Aging-US
·
2023
·
IF 5.2
Guang-Zhi Liu,Tian-Tong Niu,Qian Yu,Bao-Lei Xu,Xiao-Qing Li,Bo-Yi Yuan,Guo-Bin Yuan,Ting-Ting Yang,Hui-Qin Li,Yi Sun
The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer’s disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aβ analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aβ1–42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1β and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1β, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aβ1–42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.
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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DOI
PubMed
高影响因子
Alzheimers Research & Therapy
·
2025
·Vol. 17
·期 1
·253
·
IF 7.6
Liu Li-Rong,Li Li,Lu Li-Li,Fan Shu-Juan,Liu Li-Zhe,He Ruo-Bing,Li He,Xian Xiao-Hui,Li Wen-Bin
Background Mitochondrial dysfunction and dysregulated calcium homeostasis contribute to Alzheimer’s disease (AD) pathogenesis. The extrasynaptic N-methyl-D-aspartic acid (NMDA) receptor (eNMDAR) plays a crucial role in calcium influx and subsequent signaling cascades. In individuals with AD, the reduced expression and function of glutamate transporter-1 (GLT-1) result in glutamate spillover from the synaptic clefts to the extrasynaptic region, thereby activating eNMDAR and inducing mitochondrial damage. Ceftriaxone (Cef) has been reported to ameliorate cognitive deficits in APPswe/PS1dE9 (APP/PS1) mice by upregulating GLT-1. This study aimed to explore whether Cef alleviates mitochondrial dysfunction to improve cognitive impairment and the roles of GLT-1 and eNMDAR, particularly the participation of eNMDAR-induced intracellular calcium signaling in this process. Methods C57BL/6J, APP/PS1, and GLT-1-knockdown APP/PS1 mice were used. NMDA (1 mM, 2 µL per ventricle) was injected cerebroventricularly into APP/PS1 mice once to activate eNMDAR. Cef (200 mg/kg) was intraperitoneally administered for 14 days. Cognitive function was evaluated by novel object recognition, novel location recognition and Morris water maze tests. Hippocampal mitochondrial ultrastructure was observed using transmission electron microscopy. Hippocampal mitochondrial membrane potential (MMP) was detected using JC-1 staining. The expression of eNMDAR and proteins related to mitochondrial biogenesis and dynamics was evaluated by western blot. A neuron‒astrocyte coculture derived from the cerebral cortex of embryonic mice was used to evaluate the effects of Cef on eNMDAR-induced neuronal calcium influx, mitochondrial calcium accumulation and MMP loss using live-cell imaging. Results Cef treatment attenuated hippocampal mitochondrial dysfunction, including ultrastructural damage, reduced aspect ratio, dysregulation of MMP, impaired biogenesis and dynamics, and cognitive deficits, and prevented the upregulation of eNMDAR expression in APP/PS1 mice in a GLT-1-dependent manner. These protective effects on hippocampal mitochondrial dysfunction and cognitive deficits were counteracted by eNMDAR activation. Furthermore, Cef incubation inhibited eNMDAR-mediated calcium influx in a GLT-1-dependent way and reduced MMP in primary cortical neurons. Notably, Cef incubation significantly suppressed mitochondrial calcium overload, which was mechanistically linked to the observed decline in MMP. Conclusions Cef treatment prevented the upregulation of eNMDAR expression and the subsequent extracellular calcium influx in a GLT-1-dependent manner, thereby reducing mitochondrial calcium loading and ultimately mitigating mitochondrial damage and cognitive deficits in APP/PS1 mice.
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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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
NEUROTOXICOLOGY
·
2026
·
IF 3.8
Xuening Li,Linglong Meng,Qiang Niu,Runjiang Ma,Yuhan Li,Hailing Zhou,Xiaoya Fu,Wenjie Chen,Juan Tang,Shangzhi Xu
This study investigated the mechanisms by which a region-specific simulated PM 2.5 from Shihezi, China, exacerbates Alzheimer’s disease (AD) pathology, focusing on the protein kinase B (AKT)/mitogen-activated protein kinase (MAPK) signaling axis. APP/PS1 and wild-type mice were exposed to a simulated Shihezi PM 2.5 suspension. Cognitive function, neuroinflammation, oxidative stress, signaling activity, apoptosis, and amyloid-β (Aβ)/Tau pathology were assessed. Simulated PM 2.5 exposure aggravated cognitive deficits, induced neuroinflammation and oxidative stress, and triggered a significant AKT/MAPK imbalance characterized by MAPK hyperactivation and AKT suppression. This imbalance promoted neuronal apoptosis and exacerbated both Aβ deposition and Tau hyperphosphorylation. Our findings reveal that simulant PM 2.5 -induced neuroinflammation and oxidative stress dysregulate the AKT/MAPK axis, driving neuronal loss and AD progression, and suggest a molecular mechanism by which environmental PM 2.5 exposure may contribute to accelerated neurodegeneration.
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DOI
PubMed
高影响因子
FOOD CONTROL
·
2025
·
IF 6.3
Yun Huang,Aifen Hu,Lixue Ren,WanJun Long,Wei Lan,Yi He,Yuanbin She,Hengye Chen,Haiyan Fu
Glycyrrhizae Radix et Rhizoma (Gancao) is a functional food whose quality varies significantly owing to the genetic and geographical factors, and is often used by unscrupulous merchants as a substitute for profit. This study developed a rapid identification method for Gancao that determined the species, geographical origin, and main quality marker using a six-channel visual array sensor. This sensor detected the color changes resulting from the competitive coordination with metal ions and color-changing organic dyes. The combination of the array sensor with a random forest (RF) algorithm achieved 100% accuracy in identifying Gancao. Additionally, the smartphone app enabled the rapid and intelligent identification of Gancao within 1 min. The identification accuracy was 91.43%, and the prediction error of two quality markers was less than 13%. This research provides a foundation for rapid and reliable assessment of Gancao quality, enabling the industry to combat fraudulent practices effectively.
研究领域:
中药学
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植物学
·
机器学习
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食品科学
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DOI
高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 7
·1-8
·
IF 6.232
Liu Yaqing,Lin Xiaodong,Ji Xiangyi,Hao Zhe,Tao Zhanhui
A novel fluorescence strategy based on the outstanding catalytic capability of CuS nanoparticles (CuS NPs ) has been developed for highly sensitive and specific determination of o,o-dimethyl-o-2,2-dichlorovinyl phosphate (DDVP) under enzyme-free and hydrogen peroxide (H 2 O 2 )-free conditions. In the presence of DDVP, CuS NPs can catalyze non-fluorescence substratum of Amplex red (AR) into resorufin, which exhibits fluorescence emission at 584 nm under excitation at 540 nm. The sensing system exhibits outstanding specificity and only responds to DDVP and no other organophosphorus pesticides (OPs). A wide linear range is obtained from 0.0001 to 0.1 μg/mL, and the limit of detection (LOD) is 0.1 ng/mL. Furthermore, paper-based test strips have been constructed for visual detection of DDVP under ultraviolet light irradiation. By integrating a smartphone installed with Color Picker APP, point-of-care detection with quantitative determination is realized, demonstrating substantial potential applications of the as-developed assay for in situ detection.
Graphical abstract
研究领域:
分析化学
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环境科学
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生物技术
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材料科学
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产品关联
DOI
PubMed
高影响因子
POLYHEDRON
·
2024
·
IF 2.4
Jian Gou,Luxin Xing,Yousong Hu,Lina Zhang,Yongxin Li,Ning Bi,Yuanyuan Huang,Jun Xu,Lei Jia
A polychromatic fluorescent nanoprobe based on natural halloysite nanotubes with fluorescent dyes and porous metal–organic frameworks co-loaded on the surface and inner wall of the nanotubes was constructed for the highly sensitive visual identification of the Bacillus anthracis biomarker 2,6-dichlorophenolic acid (DPA). The limit of detection for DPA was 11.27 nM, which is significantly lower than the spore-borne dose for anthrax infection (60 uM). The multi-color fluorescent probe showed potential for rapid, accurate, and highly selective detection of Bacillus anthracis markers in actual samples. Besides, a portable fluorescence detection platform was developed in combination with a smartphone color scanning APP to simplify the detection process and realize real-time semi-quantitative analysis.
研究领域:
纳米技术
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生物技术
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分析化学
·
微生物学
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2018
·
IF 5.091
Dongmei Lin,Xingrong Zeng,Hongqiang Li,Xuejun Lai,Tongyi Wu
Waterproof and flame-retardant fabrics are widely utilized in many fields, such as automotive interiors, indoor decorations, outdoor clothing and tents. Herein, a facile one-pot sol-gel approach was developed to construct superhydrophobic and flame-retardant (SFR) coatings on cotton fabrics. The cotton fabric was activated by O 2 plasma and then immersed into the ethanol suspension containing tetraethoxysilane (TEOS), hydroxyl-terminated polydimethylsiloxane (HPDMS) and ammonium polyphosphate (APP). The hydrogen bonding interaction between APP and cellulose motivated the APP to attach to the cotton fibers during the initial stirring process. After the addition of ammonia, the in situ sol-gel reaction of TEOS and HPDMS was initiated to generate polydimethylsiloxane-silica hybrid (PDMS-silica). The micro-nano structured composite coating on cotton fabric was successfully fabricated by the PDMS-silica and APP. The SFR cotton fabric showed outstanding durability and self-cleaning ability with a water contact angle (WCA) above 160°. When exposed to fire, the SFR cotton fabric quickly charred to extinguish the fire by generating a dense intumescent char layer under the physical barrier effect of PDMS-silica and the intumescent flame-retardant effect of APP. This one-pot approach for fabricating SFR cotton fabric is simple, cost-effective and timesaving, demonstrating significant advantages in practical production.
研究领域:
材料科学
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纺织工程
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化学工程
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产品关联
DOI
PubMed
高影响因子
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
·
2022
·Vol. 48
·期 7
·e12839
·
IF 6.25
Xiaolian Ye,Lu Chen,He Wang,Shixiao Peng,Mengjia Liu,Liyang Yao,Yizhi Zhang,Yun Stone Shi,Ying Cao,Jian-Jun Yang,Guiquan Chen
Aims Abundant recent evidence has shown that 3-phosphoinositide-dependent protein kinase 1 (PDK1) is activated in Alzheimer's disease (AD). However, it remains unknown whether inhibition of PDK1 in neurons may affect AD-like pathology in animal models of AD. Here, we aim to examine the effects of specific inactivation of neuronal PDK1 on pathology and behaviour in 5×FAD mice and to identify the underlying molecular mechanisms. Methods The Cre-loxP system was employed to generate Pdk1 cKO/5×FAD mice, in which PDK1 is inactivated in excitatory neurons in the adult forebrain. Cellular and behavioural techniques were used to examine plaque burden, inflammatory responses and spatial working memory in mice. Biochemical and molecular analyses were conducted to investigate relevant mechanisms. Results First, Aβ deposition was massively decreased and gliosis was highly attenuated in Pdk1 cKO/5×FAD mice compared with 5×FAD mice. Second, memory deficits were significantly improved in Pdk1 cKO/5×FAD mice. Third, APP levels were notably decreased in Pdk1 cKO/5×FAD mice. Fourth, mammalian target of rapamycin (mTOR) signalling and ribosome biogenesis were reduced in Pdk1 cKO/5×FAD mice. Conclusions Neuron-specific deletion of PDK1 robustly ameliorates AD-like pathology and improves spatial working memory in 5×FAD mice. We propose that genetic approach to inhibit PDK1 may be an effective strategy to slow AD.
研究领域:
神经科学
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分子生物学
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药理学
·
遗传学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
·
2024
·Vol. 52
·期 1
·1-13
·
IF 2.6
Ming Huiyun,Lu Tingting,Zhou Han,Song Wencheng,Dai Haiming
Background Non-small cell lung cancer (NSCLC) is a type of lung cancer, the incidence and mortality rate have been high, and the use of monotherapy is easy to make patients develop tolerance. Atmospheric pressure plasma (APP) is an emerging technology for killing cancer cells in recent years, and combination of berberine (BBR) mechanism has not been fully elucidated for NSCLC. The article’s primary goal is to investigate the effect of combination on NSCLC and its associated characterization. Methods and results Antiproliferative effects were detected by cell viability assay and colony formation, and flow cytometry analysis of apoptosis and cycling showed that the combination synergistically induced apoptosis. Then, extracellular reactive oxygen species (ROS)levels and DCFH-DA-based kits examined intracellular ROS levels, and their effects on mitochondrial membrane potential were measured. Study reveals that co-induced apoptosis is associated with ROS accumulation. Subsequently, Western blotting (WB) detected the expression of epidermal growth factor receptor (EGFR), and the important signaling pathway proteins Ras/ERK and AKT/mTOR. Results showed that it could downregulation of EGFR protein expression and inhibit of activation of ERK/AKT signaling pathways. Simultaneous wound healing assay and epithelial-to-mesenchymal transition (EMT) marker detection were performed for the assessment of migration and EMT ability of NSCLC cells. Combination therapy inhibited migration and EMT of NSCLC cells. Conclusion The results of this study show that the combination can synergistically induce apoptosis of NSCLC by regulating ROS production. EGFR downregulation and AKT/ERK signaling pathway inhibition are linked to the synergistic effect.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Medicine
·
2023
·Vol. 21
·期 1
·1-17
·
IF 9.3
Li Wenwen,Pang Yana,Wang Yan,Mei Fan,Guo Mengmeng,Wei Yiping,Li Xinyue,Qin Wei,Wang Wei,Jia Longfei,Jia Jianping
Background The identification of pathogenic mutations in Alzheimer’s disease (AD) causal genes led to a better understanding of the pathobiology of AD. Familial Alzheimer’s disease (FAD) is known to be associated with mutations in the APP, PSEN1, and PSEN2 genes involved in Aβ production; however, these genetic defects occur in only about 10–20% of FAD cases, and more genes and new mechanism causing FAD remain largely obscure. Methods We performed exome sequencing on family members with a FAD pedigree and identified gene variant ZDHHC21 p.T209S. A ZDHHC21 T209S/T209S knock-in mouse model was then generated using CRISPR/Cas9. The Morris water navigation task was then used to examine spatial learning and memory. The involvement of aberrant palmitoylation of FYN tyrosine kinase and APP in AD pathology was evaluated using biochemical methods and immunostaining. Aβ and tau pathophysiology was evaluated using ELISA, biochemical methods, and immunostaining. Field recordings of synaptic long-term potentiation were obtained to examine synaptic plasticity. The density of synapses and dendritic branches was quantified using electron microscopy and Golgi staining. Results We identified a variant (c.999A > T, p.T209S) of ZDHHC21 gene in a Han Chinese family. The proband presented marked cognitive impairment at 55 years of age (Mini-Mental State Examination score = 5, Clinical Dementia Rating = 3). Considerable Aβ retention was observed in the bilateral frontal, parietal, and lateral temporal cortices. The novel heterozygous missense mutation (p.T209S) was detected in all family members with AD and was not present in those unaffected, indicating cosegregation. ZDHHC21 T209S/T209S mice exhibited cognitive impairment and synaptic dysfunction, suggesting the strong pathogenicity of the mutation. The ZDHHC21 p.T209S mutation significantly enhanced FYN palmitoylation, causing overactivation of NMDAR2B, inducing increased neuronal sensitivity to excitotoxicity leading to further synaptic dysfunction and neuronal loss. The palmitoylation of APP was also increased in ZDHHC21 T209S/T209S mice, possibly contributing to Aβ production. Palmitoyltransferase inhibitors reversed synaptic function impairment. Conclusions ZDHHC21 p.T209S is a novel, candidate causal gene mutation in a Chinese FAD pedigree. Our discoveries strongly suggest that aberrant protein palmitoylation mediated by ZDHHC21 mutations is a new pathogenic mechanism of AD, warranting further investigations for the development of therapeutic interventions.
研究领域:
神经科学
·
分子生物学
·
遗传学
·
病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Pengkun Ye,Lei Li,Xiating Qi,Mingyuan Chi,Jichun Liu,Meng Xie
The abnormal aggregation of β-amyloid protein (Aβ) is a major contributor to Alzheimer's disease (AD). Cu 2+ homeostasis imbalance can lead to the aggregation of Aβ, resulting in cytotoxic oligomers and fibrous aggregates, causing neuroinflammation and nerve cell damage, ultimately leading to AD. In this study, we synthesized nitrogen-doped carbon quantum dot (CQD), and designed a macrophage membrane (RAW-M) encapsulated CQD nanosystem for the first time. The abundant nitrogen-containing groups on the surface of CQD effectively capture excess Cu 2+ and inhibit rapid Aβ aggregation. Additionally, the good photothermal properties of CQD dissolve the formed fiber precipitates under near-infrared light (NIR). In vitro and in vivo studies showed that the nanosystem significantly improved BBB permeability under laser irradiation, enhancing its ability to cross the BBB and overcome traditional anti-AD drug limitations. In vivo investigations conducted on APP/PS1 mice indicate that the nanosystem strongly reduced Aβ deposition, mitigated neuroinflammation, and ameliorates deficits in learning and memory. Overall, our nanocarrier approach adjusts metal ion homeostasis, inhibits abnormal Aβ aggregation, and uses excellent photothermal properties to depolymerize mature Aβ fibrils to protect cells from Aβ neurotoxicity, providing an effective strategy for Aβ-targeted treatment of AD.
研究领域:
纳米技术
·
神经科学
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Dan Su,Zhong Chen,Xiaobin An,Junkai Yang,Jinan Yang,Xuqiao Wang,Yang Qu,Chen Gong,Yani Chai,Xiaoying Liu,Wei Cheng,Dongyang Wang,Yan Wu,Jing Ma,Xinyue Zhao,Qin Wang,Yun Xu,Haisheng Peng,Jing Ai
The complex etiologies and mechanisms of Alzheimer's disease (AD) underscore the importance for devising multitarget drugs to achieve effective therapy. MicroRNAs (miRNAs) are capable of concurrently regulating the expression of multiple proteins by selectively targeting disease- associated genes in a sequence-specific fashion. Nonetheless, as RNA-based drugs, their stability in the circulation and capacity of traversing the blood–brain barrier (BBB) is largely compromised, thereby limiting their potential clinical applications. In this study, we formulated the nanoliposomes encapsulating polyethyleneimine (PEI)/ miR-195 complex (DPMT@PEI/ miR-195 ) that was engineered through dual modifications to contain P -aminophenyl-alpha-d-mannopyranoside (MAN) and cationic cell-penetrating peptide (TAT). DPMT@PEI/ miR-195 exhibited the enhanced BBB- and cell membrane penetrating capability. As expected, we observed that DPMT@PEI/ miR-195 administered through intravenous tail injection of produced greater effectiveness than donepezil and the same range of effect as aducanumab in alleviating the cognitive decline in 7-month-old APP/PS1 mice. Moreover, the combination treatment with DPMT@PEI/ miR-195 and donepezil effectively ameliorated the deterioration of cognition in 16-month-old APP/PS1 mice, with enhanced effects than either DPMT@PEI/ miR-195 or donepezil alone. Furthermore, DPMT@PEI/ miR-195 effectively attenuated the positive signals of Aβ, AT8, and CD68 in APP/PS1 mice without notable side effects. Our findings indicate DPMT@PEI/ miR-195 as a promising potentially new agent or approach for the prophylaxis and treatment of early and advanced stages of Alzheimer's disease.
研究领域:
神经科学
·
药理学
·
分子生物学
·
药物递送系统
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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）