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1.
Front Neurol ; 13: 774654, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359655

RESUMO

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

2.
Org Lett ; 24(15): 2905-2909, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35412321

RESUMO

The first collectively asymmetric total synthesis of all members of lycorane, including (+)-α, (+)-ß, (+)-γ, and (-)-δ, in a catalytic manner has been achieved. The cornerstone of this synthesis features an asymmetric, stereodivergent Ir/amine dual catalytic α-allylation of 2-phthalimidoacetaldehyde.


Assuntos
Alcaloides de Amaryllidaceae , Catálise , Estereoisomerismo
3.
J Control Release ; 335: 515-526, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-34058269

RESUMO

Mesenchymal stem cells (MSCs) are recognized as promising drug delivery vehicles. However, the limitation of drug loading capacity and safety considerations are two obstacles to the further application of MSCs. Here, we report MSC membrane-coated mesoporous silica nanoparticles (MSN@M) that maintain the active stealth and self-positioning drug delivery abilities of MSCs and resolve issues related to MSCs-mediated drug delivery. MSN@M was established through uniformly integrating MSC membrane onto a mesoporous silica nanoparticle (MSN) core by sonication. Reduced clearance of phagocytes mediated by CD47 marker on MSC membrane was observed in vitro, which explained the only ~ 25% clearance rate of MSN@M compared with MSN in vivo within 24 h. MSN@M also showed stronger tumor targeting and penetration ability compared with MSN in HepG2 tumor bearing mice. Simultaneously, MSN@M exhibited strong capacity for drug loading and sustained drug release ability of MSN when loaded with doxorubicin (DOX), the drug loading of MSN@M increased ~ 5 folds compared with MSC membrane. In HepG2 xenograft mice, DOX-loaded MSN@M effectively inhibited the growth of tumors and decreased the side effects of treatment by decreasing the exposure of other tissues to DOX. Consequently, our MSN@M may serve as alternative vehicles for MSCs and provide more options for antitumor treatment.


Assuntos
Biomimética , Nanopartículas , Animais , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Camundongos , Porosidade , Dióxido de Silício
4.
Org Lett ; 23(3): 1086-1089, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33480703

RESUMO

The regio- and enantioselective allylic substitution of branched alkyl-substituted allylic acetates employing malonates has been achieved through a process that calls for Krische's π-allyliridium C,O-benzoate catalyst. The protocol reported herein can be applied to a diverse set of branched alkyl substrates that are generally not well tolerated in the other two types of Ir-catalyzed allylation.

5.
Water Res ; 186: 116333, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32858242

RESUMO

The effects of phosphonates, the heavily-used antiscalants in reverse osmosis systems, on microalgae are controversial, although they are harmless to most aquatic organisms. Herein, we assessed the inhibitory effects of etidronic acid (HEDP) and diethylenetriamine penta(methylene phosphonic acid) (DTPMP) on algal growth and revealed the mechanisms involved in both intrinsic toxicity and complexation. The phosphonates showed weak influences on Scenedesmus sp. LX1 in the first 4 d of cultivation. In contrast, a significant growth inhibition was observed subsequently with half maximal effective concentrations of 57.6 and 35.7 mg/L for HEDP and DTPMP, respectively, at 10 d. The phosphonates had little effect on cellular energy transfer and oxidative stress, quantified by adenosine triphosphate level and superoxide dismutase activity, respectively, demonstrating weak intrinsic toxicities to algal cells. Phosphonates blocked the algal assimilation of iron ions through complexation. Severe iron deficiency limited photosynthetic activity and caused chlorophyll decline, resulting in a functional loss of the photosystem followed by complete algal growth inhibition at the late cultivation stage. Our findings point to a potential ecological impact wherein harmful algal blooms are induced by the natural degradation of phosphonates due to the release of both iron and phosphate ions that stimulate algal regrowth after disinhibition.


Assuntos
Microalgas , Organofosfonatos , Scenedesmus , Filtração , Fotossíntese
6.
Environ Int ; 139: 105685, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32247104

RESUMO

The disposal of reverse osmosis (RO) concentrate (ROC) is a critical challenge impeding the application of RO-based wastewater reclamation. Herein, we proposed an enhanced biotreatment approach for the simultaneous removal of nitrogen, phosphorous, hardness, and methylisothiazolinone (MIT) from ROC by suspended-solid phase cultivation of Scenedesmus sp. LX1. Repeated carrier addition, guided by the developed optimal carrier addition model, efficiently enhanced algal growth and contaminant removal through dynamically controlling the suspended algal density by cell attachment. The maximum algal growth rate (212.2 mg/(L∙d)) increased by 41% compared with the control, and the time needed for reaching the maximum algal biomass (906.7 mg/L) was shortened by 1 d, attributing to the mitigation of density restriction. 91.8% of nitrogen (30.2 mg/L) was removed with 5.5 mg/(L∙d) accelerating removal rate, and phosphate (3.7 mg/L) was completely removed within 1 d. Hardness precursors calcium and inorganic carbon were also removed in large amounts, 268.4 and 128.2 mg/L, respectively. Moreover, suspended-solid phase cultivation significantly mitigated the growth inhibition caused by MIT toxicity, enabled the algae to completely biodegrade MIT of extremely high concentrations (4.7 mg/L and 11.4 mg/L) in a short time. Our results demonstrate the feasibility of suspended-solid phase algal cultivation for simultaneously and effectively removing multiple main contaminants from ROC.


Assuntos
Scenedesmus , Biomassa , Dureza , Nitrogênio , Osmose , Tiazóis , Eliminação de Resíduos Líquidos , Águas Residuárias
7.
Int J Syst Evol Microbiol ; 70(5): 3162-3166, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32250241

RESUMO

An endophytic member of the genus Trichoderma was isolated from the root of a healthy 3-year-old Panax notoginseng in Yunnan province, PR China. The results of phylogenetic analyses based on a combined of ITS, tef1 and rpb2 indicated that this isolate was distinct from other species of the genus Trichoderma and closely related to Trichoderma songyi. It can be distinguished from T. songyi by its slower growth rates on PDA and colony morphology. The novel isolate formed conidia in thick white pustules scattered mostly at the margin. Its conidiophores tended to be regularly verticillium-like, little branched, sometimes substituted by phialides singly or in whorls. Conidia are smooth, mostly broadly subglobose to ellipsoidal. In combination with the genotypic and phenotypic characteristics, all data demonstrated that the fungus studied represented a unique and distinguishable novel species of the genus Trichoderma, for which the name Trichoderma panacis sp. nov. is proposed.


Assuntos
Panax notoginseng/microbiologia , Filogenia , Trichoderma/classificação , China , DNA Fúngico/genética , Endófitos/classificação , Endófitos/isolamento & purificação , Técnicas de Tipagem Micológica , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Esporos Fúngicos/crescimento & desenvolvimento , Trichoderma/isolamento & purificação
8.
Chin Herb Med ; 12(3): 265-272, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36119006

RESUMO

Objective: In this study, we aimed to identify the genes involved in leaf margin serration in Perilla frutescens. P. frutescens (Family: Lamiaceae) is widely grown in Asian countries. Perilla leaf is the medicinal part stipulated in the Chinese Pharmacopoeia. There are mainly two types of perilla leaves: one with serrated leaf margin which is the phenotype described in the pharmacopoeia and the other with smooth leaf margin. Methods: Transcriptome sequencing, co-expression analysis, and qRT-PCR analysis of six perilla tissues sampled from two different phenotypes (serrated and smooth leaves) were performed. Results: Forty-three differentially expressed genes (DEGs), which may potentially regulate leaf shape, were identified through de novo transcriptome sequencing between the two groups. Genes involved in leaf shape regulation were identified. Simultaneously, we validated five DEGs by qRT-PCR, and the results were consistent with the transcriptome data. In addition, 1186 transcription factors (TFs) belonging to 45 TF families were identified. Moreover, the co-expression network of DEGs was constructed. Conclusion: The study identified the key genes that control leaf shape by comparing the transcriptomes. Our findings also provide basic data for further exploring P. frutescens, which can help study the mechanism of leaf shape development and molecular breeding.

9.
Nat Prod Res ; 34(14): 2007-2013, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30732477

RESUMO

Two new compounds, (7R, 2E, 5E)-3,5,7-trimethyl-2,5-octadienedioic-8-methyl ester (1) and neovasipyridone G (3), together with a new natural product compound (7R,2E,5E)-3,5,7-trimethyl-2,5-octadienedioic acid (2), and six known compounds (4-9) were isolated from Penicillium sp. SYPF7381. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 2 were determined by optical rotation. The absolute configuration of compound 3 was determined by means of electronic circular dichroism (ECD) calculation. In addition, the in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. Furthermore, the structure-antiinflammation activity relationships for these isolated compounds were summarized based on the experimental as well as the docking results.


Assuntos
Produtos Biológicos/isolamento & purificação , Penicillium/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Dicroísmo Circular , Ésteres/isolamento & purificação , Camundongos , Conformação Molecular , Estrutura Molecular , Piridonas/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-Atividade
10.
Nat Prod Res ; 34(13): 1884-1890, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30760040

RESUMO

(+) Benzomalvins E (1) and (-) Benzomalvins E (2), a pair of epimeric derivatives, together with three known benzomalvins (3-5), were isolated from solid cultures of a interrhizospheric fungus Penicillium sp. SYPF 8411. The planar structure of (+) Benzomalvins E (1) has been previously reported. While, the absolute configuration of compound 1 was established by X-ray crystallographic analysis for the first time. The planar structure of the new compound 2 were elucidated by detailed interpretation of their HR ESI-TOF MS and NMR spectroscopic data. The absolute configuration of compound 2 was established by Rh2(OCOCF3)4-induced CD spectral data and the electronic circular dichroic (ECD) method. Furthermore, the epimerization induced by pH, temperature and H2O was revealed. Benzomalvins (1-3, 5), a type of indoximod, enhanced the cytotoxic capability of 5-fluorouracil against A549.


Assuntos
Benzodiazepinas/isolamento & purificação , Codonopsis/microbiologia , Penicillium/química , Rizosfera , Células A549 , Benzodiazepinas/química , Benzodiazepinas/farmacologia , Cristalografia por Raios X , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Solo/química
11.
J Hazard Mater ; 386: 121959, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31884360

RESUMO

Methylisothiazolinone (MIT) is a widely used non-oxidizing biocide for membrane biofouling control in reverse osmosis (RO) systems usually with high dosages. However, few investigations have focused on MIT removal through bio-processes, since it is highly bio-toxic. This study proposed a novel biotreatment approach for efficient MIT degradation by Scenedesmus sp. LX1, a microalga with strong resistance capability against extreme MIT toxicity. Results showed that MIT (3 mg/L) could be completely removed within 4 days' cultivation with a half-life of only 0.79 d. Biodegradation was the primary removal mechanism and this metabolic process did not rely on bacterial consortia, soluble algal products secretion or algal growth. The main pathway was proposed as ring cleavage followed by methylation and carboxylation through the identification of MIT transformation products. MIT biodegradation followed the pseudo-first-order kinetics under growth control. A new kinetic model was presented to depict the MIT removal considering algal growth, and this model could be used for generally describing non-nutritive contaminants biodegradation. The algal biodegradation capability was independent of the initial biocide concentration, and MIT removal could be enhanced by increasing the initial algal density. Our results highlight the potential application of algal cultivation for MIT-containing wastewater biotreatment, such as RO concentrate.


Assuntos
Desinfetantes/análise , Scenedesmus/crescimento & desenvolvimento , Tiazóis/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Biodegradação Ambiental , Cinética , Modelos Teóricos
12.
Huan Jing Ke Xue ; 40(7): 3223-3232, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854722

RESUMO

Coordinated utilization of clear and reclaimed water in urban water supply systems has attracted wide attention from both academic and industrial communities. Although the potential and impacts of water reuse have been explored in previous studies, there is still a lack of model-based research that can optimize the utilization of clear and reclaimed water among multiple sectors and at multiple locations and the associated operations of multiple water treatment plants. In this study, an optimization model was developed for supporting the coordinated supply of clear and reclaimed water in urban water supply systems. This model was formulated based on the conversion relationships among clear water, wastewaters, and reclaimed water resources as well as a number of constraints such as the water reclamation capacities of existing wastewater treatment plants. The developed model provides optimal plans for allocating clear and reclaimed water and for operating wastewater treatment plants in a complex water supply system. The optimization model was applied to a case study in the central districts of Beijing, China. Optimal results were generated under both business-as-usual (BAU) and alternative scenarios in which the utilization scale of reclaimed water was capped and not capped, respectively, according to the existing city plans. Under the BAU scenario, reclaimed water accounted for 32% of the total water used, and contributed 60%, 30%, and 42% of agricultural, industrial, and environmental water consumption, respectively. The supply-demand contradiction of reclaimed water was apparent in Haidian and Shijingshan districts. Compared to the BAU scenario, the alternative scenario achieved 0.621 billion yuan more in economic gain, consumed 36.59% more reclaimed water, and reduced clear water use by 14.02%. The alternative scenario also improved the use of the capacities of existing facilities and promoted water reuse. Moreover, the operation plans of wastewater treatment plants for increasing the utilization amount of reclaimed water was provided. The developed model could be widely applied to other water-scare cities with water reclamation potential without loss of generality.

13.
Sci Rep ; 9(1): 8319, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31165765

RESUMO

A total amount of 116 fungal strains, belonging to 30 genera, were acquired from the rhizosphere soil and plant of Galinsoga parviflora. A strain SYPF 7336, isolated from the rhizospheric soil, was identified as Seltsamia galinsogisoli sp. nov., by morphological and molecular analyses, which displayed high antibacterial activity. In order to study the secondary metabolites of Seltsamia galinsogisoli sp. nov., nine compounds were successfully seperated from the strain fermentation broth, including two new compounds and seven known compounds. Their structures were elucidated based on spectral analysis including 1D and 2D NMR. All the seperated compounds were evaluated for their antimicrobial activities. Compounds 2, 5 and 1 displayed antimicrobial activities against Staphylococcus aureus with MIC values of 25, 32 and 75 µg/mL, respectively. Moreover, morphological observation showed the coccoid cells of S. aureus to be swollen to a volume of 1.4 to 1.7-fold after treatment with compounds 1, 2 and 5, respectively. Molecular docking was carried out to investigate interactions of filamentous temperature-sensitive protein Z (FtsZ) with compounds 1, 2 and 5.


Assuntos
Anti-Infecciosos/farmacologia , Asteraceae/microbiologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas do Citoesqueleto/antagonistas & inibidores , Fungos/metabolismo , Proteínas de Bactérias/genética , Proteínas do Citoesqueleto/genética , Fermentação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Filogenia , Ligação Proteica , Rizosfera , Microbiologia do Solo , Especificidade da Espécie , Staphylococcus aureus/efeitos dos fármacos , Temperatura
14.
Zhongguo Zhong Yao Za Zhi ; 44(6): 1135-1144, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989975

RESUMO

Aesculus chinensis belongs to Hippocastanaceae family,bears medicinal and ornamental values. The oleanane type triterpenoid saponin aescin is regarded as active ingredient and accumulated in seed. In order to understand its molecular basis of the triterpenoid biosynthesis,we used high-throughput sequencing under Illumina Hi Seq 2000 platform to obtain the transcriptome data of seed and flower from A. chinensis to further mine the genes involved in its metabolic pathway. Unigene's de novo splicing was performed using Trinity software; the transcriptome results were annotated with KEGG database to predict the specific pathways of the aescin triterpenoid metabolism. Terpenoid and triterpenoid pathways were found from transcriptome data,and forty seven and twenty seven corresponding genes were uncovered respectively. It was found that there are eight kinds of enzymes related to the terpenoid metabolism pathway precursors and three kinds of enzymes related to the triterpenoid metabolism pathway. In this study,five genes corresponding to triterpene cyclase were analyzed in A. chinensis for the first time,which may participate in the synthesis of triterpenoid. It' s revealed that there were thirty three differential genes associated with the ko00900 and ko00909 pathways by analysis on the difference in transcriptome expression between seeds and flowers; seventeen unigenes were up-regulated and sixteen unigenes were down-regulated in the seeds relative to flowers. In this study, qRT-PCR experiments were used to verify the expression of three key enzyme genes of SQE( Unigene25806),HMGS( Unigene36710),and ß-AS( Unigene33291). The results of qRT-PCR were consistent with the transcriptome data. The candidate genes related to triterpenoid saponin aescin synthesis in A. chinensis found in this study can provide theoretical basis for the metabolism synthesis and regulation of aescin.


Assuntos
Aesculus , Saponinas , Triterpenos , Flores , Perfilação da Expressão Gênica , Transcriptoma
15.
Sci Total Environ ; 672: 563-571, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30970286

RESUMO

As 1,2-benzisothiazol-3(2H)-one (BIT) has been widely used in high concentrations for microbial growth control in many domestic and industrial processes, its potential eco-risk should be assessed. This study investigated the interaction between BIT and microalgae in aquatic environment as the mechanism of BIT lethal effect on microalgae was unclear and whether microalgae could efficiently remove BIT was unknown. It was found that Chlorella vulgaris could be killed by high concentrations of BIT, and this lethal effect was strongly enhanced when exposed to light. Inhibition of photosystem II electron transport followed by a decrease in cellular chlorophyll led to serious damage to algal photosynthesis. The excess accumulation of reactive oxygen species caused by the photosynthetic damage under light further increased the oxidative damage and promoted cell death. Under dark condition, however, the algae could tolerate higher BIT concentrations. BIT could be efficiently removed when the growth of Scenedesmus sp. LX1 was not completely inhibited. With an initial concentration of 4.5 mg/L, over 99% of BIT was removed during 168 hour cultivation. Microalgal biodegradation was the primary reason for this removal, and the contributions of BIT hydrolytic/photolytic degradation, microalgal growth, photosynthesis and sorption were negligibly small. These results pointed to the potential application of microalgae for efficient BIT removal from wastewater.


Assuntos
Biodegradação Ambiental , Microalgas/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Chlorella vulgaris , Clorofila , Água Doce , Microalgas/fisiologia , Fotossíntese , Scenedesmus , Triazóis/metabolismo , Poluentes Químicos da Água/metabolismo
16.
J Microbiol ; 57(5): 337-342, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30806981

RESUMO

A Gram-negative, facultatively anaerobic, non-motile, nonspore- forming, coccoid or rod-shaped and creamy-pigmented bacterium, designated SYP-B2100T, was isolated from the rhizospheric soil of Codonopsis clematidea in the Xinjiang Uygur Autonomous Region, China. The optimal growth occurred at 28°C, pH 5.0, in the absence of NaCl. The cells tested positive in catalase and methyl red tests but negative in oxidase, urease, gelatinase, milk coagulation, and peptonisation, H2S production, nitrate reduction, and Voges-Proskauer tests. The major isoprenoid quinone was ubiquinone-8 (Q-8). The major cellular fatty acids were C16:0 and summed feature 8. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol. The 16S rRNA gene sequence of strain SYP-B2100T was the most similar to that of Rahnella inusitata DSM 30078T (96.9%) within the family Enterobacteriaceae. The genomic DNA G + C content of strain SYP-B2100T was 50.3 mol%. The combined data from the phylogenetic, morphological, physiological, biochemical, and chemotaxonomic analyses presented in this study support the conclusion that strain SYP-B2100T represents a novel species of a new genus, for which the name Edaphovirga cremea gen. nov., sp. nov. is proposed; the type strain is SYPB2100T (= CGMCC 1.5857T = DSM 105170T = KCTC 62024T).


Assuntos
Codonopsis/microbiologia , Enterobacteriaceae/classificação , Enterobacteriaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases/genética , DNA Bacteriano/genética , Enterobacteriaceae/genética , Enterobacteriaceae/metabolismo , Ácidos Graxos/análise , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Rizosfera , Microbiologia do Solo
17.
Adv Mater ; 31(10): e1807591, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30633395

RESUMO

Neural stem cells (NSCs), capable of ischemia-homing, regeneration, and differentiation, exert strong therapeutic potentials in treating ischemic stroke, but the curative effect is limited in the harsh microenvironment of ischemic regions rich in reactive oxygen species (ROS). Gene transfection to make NSCs overexpress brain-derived neurotrophic factor (BDNF) can enhance their therapeutic efficacy; however, viral vectors must be used because current nonviral vectors are unable to efficiently transfect NSCs. The first polymeric vector, ROS-responsive charge-reversal poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] (B-PDEA), is shown here, that mediates efficient gene transfection of NSCs and greatly enhances their therapeutics in ischemic stroke treatment. The cationic B-PDEA/DNA polyplexes can effectively transfect NSCs; in the cytosol, the B-PDEA is oxidized by intracellular ROS into negatively charged polyacrylic acid, quickly releasing the BDNF plasmids for efficient transcription and secreting a high level of BDNF. After i.v. injection in ischemic stroke mice, the transfected NSCs (BDNF-NSCs) can home to ischemic regions as efficiently as the pristine NSCs but more efficiently produce BDNF, leading to significantly augmented BDNF levels, which in turn enhances the mouse survival rate to 60%, from 0% (nontreated mice) or ≈20% (NSC-treated mice), and enables more rapid and superior functional reconstruction.


Assuntos
Isquemia Encefálica/terapia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/transplante , Espécies Reativas de Oxigênio/metabolismo , Acidente Vascular Cerebral/terapia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Camundongos , Transfecção , Resultado do Tratamento
18.
Nat Prod Res ; 33(19): 2770-2776, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30221546

RESUMO

One new indole diterpenoid, drechmerin I (1), was isolated from the fermentation broth of Drechmeria sp. isolated from the root of Panax notoginseng. Its structure was elucidated based on 1 D and 2 D nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectrum (HRESIMS), and electronic circular dichroism (ECD) spectroscopic analyses as well as TD DFT calculations of ECD spectra. Drechmerin I (1) was assayed for its antimicrobial activity against Candida albicans, Staphylococcus aureus, Bacillus cereus, B. subtillis, Pseudomonas aeruginosa, and Klebsiella pneumonia, respectively. Drechmerin I (1) showed antimicrobial activities against B. subtillis with an MIC value of 200 µg/mL. The interaction of S. aureus peptide deformylase with drechmerin I (1) was investigated by molecular docking.


Assuntos
Anti-Infecciosos/farmacologia , Alcaloides Diterpenos/farmacologia , Hypocreales/química , Alcaloides Indólicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Bacillus cereus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Dicroísmo Circular , Alcaloides Diterpenos/química , Alcaloides Diterpenos/isolamento & purificação , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray , Staphylococcus aureus/efeitos dos fármacos
19.
RSC Adv ; 9(49): 28754-28763, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-35529647

RESUMO

Two new compounds chetoseminudin F (1) and G (2) together with eleven known compounds were isolated from the solid fermentation products of the endophytic fungus Chaetomium sp. SYP-F7950. The structures of the isolated compounds were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, and HRFABMS experiments. The absolute configurations of chetoseminudin F (1) and G (2) were determined by comparing the electronic circular dichroism (ECD) spectrum with those of the reported references. A plausible biogenetic pathway for compounds 1-6 and 9-13 was proposed. These isolates were also evaluated for their antimicrobial and antitumor activity, revealing that chetoseminudin F (1) displayed more potent cytotoxicity against MDA-MB-231 cells with an IC50 value of 26.49 µmol L-1 more than the common chemotherapeutic agent (paclitaxel). In antimicrobial assay, compounds 6, 9, 11 and 12 had strong antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecium and antifungal activity against Candida albicans with minimum inhibitory concentration (MIC) values ranging from 0.12 to 9.6 µg mL-1; meanwhile compounds 6, 8, 9 and 12 exhibited strong cytotoxicity with IC50 values of 2.75-8.68 µmol L-1 against tumor cell lines A549 and MDA-MB-231. In addition, morphological observation showed that treatment with compounds 6, 9 and 12 increased the mean length of B. subtilis by 1.6 to 1.8-fold. In silico molecular docking was applied to study the binding interactions between the compounds and the active sites of filamentous temperature-sensitive protein Z (FtsZ) from B. subtilis. Compounds 6, 9 and 12 displayed the low binding energies, strong H-bond interactions with FtsZ. On the basis of the antimicrobial activities, cellular phenotype observation and docking studies, compounds 6, 9 and 12 are considered to be a promising antimicrobial inhibitor of FtsZ.

20.
Sci Rep ; 8(1): 17838, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30546118

RESUMO

Ketogulonicigenium vulgare has been widely used in vitamin C two-step fermentation. Four K. vulgare strains (WSH-001, Y25, Hbe602 and SKV) have been completely genome-sequenced, however, less attention was paid to elucidate the reason for the differences in 2-KGA yield on genetic level. Here, a novel K. vulgare SPU B805 with higher 2-keto-L-gulonic acid (2-KGA) yield, was genome-sequenced to confirm harboring one circular chromosome with plasmid free. Comparative genome analyses showed that the absence of plasmid 2 was an important factor for its high 2-KGA productivity. The amino acid biosynthetic pathways in strain SPU B805 are much more complete than those in other K. vulgare strains. Meanwhile, strain SPU B805 harbored a complete PPP and TCA route, as well as a disabled EMP and ED pathway, same as to strain SKV, whereas strain WSH-001, Y25 and Hbe602 harbored complete PPP, ED, TCA pathway and a nonfunctional EMP pathway. The transcriptome of strain SPU B805 validated the carbon metabolism in cytoplasm mainly through the PPP pathway due to its higher transcriptional levels. This is the first time to elucidate the underlying mechanism for the difference in 2-KGA yield, and it is of great significance for strain improvement in the industrial fermentation.


Assuntos
Genoma Bacteriano , Metaboloma/fisiologia , Rhodobacteraceae , Transcriptoma/fisiologia , Rhodobacteraceae/genética , Rhodobacteraceae/metabolismo , Sequenciamento Completo do Genoma
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