JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
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IF 3.4
Shijie Cao,Leyao Li,Hongwei An,Guobin Mao,Junbiao Dai,Yingxin Ma
Sensitive and accurate detection of interleukin 6 (IL-6) is crucial for the early diagnosis of cerebral infarction to improve patient survival rates. However, the low-abundance of IL-6 in cerebral infarction presents a significant challenge in developing effective diagnosis method. Herein, we studied and analyzed the strong fluorescence property of 4-aminophenol phosphate (APP) and developed an enzyme-linked immunosorbent assay (ELISA) for IL-6 detection. The detection was based on the integration of optical signal change induced by alkaline phosphatase (ALP)-catalyzed APP hydrolysis and ALP-mediated ELISA. The generated colorimetric signal of 4-aminophenol, APP hydrolysis product, was used for ELISA of IL-6 with a detection limit of 0.1 ng/mL, and the visual detection of IL-6 was achieved. The changes in APP fluorescence have a good linear relationship with the logarithm of IL-6 concentration in the range of 0.005 ng/mL to 5.0 ng/mL, with a detection limit of 0.001 ng/mL, which was 100 times lower than that of conventional pNPP-based ELISA. Furthermore, the constructed ELISA effectively distinguished between samples from patients with cerebral infarction and volunteers with non-cerebral infarction, and the severity of symptoms was well distinguished based on IL-6 measurement. The dual-mode ELISA demonstrated high feasibility of low-abundance biomarker detection and displayed good potential for accurate in vitro diagnosis.
研究领域:
生物医学工程
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临床诊断
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 6
·e18186
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IF 4.3
Bo Guan,Ming Li,Di Cui,Chen Shen,Zongyao Hao,Xiaowei Li
Clear cell renal cell carcinoma (ccRCC) represents a significant challenge in oncology, primarily due to its resistance to conventional therapies. Understanding the tumour microenvironment (TME) is crucial for developing new treatment strategies. This study focuses on the role of amyloid precursor protein (APP) in tumour-associated macrophages (TAMs) within the ccRCC TME, exploring its potential as a prognostic biomarker. Basing TAM-related genes, the prognostic model was important to constructed. Employing advanced single-cell transcriptomic analysis, this research dissects the TME of ccRCC at an unprecedented cellular resolution. By isolating and examining the gene expression profiles of individual cells, particularly focusing on TAMs, the study investigates the expression levels of APP and their association with the clinical outcomes of ccRCC patients. The analysis reveals a significant correlation between the expression of APP in TAMs and patient prognosis in ccRCC. Patients with higher APP expression in TAMs showed differing clinical outcomes compared to those with lower expression. This finding suggests that APP could serve as a novel prognostic biomarker for ccRCC, providing insights into the disease progression and potential therapeutic targets. This study underscores the importance of single-cell transcriptomics in understanding the complex dynamics of the TME in ccRCC. The correlation between APP expression in TAMs and patient prognosis highlights APP as a potential prognostic biomarker. However, further research is needed to validate these findings and explore the regulatory mechanisms and therapeutic implications of APP in ccRCC.
研究领域:
肿瘤学
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分子生物学
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转录组学
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癌症免疫学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
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IF 5.6
Fanchang Wu,Mingjun Huang,Xue Zuo,Ruiye Xie,Jinman Liu,Junyu Ke,Weirong Li,Qi Wang,Yong Liang
Alzheimer’s disease (AD) poses a significant threat to the global elderly population. Traditional Chinese medicine (TCM) has been widely utilized in the treatment of AD. Osthole, a bioactive ingredient classified as an “emperor” in many TCM formulas, has been demonstrated to effectively alleviate AD symptoms. However, its low bioavailability in the brain has limited its clinical application. This study aimed to increase the intracerebral bioavailability of osthole by using borneol as a “courier,” based on the classical “Emperor–Minister–Assistant–Courier” model, and to investigate the enhanced pharmacological performance of osthole on AD. Results indicated that a suitable in situ thermosensitive gel matrix for intranasal administration mixed with osthole and borneol consists of P407 at 20%, P188 at 7%, and PEG300 at 6%. The concentration of osthole in the cerebrospinal fluid increased almost tenfold after intranasal administration of osthole/borneol compared to oral administration. Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression, thereby expediting the nose-to-brain route and guiding osthole as “emperor” to its target in the brain. Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio, improving T-SOD and catalase expression, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice compared to osthole alone. Overall, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol and provided a wider application of TCM for AD treatment with higher intracerebral bioavailability.
研究领域:
药理学
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神经科学
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传统中药
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2021
·Vol. 139
·期 18
·52064
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IF 3.125
Xinjun Wang,Lijun Qian,Juan Li
Amino acid-triazine copolymer (CC-Lys) was prepared by using lysine (Lys) and cyanuric chloride (CC). The structure and performance of CC-Lys were tested by using Fourier transform infrared spectroscopy and thermogravimetric analysis. The CC-Lys, ammonium polyphosphate (APP) and organic montmorillonite (OMMT), were applied in ethylene-vinyl acetate (EVA) to improve its flame retardancy. The results showed that 20 wt% APP/CC-Lys/OMMT makes EVA achieve the UL-94 V0 rating. The reactions among APP/CC-Lys/OMMT release some incombustible gases and promote the formation of a porous char layer with good barrier performance during combustion. Moreover, the quality of the char layer is improved. In addition, the peak of heat release rate of EVA composite is reduced by 87% and time to ignition is delayed. This work provides a good flame retardant system for EVA.
研究领域:
材料科学
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高分子化学
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产品关联
DOI
高影响因子
EXPERIMENTAL BRAIN RESEARCH
·
2023
·Vol. 241
·期 6
·1661-1673
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IF 2
Zhang Yuhe,Chen Yan,Yuan Shushu,Yu Qingxia,Fu Jianjiong,Chen Luyun,Liu Jiaming,He Yuping
Gastrodin (Gas) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of Gas against cognitive impairment via regulating gut microbiota. APPswe/PSEN1dE9 transgenic (APP/PS1) mice were treated intragastrically with Gas for 4 weeks, and then cognitive deficits, deposits of amyloid-β (Aβ) and phosphorylation of tau were analyzed. The expression levels of insulin-like growth factor-1 (IGF-1) pathway-related proteins, such as cAMP response element-binding protein (CREB), were detected. Meanwhile, gut microbiota composition was evaluated. Our results showed that Gas treatment significantly improved cognitive deficits and Aβ deposition in APP/PS1 mice. Moreover, Gas treatment increased the level of Bcl-2 and decreased level of Bax and ultimately inhibited neuronal apoptosis. Gas treatment markedly increased the expression levels of IGF-1 and CREB in APP/PS1 mice. Moreover, Gas treatment improved abnormal composition and structure of gut microbiota in APP/PS1 mice. These findings revealed that Gas actively participated in regulating the IGF-1 pathway to inhibit neuronal apoptosis via the gut–brain axis and that it can be considered a new therapeutic strategy against Alzheimer’s disease.
研究领域:
神经科学
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药理学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
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2018
·Vol. 16
·期 6
·4951-4958
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IF 1.41
Lili Zhong,Hong Liu,Weijia Zhang,Xu Liu,Bo Jiang,Hongxin Fei,Zhongren Sun
β‑amyloid (Aβ) aggregation and tau hyperphosphorylation are considered to be the primary pathological hallmarks of Alzheimer's disease (AD). Targeted inhibition of these pathological processes may provide effective treatments for AD. Accumulating evidence has demonstrated that ellagic acid (EA) exerts neuroprotective effects in several diseases. The present study investigated the effects of EA on AD‑associated learning and memory deficits on APP/PS1 double transgenic mice and the underlying mechanisms. APP/PS1 mice or wild‑type C57BL/6 mice were intragastrically administered EA (50 mg/kg/day) or vehicle for 60 consecutive days. The learning and memory abilities of mice were investigated using the Morris water maze test. Hippocampal regions were examined for the presence of amyloid plaques, neuronal apoptosis and tau phosphorylation. Expression levels of APP, Aβ, RAC‑αserine/threonine‑protein kinase and glycogen synthase kinase (GSK)3β in the hippocampus were determined by western blot analysis and ELISA. The results demonstrated that EA treatment ameliorated spatial learning and memory impairment in APP/PS1 mice and significantly reduced neuronal apoptosis and Aβ deposition in the hippocampus (P<0.05 and P<0.01). In addition, EA significantly inhibited the hyperphosphorylation of tau and significantly decreased the activity of glycogen synthase kinase (GSK)3β (P<0.01), which is involved in tau phosphorylation. Overall, these findings indicated that the beneficial effects of EA on AD‑associated cognitive impairments may be attributed to the inhibition of Aβ production and tau hyperphosphorylation, and its beneficial action may be mediated in part, by the RAC‑α serine/threonine‑protein kinase/GSK3β signaling 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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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
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2023
·
IF 6.1
Jingwen Jiang,Hong Pan,Fanxia Shen,Yuyan Tan,Shengdi Chen
Alzheimer’s disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain. The ketogenic diet, a widely recognized therapeutic intervention for refractory epilepsy, has recently been proposed as a potential treatment for a variety of neurological diseases, including Alzheimer’s disease. However, the efficacy of ketogenic diet in treating Alzheimer’s disease and the underlying mechanism remains unclear. The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer’s disease. Male amyloid precursor protein/presenilin 1 (APP/PS1) mice were randomly assigned to either a ketogenic diet or control diet group, and received their respective diets for a duration of 3 months. The findings show that ketogenic diet administration enhanced cognitive function, attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice, and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway. Collectively, these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer’s disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation. This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer’s disease.
研究领域:
神经病学
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神经退行性疾病
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营养科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2025
·
IF 2.8
Zhisheng Zhang,Fang Zhu,Tingting Yang,Yongkun Wu,Yue Shi,Hongxiang Ou
An environmentally friendly intumescent flame retardant was developed by blending tannic acid (TA) and ammonium polyphosphate (APP), and intumescent flame-retardant polyurethane composites (IFR/TPU) were prepared via melt blending. The flame retardancy and mechanism of IFR/TPU were investigated through limiting oxygen index (LOI), cone calorimeter, and mechanical property tests. Results indicate that at a total exothermic flame retardant loading of 25 wt% and a TA:APP mass ratio of 1:1, IFR/TPU exhibits an LOI of 30.8%, achieving UL-94 V-0 rating, with a TG residue of 24.4%. The peak heat release rate (pHRR) decreased from 1102.46 kW/m 2 for pure thermoplastic polyurethane to 313.17 kW/m 2 . Furthermore, the incorporation of TA mitigated the adverse effects of flame retardants on the mechanical properties of TPU. SEM analysis of char residues revealed that TA promotes the formation of expanded carbon layers. This results in denser, more uniform char layers during combustion, enhancing both flame retardancy and smoke suppression. TA exhibits synergistic flame retardancy with APP. This approach maintains the inherent properties of polyurethane while delivering excellent flame retardancy, offering a novel design strategy for developing next-generation bio-based flame retardants.
研究领域:
材料科学
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高分子化学
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消防安全工程
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可持续材料
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Liu Ni,Yang Changwen,Liang Xiaohan,Cao Kai,Xie Jun,Luo Qingming,Luo Haiming
Background Dysbiosis or imbalance of gut microbiota in Alzheimer's disease (AD) affects the production of short-chain fatty acids (SCFAs), whereas exogenous SCFAs supplementation exacerbates brain Aβ burden in APP/PS1 mice. Bifidobacterium is the main producer of SCFAs in the gut flora, but oral administration of Bifidobacterium is ineffective due to strong acids and bile salts in the gastrointestinal tract. Therefore, regulating the levels of SCFAs in the gut is of great significance for AD treatment.Methods We investigated the feasibility of intranasal delivery of MSNs-Bifidobacterium (MSNs-Bi) to the gut and their effect on behavior and brain pathology in APP/PS1 mice.Results Mesoporous silica nanospheres (MSNs) were efficiently immobilized on the surface of Bifidobacterium. After intranasal administration, fluorescence imaging of MSNs-Bi in the abdominal cavity and gastrointestinal tract revealed that intranasally delivered MSNs-Bi could be transported through the brain to the peripheral intestine. Intranasal administration of MSNs-Bi not only inhibited intestinal inflammation and reduced brain Aβ burden but also improved olfactory sensitivity in APP/PS1 mice.Conclusion sThese findings suggested that restoring the balance of the gut microbiome contributes to ameliorating cognitive impairment in AD, and that intranasal administration of MSNs-Bi may be an effective therapeutic strategy for the prevention of AD and intestinal disease.
研究领域:
神经科学
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药学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
·
IF 7.31
Zhihui Yin,Demin Gao,Ke Du,Chen Han,Yuhan Liu,Ying Wang,Xiaoyan Gao
Mitochondrial oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease (AD). Recently, antioxidant therapy has been considered an effective strategy for the treatment of AD. Our previous work discovered that rhein relieved mitochondrial oxidative stress in β-amyloid (Aβ) oligomer-induced primary neurons by improving the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha- (PGC-1α-) regulated mitochondrial biogenesis. While encouraging results have been provided, mechanisms underlying the beneficial effect of rhein on AD are yet to be elucidated in vivo. In this study, we evaluated the therapeutic effect of rhein on an APP/PS1 transgenic (APP/PS1) mouse model of AD and explored its antioxidant mechanisms. As a result, rhein significantly reduced Aβ burden and neuroinflammation and eventually ameliorated cognitive impairment in APP/PS1 mice. Moreover, rhein reversed oxidative stress in the brain of APP/PS1 mice and protected neurons from oxidative stress-associated apoptosis. Further study revealed that rhein promoted mitochondrial biogenesis against oxidative stress by upregulating SIRT1 and its downstream PGC-1α as well as nuclear respiratory factor 1. Improved mitochondrial biogenesis not only increased the activity of superoxide dismutase to scavenge excess reactive oxygen species (ROS) but also repaired mitochondria by mitochondrial fusion to inhibit the production of ROS from the electron transport chain. Notably, the exposure of rhein in the brain analyzed by tissue distribution study indicated that rhein could permeate into the brain to exert its therapeutic effects. In conclusion, these findings drive rhein to serve as a promising therapeutic antioxidant for the treatment of AD. Our research highlights the therapeutic efficacy for AD through regulating mitochondrial biogenesis via the SIRT1/PGC-1α 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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老年医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Qing Liu,Tianzhi Xie,Yujia Xi,Ling Li,Fengfeng Mo,Xuebo Liu,Zhigang Liu,Jin-Ming Gao,Tian Yuan
Alzheimer’s disease (AD), a neurodegenerative disease, is the leading cause of dementia. Sesamol is a lignan extracted from sesame oil and has been found to exert neuroprotective effects. The present study aimed to investigate the neuroprotective effects of sesamol on APPswe/PS1dE9 transgenic AD mice. The AD mice were fed with a diet supplemented with sesamol (0.075 w/w %). Sesamol treatment improved spatial memory and learning ability in AD mice, improved neuronal damage, and decreased Aβ accumulation. Sesamol protected the synaptic ultrastructure and inhibited neuroinflammatory responses in the brain of AD mice. Sesamol also significantly inhibited the overactivated microglia and reduced the overexpression of TNF-α and IL-1β in the brain of AD mice. Notably, sesamol reshaped gut microbiota by significantly decreasing the relative abundance of Helicobacter hepaticus, Clostridium, and Bacillaceae, enhancing the relative abundance of Rikenellaceae and Bifidobacterium in AD mice. It has been found that sesamol protected the gut barrier integrity and prevented the LPS leakage into the serum. Importantly, sesamol remarkably enhanced the content of SCFAs, including acetate, propionate, isobutyrate, butyrate, and valerate, in AD mice. Correlation analysis indicated that there was a strong correlation between the levels of SCFAs and cognitive functions. These results demonstrated that sesamol attenuated AD-related cognitive dysfunction and neuroinflammatory responses, which could be partly explained by its role in mediating the gut microbe–SCFA–brain axis. Thus, sesamol is a promising nutritional intervention strategy to prevent AD via the microbiota–gut–brain axis.
研究领域:
神经科学
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药理学
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微生物学
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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
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 5
·2678-2690
·
IF 5.882
Yufei Sun,Zhiqiang Liu,Zifeng Pi,Fengrui Song,Jianlin Wu,Shu Liu
Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid beta-protein (Aβ) plaques, which are the hallmark of AD, are formed from the imbalance of Aβ production and clearance accompanied by neuroinflammation, gut dysbiosis, and metabolite dysfunction. All of these processes give rise to neurochemical deficiencies and synaptic dysfunction, which ultimately contribute to recognition dysfunction. Poria cocos (PC), which contains multiple active ingredients, plays a significant role in the treatment of multiple-pathogenesis senile diseases such as AD. Nevertheless, there are only very few investigations on the intricate action mechanism of PC for the treatment of AD. In this study, we evaluate the multi-target cure effect of PC on APP/PS1 mice by behavioral, immunohistochemical (IHC), targeted metabolomics, and 16S rRNA sequencing experiments. Mice treated with PC showed significant improvements in cognitive function as evaluated by the behavioral experiment. IHC revealed that PC treatment relieved Aβ deposition by reducing the formation of Aβ and increasing its clearance. Moreover, PC treatment improved gut dysbiosis, which reversed the metabolite dysfunction of bile acid. These findings reveal that PC is a promising therapeutic agent, which might ameliorate the cognitive function of AD by restoring the imbalance of Aβ production and clearance and gut microbiota dysbiosis.
研究领域:
神经科学
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药理学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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