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1.
J Org Chem ; 89(12): 8435-8446, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38843406

RESUMEN

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

2.
PLoS Genet ; 17(2): e1009352, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33529191

RESUMEN

Diapause, a programmed developmental arrest primarily induced by seasonal environmental changes, is very common in the animal kingdom, and found in vertebrates and invertebrates alike. Diapause provides an adaptive advantage to animals, as it increases the odds of surviving adverse conditions. In insects, individuals perceive photoperiodic cues and modify endocrine signaling to direct reproductive diapause traits, such as ovary arrest and increased fat accumulation. However, it remains unclear as to which endocrine factors are involved in this process and how they regulate the onset of reproductive diapause. Here, we found that the long day-mediated drop in the concentration of the steroid hormone ecdysone is essential for the preparation of photoperiodic reproductive diapause in Colaphellus bowringi, an economically important cabbage beetle. The diapause-inducing long-day condition reduced the expression of ecdysone biosynthetic genes, explaining the drop in the titer of 20-hydroxyecdysone (20E, the active form of ecdysone) in female adults. Application of exogenous 20E induced vitellogenesis and ovarian development but reduced fat accumulation in the diapause-destined females. Knocking down the ecdysone receptor (EcR) in females destined for reproduction blocked reproductive development and induced diapause traits. RNA-seq and hormone measurements indicated that 20E stimulates the production of juvenile hormone (JH), a key endocrine factor in reproductive diapause. To verify this, we depleted three ecdysone biosynthetic enzymes via RNAi, which confirmed that 20E is critical for JH biosynthesis and reproductive diapause. Importantly, impairing Met function, a component of the JH intracellular receptor, partially blocked the 20E-regulated reproductive diapause preparation, indicating that 20E regulates reproductive diapause in both JH-dependent and -independent manners. Finally, we found that 20E deficiency decreased ecdysis-triggering hormone signaling and reduced JH production, thereby inducing diapause. Together, these results suggest that 20E signaling is a pivotal regulator that coordinates reproductive plasticity in response to environmental inputs.


Asunto(s)
Escarabajos/genética , Diapausa/genética , Ecdisona/metabolismo , Regulación del Desarrollo de la Expresión Génica , Fotoperiodo , Animales , Escarabajos/metabolismo , Ecdisterona/metabolismo , Femenino , Hormonas Juveniles/deficiencia , Hormonas Juveniles/genética , Metamorfosis Biológica/genética , Ovario/crecimiento & desarrollo , Ovario/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Reproducción/genética , Transducción de Señal
3.
Hepatology ; 76(4): 1046-1057, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35340061

RESUMEN

BACKGROUND AND AIMS: Wilson's disease (WD) is a rare hereditary disorder due to ATP7B gene mutation, causing pathologic copper storage mainly in the liver and neurological systems. Hepatocyte transplantation showed therapeutic potential; however, this strategy is often hindered by a shortage of quality donor cells and by allogeneic immune rejection. In this study, we aimed to evaluate the function and efficacy of autologous reprogrammed, ATP7B gene-restored hepatocytes using a mouse model of WD. APPROACH AND RESULTS: Sufficient liver progenitor cells (LPCs) were harvested by reprogramming hepatocytes from ATP7B-/- mice with small molecules, which exhibited strong proliferation and hepatic differentiation capacity in vitro. After lentivirus-mediated mini ATP7B gene transfection and redifferentiation, functional LPC-ATP7B-derived hepatocytes (LPC-ATP7B-Heps) were developed. RNA sequencing data showed that, compared with LPC-green fluorescent protein-Heps (LPC-GFP-Heps) with enrichment of genes that were mainly in pathways of oxidative stress and cell apoptosis, in LPC-ATP7B-Heps under high copper stress, copper ion binding and cell proliferation pathways were enriched. LPC-ATP7B-Heps transplantation into ATP7B-/- mice alleviated deposition of excess liver copper with its associated inflammation and fibrosis, comparable with those observed using normal primary hepatocytes at 4 months after transplantation. CONCLUSIONS: We established a system of autologous reprogrammed WD hepatocytes and achieved ATP7B gene therapy in vitro. LPC-ATP7B-Heps transplantation demonstrated therapeutic efficacy on copper homeostasis in a mouse model of WD.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Degeneración Hepatolenticular , Animales , Cobre/metabolismo , ATPasas Transportadoras de Cobre/genética , ATPasas Transportadoras de Cobre/metabolismo , Modelos Animales de Enfermedad , Terapia Genética , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Hepatocitos/metabolismo , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/metabolismo , Degeneración Hepatolenticular/terapia , Mutación
4.
Mol Ecol ; 32(11): 2884-2897, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36811404

RESUMEN

Many animals, including insects, exhibit plasticity of body colour in response to environmental changes. Varied expression of carotenoids, major cuticle pigments, significantly contributes to body colour flexibility. However, the molecular mechanisms by which environmental cues regulate carotenoid expression remain largely unknown. In this study, we used the ladybird Harmonia axyridis as a model to investigate the photoperiodic-responsive plasticity of elytra coloration and its endocrine regulation. It was found that H. axyridis females under long-day conditions develop elytra that are much redder than those under short-day conditions, resulting from the differential accumulation of carotenoids. Exogenous hormone application and RNAi-mediated gene knockdown indicate that carotenoid deposition was directed through the juvenile hormone (JH) receptor-mediated canonical pathway. Moreover, we characterized an SR-BI/CD36 (SCRB) gene SCRB10 as the carotenoid transporter responding to JH signalling and regulating the elytra coloration plasticity. Taken together, we propose that JH signalling transcriptionally regulates the carotenoid transporter gene for the photoperiodic coloration plasticity of elytra in the beetles, which reveals a novel role of the endocrine system in the regulation of carotenoid-associated animal body coloration under environmental stimuli.


Asunto(s)
Escarabajos , Animales , Femenino , Escarabajos/genética , Pigmentación/genética , Carotenoides , Interferencia de ARN
5.
Anim Cogn ; 26(2): 515-522, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36131103

RESUMEN

Alarm signals and cues are crucial to animal survival and vary greatly across species. Eavesdropping on heterospecific alarm signals and cues can provide eavesdroppers with information about potential threats. In addition to acoustic alarm signals, evidence has accumulated that chemical alarm cues and disturbance cues can also play a role in alerting conspecifics to potential danger in adult anurans (frogs and toads). However, there is very little known about whether disturbance cues are exploited by heterospecifics. In the present study, we conducted a binary choice experiment and a prey chemical discrimination experiment, respectively, to test the responses of a sympatric anuran species (red webbed treefrogs, Rhacophorus rhodopus) and a sympatric predator species (Chinese green tree vipers, Trimeresurus stejnegeri) to disturbance odors emitted by serrate-legged small treefrogs (Kurixalus odontotarsus). In the binary choice experiment, we found that the presence of disturbance odors did not significantly trigger the avoidance behavior of R. rhodopus. In the prey chemical discrimination experiment, compared with odors from undisturbed K. odontotarsus (control odors) and odorless control, T. stejnegeri showed a significantly higher tongue-flick rate in response to disturbance odors. This result implies that disturbance odor cues of K. odontotarsus can be exploited by eavesdropping predators to detect prey. Our study provides partial evidence for heterospecific eavesdropping on disturbance cues and has an important implication for understanding heterospecific eavesdropping on chemical cues of adult anurans.


Asunto(s)
Señales (Psicología) , Odorantes , Animales , Anuros , Reacción de Prevención , Conducta Predatoria
6.
Pestic Biochem Physiol ; 197: 105706, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38072559

RESUMEN

The Dpp signaling, as one of the branches within the TGF-ß superfamily, plays a crucial role in regulating various biological processes in insects. However, its impact on female reproduction through vitellogenesis remains unclear. In this study, the expression profiles implied that the Dpp signaling genes, including Dpp, Punt, Mad, and Medea, were up-regulated during reproductive development in the ovary of Colaphellus bowringi. Knockdown of these five Dpp signaling genes revealed significant effects of Dpp, Tkv, Mad, and Medea on ovarian development through vitellogenesis in the fat body. Our finding further indicated that Dpp signaling influences the expression of 20-hydroxyecdysone (20E) receptor and responsive genes in the fat body. Additionally, knockdown of 20E receptor EcR resulted in similar phenotypes as observed in the Dpp pathway genes knockdown, implying a regulatory role for Dpp signaling via EcR in vitellogenesis. Furthermore, knocking down Dpp, Tkv, and EcR in female adults led to a reduction in total dry weight and protein content, as well as the expression of mTOR, a factor linked to protein intake. These results suggest that the Dpp signaling pathway modulates vitellogenesis by impacting the AA/TOR-mediated 20E pathway in the fat body, providing novel insights into the network governing insect reproduction and offering potential targets for controlling female pest reproduction.


Asunto(s)
Brassica , Escarabajos , Animales , Femenino , Escarabajos/genética , Escarabajos/metabolismo , Ecdisterona/metabolismo , Brassica/metabolismo , Vitelogénesis , Transducción de Señal , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteínas de Insectos/metabolismo
7.
Org Biomol Chem ; 20(3): 538-552, 2022 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-34935824

RESUMEN

3,3-Disubstituted oxindoles bearing a stereogenic 3-fluorinated carbon center are privileged structural motifs present in many bioactive molecules. The straightforward functionalization of 3-fluorooxindoles constitutes a powerful method for the synthesis of 3-fully substituted 3-fluorooxindoles, taking advantage of the ease of preparation of 3-fluorooxindoles with different substitution patterns and the atom efficiency of chemical reactions. In the past decade, many papers have appeared on the synthesis of 3-fully substituted 3-fluorooxindoles from 3-fluorooxindoles. Importantly, many asymmetric catalytic methods have been developed for the enantioselective synthesis of these valuable compounds. This review summarizes the achievements in this area, and overviews synthetic opportunities that still exist.

8.
Acta Pharmacol Sin ; 43(3): 724-734, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34117368

RESUMEN

Hepatocellular carcinoma (HCC), the most prevalent liver cancer, is considered one of the most lethal malignancies with a dismal outcome mainly due to frequent intrahepatic and distant metastasis. In the present study, we demonstrated that oroxylin A, a natural product extracted from Scutellaria radix, significantly inhibits transforming growth factor-beta1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) and metastasis in HCC. Oroxylin A blocked the TGF-ß1/Smad signaling via upregulating the non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) expression. Oroxylin A promoted NAG-1 transcription by regulating the acetylation of CCAAT/enhancer binding protein ß (C/EBPß), a transcription factor that binds to the NAG-1 promoter. In terms of the underlying mechanism, oroxylin A may interact with histone deacetylase 1 (HDAC1) by forming hydrogen bonds with GLY149 residue and induce proteasome-mediated degradation of HDAC1 subsequently impairing HDAC1-mediated deacetylation of C/EBPß and promoting the expression of NAG-1. Taken together, our findings revealed a previously unknown tumor-suppressive mechanism of oroxylin A. Oroxylin A should be further investigated as a potential clinical candidate for inhibiting HCC metastasis.


Asunto(s)
Carcinoma Hepatocelular/patología , Flavonoides/farmacología , Factor 15 de Diferenciación de Crecimiento/efectos de los fármacos , Neoplasias Hepáticas/patología , Factor de Unión a CCAAT/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Histona Desacetilasa 1/efectos de los fármacos , Humanos , Proteínas Smad/efectos de los fármacos , Factor de Crecimiento Transformador beta1/efectos de los fármacos
9.
Int J Mol Sci ; 24(1)2022 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-36613830

RESUMEN

Sex pheromone-binding proteins (PBPs) play an important role in sex pheromone recognition in Lepidoptera. However, the mechanisms of chemical communication mediating the response to sex pheromones remain unclear in the diurnal moths of the superfamily Zygaenoidea. In this study, Phauda flammans (Walker) (Lepidoptera: Zygaenoidea: Phaudidae) was used as a model insect to explore the molecular mechanism of sex pheromone perception in the superfamily Zygaenoidea. Two novel pheromone-binding proteins (PflaPBP1 and PflaPBP2) from P. flammans were identified. The two pheromone-binding proteins were predominantly expressed in the antennae of P. flammans male and female moths, in which PflaPBP1 had stronger binding affinity to the female sex pheromones Z-9-hexadecenal and (Z, Z, Z)-9, 12, 15-octadecatrienal, PflaPBP2 had stronger binding affinity only for (Z, Z, Z)-9, 12, 15-octadecatrienal, and no apparent binding affinity to Z-9-hexadecenal. The molecular docking results indicated that Ile 170 and Leu 169 are predicted to be important in the binding of the sex pheromone to PflaPBP1 and PflaPBP2. We concluded that PflaPBP1 and PflaPBP2 may be responsible for the recognition of two sex pheromone components and may function differently in female and male P. flammans. These results provide a foundation for the development of pest control by exploring sex pheromone blocking agents and the application of sex pheromones and their analogs for insect pests in the superfamily Zygaenoidea.


Asunto(s)
Lepidópteros , Mariposas Nocturnas , Atractivos Sexuales , Animales , Femenino , Masculino , Mariposas Nocturnas/fisiología , Feromonas/metabolismo , Atractivos Sexuales/química , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Simulación del Acoplamiento Molecular , Proteínas de Insectos/metabolismo
10.
Bioorg Med Chem Lett ; 43: 127898, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33684440

RESUMEN

A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.


Asunto(s)
Dioxoles/farmacología , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/farmacología , Lípidos/antagonistas & inhibidores , Sustancias Protectoras/farmacología , Animales , Dieta Alta en Grasa/efectos adversos , Dioxoles/síntesis química , Dioxoles/química , Relación Dosis-Respuesta a Droga , Hiperlipidemias/inducido químicamente , Hiperlipidemias/metabolismo , Hipolipemiantes/síntesis química , Hipolipemiantes/química , Ratones , Estructura Molecular , Sustancias Protectoras/síntesis química , Sustancias Protectoras/química , Relación Estructura-Actividad
11.
Bioorg Chem ; 110: 104775, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33725509

RESUMEN

The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1-18), containing three new ones, clausenanisines A-C (1-3), and three new naturally occurring carbazole alkaloids, clausenanisines D-F (4-6), as well as 12 known analogues (7-18). The chemical structures of clausenanisines A-F (1-6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7-18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7-18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1-18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities in vitro. Compounds 1-18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 ± 0.05 to 38.48 ± 0.32 µM, meanwhile, compounds 1-18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 µM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.


Asunto(s)
Alcaloides/farmacología , Carbazoles/farmacología , Clausena/química , Inhibidores Enzimáticos/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , alfa-Glucosidasas/metabolismo , Alcaloides/química , Alcaloides/aislamiento & purificación , Carbazoles/química , Carbazoles/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Frutas/química , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Relación Estructura-Actividad
12.
Med Sci Monit ; 27: e927624, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33436534

RESUMEN

BACKGROUND Traditional Chinese medicine has widely used Bolbostemma paniculatum to treat diseases, including cancer, but its underlying mechanisms remain unclear. The present study aimed to elucidate the potential pharmacological mechanisms of "Tu Bei Mu" (TBM), the Chinese name for Bolbostemmatis Rhizoma, the dry tuber of B. paniculatum, for the treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS The active components and putative therapeutic targets of TBM were explored using SwissTargetPrediction, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Search Tool for Interactions of Chemicals (STITCH). The HCC-related target database was built using DrugBank, DisGeNet, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). A protein-protein interaction network of the common targets was constructed, based on the matches between TBM potential targets and HCC-related targets, using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the cluster networks were used to elucidate the biological functions of TBM. RESULTS Pharmacological network diagrams of the TBM compound-target network and HCC-related target network were successfully constructed. A total of 22 active components, 191 predicted biological targets of TBM, and 3775 HCC-related targets were identified. Through construction of an HCC-related target database and a protein-protein interaction network of the common targets, TBM was predicted to be effective in treating HCC mainly through the PI3K-Akt, HIF-1, p53, and PPAR signaling pathways. CONCLUSIONS The PI3K/Akt, HIF1, p53, and PPAR pathways may play vital roles in TBM treatment of HCC. Also, the potential anti-cancer effect of TBM on HCC appears to stem from the synergetic effect of multiple targets and mechanisms.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Biología de Sistemas/métodos , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Bases de Datos de Compuestos Químicos , Bases de Datos Genéticas , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mapas de Interacción de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
13.
Phys Rev Lett ; 125(13): 131806, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-33034473

RESUMEN

The XENON1T collaboration has observed an excess in electronic recoil events below 5 keV over the known background, which could originate from beyond-the-standard-model physics. The solar axion is a well-motivated model that has been proposed to explain the excess, though it has tension with astrophysical observations. The axions traveling from the Sun can be absorbed by the electrons in the xenon atoms via the axion-electron coupling. Meanwhile, they can also scatter with the atoms through the inverse Primakoff process via the axion-photon coupling, which emits a photon and mimics the electronic recoil signals. We found that the latter process cannot be neglected. After including the keV photon produced via the inverse Primakoff process in the detection, the tension with the astrophysical constraints can be significantly reduced. We also explore scenarios involving additional new physics to further alleviate the tension with the astrophysical bounds.

14.
Bioorg Med Chem Lett ; 30(15): 127277, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32527456

RESUMEN

Nitric oxide (NO) dysfunction, oxidative stress, and dyslipidemia are main risk factors associated with the pathophysiology of diabetic complications. In this study, 3,4-dihydroxyphenethyl nitrate (HT-ONO2) was designed, synthesized and evaluated, which incorporated hydroxytyrosol (HT) and nitrate. HT-ONO2 significantly exhibited hypoglycemic activity after oral administration to diabetic mice induced by streptozocin (STZ). HT-ONO2 also potently decreased plasma triglyceride (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR 1339. Meanwhile, HT-ONO2 displayed NO-releasing and antioxidant activity both in diabetic and hyperlipidemia mice and in vitro. Moreover, HT-ONO2 shown definite vasodilation and α-glucosidase inhibition activity in vitro. The results suggested that the hybrid hydroxytyrosol-based nitrate with NO supplement, antioxidant, hypoglycemia and hypolipidemia provided a potential multi-target agent to ameliorate the diabetes mellitus and its complications.


Asunto(s)
Antioxidantes/farmacología , Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Nitratos/farmacología , Óxido Nítrico/metabolismo , Alcohol Feniletílico/análogos & derivados , Administración Oral , Animales , Antioxidantes/administración & dosificación , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Hipoglucemiantes/administración & dosificación , Hipolipemiantes/administración & dosificación , Ratones , Estructura Molecular , Nitratos/administración & dosificación , Alcohol Feniletílico/administración & dosificación , Alcohol Feniletílico/farmacología , Estreptozocina
15.
Bioorg Chem ; 105: 104388, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33130343

RESUMEN

A phytochemical investigation on the stems and leaves of Wikstroemia chuii resulted in the isolation of three new daphnane diterpenes, wikstroechuins A-C (1-3), together with eight known analogues (4-11). The structures of new daphnane diterpenes (1-3) were determined on the basis of extensive spectroscopic methods and the known daphnane diterpenes (4-11) were identified by comparing their observable spectroscopic data with those reported spectral data in the literature. The anti-inflammatory effects as well as anti-HIV activities in vitro of all isolated daphnane diterpenes 1-11 were assessed. As a consequence, daphnane diterpenes 1-11 displayed remarkable inhibitory activities on NO (nitric oxide) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells showing IC50 values in the range of 0.12 ± 0.03 to 10.58 ± 0.16 µM. Meanwhile, daphnane diterpenes 1-11 displayed significant anti-HIV-1 reverse transcriptase (RT) effects showing EC50 values ranging from 0.09509 to 8.62356 µM. These research results indicated that the discovery of these new daphnane diterpenes with remarkable anti-inflammatory and anti-HIV activities from W. chuii, especially these new ones, could be extremely meaningful to the discovery of new anti-inflammatory agents and anti-HIV drugs as well as their potential practical values in the health and pharmaceutical products.


Asunto(s)
Fármacos Anti-VIH/farmacología , Antiinflamatorios no Esteroideos/farmacología , Diterpenos/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Wikstroemia/química , Animales , Fármacos Anti-VIH/química , Fármacos Anti-VIH/aislamiento & purificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , VIH/efectos de los fármacos , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Hojas de la Planta/química , Células RAW 264.7 , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/aislamiento & purificación , Relación Estructura-Actividad
16.
Appl Opt ; 59(2): 333-345, 2020 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32225311

RESUMEN

Digital holographic microscopy is becoming increasingly useful for the analysis of marine plankton. In this study, we investigate autofocusing and image fusion in digital holographic microscopy. We propose an area metric autofocusing method and an improved wavelet-based image fusion method. In the area metric autofocusing method, a hologram image is initially segmented into several plankton regions for focus plane detection, and an area metric is then applied to these regions. In the improved wavelet-based image fusion method, a marked map is introduced for labeling each plankton region with the order of refocus plane images that accounts for the most pixels. The results indicate that the area metric autofocusing method applied to each plankton region provides a higher depth resolution accuracy than a number of general autofocusing methods, and the mean accuracy increases by approximately 33%. The improved wavelet-based image fusion method can fuse more than nine reconstructed plane images at a time and effectively eliminate fringes and speckle noise, and the fused image is much clearer than that of a general wavelet-based method, a sparse decomposition method, and a pulse-coupled neural networks method. This work has practical value for plankton imaging using digital holographic microscopy.


Asunto(s)
Algoritmos , Holografía/métodos , Procesamiento de Imagen Asistido por Computador , Microscopía/métodos , Plancton/fisiología
17.
Bioorg Chem ; 92: 103278, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31541802

RESUMEN

Clausena lansium (Lour.) Skeels is an evergreen small tree or shrub with great economic value, which belongs to the genus Clausena of the Rutaceae family. C. lansium is indigenous to Southern China, while currently widely cultivated in subtropical and tropical regions not only for the nutritional value and pharmacological uses of its fruits but also as a medicinal and ornamental plant. In this study, a systematic phytochemical study on the stems and leaves of C. lansium caused the separation and identification of two new geranylated carbazole alkaloids, clauselansiumines A (1) and B (2), as well as 10 known geranylated carbazole alkaloids (3-12). The chemical structures of these isolated geranylated carbazole alkaloids (1-12) were unambiguously determined based on comprehensive spectral data analyses. All these isolated geranylated carbazole alkaloids were tested for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Compounds 1-12 displayed remarkable neuroprotective effects holding the EC50 values ranging from 0.48 ±â€¯0.04 to 12.36 ±â€¯0.16 µM. These research results disclosed that the separation and purification of these geranylated carbazole alkaloids possessing remarkable neuroprotective effects separated from C. lansium could be extremely important to the discovery of new agents for the treatment and prevention for Parkinson's disease.


Asunto(s)
Alcaloides/farmacología , Carbazoles/farmacología , Clausena/química , Fármacos Neuroprotectores/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Carbazoles/química , Carbazoles/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Hojas de la Planta/química , Tallos de la Planta/química , Relación Estructura-Actividad , Células Tumorales Cultivadas
18.
Artículo en Inglés | MEDLINE | ID: mdl-30553881

RESUMEN

The vitellogenin receptor (VgR) is highly expressed in the ovaries where it is responsible for vitellogenin (Vg) deposition during oogenesis in insects. Therefore, identifying the VgR of insect pests, and understanding the mechanism regulating its expression, could lead to the development of pest management strategies based on disrupting reproduction. We cloned and identified VgR in the cabbage beetle, Colaphellus bowringi, which is a serious pest of cruciferous vegetables in Asia. The regulation of VgR transcription by juvenile hormone (JH) was also investigated. The results show that C. bowringi VgR cDNA contains an open reading frame of 5310 bp encoding 1769 amino acid residues. Protein domain prediction indicates that C. bowringi VgR belongs to the LDLR gene superfamily, having the same group of structural domains that has been well characterized in other insects. VgR mRNA was highly expressed in the ovaries of reproductive female cabbage beetles. Knockdown of VgR reduced yolk deposition in the ovaries, increased the accumulation of Vg proteins in the hemolymph and decreased the transcription of Vg1 and Vg2 in the fat body. RNA interference and hormone challenge experiments showed that JH induced VgR transcription via the JH intracellular receptor methoprene-tolerant (Met) and the JH-responsive transcription factor Krüppel homolog 1 (Kr-h1). Our results suggest that there is a feedback loop between VgR transcription in the ovaries and Vg transcription in the fat body. JH acting through Met-Kr-h1 pathway induces the transcription of the VgR that is essential for Vg uptake and reproductive development. These findings not only reveal the potential JH signaling mechanism regulating VgR transcription, but may also contribute to the development of pest control strategies based on disrupting endocrine-regulated reproduction.


Asunto(s)
Escarabajos/genética , Proteínas del Huevo/genética , Hormonas Juveniles/fisiología , Receptores de Superficie Celular/genética , Transcripción Genética/fisiología , Animales , Clonación Molecular , Diapausa , Proteínas del Huevo/metabolismo , Femenino , Ovario/metabolismo , Filogenia , Interferencia de ARN , Receptores de Superficie Celular/metabolismo
19.
Molecules ; 24(18)2019 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-31533325

RESUMEN

In the present study, a new strategy including the combination of external appearance, chemical detection, and biological analysis was proposed for the comprehensive evaluation of safflowers in different producing areas. Firstly, 40 batches of safflower samples were classified into class I and II based on color measurements and K-means clustering analysis. Secondly, a rapid and sensitive analytical method was developed for simultaneous quantification of 16 chromaticity-related characteristic components (including characteristic components hydroxysafflor yellow A, anhydrosafflor yellow B, safflomin C, and another 13 flavonoid glycosides) in safflowers by ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP®/MS2). The results of the quantification indicate that hydroxysafflor yellow A, anhydrosafflor yellow B, kaempferol, quercetin, and safflomin C had significant differences between the two types of safflower, and class I of safflower had a higher content of hydroxysafflor yellow A, anhydrosafflor yellow B, and safflomin C as the main anti-thrombotic components in safflower. Thirdly, chemometrics methods were employed to illustrate the relationship in multivariate data of color measurements and chromaticity-related characteristic components. As a result, kaempferol-3-O-rutinoside and 6-hydroxykaempferol-3-O-ß-d-glucoside were strongly associated with the color indicators. Finally, anti-thrombotic analysis was used to evaluate activity and verify the suitability of the classification basis of safflower based on the color measurements. It was shown that brighter, redder, yellower, more orange-yellow, and more vivid safflowers divided into class I had a higher content of characteristic components and better anti-thrombotic activity. In summary, the presented strategy has potential for quality evaluation of other flower medicinal materials.


Asunto(s)
Carthamus tinctorius/química , Fenómenos Químicos , Fitoquímicos/química , Fitoquímicos/farmacología , Animales , Carthamus tinctorius/clasificación , Cromatografía Líquida de Alta Presión , Fibrinolíticos/química , Fibrinolíticos/farmacología , Geografía , Espectrometría de Masas en Tándem , Pez Cebra
20.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4129-4133, 2019 Oct.
Artículo en Zh | MEDLINE | ID: mdl-31872689

RESUMEN

Traditional Chinese medicine is planted in mountainous areas with suitable natural conditions. The planting area is complex in terrain,and the planting plots are mostly irregularly shaped. It is difficult to accurately calculate the planting area by traditional survey methods. The method of extracting Chinese herbal medicine planting area combined with remote sensing and GIS technology is of great significance for the rational development and utilization of traditional Chinese medicine resources. Taking Bletilla striata planting in Ningshan county of Shaanxi province as an example,the extraction method of planting area of traditional Chinese medicine in county was studied. High-resolution ZY-3 and GF-1 multi-spectral multi-temporal remote sensing images were used as data sources. Through field sampling,samples such as B. striata,cultivated land,forest land,water body,artificial surface,alpine meadow,etc. are collected. The spectral features,texture features and shape features of remotely identifiable objects in different planting areas and cultivated land,vegetable sheds were analyzed,confusing ground objects were eliminated and interpretation marks were establish. The method of visual interpretation is used to realize the extraction of B. striata planting areas,and the B. striata planting area are calculated by combining GIS technology. The results showed that the method of visual interpretation,using high-resolution ZY-3 and GF-1 multi-spectral multi-temporal remote sensing image data extracted the planting area of 403.05 mu. It can effectively extract the B. striata planting area in research region.


Asunto(s)
Medicina Tradicional China , Orchidaceae , Tecnología de Sensores Remotos , Bosques
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