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X-ray radiation information storage, characterized by its ability to detect radiation with delayed readings, shows great promise in enabling reliable and readily accessible X-ray imaging and dosimetry in situations where conventional detectors may not be feasible. However, the lack of specific strategies to enhance the memory capability dramatically hampers its further development. Here, we present an effective anion substitution strategy to enhance the storage capability of NaLuF4:Tb3+ nanocrystals attributed to the increased concentration of trapping centers under X-ray irradiation. The stored radiation information can be read out as optical brightness via thermal, 980 nm laser, or mechanical stimulation, avoiding real-time measurement under ionizing radiation. Moreover, the radiation information can be maintained for more than 13 days, and the imaging resolution reaches 14.3 lp mm-1. These results demonstrate that anion substitution methods can effectively achieve high storage capability and broaden the application scope of X-ray information storage.
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Malignant melanoma (MM) is notorious for its high metastatic potential, with cardiac metastasis being particularly severe as it involves cardiac structures and can lead to significant cardiac functional issues. While there is no standardized treatment approach, early detection and intervention can improve prognosis.
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Ecocardiografia , Neoplasias Cardíacas , Neoplasias Intestinais , Melanoma , Humanos , Melanoma/secundário , Neoplasias Cardíacas/secundário , Neoplasias Cardíacas/diagnóstico por imagem , Ecocardiografia/métodos , Neoplasias Intestinais/secundário , Neoplasias Intestinais/diagnóstico por imagem , Masculino , Intestino Delgado , Pessoa de Meia-IdadeRESUMO
This case report describes a 35-year-old female patient who presented with palpitations and shortness of breath. Imaging findings suggested a cardiac tumor, histopathology confirmed primary cardiac angiosarcoma. This tumor is highly aggressive, usually occurs in the right atrium, lacks specificity in clinical presentation, is prone to early metastasis, and has a poor prognosis. Echocardiography is the method of choice for early detection and is important in assessing tumor size, location, mode of attachment and whether cardiac function is impaired.
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Ecocardiografia , Neoplasias Cardíacas , Hemangiossarcoma , Humanos , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Feminino , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/diagnóstico , Adulto , Ecocardiografia/métodos , Átrios do Coração/diagnóstico por imagem , Diagnóstico DiferencialRESUMO
This study was designed to explore the potential of gypenosides as a novel natural stabilizer for the production of nanosuspensions. The gypenosides-stabilized quercetin nanosuspensions(QUE-NS) were prepared using the high-speed shearing and high-pressure homogenization method with quercetin as a model drug, followed by their in vitro evaluation.Based on the measured mean particle size and polydispersity index(PDI) of QUE-NS,the single factor experiment was conducted to optimize the preparation process parameters.The freeze-drying method was used to transform QUE-NS into freeze-dried powders, whose storage stability and saturation solubility were then studied.Moreover, the effects of pH and ionic strength on the physical stability of the nanosuspension system were examined.According to the results, the optimized process parameters were listed as follows: shear rate 13 000 r·min~(-1),shear time 2 min, homogenization pressure 100 MPa, and homogenization frequency 12 times.The mean particle size of QUE-NS prepared under the optimum process conditions was(461.9±2.4) nm, and the PDI was 0.059±0.016.During the two months of storage at room temperature, the freeze-dried QUE-NS powders remained stable.The saturation solubility of freeze-dried QUE-NS powders was proved higher than those of quercetin and the physical mixture.The results of stability testing demonstrated that QUE-NS stabilized with gypenosides exhibited good stability within the pH range of 6 to 8,while coalescence was prone to occur in the presence of salt.Overall, gypenosides is expected to become a new natural stabilizer for the preparation of nanosuspensions.
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Nanopartículas , Quercetina , Estabilidade de Medicamentos , Gynostemma , Tamanho da Partícula , Extratos Vegetais , Pós , Solubilidade , SuspensõesRESUMO
Lupeol is a natural triterpenoid that widely exists in edible fruits and vegetables, and medicinal plants. In the last decade, a plethora of studies on the pharmacological activities of lupeol have been conducted and have demonstrated that lupeol possesses an extensive range of pharmacological activities such as anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. Pharmacokinetic studies have indicated that absorption of lupeol by animals was rapid despite its nonpolar characteristics, and lupeol belongs to class II BCS (biopharmaceutics classification system) compounds. Moreover, the bioactivities of some isolated or synthesized lupeol derivatives have been investigated, and these results showed that, with modification to C-3 or C-19, some derivatives exhibit stronger activities, e.g., antiprotozoal or anticancer activity. This review aims to summarize the advances in pharmacological and pharmacokinetic studies of lupeol in the last decade with an emphasis on its anticancer and anti-inflammatory activities, as well as the research progress of lupeol derivatives thus far, to provide researchers with the latest information, point out the limitations of relevant research at the current stage and the aspects that should be strengthened in future research.
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Anti-Inflamatórios , Antineoplásicos , Triterpenos Pentacíclicos , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Triterpenos Pentacíclicos/farmacocinética , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/uso terapêutico , Resultado do TratamentoRESUMO
In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.
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Nanocomposites based on molybdenum disulfide (MoS2 ) and different carbon modifications are intensively investigated in several areas of applications due to their intriguing optical and electrical properties. Addition of a third element may enhance the functionality and application areas of such nanocomposites. Herein, we present a facile synthetic approach based on directed thermal decomposition of (Ph4 P)2 MoS4 generating MoS2 nanocomposites containing carbon and phosphorous. Decomposition at 250 °C yields a composite material with significantly enlarged MoS2 interlayer distances caused by in situ formation of Ph3 PS bonded to the MoS2 slabs through MoS bonds and (Ph4 P)2 S molecules in the van der Waals gap, as was evidenced by (31) P solid-state NMR spectroscopy. Visible-light-driven hydrogen generation demonstrates a high catalytic performance of the materials.
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The biodetoxification of cyanide-rich wastewater has become increasingly popular because of its cost-effectiveness and environmental friendliness. Therefore, we have developed an effective method, optimised by response surface methodology, for detoxifying cyanide-rich wastewater using Bacillus sp. CN-22, which was newly isolated from a cyanide-contaminated electroplating sludge and could tolerate a CNâ» concentration of 700 mg L⻹. The concentration of CNâ» in the treated wastewater decreased from 200 to 6.62 mg L⻹ after cultivation with 2.38 % inocula for 72 h on the medium, consisting of 0.05 % KH2PO4, 0.15 % K2HPO4, 1.0 mM MgCl2, 1.0 mM FeCl3, 0.1 % NH4Cl, and 0.1 % glycerol. The CNâ» degradability of 96.69 % is similar to the predicted value of 96.82 %. The optimal cultivation conditions were controlled as follows: initial pH, 10.3; temperature, 31 °C; and rotary speed, 193 rpm. The maintenance of higher pH in the overall treatment procedures may avoid the production of volatile HCN and the risk associated with cyanide detoxification. Additionally, the bacterial strain Bacillus sp. CN-22, with its potent cyanide-degrading activity at the initial CNâ» concentration of 200 mg L⻹, may be employed to effectively treat cyanide-rich wastewater, especially electroplating effluent.
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Bacillus/metabolismo , Cianetos/metabolismo , Águas Residuárias/química , Águas Residuárias/microbiologia , Bacillus/classificação , Bacillus/genética , Bacillus/isolamento & purificação , Biotransformação , Meios de Cultura/química , DNA Bacteriano/química , DNA Bacteriano/genética , Dados de Sequência Molecular , Análise de Sequência de DNA , Esgotos/microbiologia , Fatores de TempoRESUMO
A highly sensitive and convenient high-performance liquid chromatography technique coupled with chemiluminescence detection for the simultaneous determination butylated hydroquinone (TBHQ) and butylated hydroxyanisole (BHA) in oil is established. The detection is based on the inhibitory effect on the CL reaction between luminol and potassium ferricyanide in an alkaline medium. Samples were separated through a reverse-phase C18 column using a mobile phase of methanol and water (80: 20, v/v) at a flow rate of 0.5 mL/min. The effects of various parameters including mobile phase, flow rate and chemiluminescence regent were studied. Under optimum conditions, both TBHQ and BHA showed good linear relationships in the range 1 × 10(-7) -1 × 10(-5) g/mL with detection limits of 24 and 33 ng/mL, respectively. The proposed method is simple and sensitive, with low costs. The method was successfully applied for the quantification of TBHQ and BHA in sesame oil. The possible inhibition mechanism is also discussed briefly.
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Hidroxianisol Butilado/análise , Cromatografia Líquida de Alta Pressão/métodos , Hidroquinonas/análise , Medições Luminescentes/métodos , Antioxidantes/análise , Antioxidantes/química , Hidroxianisol Butilado/química , Calibragem , Análise de Alimentos/métodos , Hidroquinonas/química , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Óleo de Gergelim/análiseRESUMO
Statistically based experimental designs were applied to optimize the fermentation medium and cultural conditions for the maximization of neutral protease using three agroindustrial residues (cassava pulp, soybean meal, and wheat bran) and Bacillus subtilis DES-59. The Plackett-Burman design was used to evaluate the effects of variables such as the concentration of substrates, initial pH, shaker's rotating speed, temperature, inoculum size, and incubation time. Among the eight parameters, three significant variables (cassava pulp, soybean meal, and inoculum size) were selected for the optimization study, in which a central composite design was used to optimize the concentrations of cassava pulp and soybean meal and inoculum size and investigate the interactive effects of the three variables. The optimal parameters obtained from response surface methodology are 37.78 g/L of cassava pulp, 15 g/L of soybean meal, and 6.5% (v/v) of inoculum size, respectively, resulting in a maximum neutral protease activity of 4107 ± 122 U/mL.
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Bacillus subtilis/enzimologia , Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Meios de Cultura/metabolismo , Metaloendopeptidases/biossíntese , Metaloendopeptidases/metabolismo , Proteínas de Bactérias/biossíntese , Biotecnologia/métodos , Fermentação/fisiologia , Concentração de Íons de Hidrogênio , Glycine max/metabolismo , TemperaturaRESUMO
Promoters are essential tools for basic and translational neuroscience research. An ideal promoter should possess the shortest possible DNA sequence with cell-type selectivity. However, whether ultra-compact promoters can offer neuron-specific expression is unclear. Here, we report the development of an extremely short promoter that enables selective gene expression in neurons, but not glial cells, in the brain. The promoter sequence originates from the human CALM1 gene and is only 120 bp in size. The CALM1 promoter (pCALM1) embedded in an adeno-associated virus (AAV) genome directed broad reporter expression in excitatory and inhibitory neurons in mouse and monkey brains. Moreover, pCALM1, when inserted into an all-in-one AAV vector expressing SpCas9 and sgRNA, drives constitutive and conditional in vivo gene editing in neurons and elicits functional alterations. These data demonstrate the ability of pCALM1 to conduct restricted neuronal gene expression, illustrating the feasibility of ultra-miniature promoters for targeting brain-cell subtypes.
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Neurônios , RNA Guia de Sistemas CRISPR-Cas , Camundongos , Animais , Humanos , Neurônios/metabolismo , Encéfalo/metabolismo , Neuroglia/metabolismo , Terapia Genética , Vetores Genéticos/genética , Dependovirus/genética , Dependovirus/metabolismoRESUMO
Pretreatment plays a key role in biofuel production from lignocellulosic biomass. In this study, the main factors of peroxyformic acid (PA) pretreatment were optimized in the light of enzymolysis efficiency and composition analysis of pretreated sugarcane bagasse (SCB). Lignin was significantly removed (59.0%) and a complete saccharification level (103.6%) was obtained for the pretreated SCB with slight cellulose loss (9.2%) under the optimized pretreatment conditions. The effects of PA pretreatment on the structural characteristics of SCB were also studied and the digestibility of pretreated SCB was also evaluated by dark fermentative hydrogen production with an enriched anaerobic cellulolytic microbial consortium MC1. The hydrogen production increased by 195.5% (based on initial SCB) and the abundance of dominant hemicellulose-degradation genus Thermoanaerobacterium increased from 23.8% to 40.2% due to the remaining and accessible hemicellulose in PA pretreated SCB.
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Celulase , Saccharum , Celulose , Formiatos , Hidrogênio , Hidrólise , LigninaRESUMO
Atractylodes macrocephala Koidz is a widely used as a traditional Chinese medicine. Atractylenolides (-I, -II, and -III) are a class of lactone compounds derived from Atractylodes macrocephala Koidz. Research into atractylenolides over the past two decades has shown that atractylenolides have anti-cancer, anti-inflammatory, anti-platelet, anti-osteoporosis, and antibacterial activity; protect the nervous system; and regulate blood glucose and lipids. Because of structural differences, both atractylenolide-I and atractylenolide-II have remarkable anti-cancer activities, and atractylenolide-I and atractylenolide-III have remarkable anti-inflammatory and neuroprotective activities. We therefore recommend further clinical research on the anti-cancer, anti-inflammatory and neuroprotective effects of atractylenolides, determine their therapeutic effects, alone or in combination. To investigate their ability to regulate blood glucose and lipid, as well as their anti-platelet, anti-osteoporosis, and antibacterial activities, both in vitro and in vivo studies are necessary. Atractylenolides are rapidly absorbed but slowly metabolized; thus, solubilization studies may not be necessary. However, due to the inhibitory effects of atractylenolides on metabolic enzymes, it is necessary to pay attention to the possible side effects of combining atractylenolides with other drugs, in clinical application. In short, atractylenolides have considerable medicinal value and warrant further study.
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Atractylodes/química , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Animais , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Lactonas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Camundongos , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Rizoma/química , Sesquiterpenos/uso terapêuticoRESUMO
Musk, the dried secretion from the musk sac gland which is located between the navel and genitals of mature male musk deer, is utilized as oriental medicine in east Asia. It has been utilized to treat conditions such as stroke, coma, neurasthenia, convulsions, and heart diseases in China since ancient times. This paper aims to provide a comprehensive overview of musk in zoology, chemical composition, pharmacology, clinical applications, and quality control according to the up-to-date literature. Studies found that musk mainly contains macrocyclic ketones, pyridine, steroids, fatty acids, amino acids, peptides, and proteins, whilst the main active ingredient is muscone. Modern pharmacological studies have proven that musk possesses potent anti-inflammatory effects, neuroprotective effects, anti-cancer effects, antioxidant effects, etc. Moreover, muscone, the main active ingredient, possesses anti-inflammatory, neuroprotective, antioxidant, and other pharmacological effects. In the quality control of musk, muscone is usually the main detection indicator, and the common analytical method is GC, and researchers have established novel and convenient methods such as HPLC-RI, RP-UPLC-ELSD, and Single-Sweep Polarography. In addition, quality evaluation methods based on steroids and the bioactivity of musk have been established. As for the identification of musk, due to various objective factors such as the availability of synthetic Muscone, it is not sufficient to rely on muscone alone as an identification index. To date, some novel technologies have also been introduced into the identification of musk, such as the electronic nose and DNA barcoding technology. In future research, more in vivo experiments and clinical studies are encouraged to fully explain the pharmacological effects and toxicity of musk, and more comprehensive methods are needed to evaluate and control the quality of musk.
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Rehmannia glutinosa, the fresh or dried root of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & Mey., and Gardenia, the fruit of Gardenia jasminoides Ellis from Rubiaceae, both are famous traditional Chinese medicines that have been traditionally used in China. Catalpol and geniposide, as two kinds of iridoid glycosides with high activities, are the main bioactive components in Rehmannia glutinosa and Gardenia jasminoides Ellis, respectively. Over the past few decades, catalpol and geniposide have been widely studied for their therapeutic effects. The preclinical experiments demonstrated that they possessed significant neuroprotective activities against Alzheimer's disease, Parkinson's disease, stroke, and depression, etc. In this paper, the pharmacological effects and mechanisms of catalpol and geniposide on Alzheimer's disease and Parkinson's disease from 2005 to now were systematically summarized and comprehensively analyzed. At the same time, the pharmacokinetic characteristics of the analyzed compounds were also described, hoping to provide some enlightenment for the design, research, and development of iridoid glycosides.
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Doença de Alzheimer/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Glucosídeos Iridoides/uso terapêutico , Iridoides/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Gardenia/química , Humanos , Glucosídeos Iridoides/farmacologia , Iridoides/farmacologia , Medicina Tradicional Chinesa , Rehmannia/químicaRESUMO
Introduction: Calycosin (CA), a typical phytoestrogen extracted from root of Astragalus membranaceus. On the basis of summarizing the pharmacological and pharmacokinetic studies of CA in recent years, we hope to provide useful information for CA about treating different diseases and to make suggestions for future research.Areas covered: We collected relevant information (January 2014 to March 2020) on CA via the Internet database. Keywords searched includ pharmacology, pharmacokinetics and toxicology, and the number of effective references was 118. CA is a phytoestrogen with wide range of pharmacological activities. By affecting PI3K/Akt/mTOR, WDR7-7-GPR30, Rab27B-ß-catenin-VEGF, etc. signaling pathway, CA showed the effect of anticancer, anti-inflammatory, anti-osteoporosis, neuroprotection, hepatoprotection, etc. Therefore, CA is prospective to be used in the treatment of many diseases.Expert opinion: Research shows that CA has a therapeutic effect on a variety of diseases. We think CA is a promising natural medicine. Therefore, we propose that the research directions of CA in the future include the following. Carrying out clinical research trials in order to find the most suitable medicinal concentration for different diseases; Exploring the synergistic mechanism of CA in combination with other drugs; Exploring ways to increase the blood circulation concentration of CA.
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Medicamentos de Ervas Chinesas/química , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Animais , Astragalus propinquus , Humanos , Isoflavonas/efeitos adversos , Isoflavonas/isolamento & purificação , Fitoestrógenos/efeitos adversos , Fitoestrógenos/isolamento & purificaçãoRESUMO
Tea saponins (TS), a novel multifunctional stabilizer, were explored to stabilize the nanosuspensions. The purpose of this study was to investigate the effect of TS on the stability and redispersibility of nanosuspensions. In present work, hesperidin (HDN), a poorly soluble drug, was used as a model drug. HDN nanosuspensions (HDN-NS) with particle size of 250-270 nm were prepared by high-speed shearing and high-pressure homogenization. The zeta potential of HDN-NS was -23.16 ± 1.12 mV. Compared with traditional stabilizers, TS were superior in stabilization efficiency at low concentrations. Nanosuspensions freeze-dried powder using TS and lactose as cryoprotectants had good redispersibility, and the average particle size was 266.5 ± 9.0 nm after reconstitution. TS and lactose can effectively prevent the irreversible agglomeration of HDN-NS during freeze-drying. The dissolution was enhanced owing to particle size reduction. Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) results showed that HDN nanocrystals were irregularly lumpy. The chemical structure and crystal state of HDN had not significantly changed during production. In conclusion, TS have the potential to stabilize and disperse nanosuspensions and provide a promising strategy for the development of poorly soluble drugs.
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Camellia sinensis , Excipientes/química , Hesperidina/química , Nanopartículas , Saponinas/química , Camellia sinensis/química , Crioprotetores/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Estudos de Viabilidade , Liofilização , Lactose/química , Saponinas/isolamento & purificação , Solubilidade , Propriedades de SuperfícieRESUMO
As a naturally occurring furanocoumarin, the medicinal value of imperatorin has been studied more and more. We hope to provide useful information for the further development of imperatorin by analyzing the literature of imperatorin in recent years. By collating the literature on the pharmacology of imperatorin, we found that the pharmacological activity of imperatorin is wide and imperatorin can be used for anti-cancer, neuroprotection, anti-inflammatory, anti-hypertension and antibacterial. In addition, we found that some researchers confirmed the toxicity of imperatorin. Pharmacokinetic studies demonstrated that oxidation metabolism is the main metabolic pathways of imperatorin. At present, the shortcomings of research on imperatorin mainly include: most pharmacological studies are concentrated in vitro, lacking enough in vivo experimental data; more and more studies showed that imperatorin has synergistic effect with other drugs in anticancer and other aspects, but lacking the detailed explanation of the mechanism of the synergistic effect; imperatorin has side effect, but it lacks enough experimental conclusions. Based on the above defects, we believe that more in vivo experiments of imperatorin should be carried out in the future; future research need to explore synergistic mechanisms of imperatorin with other drugs, especially in anticancer; the dose affects both the pharmacological activity and the side effect of imperatorin. The relationship between the dose and the two aspects need to be further studied in order to reduce the side effect. In addition, through structural modification of imperatorin, it is possible to improve the treatment effect and reduce side effect.
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Anti-Inflamatórios , Antineoplásicos Fitogênicos , Furocumarinas , Fármacos Neuroprotetores , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/toxicidade , Furocumarinas/farmacocinética , Furocumarinas/farmacologia , Furocumarinas/toxicidade , Humanos , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/toxicidadeRESUMO
Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB's toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB's active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.
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In the first part of the paper, the stochastic dynamics of the Peyrard-Bishop-Dauxois (PBD) DNA model is studied. A one-dimensional averaged Itô stochastic differential equation governing the total energy of the system and the associated Fokker-Planck equation governing the transition probability density function of the total energy are derived from the Langevin equations for the base-pair (bp) separation of the PBD DNA model by using the stochastic averaging method for quasinonintegrable Hamiltonian systems. The stationary probability density function of the average energy and the mean square of the bp separation are obtained by solving the reduced Fokker-Planck equation. In the second part of the paper, the local denaturation of the thermalized PBD DNA model is studied as a first-passage-time problem in the energy. A backward Kolmogorov equation and a Pontryagin equation are derived from the averaged Itô equation and solved to yield the waiting-time distribution and the mean bp opening time. All the analytical results are confirmed with those from Monte Carlo simulation. It is pointed out that the proposed method may yield a reasonable mean bp opening time if the friction coefficient is fixed using experimental results.