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1.
Anesth Analg ; 133(3): 781-793, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34403389

RESUMO

BACKGROUND: Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia. METHODS: The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia. RESULTS: Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia. CONCLUSIONS: We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.


Assuntos
Período de Recuperação da Anestesia , Anestesia por Inalação , Anestésicos Inalatórios/farmacologia , Estado de Consciência/efeitos dos fármacos , Desflurano/farmacologia , Isoflurano/farmacologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Orexinas/farmacologia , Potenciais de Ação , Animais , Eletroencefalografia , Masculino , Núcleos da Linha Média do Tálamo/metabolismo , Neurônios/metabolismo , Optogenética , Receptores de Orexina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo
2.
FASEB J ; 35(9): e21870, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34436790

RESUMO

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium-induced intestinal inflammation in mice. It inhibited the production of pro-inflammatory cytokines IL-6 and TNFα, and promoted the expression of anti-inflammatory cytokine IL-10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS-stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half-life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down-regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal-specific KLHL5 deficiency, a CUL3-interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3-KLHL5 may function as an E3 for ATF2 degradation.


Assuntos
Fator 2 Ativador da Transcrição/metabolismo , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Flavanonas/farmacologia , Glucosídeos/farmacologia , Inflamação/tratamento farmacológico , Proteólise/efeitos dos fármacos , Ubiquitina Tiolesterase/deficiência , Animais , Linhagem Celular , Colite/induzido quimicamente , Colite/tratamento farmacológico , Proteínas Culina/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/farmacologia , Sulfato de Dextrana/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Flavanonas/uso terapêutico , Glucosídeos/uso terapêutico , Inflamação/induzido quimicamente , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Pirróis/farmacologia , Pirrolidinas/farmacologia , Ubiquitina Tiolesterase/antagonistas & inibidores , Ubiquitinação
3.
J Biomed Inform ; 121: 103874, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298157

RESUMO

Extracting the chemical-induced disease relation from literatures is important for biomedical research. On one hand, it is challenging to capture the interactions among remote words and the long-distance information is not adequately exploited by existing systems for document-level relation extraction. On the other hand, there is some information particularly important to the target relations in documents, which should attract more attention than the less relevant information for the relation extraction. However, this issue is not well addressed in existing methods. In this paper, we present a method that integrates a hybrid graph and a hierarchical concentrative attention to overcome these problems. The hybrid graph is constructed by synthesizing the syntactic graph and Abstract Meaning Representation graph to acquire the long-distance information for document-level relation extraction. Meanwhile, the concentrative attention is used to focus on the most important information, and alleviate the disturbance brought by the less relevant items in the document. The experimental results demonstrate that our model yields competitive performance on the dataset of chemical-induced disease relations.


Assuntos
Pesquisa Biomédica , Mineração de Dados , Redes Neurais de Computação , Projetos de Pesquisa
4.
Sci Total Environ ; 795: 148468, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34252761

RESUMO

Perfluoroalkyl substances (PFASs) are a family of chemicals widely distributed in daily use consumer products. Most of these products become municipal solid wastes (MSWs) after they have been used. In the present study, we examined different types of PFASs in leachate, fly ash and bottom ash produced from three MSW incineration plants in southern China. High PFAS levels were found in leachate (mean concentration 215 ng/mL, range 21.4-682 ng/mL) from the incineration plants, which indicated large amounts of PFASs in the wastes leached out. The average quantities of PFASs annually discharged from the leachates of the three plants were estimated to be approximately 384 kg (Plant A), 47.3 kg (Plant B), and 2.82 kg (Plant C). Relatively lower levels of PFASs in fly ash (mean 16.4 ng/g, range 1.46-87.6 ng/g) and bottom ash (mean 14.6 ng/g, range 3.11-77.4 ng/g) indicated that high-temperature incineration destroyed most of the PFASs. The wide array of PFASs concentrations in all three matrices illustrated that some PFASs-containing industrial wastes were still entered into local MSW. In general, short chain PFASs, including perfluorobutyric acid (PFBA) and perfluorobutane sulfonate (PFBS), were the primary PFASs in leachate samples. In addition, PFOS was the predominant PFASs in fly ash samples. The results showed that leachate, fly ash, and bottom ash from MSW incineration plants are important vectors of PFASs.


Assuntos
Cinza de Carvão , Fluorcarbonetos , Materiais de Construção , Incineração , Resíduos Sólidos/análise
5.
Neurosci Bull ; 37(7): 934-946, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33847915

RESUMO

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.


Assuntos
Anestésicos , Habenula , Isoflurano , Animais , Neurônios GABAérgicos , Região Hipotalâmica Lateral , Isoflurano/farmacologia , Camundongos
6.
EBioMedicine ; 65: 103272, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33691246

RESUMO

BACKGROUND: Despite the fundamental clinical significance of general anaesthesia, the cortical mechanism underlying anaesthetic-induced loss of consciousness (aLOC) remains elusive. METHODS: Here, we measured the dynamics of two major cortical neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate, through in vivo two-photon imaging and genetically encoded neurotransmitter sensors in a cell type-specific manner in the primary visual (V1) cortex. FINDINGS: We found a general decrease in cortical GABA transmission during aLOC. However, the glutamate transmission varies among different cortical cell types, where in it is almost preserved on pyramidal cells and is significantly reduced on inhibitory interneurons. Cortical interneurons expressing vasoactive intestinal peptide (VIP) and parvalbumin (PV) specialize in disinhibitory and inhibitory effects, respectively. During aLOC, VIP neuronal activity was delayed, and PV neuronal activity was dramatically inhibited and highly synchronized. INTERPRETATION: These data reveal that aLOC resembles a cortical state with a disrupted excitatory-inhibitory network and suggest that a functional inhibitory network is indispensable in the maintenance of consciousness. FUNDING: This work was supported by the grants of the National Natural Science Foundation of China (grant nos. 81620108012 and 82030038 to H.D. and grant nos. 31922029, 61890951, and 61890950 to J.H.).

7.
Phytomedicine ; 85: 153315, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32978039

RESUMO

BACKGROUND: The traditional Chinese medicine (TCM) formula Qing-Fei-Pai-Du decoction (QFPDD) was the most widely used prescription in China's campaign to contain COVID-19, which has exhibited positive effects. However, the underlying mode of action is largely unknown. PURPOSE: A systems pharmacology strategy was proposed to investigate the mechanisms of QFPDD against COVID-19 from molecule, pathway and network levels. STUDY DESIGN AND METHODS: The systems pharmacological approach consisted of text mining, target prediction, data integration, network study, bioinformatics analysis, molecular docking, and pharmacological validation. Especially, we proposed a scoring method to measure the confidence of targets identified by prediction and text mining, while a novel scheme was used to identify important targets from 4 aspects. RESULTS: 623 high-confidence targets of QFPDD's 12 active compounds were identified, 88 of which were overlapped with genes affected by SARS-CoV-2 infection. These targets were found to be involved in biological processes related with the development of COVID-19, such as pattern recognition receptor signaling, interleukin signaling, cell growth and death, hemostasis, and injuries of the nervous, sensory, circulatory, and digestive systems. Comprehensive network and pathway analysis were used to identify 55 important targets, which regulated 5 functional modules corresponding to QFPDD's effects in immune regulation, anti-infection, anti-inflammation, and multi-organ protection, respectively. Four compounds (baicalin, glycyrrhizic acid, hesperidin, and hyperoside) and 7 targets (AKT1, TNF-α, IL6, PTGS2, HMOX1, IL10, and TP53) were key molecules related to QFPDD's effects. Molecular docking verified that QFPDD's compounds may bind to 6 host proteins that interact with SARS-CoV-2 proteins, further supported the anti-virus effect of QFPDD. At last, in intro experiments validated QFPDD's important effects, including the inhibition of IL6, CCL2, TNF-α, NF-κB, PTGS1/2, CYP1A1, CYP3A4 activity, the up-regulation of IL10 expression, and repressing platelet aggregation. CONCLUSION: This work illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation, and multi-organ protection. It may strengthen the understanding of QFPDD and facilitate more application of this formula in the campaign to SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , COVID-19/tratamento farmacológico , Biologia Computacional , Flavonoides/farmacologia , Ácido Glicirrízico/farmacologia , Hesperidina/farmacologia , Humanos , Masculino , Medicina Tradicional Chinesa , Camundongos , Simulação de Acoplamento Molecular , Quercetina/análogos & derivados , Quercetina/farmacologia , Células RAW 264.7 , Coelhos , Transdução de Sinais/efeitos dos fármacos
8.
Br J Anaesth ; 126(1): 279-292, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33131759

RESUMO

BACKGROUND: The neuropeptide orexin promotes arousal from general anaesthesia, however the neuronal circuits that mediate this effect have not been defined. We investigated whether orexinergic neurones modulate the basal forebrain (BF) and locus coeruleus (LC) in emergence from anaesthesia. METHODS: Hcrtcre rats were generated using a CRISPR/Cas9-based approach. Viruses encoding optogenetic probes were injected into the perifornical lateral hypothalamic (PeFLH) area, optogenetic fibres were embedded in the PeFLH, BF, or LC, and changes in anaesthesia state under 1.4 vol% or 0.8 vol% isoflurane were determined. RESULTS: In the PeFLH, 98.8% (0.4%) of orexin-A-positive cells expressed tdTomato, and 91.9% (2.2%) of tdTomato cells were orexin-A-positive. Under 1.4 vol% isoflurane anaesthesia, compared with control groups, burst suppression ratio was less, and emergence time was shorter in groups with optogenetic activation of orexinergic cell bodies in the PeFLH (923 [162] vs 493 [68] s, P=0.0003) or orexinergic terminals in the BF (937 (122) vs 674 (108) s, P=0.0049) or LC (913 [128] vs 742 [76] s, P=0.022). Optical stimulation of orexinergic terminals in the BF and LC also improved the movement scores of rats under 0.8 vol% isoflurane anaesthesia. CONCLUSIONS: Activation of orexinergic terminals in the FB or LC mediates facilitation of emergence from anaesthesia by orexinergic neurones during isoflurane anaesthesia.


Assuntos
Período de Recuperação da Anestesia , Prosencéfalo Basal/efeitos dos fármacos , Isoflurano/farmacologia , Locus Cerúleo/efeitos dos fármacos , Optogenética/métodos , Orexinas/fisiologia , Anestésicos Inalatórios/farmacologia , Animais , Prosencéfalo Basal/metabolismo , Eletroencefalografia/métodos , Locus Cerúleo/metabolismo , Modelos Animais , Orexinas/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Sci Total Environ ; 757: 144064, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33316510

RESUMO

6:2 chlorinated polyfluorinated ether sulfonate (with the trade name F-53B, a substitute for PFOS) is one type of Per- and polyfluoroalkyl substances (PFASs), which is widely used as a chromium mist inhibitor in China. It has been found in environment commonly. In this study, the sorption behavior of F-53B on four kinds of nano-materials: alumina nanopowder (ANP), alumina nanowires (ANW), hydrophilic bentonite nanoclay (HBNC) and surface modified nanoclay (SMNC) were investigated. The kinetics results indicated that the sorption of F-53B on four nano-materials reached equilibrium within 2 h and the sorption process were fitted better by the pseudo-second-order kinetic model than the pseudo-first-order kinetic model. The thermodynamic study showed that the sorption of F-53B on nano-materials were exothermic and spontaneous. As the increase of temperature, the maximum sorption capacity of ANP, ANW, HBNC, SMNC increased, and reached 868.75, 91.35, 5.15, 2465.09 µg/g at 25 °C, respectively. The surface modified nanoclay (SMNC) was better than the others for removing F-53B from aquatic environment. To investigate the effects of pH and ion strength, the particle size and zeta potential of sorbents at different pH and ion strength were measured by Dynamic Light Scattering (DLS), and concluded that the sorption mechanism of F-53B on two kinds of nanoalumina mainly included electrostatic attraction and agglomeration effects, while hydrophobic interaction played an important role on the sorption of F-53B on nanoclay. This study revealed the sorption behavior and mechanism of F-53B on four kinds of nano-materials, and the results provided theoretical support for removing F-53B from electroplating wastewater with nano-materials.

10.
Neurosci Bull ; 36(12): 1513-1523, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33048310

RESUMO

General anesthesia severely affects the metabolites in the brain. Glycogen, principally stored in astrocytes and providing the short-term delivery of substrates to neurons, has been implicated as an affected molecule. However, whether glycogen plays a pivotal role in modulating anesthesia-arousal remains unclear. Here, we demonstrated that isoflurane-anesthetized mice exhibited dynamic changes in the glycogen levels in various brain regions. Glycogen synthase (GS) and glycogen phosphorylase (GP), key enzymes of glycogen metabolism, showed increased activity after isoflurane exposure. Upon blocking glycogenolysis with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), a GP antagonist, we found a prolonged time of emergence from anesthesia and an enhanced δ frequency in the EEG (electroencephalogram). In addition, augmented expression of glycogenolysis genes in glycogen phosphorylase, brain (Pygb) knock-in (PygbH11/H11) mice resulted in delayed induction of anesthesia, a shortened emergence time, and a lower ratio of EEG-δ. Our findings revealed a role of brain glycogen in regulating anesthesia-arousal, providing a potential target for modulating anesthesia.

11.
Anal Chim Acta ; 1126: 91-99, 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32736729

RESUMO

Based on the successful design and preparation of Fe3O4@Au@polyethylene glycol (PEG)@chondroitin sulfate (CS) nanoparticles, a novel electrochemical biosensor was elaborately developed for MO determination by the drop coating method. This biosensor demonstrates ultra-low fouling properties in complex biological systems, especially in whole serum. Only 2.40% of the differential pulse voltammetry (DPV) signal changes are shown in the resistance test of electrode interface to 100% goat serum. The constructed biosensor also presented a good selectivity (DNA samples for M1, M2 and M3give a response around 14.2-21.4%of that obtained by the target analyte), reproducibility (the relative standard deviation (RSD) is only 4.82%) and storage stability (93.2% of the initial response is maintained after 20 day). Moreover, this biosensor exhibits high analytical performance with a wide line arranges (10-17 M âˆ¼ 10-12 M) in buffer, even in 100% goat serum. In both cases, a low limit of detection (LOD) of 3.3 aM(S/N = 3)is showed. To our knowledge, a few examples reported the application of electrochemical biosensors to the direct ultrahigh sensitive determination of MO, especially in whole serum.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Mycoplasma , Sulfatos de Condroitina , Técnicas Eletroquímicas , Eletrodos , Ouro , Fenômenos Magnéticos , Reprodutibilidade dos Testes
12.
Materials (Basel) ; 13(6)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32183427

RESUMO

This paper describes the effects of α-Al2O3 nanosheets on the direct current voltage breakdown strength and space charge accumulation in crosslinked polyethylene/α-Al2O3 nanocomposites. The α-Al2O3 nanosheets with a uniform size and high aspect ratio were synthesized, surface-modified, and characterized. The α-Al2O3 nanosheets were uniformly distributed into a crosslinked polyethylene matrix by mechanical blending and hot-press crosslinking. Direct current breakdown testing, electrical conductivity tests, and measurements of space charge indicated that the addition of α-Al2O3 nanosheets introduced a large number of deep traps, blocked the charge injection, and decreased the charge carrier mobility, thereby significantly reducing the conductivity (from 3.25 × 10-13 S/m to 1.04 × 10-13 S/m), improving the direct current breakdown strength (from 220 to 320 kV/mm) and suppressing the space charge accumulation in the crosslinked polyethylene matrix. Besides, the results of direct current breakdown testing and electrical conductivity tests also showed that the surface modification of α-Al2O3 nanosheets effectively improved the direct current breakdown strength and reduced the conductivity of crosslinked polyethylene/α-Al2O3 nanocomposites.

13.
Res Vet Sci ; 130: 179-183, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32199176

RESUMO

S. Pullorum is a causative agent of enteric disease of poultry with serious diarrhea. However, the detailed mechanism behind its injury to intestinal mucosa barrier, especially for intestinal stem cells, is unclear. In this study, S. Pullorum were orally administrated to 3 days old chicken to investigate the pathogenesis of S. Pullorum on intestinal mucosal barrier, especially on the proliferation of epithelial cells. We found that S. Pullorum could colonize in the cecum and invade into the liver through intestinal mucosa damage, which caused obvious pathological changes in liver and intestine and even leaded to death, as well as significant reduction of body weight. We also found that S. Pullorum infection enhanced the mRNA expression of IL-1ß and IL-6 through TLR4/MyD88 pathway, which was also further verified by the increased lipopolysaccharide (LPS) levels in serum. Furthermore, S. Pullorum increased the depth of crypt and density of PCNA+ cells significantly through the over-activation of Wnt/ß-catenin signaling pathway. The expression of intestinal stem cells markers Lgr5 and Bmi1 was also increased after S. Pullorum infection to support the crypt hyperplasia. In addition, we verified that S. Pullorum infection enhanced the mRNA expression of IL-1ß, TLR4, Lgr5 and Bmi1. Our study indicated that S. Pullorum infection damaged the intestinal mucosa barrier to induce diarrhea, affected the abnormal proliferation of intestinal stem cells by over-activation of Wnt/ß-catenin pathway in chicken.


Assuntos
Galinhas , Hiperplasia/veterinária , Enteropatias/veterinária , Doenças das Aves Domésticas/fisiopatologia , Salmonelose Animal/fisiopatologia , Salmonella enterica/fisiologia , Animais , Proteínas Aviárias/fisiologia , Hiperplasia/microbiologia , Hiperplasia/fisiopatologia , Enteropatias/microbiologia , Enteropatias/fisiopatologia , Intestinos/fisiopatologia , Doenças das Aves Domésticas/microbiologia , Salmonelose Animal/microbiologia , Salmonella enterica/patogenicidade , Transdução de Sinais , Células-Tronco/metabolismo , Virulência , Via de Sinalização Wnt , beta Catenina/fisiologia
14.
J Agric Food Chem ; 67(49): 13758-13766, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31789514

RESUMO

Probiotics, such as Lactobacillus, have been proven to be effective in maintaining intestinal homeostasis. The modulatory effect of Lactobacillus on intestinal epithelial development in early life is still unclear. In this study, Lactobacillus isolates with good probiotic abilities were screened and orally administered to detect their regulatory effect on intestinal development in chickens. L. reuteri 22 was isolated from chickens and chosen for subsequent chicken experiments due to its strong acid and bile salt resistance and ability to adhere to epithelial cells. The 3-day-old chickens were orally administrated with 108 CFU L. reuteri 22 for consecutive 7 days. L. reuteri 22 increased Lgr5 mRNA expression (3.23 ± 0.40, P = 0.001) and activated the Wnt/ß-catenin signaling pathway, with increasing expression of proliferating cell nuclear antigen (PCNA) (49.27 ± 9.81, P = 0.021) to support the proliferation of chicken intestinal epithelial cells. Moreover, L. reuteri 22 also inhibited the Notch signaling pathway to induce intestinal stem cell differentiation into goblet cells with increased mucin 2 (Muc-2) expression (1.72 ± 0.34, P = 0.047). L. reuteri 22 significantly enhanced lysozyme mRNA expression (2.32 ± 0.55, P = 0.019) to improve intestinal innate mucosal immunity. This study demonstrated that L. reuteri administration could regulate chicken intestinal epithelium development to ensure the function of the intestinal mucosal barrier, which is beneficial for newborn animals.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/citologia , Células Caliciformes/efeitos dos fármacos , Lactobacillus reuteri/fisiologia , Probióticos/farmacologia , Animais , Galinhas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Caliciformes/citologia , Células Caliciformes/metabolismo , Intestinos/citologia , Intestinos/efeitos dos fármacos , Mucina-2/genética , Mucina-2/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/genética , beta Catenina/metabolismo
15.
Front Neural Circuits ; 13: 73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798420

RESUMO

The ventral tegmental area (VTA) reportedly regulates sleep and wakefulness through communication with the lateral hypothalamus (LH). It has also been suggested that adequate anesthesia produced by administration of chloral hydrate, ketamine, or halothane significantly reduces the GABAergic neuronal firing rate within the VTA. However, the exact effects on GABAergic neurons in the VTA and the mechanisms through which these neurons modulate anesthesia through associated neural circuits is still unclear. Here, we used optogenetic and chemogenetic methods to specifically activate or inhibit GABAergic neuronal perikarya in the VTA or their projections to the LH in Vgat-Cre mice. Electroencephalogram (EEG) spectral analyses and burst suppression ratio (BSR) calculations were conducted following administration of 0.8 or 1.0% isoflurane, respectively; and loss of righting reflex (LORR), recovery of righting reflex (RORR), and anesthesia sensitivity were assessed under 1.4% isoflurane anesthesia. The results showed that activation of GABAergic neurons in the VTA increased delta wave power from 40.0 to 46.4% (P = 0.006) and decreased gamma wave power from 15.2 to 11.5% (P = 0.017) during anesthesia maintenance. BSR was increased from 51.8 to 68.3% (P = 0.017). Induction time (LORR) was reduced from 333 to 290 s (P = 0.019), whereas arousal time (RORR) was prolonged from 498 to 661 s (P = 0.007). Conversely, inhibition of VTA GABAergic neurons led to opposite effects. In contrast, optical activation of VTA-LH GABAergic projection neurons increased power of slow delta waves from 44.2 to 48.8% (P = 0.014) and decreased that of gamma oscillations from 10.2 to 8.0%. BSR was increased from 39.9 to 60.2% (P = 0.0002). LORR was reduced from 330 to 232 s (P = 0.002), and RORR increased from 396 to 565 s (P = 0.007). Optical inhibition of the projection neurons caused opposite effects in terms of both the EEG spectrum and the BSR, except that inhibition of this projection did not accelerate arousal time. These results indicate that VTA GABAergic neurons could facilitate the anesthetic effects of isoflurane during induction and maintenance while postponing anesthetic recovery, at least partially, through modulation of their projections to the LH.


Assuntos
Anestesia Geral , Anestésicos Inalatórios/administração & dosagem , Neurônios GABAérgicos/fisiologia , Região Hipotalâmica Lateral/fisiologia , Isoflurano/administração & dosagem , Área Tegmentar Ventral/fisiologia , Animais , Eletroencefalografia , Neurônios GABAérgicos/efeitos dos fármacos , Região Hipotalâmica Lateral/efeitos dos fármacos , Camundongos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Optogenética , Área Tegmentar Ventral/efeitos dos fármacos
16.
J Biomed Inform ; 99: 103309, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31627021

RESUMO

Temporal relations are crucial in constructing a timeline over the course of clinical care, which can help medical practitioners and researchers track the progression of diseases, treatments and adverse reactions over time. Due to the rapid adoption of Electronic Health Records (EHRs) and high cost of manual curation, using Natural Language Processing (NLP) to extract temporal relations automatically has become a promising approach. Typically temporal relation extraction is formulated as a classification problem for the instances of entity pairs, which relies on the information hidden in context. However, EHRs contain an overwhelming amount of entities and a large number of entity pairs gathering in the same context, making it difficult to distinguish instances and identify relevant contextual information for a specific entity pair. All these pose significant challenges towards temporal relation extraction while existing methods rarely pay attention to. In this work, we propose the associative attention networks to address these issues. Each instance is first carved into three segments according to the entity pair to obtain the differentiated representation initially. Then we devise the associative attention mechanism for a further distinction by emphasizing the relevant information, and meanwhile, for the reconstruction of association among segments as the final representation of the whole instance. In addition, position weights are utilized to enhance the performance. We validate the merit of our method on the widely used THYME corpus and achieve an average F1-score of 64.3% over three runs, which outperforms the state-of-the-art by 1.5%.


Assuntos
Mineração de Dados/métodos , Registros Eletrônicos de Saúde , Processamento de Linguagem Natural , Redes Neurais de Computação , Humanos
17.
J Sep Sci ; 42(23): 3503-3511, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556197

RESUMO

Forsythiaside A is the major component of Forsythia suspensa. This study investigated the degradation mechanism of forsythiaside A. Eight degraded components including forsythiaside I, forsythiaside H, forsythiaside E, caffeic acid, suspensaside A, ß-hydroxy forsythiaside I, ß-hydroxy forsythiaside H, and ß-hydroxy forsythiaside A were identified by using ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry. Then, the quantitative analysis of multi-components by a single-marker was performed with ultra-high performance liquid chromatography to simultaneously determine forsythiaside A, forsythiaside H, and forsythiaside I in Forsythia suspensa preparations. The result showed good linear relationships within 2.871-287.1, 0.231-23.1, and 0.983-98.3 µg/mL (r > 0.9998), with average recoveries of 97.7, 95.7, and 95.8% and relative standard deviations of 1.4, 2.4, and 1.8%, respectively. Using forsythiaside A as an internal reference, the relative retention values of forsythiaside H and forsythiaside I to forsythiaside A were calculated to be 0.89 and 0.61, respectively, and the relative correction factors were 0.816 and 0.799, respectively. The method for quantitative analysis of multi-components by a single-marker was applied to evaluate the overall quality of forsythia preparations. There was no significant difference in the measurement results of the method developed and the method of external standard.


Assuntos
Medicamentos de Ervas Chinesas/química , Forsythia/química , Glicosídeos/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Estrutura Molecular
18.
Vet Microbiol ; 231: 154-159, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955803

RESUMO

Pigs suffer enteritis induced by pathogenic bacteria infection and toxins in the moldy feed, which cause intestinal epithelial damage and diarrhea through the whole breeding cycle. Interleukin-22 (IL-22) plays a critical role in maintaining intestinal mucosal barrier function through repairing intestinal epithelial damage. However, little was known about the effects of IL-22 against apoptosis caused by toxins and infection of intestinal pathogens in the intestinal epithelium, especially in pigs. In this study, we had successfully used prokaryotic expression system to produce recombinant porcine interleukin-22. Meanwhile, purified rIL-22 could activate STAT3 signal pathway and have been demonstrated to be safe to IPEC-J2 cells by increasing E-cadherin expression, without proinflammatory cytokines changes. Furthermore, rIL-22 reversed apoptosis induced by deoxynivalenol (DON) and played a vital part in repairing the intestinal injury. We also found that rIL-22 stimulated epithelial cells to secrete pBD-1 against enterotoxigenic E. coli (ETEC) K88 infection, as well as alleviating apoptosis ratio. This study provided a theoretical basis for curing intestinal inflammation caused by ETEC infection and epithelial apoptosis induced by DON with rIL-22 in pigs.


Assuntos
Escherichia coli Enterotoxigênica/patogenicidade , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Interleucinas/farmacologia , Tricotecenos/efeitos adversos , Animais , Peptídeos Catiônicos Antimicrobianos/biossíntese , Apoptose , Linhagem Celular , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Inflamação , Interleucinas/imunologia , Mucosa Intestinal/citologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Suínos
19.
IEEE Trans Neural Netw Learn Syst ; 30(12): 3611-3620, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30346291

RESUMO

In this paper, the adaptive neural network (NN) tracking control problem is addressed for robot manipulators subject to dead-zone input. The control objective is to design an adaptive NN controller to guarantee the stability of the systems and obtain good performance. Different from the existing results, which used NN to approximate the nonlinearities directly, NNs are employed to identify the originally designed virtual control signals with unknown nonlinear items in this paper. Moreover, a sequence of virtual control signals and real controller are designed. The adaptive backstepping control method and Lyapunov stability theory are used to prove the proposed controller can ensure all the signals in the systems are semiglobally uniformly ultimately bounded, and the output of the systems can track the reference signal closely. Finally, the proposed adaptive control strategy is applied to the Puma 560 robot manipulator to demonstrate its effectiveness.

20.
Biosens Bioelectron ; 117: 138-144, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29894850

RESUMO

It is a novel competitive challenge for electrochemical biosensor to directly, rapidly and ultrasensitively detect the disease markers in the whole serum due to biofouling caused by the complexity of actual samples. In this paper, poly (ethylene glycol) (PEG) and hyaluronic acid (HA) were utilized to modify Fe3O4 @Au nanoparticles (NPs). Based on the successfully preparation and characterization of Fe3O4 @Au@PEG@HA NPs with TEM, SEM, XRD, FTIR and EDS, respectively, a novel immunosensor of brucellosis with high selectivity, sensitivity and almost perfect protein-resistant properties in various external environments, especially, in complex biological systems was fabricated. More importantly, this immunosensor is capable of assaying brucellosis antibody in 100% serum without suffering from any significant biological interference. In addition, a wide linear response range from 10-15 g mL-1 to 10-11 g mL-1 towards antibody in 100% serum and a low limit of detection (LOD) of 0.36 fg mL-1 (3σ, n = 13) are demonstrated, which indicates that this immunosensor has a promising potential in clinical diagnosis.


Assuntos
Anticorpos Antibacterianos/sangue , Brucelose/diagnóstico , Técnicas Eletroquímicas , Imunoensaio/métodos , Nanopartículas Metálicas/química , Brucelose/sangue , Compostos Férricos/química , Ouro/química , Humanos , Ácido Hialurônico/química , Imunoensaio/instrumentação , Limite de Detecção , Magnetismo , Polietilenoglicóis/química
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