Clinical & Translational Oncology
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2023
·Vol. 25
·期 6
·1629-1640
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IF 3.4
Zhang Yi-Dan,Zhong Rui,Liu Jin-Quan,Sun Zhen-Xuan,Wang Teng,Liu Jin-Tao
Purpose Breast cancer is one of the leading causes of tumor death worldwide in female, and the five-year overall survival of breast cancer patients remains poor. It is an urgent need to seek novel target for its treatment. Synaptotagmin 13 (SYT13) is a synaptic vesicle transporting protein that regulates the malignant phenotypes of various cancers. However, its role in breast cancer is still unclear. The current study aimed to investigate the effects of SYT13 on the progression of breast cancer. Methods Twenty-five pairs of breast cancer tissues and non-tumor tissues were obtained to assess the expression of SYT13. We manually modified the expression of SYT13 in MCF-7 and MDA-MB-231 cells. CCK-8 assay, EdU staining, and cell cycle analysis were carried out to measure the proliferated ability of cells. Annexin V/PI and TUNEL assays were used to detect the apoptotic ability of cells. Wound healing and transwell assays were employed to evaluate the migrated and invasive ability of breast cancer cells. Results The results revealed that the mRNA and protein levels of SYT13 were higher in breast cancer tissues and cell lines. Knockdown of SYT13 inhibited the cell proliferation and induced cell cycle arrest in G1 phase of MCF-7 cells by downregulating cyclin D1 and CDK4, as well as upregulating p21. The migration and invasion of MCF-7 cells were repressed by the loss of SYT13 via the gain of E-cadherin and the loss of vimentin. Overexpression of SYT13 in MDA-MB-231 cells led to the opposite effects. Silencing of SYT13 induced the apoptosis ability of MCF-7 cells by the upregulation of bax and the downregulation of bcl-2. Moreover, we found that SYT13 depletion suppressed the FAK/AKT signaling pathway. PF573228 (a FAK inhibitor) and MK2206 (an AKT inhibitor) reversed the SYT13 overexpression-induced promotion of proliferation, migration, and invasion of MDA-MB-231 cells. Conclusion The results indicated that SYT13 promoted the malignant phenotypes of breast cancer cells by the activation of FAK/AKT signaling pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症生物学
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PubMed
高影响因子
Frontiers in Molecular Neuroscience
·
2017
·
IF 5.076
Li Yun,Wang Shen,Li Tianzhi,Zhu Le,Xu Yuanyuan,Ma Cong
The Ca2+ sensor synaptotagmin-1 (Syt1) plays an essential function in synaptic exocytosis. Recently, Syt1 has been implicated in synaptic vesicle priming, a maturation step prior to Ca2+-triggered membrane fusion that is believed to involve formation of the ternary SNARE complex and require priming proteins Munc18-1 and Munc13-1. However, the mechanisms of Syt1 in synaptic vesicle priming are still unclear. In this study, we found that Syt1 stimulates the transition from the Munc18-1/syntaxin-1 complex to the ternary SNARE complex catalyzed by Munc13-1. This stimulation can be further enhanced in a membrane-containing environment. Further, we showed that Syt1, together with Munc18-1 and Munc13-1, stimulates trans ternary SNARE complex formation on membranes in a manner resistant to disassembly factors NSF and α-SNAP. Disruption of a proposed Syt1/SNARE binding interface strongly abrogated the stimulation function of Syt1. Our results suggest that binding of Syt1 to an intermediate SNARE assembly with Munc18-1 and Munc13-1 is critical for the stimulation function of Syt1 in ternary SNARE complex formation, and this stimulation may underlie the priming function of Syt1 in synaptic exocytosis.
研究领域:
神经科学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Iranian Journal of Basic Medical Sciences
·
2017
·
IF 1.424
Jimei Bu,Hengbing Zu
Objective(s): In previous studies, researchers observed that doxepin could improve cognitive processes and has protective effects on the central nervous system. Thus, this study was designed to analyze the effects of doxepin on β-amyloid (Aβ)-induced memory impairment and neuronal toxicity in rat and to explore the underlying mechanism. Materials and Methods: Rats were treated with Aβ1-42 and doxepin was injected to validate its effects on cognitive function. The Morris water maze test was performed to detect memory function. Aβ1-42-treated SH-SY5Y human neuroblastoma cell line was also used to detect the effects of doxepin and to explore the underlying mechanism. Western blotting analysis was used to detect the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. Results: After treated with 1 mg/kg of doxepin, Aβ1-42-treated rats showed markedly lower escape latency and higher platform-finding strategy score. Low doses of doxepin significantly reversed the effects of Aβ1-42 on the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. In vitro experiment showed the consistent results. Besides, PI3K inhibitor (LY294002) treatment could markedly reversed the effects of doxepin on Aβ1-42-treated SH-SY5Y cells. Conclusion: Our results demonstrated that doxepin could protect against the Aβ1-42-induced memory impairment in rats. The protective effect of doxepin was associated with the enhancement of PSD-95 and synapsin 1 expression via PI3K/AKT/mTOR signaling pathway.
研究领域:
神经科学
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药理学
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认知科学
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2023
·
IF 5.1
Wu Yuhan,Zhu Zhanpeng,Lan Tian,Li Shuhan,Li Ye,Wang Changmin,Feng Yabo,Mao Xueqin,Yu Shuyan
Depression is a common psychological disease with high morbidity and mortality. Recently, the involvement of synaptic plasticity in the pathogenesis of depression has shed light on the direction of developing novel antidepressants. Levomilnacipran is a newly approved medication for the treatment of adult major depressive disorder. However, the detailed mechanisms underlying its antidepressant-like effects have yet to be illuminated. In this study, we aimed to investigate the role of levomilnacipran in regulating synaptic plasticity and explore the possible molecular mechanisms of its antidepressant effects using a rat model of depression induced by lipopolysaccharide (LPS). The results demonstrated that levomilnacipran (30 mg/kg, i.p.) significantly ameliorated depression-like behaviors in rats, alleviated the dysregulation of synaptic plasticity, and suppressed neuroinflammation within hippocampus induced by LPS-treatment. Levomilnacipran increased the expression of postsynaptic dense 95 (PSD-95) and synaptophysin (Syn) and reversed the imbalance between pro- and anti-inflammatory cytokines within hippocampus of depressed rats. Additionally, levomilnacipran elevated expression level of brain-derived neurotrophic factor (BDNF), accompanied by increased tyrosine kinase B (TrkB), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR). Taken together, these results suggest that levomilnacipran may exert antidepressant effects via upregulating BDNF/TrkB mediated PI3K/Akt/mTOR signaling pathway to improve synaptic plasticity. These findings reveal potential mechanisms for the antidepressant effects of levomilnacipran and offer new insights into the treatments for depression. Graphical Abstract
研究领域:
神经科学
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药理学
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分子生物学
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精神病学
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·
IF 4.3
Yan Qian,Li Xiao-Jun,Wang Qi-Qi,Jia Wei,Wang Shu-Ling
Approaches of promoting a neural milieu permissive for plasticity and resilience against neuronal injury are important strategies for the treatment of a range of neurological disorders. Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective against various mental diseases. However, the underlying molecular mechanisms remain elusive. Here, we report a study of the neuroprotective effects of FGF21 by promoting 5-HT 1A R-FGFR1 heteroreceptor formation and triggering MEK 1/2 -ERK 1/2 signaling pathway in normal or abnormal neurological conditions. First, the in vitro cellular experiments demonstrated that FGF21 exerted a protective effect against glutamate-induced cytotoxicity and promoted cell differentiation and growth. Then, in wild-type and FGF21 −/− mice, exogenous FGF21 promoted FGFR1-5-HT 1A R heteromers formation in the CA3 and dentate gyrus region of the hippocampus and activated MEK 1/2 -ERK 1/2 signaling. Coordinately, FGF21 exerted similar influences in the hippocampi of IBA-induced neurological injury mice or combined stress-exposed mice. Besides, FGF21 treatment activated the phosphorylation of FGFR1 and elevated the expression of synaptophysin in these mice with neurological injury or combined stress exposure. These results illustrated that FGF21 alleviated neurological impairment through FGFR1-5-HT 1A R heteromer and ERK 1/2 signal activation and suggested that the regulation of FGFR1-5-HT 1A R heteromers and MEK 1/2 /ERK 1/2 pathway may play a key role in mediating the neuroprotective effects of FGF21 against various neurodegeneration conditions.
研究领域:
神经科学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2021
·
IF 2.63
Junbin Lin,Chizi Hao,Yu Gong,Ying Zhang,Ying Li,Zhihe Feng,Xiangdong Xu,Hailong Huang,Weijing Liao
Tetramethylpyrazine (TMP) has been widely used in ischemic stroke in China. The regulation of neuroplasticity may underlie the recovery of some neurological functions in ischemic stroke. Middle cerebral artery occlusion (MCAO) model was established in this study. Rats were divided into three groups: sham group, model group, and TMP group. The neurological function was evaluated using modified neurological severity score (mNSS). Following the neurological function test, expression of synaptophysin (SYP) and growth-associated protein 43 (GAP-43) were analyzed through immunohistochemistry at 3 d, 7 d, 14 d, and 28 d after MCAO. Finally, the synaptic structural plasticity was investigated using transmission electron microscopy (TEM). The TMP group showed better neurological function comparing to the model group. SYP levels increased gradually in ischemic penumbra (IP) in the model group and could be enhanced by TMP treatment at 7 d, 14 d, and 28 d, whereas GAP-43 levels increased from 3 d to 7 d and thereafter decreased gradually from 14 d to 28 d in the model group, which showed no significant improvement in the TMP group. The results of TEM showed a flatter synaptic interface, a thinner postsynaptic density (PSD), and a wider synaptic cleft in the model group, and the first two alterations could be ameliorated by TMP. Then, a Pearson’s correlation test revealed mNSS markedly correlated with SYP and synaptic ultrastructures. Taken together, TMP is capable of promoting functional outcome after ischemic stroke, and the mechanisms may be partially associated with regulation of neuroplasticity.
研究领域:
神经科学
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药理学
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卒中研究
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DOI
PubMed
高影响因子
PeerJ
·
2018
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IF 2.118
Yu Lei,Chengkun Wang,Quan Jiang,Xiaoyi Sun,Yongzhong Du,Yaofeng Zhu,Yingmei Lu
The toxicity of engineered nanoparticles remains a concern. The knowledge of biohazards associated with particular nanoparticles is crucial to make this cutting-edge technology more beneficial and safe. Here, we evaluated the toxicity of Ga 2 O 3 nanoparticles (NPs), which are frequently used to enhance the performance of metal catalysts in a variety of catalytic reactions. The potential inflammatory signaling associated with the toxicity of HA/β-Ga 2 O 3 :Cr 3+ NPs in primary cortical neurons was examined. We observed a dose-dependent decrease in cell viability and an increase in apoptosis in neurons following various concentrations (0, 1, 5, 25, 50, 100 µg/ml) of HA/β-Ga 2 O 3 :Cr 3+ NPs treatment. Consistently, constitutively active forms of calcineurin (48 kDa) were significantly elevated in cultured primary cortical neurons, which was consistent with calpain activation indicated by the breakdown products of spectrin. Moreover, HA/β-Ga 2 O 3 :Cr 3+ NPs result in the elevation of LC3-II formation, SQSTM/p62, and Cathepsin B, whereas phosphorylation of CaMKII (Thr286) and Synapsin I (Ser603) were downregulated in the same context. Taken together, these results demonstrate for the first time that calpain activation and a disturbance of autophagy signaling are evoked by exposure to HA/β-Ga 2 O 3 :Cr 3+ NPs, which may contribute to neuronal injury in vitro .
研究领域:
纳米技术
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神经科学
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毒理学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Cellular Neuroscience
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2022
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IF 6.147
Yuhong Wang,Kaixuan Luo,Junrui Li,Yehui Liao,Chengde Liao,Wen-Shiang Chen,Moxian Chen,Lijuan Ao
Parkinson’s disease (PD) is the second most common chronic neurodegenerative disease globally; however, it lacks effective treatment at present. Focused ultrasound (FUS) combined with microbubbles could increase the efficacy of drug delivery to specific brain regions and is becoming a promising technology for the treatment of central nervous system diseases. In this study, we explored the therapeutic potential of FUS-mediated blood–brain barrier (BBB) opening of the left striatum to deliver gastrodin (GAS) in a subacute PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration of GAS in the left hemisphere was detected by ultra-high performance liquid chromatography electrospray Q-Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap) and the distribution of tyrosine hydroxylase (TH) neurons was detected by immunohistochemical staining. The expression of TH, Dopamine transporter (DAT), cleaved-caspase-3, B-cell lymphoma 2 (Bcl-2), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYN) protein were detected by western blotting. Analysis showed that the concentration of GAS in the left hemisphere of PD mice increased by approximately 1.8-fold after the BBB was opened. FUS-mediated GAS delivery provided optimal neuroprotective effects and was superior to the GAS or FUS control group. In addition, FUS enhanced GAS delivery significantly increased the expression of Bcl-2, BDNF, PSD-95, and SYN protein in the left striatum ( P < 0.05) and reduced the levels of cleaved-caspase-3 remarkably ( P = 0.001). In conclusion, the enhanced delivery by FUS effectively strengthened the protective effect of GAS on dopaminergic neurons which may be related to the reinforcement of the anti-apoptotic activity and the expression of synaptic-related proteins in the striatum. Data suggests that FUS-enhanced GAS delivery may represent a new strategy for PD treatment.
研究领域:
神经科学
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药理学
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生物医学工程
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
·
IF 6.1
Sheng-Quan Su,Gui-Yuan Xiong,Chun-Yan Yao,Xiao-Ling Liu,Yin-Yin Xia,Jin-Yun Long,Xiu-Kuan Li,Liang-Mei Wang,Long Yi,Wu-Wei Xu,Wu-Qiang Lu,Qian-Qian Li,Ting Hu,Hao Liu,Ke-Xue Wang,Peng Luo,Tong-Jian Cai
T-2 toxin, classified as a mycotoxin, harms immune and cognitive systems. Recently, an increasing number of studies have focused on the neurotoxic effects of T-2 toxin. However, there is still a need for a better understanding of the molecular mechanisms involved. In this study, we aimed to elucidate the protective effect of resveratrol (Res) supplementation against T-2 toxin-induced spatial learning and memory impairment and to investigate the communication mechanisms between the gut and the brain. Mice received a single intraperitoneal dose of T-2 toxin (4 mg/kg) followed by Res (100 mg/kg) administered via the same route. The Morris water maze and novel object recognition tests demonstrated that T-2 toxin had a profound negative impact on spatial learning and memory in mice. However, the administration of Res successfully mitigated the cognitive impairments caused by T-2 toxin and notably enhanced the levels of brain-derived neurotrophic factor (BDNF), synaptophysin I (SYN1), and postsynaptic density protein 95 (PSD-95). Moreover, Res demonstrated a protective effect against T-2 toxin-induced damage to hippocampal tissue. Simultaneously, it played a pivotal role in restoring gut microbiota equilibrium and maintaining the integrity of intestinal tight junctions, effectively curbing both localized and systemic inflammation triggered by T-2 toxin exposure. In conclusion, our findings suggest that resveratrol may alleviate T-2 toxin-induced spatial learning and memory deficits, possibly via gut-brain axis modulation.
研究领域:
神经毒理学
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神经科学
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毒理学
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药理学
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微生物学
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免疫学
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认知科学
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产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2025
·Vol. 57
·期 8
·1234
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IF 3.4
Huihui Ju,Yile Zhou,Wanting Wei,Yan Hu,Hongwei Fang,Zhouyi Chen,Xia Sun,Yi Shi,Hao Fang
Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide in vitro . The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of Lactobacillales , elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.
研究领域:
神经科学
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微生物学
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衰老研究
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胃肠病学
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认知科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2015
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IF 3.516
Dan Lu,Anding Xu,Hongcheng Mai,Jiayi Zhao,Chanjuan Zhang,Renbin Qi,Huadong Wang,Daxiang Lu,Lihong Zhu
Neural stem cells (NSCs) transplanted is one of the hottest research to treat Alzheimer’s disease (AD), but cholinergic neurons from stem cells were also susceptible to cell death which Heat shock protein 70 (HSP70) was affirmed to reverse. Related to cognitive impairment, cholinergic nervous cells should be investigated and ginsenoside Rg1 (G-Rg1) was considered to increase them. We chose tert-butyl hydroperoxide (t-BHP) damage model to study in vitro. Functional properties of our recombination plasmid pEGFP-C2-HSP70 were affirmed by SH-SY5Y cells. To opposite the transitory appearance of HSP70, NSCs used as the vectors of HSP70 gene overexpressed HSP70 for at least 7 days in vitro. After transfection for 3 days, G-Rg1 pretreatment for 4 hours, and coculture for 3 days, the expression of acetylcholinesterase (ChAT), synaptophysin, and the ratio of NeuN and GFAP were assessed by western blot; Morphological properties were detected by 3D reconstruction and immunofluorescence. ChAT was markedly improved in the groups contained G-Rg1. In coculture system, the ratio of neurons/astrocytes and the filaments of neurons were increased; apoptosis cells were decreased, compared to monotherapy (). In conclusion, we demonstrated that, as a safe cotreatment affirmed in vitro, overexpression of HSP70 in NSCs plus G-Rg1 promoted nervous cells regeneration from chronic oxidative damage.
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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分子生物学
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干细胞研究
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yiyang Du,Tingxu Yan,Bo Wu,Bosai He,Ying Jia
Ethnopharmacological relevance Increased inflammatory response and disruption of neuroplasticity are important mechanisms in the hypothesis of the pathogenesis of depression. Thus, these two aspects are conducive to the development of treatments for depression. Suanzaoren Decoction (SZRD) is a classic traditional Chinese medicine compound for the treatment of insomnia, which can clinically relieve depression symptoms, but its antidepressant pharmacological mechanism remains to be elucidated. Aim of this study Based on the hypothesis of inflammation and neuroplasticity in depression, this study aimed to investigate the antidepressant effect of SZRD and its specific molecular mechanism through chronic unpredictable mild stress (CUMS) induced SD rat model and lipopolysaccharide (LPS) induced BV2 cell neuroinflammation model. Materials and methods The body weight and behavioral indexes of CUMS model rats treated with orally or without oral SZRD for 4 weeks were detected. Hematoxylin and eosin staining was used to observe brain pathological damage. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was used to observe neuronal apoptosis. Immunofluorescence, ELISA kit and Western blotting were used to detect the inflammatory index Iba-1 and inflammatory factors, as well as the important inflammatory pathway TLR4/MyD88/NF-κB. Enzyme linked immunosorbent assay (ELISA) and western blotting were used to detect neuroplasticity indexes proteins-brain-derived neurotrophic factor (BDNF), presynaptic membrane protein-synaptophysin (SYP), and postsynaptic protein- 95(PSD95), and the key pathway Wnt/β-catenin. The possible mechanism of SZRD antidepressant was further explored in LPS-induced BV2 cells. Results In vivo and in vitro experiments showed that SZRD treatment significantly reversed the depression-like behaviors in rats, decreased the levels of inflammatory factors and increased the expression levels of BDNF, SYP, PSD95 in depression model rats. Furthermore, SZRD treatment inhibited the activation of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways and reduced the massive nuclear translocation of NF-κB and β-catenin. The addition of NF-κB pathway agonists could partially offset the inhibitory effect of SZRD on the Wnt pathway, and the addition of Wnt pathway agonists could also partially offset the inhibitory effect of SZRD on the TLR4 pathway. Conclusion This study suggestted that SZRD may exert its antidepressant effect by regulating TLR4/MyD88/NF-κB pathway and Wnt/β-catenin pathway in combination.
研究领域:
药理学
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神经科学
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中医
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）