查找使用阿拉丁产品的科研文献

Fluorescent microsphere-based strip for sensitive and quantitative detection of etomidate and metomidate

Qingqing Liu,Aihua Qu,Chuanlai Xu,Xinxin Xu,Liqiang Liu,Hua Kuang

In this research, we used a novel hapten to generate a sensitive monoclonal antibody (mAb) 2C3 that targeted etomidate (ET) and metomidate (MT). We used this mAb to establish a lateral-flow immunoassay (LFIA) that incorporated fluorescent microsphere sensors, enabling both the qualitative and quantitative detection of ET and MT within 10 min. Analysis indicated that the visual colorimetric values for ET and MT in water samples were 0.3 µg/kg, respectively, with quantitative detection ranges of 0.08 to 1.31 µg/kg and 0.08 to 2.21 µg/kg, respectively. The visual colorimetric values for ET and MT in urine samples were 0.3 to 1 µg/kg, with quantitative detection ranges of 0.12 to 3.13 µg/kg and 0.09 to 2.98, respectively. The visual colorimetric values for ET and MT in serum samples were 3 µg/kg, with quantitative detection ranges of 0.15 to 21.2 µg/kg and 0.08 to 13.8 µg/kg, respectively. Recovery tests and detection were conducted in water, urine and serum samples, validating the reliability of this method in real clinical samples. Collectively, our novel LFIA provides a promising option for rapid on-site detection of ET and MT.

Insights into antifouling mechanisms of carbon nanomaterials and enhancing performance with polydopamine functionalization for point-of-care propofol monitoring

Shan Wang,Chunguang Kuai,Anyang Wang,Li Li,Yuzheng Guo,Mian Peng

Carbon nanomaterials, renowned for their exceptional sensitivity and selectivity towards various medical drugs, hold promise as electrode materials for electrochemical biosensors in propofol (PPF) monitoring. However, the issue of fouling has hindered their effective utilization in continuous point-of-care monitoring. In this research, we present a mechanism-driven approach to design a highly sensitive and durable electrochemical sensor tailored for PPF monitoring. We investigated the antifouling mechanism through density functional theory calculations and experiments and found that carboxyl functional groups contribute to the sensitivity and antifouling properties of the electrode. We have uncovered the antifouling ability of different carbon nanomaterials on PPF oxidation products. Factors such as hydrophilicity, geometric morphology, and active surface area played pivotal roles in antifouling. Furthermore, surface modification with hydrophilic polydopamine further enhanced the antifouling effects. In this study, we extensively investigated the electrochemical oxidation of PPF and its oxidation product on carbon nanomaterials, as well as the antifouling mechanism of carbon nanomaterials. The modified electrodes exhibit excellent antifouling performance and stability. This achievement presents a promising approach towards the development of point-of-care PPF analysis in clinical settings.

Propofol alleviates M1 polarization and neuroinflammation of microglia in a subarachnoid hemorrhage model in vitro, by targeting the mir-140-5p/TREM-1/NF-κB signaling axis

Lan Wang,Zhenyu Fan,Haijin Wang,Shougui Xiang

Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT ‒ qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.

Transcriptional Response of ATP-Binding Cassette (ABC) Transporters to Insecticide in the Brown Planthopper, Nilaparvata lugens (Stål)

Zhao Li,Tingwei Cai,Yao Qin,Yunhua Zhang,Ruoheng Jin,Kaikai Mao,Xun Liao,Hu Wan,Jianhong Li

The ATP-binding cassette (ABC) transporter superfamily is one of the largest groups of proteins and plays a non-negligible role in phase III of the detoxification process, which is highly involved in the response of insects to environmental stress (plant secondary metabolites and insecticides). In the present study, inNilaparvata lugens, we identified 32 ABC transporters, which are grouped into eight subfamilies (ABCA–H) based on phylogenetic analysis. The temporal and spatial expression profiles suggested that the nymphal stages (1st–5th) and adult males showed similarity, which was different from eggs and adult females, andNlABCA1,NlABCA2,NlABCB6,NlABCD2,NlABCG4,NlABCG12,NlABCG15, andNlABCH1were highly expressed in the midgut and Malpighian tubules. In addition,ABCG12, which belongs to the ABC transporter G subfamily, was significantly upregulated after exposure to sulfoxaflor, nitenpyram, clothianidin, etofenprox, chlorpyrifos, and isoprocarb. Moreover, verapamil significantly increased the sensitivity ofN. lugensto nitenpyram, clothianidin, etofenprox, chlorpyrifos, and isoprocarb. These results provide a basis for further research on ABC transporters involved in detoxification inN. lugens, and for a more comprehensive understanding of the response ofN. lugensto environmental stress.Keywords:ABC transporters;detoxification;Nilaparvata lugens;insecticides

Propofol alleviates traumatic brain injury through regulating Th17/Treg balance by activation of the AMPK/SIRT1 pathway

Dan Wang,Hui Sun,Kerong Hai,Ningkang Li,Yang Gu,Zengrui Ma

Traumatic brain injury (TBI), a prevalent neurological disorder in clinical practice, is primarily induced by external trauma. Propofol has been reported to alleviate the symptoms associated with TBI. In this study, a TBI model was established in mice using the controlled cortical impact (CCI) method. After treatment with propofol and BML-275, neuronal damage in the TBI model was assessed through the modified Neurological Severity Score (mNSS), Hematoxylin and Eosin (HE) staining, and Nissl staining. To investigate the role of the AMPK/SIRT1 pathway in propofol-regulated TBI, AMPKα-silenced vectors and overexpressed SIRT1 vectors were transfected. Western blot was performed to evaluate the expression of proteins involved in the AMPK/SIRT1 pathway and pyroptosis markers. The regulatory impact of Th17/Treg balance was examined by detecting the key transcription factors RORγt and FOXP3 through immunofluorescent staining and RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-17 and IL-10 concentrations. Results showed that propofol significantly reduced neuronal injury in the TBI model, an effect that was reversed by BML-275. Moreover, propofol mitigated pyroptosis by downregulating Caspase-1 and GSDMD-N expression post-TBI. Propofol inhibited Th17 differentiation while promoting Treg differentiation by modulating RORγt/FOXP3 and IL-17/IL-10 levels. Silencing AMPKα markedly diminished propofol’s effects on Th17 and Treg differentiation, with these effects being reversed upon SIRT1 overexpression. Propofol suppressed neuronal pyroptosis through the regulation of Th17/Treg balance via activation of the AMPK/SIRT1 pathway. These findings suggest propofol exerts a protective effect against neuronal damage following TBI, potentially through the modulation of the Th17/Treg balance and AMPK/SIRT1 signaling pathway.

Identification of UGTs and BCRP as potential pharmacokinetic determinants of the natural flavonoid alpinetin

Chunli Qi,Jiangnan Fu,Huinan Zhao,Huijie Xing,Dong Dong,Baojian Wu

Electrochemical sensors based on composites of porous Fe3O4/C and carbon black for sensitive and rapid detection of propofol

Shouhui Chen,Dan Zhou,Qinghao Xiong,Yinan Yang,Mingyang Zhang,Shoulin Chen

Nowadays, many people are turning to medications that can help them stay calm during surgeries and their daily lives. As an anesthetic that reduces the excitability of nerve cells, propofol can achieve sedative with the advantages of fast onset and short half-life. The development of propofol sensors has tremendous application potential because they can help healthcare professionals dynamically regulate the concentration of propofol in the blood, not only to achieve painless surgeries that patients want, to maintain the sedation that surgeons desire, but also to prevent the respiratory failure that may occur during the patient's daily sleep aids. In this paper, we prepared Fe3O4/C/CB nanocomposites by doping carbon black on the surface of the pyrolyzed product of MIL-88B. The nanocomposites-modified glassy carbon electrodes were used to detect propofol in phosphate buffer solution. The porous nanocomposites with high electrical conductivity promoted the charge transfer on the electrode surface, improving the performance of the modified electrodes. After optimization, the linear range, the detection limit, and the sensitivity for propofol were 5.0~205 μM, 0.102 μM, and 2.850 μA cm-2 μM-1, respectively. The electrochemical sensing of propofol in medical propofol emulsion injection and normal human serum showed that the method was rapid and repeatable.

Fast Determination of Propofol in Human Plasma Using C18-Functionalized Magnetic Nanomaterials Followed by Supercritical Fluid Chromatography

Liang Shan-Yan,Xu Xiao-Min,Wang Peng,Ye Ming-Li,Zhang Shui-Feng,Zhao Yong-Gang

Novel C18-functionalized magnetic nanomaterials; i.e., C18@poly-styrene-divinylbenzene-glycidyl methacrylate-Fe3O4 (C18@PS-DVB-GMA-Fe3O4) have been synthesized by using N, N-dimethyloctadecylamine as modifying agent, which could be beneficial to remove the blood phospholipids. The C18@PS-DVB-GMA-Fe3O4 nanoparticles have been used and evaluated in the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) procedure for human plasma prior to the analysis of propofol by supercritical fluid chromatography (SFC). In the QuEChERS procedure, human plasma samples are directly mixed with extraction solvent and C18@PS-DVB-GMA-Fe3O4 nanoparticles, and the extraction and cleanup procedures have been accomplished simultaneously. The SFC separation was performed with a C18 column (Thermo Scientific™ Acclaim™ 120, 250 × 4. 6 mm, 5 μm) within 5 min, using thymol as the internal standard. Supercritical carbon dioxide was used as the mobile phase with methanol as the cosolvent at the flow rate of 1.0 mL/min. The column temperature was 38°C, and detection wavelength was 275 nm. A good linearity was obtained among the propofol concentration range of 0.5–10 mg/L (R2 = 0.9997) with the limit of detection of 0.17 mg/L. Recoveries were in the range of 76.5–91.9%, with RSD less than 7.9%. These results suggested that method is convenient, rapid with high accuracy and little matrix effect, and suitable for rapid determination of propofol plasma concentration.

Potential Determinants for Metabolic Fates and Inhibitory Effects of Isobavachalcone Involving in Human Cytochrome P450, UDP-Glucuronosyltransferase Enzymes, and Efflux Transporters

Zifei Qin,Peile Wang,Shuyi Duan,Xiaoying Wan,Han Xing,Jing Yang,Xiaojian Zhang,Zhihong Yao,Xinsheng Yao

Isobavachalcone, a naturally occurring chalcone in Psoralea corylifolia , posses many biological properties including anticancer, antiplatelet, and antifungal. However, its glucuronidation, glucuronides excretion, and drug-drug interaction (DDI) involving in human cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) enzymes, and efflux transporters (BCRP and MRPs) remains unclear so far. After incubation, three glucuronides were produced by HLM and HIM with total intrinsic clearance ( CL int ) of 236.71 and 323.40 μL/min/mg, respectively. Reaction phenotyping proved UGT1A1, 1A3, 1A7, 1A8, and 1A9 played important roles in glucuronidation with total CL int values of 62.69–143.00 μL/min/mg. Activity correlation analysis indicated UGT1A1 and UGT1A3 participated more in the glucuronidation. In addition, the glucuronidation showed marked species differences, and rabbits and dogs were probably appropriate model animals to investigate the in vivo glucuronidation. Furthermore, BCRP , MRP1, and MRP4 transporters were identified as the most important contributors to glucuronides excretion in HeLa1A1 cells based on gene silencing method. Moreover, isobavachalcone demonstrated broad-spectrum inhibitory effects against CYP2B6 , CYP2C9 , CYP2C19 , CYP2D6 , CYP2E1 , UGT1A1, UGT1A9, UGT2B7 with IC 50 values of 1.08–9.78 μM. Except CYP2B6 and CYP2D6, the calculated [I]/ K i values for other enzymes were all greater than 0.1, indicating the inhibition of systemic metabolism or elimination for these enzyme substrates seems likely. Taken together, we summarized metabolic fates of isobavachalcone including glucuronidation and efflux transport as well as inhibitory effects involving in human CYP and UGT enzymes.

Potential metabolism determinants and drug–drug interactions of a natural flavanone bavachinin

Xinqiang Li,Han Xing,Zifei Qin,Jing Yang,Peile Wang,Xiaojian Zhang,Zhihong Yao,Xinsheng Yao

Bavachinin, a natural bioactive flavanone, is reported to have many pharmacological proprieties, especially anti-osteoporosis activity. Here we aim to determine the roles of cytochrome P450s (CYP), UDP-glucuronosyltransferases (UGT), and efflux transporters in metabolism and drug–drug interactions (DDI) of bavachinin. Phase I metabolism and glucuronidation were performed by human liver microsomes (HLM) and human intestine microsomes (HIM). Reaction phenotyping was used to identify the main CYPs and UGTs. Gene silencing methods were employed to investigate the roles of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in HeLa1A1 cells. Inhibition mechanisms towards CYPs and UGTs were explored through kinetic modeling. Three phase I metabolites (M1–M3) and one glucuronide (G1) were detected after incubation of bavachinin with HLM and HIM. The intrinsic clearance (CLint) values of M1 and G1 by HLM were 89.4 and 270.2 μL min−1 mg−1, respectively, while those of M3 and G1 by HIM were 25.8 and 247.1 μL min−1 mg−1, respectively. CYP1A1, 1A2, 1B1, 2C8, 2C19, and UGT1A1, 1A8 participated more in bavachinin metabolism. The metabolism showed marked species difference. BCRP and MRP4 were identified as the main contributors. Bavachinin displayed potent inhibitory effects against several CYP and UGT isozymes (Ki = 0.28–2.53 μM). Bavachinin was subjected to undergo metabolism and disposition by CYPs, UGTs, BCRP, MRP4, and was also a potent non-selective inhibitor against several CYPs and UGTs.

Propofol inhibited gastric cancer proliferation via the hsa-miR-328-3p/STAT3 pathway

Bai Z. M.,Li X. F.,Yang Y.,Yang Y. F.,Lv D. R.,Tang L. L.

Purpose The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation. Methods Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma ( n  = 435) and normal samples ( n  = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 μM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation. Results Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3′-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p. Conclusions To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation.

Multiple circulating alkaloids and saponins from intravenous Kang-Ai injection inhibit human cytochrome P450 and UDP-glucuronosyltransferase isozymes: potential drug–drug interactions

Qin Zifei,Jia Mengmeng,Yang Jing,Xing Han,Yin Zhao,Yao Zhihong,Zhang Xiaojian,Yao Xinsheng

Background Kang-Ai injection is widely used as an adjuvant therapy drug for many cancers, leukopenia, and chronic hepatitis B. Circulating alkaloids and saponins are believed to be responsible for therapeutic effects. However, their pharmacokinetics (PK) and excretion in vivo and the risk of drug–drug interactions (DDI) through inhibiting human cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes remain unclear.Methods PK and excretion of circulating compounds were investigated in rats using a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS) method. Further, the inhibitory effects of nine major compounds against eleven CYP and UGT isozymes were assayed using well-accepted specific substrate for each enzyme.Results After dosing, 9 alkaloids were found with Cmax and t1/2 values of 0.17–422.70 μmol/L and 1.78–4.33 h, respectively. Additionally, 28 saponins exhibited considerable systemic exposure with t1/2 values of 0.63–7.22 h, whereas other trace saponins could be negligible or undetected. Besides, over 90% of alkaloids were excreted through hepatobiliary and renal excretion. Likewise, astragalosides and protopanaxatriol (PPT) type ginsenosides also involved in hepatobiliary and/or renal excretion. Protopanaxadiol (PPD) type ginsenosides were mainly excreted to urine. Furthermore, PPD-type ginsenosides were extensively bound (fu-plasma approximately 1%), whereas astragalosides and PPT-type ginsenosides displayed fu-plasma values of 12.35% and 60.23–87.36%, respectively. Moreover, matrine, oxymatrine, astragaloside IV, ginsenoside Rg1, ginsenoside Re, ginsenoside Rd, ginsenoside Rc, and ginsenoside Rb1 exhibited no inhibition or weak inhibition against several common CYP and UGT enzymes IC50 values between 8.81 and 92.21 μM. Through kinetic modeling, their inhibition mechanisms towards those CYP and UGT isozymes were explored with obtained Ki values. In vitro-in vivo extrapolation showed the inhibition of systemic clearance for CYP or UGT substrates seemed impossible due to [I]/Ki no more than 0.1.Conclusion sWe summarized the PK behaviors, excretion characteristics and protein binding rates of circulating alkaloids, astragalosides and ginsenosides after intravenous Kang-Ai injection. Furthermore, weak inhibition or no inhibition towards these CYP and UGT activities could not trigger harmful DDI when Kang-Ai injection is co-administered with clinical drugs primarily cleared by these CYP or UGT isozymes.