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1.
Food Chem ; 451: 139505, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38703732

RESUMO

Constructing carrier materials with polysaccharides to enhance the solubility of insoluble active ingredients is a crucial strategy for improving bioavailability. This research constructed pectin-based hesperidin microcapsules (PHM) through self-assembly processes in the deep eutectic solvent, improving the solubility, storage stability, and bioavailability of hesperidin (HES). PHM exhibited high encapsulation efficiency (91.7%) and loading capacity (11.5%), with a small particle size (1.73 µm). The interaction mechanism was clarified through physical characterization and density functional theory (DFT) calculations. The vitro release demonstrated that the release ratio of PHM was only 6.4% in simulated gastric fluid (SGF), but reached 80.9% in simulated intestinal fluid (SIF). The release mechanism of PHM in SGF followed Fickian diffusion, while in SIF followed skeleton dissolution diffusion with a stable rate. Furthermore, the cell cytotoxicity experiments confirmed the remarkable biocompatibility of PHM toward human colon cells, which suggested its potential application in food and pharmaceutical fields.

2.
Arch Pharm (Weinheim) ; 357(4): e2300526, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294206

RESUMO

The phosphorylation of STAT3 plays a critical physiological role in the proliferation of rectal cancer. Hence, inhibiting STAT3 phosphorylation is an effective anticancer approach. In this work, we designed a novel 5-R'-1-naphthylmethylamide scaffold as a small molecule inhibitor of STAT3 phosphorylation. The results showed that 3D and 4D have exceptional inhibitory ability against three different colorectal cancer (CRC) cell lines, and can induce apoptosis of CRC cells by inhibiting STAT3 phosphorylation, while having no killing effect on normal human cells. 3D and 4D can inhibit STAT3 phosphorylation in a time- and concentration-dependent manner, and also inhibit the nuclear translocation of interleukin (IL)-6-induced STAT3. In the in vivo tumor model research, 4D significantly reduced the tumor volume of mice and had no drug toxicity on other organ tissues. Furthermore, molecular docking studies revealed that 3D and 4D had greater binding free energy when interacting with the STAT3 SH2 structural domain, and could establish H-π interaction modes. Dynamic simulation studies indicated that both compounds were able to bind tightly to STAT3.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Fosforilação , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Fator de Transcrição STAT3/química , Fator de Transcrição STAT3/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Antineoplásicos/química
3.
J Biomol Struct Dyn ; : 1-13, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902569

RESUMO

In recent years, numerous researchers have made local chemical modifications to the structure of curcumin while its basic structure remains unchanged, thus, producing curcumin derivatives. In this article, tetrahydrocurcumin was obtained by hydrogenation of curcumin, DFT calculation and characterization at the theoretical level of B3LYP/6 -311++G(d,p) were carried out. The observed IR and Raman spectra are in good agreement with the theoretical spectra. The FMO and ESP of tetrahydrocurcumin are predicted. The interaction in the system is shown graphically and analyzed by IGMH. Compared with curcumin, tetrahydrocurcumin lacks the unsaturated C = C bond, which makes it more stable and more bioavailable. Molecular docking with antioxidant targets elucidated the ligand-protein interaction and molecular dynamics simulation showed the antioxidant activity of tetrahydrocurcumin. The antioxidant activity of tetrahydrocurcumin was proved by DPPH• and •OH radical scavenging experiments. In essence, these derivatives exhibit enhanced physiological activity in certain aspects compared to the original curcumin. Moreover, the computational pharmacology techniques lay a theoretical groundwork for the development and modification of high-efficiency, low-toxicity drugs that interface with various targets of curcumin in the future.Communicated by Ramaswamy H. Sarma.

4.
Med Chem ; 19(3): 246-262, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36043763

RESUMO

Survivin is an important member of the antiapoptotic protein family and controls the cell's life cycle. Overexpression of survivin in tumor cells leads to inhibition of apoptosis, thus contributing to cancer cell proliferation. The largest binding pocket in the survivin dimer was located in the BIR domain. The key to the efficacy of 3-cyanopyridines was their surface interaction with the survivin amino acid Ile74. METHODS: Through the optimization of the 3-cyanopyridine, 29 new compounds with a 3- Cyanopyridine structure were designed, synthesized, and characterized by NMR, IR, and mass spectrometry. The antitumor activity of the compounds in vitro was detected by the MTT method. RESULTS: In vitro anti-tumor experiments showed that some compounds exhibited good anti-cancer effects. The IC50 values of the compound 2-amino-6-(2,4-difluorophenyl)-4-(4-hydroxyphenyl) nicotinonitrile (10n) against human liver cancer (Huh7), human glioma (U251), and human melanoma (A375) cells were 5.9, 6.0 and 7.2 µM, respectively. The IC50 values of the compound 6-(2,4-difluorophenyl)- 4-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (9o) against Huh7, U251 and A375 cells were 2.4, 17.5 and 7.2 µM, respectively, which were better than those of 10- hydroxycamptothecin and 5-fluorouracil. Analysis of the results of molecular dynamics simulation established that the BIR domain is the optimal binding site on the survivin protein, and the fingerprints of the eight most active compounds and the molecular docking to the survivin protein are analyzed. CONCLUSION: 3-Cyanopyridine is an excellent backbone for antitumor lead compounds, 10n and 9o, as derivatives of 3-Cyanopyridine are excellent survivin protein-targeting inhibitors worthy of further study. The key factor in inhibiting survivin protein through the action of amino acid Ile74.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Simulação de Acoplamento Molecular , Survivina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/química , Proliferação de Células , Aminoácidos , Estrutura Molecular , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Desenho de Fármacos
5.
BMC Pharmacol Toxicol ; 22(1): 1, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407916

RESUMO

BACKGROUND: The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have anticancer properties, but doses at therapeutic levels have unacceptable side effects. Here we investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug. METHODS: Synthesized TPGS-FA was characterized by FTIR, UV-visible and 1H NMR spectroscopy, and TPGS loaded with NC was evaluated for its ability to induce apoptosis in Huh7 cells by Annexin V/PI and MTT assays, and observed by laser scanning confocal microscopy and inverted phase contrast microscopy. RESULTS: TPGS-FA/NC complexes were prepared successfully, and were homogenious with a uniform size of ~ 14 nm diameter. NC was released from the TPGS-FA/NC complexes in a controlled and sustained manner under physiological conditions (pH 7.4). Furthermore, its cytotoxicity to hepatocarcinoma cells was greater than that of free NC. CONCLUSIONS: TPGS-FA is shown to be useful carrier for drugs such as NC, and TPGS-FA/NC could potentially be a potent and safe drug for the treatment of hepatocellular carcinoma.


Assuntos
Antineoplásicos/administração & dosagem , Benzofenantridinas/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Ácido Fólico/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/administração & dosagem , Vitamina E/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzofenantridinas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ácido Fólico/química , Humanos , Micelas , Nanopartículas/química , Vitamina E/química
6.
J Pharm Biomed Anal ; 194: 113782, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33279297

RESUMO

To date, the agarwood has been over exploited worldwide in the wild due to high demand. As an alternative, the agarwood obtained through artificial methods has greatly resolved the shortage of agarwood supply in the global market. However, little information about the difference in chemical constituents and bioactivities of the wild agarwood and the artificial agarwood is available. This study aims to systematically compare the chemical composition and the bioactivities between wild and artificial agarwood on the basis of the integrated method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-TOF-MS) and multivariate statistical analysis. The invitro antioxidant activity was determined using the 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radical scavenging activity assays. The cytotoxic activity of agarwood from different origin against three human cancer cell lines (i.e., A375, U251, and Skov3) were compared using the MTT assay. Fifty metabolites from UPLC-QTOF-MS spectra were identified and included in the multivariate analysis. Among these metabolites, 2-(2-phenylethyl) chromone derivatives (PECs), bi-2-(2-phenylethyl) chromone derivatives (BPECs) and sesquiterpene-2-(2-phenylethyl) chromone conjugates (SPECs) were found to be the major metabolites and acted as discriminant compounds in agarwood from different origin. The antioxidant activity study showed that the wild agarwood displayed significant antioxidant capacity compared with the artificial agarwood. Particularly, the content of secondary metabolites of SPEC analogs shown a positive effect on the radical scavenging activities, whereas the PECs were negatively correlated. Interestingly, no significant difference was observed between wild and artificial agarwood in terms of cytotoxic activity against three human cancer cell lines (i.e., A375, U251, and Skov3). To the best of our knowledge, this research is the first to study the metabolite profiles and bioactivities of the wild and the artificial agarwood in a holistic approach, and is expected to provide a rational basis for the quality assessment of artificial agarwood as a substitute for wild agarwood.


Assuntos
Thymelaeaceae , Cromatografia Líquida de Alta Pressão , Cromonas , Flavonoides , Humanos , Espectrometria de Massas
7.
Opt Express ; 28(22): 32572-32583, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114940

RESUMO

A novel vibration measurement system based on a fiber-optic extrinsic Fabry-Pérot interferometer is established. Two quadrature interferometry signals are obtained in accordance with the 90° phase shift between two output arms of a 2×2 fiber coupler. This outcome drastically simplifies the processing of collected data because only a single arctangent operation is needed to calculate the wrapped phase. Repetitive test results show that the relative micro-vibration reconstruction error of this method is less than 0.12%. This structure simplifies the extrinsic Fabry-Pérot signal demodulation process, which has guiding significance for the online measurement of high-precision physical quantities.

8.
Eur J Pharmacol ; 883: 173355, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32687921

RESUMO

Cervical cancer is the fourth leading killer of female cancer patients worldwide. Each year more than half a million women are diagnosed with cervical cancer and the disease results in over 300, 000 deaths. α-Cyperone is known as the principal active ingredient in the Cyperus rotundus (Family: Cyperaceae). However, the effects of α-Cyperone on cancers, especially on cervical cancer, are yet to be explored. In the present study, the underlying mechanism of the anti-tumor activity of α-Cyperone against HeLa cells was investigated. The results showed that α-Cyperone inhibited proliferation and induced apoptosis in HeLa cells. Mechanistically, α-Cyperone promoted HeLa cells apoptosis via a mitochondrial apoptotic pathway, which was proved by increased level of intracellular reactive oxygen species (ROS) and upregulated expression of cytochrome c, cleaved caspase-3, PARP, and Bax. Further RNA-sequencing revealed α-Cyperone inhibited the activation of PI3K/Akt/mTOR signaling pathway in HeLa cells, which confirmed by PI3K inhibitor and agonist. The PI3K inhibitor (LY294002) synergized with α-Cyperone in arresting the growth of HeLa cells, whereas the PI3K agonist (IGF-1) abrogated such an effect. Interestingly, the expression of PD-L1 was attenuated by both α-Cyperone and LY294002, while the supplement of IGF-1 rescued the low expression of PD-L1. In conclusion, our results reveal that the inhibitory effect of α-Cyperone on HeLa cell growth is triggered via the ROS-mediated PI3K/Akt/mTOR signaling pathway and closely related to a decline in the PD-L1 expression.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Naftalenos/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos dos fármacos , Antígeno B7-H1/metabolismo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células HeLa , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Transdução de Sinais , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia
9.
J Pharm Pharmacol ; 72(9): 1165-1175, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32419149

RESUMO

OBJECTIVES: Eurycoma longifolia Jack (Simaroubaceae) is commonly distributed in the Southeast Asia and Indo China, which has been shown to possess antianxiety, antibacterial, anticancer, antifungal, anti-inflammatory, antimalarial and antioxidant biological activities. 14,15ß-dihydroxyklaineanone is a diterpene isolated from E. longifolia Jack, which is cytotoxic against human lung cancer and human breast cancer cell lines. However, the effects and underlying mechanisms of 14,15ß-dihydroxyklaineanone on hepatocellular carcinoma remain unknown. METHODS: Cell viability assay and colony formation assay were used to measure HepG2 cell proliferation. Flow cytometry was used to analyse cell cycle and apoptosis. Wound-healing assay and transwell assay were used to observe cells migration. RNA sequencing and the enrichment of differentially expressed genes (DEGs) in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to find and determine underlying pathways. KEY FINDINGS: We found that 14,15ß-dihydroxyklaineanone inhibited the growth and migration of HepG2 cells but did not induce cell apoptosis. 14,15ß-dihydroxyklaineanone induced S cell cycle arrest by downregulating the expression levels of cyclin A, p-CDK2, cyclin B1, p21, E2F-1 and PCNA. In addition, RNA sequencing showed that 14,15ß-dihydroxyklaineanone regulated MAPK pathway by increasing the expression levels of phosphor-p38. Downregulating of p38 via both p38 inhibitor (SB203580) and p38-siRNA could antagonize the inhibition of cell proliferation and migration and reverse the changes in p-p38, E-cadherin, N-cadherin and PCNA expression induced by 14,15ß-dihydroxyklaineanone treatment. CONCLUSIONS: 14,15ß-dihydroxyklaineanone inhibited cell proliferation and migration through regulating p38 MAPK pathway in HCC cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Eurycoma/química , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Zhongguo Zhong Yao Za Zhi ; 44(18): 4000-4008, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31872737

RESUMO

Agarwood is a traditional and precious medicinal material and natural spice in China and other southeast Asian countries.As the head of all spices,agarwood has many pharmacological activities such as analgesia,antidiarrheal,anti-inflammatory and antibacterial effects. Due to its high price and scarce resources,there were just a few previous studies on it,mainly focusing on the chemical compositions of the agarwood essential oil and solvent extract mixture. The components of agarwood oils obtained by supercritical extraction and steam distillation were analyzed by using Gas Chromatography-Mass Spectrometer( GC-MS),and then the agarwood oils compositions and contents were compared between the traditional extraction method and the recently emerging supercritical extraction method. Antioxidant experiments of scavenging DPPH,ABTS,hydroxyl radical,total reducing power and MIC experiments of five kinds of tester strains such as staphylococcus aureus were combined to illustrate the differences between these two kinds of agarwood oils in terms of antioxidant and bacteriostatic activities. The results showed that the main components of agarwood oil were sesquiterpenoids( 68. 68%) in steam distillation extraction method,but sesquiterpenoids( 23. 78%) and chromones( 29. 42%) in supercritical extraction method. Fourteen common components included benzyl acetone,α-santalol,γ-eudesmol,agarospirol and guaiol etc. The antioxidant activity and inhibitory MIC of agarwood oils in supercritical extraction method were better than those in steam distillation method,and the inhibitory effect of agarwood oil on the growth of bacillus subtilis was found for the first time.


Assuntos
Antibacterianos/química , Antioxidantes/química , Destilação/métodos , Óleos Voláteis/química , Óleos de Plantas/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , China , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Vapor , Thymelaeaceae/química , Madeira/química
11.
Drug Des Devel Ther ; 13: 3369-3381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576111

RESUMO

BACKGROUND: Colorectal cancer is one of the common malignant tumors. Cyanopyridine and aminocyanopyridine having a carbon-nitrogen bond have been shown to have significant anticancer effects. STAT3 is a promising therapeutic target in multiple cancers. However, there are currently no effective STAT3 inhibitors in clinical practice for the treatment of colorectal cancer. MATERIALS AND METHODS: We screened 27 cyanopyridines for their anticancer activity by cell viability. The HCT-116, RKO, and DLD-1 cell lines were used to evaluate the anti-colorectal cancer effect of 3n. Scratch experiments and colony formation assays were used for the assessment of cell migration and proliferation capacity. Phosphorylated STAT3, STAT3, MCL-1, and Survivin levels were assessed by Western blot analysis. RESULTS: In this study, we synthesized 27 cyanopyridines and screened their anticancer activities in three human tumor cells, HCT-116, Hela229, and A375. We found that 2-amino-3-cyanopyridine 3n has better anticancer activity with IC50 values in the low micromolar range. Furthermore, 3n significantly inhibited the migration and colony formation of colorectal cancer cells. Mechanistically, 3n inhibited the expression of STAT3 phosphorylation in a dose- and time-dependent manner. CONCLUSION: 3n is worth of further investigations toward the discovery of STAT3 inhibitor as a drug candidate for cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Desenho de Fármacos , Piridinas/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Fosforilação/efeitos dos fármacos , Piridinas/síntese química , Piridinas/química , Fator de Transcrição STAT3/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
12.
J Sep Sci ; 42(24): 3646-3652, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31613051

RESUMO

Alkaloids are important natural products that exhibit a wide spectrum of pharmacological activities. To efficiently separate and purify them, a rosin-based polymer-bonded silica stationary phase in high-performance liquid chromatography was synthesized via the surface radical polymerization of ethylene glycol maleic rosinate acrylate and methacrylic acid onto functionalized silica. The stationary phases, columns, optimization of chromatographic conditions for alkaloids, and thermodynamic behavior of the analytes on the column were fully studied. Under the optimized conditions, the prepared column efficiently purified natural camptothecine, caffeine, and evodiamine with the corresponding purities of 92, 96, and 97%. With this work, we have developed an efficient approach to isolate alkaloids and promoted the research on rosin-based materials in biomedicine and analytical chemistry.


Assuntos
Alcaloides/isolamento & purificação , Polímeros/química , Resinas Vegetais/química , Dióxido de Silício/química , Alcaloides/química , Cromatografia Líquida de Alta Pressão , Polimerização , Polímeros/síntese química , Propriedades de Superfície , Termodinâmica
13.
Medicina (Kaunas) ; 55(6)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142005

RESUMO

Background and objectives: Existing studies concerning the associations of cognitive function with adiposity in young adults are sparse. The purpose of the study was to examine the associations of adiposity with cognitive control in young adults. Materials and Methods: Participants were 213 young adults (98 women and 115 men). Cognitive control was measured using a modified task-switching paradigm. Anthropometrics were measured by standardized procedures. Body fat mass and visceral fat area were measured by bioelectrical impedance analysis. Results: The results showed that increased body mass index (BMI, p = 0.02), body fat percentage (p = 0.02), and visceral fat area (p = 0.01) were significantly correlated with larger global switch costs of accuracy in women. In men, high levels of body fat percentage (p = 0.01) and visceral fat area (p = 0.03) were significantly correlated with larger local switch costs of reaction time. Conclusions: The results indicated that elevated adiposity was associated with worse performance on measures of cognitive control in young adults.


Assuntos
Índice de Massa Corporal , Cognição/fisiologia , Gordura Intra-Abdominal/fisiopatologia , Adolescente , Antropometria/métodos , Associação , Distribuição de Qui-Quadrado , China , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/fisiologia , Masculino , Adulto Jovem
14.
Mol Carcinog ; 58(8): 1512-1525, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31069881

RESUMO

Lung cancer is a leading cause of cancer-related death worldwide. Cyanopyridines and aminocyanopyridines with carbon-nitrogen bonds have been proved to exert significant anticancer, antibacterial, and anti-inflammatory effects. In this study, we showed that aminocyanopyridine 3o and 3k displaying potent antitumor activity via inhibiting the signal transducer and activator of transcription 3 (STAT3) pathway. They blocked the constitutive STAT3 phosphorylation in a dose- and time-dependent manner and regulated the transcription of STAT3 target genes encoding apoptosis factors. Most importantly, 3o also inhibited interleukin-6-induced STAT3 activation and nuclear localization. Furthermore, 3o significantly inhibited the tumor growth of H460-derived xenografts. Taken together, these findings suggest that 3o and 3k are promising therapeutic drug candidates for lung cancer by inhibiting persistent STAT3 signaling.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Células A549 , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Interleucina-6/metabolismo , Janus Quinase 2/biossíntese , Janus Quinase 3/biossíntese , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Pharmacol Sci ; 139(4): 340-345, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30871871

RESUMO

Aralia echinocaulis is used for the treatment of rheumatoid arthritis by Tujia Minority in China. A previous study demonstrated that A. echinocaulis had a significant anti-arthritic effect on adjuvant arthritis (AA) rats in vivo. However, it remains unclear whether A. echinocaulis can induce the apoptosis of fibroblast-like synoviocytes (FLS) from AA rats and the underlying mechanism is unknown. In this paper, CCK-8 assay, Hoechst staining and flow cytometry were used to evaluate the apoptotic effect of an A. echinocaulis ethanol extract (AEE) on AA FLS. Western blotting analysis was performed to measure the protein expression levels of Bcl-2, Bax, cleaved caspase-3, Akt, p-Akt, and Hif-1α. The results revealed that AEE could inhibit FLS proliferation in a dose and time-dependent manner. After treatment with AEE, AA FLS displayed the classical apoptotic morphology, and the apoptosis rates were significantly increased. Furthermore, we found that AEE increased the protein levels of Bax, cleaved caspase 3, and decreased the protein levels of Bcl-2, Hif-1α and p-Akt, without affecting total Akt levels. Collectively, these results suggested that the apoptosis inducing effect of AEE on AA FLS was related to the regulation of the expression of apoptosis-related proteins and the inhibition of the Akt/Hif-1α signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/genética , Aralia/química , Artrite Experimental/genética , Artrite Experimental/patologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sinoviócitos/patologia , Animais , Caspase 3/genética , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Ratos Sprague-Dawley , Fatores de Tempo
16.
Steroids ; 143: 53-61, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30590064

RESUMO

With steroid as a carrier nucleus and introducing a pyridine heterocycle as a pharmacophore on the D ring, a series of steroidal pyridine derivatives were designed and studied for their antitumor activity by molecular docking software. The compounds were synthesized as small molecule inhibitors and studied as anticancer agents. The synthesis of the analogs was performed in a one-pot multi-component reaction and the corresponding compounds were screened in vitro for their antitumor activity. Four adherently growing cancer cell lines were used and arranged before dosing. Among all compounds screened for their antitumor activity, compounds 2f and 2p were found to be the most active. Here, the most obvious changes in the morphology of the treated cells could be observed.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desenho de Fármacos , Simulação de Acoplamento Molecular , Piridinas/química , Esteroides/química , Esteroides/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Técnicas de Química Sintética , Humanos , Conformação Proteica , Esteroides/síntese química , Esteroides/metabolismo , Relação Estrutura-Atividade , Survivina/química , Survivina/metabolismo
17.
J Mol Graph Model ; 83: 53-63, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29772403

RESUMO

Survivin is the smallest member of IAP (inhibitor of apoptosis protein) family, which plays important roles in both mitosis and apoptosis. It has become an attractive drug target due to its overexpression in many human cancers. Survivin has been proven to bind to Smac/DIABLO protein that indirectly inhibits apoptosis. Meanwhile, it is the key subunit of chromosome passenger complex (CPC) which bind to the N-terminal tail of phosphorylated histone H3T3ph during mitosis. Up to now, Survivin directly targeting inhibitor has yet to merge since the difficulty of disrupting the protein-protein interactions (PPIs) between Survivin and its substrate proteins. Nevertheless, currently known binding partners of Survivin provide crucial information about conserved recognition mechanism, which can assist in the detection of some uncharted substrates and also the Survivin inhibitors. Herein, we adopted a method that using four substrates to analyze the common binding mode of Survivin. To accomplish this, conventional molecular dynamics (MD) simulations, molecular mechanics/generalized born surface area (MM-GBSA) binding free energy calculations and energy decomposition were carried out to assess the binding affinity and per-residue contributions. We found that there are two anchor sites of Survivin responsible for maintaining the binding conformation and one sub-pocket for intermolecular recognition. The results of this study synthetically describe the binding mechanism and provide valuable guidance for rational drug design of PPI inhibitor.


Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Survivina/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Desenho de Fármacos , Ligação de Hidrogênio , Ligantes , Mitose/efeitos dos fármacos , Peptídeos/química , Ligação Proteica , Conformação Proteica , Relação Quantitativa Estrutura-Atividade , Survivina/antagonistas & inibidores , Survivina/metabolismo
18.
Percept Mot Skills ; 125(2): 278-288, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29216798

RESUMO

Associations between daily physical activity (PA) and executive functioning have rarely been investigated among young adults. This study examined these associations among 162 university students (74 females and 88 males; mean age = 19.0, SD = 1.1 years). We measured PA objectively, using hip-mounted accelerometers, and assessed executive functioning in a task-switching paradigm. Anthropometrics measurements were gathered using standardized procedures. Through linear regression modeling, we found moderate-to-vigorous physical activity (ß = -0.19, 95% CI = [-0.35, -0.03], p = .02) and light physical activity (ß = -0.17, 95% CI = [-0.34, -0.01], p = .04) to be associated with smaller global reaction time switch costs. Total PA was not associated with task-switching performance, and there were no statistically significant associations between PA indicators and local switch costs. As both moderate-to-vigorous and light physical activities were associated with better executive function in young adults, there can be important cognitive benefits to remaining physically active.


Assuntos
Função Executiva/fisiologia , Exercício Físico/fisiologia , Desempenho Psicomotor/fisiologia , Acelerometria , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
19.
Mitochondrial DNA B Resour ; 2(1): 29-30, 2017 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33473705

RESUMO

Hydrocotyle sibthorpioides Lam. is a widespread and important Chinese medicinal plant. In this study, we have sequenced the complete chloroplast genome of H. sibthorpioides, which is 152,880 bp in length with large (LSC 84,064 bp) and small (SSC 18,690 bp) single-copy regions separated by a pair of inverted repeats (IRs 25,063 bp) and contains 113 unique genes with 17 genes duplicated in the IR making a total of 130 genes. The phylogenetic analysis strongly supports the position of H. sibthorpioides and indicates it belongs to the Araliaceae family, potential to facilitate a better understanding of population and phylogenetic studies in Apiales.

20.
Springerplus ; 5(1): 2036, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27995013

RESUMO

Eriobotrya japonica (Thunb.) Lindl (loquat) is an evergreen Rosaceae fruit tree widely distributed in subtropical regions. Its leaves are considered as traditional Chinese medicine and are of high medical value especially for cough and emesis. Thus, we sequenced the complete plastid genome of E. japonica to better utilize this important species. The complete plastid genome of E. japonica is 159,137 bp in length, which contains a typical quadripartite structure with a pair of inverted repeats (IR, 26,326 bp) separated by large (LSC, 89,202 bp) and small (SSC, 19,283 bp) single-copy regions. The E. japonica plastid genome encodes 112 unique genes which consist of 78 protein-coding genes, 30 tRNA genes and 4 rRNA genes. Gene structure and content of E. japonica plastid genome are quite conserved and show similarity among Rosaceous species. Five large indels are unique to E. japonica in comparison with Pyrus pyrifolia and Prunus persica, which could be utilized as molecular markers. A total of 72 simple sequence repeats (SSRs) were detected and most of them are mononucleotide repeats composed of A or T, indicating a strong A or T bias for base composition. The Ka and Ks ratios of most genes are lower than 1, which suggests that most genes are under purifying selection. The phylogenetic analysis described the evolutionary relationship within Rosaceae and fully supported a close relationship between E. japonica and P. pyrifolia.

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