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ACS Omega · 2025 · IF 4.3

Germacrone Ameliorates Diabetic Kidney Disease by Activating TFEB to Promote Autophagy and Inhibit Inflammation

Zhishen Xie,Mengmeng Wang,Qingqing Song,Xuan Su,Jenny Jie Chen,Jiangyan Xu,Zhenqiang Zhang,Tongxiang Liu,Xiaowei Zhang,Gai Gao

Diabetic kidney disease (DKD) is widely recognized as the primary cause of end-stage renal disease (ESRD). Activating autophagy is considered a key strategy to improve DKD. Here, through luciferase reporter gene screening of several sesquiterpenoids, it was found that germacrone (GER) significantly activated the transcription factor EB (TFEB), and its effect on DKD and the underlying molecular mechanism was investigated. GER significantly improved renal function impairment and alleviated renal pathological damage. GER inhibited NLR family pyrin domain containing 3 (NLRP3)-mediated inflammatory responses both in vitro and in vivo. Mechanistically, GER activated TFEB to promote autophagy and clear NLRP3 inflammasomes, and the GER-mediated degradation of NLRP3 was reversed by the autophagy inhibitor chloroquine (CQ). Additionally, GER did not affect the expression of TFEB protein but increased its expression in the nucleus. This effect was attributed to the dephosphorylation of p-TFEB (S122) protein caused by the activation of protein phosphatase 2A (PP2A) by GER. This result was further confirmed by supplementing with the PP2A inhibitor okadaic acid (OA). Docking results indicated a stable binding between GER and PP2A. These findings highlighted GER as a potential intervention for treating DKD and clarified the underlying mechanism through which it functions by regulating the PP2A-TFEB pathway.

CAS / MDL: 88-84-6
研究领域: 药理学 · 分子生物学 · 肾病学 · 生物化学 · 免疫学
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TALANTA · 2023 · IF 6.1

Oriented-aptamer encoded magnetic nanosensor with laser-induced fluorescence for ultrasensitive test of okadaic acid

Yuwei Zhou,Qingai Chen,Guobin Huang,Shukun Huang,Chenchen Lin,Xucong Lin,Zenghong Xie

Okadaic acid (OA) biotoxin acts a well-established inhibitor of protein phosphatase even a tumor promoter of human being, arouse great attention in safety monitoring. However, the powerful and convenient nanosensing technologies for addressing the demands such as rapidity, high sensitivity, and stability in the in-field test of OA shellfish toxin is still scarce. Herein, a high-performance magnetic biometric nanosensor (MBNS) integrating oriented aptamers and ultrasensitive laser-induced fluorescence (LIF) was firstly proposed for the in-field detection of trace OA in seafoods. High-density aptamers hybridized with FAM-labeled cDNA were tethered to the surface of AuNPs on magnetic MIL-101@Fe 3 O 4 , and then finely regulated by mercaptohexyl alcohol (MCH) to be orderly assembled, as was successfully utilized to engineer an active biological nanosensor for highly specific recognition of OA. Aptamers anchored on magnetic Fe 3 O 4 @MOF@AuNPs activate a biometric microreactor of OA, in which the superior LIF properties, conformation regulation of aptamer, and the specific recognition using aptamer genes were adopted. The magnetic nanosensor with an excellent specificity and super sensitivity for OA analysis was achieved within 20 min. Moreover, the content of captured OA could facilely be recorded by measuring the fluorescence intensity , and the limit of detection (LOD) and limit of quantitation of OA (LOQ) reached 0.015 and 0.050 ng/mL respectively, which was far better than most aptamer-based biometric sensing methods. The feasibility for accurate test of trace OA toxin in the fortified shellfish samples was validated with the recovery yields of 88.2–107.5% and RSD of 0.5–7.6%, respectively. The result demonstrated that the oriented-aptamer encoded MNS had significant practical values in rapid and ultrasensitive detection of OA biotoxin and the related safety applications.

研究领域: 分析化学 · 食品安全 · 生物传感技术
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2016 ·Vol. 408 ·期 20 ·5527-5535 · IF 3.125

Experimental and computational studies on molecularly imprinted solid-phase extraction for gonyautoxins 2,3 from dinoflagellate Alexandrium minutum

Lian Ziru,Li Hai-Bei,Wang Jiangtao

An innovative and effective extraction procedure based on molecularly imprinted solid-phase extraction (MISPE) was developed for the isolation of gonyautoxins 2,3 (GTX2,3) from Alexandrium minutum sample. Molecularly imprinted polymer microspheres were prepared by suspension polymerization and and were employed as sorbents for the solid-phase extraction of GTX2,3. An off-line MISPE protocol was optimized. Subsequently, the extract samples from A. minutum were analyzed. The results showed that the interference matrices in the extract were obviously cleaned up by MISPE procedures. This outcome enabled the direct extraction of GTX2,3 in A. minutum samples with extraction efficiency as high as 83 %, rather significantly, without any need for a cleanup step prior to the extraction. Furthermore, computational approach also provided direct evidences of the high selective isolation of GTX2,3 from the microalgal extracts.

研究领域: 海洋生物学 · 分析化学
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ENVIRONMENTAL POLLUTION · 2013 · IF 3.73

Study of molecularly imprinted solid-phase extraction of gonyautoxins 2,3 in the cultured dinoflagellate Alexandrium tamarense by high-performance liquid chromatography with fluorescence detection

Zi-Ru Lian,Jiang-Tao Wang

A highly selective sample cleanup procedure combined with molecularly imprinted solid-phase extraction (MISPE) was developed for the isolation of gonyautoxins 2,3 (GTX2,3) from Alexandrium tamarense sample. The molecularly imprinted polymer microspheres (MIPMs) were prepared by suspension polymerization using caffeine as the dummy template molecule, methacrylic acid as the functional monomer , ethylene glycol dimethacrylate as the cross-linker and polyvinyl alcohol as the dispersive reagent. The polymer microspheres were used as a selective sorbent for the solid-phase extraction of gonyautoxins 2,3. An off-line MISPE method followed by high-performance liquid chromatography (HPLC) with fluorescence detection for the analysis of gonyautoxins 2,3 was established. Finally, the extract samples from Alexandrium tamarense were analyzed. The results showed the imprinted polymer microspheres exhibited high affinity and selectivity for gonyautoxins 2,3. The interference matrix in the extract were obviously cleaned by MISPE and the extraction efficiency of gonyautoxins 2,3 in the sample ranged from 81.74% to 85.86%.

CAS / MDL: 9002-89-5
研究领域: 海洋生物学 · 分析化学
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CNS & Neurological Disorders-Drug Targets · 2015 ·Vol. 14 ·期 10 ·1334-1342 · IF 2.628

Jatrorrhizine Protects Against Okadaic Acid Induced Oxidative Toxicity Through Inhibiting the Mitogen-Activated Protein Kinases Pathways in HT22 Hippocampal Neurons

Wei Jiang,Wen-Biao Duan,Sheng Li,Xiu-Yin Shen,Yue Zhou,Tao Luo,Feng He,Jie Xu,Hua-Qiao Wang

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by deposit of amyloid plaques and neurofibrillary tangles and oxidative stress plays an essential role in the pathogenesis of AD. Jatrorrhizine (JAT), a Coptidis Rhizome, has multiple biological functions such as anti-oxidation and anti-inflammation. Herein, we investigated the neuroprotective effects of JAT on okadaic acid (OA)- induced cytotoxicity and apoptosis in HT22 cells. Following the exposure to 80nmol/L OA for 12h, the reduction in cell survival, activities of superoxide dismutase, glutathione peroxidase and mitochondria membrane potential has been shown in HT22 cells. In contrast, OA increased levels of lactate dehydrogenase, malondialdehyde production and intracellular reactive oxygen species. OA also enhanced the expression of Bax but decreased the levels of Bcl-2, OA also upregulated the expression of cleaved caspase-3, phosphorylated extracellular signal-regulated kinases 1/2, phosphorylated c-Jun Nterminal kinases, phosphorylated p38 and NF-kappa B p65 subunit in HT22 cells and this up-regulation was attenuated by JAT which was pre-incubated for 12h in the cells prior to OA exposure. In conclusion, our data present the protective role of JAT in OA induced cytotoxicity, via its antioxidant and anti-apoptotic properties by inhibiting the mitogen-activated protein kinases pathways in HT22 hippocampal neurons. These results indicate that JAT may be the potential target to treat AD induced by oxidative stress and apoptosis.

研究领域: 神经药理学 · 生物化学 · 细胞生物学 · 药理学 · 神经科学
✓ 已验证 DOI 高影响因子
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2014 ·Vol. 407 ·期 5 ·1303-1312 · IF 3.578

Simultaneous detection of microcysin-LR and okadaic acid using a dual fluorescence resonance energy transfer aptasensor

Wu Shijia,Duan Nuo,Zhang Hui,Wang Zhouping

Algal toxins can cause neurovirulence, hepatotoxicity, and cytotoxicity in humans through the consumption of contaminated water and food. In this work, we presented a novel aptasensor for the simultaneous detection of two algal toxins, microcysin-LR (MC-LR) and okadaic acid (OA). This system employed green and red upconversion nanoparticle (UCNP) luminescence as the donors and two quenchers (BHQ 1 and BHQ 3 ) as the corresponding acceptors. The two donor–acceptor couples were fabricated by hybridizing the aptamers with their corresponding complementary DNA. The results indicated that the green and red upconversion luminescence could be quenched by the quencher probes because of their highly overlapping spectrum. In the presence of MC-LR and OA, the aptamers preferred to bind to their corresponding analytes and de-hybridize with the complementary DNA. This effect became sufficiently large to prevent green and red luminescence quenching. Under the optimized experimental conditions, the relative luminescence intensity increased as the algal toxin concentrations increased, allowing for the quantification of MC-LR and OA. The relationships between the luminescence intensity and plotting logarithms of algal toxin concentrations were linear in the range from 0.1 to 50 ng mL −1 for MC-LR and OA. As a practical application, this type of dual fluorescence resonance energy transfer (FRET) aptasensor was used to monitor the MC-LR and OA levels in naturally contaminated food samples such as fish and shrimps. Schematic illustration of dual FRET aptasensor between the upconversion nanoparticles and quenching agent for the simultaneous detection of MC-LR and OA

研究领域: 分析化学 · 环境科学 · 食品安全 · 毒理学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

A facile and integrated aptamer-based platform for preliminary and simultaneous screening of group targets

Lele Wang,Rui Ma,Wenjing Wang,Ling Zhang,Jiao Li,Jianan Sun,Sai Wang,Xiangzhao Mao

Highly efficient detection of group targets is of great significance. Okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2) are the main diarrhetic shellfish poisons (DSPs) and have similar structures. As essential auxiliary tools, facile methods for simultaneous screening of these three DSPs are urgently needed. In this study, we report an aptamer-based platform which integrates pretreatment and quantitation for preliminary and simultaneous screening of the three DPSs. With computational study-assisted post-selection strategies, a truncated aptamer and a pair of split aptamers were generated with group-specific and high affinity towards the DSPs. The truncated aptamer was adopted to prepare an aptamer affinity column (AAC) for enrichment and purification of DSPs in real samples. The split aptamers were combined with G-quadruplex-hemin nanozyme to fabricate a label-free colorimetric aptasensor for quantitation. The prepared AAC showed good enrichment capacity. The developed colorimetric aptasensor provided high sensitivity, with limit of detection of 0.7011 nM, 14.27 nM, and 5.374 nM towards OA, DTX-1, and DTX-2, respectively, as well as high selectivity and accuracy. UPLC-MS was then only needed to analyze the suspicious positive samples, and highly efficient detection was achieved. This robust platform could be referred for preliminary screening of other group analytes.

CAS / MDL: 16009-13-5
研究领域: 分析化学 · 毒理学 · 环境科学 · 食品安全
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FOOD CHEMISTRY · 2021 · IF 7.514

Novel dual-emissive fluorescent immunoassay for synchronous monitoring of okadaic acid and saxitoxin in shellfish

Mingming Yin,Weijie Wang,Jie Wei,Xiaomei Chen,Quansheng Chen,Xi Chen,Munetaka Oyama

In this work, we present a novel dual-emissive fluoroimmunoassay for synchronous monitoring of okadaic acid (OA) and saxitoxin (STX) using multicolor fluorescent labels composed of sulfur, phosphorous co-doped graphene quantum dots (S, P-GQDs), and ovalbumin (OVA)-coated gold nanoparticles (OVA-AuNPs). The novel OVA-AuNPs were prepared by the reduction of chloroauric acid under alkaline conditions using OVA as a reducing agent. Both S, P-GQDs and OVA-AuNPs exhibit bright fluorescence, more importantly, a large emission wavelength difference (Δλ = 156 nm) under an excitation of 400 nm and relatively independent fluorescence behavior, which are essential to realizing the dual-signal marks in a directly mixing system. Using a competitive fluorescence-linked immunosorbent assay (cFLISA) format, the dual-emissive cFLISA was successfully utilized to measure OA and STX contents in Alectryonella plicatula (commonly named as fingerprint oyster) and the detection results were in good agreement with the commercial enzyme-linked immunosorbent assay (ELISA) kits.

研究领域: 分析化学 · 毒理学 · 环境科学 · 海洋生物学
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

Target-responsive DNAzyme hydrogel reinforced by click reaction for surface enhanced Raman scattering detection of okadaic acid

Ming Wang,Lizhen Zhao,Yuling Hu,Gongke Li

Shellfish toxins are common marine toxins that have attracted worldwide attention due to their serious threats to food safety and human health. In this work, DNA hydrogel based on rolling circle amplification (RCA) and click reaction was developed for surface enhanced Raman scattering (SERS) detection of okadaic acid (OA) combined with target-responsive DNAzyme signal amplification. The RCA strands containing azido-dCTP were combined with cross-linked strands with ethynyl groups via click reaction to form a DNA hydrogel framework. The click reaction strengthened the DNA hydrogel network, making it more rigid and easier to manipulate during the detection process. The aptamer and DNAzyme were introduced into the DNA hydrogel as functionalized DNA components. Upon the specific recognition of OA by the aptamer, the DNAzyme released via the displacement reaction would continuously cleave the enzyme cutting site within the substrate strand to liberate the SERS signal tag. The functionalized DNA hydrogel concurrently achieved the functions of target recognition, signal conversion and signal amplification. Under optimal conditions, this strategy could detect OA with limits of detection as low as 0.2 nmol/L within 30 min. The SERS signal intensity showed good linear relationship with OA concentration in the range of 1.0–300.0 nmol/L. The practical application was validated for detecting trace amounts of OA in aquatic product samples. The stable DNA hydrogel combined with target-responsive DNAzyme signal amplification offers a universal strategy for rapid detection of trace toxins in complex matrixes.

研究领域: 生物化学 · 分析化学 · 毒理学
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ChemNanoMat · 2019 ·Vol. 5 ·期 7 ·897-910 · IF 3.431

Peptide-Modified Mo Polyoxometalate Nanoparticles Suppress Zn2+-Induced Aβ Aggregation

Yanan Liu,Jing Sun,Youcong Gong,Hui Zhou,Xu Chen,Xufeng Zhu,Yingyu Zhao,Yayu Wen,Xiuying Qin,Jie Liu

Graphical Peptide@POMs nanoparticles with Aβ-targeting peptides are used for Alzheimer's disease treatment in mice. First, synthetic peptide-modified Mo-POM nanoparticles are synthesized. Then, the assembled Peptide@POMs nanoparticles can effectively inhibit Zn 2+ -induced Aβ40 aggregation, penetrate the blood-brain barrier, and bind to Aβ. In addition, Peptide@POMs nanoparticles protect neurons from Aβ40-mediated neurotoxicity. The abnormal metabolism of amyloid-β (Aβ) peptide, as one of the main components of senile plaques, plays a vital role in the pathogenesis of Alzheimer's disease (AD). Our previous work showed that polyoxometalates (POMs) that inhibited the formation of Aβ aggregates were promising for AD therapy. Here, peptide-modified Mo polyoxometalate (Mo-POMs) nanoparticles were synthesized by the self-assembly of Aβ target peptide and Mo-POMs based on our previous work. Importantly, after modifying with the Aβ target peptide, the Mo polyoxometalate (Mo-POMs) nanoparticles exhibited enhanced blood-brain barrier (BBB) penetration and high binding affinity with Aβ species. The interactions between the Peptide@Mo-POMs nanoparticle and Aβ in the presence of Zn 2+ were comprehensively studied using physicochemical methods (spectroscopy, ThT fluorescence, turbidity tests). Peptide@Mo-POMs could suppress Aβ aggregation, disaggregate Aβ fibrils, and suppress Zn 2+ -induced Aβ aggregation. In addition, in vitro cell experiments revealed that Peptide@Mo-POMs could target and be well absorbed by PC12 cells, leading to the inhibition of intracellular Aβ aggregation and reduced Aβ aggregates-induced cytotoxicity. The blood-brain barrier (BBB) permeability of Peptide@Mo-POMs was also revealed by the Transwell experiment. This study gives a mechanistic understanding into how Peptide@Mo-POMs can work through a synergistic interaction with metal ions and Aβ, and provides new insights into the design and synthesis of POMs as Aβ inhibitors in the treatment of AD.

研究领域: 纳米医学 · 神经科学 · 材料科学 · 生物化学
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