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1.
Catheter Cardiovasc Interv ; 101(6): 967-972, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36881746

RESUMEN

OBJECTIVES: We aimed to evaluate the long-term outcomes of the novel NeoVas sirolimus-eluting bioresorbable scaffold (BRS) for the treatment of de novo coronary artery disease. BACKGROUND: The long-term safety and efficacy of the novel NeoVas BRS are still needed to be elucidated. METHODS: A total of 1103 patients with de novo native coronary lesions for coronary stenting were enrolled. The primary endpoint of target lesion failure (TLF) was defined as a composite of cardiac death (CD), target vessel myocardial infarction (TV-MI), or ischemia-driven-target lesion revascularization (ID-TLR). RESULTS: A three-year clinical follow-up period was available for 1,091 (98.9%) patients. The cumulative TLF rate was 7.2% with 0.8% for CD, 2.6% for TV-MI, and 5.1% for ID-TLR. Additionally, 128 (11.8%) patient-oriented composite endpoint and 11 definite/probable stent thromboses (1.0%) were recorded. CONCLUSIONS: The extended outcomes of the NeoVas objective performance criterion trial demonstrated a promising 3-year efficacy and safety of the NeoVas BRS in low-risk patients with low complexity in terms of lesions and comorbidities.


Asunto(s)
Fármacos Cardiovasculares , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Sirolimus/efectos adversos , Implantes Absorbibles , Estudios Prospectivos , Resultado del Tratamiento , Infarto del Miocardio/etiología , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea/efectos adversos , Fármacos Cardiovasculares/efectos adversos
2.
Phytopathology ; 113(10): 1853-1866, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37311718

RESUMEN

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.


Asunto(s)
Malus , Malus/microbiología , Antifúngicos/farmacología , Antifúngicos/metabolismo , Proteínas de Plantas/metabolismo , Enfermedades de las Plantas/microbiología , Té/metabolismo
3.
J Asian Nat Prod Res ; 25(11): 1051-1057, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37010914

RESUMEN

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.


Asunto(s)
Cassia , Cinnamomum aromaticum , Cinnamomum aromaticum/química , Antioxidantes/farmacología , Corteza de la Planta/química , Extractos Vegetales/química
4.
Immunology ; 167(2): 221-232, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35751471

RESUMEN

Neutralizing antibody is an important indicator of vaccine efficacy, of which IgG is the main component. IgG can be divided into four subclasses. Up to now, studies analysing the humoral response to SARS-CoV-2 vaccination have mostly focused on measuring total IgG, and the contribution of specific IgG subclasses remains elusive. The aim of this study is to investigate the kinetics of neutralizing antibodies and IgG subclasses, and to explore their relationships in people vaccinated with inactivated COVID-19 vaccine. We conducted a prospective cohort study in 174 healthy adults aged 18-59 years old who were administrated 2 doses of CoronaVac 14 days apart and a booster dose 1 year after the primary immunization, and followed up for 15 months. Blood samples were collected at various time points after primary and booster immunization. We used live SARS-CoV-2 virus neutralizing assay to determine neutralizing ability against the wild-type strain and 4 variants (Beta, Gamma, Delta and Omicron) and ELISA to quantify SARS-CoV-2 RBD-specific IgG subclasses. The results showed that the 2-dose primary immunization only achieved low neutralizing ability, while a booster shot can significantly enhance neutralizing ability against the wild-type strain, Beta, Gamma, Delta and Omicron variants. IgG1 and IgG3 were the most abundant serum antibodies, and IgG2 and IgG4 were hardly detected at any time. The ratio of IgG1/IgG3 was positively associated with the neutralization ability. The underlying mechanism requires further exploration.


Asunto(s)
COVID-19 , Vacunas Virales , Adolescente , Adulto , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunoglobulina G , Cinética , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2 , Vacunas de Productos Inactivados , Adulto Joven
5.
BMC Cardiovasc Disord ; 22(1): 307, 2022 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-35799104

RESUMEN

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.


Asunto(s)
Insuficiencia Cardíaca , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Pronóstico , Factores de Riesgo
6.
J Nat Prod ; 85(10): 2312-2331, 2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36137221

RESUMEN

Twenty new malabaricane triterpenoids, astramalabaricosides A-T (1-20), were isolated from the roots of Astragalus membranaceus var. mongholicus (Astragali Radix). Their structures were determined by spectroscopic analysis, and the use of the circular dichroism exciton chirality method, quantum chemical calculations, and chemical methods. Malabaricane triterpenoids, an unusual group with the 6-6-5-tricyclic core, are distributed in plants (e.g., Simaroubaceae, Polypodiaceae, and Fabaceae), a marine sponge, and fungi, and their number obtained to date is limited. Compounds 1-20 were characterized as glycosides with a highly oxygenated side chain, and 13-20 were the first cyclic carbonate derivatives among the malabaricane triterpenoids. The stereocluster formed from the continuous hydroxylated chiral carbons in each highly oxygenated side chain and the 6-6-5-tricyclic core system were entirely segregated, and the independent identification of their stereoconfigurations required considerable effort. The migratory inhibitory and antiproliferative activities of 1-20 were evaluated by wound-healing and cell-viability assays, respectively. Most compounds showed significant migratory inhibitory activity, and a preliminary structure-activity relationship was developed. Malabaricane triterpenoids are being reported in the genus Astragalus for the first time.


Asunto(s)
Planta del Astrágalo , Triterpenos , Astragalus propinquus/química , Triterpenos/farmacología , Triterpenos/análisis , Raíces de Plantas/química
7.
Bioorg Chem ; 116: 105307, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34482167

RESUMEN

Eight new (1-7 and 15) and 18 known (8-14 and 16-26) phenylpropanoid derivatives were isolated from the fruits of Lycium ruthenicum Murr. (black wolfberry). Their structures were determined by comprehensive spectroscopic analyses, chemical methods, and comparisons of spectroscopic data. Four known compounds (16, 17, 24, and 26) were firstly isolated from the genus Lycium. Interestingly, compounds 1/2 and 4/5 were isolated as two pairs of inseparable anomers owing to the tautomerism of the free hemiacetal at C-1'' in solution. The antioxidant, α-glucosidase inhibitory, and acetylcholinesterase (AChE) inhibitory activities of compounds 1-26 were evaluated. Some compounds possessed DPPH radical scavenging activity, and all compounds (1-26) exhibited different levels of oxygen radical absorbance capacity (ORAC). One compound displayed α-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).


Asunto(s)
Antioxidantes/farmacología , Inhibidores de la Colinesterasa/farmacología , Frutas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Lycium/química , Propionatos/farmacología , Acetilcolinesterasa/metabolismo , Antioxidantes/síntesis química , Antioxidantes/química , Compuestos de Bifenilo/antagonistas & inhibidores , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Relación Dosis-Respuesta a Droga , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/química , Estructura Molecular , Picratos/antagonistas & inhibidores , Propionatos/síntesis química , Propionatos/química , Relación Estructura-Actividad , alfa-Glucosidasas/metabolismo
8.
Ecotoxicol Environ Saf ; 212: 111984, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33517036

RESUMEN

As a natural enemy of green peach aphids, harlequin ladybirds, Harmonia axyridis Pallas (Coleoptera: Coccinellidae), are also indirectly affected by azadirachtin. In this study, we evaluated the effects of ladybird exposure to azadirachtin through azadirachtin-treated aphids. About 2 mg/L azadirachtin treated aphid can deliver the azadirachtin to ladybird larvae in 12 and 24 h. And azadirachtin treatment affected the rate at which fourth instar larvae and adult ladybirds preyed on aphids. Furthermore, the antifeedant effect increased with increasing azadirachtin concentrations. Twelve hours after exposing fourth instar ladybird larvae to aphids treated with 10 mg/L azadirachtin, the antifeedant effect was 47.70%. Twelve hours after exposing adult ladybirds to aphids treated with 2 mg/L azadirachtin, the antifeedant effect was 67.49%. Forty-eight hours after exposing ladybird larvae to azadirachtin-treated aphids, their bodyweights were 8.37 ± 0.044 mg (2 mg/L azadirachtin), 3.70 ± 0.491 mg (10 mg/L azadirachtin), and 2.39 ± 0.129 mg (50 mg/L azadirachtin). Treatment with azadirachtin affected the ability of ladybirds to prey on aphids. The results indicated that the instant attack rate of ladybird larvae and adults and the daily maximum predation rate were reduced by azadirachtin treatment. Superoxide dismutase (SOD), peroxidase (POD), and peroxide (CAT) enzyme activities of ladybirds were affected after feeding on aphids treated with azadirachtin. Azadirachtin has certain antifeedant effects on ladybirds and affects the ability of ladybirds to prey on aphids and the activities of SOD, POD, and CAT enzymes, which results in inhibition of normal body development.


Asunto(s)
Áfidos/fisiología , Escarabajos/enzimología , Limoninas/toxicidad , Conducta Predatoria/efectos de los fármacos , Animales , Escarabajos/efectos de los fármacos , Escarabajos/crecimiento & desarrollo , Escarabajos/fisiología , Larva/crecimiento & desarrollo , Pisum sativum
9.
Pestic Biochem Physiol ; 173: 104778, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33771257

RESUMEN

Azadirachtin is a good growth inhibitor for Lepidopteran larvae, but its effect on the brain neurons, intestinal flora and intestinal contents caused by the growth inhibition mechanism has not been reported yet. This study explored the mechanism of azadirachtin on the growth and development of Spodoptera litura larvae and brain neurons through three aspects: intestinal pathology observation, intestinal flora sequencing, and intestinal content analysis. The results showed that the treatment of azadirachtin led to the pathological changes in the structure of the midgut and the goblet cells in the intestinal wall cells to undergo apoptosis. Changes in the host environment of the intestinal flora lead to changes in the abundance value of the intestinal flora, showing an increase in the abundance value of harmful bacteria such as Sphingomonas and Enterococcus, as well as an increase in the abundance value of excellent flora such as Lactobacillus and Bifidobacterium. Changes in the abundance of intestinal flora will result in changes in intestinal contents and metabolites. The test results show that after azadirachtin treatment, the alkane compounds in the intestinal contents of the larvae are greatly reduced, and the number of the long carbon chain and multi-branched hydrocarbon compounds is increased, unsaturated fatty acids, silicon­oxygen compounds and ethers. The production of similar substances indicates that azadirachtin has an inhibitory effect on digestive enzymes in the intestines, which results in the inhibition of substance absorption and energy transmission, and ultimately the inhibition of larval growth and brain neurons.


Asunto(s)
Contenido Digestivo , Microbioma Gastrointestinal , Animales , Encéfalo , Intestinos , Larva , Limoninas , Neuronas , Spodoptera
10.
Ecotoxicol Environ Saf ; 194: 110391, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32155480

RESUMEN

Corpse-removal behavior of the red imported fire ant (RIFA) and the effects of lethal substances on RIFA signal communication were investigated in this study. The RIFA corpses, obtained through freezing, ether, 0.25 mg/L thiamethoxam, and starvation to death treatments, and naturally dead red fire ants were subjected to gas chromatography-mass spectrometry to identify the cuticular hydrocarbon profiles that had an effect on the corpse-removal behavior. The results showed that lethal toxic substances altered the epidermal compounds of RIFA and affected their corpse-removal behavior. Lethal toxic substances increased the number of worker touches with corpses and identification time of corpses. In addition, the content of piperidine (1,1'-(1,2-ethanediyl)bis-) on the surface of the corpse was different following the various treatments. Contamination with toxic substances resulted in the increased secretion of piperidine and led to increased identification time of corpses, number of touch with corpses, and total time for removal of corpses. Piperidine content was higher under conditions of natural death (4.67 ± 0.55%) and with thiamethoxam (10.43 ± 0.78%), freezing (0.83 ± 0.25%), and ether treatment (12.50 ± 0.70%) than under starvation treatment (0). The higher content of piperidine led to a longer number of touches with corpses and identification time. Piperidine compounds may be an element in warning information, which could affect the occurrence of different corpse-removal behaviors.


Asunto(s)
Hormigas/fisiología , Conducta Animal/fisiología , Epidermis/química , Piperidinas/análisis , Conducta Social , Animales , Hormigas/química , Hormigas/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Cadáver , Congelación , Cromatografía de Gases y Espectrometría de Masas , Insecticidas/farmacología , Piperidinas/química , Inanición , Tiametoxam/farmacología
11.
J Asian Nat Prod Res ; 22(10): 905-913, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32654511

RESUMEN

Three new (1-3) and 11 known (4-14) cycloartane-type triterpenoids were isolated from the root of Astragalus membranaceus var. mongholicus. Their structures were determined by spectroscopic analyses and chemical methods. Cycloartane-type triterpenoids are a class of major bioactive constituents in the root of A. membranaceus var. mongholicus, and the discovery of compounds 1-3 added new members of this kind of natural product. [Formula: see text].


Asunto(s)
Astragalus propinquus , Triterpenos , Estructura Molecular
12.
J Asian Nat Prod Res ; 22(8): 746-753, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31163996

RESUMEN

Zeaxanthin dipalmitate (3) and two zeaxanthin dipalmitate derivatives, including one new compound (1), were obtained from wolfberry [the fruit of Lycium barbarum L. (Solanaceae)]. Their structures were unambiguously elucidated by spectroscopic analyses. Compound 2 is isolated from the genus Lycium for the first time, and its 1D/2D NMR data are firstly reported. All the compounds belong to carotenoids which are a kind of major bioactive constituents in wolfberry and are also responsible for wolfberry's red color.


Asunto(s)
Lycium , Frutas , Estructura Molecular , Palmitatos , Xantófilas
13.
J Nat Prod ; 80(11): 3010-3013, 2017 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-29099182

RESUMEN

Houttuynoid M (1), a new houttuynoid, and the related known compound houttuynoid A (2) were isolated from Houttuynia cordata. Their structures were defined using NMR data analysis, HR-MSn experiment, and chemical derivatization. Houttuynoid M is the first example of a houttuynoid with a bis-houttuynin chain tethered to a flavonoid core. A putative biosynthetic pathway of houttuynoid M (1) is proposed. The anti-herpes simplex virus (anti-HSV) activities of 1 and 2 (IC50 values of 17.72 and 12.42 µM, respectively) were evaluated using a plaque formation assay with acyclovir as the positive control.


Asunto(s)
Antivirales/aislamiento & purificación , Antivirales/farmacología , Flavonoides/aislamiento & purificación , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Houttuynia/química , Aciclovir/farmacología , Aldehídos/química , Antivirales/química , Medicamentos Herbarios Chinos/química , Flavonoides/química , Flavonoides/farmacología , Glicósidos/química , Estructura Molecular
14.
J Nat Prod ; 80(11): 2923-2929, 2017 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-29116780

RESUMEN

Eight new (1a/1b, 2a, 3a, 4a/4b, and 5a/5b) and seven known (2b, 3b, and 6-10) asarone-derived phenylpropanoids, a known asarone-derived lignan (12), and four known lignan analogues (11 and 13-15) were isolated from the rhizome of Acorus tatarinowii Schott. The structures were elucidated via comprehensive spectroscopic analyses, modified Mosher's method, and quantum chemical calculations. Compounds 1-8 were present as enantiomers, and 1-5 were successfully resolved via chiral-phase HPLC. Compounds 1a/1b were the first cases of asarone-derived phenylpropanoids with an isopropyl C-3 side-chain tethered to a benzene core from nature. Hypoglycemic, antioxidant, and AChE inhibitory activities of 1-15 were assessed by the α-glucosidase inhibitory, ORAC, DPPH radical scavenging, and AChE inhibitory assays, respectively. All compounds except 3a showed α-glucosidase inhibitory activity. Compound 3b has the highest α-glucosidase inhibitory effect with an IC50 of 80.6 µM (positive drug acarbose IC50 of 442.4 µM). In the antioxidant assays, compounds 13-15 exhibited ORAC and DPPH radical scavenging activities. The results of the AChE inhibitory assay indicated that all compounds exhibited weak AChE inhibitory activities.


Asunto(s)
Acorus/química , Anisoles/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Inhibidores de la Colinesterasa/farmacología , Medicamentos Herbarios Chinos/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Fenilpropionatos/aislamiento & purificación , Fenilpropionatos/farmacología , Derivados de Alilbenceno , Antioxidantes/análisis , Inhibidores de la Colinesterasa/química , Cromatografía Líquida de Alta Presión , Inhibidores de Glicósido Hidrolasas/química , Lignanos/química , Estructura Molecular , Fenilpropionatos/química , Rizoma/química , Estereoisomerismo , alfa-Glucosidasas/efectos de los fármacos
15.
Xenobiotica ; 47(4): 284-289, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27237303

RESUMEN

1. A filamentous fungus, Cunninghamella blakesleeana CGMCC 3.970, was applied as a microbial system to mimic mammalian metabolism of 4,5-dimethoxyl-canthin-6-one (1). Compound 1 belongs to canthin-6-one type alkaloids, which is a major bioactive constituent of a traditional Chinese medicine (the stems of Picrasma quassioides). 2. After 72 h of incubation in potato dextrose broth, 1 was metabolized to seven metabolites as follows: 4-methoxyl-5-hydroxyl-canthin-6-one (M1), 4-hydroxyl-5-methoxyl-canthin-6-one (M2), canthin-6-one (M3), canthin-6-one N-oxide (M4), 10-hydroxyl-4,5-dimethoxyl-canthin-6-one (M5), 1-methoxycarbonl-ß-carboline (M6), and 4-methoxyl-5-O-ß-D-glucopyranosyl-canthin-6-one (M7). 3. The structures of metabolites were determined using spectroscopic analyses, chemical methods, and comparison of NMR data with those of known compounds. Among them, M7 was a new compound. 4. The metabolic pathways of 1 were proposed, and the metabolic processes involved phase I (O-demethylation, dehydroxylation, demethoxylation, N-oxidation, hydroxylation, and oxidative ring cleavage) and phase II (glycosylation) reactions. 5. This was the first research on microbial transformation of canthin-6-one alkaloid, which could be a useful microbial model for producing the mammalian phase I and phase II metabolites of canthin-6-one alkaloids. 6. 1, M1-M5, and M7 are canthin-6-one alkaloids, whereas M6 belongs to ß-carboline type alkaloids. The strain of Cunninghamella blakesleeana can supply an approach to transform canthin-6-one type alkaloids into ß-carboline type alkaloids.


Asunto(s)
Biotransformación , Carbolinas/metabolismo , Cunninghamella/metabolismo , Alcaloides Indólicos/metabolismo
16.
PLoS Genet ; 10(10): e1004644, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25329901

RESUMEN

Axonal transport of synaptic vesicles (SVs) is a KIF1A/UNC-104 mediated process critical for synapse development and maintenance yet little is known of how SV transport is regulated. Using C. elegans as an in vivo model, we identified SAM-4 as a novel conserved vesicular component regulating SV transport. Processivity, but not velocity, of SV transport was reduced in sam-4 mutants. sam-4 displayed strong genetic interactions with mutations in the cargo binding but not the motor domain of unc-104. Gain-of-function mutations in the unc-104 motor domain, identified in this study, suppress the sam-4 defects by increasing processivity of the SV transport. Genetic analyses suggest that SAM-4, SYD-2/liprin-α and the KIF1A/UNC-104 motor function in the same pathway to regulate SV transport. Our data support a model in which the SV protein SAM-4 regulates the processivity of SV transport.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de la Membrana/metabolismo , Vesículas Sinápticas/metabolismo , Animales , Animales Modificados Genéticamente , Transporte Axonal/genética , Sitios de Unión , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Péptidos y Proteínas de Señalización Intercelular , Proteínas de la Membrana/genética , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuritas/metabolismo , Neuronas/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo
17.
J Recept Signal Transduct Res ; 36(5): 459-64, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26671640

RESUMEN

Rap2b, a member of the guanosine triphosphate-binding proteins, is widely up-regulated in many types of tumors. However, the functional role of Rap2b in tumorigenesis of lung cancer remains to be fully elucidated. In this study, we investigated the effect of Rap2b on the lung cancer malignant phenotype, such as cell proliferation and metastasis. We found that Rap2b could promote the abilities of lung cancer cell wound healing, migration, and invasion via increasing matrix metalloproteinase-2 enzyme activity. Furthermore, Rap2b overexpression could increase the phosphorylation level of extracellular signal-regulated protein kinases 1/2. In conclusion, our results suggested that Rap2b may be a potential therapeutic target for lung cancer.


Asunto(s)
Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Pulmonares/genética , Proteínas de Unión al GTP rap/biosíntesis , Células A549 , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/patología , Metaloproteinasa 2 de la Matriz/biosíntesis , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Proteínas de Unión al GTP rap/genética
18.
Development ; 138(1): 87-96, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21115607

RESUMEN

Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the Caenorhabditis elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian single-stranded DNA-binding protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation, as well as positioning of, a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted colocalization of active zone and synaptic vesicles. SAM-10 functions coordinately with Lim domain-binding protein 1 (LDB-1), demonstrated by our observations that: (1) mutations in either gene show similar defects in PLM neurons; and (2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriología , Diferenciación Celular/fisiología , Neuritas/metabolismo , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Diferenciación Celular/genética , Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Microscopía , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sinapsis/metabolismo
19.
Environ Toxicol ; 29(11): 1236-44, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23436320

RESUMEN

Microcystin-LR (MC-LR) is a potent inhibitor of protein phosphatases 1 and 2A, and has potent hepatotoxicity and tumor promotion activity. Numerous studies on MC-LR toxicity have been conducted in rat hepatocytes, but few studies of the effects of microcystins on human hepatocytes have been done. In this study, HL7702 cells (a human normal liver cell line) were incubated in MC-LR for 24 h. The existence of MC-LR in HL7702 cells was confirmed. Furthermore, PP2A activity and the alteration of PP2A subunits were assessed. The results show that PP2A activity decreased from the concentration of 1 µM MC-LR, showing a concentration-dependent decline, to about 34% at 10 µM MC-LR. This activity undergone opposite change with alternations of phosphorylated Y307-PP2A/C and PP2A/C subunit but showed same change with the alteration of the ratio of methylated L309-PP2A/C to PP2A/C. B55α, a regulatory subunit of PP2A, was slightly increases in cells treated with the highest concentration of MC-LR (10 µM), and colocalized increasedly with rearranged-microtubules after 1 µM MC-LR exposure. However, the proportion of early apoptotic cells did not show any change at various concentration of MC-LR for 24 h. To our knowledge, this is the first report showing MC-LR-induced alteration of PP2A phosphatase in human cultured hepatocytes, and the mechanism of action seems to be similar as described before in vitro. The alteration of PP2A and microtubule seems to be the early event induced by MC-LR exposure.


Asunto(s)
Hepatocitos/efectos de los fármacos , Hígado/efectos de los fármacos , Microcistinas/toxicidad , Proteína Fosfatasa 2/metabolismo , Línea Celular , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Hígado/citología , Hígado/metabolismo , Toxinas Marinas , Microtúbulos/efectos de los fármacos , Microtúbulos/metabolismo , Fosforilación , Subunidades de Proteína/metabolismo
20.
Front Endocrinol (Lausanne) ; 15: 1378291, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38868747

RESUMEN

Introduction: Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes. Methods: Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. Results: Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies. Discussion: Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.


Asunto(s)
Modelos Animales de Enfermedad , Receptor del Péptido 1 Similar al Glucagón , Liraglutida , Osteoporosis , Liraglutida/uso terapéutico , Liraglutida/farmacología , Animales , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoporosis/patología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Densidad Ósea/efectos de los fármacos
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