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1.
Mitochondrial DNA B Resour ; 6(9): 2628-2629, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409160

RESUMO

Paeonia rockii subsp. taibaishanica (Paeoniaceae), one of the tree peony species, is endemic to the Qinling Mountains in central China. In this study, we characterized its whole plastid genome sequence using the Illumina sequencing platform. The complete plastid genome size of P. rockii subsp. taibaishanica is 153,368 bp in length, including a large single copy (LSC) region of 85,030 bp, a small single copy (SSC) region of 17,042 bp, and a pair of inverted repeats (IRs) of 25,648 bp. The genome contains 131 genes, including 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The GC contents in chloroplast genome, LSC region, SSC region, and IR region were 38.3%, 36.6%, 32.6%, and 43.1%, respectively. A total of 16 species are used to construct the phylogenetic tree of Paeoniaceae, the results showed that P. rockii subsp. taibaishanica is more closely related with congeneric Paeonia suffruticosa and Paeonia ostii, these species were clustered into a clade with high bootstrap support.

2.
Genes (Basel) ; 12(6)2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071968

RESUMO

Cotton is one of the most important fiber and oil crops in the world. Chloroplast genomes harbor their own genetic materials and are considered to be highly conserved. Transfer RNAs (tRNAs) act as "bridges" in protein synthesis by carrying amino acids. Currently, the variation and evolutionary characteristics of tRNAs in the cotton chloroplast genome are poorly understood. Here, we analyzed the structural variation and evolution of chloroplast tRNA (cp tRNA) based on eight diploid and two allotetraploid cotton species. We also investigated the nucleotide evolution of chloroplast genomes in cotton species. We found that cp tRNAs in cotton encoded 36 or 37 tRNAs, and 28 or 29 anti-codon types with lengths ranging from 60 to 93 nucleotides. Cotton chloroplast tRNA sequences possessed specific conservation and, in particular, the Ψ-loop contained the conserved U-U-C-X3-U. The cp tRNAs of Gossypium L. contained introns, and cp tRNAIle contained the anti-codon (C-A-U), which was generally the anti-codon of tRNAMet. The transition and transversion analyses showed that cp tRNAs in cotton species were iso-acceptor specific and had undergone unequal rates of evolution. The intergenic region was more variable than coding regions, and non-synonymous mutations have been fixed in cotton cp genomes. On the other hand, phylogeny analyses indicated that cp tRNAs of cotton were derived from several inferred ancestors with greater gene duplications. This study provides new insights into the structural variation and evolution of chloroplast tRNAs in cotton plants. Our findings could contribute to understanding the detailed characteristics and evolutionary variation of the tRNA family.


Assuntos
Evolução Molecular , Genes de Cloroplastos , Variação Estrutural do Genoma , Gossypium/genética , RNA de Transferência/genética , Códon/genética , Gossypium/classificação , Filogenia
3.
Toxicol In Vitro ; 70: 105047, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33137447

RESUMO

Silibinin, one of the flavonoids isolated from milk thistle seeds of Silybum marianum, has hepatoprotective properties against toxins in clinical. However, the detailed mechanisms have remained unclear. This study investigates the underlying mechanism of silibinin in the protection against ethanol- or acetaldehyde-induced damage of neonatal mouse primary hepatocytes in vitro. The results show that ethanol inhibited proliferation of hepatocytes in a time (12, 24, 36 h) and dose-dependent (0-800 mM) manner. However, silibinin did not show protective effect on ethanol (500 mM)-induced suppression of hepatocyte proliferation. Acetaldehyde, the toxic metabolite of ethanol, appearing immediately in individuals after drink also inhibited the proliferation of hepatocytes in a dose-dependent (0-12 mM) manner. Surprisingly, silibinin significantly increased the cell viability and reduced the leakage of alanine amino transferase (ALT) and aspartate amino transferase (AST) in acetaldehyde-treated hepatocytes, suggesting that silibinin protected cell injury caused by acetaldehyde treatment. The apoptosis-inducing effect of acetaldehyde was demonstrated by the increased number of cells in sub-G1 phase as well as caspase-3 activation. Further study shows that acetaldehyde induced autophagy in the hepatocytes. The autophagy inhibitors, 3-Methyladenine (3-MA) and chloroquine (CQ), further decreased the viability of cells treated with acetaldehyde, suggesting that autophagy plays a protective role against apoptosis. Consistently, silibinin (20 µM) significantly reduced the activation of caspase 3 or apoptosis and increased the conversion of LC3-I to LC3-II or autophagy. Taken together, it is concluded that silibinin does not repress the ethanol- induced hepatocyte injury, whereas silibinin reduces acetaldehyde-caused hepatocyte injury through down-regulation of apoptosis and up-regulation of autophagy.


Assuntos
Acetaldeído/toxicidade , Etanol/toxicidade , Hepatócitos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Silibina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Camundongos
4.
Front Microbiol ; 11: 590451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362737

RESUMO

Tomato spotted wilt orthotospovirus (TSWV) causes serious crop losses worldwide and is transmitted by Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). NSs protein is the silencing suppressor of TSWV and plays an important role in virus infection, cycling, and transmission process. In this research, we investigated the influences of NSs protein on the interaction of TSWV, plants, and F. occidentalis with the transgenic Arabidopsis thaliana. Compared with the wild-type Col-0 plant, F. occidentalis showed an increased number and induced feeding behavior on transgenic Arabidopsis thaliana expressing exogenous NSs. Further analysis showed that NSs reduced the expression of terpenoids synthesis-related genes and the content of monoterpene volatiles in Arabidopsis. These monoterpene volatiles played a repellent role in respect to F. occidentalis. In addition, the expression level of plant immune-related genes and the content of the plant resistance hormone jasmonic acid (JA) in transgenic Arabidopsis were reduced. The silencing suppressor of TSWV NSs alters the emission of plant volatiles and reduces the JA-regulated plant defenses, resulting in enhanced attractiveness of plants to F. occidentalis and may increase the transmission probability of TSWV.

5.
Bioorg Chem ; 102: 104131, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32738569

RESUMO

Five terpenoids (1-5), including three new ent-kaurane diterpenoids (1-3), one new ent-rosane type diterpenoid (4) and one known triterpenoid (5), were isolated from stigma maydis (Zea mays L.). The structures of the compounds were elucidated by comprehensive spectroscopic analyses. The relative configurations of stigmanes A-D (1-4) were determined by NOESY experiments. In addition, the relative configuration of stigmane D (4) was further established by NMR calculations. The absolute configurations of these compounds were identified by a comparison of experimental and calculated specific rotations. The neuroprotective effects of these compounds against H2O2-induced injury in human neuroblastoma SH-SY5Y cells were evaluated, and the results showed that among the compounds, 2 exhibited the most significant neuroprotection. Further study demonstrated that 2 could activate nuclear factor E2-related factor (Nrf2), downregulate apoptosis and reactive oxygen species (ROS) generation, and increase antioxidant enzyme activities in SH-SY5Y cells. However, the neuroprotective effect was reversed when Nrf2 was silenced. In conclusion, this study suggested that terpenoids from stigma maydis exerted neuroprotective effects through Nrf2 activation.


Assuntos
Peróxido de Hidrogênio/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Terpenos/farmacologia , Zea mays/química , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Peróxido de Hidrogênio/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação , Células Tumorais Cultivadas
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(4): 567-572, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32691569

RESUMO

Objective: To identify the risk factors of ESKAPE pathogens infection and related death in cancer patients, and to supply evidence for clinical precaution and diagnosis. Methods: A retrospective study of clinical and experimental data of cancer patients with bloodstream infection were carried out in Sichuan Cancer Hospital from 2013 to 2018. The clinical feature, predisposing factors and risk factors of death in ESKAPE group and non-ESKAPE group were analyzed by univariate analysis and multivariate logistic regression. Results: A total of 753 patients were enrolled in the study. Totally 795 pathogenic bacteria strains were isolated from blood culture and there were 278 ESKAPE strains, which took up 34.97% of isolated strains. Univariate analysis and multivariate logistic regression analysis showed that gender of male, multiple pathogens, history of exposure to enzyme inhibitors and agranulocytosis were independent risk factors of ESKAPE pathogens bloodstream infection. Peritoneal infection and combined fungal infection were independent risk factors of ESKAPE bloodstream infection related death. Conclusion: The bloodstream infection of ESKAPE pathogens is a problem worthy of clinical attention for cancer patients with neutrophil deficiency, previous antibiotic exposure, and fungal infection and peritoneal infection.


Assuntos
Bacteriemia , Neoplasias , Antibacterianos/uso terapêutico , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , China/epidemiologia , Humanos , Masculino , Micoses/complicações , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/microbiologia , Neutrófilos/patologia , Doenças Peritoneais/complicações , Doenças Peritoneais/microbiologia , Estudos Retrospectivos , Fatores de Risco
7.
EMBO J ; 39(10): e103111, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187724

RESUMO

The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2-/- mice display aggravated infarct phenotypes and reduced Beclin 1 p-Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2-induced autophagy in cell survival. Taken together, these results indicate that the ROS-ATM-CHK2-Beclin 1-autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress-induced tissue damage.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteína Beclina-1/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , AVC Isquêmico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Autofagia , Linhagem Celular , Modelos Animais de Doenças , Células HCT116 , Células HEK293 , Células HeLa , Humanos , Camundongos , Estresse Oxidativo , Fosforilação
8.
Nat Prod Res ; 34(10): 1352-1359, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30417665

RESUMO

As a part of our ongoing search for neuroprotective compounds from natural products, two new iridoid glycosides, vibsansuspenside A-B (1-2), along with five known terpenoids (3-7), were isolated from the dry leaves of Viburnum odoratissimum. Their chemical structures were well determined by means of NMR spectroscopic data as well as HRESIMS analysis. All compounds were detected for their neuroprotective effects against H2O2-induced damage in human dopaminergic neuroblastoma cells (SH-SY5Y). Among them, compound 3 displayed the most potent neuroprotective ability, and further investigation by Annexin V/PI and Western blot analysis demonstrated that compound 3 could protect SH-SY5Y cells from oxidative damage through inhibiting cell apoptosis.[Formula: see text].


Assuntos
Fármacos Neuroprotetores/isolamento & purificação , Folhas de Planta/química , Terpenos/isolamento & purificação , Viburnum/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Glicosídeos/isolamento & purificação , Humanos , Peróxido de Hidrogênio/farmacologia , Estrutura Molecular , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Fármacos Neuroprotetores/farmacologia , Terpenos/análise , Terpenos/farmacologia
9.
Front Psychol ; 10: 2540, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798501

RESUMO

Information-sharing behavior is affected by identity recognition perception. The current study aims to delve into the impact of familiarity and anonymity on information-sharing behavior, and the mediating role of intrinsic motivations on WeChat Moments. We hypothesized a mediator role of intrinsic motivations in the relationship between an individual's perceptions and information sharing. Based on the self-determination theory, a model was created and tested using a sample of 531 frequent users. In this study, these users were asked to use WeChat Moments, the most popular mobile private social networking site in China. The results demonstrate the significance of familiarity and identifiability in an interpersonal relationship, when using social networking sites. Moreover, the influence of perceived anonymity on information-sharing behavior, which is entirely mediated by intrinsic motivation has been validated from an empirical perspective. Our findings extend previous studies by showing the totally mediated effect of perceived anonymity on information-sharing behavior on WeChat Moments and the influential mechanism of intrinsic motivation. The results will inform researchers about the importance of incorporating the interpersonal structural features and intrinsic motivation of social networking sites into future studies on online information-sharing behavior. Important ways to promote attention and share information involve building a familiar relationship with communities and equipping oneself with off-line relations. Final indications for future developments are provided, with a special emphasis on the development of these findings in various social networking sites contexts.

10.
Sci Rep ; 9(1): 15762, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673032

RESUMO

Proinflammatory processes in adipose tissue contribute to development of breast cancer and insulin resistance. Crown-like structures (CLS) are histologic hallmarks of the proinflammatory process in adipose tissue. CLS are microscopic foci of dying adipocytes surrounded by macrophages mostly derived from monocytes in blood. Estrogen receptor ß (ERß) is expressed in microglia, macrophages within the central nervous system (CNS), where it evokes an anti-inflammatory response. The present study investigates the function of ERß in macrophages within CLS. We report that even though monocytes in the blood have no detectable levels of ERß, macrophages in CLS do express ERß. In ERß-/- mice, there was a significant increase in the number of CLS in both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). CLS in these mice were dominated by pro-inflammatory macrophages (M1 macrophages) with higher expression of osteopontin (OPN) and an increase in number of proliferating macrophages. In mice made obese by Western diet, treatment with an ERß selective agonist (LY3201) reduced the number of CLS in both SAT and VAT with downregulation of OPN, activated hypoxia-inducible factor-1α (HIF-1α), proliferation and upregulation prolyl hydroxylase 2 (PHD2), the enzyme which prevents activation of HIF1α, in macrophages. We conclude that ERß expression is induced in macrophages in CLS within adipose tissue where it plays a pivotal role in suppression of CLS. Thus ERß agonists may be used to alleviate CLS-related breast cancer and insulin resistance in adipose tissue.


Assuntos
Tecido Adiposo/metabolismo , Receptor beta de Estrogênio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/metabolismo , Osteopontina/metabolismo , Tecido Adiposo/patologia , Animais , Receptor beta de Estrogênio/genética , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout , Osteopontina/genética
11.
Antibiotics (Basel) ; 8(4)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766670

RESUMO

Volatile organic compounds (VOCs) from endophytic fungi are becoming a potential antibiotic resource. The inhibitive effects of VOCs produced by an endophytic fungus in Leucaena leucocephala were investigated on plant pathogens in this study. Using standard morphological methods and multigene phylogeny, the fungus was identified as Diaporthe apiculatum strain FPYF 3052. Utilizing a two- compartment Petri plate bioassay method, the VOCs from this fungus showed bioactivity ranging from 23.8% to 66.7% inhibition on eight plant pathogens within 24 hours. The SPME-GC/MS technique identified fifteen volatile compounds with dominant terpenoids γ-terpinene (39.8%), α-terpinene (17.2%), and (-)-4-terpineol (8.4%) from the VOCs. Commercial α-terpinene, γ-terpinene, and (-)-4-terpineol demonstrated inhibition on the tested pathogens at concentrations from 0.2 to 1.0 µl/ml within 72 h in the bioassay system. The inhibition rates were from 28% to 100% percent using 1.0 µl/ml within 48 h. (-)-4-Terpineol was the most active of the terpenoids causing up to 100% inhibition. The data illustrate that these monoterpenes play an important role in the inhibitive bioactivity of the VOCs of D. apiculatum FPYF 3052. Most importantly, (-)-4-terpineol is now for the first time, reported to have capability of strong antifungal activity and could be developed as an antibiotic substance.

12.
Proc Natl Acad Sci U S A ; 116(33): 16507-16512, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31371497

RESUMO

The retina is an extension of the brain. Like the brain, neurodegeneration of the retina occurs with age and is the cause of several retinal diseases including optic neuritis, macular degeneration, and glaucoma. Liver X receptors (LXRs) are expressed in the brain where they play a key role in maintenance of cerebrospinal fluid and the health of dopaminergic neurons. Herein, we report that LXRs are expressed in the retina and optic nerve and that loss of LXRß, but not LXRα, leads to loss of ganglion cells in the retina. In the retina of LXRß-/- mice, there is an increase in amyloid A4 and deposition of beta-amyloid (Aß) aggregates but no change in the level of apoptosis or autophagy in the ganglion cells and no activation of microglia or astrocytes. However, in the optic nerve there is a loss of aquaporin 4 (AQP4) in astrocytes and an increase in activation of microglia. Since loss of AQP4 and microglial activation in the optic nerve precedes the loss of ganglion cells, and accumulation of Aß in the retina, the cause of the neuronal loss appears to be optic nerve degeneration. In patients with optic neuritis there are frequently AQP4 autoantibodies which block the function of AQP4. LXRß-/- mouse is another model of optic neuritis in which AQP4 antibodies are not detectable, but AQP4 function is lost because of reduction in its expression.


Assuntos
Receptores X do Fígado/deficiência , Degeneração Neural/patologia , Nervo Óptico/patologia , Retina/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Feminino , Receptores X do Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Degeneração Neural/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Oligodendroglia/metabolismo , Nervo Óptico/metabolismo , Retina/metabolismo , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia
13.
Free Radic Res ; 53(6): 655-668, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31185752

RESUMO

Oxidative stress accompanying excessive accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction leads to the occurrence of neurodegenerative diseases. Our previous study showed that Eclalbasaponin I (EcI), a triterpene saponin isolated from Aralia elata (Miq.) Seem. (A. elata), repressed oxidative stress in human neuroblastoma SH-SY5Y cells. However, the detailed mechanism remains unclear. In this study, pretreatment with EcI in SH-SY5Y cells significantly activated the p38-mitogenactivated protein kinase (p38), the extracellular regulated protein kinase (ERK), whereas it did not affect the c-jun NH2 terminal kinases (JNK). In accordance with the initial findings, EcI-induced neuroprotective effect was attenuated by SB203580 (SB, a p38 inhibitor) or FR180204 (FR, an ERK inhibitor), being further confirmed by specific small interfering RNA (siRNA). Inhibition of either p38 or ERK up-regulated the apoptosis induction in EcI- and H2O2-cotreated cells. Furthermore, p38 or ERK suppression enhanced intracellular and mitochondrial ROS generation, decreased the activities of endogenous antioxidant defences as well as the mitochondrial membrane potential (MMP), resulting in dysfunction of mitochondria. In addition, EcI-induced autophagy and mitophagy were obviously down-regulated when p38 or ERK activation was blocked. Cumulatively, these findings supported that EcI-caused mitophagy contributed to the neuroprotective effect through p38 or ERK activation. Mitophagy induction might be an effective therapeutic intervention in neurodegenerative diseases.


Assuntos
Apoptose/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Mitofagia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Saponinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Aralia/química , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Imidazóis/farmacologia , Modelos Moleculares , Conformação Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Piridazinas/farmacologia , Piridinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Células Tumorais Cultivadas
14.
Bioorg Chem ; 88: 102926, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31005021

RESUMO

A pair of new cycloneolignan enantiomers (1a and 1b) were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated by extensive spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, MS/MS analysis, together with theoretical electronic circular dichroism (ECD) calculations. Compounds 1a and 1b were then evaluated for their neuroprotective effects against MPP+-induced SH-SY5Y cell injury. As a result, compounds 1a (77.64%) and 1b (78.62%) exhibited moderate neuroprotective activity at the concentration of 12.5 µM compared with that of MPP+ treated group (62.00% at 1 mM) by MTT assay. Furthermore, Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 10.99% and 9.31%, respectively.


Assuntos
1-Metil-4-fenilpiridínio/antagonistas & inibidores , Descoberta de Drogas , Isatis/química , Lignanas/farmacologia , Fármacos Neuroprotetores/farmacologia , 1-Metil-4-fenilpiridínio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Folhas de Planta/química , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
15.
Steroids ; 146: 57-64, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30951756

RESUMO

Timosaponin AIII (TAIII), a steroidal saponin isolated from the rhizome of Anemarrhena asphodeloides, exerted cytotoxic effect in many cancer cell lines. However, the effect of TAIII on resistant tumor cancer cells was unclear. In this study, MTT assay showed that TAIII exhibited significant cytotoxicity against A549/Taxol and A2780/Taxol cells in vitro. Annexin V-FITC/PI staining revealed that TAIII induced apoptosis in A549/T and A2780/T cells. Furthermore, Western blot analysis demonstrated that TAIII inhibited the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) as well as Ras, Raf, mitogen-activated protein kinase (MEPK), extracellular regulated protein kinases (ERK) in two taxol-resistant cancer cell lines. Besides, in vivo studies demonstrated that TAIII inhibited tumor growth in a nude mouse xenograft model. Additionally, TAIII (2.5 and 5 mg/kg) also down-regulated the protein expressions of PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways in vivo. Taken together, these findings demonstrated that TAIII exhibited significant anti-tumor effect on taxol-resistant cells.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Paclitaxel/farmacologia , Saponinas/farmacologia , Esteroides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Artigo em Inglês | MEDLINE | ID: mdl-30978931

RESUMO

Private science parks (PSPs) are infrastructure elements of national high technology industrial development zones. Increasing private capital is being invested in this field to transform abandoned factories into science parks through brownfield regeneration, which not only effectively utilizes urban space, but also greatly strengthens the power of scientific and technological innovation. The evolution of these PSPs, however, is not satisfactory, and some operation and innovation-related problems often lead to their failures. Therefore, identifying key success factors is crucial for the sustainable growth of PSPs. This study employs Fuzzy Analytic hierarchy process (FAHP) and Fuzzy-DEMATEL (Decision Making Trial and Evaluation Laboratory) methods to construct an identification model for key success factors of PSPs established from brownfield regeneration. Associated influencing factors were collected through literature analysis, on-site interviews, and questionnaire, based on which key success factors were identified. The results of the study showed that five factors-resources sharing capacity of the park, park scale, financing and financial services, legal policy services and administrative capability, and construction level of facilities in the park-are the key success factors for such PSPs. The results also provide a theoretical basis for the development of PSPs established from brownfield regeneration, and support the formulation of PSP-related policies.


Assuntos
Ecologia/educação , Recuperação e Remediação Ambiental/métodos , Recuperação e Remediação Ambiental/estatística & dados numéricos , Indústrias/métodos , Setor Privado/estatística & dados numéricos , Urbanização , China , Humanos
17.
J Nat Prod ; 82(4): 714-723, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30917277

RESUMO

Quassinoids are a class of highly oxygenated degraded triterpenoids exclusively discovered from plants of the Simaroubaceae family. In this study, eight new (1-8) and 15 known quassinoids (9-23) were isolated from an extract of the stems of Picrasma quassioides. The structures were elucidated by spectroscopic analysis and electronic circular dichroism spectra combined with quantum chemical calculations. Compounds 4 and 5 represent the first examples of 18-nor-quassinoids from P. quassioides. All isolates were screened for their neuroprotective activities toward H2O2-induced cell damage in SH-SY5Y cells. Further study revealed that the potential protective activities of these compounds appeared to occur via the suppression of cell apoptosis and downregulation of caspase-3 activation.


Assuntos
Fármacos Neuroprotetores/farmacologia , Picrasma/química , Quassinas/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio/toxicidade , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Espectroscopia de Prótons por Ressonância Magnética , Quassinas/química , Quassinas/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray
18.
Int J Biol Sci ; 15(3): 568-578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30745843

RESUMO

Hyperthermia has been clinically utilized as an adjuvant therapy in the treatment of cervical carcinoma. However, thermotolerance induced by heme oxygenase-1 (HO-1), a stress-inducible cytoprotective protein, limits the efficacy of hyperthermic therapy, for which the exact mechanism remains unknown. In the present study, we found that heat treatment induced HO-1 expression and decreased copy number of HPV16 in cervical cancer cells and tissues from cervical cancer and precursor lesions. Knockdown of HO-1 stimulated autophagy accompanied by downregulation of X-linked inhibitor of apoptosis protein. Furthermore, silencing of HO-1 led to cell intolerance to hyperthermia, as manifested by inhibition of cell viability and induction of autophagic apoptosis. Moreover, HO-1 modulated hyperthermia-induced, autophagy-dependent antiviral effect. Thus, the findings indicate that blockade of HO-1 enhances hyperthermia-induced autophagy, an event resulting in apoptosis of cervical cancer cells through an antiviral mechanism. These observations imply the potential clinical utility of hyperthermia in combination with HO-1 inhibition in the treatment of cervical cancer.


Assuntos
Autofagia/fisiologia , Heme Oxigenase-1/metabolismo , Neoplasias do Colo do Útero/metabolismo , Apoptose/genética , Apoptose/fisiologia , Autofagia/genética , Western Blotting , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Cromatografia Líquida , Feminino , Citometria de Fluxo , Heme Oxigenase-1/genética , Humanos , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de Massas em Tandem
19.
Fitoterapia ; 133: 225-230, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30660653

RESUMO

The investigation of the ethanol extract of the seeds of Crataegus pinnatifida led to the isolation of seven new 8-O-4' type sesquineolignans crasesquineolignan A-G (1-7), along with a reported analogue, leptolepisol B (8). The chemical structures of these compounds were elucidated based on complex analysis of their MS, 1D and 2D NMR data. All the isolated compounds were tested for their neuroprotective effects against the damage of human neuroblastoma SH-SY5Y cells induced by H2O2, and most of them showed significant neuroprotective activity. Among them, compound 4 (77.58%) showed the best protective effect, even better than the positive control (69.26%) at 25 µM.


Assuntos
Crataegus/química , Lignanas/farmacologia , Fármacos Neuroprotetores/farmacologia , Sementes/química , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio , Lignanas/isolamento & purificação , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química
20.
Phytochemistry ; 161: 163-171, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30661806

RESUMO

Five pairs of enantiomeric lignanamides including nine undescribed compounds along with a known one were obtained from Solanum nigrum L. (Solanaceae). Their structures with absolute configurations were elucidated based on comprehensive spectroscopic analyses and quantum chemical calculations of electronic circular dichroism (ECD) curves. Additionally, all isolates were evaluated for their neuroprotective activity against MPP+ (1-methyl-4-phenylpyridinium)-induced SH-SY5Y cells injury. Among them, cannabisin F showed the most significant neuroprotective effects at different concentrations (12.5, 25, 50 µM). Further studies by Hoechst 33258 staining, monodansylcadaverine (MDC) staining and Annexin V/PI analysis demonstrated that cannabisin F could induce protective autophagy to protect SH-SY5Y cells from MPP+-induced apoptosis.


Assuntos
Amidas/farmacologia , Lignanas/farmacologia , Fármacos Neuroprotetores/farmacologia , Solanum nigrum/química , 1-Metil-4-fenilpiridínio/farmacologia , Amidas/química , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Lignanas/química , Estrutura Molecular , Fármacos Neuroprotetores/química , Estereoisomerismo , Relação Estrutura-Atividade
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