecular docking were further exploited to identified three THPs, including RCWPDCR, FGFDGDF, and WFCEGSF. Furthermore, RIN-14B cells, characterized by the high expression of TRPA1 on cell surfaces, were used as the cell model to investigate the biological effect of THPs. Immunofluorescence and ELISA were conducted and showed that THPs can increase the intracellular Ca2+concentration and serotonin (5-HT) secretion in RIN-14B cells by activating TRPA1, which is evidenced by impaired upregulation of intracellular Ca2+levels and 5-HT secretion after pretreatment with the TRPA1 inhibitor (HC-030031). Moreover, an analysis of Western blots displayed that THPs up-regulated the expression levels of the 5-HT synthesis rate-limiting enzyme (TPH1) and 5-hydroxytryptophan decarboxylase (Ddc), while serotonin reuptake transporter (SERT) levels were down-regulated, suggesting that THPs enhance 5-HT secretion by regulating the 5-HT synthesis pathway. In summary, our findings demonstrate that THPs, which were identified from SAH digest via TRPA1-targeted affinity panning, exhibited the activation of the TRPA1 channel and enhanced 5-HT release in RIN-14B cells.
研究领域:
药理学
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分子生物学
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传统中药
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细胞生物学
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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
MEDICAL SCIENCE MONITOR
·
2018
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IF 1.894
Hong Jiang,Chen Zhang,Wen He
Background Dracocephalum heterophyllum Benth flavonoid (DHBF) is a Tibetan and Uighur traditional medicine used to treat various disorders such as hypertension, lung heat, cough, and bronchitis; it has good antioxidant activity. Previous studies have shown that DHBF can reduce blood pressure in renovascular hypertensive rats, improve left ventricular systolic and diastolic function, and improve myocardial contractility. Therefore, we aimed to study the effect of DHBF on cardiomyocyte hypertrophy in cultured cells. Material/Methods Neonatal rat cardiomyocytes were cultured, and hypertrophy was induced by angiotensin II (Ang II), with or without varying concentrations of the DHBF extract. Cell Counting Kit-8 assay was used to assess cell viability, RT-qPCR was used to determine mRNA levels, confocal laser scanning microscopy was used to measure cell surface area and intracellular Ca 2+ concentrations ([Ca 2+ ] i ), and colorimetric assays were used to assess nitric oxide (NO) levels and nitric oxide synthase (NOS) activity. Results Ang II treatment of cardiomyocytes reduced cell viability to ~75% that of controls. Ang II treatment also increased cell surface area; increased mRNA expression of c-jun, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC); increased [Ca 2+ ] i ; and reduced NOS activity and NO production. DHBF treatment could reverse these effects in a concentration-dependent manner. Conclusions These results showed that DHBF can ameliorate cardiomyocyte hypertrophy induced by Ang II, as indicated by the downregulation of cardiac hypertrophy genes ( ANP , BNP , and β -MHC ) and reduction in cell surface area. The mechanism may be related to NO release and [Ca 2+ ] I regulation.
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
CARBOHYDRATE POLYMERS
·
2023
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IF 11.2
Yonggang Lv,Xi Chen,Yaping Shen
Although various drug delivery systems that regulated Ca 2+ concentration has been developed for tumor therapy, their application still presented significant challenges due to the complex preparation and introduction of a large number of inorganic molecules that might cause serious toxic effects. To solve these problems, a folate-functionalized carboxymethyl chitosan (CMCS)/calcium phosphate hybrid nanoparticle (CF/CaP) with Ca 2+ production was designed to treat breast cancer combined with the Ca 2+ inhibitory effect of encapsulated curcumin (Cur). It was demonstrated that the optimal CF/CaP nanoparticles loaded with Cur (C@CF/CaP) were spherical nanoparticles, which exhibited a smaller size at about 179 nm than non-targeted nanoparticles with size at about 234 nm. C@CF/CaP had good biocompatibility, high stability and acid responsive drug release. Compared with the neutral environment, the cumulative release of Cur was >70 % after culture for 36 h at pH 5.0. Compared with non-targeted nanoparticles, C@CF/CaP could specifically target tumor tissues and then enter tumor cells through folate receptor-mediated endocytosis . C@CF/CaP could cause mitochondrial Ca 2+ overload, trigger the mitochondrial apoptotic pathway, destroy the mitochondrial structure and finally have good anti-tumor efficiency. The results proved that Ca 2+ nanomodulators based on CMCS might provide a potential organelle targeting strategy for cancer therapy.
研究领域:
药学
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纳米技术
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肿瘤学
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生物医学工程
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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
Xiuwen Zheng,Qianrong Xue,Yinghuan Wang,Lu Lu,Yipeng Pan,Jian Xu,Junqing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance is a perennial natural medicine herbivorous plant, has been used in the management of treat stomach pain and diabetes, it is abundantly cultivated in Qiongzhong, Baisha and other places. P. cablin (Blanco) Benth, one of the most important traditional Chinese plants, which plays functions in antioxidant and gastrointestinal regulation, has been extensively planted in Hainan, Guangdong and other regions. Aim of the study In this study, we investigated the role and underlying molecular mechanism of AP on diabetic gastroparesis (DGP) in vitro and in vivo . Materials and methods In this study, using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum Hance– P. cablin (Blanco) Benth drug pair (AP). Molecular docking were utilized to explore the potential mechanism of AP treatment of DGP. In in vitro assays, gastric smooth muscle cells (GSMCs) were treated with 35 mM glucose to promote apoptosis and construct the DGP model, which was treated with different concentrations of AP. Furthermore, transfection technology was used to overexpress RAGE in GSMCs and elucidate the underlying mechanisms of alleviation of DGP by AP. Results Using UPLC-MS/MS analysis, nine components of AP were identified. We found that AP effectively blocked the increase in apoptosis, oxidative stress, and intracellular Ca 2+ concentrations. For in vivo experiments, mice were fed with a high-fat irregular diet to construct DGP model, and AP was co-administered via oral gavage daily to prevent the development of DGP. Compared with DGP mice, AP significantly decreased fasting blood glucose levels and increased gastric emptying levels. Consistent with in vitro experiments, AP also considerably decreased the increase in oxidative stress in DGP mice. Mechanistically, AP alleviates apoptosis and DGP by decreasing oxidative stress and intracellular Ca 2+ concentrations via the inhibition of the AGE/RAGE axis. Conclusions Collectively, this study has established that AP can improve DGP, and the mechanism may be related to the inhibition the AGE/RAGE axis to mitigate apoptosis and DGP. To summarize, this study provides a novel supplementary strategy for DGP treatment.
研究领域:
民族药理学
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药理学
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分子生物学
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糖尿病
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胃肠病学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Yunbo Jia,Xiaoxi Xu,Yang Liu,Hongfei Shen,Siyu Sun,Guangwei Sun
Changes in sodium alginate and calcium ion concentrations have a considerable impact on the structural properties of calcium alginate gel (ALG) beads, consequently influencing the biological characteristics of the cells encapsulated within them. This study aimed to examine the effects of calcium on the metastatic potential of hepatocellular carcinoma (HCC) cells encapsulated in ALG beads. The results showed that the invasion ability of HCC cells significantly increased when they were encapsulated in beads prepared with a calcium concentration of 200 mM compared to those prepared with a calcium concentration of 50 mM. Furthermore, the expression levels of genes related to metastasis were significantly elevated in ALG beads prepared with a calcium concentration of 200 mM. Specifically, the expression of activated matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and urokinase-type plasminogen activator system proteins was found to be high. Conversely, the expression of phosphatase and tensin homolog deleted on chromosome 10 was observed to be significantly reduced. These findings indicate that manipulating the calcium ion concentration during the fabrication of ALG beads enables the generation of three-dimensional HCC cells with varying metastatic capacities. This model offers a valuable tool for investigating the mechanisms underlying liver cancer metastasis and screening potential therapeutic drugs.
研究领域:
癌症生物学
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细胞生物学
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药理学
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PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
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2020
·Vol. 97
·期 2
·398-407
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IF 2.721
Zhang Huilan,Wang Juan,Zhang Wen,Han Dong,Zhang Aiping
In the paper, a composite TiO 2 /SiO 2 -NHOC-FA was prepared using the coupling method which is a folic acid-targeted silica-coated titanium dioxide. Their structures were characterized by Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis), X-ray diffraction (XRD), transmission electron microscope (TEM) and zeta potential method. The results showed that the average diameter of the prepared TiO 2 /SiO 2 -NHOC-FA composite is 18 nm, which is spherical. Compared with unmodified TiO 2 , TiO 2 /SiO 2 -NHOC-FA composite had superior water solubility and dispersion, and enhanced its photokilling activity by folic acid-targeted to FR (+) cells. In addition, photocatalytic TiO 2 /SiO 2 -NHOC-FA arrested cell cycle in G2/M phase of MCF-7 cells, resulting in a significant reduction of mitochondrial membrane potential (MMP), and also made the apoptosis rate, ROS components and intracellular calcium concentration increased. It killed the MCF-7 cells through apoptosis pathway. These results for the TiO 2 /SiO 2 -NHOC-FA composite can provide a theoretical basis for the photodynamic development of TiO 2 .
研究领域:
纳米技术
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癌症研究
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光催化
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
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IF 4.679
Desen Yang,Wanqin Wu,Guoping Gan,Dingkun Wang,Jing Gong,Ke Fang,Fuer Lu
The neuroprotective effects and potential mechanisms of (-)-Syringaresinol-4-O-β-D-glucopyranoside (SRG), a natural lignan glycoside extracted from Cortex Albizziae , were investigated using corticosterone (CORT)-induced PC12 cells as an in vitro anxiety model. PC12 cells were treated with 100 μM CORT and 5, 10, or 20 μM SRG for 48 h. Cell viability and lactate dehydrogenase (LDH) leakage were measured. Apoptosis were detected using FITC-coupled Annexin V (AV) and propidium iodide (PI) staining flow cytometric analyses and TUNEL assays. Rhodamine 123 and Fluo-3-AM staining flow cytometric analyses were used to detect mitochondrial membrane potential (ΔΨm) and intracellular calcium concentration ([Ca 2+ ] i ), respectively. Western blot was used to detect brain-derived neurotrophic factor (BDNF), Bax, Bcl-2, cAMP-response element binding protein (CREB), cytosolic cytochrome c (Cyt c ), caspase-3, and cleaved caspase-3. Experimental data showed that SRG promoted cell proliferation , reduced LDH release, inhibited apoptosis, improved ΔΨm values, decreased [Ca 2+ ] i , up-regulated CREB, BDNF, and Bcl-2, down-regulated Bax and Cyt c protein expression levels, and reduced caspase-3 activity. This suggests that SRG has neuroprotective and antiapoptotic effects in the pathogenesis of anxiety disorders, and its mechanisms are partly connecte to inhibition of the mitochondrial apoptotic pathway and activation of pathways involving CREB and BDNF.
研究领域:
神经科学
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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
APPLIED BIOCHEMISTRY AND MICROBIOLOGY
·
2023
·Vol. 58
·期 1
·S138
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IF 0.8
Zhang Q.,Li J.,Sun Y.,Song S.,Li X.,Chen G.
Abstract Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Neuritic plaques containing amyloid-β protein (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein constitute major neuropathological hallmarks of AD. The neurotoxicity of aggregated Aβ has been implicated as a critical cause in the pathogenesis of AD. The aim of this study was to exam the use of neoagarohexaose (NAH) in the potential treatment of AD effects, using SH-SY5Y neuronal cell line exposed to β-amyloid protein (Aβ 1-42 ). The present study was designed to explore the neuroprotective effects of NAH on neuroblastoma SH-SY5Y cells as a function of dosage. The cells were exposed to Aβ 1-42 with or without NAH (26.7, 53.4, and 106.8 μM) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used for detecting the viability of treated cells. In treated cells, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were determined using their manufacturer kits. Flow cytometry analysis was used to assess apoptosis, changes in intracellular calcium concentration, and the mitochondrial membrane potential (MMP) after treatment. Additionally, changes in the mechanism of Aβ 1-42 aggregation in the presence of NAH were explored using thioflavin T (ThT) and Congo red (CR) assays. The results showed that incubation with NAH prior to Aβ 1-42 exposure increased cell survival and prevented reactive oxygen species generation. Moreover, NAH decreased the apoptotic rate, inhibited MMP depolarization, reversed the change in intracellular calcium concentration, enhanced the activities of SOD and GSH-Px, and decreased the level of MDA. In addition, the results showed that NAH, which reduced the absorption of the amyloid indicator ThT and CR dyes, was a potent inhibitor of Aβ fibrillogenesis. In conclusion, NAH protects SH-SH5Y cells from Aβ-induced damage by reducing oxidative stress and weakens the spontaneous amyloid formation of Aβ fibrils in vitro and can inhibit the amyloidization of amyloid β protein (Aβ). This study shows that NAH may be a promising anti-AD drug candidate for AD treatment.
研究领域:
神经科学
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药理学
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细胞生物学
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DOI
高影响因子
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