RESUMO
Endophytic bacteria play crucial roles in the growth and bioactive compound synthesis of host plants. In this study, the composition and diversity of endophytic bacteria in the roots, stems, and leaves from 3-year-old artificially cultivated Huperzia serrata were investigated using Illumina HiSeq sequencing technology. Total effective reads were assigned to 936 operational taxonomic units (OTUs), belonging to 12 phyla and 289 genera. A total of 28, 3, and 2 OTUs were exclusive to the roots, stems, and leaves, respectively. The bacterial richness and diversity in the roots were significantly lower than those in the leaves and stems. The dominant genera with significant distribution differences among these plant tissue samples were Burkholderia-Caballeronia-Paraburkholderia, Sphingomonas, Acidibacter, Bradyrhizobium, Bryobacter, Methylocella, Nocardioides, Acidothermus, and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium. Furthermore, the differences in the bacterial communities associated with these plant tissue samples were visualized using principal coordinate analysis and cluster pedigree diagrams. Linear discriminant analysis effect size explained statistically significant differences among the endophytic bacterial microbiota in these plant tissue samples. Overall, this study provides new insights into the diversity and distribution patterns of endophytic bacteria in the different tissues of H. serrata.
Assuntos
Actinomycetales , Huperzia , Huperzia/microbiologia , Endófitos/genética , Bactérias/genética , Plantas , Raízes de Plantas/microbiologiaRESUMO
Leukemia is a type of malignant hematological disease that is generally resistant to chemotherapy and has poor therapeutic outcomes. Werner (WRN) DNA helicase, an important member of the RecQ family of helicases, plays an important role in DNA repair and telomere stability maintenance. WRN gene dysfunction leads to premature aging and predisposes humans to various types of cancers. However, the biological function of WRN in cancer remains unknown. In this study, the expression of this RecQ family helicase was investigated in different types of leukemia cells, and the leukemia cell line K562 with high WRN expression was selected to construct a WRN knockdown cell line. The results showed that WRN knockdown inhibited leukemia occurrence and development by regulating the proliferation, cell cycle, differentiation, and aging of cells and other biological processes. The results of transcriptome sequencing revealed that WRN promoted the sensitivity of leukemia cells to the DNA damage inducer Etoposide by regulating cell cycle-related proteins, such as CDC2, cyclin B1, p16, and p21, as well as key proteins in DNA damage repair pathways, such as p53, RAD50, RAD51, and MER11. Our findings show that WRN helicase is a promising potential target for leukemia treatment, providing new ideas for the development of targeted drugs against leukemia.
Assuntos
Exodesoxirribonucleases , Leucemia , Humanos , Helicase da Síndrome de Werner/genética , Helicase da Síndrome de Werner/metabolismo , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , RecQ Helicases/genética , RecQ Helicases/metabolismo , Ciclo Celular/genética , Reparo do DNA , Dano ao DNA , Leucemia/genéticaRESUMO
The enzyme activity of superoxide dismutase was improved in the pyrogallol autoxidation system by about 27%, after interaction between hydroxypropyl-ß-cyclo-dextrin and superoxide dismutase. Fluorescence spectrometry was used to study the interaction between hydroxypropyl-ß-cyclodextrin and superoxide dismutase at different temperatures. By doing this, it can be found that these interactions increase fluorescence sensitivity. In the meantime, the synchronous fluorescence intensity revealed the interaction sites to be close to the tryptophan (Trp) and tyrosine (Tyr) residues of superoxide dismutase. Furthermore, molecular docking was applied to explore the binding mode between the ligands and the receptor. This suggested that HP-ß-CD interacted with the B ring, G ring and the O ring and revealed that the lysine (Lys) residues enter the nanocavity. It was concluded that the HP-ß-CD caused specific conformational changes in SOD by non-covalent modification.
Assuntos
Modelos Moleculares , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Sítio Alostérico , Simulação por Computador , Ativação Enzimática , Ligação de Hidrogênio , Oxirredução , Ligação Proteica , Conformação Proteica , Espectrometria de FluorescênciaRESUMO
Aurora kinases have emerged as attractive targets for the design of anticancer drugs. 3D-QSAR (comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)) and Surflex-docking studies were performed on a series of pyrrole-indoline-2-ones as Aurora A inhibitors. The CoMFA and CoMSIA models using 25 inhibitors in the training set gave r(2) (cv) values of 0.726 and 0.566, and r(2) values of 0.972 and 0.984, respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to rationalize the key structural requirements responsible for the activity. Surflex-docking studies revealed that the sulfo group, secondary amine group on indolin-2-one, and carbonyl of 6,7-dihydro-1H-indol-4(5H)-one groups were significant for binding to the receptor, and some essential features were also identified. Based on the 3D-QSAR and docking results, a set of new molecules with high predicted activities were designed.
Assuntos
Aurora Quinase A/antagonistas & inibidores , Indóis/química , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/química , Relação Quantitativa Estrutura-Atividade , Aurora Quinase A/metabolismo , Sítios de Ligação , Indóis/metabolismo , Ligação Proteica , Inibidores de Proteínas Quinases/metabolismo , Estrutura Terciária de Proteína , Pirróis/químicaRESUMO
CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r(2) (cv) values of 0.747 and 0.518 and r(2) values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.
Assuntos
Ciclina A/química , Quinase 2 Dependente de Ciclina/química , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/química , Relação Quantitativa Estrutura-Atividade , Quinazolinas/química , Sequência de Aminoácidos , Ciclina A/metabolismo , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/metabolismo , Dados de Sequência Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologiaRESUMO
A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed on a series of the 11H-dibenz[b,e]azepine and dibenz[b,f][1,4]oxazepine derivatives as potent agonists of the human TRPA1 receptor. The CoMFA and CoMSIA models resulting from a 21 molecule training set gave r²(cv) values of 0.631 and 0.542 and r² values of 0.986 and 0.981, respectively. The statistically significant models were validated by a test set of five compounds with predictive r²(pred). values of 0.967 and 0.981 for CoMFA and CoMSIA, respectively. A systemic external validation was also performed on the established models. The information obtained from 3D counter maps could facilitate the design of more potent human TRPA1 receptor agonists.
Assuntos
Azepinas/química , Canais de Cálcio/química , Simulação por Computador , Modelos Moleculares , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/química , Canais de Potencial de Receptor Transitório/agonistas , Canais de Potencial de Receptor Transitório/química , Humanos , Canal de Cátion TRPA1RESUMO
To study xanthones from the barks of Garcinia xanthochymus, the constituents were isolated by normal-phase and reverse-phase silica gel column chromatography from the EtOAc extract. Their structures were elucidated by spectral analysis. Three new xanthones were purified and identified as 1,2,5-trihydroxy-6-methoxyxanthone (1), 1,4,6-trihydroxy-5-methoxyxanthone (2), 1,2,7-trihydroxy-4-(1,1-dimethylallyl) xanthone (3).
Assuntos
Garcinia/química , Xantonas/química , Estrutura Molecular , Casca de Planta/química , Plantas Medicinais/química , Xantonas/isolamento & purificaçãoRESUMO
The shortage of molecular information for taxol-producing fungi has greatly impeded the understanding of fungal taxol biosynthesis mechanism. In this study, the transcriptome of one taxol-producing endophytic fungus Cladosporium cladosporioides MD2 was sequenced for the first time. About 1.77 Gbp clean reads were generated and further assembled into 16,603 unigenes with an average length of 1110 bp. All of the unigenes were annotated against seven public databases to present the transcriptome characteristics of C. cladosporioides MD2. A total of 12,479 unigenes could be annotated with at least one database, and 1593 unigenes could be annotated in all queried databases. In total, 8425 and 3350 unigenes were categorized into 57 GO functional groups and 262 KEGG pathways, respectively, exhibiting the dominant GO terms and metabolic pathways in the C. cladosporioides MD2 transcriptome. One potential and partial taxol biosynthetic pathway was speculated including 9 unigenes related to terpenoid backbone biosynthesis and 40 unigenes involved in the biosynthetic steps from geranylgeranyl diphosphate to 10-deacetylbaccatin III. These results provided valuable information for the molecular mechanism research of taxol biosynthesis in C. cladosporioides MD2.