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Efficient pure-red emission light-emitting diodes (LEDs) are essential for high-definition displays, yet achieving pure-red emission is hindered by challenges like phase segregation and spectral instability when using halide mixing. Additionally, strongly confined quantum dots (QDs) produced through traditional hot-injection methods face byproduct contamination due to poor solubility of metal halide salts in the solvent octadecene (ODE) at low temperatures. Herein, we introduced a novel method using a benzene-series strongly electrostatic potential solvent instead of ODE to prevent PbI2 intermediates and promote their dissolution into [PbI3]-. Increasing methyl groups on benzene yields precisely sized (4.4 ± 0.1 nm) CsPbI3 QDs with exceptional properties: a narrow 630 nm PL peak with photoluminescence quantum yield (PLQY) of 97%. Sequential ligand post-treatment optimizes optical and electrical performance of QDs. PeLEDs based on optimized QDs achieve pure-red EL (CIE: 0.700, 0.290) approaching Rec. 2020 standards, with an EQE of 25.2% and T50 of 120 min at initial luminance of 107 cd/m2.
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The development of pure-blue perovskite light-emitting diodes (PeLEDs) faces challenges of spectral stability and low external quantum efficiency (EQE) due to phase separation in mixed halide compositions. Perovskite quantum dots (QDs) with strong confinement effects are promising alternatives to achieve high-quality pure-blue PeLEDs, yet their performance is often hindered by the poor size distribution and high trap density. A strategy combining thermodynamic control with a polishing-driven ligand exchange process to produce high-quality QDs is developed. The strongly-confined pure-blue (≈470 nm) CsPbBr3 QDs exhibit narrow size distribution (12% dispersion) and are achieved in Br-rich ion environment based on growth thermodynamic control. Subsequent polishing-driven ligand exchange process removes imperfect surface sites and replaces initial long-chain organic ligands with short-chain benzene ligands. The resulting QDs exhibit high photoluminescence quantum yield (PLQY) to near-unity. The resulting PeLEDs exhibit a pure-blue electroluminescence (EL) emission at 472 nm with narrow full-width at half-maximum (FWHM) of 25 nm, achieving a maximum EQE of 10.7% and a bright maximum luminance of 7697 cd m-2. The pure-blue PeLEDs show ultrahigh spectral stability under high voltage, a low roll-off of EQE, and an operational half-lifetime (T50) of 127 min at an initial luminance of 103 cd m-2 under continuous operation.
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AIMS: Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD. MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis. RESULTS: The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered. CONCLUSIONS: We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.
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Diabetes Mellitus , Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Metabolômica/métodos , Metaboloma , Biomarcadores/metabolismoRESUMO
Here, we develop an in situ photoluminescence (PL) system to monitor the nucleation and growth of perovskite nanocrystals and control the monomer supply rate to achieve strongly confined and monodispersed quantum dots (QDs) with average size of 3.4 nm. Pure-blue (460 nm wavelength) CsPbBr3 QDs with near unity PL quantum yield and narrow size distribution (small size dispersion of 9.6%) were thus produced. Light-emitting diodes (LEDs) based on these QDs were prepared by using an all-solution processing route, which showed narrow electroluminescence with full width at half-maximum of 20 nm and a high color purity of 97.3%. The device also had a high external quantum efficiency of 10.1%, maximum luminance of 11â¯610 cd m-2, and continuous operation lifetime of 21 h at the initial luminance of 102 cd m-2, corresponding to the state-of-art for pure-blue perovskite LEDs.
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It is still challenging to achieve high-efficiency pure-red (620-650 nm wavelength) perovskite light-emitting diodes (PeLEDs). Herein, we report pure-red PeLEDs with Commission Internationale de l'Eclairage coordinates (0.703, 0.297) meeting the Rec. 2020, an external quantum efficiency of 20.8%, and a luminance of 3775 cd/m2. This design is based on the strong quantum confinement CsPbI3 quantum dots (QDs) capped by composite ligands of 3-phenyl-1-propylamine and tetrabutylammonium iodide. This strategy stabilized the structure of the strong-confined QDs and reduced the influence of the electric field-induced Stark effect on the PeLEDs. Furthermore, the exciton binding energy of the QDs was decreased by the composited ligands to suppress Auger recombination within the devices. Additionally, the valence-band maximum of the QDs was lifted to match the hole-transport layer, thus balancing charge injection in the PeLEDs. Our device also demonstrated a stable electroluminescence spectrum and a lifetime of 5.6 times longer than the control device.
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Perovskite colloidal quantum wells (QWs) are promising to realize narrow deep-blue emission, but the poor optical performance and stability suppress their practical application. Here, we creatively propose a water-driven synthesis strategy to obtain size-homogenized and strongly confined deep-blue CsPbBr3 QWs, corresponding to three monolayers, which emit at the deep-blue wavelength of 456â nm. The water controls the orientation and distribution of the ligands on the surface of the nanocrystals, thus inducing orientated growth through the Ostwald ripening process by phagocytizing unstable nanocrystals to form well-crystallized QWs. These QWs present remarkable stability and high photoluminescence quantum yield of 94 %. Furthermore, we have prepared light-emitting diodes based on the QWs via the all-solution fabrication strategy, achieving an external quantum efficiency of 1 % and luminance of 2946â cd m-2 , demonstrating state-of-the-art brightness for perovskite QW-based LEDs.
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The metal halide perovskite nanocrystals (NCs) have attracted much attention because of their excellent optical properties and potential for application in optoelectronic devices. However, their photo- and thermostability are still practical challenges and need further optimization. Here, we have studied the degradation behaviors of CsPbI3 NCs utilized as optical conversion layer in InGaN based blue micro-LEDs in situ. Furthermore, the effects of temperature and light irradiation on perovskite NCs were investigated respectively. The results indicate that both blue light irradiation and high temperature can cause the increased nonradiative recombination rate, resulting in the degradation of perovskite NCs and reduction of the photoluminescence quantum yield (PLQY). Especially in high-temperature condition, both the single-exciton nonradiative recombination rate and the biexciton nonradiative recombination rate are increased, causing the significant reduction of PLQY of perovskite NCs in high temperature environment than blue light irradiation. Our work provides a detailed insight about the correlation between the light irradiation and temperature consequences for CsPbI3 NCs and may help to pave the way toward optoelectronic device applications.
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INTRODUCTION: Epimedium koreanum Nakai (EKN), is a well-known Chinese herbal medicine for the treatment of osteoporosis, immunosuppression, tumours and cardiovascular diseases. Comprehensive component identification is essential for elucidation of its pharmacological mechanism and quality control. However, its complex chemical composition has caused certain difficulties in the analysis of this traditional Chinese medicine (TCM). Therefore, there is an urgent need to establish a method for rapid classification and identification of EKN chemical components. OBJECTIVE: To establish a method for rapid classification and identification of the main components of flavonoids, organic acids and alkaloids in EKN. METHODS: The samples were analysed by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. The UPLC system used a BEH C18 column to separate the total extract of EKN. The mobile phase consisted of 0.1% formic acid in water and acetonitrile, and the EKN extract was analysed by gradient elution at a flow rate of 0.4 mL/min. In both the positive and negative ion modes, the fragment information was obtained and compared with those of the characteristic fragmentations and neutral losses described in the literature to quickly identify the target compounds. RESULTS: Finally, we successfully screened out 51 chemical components, including 40 flavonoids, nine organic acids, and two alkaloids. CONCLUSION: The established method not only comprehensively analysed the chemical compositions of EKN, solved the difficult problems of analysis and identification of the complex chemical compositions of the TCM, but also further promoted the development of the application of chemical compositions of TCM.
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Medicamentos de Ervas Chinesas , Epimedium , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Espectrometria de Massas em TandemRESUMO
Viruses remain a major challenge in the fierce fight against diseases. There have been many pandemics caused by various viruses throughout the world over the years. Recently, the global outbreak of COVID-19 has had a catastrophic impact on human health and the world economy. Antiviral drug treatment has become another essential means to overcome pandemics in addition to vaccine development. How to quickly find effective drugs that can control the development of a pandemic is a hot issue that still needs to be resolved in medical research today. To accelerate the development of drugs, it is necessary to target the key target proteins in the development of the pandemic, screen active molecules, and develop reliable methods for the identification and characterization of target proteins based on the active ingredients of drugs. This article discusses key target proteins and their biological mechanisms in the progression of COVID-19 and other major epidemics. We propose a model based on these foundations, which includes identifying potential core targets, screening potential active molecules of core targets, and verifying active molecules. This article summarizes the related innovative technologies and methods. We hope to provide a reference for the screening of drugs related to pandemics and the development of new drugs.
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Desenvolvimento de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Pandemias , Proteômica/métodos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , COVID-19 , Técnicas de Química Analítica , Infecções por Coronavirus/tratamento farmacológico , Bases de Dados de Proteínas , Humanos , Peste/tratamento farmacológico , Pneumonia Viral/tratamento farmacológicoRESUMO
Currently, research on cardiac injury by aconitine focuses on its effect to directly interfere with the function of cardiac ion channels. Further, abnormal lipid metabolism could cause cardiac injury via inflammatory signaling pathway. In our preliminary study, we discovered that aconitine could alter the metabolism processes of various substances, including palmitic acid. Inspired by these studies, we investigated how elevation of palmitic acid by aconitine causes cardiac injury. Aconitine induced cardiac injury in rats (0.32 mg/kg, d = 7), and the cardiac injury was confirmed by electrocardiogram and serum biochemical study. The proteomic and metabolomic results showed that the palmitic acid level increases in heart tissue, and the NOD-like receptor (NLR) signaling pathway showed a strong effect of cardiac injury. The palmitic acid results in cell viability decline and activates NLR signaling in vitro. The shRNA-mediated knockdown of NLRP3 and NOD1/2 attenuates palmitic acid-induced inhibitory effect on cells and inhibited activation of the NLR signaling pathway. Collectively, this study reveals that aconitine provoked palmitic acid elevation could aggravate cardiac injury via the NLR signaling pathway. This study suggests that drug triggered disorder of the metabolism process could evoke cardiac injury and could propose a new strategy to study drug cardiac injury.
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Aconitina/farmacologia , Metabolômica , Miócitos Cardíacos/efeitos dos fármacos , Ácido Palmítico/metabolismo , Proteômica , Aconitina/metabolismo , Animais , Linhagem Celular , Masculino , Camundongos , Miócitos Cardíacos/metabolismo , Ratos , Ratos WistarRESUMO
Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography-tandem quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, argininic acid, galactonic acid, lactic acid, equol 4'-O-glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1-phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3-dehydrocarnitine, m-methylhippuric acid, 3-hydroxyoctanoic acid, p-cresol sulfate, estriol 3-sulfate 16-glucuronide, 10-hydroxy-9-(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.
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Artrite Gotosa/sangue , Artrite Gotosa/metabolismo , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Animais , Análise Multivariada , RatosRESUMO
Near-Infrared (NIR) light emitting metal halides are emerging as a new generation of optical materials owing to their appealing features, which include low-cost synthesis, solution processability, and adjustable optical properties. NIR-emitting perovskite-based light-emitting diodes (LEDs) have reached an external quantum efficiency (EQE) of over 20% and a device stability of over 10,000 h. Such results have sparked an interest in exploring new NIR metal halide emitters. In this review, several different types of NIR-emitting metal halides, including lead/tin bromide/iodide perovskites, lanthanide ions doped/based metal halides, double perovskites, low dimensional hybrid and Bi3+/Sb3+/Cr3+ doped metal halides, are summarized, and their recent advancement is assessed. The characteristics and mechanisms of narrow-band or broadband NIR luminescence in all these materials are discussed in detail. Also, the various applications of NIR-emitting metal halides are highlighted and an outlook for the field is provided.
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BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.
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The stable cross-shaped CsPbI3 nanoplates (NPs) with red emission were achieved by chemical synthesis with the assistance of YCl3. Y3+ replacing Pb2+ results in the anisotropic growth of the CsPbI3 nanocrystal to form NPs. Four corners of the NPs dissolved, thus forming the cross-shaped NPs. The emission of NPs was shifted from near-infrared (690 nm) to red emission (640 nm) as the dopant amount of Y3+ increased. Y3+ widens the width of the bandgap, which is also proved by first-principles calculations. In addition, the Cl- passivated the surface defects of the NPs, suppressing the nonradiative recombination. The NPs showed remarkable high photoluminescence quantum yields (PLQY) of 96%. PLQY is even more than 60% when NPs have been stored in a glovebox for more than 90 days. The NPs with adjustable wavelength and enhanced stability have a huge application potential in the field of a high-definition display.
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Objectives: Colorectal cancer (CRC) is one of the most common solid tumors worldwide, but its diagnosis and treatment are limited. The objectives of our study were to compare the metabolic differences between CRC patients and healthy controls (HC), and to identify potential biomarkers in the serum that can be used for early diagnosis and as effective therapeutic targets. The aim was to provide a new direction for CRC predictive, preventive, and personalized medicine (PPPM). Methods: In this study, CRC patients (n = 30) and HC (n = 30) were recruited. Serum metabolites were assayed using an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology. Subsequently, CRC cell lines (HCT116 and HCT8) were treated with metabolites to verify their function. Key targets were identified by molecular docking, thermal shift assay, and protein overexpression/inhibition experiments. The inhibitory effect of celastrol on tumor growth was also assessed, which included IC50 analysis, nude mice xenografting, molecular docking, protein overexpression/inhibition experiments, and network pharmacology technology. Results: In the CRC group, 15 serum metabolites were significantly different in comparison with the HC group. The level of glycodeoxycholic acid (GDCA) was positively correlated with CRC and showed high sensitivity and specificity for the clinical diagnostic reference (AUC = 0.825). In vitro findings showed that GDCA promoted the proliferation and migration of CRC cell lines (HCT116 and HCT8), and Poly(ADP-ribose) polymerase-1 (PARP-1) was identified as one of the key targets of GDCA. The IC50 of celastrol in HCT116 cells was 121.1 nM, and the anticancer effect of celastrol was supported by in vivo experiments. Based on the potential of GDCA in PPPM, PARP-1 was found to be significantly correlated with the anticancer functions of celastrol. Conclusion: These findings suggest that GDCA is an abnormally produced metabolite of CRC, which may provide an innovative molecular biomarker for the predictive identification and targeted prevention of CRC. In addition, PARP-1 was found to be an important target of GDCA that promotes CRC; therefore, celastrol may be a potential targeted therapy for CRC via its effects on PARP-1. Taken together, the pathophysiology and progress of tumor molecules mediated by changes in metabolite content provide a new perspective for predictive, preventive, and personalized medical of clinical cancer patients based on the target of metabolites in vivo.Clinical trials registration number: ChiCTR2000039410. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-021-00269-8.
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The inorganic perovskite CsPbI3 that exists in the form of a quantum dot (QD) shows a stable cubic structure, attracting much attention for its application in solar cells. However, too many grain boundaries in the perovskite QD (PQD) layer block the transport of carriers, resulting in the potential loss of solar cells. Herein, we devise a gradient-band alignment (GBA) homojunction, which is constructed from three layers of PQDs with different band-gaps to form a gradient energy alignment. The GBA structure facilitated the charge extraction and increased the carrier diffusion length of the PQD layer because of the additional driving force for the electrons. In addition, the homojunction made from the same substance could minimize the lattice mismatch of the active layer. As a result, the champion solar cell based on the GBA homojunction layer achieved a high open voltage VOC of 1.25 V and a power conversion efficiency (PCE) of 13.2%.
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The research on metal halide perovskite light-emitting diodes (PeLEDs) with green and infrared emission has demonstrated significant progress in achieving higher functional performance. However, the realization of stable pure-blue (≈470 nm wavelength) PeLEDs with increased brightness and efficiency still constitutes a considerable challenge. Here, a novel acid etching-driven ligand exchange strategy is devised for achieving pure-blue emitting small-sized (≈4 nm) CsPbBr3 perovskite quantum dots (QDs) with ultralow trap density and excellent stability. The acid, hydrogen bromide (HBr), is employed to etch imperfect [PbBr6 ]4- octahedrons, thereby removing surface defects and excessive carboxylate ligands. Subsequently, didodecylamine and phenethylamine are successively introduced to bond the residual uncoordinated sites of the QDs and attain in situ exchange with the original long-chain organic ligands, resulting in near-unity quantum yield (97%) and remarkable stability. The QD-based PeLEDs exhibit pure-blue electroluminescence at 470 nm (corresponding to the Commission Internationale del'Eclairage (CIE) (0.13, 0.11) coordinates), an external quantum efficiency of 4.7%, and a remarkable luminance of 3850 cd m-2 , which is the highest brightness reported so far for pure-blue PeLEDs. Furthermore, the PeLEDs exhibit robust durability, with a half-lifetime exceeding 12 h under continuous operation, representing a record performance value for blue PeLEDs.
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Cutaneous eruptions caused by the combination of Chinese and Western medicine have attracted widespread attention; however, the underlying mechanism remains unclear. This study aimed to evaluate the potential mechanism of cutaneous eruptions in vivo and in vitro using the combination of Shuanghuanglian injection powder (SHL) and aspirin (ASA) as an example. ASA and SHL co-administration induced inflammatory responses in HaCat cells, as evidenced by marked increases in the expression of IL-4 and TNF-α, and the level of apoptosis. Additionally, histopathological investigation of mice skin tissues showed local inflammatory cell infiltration. Western boltting was used to detect the effects of ASA on desmoglein-1 (DSG1) expression; we found that DSG1 expression was down-regulated in vivo and in vitro. Finally, the key components of SHL were administered to HaCat cells with down-regulated DSG1; it was seen that neochlorogenic acid and rutin have a significant effect on HaCat cell apoptosis. These results demonstrate that DSG1 deficiency is a potential cause of cutaneous eruptions caused by the combination of SHL and ASA, and neochlorogenic acid and rutin are the main allergenic components. This study provides a new research strategy for the safety evaluation of integrated traditional Chinese and Western medicine.
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Apoptose/efeitos dos fármacos , Aspirina/toxicidade , Desmogleína 1/antagonistas & inibidores , Toxidermias/etiologia , Medicamentos de Ervas Chinesas/toxicidade , Queratinócitos/efeitos dos fármacos , Animais , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/toxicidade , Desmogleína 1/metabolismo , Toxidermias/metabolismo , Toxidermias/patologia , Feminino , Células HaCaT , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-4/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos Endogâmicos ICR , Ácido Quínico/análogos & derivados , Ácido Quínico/toxicidade , Rutina/toxicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Fluoxetine hydrochloride is one of the familiar antidepressants of the second generation and has the effect of inhibiting the reuptake of 5-hydroxytryptamine by central nervous system. Both clinical trials and animal experiments show that it has good antidepressant effect, but there are few reports on its clinical efficacy in treating depression patients from the perspective of metabolomics. This study aimed at evaluating the antidepressant effect of fluoxetine hydrochloride by metabolomics, so that to find out its specific biomarkers and related metabolic characteristics of depression in the treatment of depression and analyze the intervention mechanism of fluoxetine hydrochloride in depression. METHOD: Twenty depression patients and twenty healthy volunteers were recruited in clinical. Using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to analyze serum metabolites of depression patients pretherapy and post-treatment and compared with healthy people. RESULT: Finally, we have detected 16 specific biomarkers of depression. Compared with the healthy group, the level of 10 biomarkers in the depression group was significantly increased (P < 0.05) and 6 biomarkers were significantly decreased (P < 0.01). After 8 weeks of fluoxetine hydrochloride treatment, all the biomarkers have showed a tendency of callback. The metabolic pathways involved amino acid metabolism, energy metabolism and lipid metabolism. CONCLUSION: In our study, the antidepressant effect of fluoxetine hydrochloride in clinic was proved by metabolomics and provided basis for clinical use of fluoxetine hydrochloride. At the same time, the biomarkers that may be related to the occurrence of depression are determined to provide objective basis for the diagnosis of depression.
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Antidepressivos de Segunda Geração/uso terapêutico , Depressão/sangue , Depressão/tratamento farmacológico , Fluoxetina/uso terapêutico , Metabolômica/métodos , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Depressão/diagnóstico , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Adulto JovemRESUMO
Heart failure is a common systemic disease with high morbidity and mortality worldwide. Doxorubicin (DOX) is a commonly used anthracycline broad-spectrum antitumor antibiotic with strong antitumor effect and definite curative effect. However, cardiotoxicity is the adverse reaction of drug dose cumulative toxicity, but the mechanism is still unclear. In this study, proteomics and metabonomics techniques were used to analyze the tissue and plasma of DOX-induced heart failure (HF) in rats and to clarify the molecular mechanism of the harmful effects of DOX on cardiac metabolism and function in rats from a new point of view. The results showed that a total of 278 proteins with significant changes were identified by quantitative proteomic analysis, of which 118 proteins were significantly upregulated and 160 proteins were significantly downregulated in myocardial tissue. In the metabonomic analysis, 21 biomarkers such as L-octanoylcarnitine, alpha-ketoglutarate, glutamine, creatine, and sphingosine were detected. Correlation analysis showed that DOX-induced HF mainly affected phenylalanine, tyrosine, and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, and other metabolic pathways, suggesting abnormal amino acid metabolism, fatty acid metabolism, and glycerol phospholipid metabolism. It is worth noting that we have found the key upstream target of DOX-induced HF, PTP1B, which inhibits the expression of HIF-1α by inhibiting the phosphorylation of IRS, leading to disorders of fatty acid metabolism and glycolysis, which together with the decrease of Nrf2, SOD, Cytc, and AK4 proteins lead to oxidative stress. Therefore, we think that PTP1B may play an important role in the development of heart failure induced by doxorubicin and can be used as a potential target for the treatment of heart failure.