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1.
Front Physiol ; 15: 1364632, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887320

RESUMEN

Purpose: This review aimed to assess the impact of different exercise dosages on cognitive function in individuals with post-stroke cognitive impairment (PSCI). Methods: Four electronic databases-Embase, PubMed, Web of Science, and Cochrane Library-were systematically searched from inception to 01 January 2024, focusing on the impact of exercise therapy on cognitive function in individuals with PSCI. Only randomized controlled trials meeting the criteria were included. The exercise therapy dose and adherence were evaluated following the American College of Sports Medicine (ACSM) guidelines, categorized into a high compliance group with ACSM recommendations and a low or uncertain compliance group. A random-effects model compared the effect of ACSM compliance on cognitive function in individuals with PSCI, with the effect size represented by the standardized mean difference (SMD) and a 95% confidence interval (CI). Results: In total, 18 studies meeting the criteria were included, with data from 1,742 participants. The findings suggested a beneficial effect of exercise on cognitive function in individuals with PSCI [SMD = 0.42, 95% CI (0.20, 0.65)]. Ten studies were categorized as the "high adherence group" and eight in the "low or uncertain adherence group" based on the ACSM recommendations. The subgroup analysis revealed that the SMD of the high compliance group was 0.46 (95% CI: 0.10, 0.82) (p = 0.01), while the SMD of the low or uncertain compliance group was 0.38 (95% CI: 0.07, 0.70) (p = 0.02). Conclusion: Our study indicates the beneficial impact of exercise for patients with PSCI over no exercise. Furthermore, high adherence to the exercise dose recommended by ACSM guidelines demonstrated a more substantial improvement in cognitive function than low or uncertain adherence in patients with PSCI. Systematic Review Registration: https:// www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023487915.

2.
Arab J Gastroenterol ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38755047

RESUMEN

BACKGROUND AND STUDY AIMS: The integration of traditional Chinese medicine and Western medicine holds promise for the treatment of gastrointestinal disorders, which are influenced by intestinal microbiota and metabolites. This study reports a possible mechanism for the combination of Simo Decoction and Golden Bifid in functional dyspepsia (FD) by regulating intestinal microbiota and short-chain fatty acids (SCFAs). PATIENTS AND METHODS: A mouse model of food stagnation was constructed and treated with Simo Decoction combined with different concentrations of Golden Bifid. Meta-genomics sequencing was conducted to analyze the cecum contents of the mice. Following analyses of the composition and abundance of intestinal microbiota, gas chromatography-mass spectrometry was performed to measure SCFAs in the colonic content of mice. Finally, ELISA was utilized to determine the levels of pro-inflammatory factors in the duodenal mucosa of mice and the infiltration of eosinophils in the duodenum was observed by immunohistochemical staining. RESULTS: Combination of Simo Decoction and Golden Bifid more significantly alleviated dyspepsia in mice with food stagnation compared with Simo Decoction alone. The optimal ratio of combined treatment was 0.0075 mL/g (body weight) Simo Decoction and 0.0032 mg/g (body weight) Golden Bifid. The combined treatment increased the abundance of Bifidobacterium and Bacteroides in the intestine. The levels of SCFAs in the colonic contents of mice were increased after the combined treatment, contributing to diminished pro-inflammatory factors in the duodenal mucosa and reduced eosinophil infiltration. CONCLUSION: Combination of Simo Decoction and Golden Bifid increases the abundance of Bacteroides and Bifidobacterium and promotes the production of SCFAs, which is instrumental for alleviation of FD.

3.
Prep Biochem Biotechnol ; : 1-11, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38592940

RESUMEN

We established an efficient method using high-speed countercurrent chromatography (HSCCC) combined with preparative high-performance liquid chromatography (prep-HPLC) for isolating and purifying Gelsemium elegans (G. elegans) alkaloids. First, the two-phase solvent system composed of 1% triethylamine aqueous solution/n-hexane/ethyl acetate/ethanol (volume ratio 4:2:3:2) was employed to separate the crude extract (350 mg) using HSCCC. Subsequently, the mixture that resulted from HSCCC was further separated by Prep-HPLC, resulting in seven pure compounds including: 14-hydroxygelsenicine (1, 12.1 mg), sempervirine (2, 20.8 mg), 19-(R)-hydroxydihydrogelelsevirine (3, 10.1 mg), koumine (4, 50.5 mg), gelsemine (5, 32.2 mg), gelselvirine (6, 50.5 mg), and 11-hydroxyhumanmantenine (7, 12.5 mg). The purity of these seven compounds were 97.4, 98.9, 98.5, 99, 99.5, 96.8, and 85.5%, as determined by HPLC. The chemical structures of the seven compounds were analyzed and confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear magnetic resonance (1H NMR), and 13 C-nuclear magnetic resonance (13 C NMR) spectra. The results indicate that the HSCCC-prep-HPLC method can effectively separate the major alkaloids from the purified G. elegans, holding promising prospects for potential applications in the separation and identification of other traditional Chinese medicines.

4.
Heliyon ; 10(3): e25095, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38317955

RESUMEN

Knowledge-intensive service industry has become an important part of social economy, which not only promotes the innovation of modern service industry, but also promotes the upgrading and transformation of manufacturing industry. The agglomeration of knowledge-intensive service industry is not only the inevitable result of economic growth, but also the premise of sustained economic growth. Moreover, China's national economy is transforming from an industrialized economy to a service-oriented and knowledge-based economy, and the importance of knowledge-intensive service industry is increasing day by day. This paper constructs a theoretical framework of the influence of population agglomeration on the economic development of urban agglomerations. The article holds that population agglomeration promotes the economic development of urban agglomerations through the upgrading of industrial structure and the promotion of human capital. In the future, we need to focus on the similarities and differences between population agglomeration and economic development of urban agglomerations in central China, explore the factors of economic development of urban agglomerations, and provide reasonable suggestions for the government to formulate relevant economic policies. This paper, from an innovative research perspective, based on the perspective of population agglomeration, studies the path of its role in regional economic development, which can make up for this defect to some extent. Moreover, the research object has been innovated and the research method has been improved. On the basis of the above, the panel data of the Yangtze River Delta from 2012 to 2021 is selected as the research sample, the location entropy index is taken as the explanatory variable, the regional gross domestic product (GDP) is taken as the explanatory variable, and the rationality of economic theory and the significance of econometric test are considered. Finally, the data are analyzed and tested by regression. The empirical analysis of the Yangtze River Delta urban agglomeration proves the importance of knowledge-intensive service industry agglomeration to regional economic development. Finally, based on the contribution of knowledge-intensive service industry agglomeration to regional economy, the development of knowledge-intensive service industry and the promotion of industrial agglomeration are studied.

5.
Small ; 19(52): e2304412, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37649192

RESUMEN

Due to the simple installation and convenient maintenance, the floating water wave energy harvesting devices have significant economic advantages. Mass power density is the most important index to evaluate the advancement of floating wave energy harvesting devices. Herein, a self-adaptive rotating triboelectric nanogenerator (SR-TENG) with a compound pendulum and a functional gear-set is provided for wave energy harvesting. First, a compound pendulum structure with a low center of gravity and high moment of inertia is obtained by the geometric design and mechanical study. Besides, compared with the previous triboelectric nanogenerator with one-way clutch, SR-TENG can harvest twice the kinetic energy utilization through the functional gear-set. Importantly, depending on the structure design, the SR-TENG obtains the average mass power density of 45.18 mW kg-1 under low frequency driving conditions, which is about 10 times the reference electromagnetic generator with a similar structure and size. This result shows that the SR-TENG has a significant advantage in small water wave energy harvesting. These findings provide an important example of the floating water wave energy harvesting devices.

6.
J Ovarian Res ; 16(1): 136, 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37430376

RESUMEN

BACKGROUND: Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer. METHODS: An electronic search following PRISMA guidelines was conducted (Prospero registration number: CRD42020187622), and then a systematic review and meta-analysis of included literature were initiated to determine which regimen was better. RESULTS: Four randomized controlled trials were included in the qualitative evaluation, and 3699 ovarian cancer patients were included in the meta-analysis. The meta-analysis revealed that the dose-dense regimen could prolong PFS (HR0.88, 95%CI 0.81-0.96; p = 0.002) and OS (HR0.90, 95%CI 0.81-1.02; p = 0.09), but it also increased the overall toxicity (OR = 1.102, 95%CI 0.864-1.405; p = 0.433), especially toxicity of anemia (OR = 1.924, 95%CI 1.548-2.391; p < 0.001), neutropenia (OR = 2.372, 95%CI 1.674-3.361; p < 0.001). Subgroup analysis indicated that the dose-dense regimen could significantly prolong not only PFS (HR0.76, 95%CI 0.63-0.92; p = 0.005 VS HR0.91, 95%CI 0.83-1.00; p = 0.046) but also OS (HR0.75, 95%CI 0.557-0.98; p = 0.037 VS HR0.94, 95%CI 0.83-1.07; p = 0.371) in Asian, and overall toxicity was significantly increased in Asians (OR = 1.28, 95%CI: 0.877-1.858, p = 0.202) compared to non-Asians (OR = 1.02, 95%CI 0.737-1.396, p = 0.929). CONCLUSION: Paclitaxel dose-dense regimen could prolong PFS and OS, but it also increased the overall toxicity. Therapeutic benefits and toxicity of dose-dense are more obvious in Asians compared to non-Asians, which need to be further confirmed in clinical trials.


Asunto(s)
Neoplasias Ováricas , Paclitaxel , Humanos , Femenino , Carboplatino/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
ACS Omega ; 8(7): 6838-6846, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36844549

RESUMEN

Humic acid (HA) has been widely used in agricultural production processes because it improves soil nutrients and has a growth-promoting effect on plants. Understanding the relationship between the structure and function of HA is the key to efficient utilization of HA in the field of activating soil legacy phosphorus (P) and promoting crop growth. In this work, HA was prepared using lignite as raw materials by the ball milling method. Moreover, a series of HAs with different molecular weights (<10, 10-50, and >50 kDa) were prepared through ultrafiltration membranes. The chemical composition and physical structure characteristics of the prepared HA were tested. The effects of HA with different molecular weights on activating accumulated P in calcareous soil and root promotion of Lactuca sativa were investigated. Results showed that HAs with different molecular weights have different functional group structures, molecular compositions, and micromorphologies, and the molecular weight of HA can significantly affect the activation performance on soil accumulated P. Moreover, the HA with low molecular weight more easily enhanced the seed germination and growth of Lactuca sativa than that of raw HA. It is expected that more efficient HA can be prepared in the future for the activation of accumulated P and promoting crop growth.

8.
IEEE Trans Neural Netw Learn Syst ; 34(8): 4386-4400, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34609944

RESUMEN

Search engines can quickly respond to a hyperlink list according to query keywords. However, when a query is complex, developers need to repeatedly refine search keywords and open a large number of web pages to find and summarize answers. Many research works of question and answering (Q&A) system attempt to assist search engines by providing simple, accurate, and understandable answers. However, without original semantic contexts, these answers lack explainability, making them difficult for users to trust and adopt. In this article, a brain-inspired search engine assistant named DeveloperBot based on knowledge graph is proposed, which aligns to the cognitive process of humans and has the capacity to answer complex queries with explainability. Specifically, DeveloperBot first constructs a multilayer query graph by splitting a complex multiconstraint query into several ordered constraints. Then, it models a constraint reasoning process as a subgraph search process inspired by a spreading activation model of cognitive science. In the end, novel features of the subgraph are extracted for decision-making. The corresponding reasoning subgraph and answer confidence are derived as explanations. The results of the decision-making demonstrate that DeveloperBot can estimate answers and answer confidences with high accuracy. We implement a prototype and conduct a user study to evaluate whether and how the direct answers and the explanations provided by DeveloperBot can assist developers' information needs.

9.
Signal Transduct Target Ther ; 7(1): 317, 2022 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-36097006

RESUMEN

Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation's pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.


Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Animales , Antineoplásicos/farmacología , Apoptosis , Línea Celular Tumoral , Femenino , Humanos , Macrólidos , Ratones , Proteínas Quinasas Activadas por Mitógenos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética
10.
J Environ Public Health ; 2022: 4502628, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36081418

RESUMEN

Under the dual background of Britain's blatant "Brexit" and the steady "expansion" of the European Union (EU) audit list, the economic effect of the development of regional alliances, in the end, is a question worthy of in-depth discussion. Using data from a sample of 27 EU member states from 2000 to 2018, this study examines and compares the impact of EU enlargement on economic growth for countries as a whole, developed and developing countries, and Central and Eastern European (CEE) countries using a multi-period difference-in-difference (DID) method and explores the mechanisms underlying that. The results show that EU enlargement contributes to the expected regional economic growth, and the effect is more evident in developed countries and CEE countries; the robustness of the results is tested by the dynamic effect test and counterfactual method; EU enlargement improves the spatial allocation of factor markets through regional integration, increases productivity, and positively promotes the overall national economic growth. As a typical quasi-natural experiment of the development of regional integration, the research results of this study on the enlargement of the EU provide a useful reference for the promotion of the development of cross-administrative integration around the world.


Asunto(s)
Desarrollo Económico , Eficiencia , Europa (Continente) , Unión Europea
11.
Mol Med Rep ; 25(6)2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35506437

RESUMEN

Breast cancer is one of the most common malignant tumors in women. Cell division cycle­associated 5 (CDCA5) is closely associated with the behavior of various cancer types. The aim of the present study was to explore the effect of CDCA5 on breast cancer. Western blot analysis and reverse transcription­quantitative PCR were used to detect the expression level of CDCA5 in human normal mammary cells and human breast cancer cell lines. To determine its function in MDA­MB­231 cells, CDCA5 was silenced in MDA­MB­231 cells by transient short hairpin RNA transfection. Cell Counting Kit­8 and clonogenicity assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to detect cell invasion and migration. Western blot analysis was used to detect the protein expressions of Ki67 and PCNA associated with proliferation, MMP2 and MMP9 associated with migration. CDCA5 was found to be markedly increased in breast cancer cell lines. CDCA5 knockdown was able to suppress cell proliferation, invasion and migration. CDCA5 inhibition downregulated PDS5 cohesin­associated factor A (PDS5A) expression in breast cancer cells. PDS5A overexpression was found to reverse the effect of CDCA5 inhibition on breast cancer cell proliferation and migration. CDCA5 knockdown was shown to suppress the malignant progression of breast cancer cells by regulating PDS5A. The present findings may provide new potential targets for breast cancer therapy.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Neoplasias de la Mama , Proteínas de Ciclo Celular , Proteínas Nucleares , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias de la Mama/patología , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Humanos , Células MCF-7 , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo
12.
ACS Appl Mater Interfaces ; 13(22): 26394-26403, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34032400

RESUMEN

Human bodily kinesthetic sensing is generally complicated and ever-changing due to the diversity of body deformation as well as the complexity of mechanical stimulus, which is different from the unidirectional mechanical motion. So, there exists a huge challenge for current flexible sensors to accurately differentiate and identify what kind of external mechanical stimulus is exerted via analyzing digital signals. Here, we report a flexible dual-interdigital-electrode sensor (FDES) that consists of two interdigital electrodes and a highly pressure-sensitive porous conductive sponge. The FDES can precisely identify multiple mechanical stimuli, e.g., pressing, positive bending, negative bending, X-direction stretching, and Y-direction stretching, and convert them into corresponding current variation signals. Moreover, the FDES exhibits other exceptional properties, such as high sensitivity, stretchability, large measurement range, and outstanding stability, accompanied by simple structural design and low-cost processing simultaneously. Additionally, our FDES successfully identifies various complex activities of the human body, which lays a foundation for the further development of multimode flexible sensors.


Asunto(s)
Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Conductividad Eléctrica , Electrodos , Monitoreo Fisiológico/métodos , Dispositivos Electrónicos Vestibles , Humanos , Presión , Resistencia a la Tracción
13.
ACS Appl Mater Interfaces ; 13(20): 24062-24069, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-33977715

RESUMEN

Flexible pressure sensors have emerged as an indispensable part of wearable devices due to their application in physiological activity monitoring. To realize long-term on-body service, they are increasingly required for properties of conformability, air permeability, and durability. However, the enhancement of sensitivity remains a challenge for ultrathin capacitive sensors, particularly in the low-pressure region. Here, we introduced a highly sensitive and ultrathin capacitive pressure sensor based on a breathable all-fabric network with a micropatterned nanofiber dielectric layer, an all-fabric capacitive sensor (AFCS). This all-fabric network endows a series of exceptional performances, such as high sensitivity (8.31 kPa-1 under 1 kPa), ultralow detection limit (0.5 Pa), wide detection range (0.5 Pa to 80 kPa), and excellent robustness (10 000 dynamic cycles). Besides, the all-fabric structure provides other properties for the AFCS, e.g., high skin conformability, super thinness (dozens of micrometers), and exceptional air permeability. Our AFCS shows promising potential in breathing track, muscle activity detection, fingertip pressure monitoring, and spatial pressure distribution, paving way for comfortable skinlike epidermal electronics.


Asunto(s)
Monitoreo Fisiológico/instrumentación , Nanofibras/química , Dispositivos Electrónicos Vestibles , Capacidad Eléctrica , Diseño de Equipo , Humanos , Sensibilidad y Especificidad
14.
Biomed Pharmacother ; 137: 111284, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33561641

RESUMEN

BACKGROUND: Gelsemium elegans (G. elegans) is a flowering plant of the Loganiaceae family, which had been used in traditional Chinese herb medicine for many years for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers, anxiety and cancer. Acute toxicity of the plant severely limits the application and development of G. elegans; however, long-term toxicity of exposure to G. elegans has not been illuminated. PURPOSE: This study is a comprehensive observation of the effects of long-term exposure (21 days at 70 mg/kg) to G. elegans in rats. METHODS AND RESULTS: The histopathological examination showed only a mild glial cell proliferation in the brain, and no lesions were observed in other organs. No abnormal changes in the biochemical parameters were observed that would have significant effects. The identification and analysis of absorbed natural ingredients showed that the active ingredients of the G. elegans could distribute to various tissues, and six compounds were identified in the brain, suggesting that they could cross the blood-brain barrier. Based on the intestinal content metabolomics, the tryptophan (Trp) biosynthesis, bile acid synthesis and bile secretion pathways have attracted our attention. Plasma metabolomic results showed that uric acid (UA) was significantly increased. The results of the brain metabolomic tests showed that the level of pyridoxal (PL) was decreased; considering the expression levels of the related enzymes, it was hypothesized that the level of pyridoxal 5'-phosphate (PLP) was decreased. PLP was important for the regulation of the neuronal γ-aminobutyric acid (GABA)/glutamate (Glu) interconversion and therefore neuronal excitability. The data of the study suggested that toxic reaction caused by G. elegans was due to a disruption of the balance of the neurotransmitter GABA/Glu transformation. CONCLUSIONS: Overall, G. elegans did not cause significant toxic reaction in the rats after long-term exposure. The results were significant for the future clinical applications of G. elegans and suggested that G. elegans could be potentially developed as a drug. The study provided a scientific basis for investigation of the mechanisms of toxicity and detoxification.


Asunto(s)
Encéfalo/efectos de los fármacos , Gelsemium/toxicidad , Neuroglía/efectos de los fármacos , Extractos Vegetales/toxicidad , Pruebas de Toxicidad Crónica , Administración Oral , Animales , Encéfalo/metabolismo , Encéfalo/patología , Proliferación Celular/efectos de los fármacos , Ácido Glutámico/metabolismo , Masculino , Metaboloma/efectos de los fármacos , Metabolómica , Neuroglía/metabolismo , Neuroglía/patología , Extractos Vegetales/administración & dosificación , Ratas Sprague-Dawley , Medición de Riesgo , Factores de Tiempo , Ácido gamma-Aminobutírico/metabolismo
15.
Artículo en Inglés | MEDLINE | ID: mdl-33387860

RESUMEN

A method for the simultaneous determination of aspartic acid (Asp), glutamic acid (Glu), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA) in animal blood and brain by two-dimensional liquid chromatography (2D-LC) combined with ultraviolet detection was established for the first time. First, the amino acid neurotransmitters (AANTs) were labeled on the corresponding fluorescent derivatives with 4-fluoro-7-nitrobenzofurazan (NBD-F), enriched on the extraction column and automatically transferred to the analytical column to achieve on-line extraction and complete separation of the target components. This method exhibited good selectivity, and the correlation coefficients for the analyte calibration curves of were > 0.99. The intra- and inter-day precisions were ≤ 16.03, and the accuracies were in the range of 70.59-116.20%. The system realizes the rapid detection and stability quantification of the five AANTs, which proves that the alternative dilution method is feasible. The results show that the system has high loading capacity, excellent resolution, and good peak shape and is not affected by other endogenous substances. Moreover, the developed method has been successfully applied to the analysis of biological samples in the blood and whole brain of rats and pigs. The content of AANTs in the hippocampus and cortex of rats was higher than that in those of pigs. This method is expected to provide applicability for the determination of AANTs in pharmacological, pharmaceutical and clinical research in nervous science.


Asunto(s)
Aminoácidos/análisis , Cromatografía Líquida de Alta Presión/métodos , Neurotransmisores/análisis , Ácido gamma-Aminobutírico/análisis , Aminoácidos/sangre , Aminoácidos/química , Animales , Química Encefálica , Límite de Detección , Modelos Lineales , Neurotransmisores/sangre , Neurotransmisores/química , Ratas , Reproducibilidad de los Resultados , Porcinos , Ácido gamma-Aminobutírico/química
16.
Rapid Commun Mass Spectrom ; 34(17): e8843, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32453886

RESUMEN

RATIONALE: Gelsemium elegans (G. elegans) is highly toxic to humans and rats but has insecticidal and growth-promoting effects on pigs and goats. However, the mechanisms behind the toxicity differences of G. elegans are unclear. Gelsenicine, isolated from G. elegans, has been reported to be a toxic alkaloid. METHODS: In this study, the in vitro metabolism of gelsenicine was investigated and compared for the first time using human (HLM), pig (PLM), goat (GLM) and rat (RLM) liver microsomes and high-performance liquid chromatography/mass spectrometry (HPLC/MS). RESULTS: In total, eight metabolites (M1-M8) were identified by using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). Two main metabolic pathways were found in the liver microsomes of the four species: demethylation at the methoxy group on the indole nitrogen (M1) and oxidation at different positions (M2-M8). M8 was identified only in the GLM. The degradation ratio of gelsenicine and the relative percentage of metabolites produced during metabolism were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/QqQ-MS/MS). The degradation ratio of gelsenicine in liver microsomes decreased in the following order: PLM ≥ GLM > HLM > RLM. The production of M1 decreased in the order of GLM > PLM > RLM > HLM, the production of M2 was similar among the four species, and the production of M3 was higher in the HLM than in the liver microsomes of the other three species. CONCLUSIONS: Based on these results, demethylation was speculated to be the main gelsenicine detoxification pathway, providing vital information to better understand the metabolism and toxicity differences of G. elegans among different species.


Asunto(s)
Alcaloides Indólicos , Microsomas Hepáticos/metabolismo , Animales , Cromatografía Líquida de Alta Presión/métodos , Gelsemium , Cabras , Humanos , Alcaloides Indólicos/análisis , Alcaloides Indólicos/química , Alcaloides Indólicos/metabolismo , Espectrometría de Masas/métodos , Ratas , Porcinos
17.
Hum Gene Ther ; 31(5-6): 325-338, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32024383

RESUMEN

Refractoriness to conventional chemotherapy is a major challenge in the treatment of advanced ovarian cancer (OC). There is increasing evidence that mitochondrial priming correlates with cisplatin response in various cancers. Notably, Bim and Bid, two of the proapoptotic BH3-only proteins, are recognized as the most effective inducers of mitochondrial priming in OC. In this study, we constructed two tumor-specific oncolytic adenoviruses (Ads) coding for Bim (Ad-Bim) or truncated Bid (Ad-tBid), respectively, and performed gain-of-function assays in nine OC cell lines. Ad-tBid exhibited significant antitumor efficacy than the controls. On addition of Ad-tBid pretreatment, mito-primed cells displayed more sensitivity to cisplatin both in vitro and ex vivo. We also found that Ad-tBid induced mitochondrial apoptosis in a Bak-dependent manner. Furthermore, a combined cisplatin plus Ad-tBid therapy markedly inhibited tumor growth in a subcutaneous xenotransplanted tumor model. In mice bearing peritoneal disseminated OC, intraperitoneal administration of Ad-tBid potentiated the antitumor effect of cisplatin. Our findings suggest that Ad-tBid enhances cisplatin response in OC cells, establishing the potential treatment of advanced OC via a combination of cisplatin and Ad-tBid.


Asunto(s)
Proteína Proapoptótica que Interacciona Mediante Dominios BH3/genética , Proteína 11 Similar a Bcl2/genética , Cisplatino/farmacología , Mitocondrias/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Adenoviridae/genética , Adenoviridae/metabolismo , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Proteína 11 Similar a Bcl2/metabolismo , Caspasa 3/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Terapia Genética , Vectores Genéticos/uso terapéutico , Células HEK293 , Humanos , Ratones , Ratones Endogámicos BALB C , Mitocondrias/genética , Células Tumorales Cultivadas
18.
J Ethnopharmacol ; 252: 112617, 2020 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-31988014

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine contains hundreds of natural products, and studying their absorption, metabolism, distribution, and elimination presents great challenges. Gelsemium elegans (G. elegans) is a flowering plants in the Loganiaceae family. The plant is known to be toxic and has been used for many years as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, neuropathic pain, spasticity, skin ulcers and cancer. It was also used as veterinary drugs for deworming, promoting animal growth, and pesticides. At present, studies on the metabolism of G. elegans have primarily focused on only a few single available reference ingredients, such as koumine, gelsemine and gelsedine. MATERIAL AND METHODS: The goal of this work is to elucidate the overall metabolism of whole G. elegans powder in goats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS). RESULTS: Analyses of plasma, urine and fecal samples identified or tentatively characterized a total of 44 absorbed natural products and 27 related produced metabolites. Gelsedine-type, sarpagine-type and gelsemine-type alkaloids were the compounds with the highest metabolite formation. In the present study, most natural products identified in G. elegans were metabolized through glucuronidation and oxidation. Hydrogenation, dehydrogenation and demethylation also occurred. CONCLUSION: To our knowledge, this is the first report of the metabolite profiling of the G. elegans crude extract in goats, which is of great significance for a safer and more rational application of this herbal medicine.


Asunto(s)
Gelsemium , Extractos Vegetales/farmacocinética , Animales , Cromatografía Líquida de Alta Presión , Heces/química , Cabras , Absorción Intestinal , Masculino , Espectrometría de Masas , Medicina Tradicional China , Extractos Vegetales/sangre , Extractos Vegetales/orina
19.
Adv Mater ; 32(1): e1904988, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31746041

RESUMEN

Triboelectrification-enabled self-powered flexible electronic/optical systems have aroused a new surge of interest in recent years. All-in-one integration of such a system, which could significantly improve its adaptability, operability, and portability, still remains a challenge due to the absence of suitable architectures and integration schemes. Herein, a previously reported self-powered optical switch (OS) is thoroughly remolded and upgraded to a fully integrated contact-sliding-triboelectrification-driven dynamic optical transmittance modulator (OTM). The OTM is constructed with a multilayered structure, comprising a transparent triboelectrification top layer, a SiO2 -spaced polymer dispersed liquid crystal (PDLC) intermediate layer, and a flexible transparent conductive substrate. The working mechanism is that an alternating electric field can be induced once contact-sliding occurs upon the OTM, rendering the PDLC layer immediately switching its initial translucent state to an instantaneous transparent state. As such, a decent dimming range with the relative transmitted light intensity from 0.17 to 0.72 can be achieved at low mechanical thresholds of contact pressure (≈20 kPa) and sliding velocity (≈0.3 m s-1 ). Moreover, for practical applications, demonstrations of information covering and selective visualization are successfully implemented without any extra optical elements nor external power supplies, explicitly showing great potential for the OTM in various self-powered optical interactive applications.

20.
J Exp Clin Cancer Res ; 38(1): 415, 2019 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-31615580

RESUMEN

In the original publication of this manuscript [1], Fig. 5E lower panel was incorrect due to an error in the preparation of these figures for publication. It was noticed that in the lower panel of Fig. 5E, one mouse image of ApoE-/- + PBS group (upper) was a photograph coming from ApoE-/- + BAPN pre-treatment group (lower). The corrected figure appears below. We apologize for any confusion this may have caused.

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