Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Environ Res ; 251(Pt 2): 118640, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38479720

RESUMEN

The effects of long-term ammunition pollution on microecological characteristics were analyzed to formulate microbial remediation strategies. Specifically, the response of enzyme systems, N/O stable isotopes, ion networks, and microbial community structure/function levels were analyzed in long-term (50 years) ammunition-contaminated water/sediments from a contamination site, and a compound bacterial agent capable of efficiently degrading trinitrotoluene (TNT) while tolerating many heavy metals was selected to remediate the ammunition-contaminated soil. The basic physical and chemical properties of the water/sediment (pH (up: 0.57-0.64), nitrate (up: 1.31-4.28 times), nitrite (up: 1.51-5.03 times), and ammonium (up: 7.06-70.93 times)) were changed significantly, and the significant differences in stable isotope ratios of N and O (nitrate nitrogen) confirmed the degradability of TNT by indigenous microorganisms exposed to long-term pollution. Heavy metals, such as Pb, Zn, Cu, Cd, Cs, and Sb, have synergistic toxic effects in ammunition-contaminated sites, and significantly decreased the microbial diversity and richness in the core pollution area. However, long-term exposure in the edge pollution area induced microorganisms to use TNT as a carbon and nitrogen sources for life activities and growth and development. The Bacteroidales microbial group was significantly inhibited by ammunition contamination, whereas microorganisms such as Proteobacteria, Acidobacteriota, and Comamonadaceae gradually adapted to this environmental stress by regulating their development and stress responses. Ammunition pollution significantly affected DNA replication and gene regulation in the microecological genetic networks and increased the risk to human health. Mg and K were significantly involved in the internal mechanism of microbial transport, enrichment, and metabolism of TNT. Nine strains of TNT-utilizing microbes were screened for efficient TNT degradation and tolerance to typical heavy metals (copper, zinc and lead) found in contaminated sites, and a compound bacterial agent prepared for effective repair of ammunition-contaminated soil significantly improved the soil ecological environment.


Asunto(s)
Sedimentos Geológicos , Contaminantes Químicos del Agua , China , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Sedimentos Geológicos/microbiología , Sedimentos Geológicos/química , Biodegradación Ambiental , Metales Pesados/toxicidad , Metales Pesados/análisis , Bacterias/metabolismo , Sustancias Explosivas/metabolismo , Trinitrotolueno/metabolismo
2.
Pestic Biochem Physiol ; 201: 105874, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685243

RESUMEN

In insects, chemosensory proteins (CSPs) play an important role in the perception of the external environment and have been widely used for protein-binding characterization. Riptortus pedestris has received increased attention as a potential cause of soybean staygreen syndrome in recent years. In this study, we found that RpedCSP4 expression in the antennae of adult R. pedestris increased with age, with no significant difference in expression level observed between males and females, as determined through quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, we investigated the ability of RpedCSP4 to bind various ligands (five aggregated pheromone components and 13 soybean volatiles) using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP4 binds to three aggregated pheromone components of R. pedestris, namely, ((E)-2-hexenyl (Z)-3-hexenoate (E2Z3), (E)-2-hexenyl (E)-2-hexenoate (E2E2), and (E)-2-hexenyl hexenoate (E2HH)), and that its binding capacities are most stable under acidic condition. Finally, the structure and protein-ligand interactions of RpedCSP4 were further analyzed via homology modeling, molecular docking, and targeted mutagenesis experiments. The L29A mutant exhibited a loss of binding ability to these three aggregated pheromone components. Our results show that the olfactory function of RpedCSP4 provides new insights into the binding mechanism of RpedCSPs to aggregation pheromones and contributes to discover new target candidates that will provide a theoretical basis for future population control of R. pedestris.


Asunto(s)
Proteínas de Insectos , Feromonas , Animales , Feromonas/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/química , Masculino , Femenino , Unión Proteica , Heterópteros/metabolismo , Heterópteros/genética
3.
Pestic Biochem Physiol ; 191: 105348, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36963930

RESUMEN

A precise chemosensory system can help insects complete various important behavioral responses by accurately identifying different external odorants. Therefore, deeply understanding the mechanism of insect recognition of important odorants will help us develop efficient and environmentally-friendly behavioral inhibitors. Spodoptera frugiperda is a polyphagous pest that feeds on >350 different host plants worldwide and also harms maize production in China. However, the molecular mechanism of the first step for males to use odorant-binding proteins (OBPs) to recognize sex pheromones remains unclear. Here, we obtained 50 OBPs from the S. frugiperda genome, and the expression level of SfruGOBP1 in females was significantly higher than that in males, whereas SfruGOBP2 displayed male-biased expression. Fluorescence competitive binding assays showed that only SfruGOBP2 showed binding affinities for the four sex pheromones of female S. frugiperda. Subsequently, we identified some key amino acid residues that can participate in the interaction between SfruGOBP2 and sex pheromones using molecular docking and site-directed mutagenesis methods. These findings will help us explore the interaction mechanism between GOBPs and sex pheromones in moths, and provide important target genes for developing new mating inhibitors of S. frugiperda in the future.


Asunto(s)
Mariposas Nocturnas , Atractivos Sexuales , Animales , Femenino , Masculino , Atractivos Sexuales/metabolismo , Spodoptera/genética , Spodoptera/metabolismo , Odorantes , Simulación del Acoplamiento Molecular , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/metabolismo , Feromonas/metabolismo
4.
Pestic Biochem Physiol ; 192: 105394, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37105632

RESUMEN

Callosobruchus chinensis (Coleoptera: Fabaceae) is a worldwide pest that feeds exclusively on legumes, and is the most serious pest affecting mung beans. Usually, the insect olfactory system plays a predominant role in searching for host plants and egg-laying locations. Chemosensory proteins (CSPs), are mainly responsible for transporting specific odour molecules from the environment. In this study, we found that the CSP1 gene of adult C. chinensis displayed antennae-biased expression using quantitative real-time PCR (qRT-PCR) analysis. The binding properties of 23 mung bean volatiles were then determined through several analyses of in vitro recombinant CSP1 protein, including fluorescence competitive binding assay, homology modelling, molecular docking, and site-directed mutagenesis. Fluorescence competitive binding assays showed that CchiCSP1 protein could bind to four mung bean volatiles and was most stable at pH 7.4. After site-directed mutation of three key amino acid bases (L39, V25, and Y35), their binding affinities to each ligand were significantly decreased or lost. This indicated that these three amino acid residues may be involved in the binding of CchiCSP1 to different ligands. We further used Y-tube behavioural bioassays to find that the four mung bean volatiles had a significant attraction or repulsion response in adult C. chinensis. The above findings confirm that the CchiCSP1 protein may be involved in the response of C. chinensis to mung bean volatiles and plays an important role in olfactory-related behaviours. The four active volatiles are expected to develop into new behavioural attractants or repellents in the future.


Asunto(s)
Escarabajos , Fabaceae , Vigna , Animales , Simulación del Acoplamiento Molecular , Ligandos
5.
Pestic Biochem Physiol ; 194: 105513, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37532328

RESUMEN

Riptortus pedestris (bean bug), a common soybean pest, has a highly developed olfactory system to find hosts for feeding and oviposition. Chemosensory proteins (CSPs) have been identified in many insect species; however, their functions in R. pedestris remain unknown. In this study, quantitative real time-polymerase chain reaction (qRT-PCR) revealed that the expression of RpedCSP12 in the adult antennae of R. pedestris increased with age. Moreover, a significant difference in the expression levels of RpedCSP12 was observed between male and female antennae at one and three days of age. We also investigated the binding ability of RpedCSP12 to different ligands using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP12 only bound to one aggregation pheromone, (E)-2-hexenyl (Z)-3-hexenoate, and its binding decreased with increasing pH. Furthermore, homology modelling, molecular docking, and site-directed mutagenesis revealed that the Y27A, L74A, and L85A mutants lost their binding ability to (E)-2-hexenyl (Z)-3-hexenoate. Our findings highlight the olfactory roles of RpedCSP12, providing insights into the mechanism by which RpedCSPs bind to aggregation pheromones. Therefore, our study can be used as a theoretical basis for the population control of R. pedestris in the future.


Asunto(s)
Heterópteros , Feromonas , Animales , Femenino , Simulación del Acoplamiento Molecular , Heterópteros/genética , Glycine max
6.
Insect Mol Biol ; 31(6): 760-771, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35833827

RESUMEN

The bean bug Riptortus pedestris is a notorious insect pest that can damage various crops, especially soybean, in East Asia. In insects, the olfactory system plays a crucial role in host finding and feeding behaviour in which the odorant-binding proteins (OBPs) are believed to be involved in initial step in this system. In this study, we produced the R. pedestris adult antennae-expressed RpedOBP4 protein using a recombinant expression system in E. coli. Fluorescence competitive binding confirmed that RpedOBP4 has binding affinities to 7 of 20 soybean volatiles (ligands), and that a neutral condition is the best environment for it. The binding property of RpedOBP4 to these ligands was further revealed by integrating data from molecular docking, site-directed mutagenesis and ligand binding assays. This demonstrated that five amino acid residues (I30, L33, Y47, I57 and Y121) are involved in the binding process of RpedOBP4 to corresponding ligands. These findings will not only help us to more thoroughly explore the olfactory mechanism of R. pedestris during feeding on soybean, but also lead to the identification of key candidate targets for developing environmental and efficient behaviour inhibitors to prevent population expansion of R. pedestris in the future.


Asunto(s)
Heterópteros , Receptores Odorantes , Animales , Glycine max/metabolismo , Simulación del Acoplamiento Molecular , Escherichia coli , Heterópteros/metabolismo , Receptores Odorantes/metabolismo , Ligandos , Proteínas de Insectos/metabolismo , Unión Proteica
7.
Bioorg Med Chem Lett ; 72: 128876, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35788036

RESUMEN

Pyrrolobenzodiazepine (PBD) dimers are well-known highly potent antibody drug conjugate (ADC) payloads. The corresponding PBD monomers, in contrast, have received much less attention from the ADC community. We prepared several novel polyamide-linked PBD monomers and evaluated their utility as ADC payloads. The unconjugated polyamide-PBD hybrids exhibited potent antiproliferative activity (IC50 range: 10-11-10-8 M) against a variety of HER2-expressing cancer cell lines. Several peptide-linked variants of the lead compound were prepared and conjugated to trastuzumab to afford ADCs with drug-to-antibody (DAR) ratios ranging from 3 to 5. The ADCs exhibited antigen-dependent cytotoxicity in vitro and potently suppressed tumor xenograft growth in vivo in a target-dependent manner. Moreover, the ADCs were well-tolerated in both mouse and rat. This work demonstrates for the first time that PBD polyamide hybrids can serve as effective ADC payloads.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Animales , Antineoplásicos/farmacología , Benzodiazepinas , Línea Celular Tumoral , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Ratones , Nylons/farmacología , Pirroles , Ratas , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Dermatol Ther ; 33(4): e13690, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32468693

RESUMEN

The aim of this study was to explore the main factors affecting the occurrence of dandruff in healthy people (nondisease-induced scalp desquamation). This study analyzed the fungal microbial diversity of the scalp in Chinese teenage volunteers and measured scalp sebum secretion, the scalp pH value, and scalp transepidermal water loss. The amount and size of dandruff were measured, and the main factors that influence dandruff in the normal population were identified using principal component analysis. The results showed that an increase in Malassezia restricta led to an increased amount of dandruff in the mild and moderate groups. Conversely, this was not found for individuals in the severe group, whose dandruff symptoms were influenced by scalp barrier function. In terms of dandruff area grouping, the pH value and the amount of sebum secretion were the main factors, with the barrier function and microbial diversity being secondary factors. Dandruff cosmetics should emphasize different treatments for different types of dandruff to achieve better antidandruff effects. The results of this study provide a new theoretical basis for the development of multiple targets for antidandruff agents aimed at the normal population.


Asunto(s)
Caspa , Malassezia , Adolescente , Caspa/diagnóstico , Análisis Factorial , Humanos , Cuero Cabelludo
9.
J Asian Nat Prod Res ; 21(5): 476-493, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-29322879

RESUMEN

Diabetic cardiomyopathy (DCM) is one of the chief diabetes mellitus complications. Inflammation factors may be one reason for the damage from DM. The purpose of this research is to study the potential protective effects of puerarin on DM and the possible mechanisms of action related to NF-κB signal pathway. Following administration of puerarin to the disease model rat, several changes were observed including the changes of serum biochemical index, improved diastolic dysfunction, and enhanced endogenous antioxidant enzymes activities, further NF-κB signaling activation. Puerarin showed cardio-protective effects on DCM by inhibiting inflammation, and it might be a potential candidate for the treatment of DCM.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Cardiomiopatías Diabéticas/prevención & control , Inflamación/tratamiento farmacológico , Isoflavonas/farmacología , Animales , Línea Celular , Células Cultivadas , Glucosa/toxicidad , Isoflavonas/química , Estructura Molecular , Mioblastos Cardíacos/efectos de los fármacos , Miocardio/citología , FN-kappa B , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
10.
J Sep Sci ; 40(24): 4700-4708, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29044953

RESUMEN

A novel approach that involved the grafting of diblock copolymer with two types of monomer onto substrate by sequential surface initiated-atom transfer radical polymerization was proposed to prepare a mixed-mode chromatographic stationary phase. The distinguishing feature of this method is that it can be applied in the preparation of various mixed-mode stationary phases. In this study, a new reverse-phase/ion-exchange stationary phase was prepared by grafting hydrophobic styrene and cationic sodium 4-styrenesulfonate by the proposed approach onto silica surface. The chromatographic properties of the prepared stationary phase were evaluated by the separation of benzene derivatives, anilines, and ß-agonists, and by the effect of pH values and acetonitrile content on the retention. Compared with typical RP columns, the prepared stationary phase achieved the better resolution and higher selectivity at a shorter separation time and lower organic content. Moreover, the application of the prepared column was proved by separating widely distributed polar and charged compounds simultaneously.

11.
J Asian Nat Prod Res ; 18(6): 562-75, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26898948

RESUMEN

We propose to further research the protective effect of MMI on myocardium ischemic rat model and H9c2 cells that underwent cell apoptosis induced by hypoxia. We established the myocardium ischemic rat model via the cardiac surgical procedures in vivo and treated the model rats with different concentration of MMI. In vitro, with the pretreatment of MMI for 12 h in the model of Na2S2O4-induced hypoxia injury, the H9c2 cells viability was determined by MTT assay. We found that MMI had significantly improved cardiac function of the myocardial ischemia, and significantly decreased the reactive oxygen species level. The expression of P53, Bcl-2, Bax, and caspase-9 was also induced by MMI. In vitro study revealed a concentration-dependent increase in cell viability associated with MMI pretreatment. Annexin V-FITC and PI staining results showed that MMI had a preventive effect on hypoxia-induced apoptosis in H9c2 cells. MMI also inhibited the mitochondrial membrane potential decrease and increased total ATPase activity during hypoxia in H9c2 cells. In conclusion, MMI can enhance the cardiac function in myocardial ischemic rat and increase cell viability and attenuate the apoptosis in H9c2 cells induced by hypoxia, which was associated with inhibiting MMP decreasion and increasing total ATPase activity.


Asunto(s)
Adenosina Trifosfatasas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Isoflavonas/farmacología , Animales , Caspasa 9/metabolismo , Supervivencia Celular/efectos de los fármacos , Isoflavonas/química , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Ratas , Especies Reactivas de Oxígeno/metabolismo
12.
Zhong Yao Cai ; 38(10): 2070-5, 2015 Oct.
Artículo en Zh | MEDLINE | ID: mdl-27254918

RESUMEN

OBJECTIVE: To establish the gel permeation chromatography (GPC) fingerprint chromatograms of polysaccharides in Aloe vera leaf gel from the same habitat (Beijing) and different habitats for evaluating the quality of Aloe vera leaf gel products commercially available and testing common adulterated substances. METHODS: The samples were prepared by water-extraction and alcohol-precipitation method. GPC separation was performed on a Shodex SUGAR KS-805 (300 mm x 8.0 mm, 7 µm) column and a Shodex SUGAR KS-803 (300 mm x 8.0 mm, 6 µm) column at the temperature of 60 degrees C by eluting with 0.1 mol/L NaNO3 (containing 0.2 per thousand NaN) at a flow rate of 0.8 mL/min, the chromatographic effluent was detected by refractive index detector (RID) at the temperature of 50 degrees C. RESULTS: The common pattern of GPC fingerprint chromatograms was established and four common peaks were demarcated. The similarities of samples from the same habitat (Beijing) and different habitats were over 0.9. Taking the GPC fingerprint chromatograms for the qualified model, three commercially available aloe products were evaluated to be made of Aloe vera by the different manufacturing processes and four common adulterated substances of aloe polysaccharides were identified effectively. CONCLUSION: The method is simple and accurate with a good reproducibility, and it can be used for the identification and quality evaluation of Aloe vera leaf gel products.


Asunto(s)
Aloe/química , Cromatografía en Gel , Extractos Vegetales/química , Hojas de la Planta/química , Polisacáridos/química , Reproducibilidad de los Resultados
13.
J Hazard Mater ; 478: 135489, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39137547

RESUMEN

Novel microbial strains capable of efficient degradation of TNT and typical intermediates (2-ADNT and 4-ADNT) in aerobic/anaerobic environment were screened and isolated from ammunition-contaminated sites. The key genomes, transcriptomes, proteins, and metabolic factors for microbial detoxification/tolerance to pollutants in anaerobic and aerobic environments were analyzed for the first time. The bacterial genome, which is rich in metabolism and environmental information-processing functional genes, provides transcriptional and translational-related proteins for detoxifying/tolerating pollutants. At the transcriptional level, bacteria significantly expressed genes related to inositol phosphate metabolism for regulating membrane transport, maintaining the cytoskeleton, and signal transduction. At the protein level, genes involved in antioxidation, fat metabolism, sugar synthesis/degradation, and pyruvate metabolism were significantly expressed. At the metabolic level, riboflavin metabolism, which regulates membrane integrity, protects against oxidative stress, and maintains the sugar-protein-fat balance, showed significant responses. Bacteria simultaneously regulate amino acid metabolism, carbohydrate metabolism, and N/P/S cycles to maintain homeostatic cellular energy supplies. The key pathway for pollutant degradation in bacteria is nitrotoluene degradation. The molecular mechanism of bacterial tolerance to pollutants involves the regulation of oxidative phosphorylation and basic cycle pathways to maintain gene transcription, protein translation, and metabolic cycles.

14.
J Agric Food Chem ; 72(7): 3755-3762, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38346446

RESUMEN

Picolinamide fungicides, structurally related to UK-2A and antimycin-A, bind into the Qi-site in the bc1 complex. However, the detailed binding mode of picolinamide fungicides remains unknown. In the present study, antimycin-A and UK-2A were selected to study the binding mode of picolinamide inhibitors with four protonation states in the Qi-site by integrating molecular dynamics simulation, molecular docking, and molecular mechanics Generalized Born surface area (MM/GBSA) calculations. Subsequently, a series of new picolinamide derivatives were designed and synthesized to further understand the effects of substituents on the tail phenyl ring. The computational results indicated that the substituted aromatic rings in antimycin-A and UK-2A were the pharmacophore fragments and made the primary contribution when bound to a protein. Compound 9g-hydrolysis formed H-bonds with Hie201 and Ash228 and showed an IC50 value of 6.05 ± 0.24 µM against the porcine bc1 complex. Compound 9c, with a simpler chemical structure, showed higher control effects than florylpicoxamid against cucumber downy mildew and expanded the fungicidal spectrum of picolinamide fungicides. The structural and mechanistic insights obtained from the present study will provide a valuable clue for the future designing of new promising Qi-site inhibitors.


Asunto(s)
Antimicina A/análogos & derivados , Fungicidas Industriales , Ácidos Picolínicos , Animales , Porcinos , Fungicidas Industriales/farmacología , Simulación del Acoplamiento Molecular , Citocromos , Complejo III de Transporte de Electrones , Lactonas , Piridinas
15.
J Agric Food Chem ; 72(21): 12003-12013, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38748811

RESUMEN

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.


Asunto(s)
Conducta Alimentaria , Proteínas de Insectos , Larva , Spodoptera , Animales , Spodoptera/metabolismo , Spodoptera/fisiología , Spodoptera/genética , Spodoptera/crecimiento & desarrollo , Larva/metabolismo , Larva/crecimiento & desarrollo , Larva/fisiología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética
16.
Mol Cancer Ther ; 23(4): 541-551, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38354416

RESUMEN

Although microtubule inhibitors (MTI) remain a therapeutically valuable payload option for antibody-drug conjugates (ADC), some cancers do not respond to MTI-based ADCs. Efforts to fill this therapeutic gap have led to a recent expansion of the ADC payload "toolbox" to include payloads with novel mechanisms of action such as topoisomerase inhibition and DNA cross-linking. We present here the development of a novel DNA mono-alkylator ADC platform that exhibits sustained tumor growth suppression at single doses in MTI-resistant tumors and is well tolerated in the rat upon repeat dosing. A phosphoramidate prodrug of the payload enables low ADC aggregation even at drug-to-antibody ratios of 5:1 while still delivering a bystander-capable payload that is effective in multidrug resistant (MDR)-overexpressing cell lines. The platform was comparable in xenograft studies to the clinical benchmark DNA mono-alkylator ADC platform DGN459 but with a significantly better tolerability profile in rats. Thus, the activity and tolerability profile of this new platform make it a viable option for the development of ADCs.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Neoplasias , Humanos , Ratas , Animales , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Alquilantes , Neoplasias/tratamiento farmacológico , ADN/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología
17.
J Agric Food Chem ; 71(47): 18292-18300, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-37738510

RESUMEN

Scaffold hopping strategy has become one of the most successful methods in the process of molecular design. Seeking to develop novel succinate dehydrogenase inhibitors (SDHIs), we employed a scaffold hopping strategy to design compounds featuring geminate dichloralkenes (gem-dichloralkenes) fragment. After stepwise modifications, a series of N-cyclopropyl-dichloralkenes-pyrazole-carboxamide derivatives was synthesized. Among them, compounds G28 (IC50 = 26.00 nM) and G40 (IC50 = 27.00 nM) were identified as the best inhibitory activity against porcine SDH, with IC50 values reaching the nanomolar range, outperforming the lead compound pydiflumetofen. Additionally, the greenhouse assay indicated that compounds G37 (EC90 = 0.031 mg/L) and G34 (EC90 = 1.67 mg/L) displayed extremely high activities against wheat powdery mildew (WPM) and cucumber powdery mildew (CPM), respectively. Computational results further revealed that the gem-dichloralkene fragment and fluorine substituted pyrazole form an extra hydrophobic interaction and dipolar-dipolar interaction with SDH. In summary, our study provides a novel gem-dichloralkene scaffold with outstanding fungicidal properties, obtained through scaffold hopping, that holds great potential for future research on PM control.


Asunto(s)
Fungicidas Industriales , Succinato Deshidrogenasa , Animales , Porcinos , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Pirazoles/farmacología , Pirazoles/química , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular
18.
Environ Sci Pollut Res Int ; 30(54): 116227-116238, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37907824

RESUMEN

2,4,6-trinitrotoluene (TNT) is a nitroaromatic compound that causes soil and groundwater pollution during manufacture, transportation, and use, posing significant environmental and safety hazards. In this study, a TNT-degrading strain, Bacillus cereus strain T4, was screened and isolated from TNT-contaminated soil to explore its degradation characteristics and proteomic response to TNT. The results showed that after inoculation with the bacteria for 4 h, the TNT degradation rate reached 100% and was transformed into 2-amino-4,6-dinitrotoluene (2-ADNT), 4-amino-2,6-dinitrotoluene (4-ADNT), 2,4-diamino-6-nitrotoluene (2,4-DANT), and 2,6-diamino-4-nitrotoluene (2,6-DANT), accompanied by the accumulation of nitrite and ammonium ions. Through proteomic sequencing, we identified 999 differentially expressed proteins (482 upregulated, 517 downregulated), mainly enriched in the pentose phosphate, glycolysis/gluconeogenesis, and amino acid metabolism pathways. In addition, the significant upregulation of nitroreductase and N-ethylmaleimide reductase was closely related to TNT denitration and confirmed that the strain T4 converted TNT into intermediate metabolites such as 2-ADNT and 4-ADNT. Therefore, Bacillus cereus strain T4 has the potential to degrade TNT and has a high tolerance to intermediate products, which may effectively degrade nitroaromatic pollutants such as TNT in situ remediation in combination with other bacterial communities.


Asunto(s)
Trinitrotolueno , Trinitrotolueno/metabolismo , Proteómica , Nitrorreductasas/metabolismo , Bacterias/metabolismo , Biodegradación Ambiental , Suelo
19.
Int J Biol Macromol ; 250: 126137, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37544560

RESUMEN

Chemosensory proteins (CSPs) are involved in the earliest steps of the olfactory process by binding and transporting odorants and play a crucial role in the insect's search for food and egg-laying sites. In the present study, the tissue expression profiles showed that both CchiCSP3 and CchiCSP5 of Callosobruchus chinensis were highly expressed in the adult antennae. Subsequently, the recombinant CchiCSP3 and CchiCSP5 proteins were analysed using fluorescence competitive binding assays, and both showed binding affinities for the three mung bean volatiles. Molecular docking and site-directed mutagenesis revealed four key amino acid residues in CchiCSP3 (L47, W80, Y81, and L84) and CchiCSP5 (Y28, K46, L49, and I72). Electroantennogram (EAG) and dual-choice biobehavioral assays showed that the antennae of adult C. chinensis were electrophysiologically active in response to stimulation with all three behaviorally active compounds and that octyl 4-methoxycinnamate and ß-ionone had a significant luring effect on adult C. chinensis, whereas vanillin had a significant avoidance effect. Our study screened three effective behaviorally active compounds based on the involvement of two CchiCSPs in the recognition of mung bean volatiles, providing an opportunity to develop an alternative control strategy using behavioral disruptors to limit the impact of pests.

20.
Drug Des Devel Ther ; 17: 341-361, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776447

RESUMEN

Background: Adaptogens are a class of medicinal plants that can nonspecifically enhance human resistance. Most of the plant adaptogens have relevant applications in dermatology, but there are still few studies related to their particular action and co-operative mechanisms in topical skin application. Methods: Plant adaptogens related articles and reviews that published between 1999 and 2022 were obtained from the Web of Science Core Collection database. Various bibliographic elements were collected, including the annual number of publications, countries/regions, and keywords. CiteSpace, a scientometric software, was used to conduct bibliometric analyses. Also, the patsnap global patent database was used to analyze the patent situation of plant adaptogens in the field of cosmetics up to 2021. Results: We found that the effects of plant adaptogens on skin diseases mainly involve atopic dermatitis, acne, allergic contact dermatitis, psoriasis, eczema, and androgenetic alopecia, etc. And the effects on skin health mainly involve anti-aging and anti-photoaging, anti-bacterial and anti-fungal, anti-inflammatory, whitening, and anti-hair loss, etc. Also, based on the results of patent analysis, it is found that the effects of plant adaptogens on skin mainly focus on aging retardation. The dermatological effects of plant adaptogens are mainly from Fabaceae Lindl., Araliaceae Juss. and Lamiaceae Martinov., and their mainly efficacy phytochemical components are terpenoids, phenolic compounds and flavonoids. Conclusion: The plant adaptogens can repair the skin barrier and maintain skin homeostasis by regulating the skin HPA-like axis, influencing the oxidative stress pathway to inhibit inflammation, and regulating the extracellular matrix (ECM) components to maintain a dynamic equilibrium, ultimately achieving the treatment of skin diseases and the maintenance of a healthy state.


Asunto(s)
Dermatología , Plantas Medicinales , Enfermedades de la Piel , Humanos , Extractos Vegetales/farmacología , Envejecimiento , Enfermedades de la Piel/tratamiento farmacológico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA