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In this study, the molecular mechanism of astragaloside â £(AS-â £) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-â £ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-â £ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-â £ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-â £ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-â £ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-â £ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-â £ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-â £.
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Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Animais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Células PC12 , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Saponinas , Transdução de Sinais , TriterpenosRESUMO
BACKGROUND: Children are especially vulnerable to pneumonia and the effects of air pollution. However, little is known about the impacts of air pollutants on pediatric admissions for Mycoplasma pneumonia. This study was conducted to investigate the impacts of air pollutants on pediatric hospital admissions for Mycoplasma pneumonia in Shanghai, China. METHODS: A cross-sectional design was applied to explore the association between pediatric hospital admissions and levels of air pollutants (fine particulate matter, particulate matter, ozone, sulfur dioxide, nitrogen dioxide, and carbon monoxide). Data on hospital admissions for pneumonia and levels of ambient air pollutants were obtained for the period of 2015 to 2018. Associations between pediatric admissions for Mycoplasma pneumonia and ambient air pollutants were calculated using logistic regression and described by the odds ratio and relevant 95% confidence interval. The hysteresis effects of air pollutants from the day of hospital admission to the previous 7 days were evaluated in single-pollutant models and multi-pollutant models with adjustments for weather variables and seasonality. Lag 0 was defined as the day of hospital admission, lag 1 was defined as the day before hospital admission, and so forth. RESULTS: In the single-pollutant models (without adjustment for other pollutants), pediatric hospital admissions for pneumonia were positively associated with elevated concentrations of nitrogen dioxide and fine particulate matter. A 0.5% increase in daily admissions per 10-µg/m3 increase in the nitrogen dioxide level occurred at lag 1 and lag 2, and a 0.3% increase in daily admissions per 10-µg/m3 increase in fine particulate matter occurred at lag 1. In the multi-pollutant models, nitrogen dioxide and fine particulate matter remained significant after inclusion of particulate matter, ozone, sulfur dioxide, and carbon monoxide. CONCLUSIONS: This study illustrated that higher levels of nitrogen dioxide and fine particulate matter increase the risk of pediatric hospitalization for Mycoplasma pneumonia in Shanghai, China. These findings imply that the high incidence of Mycoplasma pneumonia in children in Asia might be attributed to the high concentration of specific air pollutants in Asia.
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Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Hospitalização/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Pneumonia por Mycoplasma/epidemiologia , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monóxido de Carbono/análise , Monóxido de Carbono/toxicidade , Criança , China/epidemiologia , Estudos Transversais , Monitoramento Ambiental , Feminino , Humanos , Modelos Logísticos , Masculino , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Razão de Chances , Ozônio/análise , Ozônio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Pneumonia por Mycoplasma/etiologia , Dióxido de Enxofre/análise , Dióxido de Enxofre/toxicidade , Tempo (Meteorologia)RESUMO
The gut microbiota of infants changes over time and is affected by various factors during early life. However, rarely have studies explored the gut microbiota development and affecting factors in the Chinese infant population. We enrolled 102 infants and collected stool samples from them at birth, 42 days, 3 mo, and 6 mo after delivery to characterize the microbiota signatures and the effects of different factors that modulate the gut microbiota diversity, composition, and function over time. DNA extracted from the bacteria in the stool samples was subjected to high-throughput sequencing and bioinformatics analysis. Microbial richness and diversity increased significantly during the first 6 mo of life. Beneficial microbes such as Bifidobacterium, Lactobacillus, and Blautia were found to be increased in the infant's gut at 6 mo, while pathological bacteria such as Escherichia-Shigella, Enterobacter, Staphylococcus, and Klebsiella decreased over time. The changes in the infant delivery mode and infant-feeding mode only produced changes in the microbial composition, whereas changes in bacterial richness, diversity and effects sizes on the microbial architecture were all time dependent. A comparison of infant delivery modes conveyed a decrease in abundance of Bacteroidetes over time in the gut of infants born via C-section, while the Bifidobacterium was the most dominant genus in the vaginal delivery group. The gut microbiota of infants changed extensively during the first 6 mo of life. Delivery and feeding modes were strong factors that significantly affected microbial architecture and functions.
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Alimentação com Mamadeira , Aleitamento Materno , Microbioma Gastrointestinal/genética , Parto/fisiologia , Bacteroidetes/genética , Bifidobacterium/genética , Cesárea , China , DNA Bacteriano/genética , Fezes/microbiologia , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
Photocatalytic coatings can degrade volatile organic compounds into non-toxic products, which has drawn the attention of scholars around the world. However, the pollution of dust on the coating adversely affects the photocatalytic efficiency and service life of the coating. Here, a series of TiO2-polyfluoroalkoxy (PFA) coatings with different contents of PFA were fabricated by suspension plasma spraying technology. The results demonstrate that the hybrid coatings contain a large number of circular and ellipsoidal nanoparticles and a porous micron-nano structure due to the inclusion of PFA. According to the optimized thermal spraying process parameters, TiO2 nanoparticles were partially melted to retain most of the anatase phases, whereas PFA did not undergo significant carbonization. As compared to the TiO2 coating, the static contact angle of the composite coating doped with 25 wt.% PFA increased from 28.2° to 134.1°. In addition, PFA strongly adsorbs methylene blue, resulting in a greater involvement of methylene blue molecules in the catalyst, where the catalytic rate of hybrid coatings is up to 95%. The presented nanocomposite coatings possess excellent photocatalytic and self-cleaning properties and are expected to find wider practical applications in the field of photocatalysis.
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Oxygenated fuel has the function of self-supplying oxygen during the combustion process, which can greatly improve emission performance and reduce diesel fuel soot production. In this paper, a novel oxygenated fuel poly(oxymethylene) dibutyl ether (PODBE n ) is designed and synthesized through experiments in combination with density functional theory (DFT) calculation. The experimental results show that PODBE n has the advantages of high cetane number (73.6), moderate density (868 kg/m3), and low condensation point (-72 °C). According to the DFT calculation results, the molecular (PODBE n ) polarity index of different polymerization degrees is similar to the value of diesel and has good mutual solubility with diesel. Moreover, the mechanism of the entire path of synthesis is calculated at the M06-2X/6-311G(d,p) level of theory. The energetic profile reveals that the rate-determining step is the nucleophilic addition step with the highest barrier energy (TS1 = 21.59 kcal/mol). This work provides a feasible method to synthesize high-performance oxygenated fuel PODBE n using NKC-9 ion-exchange resins.
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BACKGROUND: Sinisan (SNS) consists of four kinds of herbs, which is the core of antidepressant prescription widely used in traditional Chinese medicine clinic treatment for depression induced by early life stress. However, the role and precise mechanism of SNS antidepressant have not yet been elucidated. PURPOSE: This study aimed to investigate the mechanism SNS on antidepressant of regulating mitochondrial function to improve hippocampal synaptic plasticity. METHODS: 90 Sprague-Dawley (SD) rats male pups on Post-Natal Day (PND) 0 were randomly divided into Control group (ddH20), Model group (ddH20), Fluoxetine group (5.0â¯mg/kg fluoxetine), and SNS-L group (2.5â¯g/kg SNS), SNS-M group (5.0â¯g/kg SNS) and SNS-H group (10.0â¯g/kg SNS), 15 animals per group. Maternal separation (MS) from PND1 to PND21, drug intervention from PND60 to PND90, and behavior tests including sucrose preference test, open field test and forced swimming test from PND83 to PND90 were performed. Synaptic structure and mitochondrial structure were observed by TEM. The expression levels of PSD-95 and SYN were detected by immunohistochemistry and western blot test, the adenosine triphosphate (ATP) content in the hippocampus was detected by assay kits, and the expression levels of Mfn2, Drp1 and Fis1 protein were detected by western bolt test. RESULTS: SNS can alleviate depression-like and anxiety-like behaviors in MS rats, improve the damage of synapses and mitochondria, reduce the decrease of ATP in hippocampus, and reverse the expression levels of PSD-95, SYN, Mfn2, Drp1, and Fis1 proteins. CONCLUSION: SNS reduced the risk of early life stress induced depression disorder via regulating mitochondrial function and synaptic plasticity. Targeting mitochondrial may be a novel prospective therapeutic avenue for antidepressant.
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Fluoxetina , Privação Materna , Trifosfato de Adenosina/metabolismo , Animais , Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas , Fluoxetina/farmacologia , Hipocampo , Masculino , Mitocôndrias , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/tratamento farmacológico , Sacarose/metabolismoRESUMO
The Huangjia Ruangan granule (HJRG) is a clinically effective Kampo formula, which has a significant effect on liver fibrosis and early liver cirrhosis. However, the mechanism underlying HJRG in treating liver fibrosis remains unclear. In this study, carbon tetrachloride (CCl4) was used to induce liver fibrosis in rats to clarify the effect of HJRG on liver fibrosis and its mechanism. Using network pharmacology, the potential mechanism of HJRG was initially explored, and a variety of analyses were performed to verify this mechanism. In the liver fibrosis model, treatment with HJRG can maintain the liver morphology, lower the levels of AST and ALT in the serum, and ameliorate pathological damage. Histopathological examinations revealed that the liver structure was significantly improved and fibrotic changes were alleviated. It can effectively inhibit collagen deposition and the expression of α-SMA, reduce the levels of the rat serum (HA, LN, PC III, and Col IV), and inhibit the expression of desmin, vimentin, and HYP content in the liver. Analyzing the results of network pharmacology, the oxidative stress, inflammation, and the related pathways (primarily the TNF signaling pathway) were identified as the potential mechanism of HJRG against liver fibrosis. Experiments confirmed that HJRG can significantly increase the content of superoxide dismutase and glutathione and reduce the levels of malondialdehyde and myeloperoxidase in the rat liver; in addition, HJRG significantly inhibited the content of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and reduced the expression of inflammatory regulators (Cox2 and iNOS). Meanwhile, treatment with HJRG inhibited the phosphorylation of NF-κB P65, IκBα, ERK, JNK, and MAPK P38. Moreover, HJRG treatment reversed the increased expression of TNFR1. The Huangjia Ruangan granule can effectively inhibit liver fibrosis through antioxidation, suppressing liver inflammation by regulating the TNF/MAPK and NF-κB signaling pathways, thereby preventing the effect of liver fibrosis.
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Psychological stress is a common etiology among patients with lung cancer and serves as a potential indication of poor prognosis and advanced cancer clinical stage. Evidence indicates that depression is positively correlated with the evolvement of lung carcinoma. Nevertheless, the mechanisms underlying the effects of mental disorder on lung cancer have not been considerably and systemically explored. We hypothesized that mental disorder may affect the adjustment of the tumor microenvironment and immune cells. We used the chronic unpredictable mild stress (CUMS) procedure to induce depressed mice models and established tumor-bearing models of C57BL/6â¯J mice. Results revealed that the worsening of lung cancer was notably hastened in the CUMSâ¯+â¯tumor group. Notably, the expression of PD-L1 in tumor issues increased in the tumor microenvironment, accompanied with a decline in the levels of CD8. On the basis of the date of tumor migration, our results indicated that MMPs and VEGF significantly increased after CUMSâ¯+â¯tumor treatment. Thus, we demonstrated that modulation of the tumor microenvironment is pivotal for depression-promoted lung cancer migration.
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Carcinoma Pulmonar de Lewis/secundário , Depressão/complicações , Neoplasias Pulmonares/patologia , Estresse Psicológico/complicações , Microambiente Tumoral/imunologia , Animais , Antidepressivos/administração & dosagem , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/prevenção & controle , Carcinoma Pulmonar de Lewis/psicologia , Linhagem Celular Tumoral , Depressão/tratamento farmacológico , Depressão/imunologia , Depressão/psicologia , Progressão da Doença , Humanos , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/psicologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico/imunologia , Estresse Psicológico/psicologia , Linfócitos T Citotóxicos , Microambiente Tumoral/efeitos dos fármacosRESUMO
More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague-Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC-MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5ß-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses.
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BACKGROUND: Adverse stress in early life negatively influences psychiatric health by increasing the risk of developing depression and suicide in adulthood. Clinical antidepressants, such as fluoxetine, exhibit unsatisfactory results due to their low efficacy or intolerable side effects. SiNiSan (SNS), a traditional Chinese herbal formula, has been proven to have affirmatory antidepressive effects. However, the underlying mechanism remains poorly understood. Therefore, this study aimed to explore the impact and molecular mechanism of SNS treatment in rats exposed to neonatal maternal separation (MS)-combined young-adult chronic unpredictable mild stress (CUMS). METHOD: Seventy-two neonatal male Sprague-Dawley rats were randomly divided into six groups of 12 rats each: control + ddH2O, model + ddH2O, positive (fluoxetine: 5 mg/kg), SNS-low dose (2.5 g/kg), SNS-medium dose (5 g/kg), and SNS-high dose (10 g/kg). Behavioral tests included sucrose preference test, open-field test, and forced swimming test. Calcium sensitive receptor (CaSR), protein kinase C (PKC), ERK1/2, and synapse-associated proteins (PSD-95, GAP-43, and synaptophysin [Syn]) in the hippocampus (HIP) and prefrontal cortex (PFC) were assayed using Western blot. CaSR and Syn protein expression was measured by immunohistochemistry. RESULTS: MS-combined CUMS rats exhibited depression-like behavior. SNS exerted antidepressant effects on stress-induced depression-like behavior. The levels of CaSR, PKC, and p-ERK1/2 in the HIP and PFC decreased in stressed rats. SNS treatment significantly upregulated the expression of CaSR, PKC, and p-ERK1/2 in the HIP and PFC of adult stressed rats. CONCLUSION: MS-combined CUMS could develop depression-like behavior in adult. SNS exhibited antidepressive effects accompanied by improving synaptic plasticity by activation of the CaSR-PKC-ERK signaling pathway.
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Antidepressivos/farmacologia , Depressão/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Animais , Escala de Avaliação Comportamental , Comportamento Animal/efeitos dos fármacos , Depressão/metabolismo , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large , Medicamentos de Ervas Chinesas , Feminino , Proteína GAP-43/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Privação Materna , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico , Sinaptofisina/metabolismoRESUMO
A novel class of CdS@UIO-66-NH2 core shell heterojunction was fabricated by the facile in-situ solvothermal method. Characterizations show that porous UIO-66-NH2 shell not only allows the visible light to be absorbed on CdS nanorod core, but also provides abundant catalytic active sites as well as an intimate heterojunction interface between UIO-66-NH2 shell and CdS nanorod core. By taking advantage of this property, the core-shell composite presents highly solar-driven photocatalytic performance compared with pristine UIO-66-NH2 and CdS nanorod for the degradation of organic dyes including malachite green (MG) and methyl orange (MO), and displays superior photostability after four recycles. Furthermore, the photoelectrochemical performance of CdS@UIO-66-NH2 can be measured by the UV-vis spectra, Mott-Schottky plots and photocurrent. The remarkably enhanced photocatalytic activity of CdS@UIO-66-NH2 can be ascribed to high surface areas, intimate interaction on molecular scale and the formation of one-dimensional heterojunction with n-n type. What's more, the core-shell heterostructural CdS@UIO-66-NH2 can facilitate the effective separation and transfer of the photoinduced interfacial electron-hole pairs and protect CdS nanorod core from photocorrosion.
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A novel triptycene-based covalent polymer (TCP) with a high surface area was constructed through the Suzuki coupling reaction. A very high photocatalytic H2 production rate of 50 670 µmol h-1 g-1 and superior photostability were achieved due to the intimate synergistic interactions between the TCP and Cd0.5Zn0.5S.