JOURNAL OF FLUORESCENCE
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2026
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IF 3.4
Liu Xiujin,Lai Gengneng,Shu Zongcheng,Li Wei,Ke Fang
Thyroid-associated ophthalmopathy (TAO) is a complex autoimmune inflammatory disease. There is an urgent clinical need for highly sensitive and minimally invasive biomarkers to enable early diagnosis and dynamic disease monitoring. Among them, miR-320a has been confirmed to be closely associated with oxidative stress regulation, fibroblast activation, and fibrosis progression. However, current detection methods, especially those based on real-time quantitative polymerase chain reaction (RT-qPCR), still suffer from cumbersome procedures, high instrumentation costs, and limited adaptability for rapid point-of-care diagnostics. To address this, we developed a nanozyme-assisted colorimetric biosensing platform integrating target-triggered probe hybridization with Co-g-C 3 N 4 , which exhibits enhanced peroxidase-like activity and stability. The method involves Co-g-C 3 N 4 synthesis, probe-nanozyme interface construction, catalytic optimization, and colorimetric detection via TMB oxidation, validated in spiked serum and with smartphone readout. The platform achieves sensitive miR-320a detection down to picomole levels with excellent linearity and specificity. In spiked human serum analysis, it reliably quantifies endogenous miR-320a with strong recovery rates (94.6-108.9%). However, we acknowledge that direct clinical validation using confirmed TAO patient samples is required for full diagnostic implementation, and this represents a limitation of the current study. Generally speaking, this work provides a portable, cost-effective, amplification-free colorimetric nanozyme platform for miRNA detection, requiring only basic laboratory equipment, and holding significant promise for point-of-care precision diagnostics in autoimmune and fibrotic diseases.
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Pharmaceuticals
·
2026
·Vol. 19
·期 3
·490
·
IF 5.7
Hailong Zhang,Jiaxin Huang,Wenji Yang,Wenhu Zhou,Jinsong Ding,Qianbin Li,Gaoyun Hu
Background : Hyperuricemia (HUA) is a metabolic disorder that severely threatens human health. Chronic uric acid (UA) overload promotes the progression of tubulointerstitial fibrosis (TIF), leading to impaired UA excretion. Our previous studies identified HIPK2 inhibitor XRF-1021, which exhibits robust anti-TIF activity and lowers UA levels in vivo. This study aimed to elucidate its UA-lowering mechanism and therapeutic potential for HUA. Methods : Uricase and xanthine oxidase (XOD) assays were performed to assess effects on UA degradation/production. HEK293T cells transiently expressing UA transporters and gene-knockdown rats were used to evaluate transporter inhibition, while HK-2 cells were analyzed by Western blot. Pharmacokinetics were characterized in rats. Efficacy was tested in potassium oxonate-induced acute HUA rats, diet/adenine-induced chronic HUA quails, and adenine-induced mice with HUA secondary to TIF. Maximum tolerated dose and long-term toxicity were assessed in rats. Results : XRF-1021 neither activated uricase nor inhibited XOD, indicating no direct effect on UA catabolism or synthesis. Instead, XRF-1021 inhibited URAT1 and GLUT9, reducing renal UA reabsorption, while sparing OAT3, OAT4, and ABCG2 activity and upregulating OAT3 and NPT4, suggesting minimal risk of disrupting drug or uremic toxin handling. XRF-1021 showed dose-dependent systemic exposure in rats, lowered serum UA, and provided renal protection in vivo. LD 50 values were 2345.4 mg/kg (male) and 1078.9 mg/kg (female), with no obvious toxicity after long-term dosing. Conclusions : XRF-1021 lowers UA by inhibiting URAT1 and GLUT9 to enhance renal UA excretion and provides kidney protection, supporting XRF-1021 as a promising candidate for HUA therapy.
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XENOBIOTICA
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2020
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IF 1.902
Ruicong Ma,Gentao Li,Xue Wang,Yajuan Bi,Youcai Zhang
To date, relatively little is known about the interactions of pharmaceutical excipients with hepatic and renal drug uptake transporters. The present study was designed to systematically evaluate the effects of 16 commonly consumed excipients on human organic cation transporter 1 and 2 (hOCT1 and hOCT2), human organic anion transporter 1 and 3 (hOAT1 and hOAT3) and human organic anion transporting polypeptide 1B1 and 1B3 (hOATP1B1 and hOATP1B3).The inhibitory effects and mechanisms of excipients on transporters were investigated using in vitro uptake studies, cell viability assays, concentration-dependent studies, and the Lineweaver–Burk plot method.Triton X-100 is a non-competitive inhibitor for all six transporters. Tween 20 inhibits hOCT2, hOAT1, hOAT3, and hOATP1B3 in a mixed way, whereas it competitively inhibits hOATP1B1. The inhibition of Tween 80 is competitive for hOCT2, non-competitive for hOATP1B1 and hOATP1B3, and mixed for hOAT1 and hOAT3. Concentration-dependent studies identify Triton X-100 as a strong inhibitor of hOCT1 and hOCT2 with IC50 values of 20.1 and 4.54 μg/mL, respectively. Additionally, Triton X-100, Tween 20, and Tween 80 strongly inhibit hOAT3 with IC50 values ≤31.0 μg/mL.The present study is significant in understanding the excipient–drug interactions and provides valuable information for excipient selection in drug development.
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BIOSENSORS & BIOELECTRONICS
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2021
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IF 10.618
Mingliang Mei,Lixuan Mu,Sen Liang,Yuan Wang,Guangwei She,Wensheng Shi
The aptasensor , developed from the aptamer, has aroused wide concern in recent years owing to its high sensitivity and specificity. However, the quenching unit involved in the most of the aptasensors is indispensable to the fabrication of an aptasensor, which would undoubtedly increase the complexity of the device. In this study, a facile strategy was developed for construction of the quencher-free aptasensors, in which the quenching units can be omitted, and only an aptamer strand and a fluorophore are necessary. Distinguishable from the configuration of the traditional ones, the aptasensors developed in this work rationally employed the intrinsic quenching abilities of the analytes to directly regulate the fluorescence of the fluorophore. Furthermore, the aptamer strand as a discriminatory unit efficiently captured the corresponding analytes to around the fluorophores. As a result, the fluorescence of the aptasensor can be significantly sensitive to the analytes. The generality of the current design is evidenced by the successful fabrication of seven quencher-free aptasensors for Cu 2+ , Ag + , Hg 2+ , ATP and dopamine through 6-FAM labeling aptamers of Cu 2+ , Ag + , Hg 2+ , ATP, dopamine, 5-TAMRA and ROX labeling aptamers of Cu 2+ . Present strategy endows an aptasensor with a simple structure, high selectivity and fine sensitivity. The configuration of the quencher-free aptasensors fabricated in this work can be readily utilized for more aptasensors.
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TOXICOLOGICAL SCIENCES
·
2020
·Vol. 175
·期 2
·279-291
·
IF 3.703
Li Caiyu,Wang Xue,Bi Yajuan,Yu Heshui,Wei Jing,Zhang Yi,Han Lifeng,Zhang Youcai
Organic anion transporters 1 and 3 (OAT1 and OAT3) play a critical role in renal drug-drug interactions and are involved in the nephrotoxicity of many anionic xenobiotics. To date, relatively little is known about the interaction of natural compounds with OAT1 and OAT3. Of the 270 natural compounds screened in the present study, 21 compounds inhibited OAT1 and 45 compounds inhibited OAT3. Further concentration-dependent studies identified 7 OAT1 inhibitors and 10 OAT3 inhibitors with IC50 values of <10 μM, and most of them were flavonoids, the most commonly ingested polyphenolic compounds in the diet and herbal products. Computational modeling of OAT1 and OAT3 revealed the important residues for the recognition of inhibitors. The two strong OAT inhibitors, namely wedelolactone and wogonin, were evaluated for their in vivo interactions with the OAT substrate aristolochic acid I (AAI), a natural compound causing aristolochic acid-induced nephropathy (AAN) in many species. The cytotoxicity of AAI increased in two OAT-overexpressing cell lines, with more cytotoxicity in OAT1-overexpressing cells, suggesting a more important role of OAT1 than OAT3 in AAN. Both wedelolactone and wogonin markedly increased serum AAI concentrations in AAI-treated rats and ameliorated kidney injuries in AAI-treated mice. To conclude, the present findings are of significant value in understanding natural compound-drug interactions and provide a natural source for developing treatments for AAN.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2019
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IF 6.393
Xiaobo Fan,Wei Xu,Wei Gao,Xinglu Jiang,Guoqiu Wu
Graphene oxide (GO) absorbed aromatic and charged materials due to its high volume-to-surface ratio and unique physical and electrical properties. Antimicrobial peptides can inhibit bacterial growth by intercalating into the bacterial envelope and their antimicrobial efficiencies vary depending on the species and are sensitive to metal cations. Herein, a turn-off sensor array based on graphene oxide and antimicrobial peptide that was fused with a poly-histidine adaptor was described and used for bacterial discrimination. The poly-histidine adaptor prone to binding with graphene oxide helped GO to quench the fluorophore labelled peptides efficiently. As illustrated by the titration assays presented herein, GO quenched the 6-carboxyfluorescein-labelled peptides at a >99.6 % quenching efficiency, ensuring a very low background. A sensor array was established with various antimicrobial peptide types and calcium concentrations under optimized parameters. The 13 most frequently observed clinical species were subjected to the sensor array, and the obtained fluorescent signals ranged from several thousand to several million, with superior resolution between species. The sensor array was evaluated by comparing its accuracy in a blind assay using single or combined parameters. The accuracy reached >70 % for single parameters and >95 % for combinations, and all 155 bacteria were identified using this sensor array. In addition, the interaction between the membrane components and antimicrobial peptides were examined by quartz crystal microbalance with dissipation and the effect of calcium ions was elucidated by monolayer assays.
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JOURNAL OF NATURAL PRODUCTS
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2019
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IF 4.257
Xue Li,Yilin Qiao,Xue Wang,Ruicong Ma,Tianxiang Li,Youcai Zhang,Robert P. Borris
Organic anion transporters 1 (OAT1) and 3 (OAT3) play important roles in the renal elimination of a range of substrate molecules. Little is known about natural products that can modulate OAT1 and OAT3 activities. The medullae of Juncus effusus is often used for the treatment of dysuria in traditional Chinese medicine. To study the interactions of phytochemicals in J. effusus with human OAT1 and OAT3, a bioactivity guided phytochemical investigation led to seven new phenanthrenoids along with nine known compounds, including eight phenanthrenoids and a benzophenone from the dichloromethane soluble fraction of a methanol extract of the medullae of J. effusus. The structures were established by physical data analysis, including high-resolution electrospray ionization mass spectrometry and 1D and 2D NMR. The compounds were evaluated for inhibition of OAT1 and OAT3 in vitro. Compounds 10 and 16 were inhibitors for OAT1, and compounds 1–3, 10, and 16 were inhibitors for OAT3 with IC50 values less than 5.0 μM. Dihydrophenanthrene 1 markedly altered the pharmacokinetic parameters of the diuretic drug furosemide, a known substrate of both OAT1 and OAT3, in vivo.
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CHEMICAL & PHARMACEUTICAL BULLETIN
·
2023
·
IF 1.7
Qiang Chen,Lili Zheng,Xiaoqin Deng,Menghan Zhang,Wendi Han,Zhengjun Huang,Chenfang Miao,Shaohuang Weng
Tyrosinase (TYR) plays a pivotal role in the biosynthesis of melanin, and its activity level holds critical implications for vitiligo, melanoma cancer, and food nutritional value. The sensitive determination of TYR activity is of great significance for both fundamental research and clinical investigations. In this work, we successfully synthesized silicon-doped carbon quantum dots (Si-CQDs) through a one-pot hydrothermal method with trans-aconitic acid as carbon source and N-[3-(Trimethoxysilyl)propyl]ethylenediamine as the dopant, exhibiting remarkable fluorescence quantum yield (QY) and photostability. Correspondingly, Si-CQDs were used as a probe to construct a sensitive, rapid, and user-friendly fluorescence method for TYR detection. The method relied on the oxidation of isoprenaline (ISO) by TYR, where Si-CQDs were employed as a highly efficient probe. The testing mechanism was the internal filtering effect (IFE) observed between Si-CQDs and the oxidative system of ISO and TYR. Under the optimized conditions, the fluorescence strategy exhibited a detection range of 0.05-2.0 U/mL for TYR with a limit of detection (LOD) of 0.041 U/mL. Furthermore, we successful demonstrated the accurate determination of TYR levels in human serum, showcasing the promising potential of this method in various practical scenarios.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2019
·
IF 2.705
Yilin Qiao,Xueling Liu,Xue Li,Xue Wang,Caiyu Li,Manana Khutsishvili,Valida Alizade,Daniel Atha,Youcai Zhang,Robert P. Borris
Organic anion transporters (OATs in humans, Oats in rodents) play an important role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions , including a host of widely prescribed drugs. Their ligand recognition is also important for drug therapy and development. In this study, the n -butanol and dichloromethane soluble fractions of Juniperus oblonga were found to inhibit OAT3 in vitro and three biflavonoids were found to be responsible for this activity. One of these compounds, amentoflavone exhibited stronger inhibition than probenecid, a known strong inhibitor of OAT3. Biological characterization of amentoflavone in vivo also showed inhibition of Oat3. Preliminary observations of structure-activity relationships suggest that the biflavonoids are more potent inhibitors of this transporter than their corresponding monomer, and that methylation of even a single hydroxyl group results in a substantial decrease in activity. This greater potency of the biflavonoids may indicate the need for a more in-depth investigation of the distribution of biflavonoids in plants used as foodstuffs and herbal medicines, due to their potential for causing interactions with OAT3 substrate drugs.
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Scientific Reports
·
2019
·Vol. 9
·期 1
·1-9
·
IF 4.011
Li Xue,Wang Xue,Li Caiyu,Khutsishvili Manana,Fayvush George,Atha Daniel,Zhang Youcai,Borris Robert P.
A bioactivity guided program exploring the interaction of phytochemicals in the entire plant Primula macrocalyx with the organic anion transporters (OAT1 and OAT3) and microorganisms led to the elucidation of ten known flavones ( 1 – 4 , 6 – 10 , 12 ) and two previously undescribed flavones ( 5 , 11 ). The structures of the compounds were determined by extensive analysis of spectroscopic data, as well as by comparison with data from previous reports. Two known flavones ( 9 , 12 ) are reported for the first time from the family Primulaceae. All compounds were evaluated for inhibition of OAT1 and OAT3. Six flavones ( 2 , 3 , 6 – 8 , 12 ) showed potent inhibitory activity on OAT1, while seven flavones ( 2 , 3 , 6 – 9 , 12 ) showed marked inhibitory activity on OAT3, with IC 50 ≤ 10.0 µ M. Antimicrobial activities of crude fractions against sixteen microorganisms were tested to give a target yeast strain Candida rugosa for further evaluation of MICs on the isolates. Three flavones ( 7 , 8 , 12 ) showed marked antifungal activity with MIC < 2.0 µ M. To our knowledge, this study is the first to evaluate these flavones as inhibitors of the OAT1 and OAT3, and as antifungal agents.
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NATURAL PRODUCT RESEARCH
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2018
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IF 1.928
Xu Pang,Li-Ming Wang,You-Cai Zhang,Li-Ping Kang,He-Shui Yu,Guan-Wei Fan,Li-Feng Han
A continuous phytochemical study on the seeds of Senna obtusifolia (Syn.: Cassia obtusifolia) led to the isolation of a new anthraquinone analogue, obtusifolin-2-O-β-D-(6’-O-α,β-unsaturated butyryl)-glucopyranoside (1) and a new eurotinone analogue, epi-9-dehydroxyeurotinone-β-D-glucopyranoside (2). Their structures were established mainly by NMR and MS experiments as well as the necessary chemical evidences. Their inhibitory effects on two organic anion transporters (OAT1 and OAT3) were investigated and the results showed that 1 exhibited a strongly specific inhibitory effect on OAT1 at 100 μM.
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JOURNAL OF ETHNOPHARMACOLOGY
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2019
·
IF 3.414
Peter Yaro,Jing Nie,Mingcheng Xu,Kui Zeng,Houhong He,Jianbiao Yao,Ruwei Wang,Su Zeng
Ethnopharmacological relevance The major terpene lactones of ginkgo biloba extract (GBE) include ginkgolide A , B, C and bilobalide are used for the protection of cardiovascular, cerebrovascular and neurodegenerative diseases. Terpene lactones are orally bioavailable and predominantly eliminated via the renal pathway. However, information on the transporters involved in the pharmacokinetics (PK) and renal excretion of terpene lactones is limited. Aim of the study The objective of this study is to assess the role of OAT1/3 which are important transporters in the human kidney in the PK and renal excretion ginkgolide A, B, C and bilobalide. Materials and methods Uptake of ginkgolide A, B, C and bilobalide in Madin-Darby Canine Kidney (MDCK) and human embryonic kidney 293 (HEK293) cells overexpressing OAT1 or OAT3, respectively were studied. To verify the result from in vitro cell models, the studies on PK, kidney accumulation and urinary excretion of ginkgolide A, B, C and bilobalide were carried out in rats. Results The result showed that ginkgolide A, B, C and bilobalide are low-affinity substrates of OAT1/3. Following co-administration with probenecid , a typical inhibitor of OAT1/3, the rat plasma concentrations of ginkgolide A, B, C and bilobalide increased significantly. AUC showed a significant increase in the probenecid-treated rats compared to control rats (893.48 vs. 1123.85, 314.91 vs. 505.74, and 2724.97 vs. 3096.40 μg/L*h for ginkgolide A, B and bilobalide, respectively), while the clearance of these compounds significantly decreased. The accumulation of ginkgolide A, B and bilobalide in the kidney of the probenecid-treated rats was reduced by 1.8, 2.4, and 1.5-fold, respectively; further reducing the cumulative urinary recovery of these compounds. Conclusion The findings indicated that ginkgolide A, B and bilobalide are excreted via OAT1/3-mediated transport in the kidney and OAT1/3 inhibitor significantly influence the PK ginkgolides and bilobalide.
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