Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
J Comput Chem ; 45(24): 2080-2090, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38742401

RESUMO

We show herein that 1,10-dicyano substitution restricts the paragon fluxionality of bullvalene to just 14 isomers which isomerize along a single cycle. The restricted fluxionality of 1,10-dicyanobullvalene (DCB) is investigated by means of: (i) Bonding analyses of the isomer structures using the adaptive natural density partitioning (AdNDP). (ii) Quantum dynamical simulations of the isomerizations along the cyclic intrinsic reaction coordinate of the potential energy surface (PES). The PES possesses 14 equivalent potential wells supporting 14 isomers which are separated by 14 equivalent potential barriers supporting 14 transition states. Accordingly, at low temperatures, DCB appears as a hindered molecular rotor, without any delocalization of the wavefunction in the 14 potential wells, without any nuclear spin isomers, and with completely negligible tunneling. These results are compared and found to differ from those for molecular boron rotors. (iii) Born-Oppenheimer molecular dynamics (BOMD) simulations of thermally activated isomerizations. (iv) Calculations of the rate constants in the frame of transition state theory (TST) with reasonable agreement achieved with the BOMD results. (v) Simulations of the equilibration dynamics using rate equations for the isomerizations with TST rate coefficients. Accordingly, in the long-time limit, isomerizations of the 14 isomers, each with Cs symmetry, approach the "14 Cs → C7v" thermally averaged structure. This is a superposition of the 14 equally populated isomer structures with an overall C7v symmetry. By extrapolation, the results for DCB yield working hypotheses for so far un-explored properties e.g. for the equilibration dynamics of C10H10.

2.
Int J Clin Oncol ; 27(5): 871-881, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35171361

RESUMO

PURPOSE: Clinical evidence of metastasis with ground-glass nodules (GGNs) has been reported, including pulmonary metastasis and distant metastasis. However, the clonal relationships of multiple GGNs at the genetic level remain unclear. EXPERIMENTAL DESIGN: Sixty tissue specimens were obtained from 19 patients with multiple GGN lung cancer who underwent surgery in 2019. Whole exome sequencing (WES) was performed on tissue samples, and genomic profiling and clone evolution analysis were conducted to investigate the genetic characteristics and clonality of multiple GGNs. RESULTS: A total of 15,435 nonsynonymous mutations were identified by WES, and GGNs with shared nonsynonymous mutations were observed in seven patients. Copy number variant (CNV) analysis showed that GGNs in ten patients had at least one shared arm-level CNV. Mutational spectrum analysis showed that GGNs in three patients had similar six substitution profiles and GGNs in fou patients had similar 96 substitution profiles. According to the clone evolution analysis, we found that GGNs in five patients had shared clonal driver gene mutations. Taken together, we identified that 5 patients may have multiple primary GGNs without any similar genetic features, 2 patients may have intrapulmonary metastatic GGNs with ≥ 3 similar genetic features, and the other 12 patients cannot be determined due to insufficient evidences in our cohort. CONCLUSIONS: Our findings suggest that the intrapulmonary metastasis exist in multiple GGNs, but the number of GGNs was not associated with the probability of metastasis. Application of genomic profiling may prove to be important to precise management of patients with multiple GGNs.


Assuntos
Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Humanos , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Sequenciamento do Exoma
3.
Phys Chem Chem Phys ; 23(35): 19146-19149, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524319

RESUMO

La-[B2@B18]-La demonstrates decisive changes of the properties of molecular rotors, from multiple (here 18) equivalent individual global minimum structures to a quantum mechanical unified structure. This affects their geometries, their symmetries (18*C2h → D9d), the generation of energy bands, and high-resolution spectroscopy.

4.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430468

RESUMO

Alterations in miRNAs are associated with many metabolic disorders, such as type 2 diabetes (T2DM). The miR-23b/27b/24-1 cluster contains miR-23b, miR-27b, and miR-24-1, which are located within 881 bp on chromosome 9. Studies examining the roles of miR-23b, miR-27b, and miR-24-1 have demonstrated their multifaceted functions in variable metabolic disorders. However, their joint roles in metabolism in vivo remain elusive. To investigate this subject, we constructed miR-23b/27b/24-1 cluster knockout (KO) mice. Compared with wild-type (WT) mice, the KO mice exhibited impaired glucose tolerance, which was accompanied by a reduction in the respiratory exchange rate (RER). These alterations were more noticeable after a high-fat diet (HFD) induction. Hepatic metabolomic results showed decreased expression of reduced nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide (NAD), phosphoenolpyruvic acid (PEP), and phosphoric acid, which are involved in the glycolysis pathway. The transcriptomic results indicated that genes involved in glycolysis showed a downregulation trend. qPCR and Western blot revealed that pyruvate kinase (PKLR), the key rate-limiting enzyme in glycolysis, was significantly reduced after the deletion of the miR-23b/27b/24-1 cluster. Together, these observations suggest that the miR-23b/27b/24-1 cluster is involved in the regulation of glucose homeostasis via the glycolysis pathway.


Assuntos
Diabetes Mellitus Tipo 2/genética , Intolerância à Glucose/genética , Glucose/genética , MicroRNAs/genética , Animais , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Glicólise/genética , Humanos , Camundongos , Camundongos Knockout , Família Multigênica/genética , NAD/metabolismo , Taxa Respiratória/genética , Transdução de Sinais/genética
5.
Zhongguo Zhong Yao Za Zhi ; 46(2): 347-358, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33645121

RESUMO

Artemisiae Annuae Herba is a traditional Chinese medicine for clearing deficiency and heat. It is the only natural source of artemisinin, which is a specific antimalarial drug, and has been widely concerned all over the world. In addition to artemisinin, Artemisiae Annuae Herba also contains many sesquiterpenes, coumarins, flavonoids, volatile oils, polysaccharides and other chemical components, which show antipyretic, anti-inflammatory, antiviral microorganisms, anti-asthma, anti-oxidation, anti-tumor and other pharmacological activities. In addition to their own pharmacological activities, some components could enhance the antimalarial activity of artemisinin through different mechanisms at absorption and metabolism in vivo. In order to understand the pharmacokinetic characte-ristics of the chemical constituents contained in Artemisiae Annuae Herba and provide reference for the full development and clinical utilization of Artemisiae Annuae Herba resources in China, this present paper systematically collated the modern research literatures, and summarized the biosynthesis, in vivo analysis and pharmacokinetics of the chemical constituents in Artemisiae Annuae Herba.


Assuntos
Antimaláricos , Medicamentos de Ervas Chinesas , Óleos Voláteis , China , Medicina Tradicional Chinesa
6.
Plant J ; 98(3): 418-433, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30673148

RESUMO

Root hairs, as lateral extensions of epidermal cells, provide large absorptive surfaces to the root and are major actors in plant hydromineral nutrition. In contact with the soil they also constitute a site of interactions between the plant and rhizospheric microorganisms. In legumes, initiation of symbiotic interactions with N2 -fixing rhizobia is often triggered at the root hair cell membrane in response to nodulation factors secreted by rhizobia, and involves early signaling events with changes in H+ , Ca2+ , K+ and Cl- fluxes inducing transient depolarization of the cell membrane. Here, we aimed to build a functional repertoire of the major root hair conductances to cations and anions in the sequenced legume model Medicago truncatula. Five root hair conductances were characterized through patch-clamp experiments on enzymatically recovered root hair protoplasts. These conductances displayed varying properties of voltage dependence, kinetics and ion selectivity. They consisted of hyperpolarization- and depolarization-activated conductances for K+ , cations or Cl- . Among these, one weakly outwardly rectifying cationic conductance and one hyperpolarization-activated slowly inactivating anionic conductance were not known as active in root hairs. All five conductances were detected in apical regions of young growing root hairs using membrane spheroplasts obtained by laser-assisted cell-wall microdissection. Combined with recent root hair transcriptomes of M. truncatula, this functional repertoire of conductances is expected to help the identification of candidate genes for reverse genetics studies to investigate the possible role of each conductance in root hair growth and interaction with the biotic and abiotic environment.


Assuntos
Ânions/metabolismo , Cátions/metabolismo , Membrana Celular/metabolismo , Medicago truncatula/metabolismo , Raízes de Plantas/metabolismo , Proteínas de Plantas/metabolismo
7.
Undersea Hyperb Med ; 45(1): 33-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29571230

RESUMO

INTRODUCTION: The Republic of China Navy instituted the pressure test as one of the selection tools for diving troops and submarine crews. We analyzed factors associated with failure in the pressure test. METHODS: This was a retrospective cohort study designed to investigate pressure test failure in Navy recruits between January 2010 and August 2015. The recruits received pressurization in a hyperbaric chamber to a simulated depth of 112 feet of seawater (fsw) at a rate of 25 fsw/minute. Data describing trainee demographics, disease history, causes and depth of failure, as well as type of injury, were extracted from case notes and facility databases for statistical analysis. RESULTS: Of 3,608 trial cohorts, there were 435 failures, with an overall failure rate of 12.06%. About 95% of these failure trials were within a simulated depth of 60 fsw. Fifty-seven (57) failures did not record causes of failure. Among the other 378 failures, the most commonly identified causes were ear barotrauma (365 trials, 96.56%) and sinus barotrauma (10 trials, 2.65%). Statistical analysis revealed that recent upper respiratory tract infection, allergic rhinitis, and cigarette smoking were all significantly associated with higher incidence of middle ear barotrauma. CONCLUSIONS: Our results suggest that pressure testing to a depth of 60 fsw is effective in disqualifying personnel entering diving and submarine service. Recent infection of the upper respiratory tract, allergic rhinitis and cigarette smoking are risk factors for middle ear barotrauma, resulting in failure of the pressure test.


Assuntos
Barotrauma/etiologia , Mergulho/efeitos adversos , Orelha Média/lesões , Militares , Adolescente , Adulto , Barotrauma/classificação , Índice de Massa Corporal , Humanos , Pessoa de Meia-Idade , Seios Paranasais/lesões , Seleção de Pessoal/métodos , Análise de Regressão , Infecções Respiratórias/complicações , Estudos Retrospectivos , Rinite Alérgica/complicações , Fatores de Risco , Água do Mar , Fumar/efeitos adversos , Medicina Submarina , Taiwan , Adulto Jovem
8.
Zhongguo Zhong Yao Za Zhi ; 43(10): 1985-1989, 2018 May.
Artigo em Zh | MEDLINE | ID: mdl-29933660

RESUMO

Sojae Semen Praeparatum (SSP) is commonly used as a type of dietetic Chinese herb. By collecting and analyzing ancient and recent literatures, a textual criticism was conducted on the historical evolution of the processing of SSP. Fermented soybean was recorded in Shijing, and relevant rational processing was described in Qimin Yaoshu. In the early time, fermented soybean included the type of "salty" and "light". After the Ming Dynasty, "light" fermented soybean or SSP was recognized as a better medicinal matter than salty fermented soybean, and the fermentation processing was recorded more clearly. In modern time, many characteristic methods for processing SSP have been developed. Today, the processing of SSP is mainly based on the Chinese Pharmacopoeia, which records soybean as a main ingredient and Artemisiae Annuae Herba, Mori Folium as excipients.


Assuntos
Medicamentos de Ervas Chinesas/química , Glycine max/química , Artemisia/química , Fermentação , Morus/química
9.
Zhongguo Zhong Yao Za Zhi ; 43(18): 3668-3675, 2018 Sep.
Artigo em Zh | MEDLINE | ID: mdl-30384531

RESUMO

Hyaluronic acid (HA) and cell-penetrating peptide (CPP) R6H4-SA modified artesunate nanostructured lipid carrier (HA-R6H4-NLC/ART) for anti-tumor therapy was prepared. The physicochemical properties and in vitro drug release of HA-R6H4-NLC/ART were evaluated, and the uptake and cytotoxicity of liver cancer HepG2 cells were studied. The results showed that HA-R6H4-NLC/ART was spherical like in appearance, and the average particle size was about 160 nm. In vitro release experiments showed that the drug delivery system had sustained release characteristics. Cell results showed that, in slightly acidic environment, pH sensitive CPP R6H4-SA mediated cellular uptake of nanoparticles was significantly higher than that of non-sensitive peptide R8-SA. Meanwhile, HA-R6H4-NLC/ART had a targeting effect on HepG2 cells, and the HA receptor saturation experiment showed that the endocytosis of HA-R6H4-NLC/ART was mediated by the HA receptor on the cell surface. As compared with the unmodified or R6H4-SA single modified group, HA and R6H4-SA co-modified HA-R6H4-NLC/ART significantly improved the cell uptake and had a stronger anti-tumor effect under the conditions of the slightly acid environment and hyaluronidase degradation. The above results showed that hyaluronic acid and CPP R6H4-SA co-modified artesunate nanostructured lipid carrier, which can effectively identify and penetrate the tumor cell membrane into the cell, is a potentially efficient targeting delivery system for anti-tumor drugs.


Assuntos
Antineoplásicos/farmacologia , Artesunato/farmacologia , Peptídeos Penetradores de Células/química , Portadores de Fármacos/química , Ácido Hialurônico/química , Células Hep G2 , Humanos , Nanopartículas
10.
Plant J ; 85(5): 675-85, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26846460

RESUMO

Efficient stomatal opening requires activation of KAT-type K(+) channels, which mediate K(+) influx into guard cells. Most KAT-type channels are functionally facilitated by extracellular acidification. However, despite sequence and structural homologies, the maize counterpart of Arabidopsis KAT1 (ZmK2.1) is resistant to pH activation. To understand the structural determinant that results in the differential pH activation of these counterparts, we analysed chimeric channels and channels with point mutations for ZmK2.1 and its closest Arabidopsis homologue KAT1. Exchange of the S1-S2 linkers altered the pH sensitivity between the two channels, suggesting that the S1-S2 linker is essentially involved in the pH sensitivity. The effects of D92 mutation within the linker motif together with substitution of the first half of the linker largely resemble the effects of substitution of the complete linker. Topological modelling predicts that one of the two cysteines located on the outer face section of the S5 domain may serve as a potential titratable group that interacts with the S1-S2 linker. The difference between ZmK2.1 and KAT1 is predicted to be the result of the distance of the stabilized linkers from the titratable group. In KAT1, residue K85 within the linker forms a hydrogen bond with C211 that enables the pH activation; conversely, the linker of ZmK2.1 is distantly located and thus does not interact with the equivalent titration group (C208). Thus, in addition to the known structural contributors to the proton activation of KAT channels, we have uncovered a previously unidentified component that is strongly involved in this complex proton activation network.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas de Plantas/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Zea mays/genética , Sequência de Aminoácidos , Aminoácidos/química , Aminoácidos/genética , Aminoácidos/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Sítios de Ligação/genética , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Modelos Moleculares , Proteínas Mutantes Quiméricas/química , Proteínas Mutantes Quiméricas/genética , Proteínas Mutantes Quiméricas/metabolismo , Mutação , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/química , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Ligação Proteica , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Zea mays/metabolismo
11.
J Asian Nat Prod Res ; 19(10): 987-992, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28649852

RESUMO

Two new guaiane-type sesquiterpenoids, named 4α,5α-epoxy-8ß-hydroxy-1α-hydro-α-guaiene (1) and 4α,5α-epoxy-1-hydroxy-α-guaiene (2), were isolated from the whole plants of Valeriana hardwickii. Their structures were elucidated on the basis of spectroscopic analysis. Compounds 1 and 2 showed weak cytotoxicity against the lung adenocarcinoma (A549) and hepatoma (Bel7402) cell lines with IC50 values of 9.2 and 8.5 µM, respectively.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Sesquiterpenos de Guaiano/isolamento & purificação , Valeriana/química , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Azulenos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Paclitaxel/farmacologia , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/farmacologia
12.
Saudi Pharm J ; 23(4): 377-80, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27134538

RESUMO

OBJECTIVE: Pandrug-resistant (PDR) bacterial infections are associated with considerable prolongation of hospitalization and mortality in clinical practice. METHOD: This case-series study was conducted during a 3-year period from 2011 to 2013. A total of 30 PDR patients consulted by clinical pharmacist were recorded to evaluate the anti-infection treatment. RESULTS: All isolates of PDR bacteria from patients were identified as pan-drug resistant acine-tobacter baumannii (63.3%), pan-drug resistant klebsiella pneumonia (20.0%), and pandrug-resistant pseudomonas aeruginosa (16.7%). Of the 30 patients, 96.7% therapeutic regimens supposed by clinical pharmacists were applied to treat the infectious patients up to 82.8% clinical cure rates. 30 patients completed the prescribed treatment, of which 19 underwent monotherapy that the clinical cure rate was 78.9%, and 10 underwent combination therapy that the clinical cure rate was 90.0%. In the following therapy, doxycycline, cefoperazone shubatan and amikacin have the certain effect on anti-infection therapy. Combination therapy combined with doxycycline was better treatment option for PDR infectious patients. CONCLUSION: In a word, it appears to be effective for the successful therapy of PDR infections upon tetracyclines administration.

13.
Zhongguo Zhong Yao Za Zhi ; 40(20): 4007-11, 2015 Oct.
Artigo em Zh | MEDLINE | ID: mdl-27062818

RESUMO

Chemical investigation of the whole plants of Valeriana hardwickii has led to the isolation of 11 flavones and 2 monoterpe- noids by using various chromatographic techniques including column chromatography on silica gel and Sephadex LH-20, preparative TLC, and preparative HPLC. Their structures were identified by spectroscopic data analysis as syzalterin (1), 6-methylapigenin (2), 5-hydroxy-7,4'-dimethoxyflavone (3), genkwanin (4), acacetin (5), apigenin (6), quercetin (7), tricin (8), (-)-farrerol (9), sosakuranetin (10), 5,3',4'-trihydroxy-7-methoxyflavanone (11), (-)-bornyl ferulate ( 12) , and (-)-bornyl caffeate ( 13). All compounds were isolated from this plant for the first time, while compounds 1, 9-13 were obtained from this genus for the first time.


Assuntos
Medicamentos de Ervas Chinesas/química , Valeriana/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray
14.
Zhongguo Zhong Yao Za Zhi ; 40(23): 4629-33, 2015 Dec.
Artigo em Zh | MEDLINE | ID: mdl-27141674

RESUMO

The aim of this study was to elucidate the scientific connotation of Bombyx Batryticatus processing with wheat bran under high temperature. The contents of soluble protein extracted from Bombyx Batryticatus and its processed products and the limited content of AFT in Bombyx Batryticatus and the processed one were compared. The concentration of protein was measured with the Bradford methods and the difference of protein between Bombyx Batryticatus and its processed products was compared by SDS-PAGE analysis. Aflatoxin B1, B2, G1, and G2 were determined by reversed-phase HPLC. The results showed that the soluble protein content of Bombyx Batryticatus and its processed products were (47.065 +/- 0.249), (29.756 +/- 1.961) mg x g(-1), correspondingly. Analysis of protein gel electrophoresis showed that there were no significant differences between the crude and processed one in protein varieties. 6 bands were detected: 31.90, 26.80, 18.71, 15.00, 10.18, 8.929 kDa. Below 10 kDa, the color of bands of the processed one was deeper than the crude one, which demonstrate that macromolecular protein was degradated into micromolecule. The content of AFG1, AFB1, AFG2, AFB2 were 0.382, 0.207, 0.223, 0.073 g x kg(-1), not exceeded 5 microg x kg(-1) while the processed one was not detected. Through processing with wheat bran under high temperature, the content of soluble protein in Bombyx Batryticatus decreased, the processing purpose for alleviating drug property was achieved. Meanwhile, the limited content of aflatoxins were reduced or cleared by processing procedure or absorbed by processing auxillary material, adding the safety of the traditional Chinese Medicine. In conclusion, as a traditional processing method, bran frying Bombyx Batryticatus was scientific and reasonable.


Assuntos
Bombyx/química , Proteínas de Insetos/química , Animais , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Poliacrilamida , Temperatura Alta , Peso Molecular
15.
Artigo em Zh | MEDLINE | ID: mdl-25726605

RESUMO

Artemisinin-resistant Plasmodium falciparum has been identified by WHO in the Greater Mekong subregion. While there is no report on artemisinin resistance in Africa and South America by now, related surveillance measures have been taken place. The genes related artemisinin-resistance has been identified and the molecular markers will be used for large-scale surveillance efforts to contain artemisinin resistance. The emergence and spread of artemisinin resistance worldwide is a present danger and needs more attention. This article reviews the progress of artemisininresistance malaria parasites and artemisinin-based combination therapies.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Humanos
16.
Zhongguo Zhong Yao Za Zhi ; 39(23): 4629-36, 2014 Dec.
Artigo em Zh | MEDLINE | ID: mdl-25911814

RESUMO

In the current study, a total of nineteen triterpenoids (1-19) from 60% EtOH extracts of Stauntonia obovatifoliola Hayata subsp. intermedia stems were separated and purified by solvent extraction and chromatographic methods including silica gel, ODS as well as preparative HPLC. According to the results of chemical reactions and spectral data, compounds were identified as: lupeol (1), betulinonic acid (2), betulinic acid (3), 3-epi-betulinic acid (4), quinatic acid (5), 24-O-acetyl quinatic acid (6), 3-O-α- L-arabinopyranosyl-30-nor-hederagenin-28-O-α-L-rhamnopyranosyl-(1 --> 4) -ß-D-glucopyranosyl-(1 --> 6) -ß-D-glucopyranosyl ester (7), Stauntoside A (8), kalopanax saponin A (9), kalopanax saponin J (10), Kizuta saponin K10 (11), 3-O-α-L-rhamnopyranosyl (1--> 2) -α-L-arabinopyranosyl-hederagenin-28-O-ß-D-xylopyranosyl-(1 --> 6) -ß-D-glucopyranosyl ester (12), kalopanax saponin B (13), 3-O-α-L-rhamnopyranosyl-(1 --> 2) -α-L-arabinopyranosyl-hederagenin-28-O-ß-D-glucopyranosyl-(1 --> 6) -ß-D-glucopyranosyl ester (14), sieboldianoside A (15), septemoside A (16), kalopanax saponin K (17), septemloside I (18), and 3-O-α-L-arabinopyranosyl (1 --> 2)-ß-D-glucuronopyranosyl- hederagenin (19). Among them, compounds 4, 6, 10, 12, 14, and 16-19 were isolated from the Stauntonia genus for the first time, and compound 6 was a new natural product.


Assuntos
Medicamentos de Ervas Chinesas/química , Magnoliopsida/química , Triterpenos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Caules de Planta/química , Espectrometria de Massas por Ionização por Electrospray
17.
Zhongguo Zhong Yao Za Zhi ; 39(17): 3306-10, 2014 Sep.
Artigo em Zh | MEDLINE | ID: mdl-25522617

RESUMO

The objective of this study is to develop a sensitive and reliable high-performance liquid chromatography mass spectrometry (LC-MS) method for simultaneous determination of artemisinin, arteannuin B, artemisic acid, and scopoletin, and study the pharmacokinetics of the four constituents in mouse serum after oral administration of the four components to mice. The analytical column used was Agilent Zorbax SB-C18 (2.1 mm x 150 mm, 5 mm). The mobile phase was acetonitrile: 0.5% acetic acid (60: 40) and the flow rate was 0.3 mL x min(-1). The temperature of the column was 40.0 degrees C. In this condition, we established an analysis method to simultaneously determine the four components. A sensitive and specific liquid chromatography-mass spectrometric (LC-MS) method was developed and validated for the determination of artemisin in derivatives in mice plasma. The method we established has a linear range of 5-3 000 µg x L(-1) with a good sensitivity and specificity for all of the four components. This method is simple, rapid, accurate and suitable for the determination of the content of the four compounds.


Assuntos
Artemisininas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Escopoletina/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Artemisininas/farmacocinética , Cromatografia Líquida de Alta Pressão/instrumentação , Relação Dose-Resposta a Droga , Masculino , Camundongos , Reprodutibilidade dos Testes , Escopoletina/farmacocinética
18.
Cancer Chemother Pharmacol ; 93(1): 41-54, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37741955

RESUMO

INTRODUCTION: LUAD (Lung adenocarcinoma), the most common subtype of lung carcinoma and one of the highest incidences and mortality cancers in the world remains still a substantial treatment challenge. Ivermectin, an avermectin derivative, has been traditionally used as an antiparasitic agent in human and veterinary medicine practice during the last few decades. Though ivermectin has been shown to be effective against a variety of cancers, however, there is few available data reporting the antitumor effects of ivermectin in LUAD. METHODS: The effect of ivermectin on cell viability and proliferative ability of LUAD cells was evaluated using CCK-8 and colony formation assay. Apoptosis rate and autophagy flux were detected using flow cytometry based on PI/Annexin V staining and confocal laser scanning microscope based on LC3-GFP/RFP puncta, respectively. Western blotting experiment was conducted to verify the results of changes in apoptosis and autophagy. LUAD-TCGA and GEO databases were used to analyse the expression and predictive value of PAK1 in LUAD patients. Xenograft model and immumohistochemical staining were used for verification of the inhibitor effect of ivermectin in vivo. RESULTS: Ivermectin treatment strikingly impeded the colony formation, and the viability of the cell, along with cell proliferation, and caused the apoptosis and enhanced autophagy flux in LUAD cells. In addition, ivermectin-induced nonprotective autophagy was confirmed by treating LUAD cells with 3-MA, an autophagy inhibitor. Mechanistically, we found that ivermectin inhibited PAK1 protein expression in LUAD cells and we confirmed that overexpression of PAK1 substantially inhibited ivermectin-induced autophagy in LUAD cells. Based on TCGA and GEO databases, PAK1 was highly expressed in LUAD tissues as compared with normal tissues. Furthermore, LUAD patients with high PAK1 level have poor overall survival. Finally, in vivo experiments revealed that ivermectin efficiently suppressed the cellular growth of LUAD among nude mice. CONCLUSION: This study not only revealed the mechanism of ivermectin inhibited the growth of LUAD but also supported an important theoretical basis for the development of ivermectin during the therapy for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Ivermectina/farmacologia , Camundongos Nus , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Autofagia , Proliferação de Células , Apoptose , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/farmacologia
19.
Cancer Med ; 13(11): e7383, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38864483

RESUMO

OBJECTIVE: The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC. METHODS: Thirty-five patients with ground-glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA-Seq were subsequently analyzed. RESULTS: The findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co-mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD. CONCLUSIONS: Our findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.


Assuntos
Adenocarcinoma de Pulmão , Sequenciamento do Exoma , Neoplasias Pulmonares , Mutação , Invasividade Neoplásica , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Perfilação da Expressão Gênica , Adenocarcinoma in Situ/genética , Adenocarcinoma in Situ/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Biomarcadores Tumorais/genética
20.
Zhongguo Zhong Yao Za Zhi ; 38(6): 871-4, 2013 Mar.
Artigo em Zh | MEDLINE | ID: mdl-23717970

RESUMO

OBJECTIVE: To investigate the intervention effect of Danggui Shaoyao San on rats with cirrhotic ascites, and discuss the effect of arginine vasopressin (AVP) on cirrhotic ascites. METHOD: Male SD rats were randomly divided into the control group, the model group, Danggui Shaoyao San low, middle and high dose groups. The cirrhotic ascites rat model was established by CCl4 combined with phenobarbital. Their urines were collected at 24 h to observe urine excretion of each group. Filter papers were used to determine the amount of ascites. The levels of serum alanine aminotransferasa (ALT) , aspartate aminotransferase (AST) were detected by the automatic biochemistry analyzer. Plasma prothrombin time (PT) was evaluated by the blood coagulation analyzer. The concentration of AVP in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Pathological changes in livers were observed by HE staining. RESULT: Compared with the model group, the Danggui Shaoyao San group showed significant improvement in live indexes, with notable decrease in serum ALT and AST and the time of PT, improvement in liver pathological changes. Simultaneously, the amount of ascites decreased to varying degrees, with notable increase in urine in 24 h and decrease in AVP concentration in plasma. CONCLUSION: Danggui Shaoyao San can notably improve liver functions of rats with cirrhotic ascites, reduce the generation of ascites and delay the progress of liver pathological changes. Its mechanism may be related to AVP.


Assuntos
Ascite/complicações , Ascite/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/complicações , Animais , Arginina Vasopressina/sangue , Ascite/sangue , Ascite/fisiopatologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa