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1.
Dev Biol ; 512: 57-69, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38750688

RESUMEN

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Proteínas Hedgehog , Larva , Metamorfosis Biológica , Desarrollo de Músculos , Mytilus , Transducción de Señal , Animales , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Mytilus/crecimiento & desarrollo , Mytilus/metabolismo , Alcaloides de Veratrum/farmacología , Músculos/metabolismo
2.
J Org Chem ; 89(4): 2637-2648, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38277477

RESUMEN

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with B2pin2 and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

3.
Ecotoxicol Environ Saf ; 277: 116339, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38669873

RESUMEN

Children's exposures to environmental antibiotics are a major public health concern. However, limited data are available on the effects of environmental antibiotic exposures on childhood obesity. Our study aimed to explore this relationship. We conducted a cross-sectional case-control study nested in a population-based survey of primary school students, including 1855 obese and 1875 random selected control children. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression was used to assess the associations between environmental antibiotics exposures and childhood obesity. After adjusting for potential confounders, increased odds of obesity were observed in children exposed to tetracycline (OR = 1.31, 95% CI: 1.09-1.57) and sulfamonomethoxine (OR = 1.43, 95% CI: 1-2.05). Comparing none (

Asunto(s)
Antibacterianos , Exposición a Riesgos Ambientales , Obesidad Infantil , Humanos , Estudios de Casos y Controles , Antibacterianos/efectos adversos , Masculino , Niño , Estudios Transversales , Femenino , Exposición a Riesgos Ambientales/estadística & datos numéricos , Obesidad Infantil/epidemiología , Obesidad Infantil/inducido químicamente , Contaminantes Ambientales/orina , Modelos Logísticos
4.
Matern Child Nutr ; : e13685, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886166

RESUMEN

Iodine, an essential trace element for the human body, plays a pivotal role in sustaining health. Malnutrition has emerged as a pressing public health concern, posing a significant threat to human well-being. Iodine deficiency poses a substantial threat to the development of children, potentially leading to neurological developmental disorders and mental retardation. Conversely, excessive iodine intake can result in structural and functional abnormalities in the thyroid gland. In this study, we selected children aged 3-6 years through a stratified cluster sampling approach in six regions across China to explore the correlation between iodine nutrition and their physical growth. A total of 5920 preschool children participated in this study, with a median urinary iodine concentration (UIC) of 177.33 [107.06, 269.92] µg/L. Among these children, 250 (4.2%) exhibited stunting, 180 (3.0%) were underweight, 198 (3.3%) experienced wasting, 787 (3.3%) were overweight and 414 (7.0%) were classified as obese. The multivariate linear regression revealed that UIC exhibited a positive correlation with body mass index z-Score (BMIZ) in overweight children (ß = 0.038; 95% CI: 0.001, 0.075). In normally growing children, the associations between UIC and height-for-age z-score, weight-for-age z-score and BMIZ displayed nonlinear patterns. Our findings suggest that iodine nutrition is adequate for Chinese children aged 3-6 years. Furthermore, iodine nutrition is intricately linked to the growth and development of these children. Consequently, it is imperative to implement decisive measures to prevent both iodine deficiency and excess.

5.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2468-2477, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38812146

RESUMEN

In order to characterize and identify the chemical components in different parts of Artemisia argyi(roots, stems, leaves, and seeds), compounds with antioxidant activity were screened. In this study, ultra-performance liquid chromatography-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt-quadrupole time-of-flight-tandem mass spectrometry(UPLC-ABTS-Q-TOF-MS) was used as an online combination technique. Poroshell 120 SB-Aq(3.0 mm×150 mm, 2.7 µm) was used as the column, and acetonitrile(A)-0.2% formic acid water(B) was adopted as the mobile phase to perform gradient elution and was scanned in positive and negative ion modes. MassLynx software was utilized, and combined with reference substances and related literature, the chemical components of different parts of A. argyi were identified and compared. The antioxidant active components were detected by using the online detection system, and the antioxidant activities of active components of different parts of A. argyi were compared and evaluated by scavenging efficiency. As a result, a total of 87 compounds were identified from extracts of different parts of A. argyi, and 38, 72, 85, and 33 components were identified from roots, stems, leaves, and seeds. 22 compounds with antioxidant activity were screened, and 14, 17, 20, and 11 compounds with antioxidant activity were identified from roots, stems, leaves, and seeds. The results show that there are certain differences in chemical components and antioxidant components of different parts of A. argyi, which provides data support for the resource utilization and further research and development of A. argyi.


Asunto(s)
Antioxidantes , Artemisia , Artemisia/química , Antioxidantes/química , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/química , Hojas de la Planta/química , Espectrometría de Masas/métodos , Ácidos Sulfónicos/química , Semillas/química , Benzotiazoles/química , Raíces de Plantas/química
6.
Eur Radiol ; 33(12): 8669-8681, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37368105

RESUMEN

OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Antineoplásicos/uso terapéutico , Quimioembolización Terapéutica/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos
7.
Biomed Chromatogr ; 37(1): e5509, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36097410

RESUMEN

Hyperlipidemia has been highlighted as one of the most prominent and global chronic conditions nowadays. Bidens bipinnata L. (BBL), a folk medicine in contemporary China, has efficacy in the treatment of hyperlipidemia (HLP) in China. Although some physiological and pathological function parameters of hyperlipidemia have been investigated, little information about the changes in small metabolites in biofluids has been reported. In the present study, global metabolic profiling with high-performance liquid chromatography-linear ion trap/Orbitrap high-resolution mass spectrometry (HPLC-LTQ/Orbitrap MS) combined with a pattern recognition method was performed to discover the underlying lipid-regulating mechanisms of BBL on hyperlipidemic rats induced by high-fat diet (HFD). The total of four metabolites, up- or down-regulated (p < 0.05 or 0.01), were identified and contributed to the progression of hyperlipidemia. These promising identified biomarkers underpin the metabolic pathway, including glyoxylate and dicarboxylate metabolism, the TCA cycle, sphingolipid metabolism and purine metabolism. They are disturbed in hyperlipidemic rats, and are identified using pathway analysis with MetPA. The altered metabolite indices could be regulated closer to normal levels after BBL intervention. The results demonstrated that urinary metabolomics is a powerful tool in the clinical diagnosis and treatment of hyperlipidemia to provide information on changes in metabolite pathways.


Asunto(s)
Bidens , Hiperlipidemias , Ratas , Animales , Ratas Sprague-Dawley , Metabolómica/métodos , Redes y Vías Metabólicas , Hiperlipidemias/metabolismo , Cromatografía Líquida de Alta Presión
8.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2868-2875, 2023 Jun.
Artículo en Zh | MEDLINE | ID: mdl-37381949

RESUMEN

With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.


Asunto(s)
Medicina , Biología de Sistemas , Humanos , Diseño de Fármacos , Desarrollo de Medicamentos , Genómica
9.
Zhongguo Zhong Yao Za Zhi ; 47(2): 499-510, 2022 Jan.
Artículo en Zh | MEDLINE | ID: mdl-35178995

RESUMEN

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1ß, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.


Asunto(s)
Microbioma Gastrointestinal , Nardostachys , Enfermedad de Parkinson , Animales , FN-kappa B/metabolismo , Nardostachys/genética , Nardostachys/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley
10.
Acta Pharmacol Sin ; 42(11): 1860-1874, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34363007

RESUMEN

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor, and 95% of patients die within 2 years after diagnosis. In this study, aiming to overcome chemoresistance to the first-line drug temozolomide (TMZ), we carried out research to discover a novel alternative drug targeting the oncogenic NFAT signaling pathway for GBM therapy. To accelerate the drug's clinical application, we took advantage of a drug repurposing strategy to identify novel NFAT signaling pathway inhibitors. After screening a set of 93 FDA-approved drugs with simple structures, we identified pimavanserin tartrate (PIM), an effective 5-HT2A receptor inverse agonist used for the treatment of Parkinson's disease-associated psychiatric symptoms, as having the most potent inhibitory activity against the NFAT signaling pathway. Further study revealed that PIM suppressed STIM1 puncta formation to inhibit store-operated calcium entry (SOCE) and subsequent NFAT activity. In cellula, PIM significantly suppressed the proliferation, migration, division, and motility of U87 glioblastoma cells, induced G1/S phase arrest and promoted apoptosis. In vivo, the growth of subcutaneous and orthotopic glioblastoma xenografts was markedly suppressed by PIM. Unbiased omics studies revealed the novel molecular mechanism of PIM's antitumor activity, which included suppression of the ATR/CDK2/E2F axis, MYC, and AuroraA/B signaling. Interestingly, the genes upregulated by PIM were largely associated with cholesterol homeostasis, which may contribute to PIM's side effects and should be given more attention. Our study identified store-operated calcium channels as novel targets of PIM and was the first to systematically highlight the therapeutic potential of pimavanserin tartrate for glioblastoma.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Inhibidores de la Calcineurina/farmacología , Señalización del Calcio/efectos de los fármacos , Glioblastoma/metabolismo , Factores de Transcripción NFATC/metabolismo , Piperidinas/farmacología , Urea/análogos & derivados , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Calcineurina/metabolismo , Inhibidores de la Calcineurina/uso terapéutico , Señalización del Calcio/fisiología , Proteínas de Unión al Calcio/antagonistas & inhibidores , Proteínas de Unión al Calcio/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Glioblastoma/tratamiento farmacológico , Células HeLa , Humanos , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Factores de Transcripción NFATC/antagonistas & inhibidores , Piperidinas/uso terapéutico , Urea/farmacología , Urea/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
11.
Biomed Chromatogr ; 35(4): e5026, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33169423

RESUMEN

Bidens bipinnata L. is a folk medicinal plant in China that shows significant antihyperlipidemia effectiveness. However, studies of the underlying mechanism study are lacking. In order to explore the potential action sites and the underlying mechanism of treating hyperlipidemic, this work undertook tissue distribution and molecular docking research on the markers of B. bipinnata L., which were obtained through serum pharmacochemistry and network database retrieval. The results showed that seven compounds (gallic acid, protocatechuic acid, rutin, hyperoside, bipinnate polyacetylenicloside, luteolin and quercetin) were screened out as markers. Owing to the diversity of chemical structures, they exhibited an inconsistent trend in tissue distribution. However, all of them had high levels in the liver and no specific distribution in other tissues. More interestingly, seven proteins-HMGCR (1HWK), NR3C1 (4P6W), CYP1A2 (2HI4), RXRA (4PP3), CES1 (1MX1), HSD11B1 (2RBE) and CYP1A1 (4I8V)-showed significant binding affinity with three or more markers, suggesting that they may be the target proteins of B. bipinnata L. This study preliminarily sheds light on the tissue distribution and targets of B. bipinnata L., providing some useful information on the underlying mechanisms of the antihyperlipidemia effect.


Asunto(s)
Bidens/química , Medicamentos Herbarios Chinos , Hiperlipidemias/metabolismo , Animales , Catequina/análisis , Catequina/farmacocinética , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/farmacocinética , Ácido Gálico/análisis , Ácido Gálico/farmacocinética , Modelos Lineales , Hígado/química , Hígado/metabolismo , Simulación del Acoplamiento Molecular , Ratas , Reproducibilidad de los Resultados , Rutina/análisis , Rutina/farmacocinética , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem , Distribución Tisular
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 844-848, 2021 Sep.
Artículo en Zh | MEDLINE | ID: mdl-34622603

RESUMEN

OBJECTIVE: To compare and analyze the clinical manifestations and sleep structure of children with obstructive sleep apnea-hypopneasyndrome (OSAHS) with different body mass index (BMI). METHODS: 452 children who were diagnosed with OSAHS between December 2016 and February 2021 by the Department of Respiratory Medicine, Children's Hospital of Soochow University were included in the study. All of them did polysomnography (PSG). They were divided, according to their BMI, into the normal BMI group, the overweight group, and the obesity group. Their clinical data and PSG results were collected. RESULTS: 287 boys (63.5%) and 165 girls (36.5%) were enrolled, with their age ranging between 3 and 15, and the median age being 5.5 (4.5, 7.0). Their BMI ranged between 12.09 kg/m 2 and 38.48 kg/m 2, with the median being 16.29 kg/m 2. 275 cases (60.8%) had normal BMI, 76 cases (16.8%) were overweight, and 101 cases (22.3%) were obese. There was no significant difference in the distribution of clinical manifestations and severity of OSAHS among the three groups. The duration and proportion of rapid eye movement (REM) stage sleep in the obese group was lower than that of the overweight and the normal BMI groups ( P<0.05). The lowest oxyhemoglobin saturation (LSaO 2) of children in the overweight group was lower than that of the normal BMI group ( P=0.050). The oxygen desaturation index (ODI) of the obese group was higher than that of the normal BMI and the overweight groups ( P<0.05). CONCLUSION: Obesity worsens the degree of hypoxia in children with OSAHS and affects their sleep structure.


Asunto(s)
Apnea Obstructiva del Sueño , Índice de Masa Corporal , Niño , Femenino , Humanos , Masculino , Polisomnografía , Sueño , Apnea Obstructiva del Sueño/complicaciones , Sueño REM
13.
J Integr Neurosci ; 19(1): 21-29, 2020 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-32259883

RESUMEN

The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.


Asunto(s)
Encéfalo/efectos de los fármacos , Broussonetia , Trastornos Cerebrovasculares/complicaciones , Disfunción Cognitiva/fisiopatología , Aprendizaje por Laberinto/efectos de los fármacos , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Memoria Espacial/efectos de los fármacos , Animales , Encéfalo/fisiopatología , Trastornos Cerebrovasculares/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/prevención & control , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Microglía/fisiología , Ratas Sprague-Dawley
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(6): 505-510, 2019 Jun.
Artículo en Zh | MEDLINE | ID: mdl-31208500

RESUMEN

OBJECTIVE: To investigate the viral etiology and allergen distribution in infants and young children at high risk of asthma during a wheezing episode. METHODS: A total of 135 infants and young children at high risk of asthma were enrolled who were admitted due to asthmatic bronchitis or asthmatic bronchopneumonia between April 2016 and August 2017. Fluorescent probe PCR was used to measure influenza A (Flu A), respiratory syncytium virus (RSV), adenovirus (ADV), parainfluenza virus (PinF), human rhinovirus (HRV), human partial lung virus (hMPV) and human bocavirus (HBoV) in nasopharyngeal aspirates. ImmunoCAP was used to measure inhaled allergens, food allergens, and total IgE concentration. RESULTS: Among the 135 patients, the overall virus detection rate of nasopharyngeal aspirates was 49.6%, and HRV had the highest detection rate of 25.2%, followed by HBoV (9.6%), RSV (8.1%), PinF (5.9%), Flu-A (3.7%), ADV (1.5%) and hMPV (0.7%). The 1-3 years group had a significantly higher detection rate of HRV than the <1 year group (P<0.05). The positive rate of allergen screening was 59.3%, with 44% for inhaled allergens and 89% for food allergens. Among the inhaled allergens, dust mites had the highest positive rate of 77%, followed by mould (37%), pollen (26%) and animal dander (9%). Among the food allergens, egg white had a positive rate of 73% and milk had a positive rate of 68%. The <1 year group had a significantly higher positive rate of inhaled allergens than the 1-3 years group (P<0.05). The 1-3 years age group had a significantly higher level of T-IgE than the <1 year group (P<0.05). The positive virus group had a significantly higher positive rate of inhaled allergens than the non-virus group (P<0.05). The children with the second wheezing episode had significantly higher positive rates of inhaled allergens and food allergens and level of T-IgE than those with the first wheezing episode (P<0.05). The children with the second wheezing episode also had significantly higher positive rates of dust mites and mould than those with the first wheezing episode (P<0.05). CONCLUSIONS: Early HRV infection and inhaled allergen sensitization are closely associated with the development of wheezing in infants and young children at high risk of asthma.


Asunto(s)
Asma , Hipersensibilidad al Huevo , Alérgenos , Animales , Niño , Preescolar , Humanos , Lactante , Pyroglyphidae , Ruidos Respiratorios
15.
Anticancer Drugs ; 29(6): 491-502, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29683800

RESUMEN

The main aim of this study was to establish a novel paclitaxel (PTX)-resistant human gastric carcinoma cell line and to investigate its biological significance. A cell line, MGC803/PTX, was established by gradually increasing PTX density on the basis of MGC803 over a period of 10 months. In addition, a pair of resistant cell lines (SW620 and SW620/PTX) were added to further explain the resistant mechanism of PTX. The drug resistance index and stability of MGC803/PTX cells were detected using the Cell Counting Kit-8 method. The morphological features were observed using inverted microscopy. Apoptosis was measured by flow cytometry (FCM) and Hoechst 33258 fluorescence staining. The distribution of the cell cycle was determined by FCM, and protein expressions of P-gp, Bcl-2, Bax, and PARP were detected by western blot analysis. When characterizing the resistance in vitro, we found that MGC803/PTX cells were 10.3-fold more resistant to PTX compared with MGC803 cells. In addition, MGC803/PTX cells showed cross-resistance to 5-fluorouracil and adriamycin. FCM and Hoechst 33258 fluorescence staining indicated that MGC803/PTX cells had a significantly lower percentage of apoptotic cells after treatment with PTX compared with MGC803 cells. Other differences between parental cells and resistant cells included morphology, proliferation rate, doubling time, cell cycle distribution, and colony-formation rate. Western blot analysis indicated that P-gp, Bcl-2, and PARP protein were more abundant in MGC803/PTX and SW620/PTX cells compared with MGC803 and SW620 cells, whereas Bax protein levels were lower in resistant cells. Furthermore, MGC803/PTX cells showed obvious resistance to PTX in vivo. To our knowledge, this is the first report on the establishment of a PTX-resistant MGC803 cell line, which is an important tool to explore the resistance of anticancer drugs and to overcome tumor drug resistance.


Asunto(s)
Línea Celular Tumoral , Paclitaxel/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Procesos de Crecimiento Celular/efectos de los fármacos , Procesos de Crecimiento Celular/fisiología , Resistencia a Antineoplásicos , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Fenotipo , Distribución Aleatoria , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Fish Shellfish Immunol ; 76: 380-390, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29475049

RESUMEN

Galactoside-binding lectins, also known as galectins, play crucial roles in innate immune response in invertebrates. In this study, three cDNA sequences from Hyriopsis cumingii were identified and collectively called HcGalec genes. Each of the three deduced HcGalec proteins contained a galactose-binding lectin domain or a GLECT domain. All the three HcGalec genes are mainly present in the hepatopancreas and gills, and their expression is induced at 24 h after bacterial challenge. Three recombinant HcGalec proteins can bind and agglutinate (Ca2+-dependent) various microorganisms, including Gram-positive and Gram-negative bacteria. These proteins can attach to mannan and peptidoglycan. Meanwhile, the expression of the three HcGalec genes in the gills were significantly down-regulated after dsRNA interference (HcGalec1-RNAi, HcGalec2-RNAi, and HcGalec3-RNAi) and Vibrio parahaemolyticus injection. The expression levels of some antimicrobial peptides, including lysozyme 1 and lysozyme 2, were also markedly decreased after dsRNA interference. Overall, these results suggested that these three HcGalec proteins may function as potential receptors participating in the innate immune responses of H. cumingii against bacterial infection.


Asunto(s)
Galectinas/genética , Galectinas/inmunología , Inmunidad Innata/genética , Receptores de Reconocimiento de Patrones/genética , Receptores de Reconocimiento de Patrones/inmunología , Unionidae/genética , Unionidae/inmunología , Animales , Perfilación de la Expresión Génica , Bacterias Gramnegativas/fisiología , Bacterias Grampositivas/fisiología
17.
Am J Emerg Med ; 36(5): 910.e1-910.e4, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29519759

RESUMEN

There is often a delay in offering quality and prompt treatment after a stingray sting. We present 3 cases of stings and discuss the Poisoning Severity Score (PSS) and a simple tool to assess the severity of such injuries. A 34-year-old man, who worked as an aquarium keeper, presented a wound on the left fifth digit caused by a stingray. Acute myocardial injury and rhabdomyolysis were detected. After 6weeks, the wound had almost healed. A 27-year-old man who experienced a stingray injury on the left second digit recovered without sequelae after 5weeks. A 45-year-old man with a history of diabetes, who was accidentally stung in the right palm by a stingray, experienced rhabdomyolysis and returned to work after 2months. We performed debridement, administered the tetanus toxoid and antibiotics, and immersed the wounded hand in warm water (about 43°C) for all three cases. Meanwhile, patients with rhabdomyolysis were administered intravenous hydration. Upon presentation at the emergency department, we recorded the severity of the injury by using PSS. We found that relatively high PSSs were associated with lower platelet counts that happen due to various adverse events. We suggest that dynamic changes in platelet counts may be associated with the severity of the injury. Furthermore, lower platelet counts in the normal or abnormal range may indicate poor prognoses.


Asunto(s)
Mordeduras y Picaduras/sangre , Recuento de Plaquetas/clasificación , Rajidae , Adulto , Animales , Traumatismos de la Mano/sangre , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Factores de Tiempo
18.
Molecules ; 23(2)2018 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-29473874

RESUMEN

G-quadruplexes are four-stranded nucleic acid secondary structures that are formed in guanine-rich sequences. G-quadruplexes are widely distributed in functional regions of the human genome and transcriptome, such as human telomeres, oncogene promoter regions, replication initiation sites, and untranslated regions. Many G-quadruplex-forming sequences are found to be associated with cancer, and thus, these non-canonical nucleic acid structures are considered to be attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this mini review, we summarize recent advances made by our lab in the study of G-quadruplex-targeted natural alkaloids and their derivatives toward the development of potential anticancer agents.


Asunto(s)
Alcaloides/química , Alcaloides/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , G-Cuádruplex , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Diseño de Fármacos , Humanos , Ligandos , Oncogenes , Regiones Promotoras Genéticas , ARN/química , ARN/genética , Relación Estructura-Actividad
19.
Zhongguo Zhong Yao Za Zhi ; 43(12): 2570-2574, 2018 Jun.
Artículo en Zh | MEDLINE | ID: mdl-29950077

RESUMEN

The present research aimed to establish an associated two-dimensional fingerprint of Huanglian between characteristic chemical composition and antioxidant activity, which was applied to on-line screen the active constituents. In this study, the HPLC-ABTS-DAD-Q-TOF/MS method, which can simultaneously identify individual components and rapidly screen for antioxidant compounds, was used to screen and identify antioxidant components in Huanglian. Fourteen compositions were discovered, and eight of them displayed antioxidant activity. The antioxidant activity of different ingredients was evaluated by antioxidant efficiency. The data showed that 2, 3, 4-trihydroxy phenylpropionic acid, chlorogenic acid, ferulic acid, cularine, 3-O-feruloylquinic acid and feruloyltyramine showed stronger antioxidant activity than that of alkaloids. These experimental data can provide data support for the basic research of the antioxidant ingredients of Huanglian.


Asunto(s)
Antioxidantes/farmacología , Medicamentos Herbarios Chinos/farmacología , Cromatografía Líquida de Alta Presión
20.
J Am Chem Soc ; 139(11): 3966-3969, 2017 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-28257193

RESUMEN

A series of pyridine-type ligands containing C≡C bonds were designed and synthesized for selective oxidative Heck reaction. These ligands were utilized as functional units and integrated into the skeleton of conjugated microporous polymers. 6,6'-diiodo-2,2'-bipyridine and 1,3,5-triethynylbenzene were polycondensed via Sonogashira cross-coupling strategy to afford CMP-1 material. The resultant CMP-1 was used as a heterogeneous catalytic ligand for the PdII-catalyzed oxidative Heck reaction with high linear selectivity. The linear selectivity of CMP-1 is about 30 times higher than that of bipyridine-based monomer ligand. This work opens a new front of using CMP as an intriguing platform for developing highly efficient catalysts in controlling the regioselectivity in organic reactions.

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