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Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in newborns, which severely influences the health of infants and lacks effective clinical treatment strategies. The pathogenesis of BPD is correlated to enhanced inflammation and activated oxidative stress (OS). The application of antioxidants and anti-inflammatory treatment could be hot spots for BPD treatment. Nesfatin-1, a peptide with a suppressive property against inflammation, was tested herein for its potential therapeutic value in BPD. Neonatal SD rats were stimulated with hyperoxia, followed by being intraperitoneally administered with 20 µg/kg/day Nesfatin-1 for 2 weeks. Decreased RAC value in lung tissues, increased wet weight/dry weight (W/D) pulmonary ratio and bronchoalveolar lavage fluid (BALF) proteins, elevated cytokine release in BALF, increased malondialdehyde (MDA) content, and declined superoxide dismutase (SOD) activity were observed in BPD rats, all of which were sharply mitigated by Nesfatin-1. Rat epithelial type II cells (AECIIs) were handled with hyperoxia, and then cultured with 1 and 10 nM Nesfatin-1. Reduced cell viability, elevated lactate dehydrogenase production, elevated cytokine secretion, elevated MDA content, and decreased SOD activity were observed in hyperoxia-handled AECIIs, all of which were markedly alleviated by Nesfatin-1. Furthermore, activated nuclear factor-κB (NF-κB) signaling observed in both BPD rats and hyperoxia-handled AECIIs were notably repressed by Nesfatin-1. Collectively, Nesfatin-1 alleviated hyperoxia-triggered BPD by repressing inflammation and OS via the NF-κB signaling pathway.
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Displasia Broncopulmonar , Hiperóxia , Animais , Humanos , Recém-Nascido , Ratos , Animais Recém-Nascidos , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hiperóxia/metabolismo , Inflamação/metabolismo , Pulmão/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Superóxido Dismutase/metabolismoRESUMO
Information about intralesional pharmacokinetics (PK) and spatial distribution of tuberculosis (TB) drugs is limited and has not been used to optimize dosing recommendations for new or existing drugs. While new techniques can detect drugs and their metabolites within TB granulomas, they are invasive, rely on accurate resection of tissues, and do not capture dynamic drug distribution in the tissues of interest. In this study, we assessed the in situ distribution of (11)C-labeled rifampin in live, Mycobacterium tuberculosis-infected mice that develop necrotic lesions akin to human disease. Dynamic positron emission tomography (PET) imaging was performed over 60 min after injection of [(11)C]rifampin as a microdose, standardized uptake values (SUV) were calculated, and noncompartmental analysis was used to estimate PK parameters in compartments of interest. [(11)C]rifampin was rapidly distributed to all parts of the body and quickly localized to the liver. Areas under the concentration-time curve for the first 60 min (AUC0-60) in infected and uninfected mice were similar for liver, blood, and brain compartments (P > 0.53) and were uniformly low in brain (10 to 20% of blood values). However, lower concentrations were noted in necrotic lung tissues of infected mice than in healthy lungs (P = 0.03). Ex vivo two-dimensional matrix-assisted laser desorption ionization (MALDI) imaging confirmed restricted penetration of rifampin into necrotic lung lesions. Noninvasive bioimaging can be used to assess the distribution of drugs into compartments of interest, with potential applications for TB drug regimen development.
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Antituberculosos/farmacocinética , Mycobacterium tuberculosis/patogenicidade , Rifampina/farmacocinética , Animais , Feminino , Camundongos , Tomografia por Emissão de Pósitrons , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tuberculose/metabolismo , Tuberculose/microbiologiaRESUMO
The current study aims to use the molecular dynamics (MD) simulation method to discuss the glass transition behaviour and fractional free volume (FFV) of the pure polyethylene terephthalate (PET) and the plasticized PET induced by supercritical carbon dioxide (SC-CO2) sorption. The adsorption concentration reproduced through sorption relaxation cycles (SRC) was firstly estimated and in an order of magnitude with the known experimental results available in the reported literature. The FFV induced by SC-CO2 in PET polymer changes regularly, which is proportional to the capacity of SC-CO2 adsorption with the changes in temperature and pressure. The glass transition temperature (T g) was further estimated to be almost identical to the known experimental values and shows a gradually decreasing tendency with the increase of pressure. Meanwhile, the plasticization of PET polymer studied by radial distribution functions showed that CO2 molecules occupying the sorption sites on the PET backbone promoted plasticization by increasing the fluidity of the PET backbone chain.
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The soybean is a significant legume crop, providing several vital dietary components. Extreme heat stress negatively affects soybean yield and quality, especially at the germination stage. Continuous change in climatic conditions is threatening the global food supply and food security. Therefore, it is a critical need of time to develop heat-tolerant soybean genotypes. Different molecular techniques have been developed to improve heat stress tolerance in soybean, but until now complete genetic mechanism of soybean is not fully understood. Various molecular methods, like quantitative trait loci (QTL) mapping, genetic engineering, transcription factors (TFs), transcriptome, and clustered regularly interspaced short palindromic repeats (CRISPR), are employed to incorporate heat tolerance in soybean under the extreme conditions of heat stress. These molecular techniques have significantly improved heat stress tolerance in soybean. Besides this, we can also use specific classical breeding approaches and different hormones to reduce the harmful consequences of heat waves on soybean. In future, integrated use of these molecular tools would bring significant results in developing heat tolerance in soybean. In the current review, we have presented a detailed overview of the improvement of heat tolerance in soybean and highlighted future prospective. Further studies are required to investigate different genetic factors governing the heat stress response in soybean. This information would be helpful for future studies focusing on improving heat tolerance in soybean.
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Caffeoylquinic acids, as plant-derived polyphenols, exhibit multiple biological activities such as antioxidant, anti-inflammatory, and neuroprotective activities. However, only limited information about their effect on longevity is available. In the current study, molecular docking was employed to explore the interactions between six representative caffeoylquinic acids and the insulin-like growth factor-1 receptor (IGFR), which is an important target protein for longevity. The results indicated that all six compounds were embedded well in the active pocket of IGFR, and that 3,5-diCQA exhibited the strongest affinity to IGFR. Moreover, ASP1153, GLU1080, ASP1086, and ARG1003 were the key amino acid residues during the interaction of these 6 compounds with IGFR. Furthermore, the lifespan extension effect of caffeoylquinic acids was evaluated in a Caenorhabditis elegans (C. elegans) model. The results revealed that all the caffeoylquinic acids significantly extended the lifespan of wild-type worms, of which 3,5-diCQA was the most potent compound. Meanwhile, 3,5-diCQA enhanced the healthspan by increasing the body bending and pharyngeal pumping rates and reducing the intestinal lipofuscin level. Further studies demonstrated that 3,5-diCQA induced longevity effects by downregulating the insulin/insulin-like growth factor signaling (IIS) pathway. This study suggested that the combination of molecular docking and genetic analysis of specific worm mutants could be a promising strategy to reveal the anti-aging mechanisms of small molecule natural compounds.
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Caenorhabditis elegans/efeitos dos fármacos , Ácido Clorogênico/farmacologia , Cinamatos/farmacologia , Longevidade/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Envelhecimento/efeitos dos fármacos , Animais , Sítios de Ligação , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/química , Ácido Clorogênico/metabolismo , Cinamatos/química , Cinamatos/metabolismo , Regulação da Expressão Gênica , Insulina/metabolismo , Simulação de Acoplamento Molecular , Ácido Quínico/química , Ácido Quínico/metabolismo , Ácido Quínico/farmacologia , Receptor IGF Tipo 1/química , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/genéticaRESUMO
OBJECT: To evaluate the correlation between prothrombin gene G20210A mutation and deep vein thrombosis after total joint replacement through detecting distribution frequency of single nucleotide polymorphism of the gene in patients undergoing total joint replacement. METHOD: PCR and direct sequencing of DNA are used to analyze the frequency of prothrombin gene G20210A mutation in 55 patients undergoing total joint replacement, and the relationship between the mutation and deep vein thrombosis after total joint replacement is evaluated. RESULT: Morbidity of prothrombin gene G20210A mutation in 55 patients is 0, both in the DVT group and non-DVT group. There is no significant difference between the two groups (p > 0.05). CONCLUSION: Mutation of prothrombin gene G20210A in Chinese patients is rare, and there is no correlation between the genetic mutation and deep vein thrombosis after total joint replacement.
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Artroplastia de Substituição/efeitos adversos , Povo Asiático/genética , Polimorfismo de Nucleotídeo Único , Protrombina/genética , Trombose Venosa/etiologia , Trombose Venosa/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da PolimeraseRESUMO
Finance plays a crucial role in a fast-growing economy that can lead to environmental degradation. The present study utilizes balanced panel data of 105 countries for the time span 1980-2016 to investigate empirical linkage among environmental degradations: economy and finance. It also unfolds the nonlinear impact of economy and finance on environmental degradation. Existing literature on environmental issues mainly focuses on individual case studies uncovering particular regions, but the comprehensive analysis is not available. To fill this gap, panels were classified into five divisions: global, regional, income-based, OECD-based, and carbon emission. The cross-sectional dependence test is applied to identify the degree of cross-sectional dependence among concerned 16 divisions. The second-generation panel models (CADF and Westerlund cointegration, DOLS, and DH heterogenous causality) are employed on a sample set to compute to unit root, cointegration, and long-run and short-run dynamics among concerned variables, respectively. The findings infer the inverted EKC and U-shaped EKC in 10 and 3 out of 16 divisions with respect to environmental degradation-economy nexus, respectively, while 8 and 2 out of 16 divisions indicate the inverted EKC and U-shaped EKC, respectively, in terms of environmental degradation-finance nexus. In 12 out of 16 divisions, the energy consumption uplifts the CO2 emissions. The DH causality affirmed a bidirectional causality among economy, finance, and energy consumption, respectively.
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Dióxido de Carbono/análise , Dióxido de Carbono/química , Estudos Transversais , Desenvolvimento Econômico , Estudos ProspectivosRESUMO
Among the regulatory policies, feed-in tariffs (FIT) and renewable portfolio standards (RPS) are the most popular to promote the development of renewable energy power industry. They can significantly contribute to the expansion of domestic industrial activities in terms of sustainable energy. This paper uses system dynamics (SD) to establish models of long-term development of China's waste incineration power industry under FIT and RPS schemes, and provides a case study by using scenario analysis method. The model, on the one hand, not only clearly shows the complex logical relationship between the factors but also assesses policy effects of the two policy tools in the development of the industry. On the other hand, it provides a reference for scholars to study similar problems in different countries, thereby facilitating an understanding of waste incineration power's long-term sustainable development pattern under FIT and RPS schemes, and helping to provide references for policy-making institutions. The results show that in the perfect competitive market, the implementation of RPS can promote long-term and rapid development of China's waste incineration power industry given the constraints and actions of the mechanisms of RPS quota proportion, the TGC valid period, and fines, compared with FIT. At the end of the paper, policy implications are offered as references for the government.
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Conservação dos Recursos Naturais , Incineração , China , Política Ambiental , IndústriasRESUMO
Among various therapeutic approaches for stroke, treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) has acquired some promising results. However, the underlying mechanisms remain unclear. We analyzed the protein expression spectrum of the cortical peri-infarction region after ischemic stroke followed by treatment with hUC-MSCs, and found 16 proteins expressed differentially between groups treated with or without hUC-MSCs. These proteins were further determined by Gene Ontology term analysis and network with CD200-CD200R1, CCL21-CXCR3 and transcription factors. Three of them: Abca13, Grb2 and Ptgds were verified by qPCR and ELISA. We found the protein level of Abca13 and the mRNA level of Grb2 consistent with results from the proteomic analysis. Finally, the function of these proteins was described and the potential proteins that deserve to be further studied was also highlighted. Our data may provide possible underlying mechanisms for the treatment of stroke using hUC-MSCs.
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OBJECTIVE: A possible relationship between fibrosis along the route of cerebrospinal fluid (CSF) flow and the subsequent development of hydrocephalus has been indicated in previous studies. These changes in the fibrosis index may reflect the severity of hydrocephalus and could potentially become a diagnostic tool. The object of this study was to analyze the levels of procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), hyaluronic acid (HA), and laminin (LN) in the CSF of patients with post-traumatic hydrocephalus and determine the significance of their presence. SUBJECTS AND METHODS: Forty-four patients were included in the study: 24 patients with shunt-dependent post-traumatic hydrocephalus (group A - hydrocephalus group); ten brain trauma patients without any sign of hydrocephalus (group B - trauma group); ten patients without brain trauma and hydrocephalus (group C - normal control group). CSF levels of PICP, PIIINP, HA, LN and transforming growth factor-ß1(TGF-ß1) were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of PICP, PIIINP, HA, and LN in the group of hydrocephalus patients were significantly higher than those in the post-trauma patients without hydrocephalus (p < 0.05) and normal control patients (p < 0.05). Moreover, the increased levels of PICP, PIIINP, HA, and LN were positively correlated with the level of TGF-ß1 (p < 0.05). CONCLUSION: We demonstrated an increase of fibrosis factors including PICP, PIIINP, HA, and LN, that was positively correlated with TGF-ß1 levels. This indicates an important role for the process of fibrosis in the development of post-traumatic chronic hydrocephalus and shows the potential utility of PICP, PIIINP, HA, and LN as a diagnostic index in shunt-dependent post-traumatic chronic hydrocephalus.
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We developed an EEG- and audio-based sleep sensing and enhancing system, called iSleep (interactive Sleep enhancement apparatus). The system adopts a closed-loop approach which optimizes the audio recording selection based on user's sleep status detected through our online EEG computing algorithm. The iSleep prototype comprises two major parts: 1) a sleeping mask integrated with a single channel EEG electrode and amplifier, a pair of stereo earphones and a microcontroller with wireless circuit for control and data streaming; 2) a mobile app to receive EEG signals for online sleep monitoring and audio playback control. In this study we attempt to validate our hypothesis that appropriate audio stimulation in relation to brain state can induce faster onset of sleep and improve the quality of a nap. We conduct experiments on 28 healthy subjects, each undergoing two nap sessions - one with a quiet background and one with our audio-stimulation. We compare the time-to-sleep in both sessions between two groups of subjects, e.g., fast and slow sleep onset groups. The p-value obtained from Wilcoxon Signed Rank Test is 1.22e-04 for slow onset group, which demonstrates that iSleep can significantly reduce the time-to-sleep for people with difficulty in falling sleep.
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Sono , Estimulação Acústica , Algoritmos , Amplificadores Eletrônicos , Encéfalo , Eletroencefalografia , HumanosRESUMO
RNA interference (RNAi) is a process by which introduced small interfering RNA (siRNA) can cause the specific degradation of mRNA with identical sequences. In this study, we applied siRNAs targeting the UL39 gene of human herpes simplex virus type 1 (HSV-1), which encodes the large subunit of ribonucleotide reductase, ICP6. Using an ICP6 expression reporter plasmid and an in vitro model of infection, we showed that synthetic siRNA silenced effectively and specifically UL39 mRNA expression and inhibited HSV-1 replication. Our work offers new possibilities for RNAi as a genetic tool for inhibition of HSV-1 replication.