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1.
Front Pharmacol ; 15: 1415147, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38803438

RESUMEN

As a traditional Chinese medicinal herb with a long history, Codonopsis pilosula (CP) has attracted much attention from the medical community in recent years. This review summarizes the research progress of CP in the medical field in the past 5 years. By searching and analyzing the literature, and combining with Cytoscape software, we comprehensively examined the role and mechanism of action of CP in individual application, combination drug application, and the role and mechanism of action of codonopsis pilosula's active ingredients in a variety of diseases. It also analyzes the medicinal use of CP and its application value in medicine. This review found that CP mainly manifests important roles in several diseases, such as cardiovascular system, nervous system, digestive system, immune system, etc., and regulates the development of many diseases mainly through the mechanisms of inflammation regulation, oxidative stress, immunomodulation and apoptosis. Its rich pharmacological activities and diverse medicinal effects endow CP with broad prospects and application values. This review provides valuable reference and guidance for the further development of CP in traditional Chinese medicine.

2.
Int J Pharm ; 657: 124145, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38679242

RESUMEN

In this study, we have developed an innovative pH-triggered nanomedicine delivery system, targeting HER2-positive breast cancer cells for effective low-cost, imaging-guided drug delivery and precise therapy. The key feature of this system lies in its unique tumor interstitial fluid microenvironment-responsive drug release behavior which achieved tumor site-specific drug delivery. Our in vitro experiments demonstrated that the carbon dot-integrated material achieves more efficient DTX release (96.13 % at 72 h) in the tumor interstitial fluid microenvironment (pH 6.5), thereby boosting drug concentration at the tumor site and enhancing therapeutic efficacy. Further cell experiments confirmed the system's significant inhibitory effect on HER2-positive tumor cells SKBR3 in a pH 6.5 environment, and apoptosis assays indicating a notable increase in early cell apoptosis (from 8.39 % to 24.61 % compared with pH 7.4). Furthermore, the integration of HER2 aptamer within the carbon dot-based system enables targeted recognition and binding to tumor cells, ensuring more precise delivery of DTX while minimizing potential side effects. Crucially, the carbon dots in this system emit superior red fluorescence (the QY = 47.64 % excited at 535 nm compared with Rodamine 6G), enabling real-time visualization of the drug delivery process. This feature provides valuable feedback on treatment effectiveness, facilitating necessary adjustments. The small size (1.88 ± 0.48 nm) of carbon dots significantly improved their ability to penetrate biological barriers, while their low toxicity (no significant cell toxicity under 350 µg/mL) contributed to the formulation's outstanding biocompatibility. Overall, this carbon dot-enhanced drug delivery system offers immense potential for enhancing drug efficacy, minimizing side effects, and providing real-time treatment monitoring, thus proposing a innovate strategy for breast cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Carbono , Docetaxel , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Receptor ErbB-2 , Neoplasias de la Mama/tratamiento farmacológico , Humanos , Receptor ErbB-2/metabolismo , Carbono/química , Carbono/administración & dosificación , Femenino , Línea Celular Tumoral , Docetaxel/administración & dosificación , Docetaxel/farmacología , Sistemas de Liberación de Medicamentos/métodos , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/química , Concentración de Iones de Hidrógeno , Apoptosis/efectos de los fármacos , Líquido Extracelular/metabolismo , Microambiente Tumoral/efectos de los fármacos , Nanopartículas/administración & dosificación , Nanopartículas/química , Animales , Puntos Cuánticos/química , Puntos Cuánticos/administración & dosificación
3.
Front Psychiatry ; 15: 1297204, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38322142

RESUMEN

Background: Alterations in brain structure and function in major depressive disorder (MDD) have been identified in a number of studies, but findings regarding cortical thickness were various and inconsistent. Our current study aims to explore the differences in cortical thickness between individuals with MDD and healthy controls (HC) in a Chinese population. Methods: We investigated T1-weighted brain magnetic resonance imaging data from 61 participants (31 MDD and 30 HC). The cortical thickness between the two groups and analyzed correlations between cortical thickness and demographic variables in the MDD group for regions with significant between-group differences were conducted. Results: Compared with the HC group, patients with MDD had significantly decreased cortical thickness, in left pars triangularis, left pars orbitalis, left rostral middle frontal gyrus, left supramarginal gyrus, right parahippocampal gyrus, right lingual gyrus, right fusiform and right inferior parietal gyrus. The cortical thickness of left rostral middle frontal gyrus was negatively correlated (r = -0.47, p = 0.028) with the illness duration in patients with MDD. Conclusion: Our study distinguished that cortical thickness decreases in numerous brain regions both in the left and right hemisphere in individuals with MDD, and the negative correlation between the cortical thickness of left rostral middle frontal gyrus illness duration. Our current findings are valuable in providing neural markers to identify MDD and understanding the potential pathophysiology of mood disorders.

4.
Plant Sci ; 340: 111974, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38199385

RESUMEN

The AGL6 (AGMOUSE LIKE 6) gene is a member of the SEP subfamily and functions as an E-class floral homeotic gene in the development of floral organs. In this study, we cloned IiAGL6, the orthologous gene of AGL6 in Isatis indigotica. The constitutive expression of IiAGL6 in Arabidopsis thaliana resulted in a late-flowering phenotype and the development of curly leaves during the vegetative growth period. Abnormal changes in floral organ development were observed during the reproductive stage. In woad plants, suppression of IiAGL6 using TRV-VIGS (tobacco rattle virus-mediated virus-induced gene silencing) decreased the number of stamens and led to the formation of aberrant anthers. Similar changes in stamen development were also observed in miRNA-AGL6 transgenic Arabidopsis plants. Yeast two-hybrid and BiFC tests showed that IiAGL6 can interact with other MADS-box proteins in woad; thus, playing a key role in defining the identities of floral organs, particularly during stamen formation. These findings might provide novel insights and help investigate the biological roles of MADS transcription factors in I. indigotica.


Asunto(s)
Arabidopsis , Isatis , Isatis/genética , Isatis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Flores , Arabidopsis/metabolismo , Polen/genética , Polen/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo , Filogenia
5.
Ann Indian Acad Neurol ; 26(5): 742-748, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38022444

RESUMEN

Objective: In patients with post-stroke oropharyngeal dysphagia (PSOD), classical dysphagia therapy (CDT) continues to provide unsatisfactory outcomes and makes it challenging for them to remove the nasal feeding tube. Increasing bolus viscosity helps prevent aspiration in PSOD. However, conventional starch thickeners enhance post-digestion residue. This study aims to evaluate the efficacy of swallow training with xanthan gum-based thickener (XGT) (Softia G, NUTRI Co., Ltd., Yokkaichi, Japan) additional to CDT in Chinese PSOD patients with a nasogastric tube when compared to CDT alone. Methods: Patients with PSOD who had a nasogastric tube were randomly assigned to either the experimental group (E-group) or the control group (C-group) in this randomized controlled, single-blind, parallel-group study. Both groups received CDT for 4 weeks. The E-group cases received additional swallow training with a Softia G-prepared hydrogel training material. The Functional Oral Intake Scale (FOIS) and modified volume-viscosity swallow test (M-VVST) for swallowing safety and efficacy according to adjusted Chinese dietary habits were administered before and after treatment. Post-training, both groups' nasogastric tube removal rates were calculated. Results: One hundred sixty-seven participants (E-group: 82 and C-group: 85) completed the study. The E-group's median score of FOIS improved significantly than the C-group after training (median = 5 vs. 3, P < 0.001). The incidence of coughing, voice changes, oxygen desaturation of 3% or more, pharyngeal residue and piecemeal deglutition in the E-group was significantly lower than that in the C-group (P < 0.05). The E-group had 100% nasogastric tube removal, while the C-group had 28.24% (P < 0.001). Conclusion: Swallow training with XGT Softia G in addition to CDT can promote swallowing safety and efficacy in Chinese patients with PSOD more effectively than CDT alone.

6.
Mikrochim Acta ; 190(8): 328, 2023 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-37495854

RESUMEN

Thrombin, a crucial enzyme involved in blood coagulation and associated diseases, requires accurate detection of its activity and screening of inhibitors for clinical diagnosis and drug discovery. To address this, an electrochemiluminescence (ECL) method was developed to detect thrombin activity based on the sensitization of Ti3C2Tx MXene, which could sensitize the Ru(bpy)32+ ECL system greatly. The thrombin-cleavable substrate bio-S-G-R-P-V-L-G-C was used as recognizer to evaluate the activity of thrombin. Under the optimal conditions, the limit of detection for thrombin in serum was 83 pU/mL (S/N = 3) with a linear range from 0.1 nU/mL to 1 µU/mL. Moreover, the developed ECL biosensor was employed to screen for thrombin inhibitors from Artemisiae argyi Folium. Four potential thrombin inhibitors (isoquercitrin, nepetin, L-camphor, L-borneol) were screened out with inhibition rates beyond 50%, among which isoquercitrin had the best inhibition rate of 90.26%. Isoquercitrin and nepetin were found to be competitive inhibitors of thrombin, with [Formula: see text] values of 0.91 µM and 2.18 µM, respectively. Molecular docking results showed that these compounds could interact with the active sites of thrombin through hydrogen bonds including ASP189, SER195, GLY216, and GLY219. The electrochemical biosensor constructed provides a new idea for the detection of thrombin activity and screening of its inhibitors.


Asunto(s)
Técnicas Biosensibles , Trombina , Simulación del Acoplamiento Molecular , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos
7.
BJPsych Open ; 9(3): e101, 2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37246576

RESUMEN

BACKGROUND: Major depressive disorder (MDD) is a serious psychiatric disorder marked by low mood and anhedonia. Understanding the neural mechanism of MDD is essential for the treatment of depression. White matter fibres, connecting different computational units in the brain, have an important effect on brain function; however, the mechanism of white matter fibre abnormality in MDD is still unclear. AIMS: Our study expected to find white matter abnormalities associated with the frontal lobe and hippocampus in individuals with MDD. METHOD: Using diffusion tensor imaging data and tract-based spatial statistics, we investigated the microstructural differences in white matter fibre tracts between 30 adults with MDD compared with 31 healthy controls, and calculated the association between MDD-related microstructural changes and illness duration. RESULTS: It was found that patients with MDD showed reduced fractional anisotropy in the genu and body of the corpus callosum, right corona radiata and part of the thalamic radiations, suggesting lower fibrous myelination levels in these regions; the decreased fractional anisotropy in these regions was associated with longer illness duration. CONCLUSIONS: Our results suggest that MDD may be associated with microstructural damage of key fibre tracts, which could provide insights into the understanding and treatment of MDD.

8.
Nanoscale Adv ; 5(7): 1830-1852, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-36998669

RESUMEN

Artificial light-harvesting systems, an elegant way to capture, transfer and utilize solar energy, have attracted great attention in recent years. As the primary step of natural photosynthesis, the principle of light-harvesting systems has been intensively investigated, which is further employed for artificial construction of such systems. Supramolecular self-assembly is one of the feasible methods for building artificial light-harvesting systems, which also offers an advantageous pathway for improving light-harvesting efficiency. Many artificial light-harvesting systems based on supramolecular self-assembly have been successfully constructed at the nanoscale with extremely high donor/acceptor ratios, energy transfer efficiency and the antenna effect, which manifests that self-assembled supramolecular nanosystems are indeed a viable way for constructing efficient light-harvesting systems. Non-covalent interactions of supramolecular self-assembly provide diverse approaches to improve the efficiency of artificial light-harvesting systems. In this review, we summarize the recent advances in artificial light-harvesting systems based on self-assembled supramolecular nanosystems. The construction, modulation, and applications of self-assembled supramolecular light-harvesting systems are presented, and the corresponding mechanisms, research prospects and challenges are also briefly highlighted and discussed.

9.
ACS Appl Mater Interfaces ; 15(8): 11004-11015, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36802465

RESUMEN

Developing an artificial dynamic nanoscale molecular machine that dissipatively self-assembles far from equilibrium is fundamentally important but is significantly challenging. Herein, we report dissipatively self-assembling light-activated convertible pseudorotaxanes (PRs) that show tunable fluorescence and enable deformable nano-assemblies. A pyridinium-conjugated sulfonato-merocyanine derivative (EPMEH) and cucurbit[8]uril (CB[8]) form the 2EPMEH ⊂ CB[8] [3]PR in a 2:1 stoichiometry, which phototransforms into a transient spiropyran containing 1:1 EPSP ⊂ CB[8] [2]PR when exposed to light. The transient [2]PR thermally relaxes (reversibly) to the [3]PR in the dark accompanied by periodic fluorescence changes that include near-infrared emission. Moreover, octahedral and spherical nanoparticles are formed through the dissipative self-assembly of the two PRs, and the Golgi apparatus is dynamically imaged using fluorescent dissipative nano-assemblies.

10.
Plant Cell Rep ; 42(3): 561-574, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36609767

RESUMEN

KEY MESSAGE: IiSVP of Isatis indigotica was cloned and its expression pattern was analyzed. Ectopic expression of IiSVP in Arabidopsis could delay the flowering time and reduce the size of the floral organs. SVP (SHORT VEGETATIVE PHASE) can negatively regulate the flowering time of Arabidopsis. In the present work, the cDNA of IiSVP, an orthologous gene of AtSVP in I. indigotica, was cloned. IiSVP was highly expressed in rosette leaves, inflorescences and petals, but weakly expressed in sepals, pistils and young silicles. The results of subcellular localization showed that IiSVP was localized in nucleus. Bioinformatics analysis indicated that this protein was a MADS-box transcription factor. Constitutive expression of IiSVP in Arabidopsis thaliana resulted in decrease of the number of petals and stamens, and curly sepals were formed. In IiSVP transgenic Arabidopsis plants, obvious phenotypic variations in flowers could be observed, especially the size of the floral organs. In comparison with the wild-type plants, the size of petals, stamens and pistil in IiSVP transgenic Arabidopsis plants was decreased significantly. In some transgenic plants, the petals were wrapped by the sepals. Yeast two-hybrid experiments showed that IiSVP could form higher-order complexes with other MADS proteins, including IiSEP1, IiSEP3, IiAP1 and IiSEP4, but could not interact with IiSEP2. In this work, it was proved that the flowering process and the floral development in Arabidopsis could be affected by IiSVP from I. indigotica Fortune.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Isatis , Arabidopsis/metabolismo , Isatis/genética , Isatis/metabolismo , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Proteínas de Plantas/metabolismo , Flores , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/genética , Proteínas de Arabidopsis/genética
11.
Front Psychiatry ; 13: 1028518, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36465288

RESUMEN

Objective: Currently, findings regarding resting-state functional magnetic resonance imaging studies of major depressive disorder (MDD) are inconsistent. In contrast to the previously used a priori seed-based functional connectivity analyses, this study employed whole-brain exploratory analyses and aimed to explore neural activity patterns in Chinese adults with MDD. Materials and methods: Specifically, this study examined the amplitude of low-frequency fluctuations within the whole brain and adopted a large-scale brain network template to explore the core dysfunctional brain regions in individuals with MDD. Results: Overall, 32 individuals with MDD and 32 healthy controls were evaluated. Compared to healthy controls, individuals with MDD showed more profound alterations in the amplitude of low-frequency fluctuations in the temporolimbic affective circuit (e.g., middle temporal gyrus and parahippocampus) and default mode network (e.g., precuneus and thalamus). Moreover, functional connectivity between the left mid-insula and parietal regions within the sensorimotor network was weaker in individuals with MDD than in healthy controls. Conclusion: In conclusion, the neural characteristics of MDD correspond to cognitive deficits in self-referential processing and emotional processing and are related to a risk of sensory disorders or psychomotor retardation. These findings present neural markers that may be used to identify MDD, contributing to clinical diagnosis.

12.
ACS Appl Mater Interfaces ; 14(19): 22443-22453, 2022 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-35513893

RESUMEN

Artificial supramolecular light-harvesting systems have expanded various properties on photoluminescence, enabling promising applications on cell imaging, especially for imaging in organelles. Supramolecular light-harvesting systems have been used for imaging in some organelles such as lysosome, Golgi apparatus, and mitochondrion, but developing a supramolecular light-harvesting platform for imaging two organelles synchronously still remains a great challenge. Here, we report a series of lower-rim dodecyl-modified sulfonato-calix[4]arene-mediated supramolecular light-harvesting platforms for efficient light-harvesting from three naphthalene diphenylvinylpyridiniums containing acceptors, Nile Red, and Nile Blue. All of the constructed supramolecular light-harvesting systems possess high light-harvesting efficiency. Furthermore, when the two acceptors are loaded simultaneously in a single light-harvesting donor system for imaging in human prostate cancer cells, organelle imaging in lysosome and Golgi apparatus can be realized at the same time with distinctive wavelength emission. Nile Red receives the light-harvesting energy from the donors, reaching orange emissions (625 nm) in lysosome while Nile Blue shows a near-infrared light-harvesting emission at 675 nm in Golgi apparatus in the same cells. Thus, the light harvesting system provides a pathway for synchronously efficient cell imaging in two distinct organelles with a single type of photoluminescent supramolecular nanoparticles.


Asunto(s)
Calixarenos , Nanopartículas , Diagnóstico por Imagen , Aparato de Golgi , Humanos , Lisosomas
13.
Nat Commun ; 12(1): 4993, 2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34404798

RESUMEN

Dissipative self-assembly, which requires a continuous supply of fuel to maintain the assembled states far from equilibrium, is the foundation of biological systems. Among a variety of fuels, light, the original fuel of natural dissipative self-assembly, is fundamentally important but remains a challenge to introduce into artificial dissipative self-assemblies. Here, we report an artificial dissipative self-assembly system that is constructed from light-induced amphiphiles. Such dissipative supramolecular assembly is easily performed using protonated sulfonato-merocyanine and chitosan based molecular and macromolecular components in water. Light irradiation induces the assembly of supramolecular nanoparticles, which spontaneously disassemble in the dark due to thermal back relaxation of the molecular switch. Owing to the presence of light-induced amphiphiles and the thermal dissociation mechanism, the lifetimes of these transient supramolecular nanoparticles are highly sensitive to temperature and light power and range from several minutes to hours. By incorporating various fluorophores into transient supramolecular nanoparticles, the processes of aggregation-induced emission and aggregation-caused quenching, along with periodic variations in fluorescent color over time, have been demonstrated. Transient supramolecular assemblies, which act as fluorescence modulators, can also function in human hepatocellular cancer cells.


Asunto(s)
Colorantes Fluorescentes/química , Nanopartículas/química , Agua/química , Fluorescencia , Células Hep G2 , Humanos , Cinética , Sustancias Macromoleculares , Temperatura
14.
J Sep Sci ; 44(16): 3061-3069, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34110096

RESUMEN

Carthami flos, commonly known as Honghua in China, is the dried floret of safflower and widely acknowledged as a blood stasis promoting herb. The study aimed at investigating the relationship between thrombin and carthami flos through a high-performance thrombin affinity chromatography combined with a high-performance liquid chromatography-tandem mass spectrometry system. First, thrombin was immobilized on the glutaraldehyde-modified amino silica gel to prepare the thrombin affinity stationary phase, which was packed into a small column (1.0 × 2.0 mm, id) for recognizing the anticoagulant active components of carthami flos. The target component was enriched and analyzed by the high-performance liquid chromatography-tandem mass spectrometry system. Finally, hydroxysafflor yellow A was screened out and identified as the active component. The anticoagulant effects of hydroxysafflor yellow A were analyzed by anticoagulant experiments in vitro, and the interaction of hydroxysafflor yellow A with thrombin was investigated by the molecular docking method. The results proved that hydroxysafflor yellow A (30 µg/mL, 0.05 mM) and carthami flos extract (30 µg/mL) could prolong activated partial thrombin time and thrombin time by 50 and 11%, respectively. Moreover, hydroxysafflor yellow A exhibits a good hydrogen bond field and stereo field matching with thrombin. Overall, it was concluded that hydroxysafflor yellow A might exert an anticoagulation effect by interacting with thrombin and thus could be potential anticoagulant drugs for the prevention and treatment of venous thrombosis.


Asunto(s)
Anticoagulantes/análisis , Carthamus tinctorius/metabolismo , Cromatografía de Afinidad/métodos , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/metabolismo , Espectrometría de Masas en Tándem/métodos , Trombina/química , Animales , Chalcona/análogos & derivados , Chalcona/química , Enlace de Hidrógeno , Técnicas In Vitro , Masculino , Simulación del Acoplamiento Molecular , Polvos , Quinonas/química , Conejos , Reproducibilidad de los Resultados , Trombina/análisis , Tiempo de Trombina , Trombosis de la Vena/tratamiento farmacológico
15.
Nanoscale Adv ; 3(8): 2316-2324, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-36133763

RESUMEN

Carbon dots (CDots) are defined as surface-passivated small carbon nanoparticles, with the effective passivation generally achieved by organic functionalization. Photoexcited CDots are both potent electron donors and acceptors, and their characteristic bright and colorful fluorescence emissions make them excellent fluorescence sensors for organic analytes and metal ions. For the latter extraordinarily low detection limits based on extremely efficient quenching of fluorescence intensities by the targeted metal cations have been observed and reported in the literature. However, all of the dot samples in those reported studies were made from "one-pot" carbonization of organic precursors mostly under rather mild processing conditions, unlikely to be sufficient for the required level of carbonization. Those dot samples should therefore be more appropriately considered as "nano-carbon/organic hybrids", characterized structurally as being highly porous and spongy, which must be playing a dominating role in the reported sensing results. In this study, we compared the dot samples from carbonization syntheses under similarly mild and also more aggressive processing conditions with the classically defined and structured CDots for the fluorescence sensing of copper(ii) cations in aqueous solutions. The observed dramatic decoupling between quenching results for fluorescence intensities and lifetimes of the carbonization samples, with the former being extraordinary and the latter within the diffusion controlled limit, suggested that the quenching of fluorescence intensities was greatly affected by the higher local quencher concentrations than the bulk associated with the porous and spongy sample structures, especially for the sample from carbonization under too mild processing conditions. The major differences between the classical CDots and the nano-carbon/organic hybrids are highlighted, and the tradeoffs between sensitivity and accuracy or reproducibility in the use of the latter for fluorescence sensing are discussed.

16.
Acta Pharm Sin B ; 10(10): 1800-1813, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33163336

RESUMEN

Natural products have provided numerous lead compounds for drug discovery. However, the traditional analytical methods cannot detect most of these active components, especially at their usual low concentrations, from complex natural products. Herein, we reviewed the recent technological advances (2015-2019) related to the separation and screening bioactive components from natural resources, especially the emerging screening methods based on the bioaffinity techniques, including biological chromatography, affinity electrophoresis, affinity mass spectroscopy, and the latest magnetic and optical methods. These screening methods are uniquely advanced compared to other traditional methods, and they can fish out the active components from complex natural products because of the affinity between target and components, without tedious separation works. Therefore, these new tools can reduce the time and cost of the drug discovery process and accelerate the development of more effective and better-targeted therapeutic agents.

17.
Artículo en Inglés | MEDLINE | ID: mdl-31973978

RESUMEN

In order to develop an affinity HPLC method for screening direct thrombin inhibitors from Traditional Chinese Medicine (TCM), thrombin was immobilized on the glutaraldehyde-modified amino silica gel and was used as thrombin stationary phase. A thrombin affinity column (TAC) was made by packing the thrombin stationary phase into a bare column (2.0 * 1.0 mm, i.d.). The direct thrombin inhibitors could be screened through this TAC column. For the purpose of improvement of the discovery efficiency, a TAC-HPLC-MS/MS system was used to screen thrombin inhibitors from Radix Salviae Miltiorrhiae (RSM), a famous traditional Chinese medicine. After optimization of all the conditions, cryptotanshinone (Cry), dihydrotanshinone I (Dih-I) and tanshinone IIA (Tan-IIA) were screened out and identified as potential active components. The anticoagulant effects of these three compounds were tested by anticoagulant experiments in vitro. Furthermore, the interaction of three compounds with thrombin was studied by molecular docking. The result shows they have the potential to be used as preventive drugs. In short, this method can be used to screen anticoagulant drugs from traditional Chinese medicine, which provides convenience for screening anticoagulant drugs.


Asunto(s)
Antitrombinas , Cromatografía de Afinidad , Medicamentos Herbarios Chinos/química , Salvia miltiorrhiza/química , Trombina/metabolismo , Animales , Antitrombinas/análisis , Antitrombinas/metabolismo , Pruebas de Coagulación Sanguínea , Cromatografía de Afinidad/instrumentación , Cromatografía de Afinidad/métodos , Cromatografía Líquida de Alta Presión/métodos , Masculino , Simulación del Acoplamiento Molecular , Conejos , Espectrometría de Masas en Tándem/métodos , Trombina/química
18.
J Anal Methods Chem ; 2019: 3150942, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31467767

RESUMEN

Tianwang Buxin pill (TWBXP) is an ancient Chinese classic prescription. Liquiritin, deoxyschizandrin, and tanshinone II A are three bioactive components in TWBXP, which have been proven to be closely related to the therapy effect of neurodegenerative disease. Their contents are very low in TWBXP. In this study, we used a diode array detector (DAD) to perform a full wavelength scanning in order to choose a most suitable detection wavelength to establish an HPLC method for the simultaneous determination of these three components in TWBXP. Various chromatographic conditions were investigated to verify its applicability. Finally, a Kromasil C18 column (250 × 4.6 mm, 5 µm) thermostated at 30°C, mobile phase as 0.2% phosphoric acid solution (eluent A), and 0.1% phosphoric acid-acetonitrile solution (eluent B) were used. Both external standard method and internal standard method were used for quantification. The results showed that both methods were simple and convenient in operation without special pretreatment and exhibits excellent precision, repeatability (RSD < 3.0%), good linearity (R 2 > 0.9990), and good recoveries (recovery value between 95% and 105%). Because of the low contents in samples, the internal standard method provided a better accurate result than the external standard method. The stability results showed the sample became stable within 24 hours at room temperature. The method provides a convenient and effective way for the quality control of TWBXP, and it can help the research about AD in the future.

19.
J Pharm Anal ; 9(1): 55-61, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30740258

RESUMEN

Cow's milk allergy is mainly observed in infants and young children. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems. Conventional diagnosis is based on positive allergy studies and evaluation of parameters including IgE and IgG1 levels, acute allergic skin response and anaphylactic shock reactions. We developed a cell membrane chromatographic (CMC) method based on human mast cells (HMC-1) for screening potential allergens in infant formula milk powders (IFMP). HMC-1 cell membranes were extracted and mixed with silica to prepare cell membrane chromatography columns (10 mm × 2 mm i.d., 5 µm). Under the conditions of 0.2 mL/min flow rate and 214 nm detection wavelength, human breast milk showed no retention. However, IFMP showed clear retention. The retained fractions were collected and analyzed through matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Four major milk proteins, i.e., α-casein, ß-casein, α-lactalbumin, and ß-lactoglobulin A, were identified. Furthermore, these proteins and ß-lactoglobulin B showed clear retention on HMC-1/CMC columns. To test the degranulation effects of the five proteins, histamine and ß-hexosaminidase release assays were carried out. All five proteins induced HMC-1 cells to release histamine and ß-hexosaminidase. Also, we established a reversed phase liquid chromatographic (RPLC) method for the determination of the five proteins in IFMP and the results showed that 90% proteins in IFMP were α-casein and ß-casein. We concluded that cow's milk proteins may be potential allergens and caseins cause more ß-casein allergic risk than other proteins. This conclusion was consistent with other studies.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1502-1506, 2018 Oct.
Artículo en Chino | MEDLINE | ID: mdl-30295275

RESUMEN

OBJECTIVE: To explore the immunopathogenesis of Henoch-Schonlein purpara (HSP) by detecting the levels of Th17 cells, IL-17 and matrix metallo proteinase-13 (MMP-13) in peripheral blood and the expression of IL-17 in skin lesions at acate phase of HSP. METHODS: Th17 cell ratio in peripheral blood of HSP group and healthy control group was defected by flow cytometry, the plasma levels of IL-17 and MMP-13 in HSP group and healthy control group were defected by ELISA, and expression level of IL-17 in skin lesion of HSP group and skin tissue of healthy control group was deternined by: immunohistochemistry method. RESULTS: the ratio of Th17 cells in periphral blood of HSP group (1.21±0.59%) was very signif cantly higher than that in peripheral blood of control group (0.71±0.26%) ( t=4.907, P<0.01). The plasma levels of IL-17 and MMP-13 at acute phase of HSP were very significantly higher than those in control group (64.58±36.21) pg/ml vs (26.16±14.90) pg/ml and (17.57±5.40) pg/ml vs (11.53±4.40) pg/ml respectively (t=6.183, P<0.01 and t=5.022, P<0.01). The integrool optical density of IL-17 in skin lesin tissue of HSP group (7.26±2.34) was higher than that in control group (4.61±1.82) ( t=2.877, P<0.01). CONCLUSION: Th17 cells, IL-17 and MMP-13 may be involved in the immunological pathogenesis of HSP.


Asunto(s)
Vasculitis por IgA , Células Th17 , Citometría de Flujo , Humanos , Interleucina-17 , Metaloproteinasa 13 de la Matriz
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