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1.
Fish Shellfish Immunol ; 120: 82-91, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34780976

RESUMO

Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) is a multifunctional mediator of the conserved MAPK signaling pathway that plays essential roles in the regulation of immune responses in mammals. However, the function of teleost MAP3K4s in innate immunity, especially in the intestinal immune system, is still poorly understood. In the current study, we identified a fish MAP3K4 homolog (CiMAP3K4) in Ctenopharyngodon idella as well as its immune function in intestine following bacterial infection in vivo and in vitro. The open reading frame (ORF) of CiMAP3K4 encodes putative peptide of 1544 amino acids containing a predicted serine/threonine protein kinase (S_TKc) domain with high identity with other fish MAP3K4s. Phylogenetic analysis revealed the CiMAP3K4 belonged to the fish cluster and showed the closest relationship to Pimephales promelas. Quantitative real-time PCR (qRT-PCR) analysis revealed that CiMAP3K4 transcripts were widely distributed in all tested tissues, especially with high expression in the muscle and intestine of healthy grass carp. In vitro, CiMAP3K4 gene expression was upregulated by bacterial PAMPs (lipolysaccharide (LPS), peptidoglycan (PGN), L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP) and muramyl dipeptide (MDP)) and pathogens (Aeromonas hydrophila and Aeromonas veronii) in primary intestinal cells. In vivo, the mRNA expression levels of CiMAP3K4 in the intestine were significantly induced by bacterial MDP challenge in a time-dependent manner; however, this effect could be inhibited by the bioactive dipeptides ß-alanyl-l-histidine (carnosine) and alanyl-glutamine (Ala-Gln). Moreover, CiMAP3K4 was located primarily in the cytoplasm, and its overexpression increased the transcriptional activity of AP-1 in HEK293T cells. Collectively, these results suggested that CiMAP3K4 might play an important role in the intestinal immune response to bacterial infections, which paves the way for a better understanding of the intestinal immune system of grass carp.

2.
Front Plant Sci ; 12: 739091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630492

RESUMO

Chayote (Sechium edule), a member of the Cucurbitaceae family, is cultivated throughout tropical and subtropical regions of the world and utilized in pharmaceutical, cosmetic and food industries because it is an excellent source of minerals, dietary fibers, protein, vitamins, carotenoids, polysaccharides, phenolic and flavonoid compounds, and other nutrients. Chayote extracts process various medicinal properties, such as anti-cardiovascular, antidiabetic, antiobesity, antiulcer, and anticancer properties. With the rapid advancements of molecular biology and sequencing technology, studies on chayote have been carried out. Research advances, including molecular makers, breeding, genomic research, chemical composition, and pests and diseases, regarding chayote are reviewed in this paper. Future exploration and application trends are briefly described. This review provides a reference for basic and applied research on chayote, an important Cucurbitaceae vegetable crop.

3.
Fungal Genet Biol ; 157: 103632, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34710583

RESUMO

Autophagy plays vital roles in the interaction between the necrotrophic fungal pathogen Sclerotinia sclerotiorum and its hosts. However, so far, only little is known about the impacts of autophagy machinery in S. sclerotiorum per se on the fungal morphogenesis and pathogenesis. Here, through functional genomic approaches, we showed that SsATG8, one of the core components of the autophagy machinery, and its interactor SsNBR1, an autophagy cargo receptor, are important for vegetative growth, sclerotial formation, oxalic acid (OA) production, compound appressoria development, and virulence of S. sclerotiorum. Complementation assays with chimeric fusion constructs revealed that both LDS [AIM (ATG8 interacting motif) / LIR (LC3-interacting region) docking site] and UDS [UIM (ubiquitin-interacting motif) docking site] sites of the SsATG8 are required for its functions in autophagy and pathogenesis. Importantly, ΔSsatg8 and ΔSsnbr1 mutants showed enhanced sensitivity to the exogenous treatment with the proteasome inhibitors bortezomib and carfilzomib, and ΔSsnbr1 mutant had decreased expression of SsATG8 under the proteasomal stress conditions, suggesting that a cross-talk exists between ubiquitin-proteasome and selective autophagy pathways, which enables downstream protein degradation to proceed properly during diverse biological processes. Collectively, our data indicate that SsATG8- and SsNBR1-mediated autophagy is crucial for S. sclerotiorum development, proteasomal stress response and virulence.

4.
J Exp Bot ; 72(15): 5751-5765, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34195821

RESUMO

Due to their sessile nature, plants must respond to various environmental assaults in a coordinated manner. The endoplasmic reticulum is a central hub for plant responses to various stresses. We previously showed that Phytophthora utilizes effector PsAvh262-mediated binding immunoglobulin protein (BiP) accumulation for suppressing endoplasmic reticulum stress-triggered cell death. As a BiP binding partner, Bcl-2-associated athanogene 7 (BAG7) plays a crucial role in the maintenance of the unfolded protein response, but little is known about its role in plant immunity. In this work, we reveal a double-faced role of BAG7 in Arabidopsis-Phytophthora interaction in which it regulates endoplasmic reticulum stress-mediated immunity oppositely in different cellular compartments. In detail, it acts as a susceptibility factor in the endoplasmic reticulum, but plays a resistance role in the nucleus against Phytophthora. Phytophthora infection triggers the endoplasmic reticulum-to-nucleus translocation of BAG7, the same as abiotic heat stress; however, this process can be prevented by PsAvh262-mediated BiP accumulation. Moreover, the immunoglobulin/albumin-binding domain in PsAvh262 is essential for both pathogen virulence and BiP accumulation. Taken together, our study uncovers a double-faced role of BAG7; Phytophthora advances its colonization in planta by utilizing an effector to detain BAG7 in the endoplasmic reticulum.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Phytophthora , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Estresse do Retículo Endoplasmático , Doenças das Plantas , Imunidade Vegetal/genética
5.
Front Public Health ; 9: 685596, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095080

RESUMO

There is uncertainty in the neuromusculoskeletal system, and deterministic models cannot describe this significant presence of uncertainty, affecting the accuracy of model predictions. In this paper, a knee joint angle prediction model based on surface electromyography (sEMG) signals is proposed. To address the instability of EMG signals and the uncertainty of the neuromusculoskeletal system, a non-parametric probabilistic model is developed using a Gaussian process model combined with the physiological properties of muscle activation. Since the neuromusculoskeletal system is a dynamic system, the Gaussian process model is further combined with a non-linear autoregressive with eXogenous inputs (NARX) model to create a Gaussian process autoregression model. In this paper, the normalized root mean square error (NRMSE) and the correlation coefficient (CC) are compared between the joint angle prediction results of the Gaussian process autoregressive model prediction and the actual joint angle under three test scenarios: speed-dependent, multi-speed and speed-independent. The mean of NRMSE and the mean of CC for all test scenarios in the healthy subjects dataset and the hemiplegic patients dataset outperform the results of the Gaussian process model, with significant differences (p < 0.05 and p < 0.05, p < 0.05 and p < 0.05). From the perspective of uncertainty, a non-parametric probabilistic model for joint angle prediction is established by using Gaussian process autoregressive model to achieve accurate prediction of human movement.


Assuntos
Articulação do Joelho , Movimento , Eletromiografia , Humanos , Articulação do Joelho/diagnóstico por imagem , Distribuição Normal
6.
Front Neurosci ; 15: 630250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935628

RESUMO

Two-photon Ca2+ imaging is a leading technique for recording neuronal activities in vivo with cellular or subcellular resolution. However, during experiments, the images often suffer from corruption due to complex noises. Therefore, the analysis of Ca2+ imaging data requires preprocessing steps, such as denoising, to extract biologically relevant information. We present an approach that facilitates imaging data restoration through image denoising performed by a neural network combining spatiotemporal filtering and model blind learning. Tests with synthetic and real two-photon Ca2+ imaging datasets demonstrate that the proposed approach enables efficient restoration of imaging data. In addition, we demonstrate that the proposed approach outperforms the current state-of-the-art methods by evaluating the qualities of the denoising performance of the models quantitatively. Therefore, our method provides an invaluable tool for denoising two-photon Ca2+ imaging data by model blind spatiotemporal processing.

7.
Front Public Health ; 9: 615597, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937165

RESUMO

Early accurate diagnosis of patellofemoral pain syndrome (PFPS) is important to prevent the further development of the disease. However, traditional diagnostic methods for PFPS mostly rely on the subjective experience of doctors and subjective feelings of the patient, which do not have an accurate-unified standard, and the clinical accuracy is not high. With the development of artificial intelligence technology, artificial neural networks are increasingly applied in medical treatment to assist doctors in diagnosis, but selecting a suitable neural network model must be considered. In this paper, an intelligent diagnostic method for PFPS was proposed on the basis of a one-dimensional convolutional neural network (1D CNN), which used surface electromyography (sEMG) signals and lower limb joint angles as inputs, and discussed the model from three aspects, namely, accuracy, interpretability, and practicability. This article utilized the running and walking data of 41 subjects at their selected speed, including 26 PFPS patients (16 females and 10 males) and 16 painless controls (8 females and 7 males). In the proposed method, the knee flexion angle, hip flexion angle, ankle dorsiflexion angle, and sEMG signals of the seven muscles around the knee of three different data sets (walking data set, running data set, and walking and running mixed data set) were used as input of the 1D CNN. Focal loss function was introduced to the network to solve the problem of imbalance between positive and negative samples in the data set and make the network focus on learning the difficult-to-predict samples. Meanwhile, the attention mechanism was added to the network to observe the dimension feature that the network pays more attention to, thereby increasing the interpretability of the model. Finally, the depth features extracted by 1D CNN were combined with the traditional gender features to improve the accuracy of the model. After verification, the 1D CNN had the best performance on the running data set (accuracy = 92.4%, sensitivity = 97%, specificity = 84%). Compared with other methods, this method could provide new ideas for the development of models that assisted doctors in diagnosing PFPS without using complex biomechanical modeling and with high objective accuracy.


Assuntos
Síndrome da Dor Patelofemoral , Inteligência Artificial , Feminino , Humanos , Joelho , Masculino , Redes Neurais de Computação , Síndrome da Dor Patelofemoral/diagnóstico , Caminhada
8.
Nat Commun ; 12(1): 2218, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850117

RESUMO

Revealing the atomistic mechanisms for the high-temperature mechanical behavior of materials is important for optimizing their properties for service at high-temperatures and their thermomechanical processing. However, due to materials microstructure's dynamic recovery and the absence of available in situ techniques, the high-temperature deformation behavior and atomistic mechanisms of materials are difficult to evaluate. Here, we report the development of a microelectromechanical systems-based thermomechanical testing apparatus that enables mechanical testing at temperatures reaching 1556 K inside a transmission electron microscope for in situ investigation with atomic-resolution. With this unique technique, we first uncovered that tungsten fractures at 973 K in a ductile manner via a strain-induced multi-step body-centered cubic (BCC)-to-face-centered cubic (FCC) transformation and dislocation activities within the strain-induced FCC phase. Both events reduce the stress concentration at the crack tip and retard crack propagation. Our research provides an approach for timely and atomic-resolved high-temperature mechanical investigation of materials at high-temperatures.

9.
Front Public Health ; 9: 643191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643997

RESUMO

Patellofemoral pain syndrome (PFPS) is a common disease of the knee. Despite its high incidence rate, its specific cause remains unclear. The artificial neural network model can be used for computer-aided diagnosis. Traditional diagnostic methods usually only consider a single factor. However, PFPS involves different biomechanical characteristics of the lower limbs. Thus, multiple biomechanical characteristics must be considered in the neural network model. The data distribution between different characteristic dimensions is different. Thus, preprocessing is necessary to make the different characteristic dimensions comparable. However, a general rule to follow in the selection of biomechanical data preprocessing methods is lacking, and different preprocessing methods have their own advantages and disadvantages. Therefore, this paper proposes a multi-input convolutional neural network (MI-CNN) method that uses two input channels to mine the information of lower limb biomechanical data from two mainstream data preprocessing methods (standardization and normalization) to diagnose PFPS. Data were augmented by horizontally flipping the multi-dimensional time-series signal to prevent network overfitting and improve model accuracy. The proposed method was tested on the walking and running datasets of 41 subjects (26 patients with PFPS and 15 pain-free controls). Three joint angles of the lower limbs and surface electromyography signals of seven muscles around the knee joint were used as input. MI-CNN was used to automatically extract features to classify patients with PFPS and pain-free controls. Compared with the traditional single-input convolutional neural network (SI-CNN) model and previous methods, the proposed MI-CNN method achieved a higher detection sensitivity of 97.6%, a specificity of 76.0%, and an accuracy of 89.0% on the running dataset. The accuracy of SI-CNN in the running dataset was about 82.5%. The results prove that combining the appropriate neural network model and biomechanical analysis can establish an accurate, convenient, and real-time auxiliary diagnosis system for PFPS to prevent misdiagnosis.


Assuntos
Síndrome da Dor Patelofemoral , Diagnóstico por Computador , Eletromiografia , Humanos , Joelho , Redes Neurais de Computação , Síndrome da Dor Patelofemoral/diagnóstico
10.
Poult Sci ; 100(4): 101003, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33676095

RESUMO

Previously, a fungus was isolated from a diseased pigeon group clinically suspected of being infected with Candida. The fungus was subsequently identified as Candida glabrata using morphology, physiology, biochemistry, and molecular biology testing methods. In the present study, to determine the controlling effects of Chinese herbal medicine for C. glabrata, the bacteriostatic effects of the ethanol extracts Acorus gramineus, Sophora flavescens, Polygonum hydropiper, Cassia obtusifolia, Pulsatilla chinensis, Dandelion, and Cortex phellodendri on C. glabrata in vitro were analyzed. The results showed that the minimum inhibitory concentrations (MIC80) of Cortex phellodendri was 0.25 µg/µL. Meanwhile, that of S. flavescens was 32 µg/µL; C. obtusifolia was 56 µg/µL; A. gramineus and Polygonum hydropiper was 64 µg/µL; and P. chinensis was 112 µg/µL. However, MIC80 for Dandelion was undetectable. In addition, improved drug sensitivity tests revealed that colonies had grown after 24 h in the blank group, as well as the Polygonum hydropiper, P. chinensis, Dandelion, and ethanol groups. The colonies first appeared at the 48-hour point in the other drug-sensitive medium of Chinese herbal medicine. However, no colony growth was found in Cortex phellodendri medium, and the formation of the maximum colony diameter in that group was later than the blank group (e.g., 96 h in the blank group and 120 h in the Chinese herbal medicine group). It was observed that only 17 colony-forming units had grown in 125 µg/µL of the S. flavescens medium, which was significantly different from other groups. Also, the final colony diameter was significantly smaller than that of the other experimental groups. Therefore, it was determined that the A. gramineus, S. flavescens, Polygonum hydropiper, Cassia obtusifolia, P. chinensis, and Cortex phellodendri had certain inhibitory effects on the growth of the C. glabrata. Among those, it was observed that the Cortex phellodendri had the strongest inhibitory effects, followed by the S. flavescens. In the future, these Chinese herbal medicines are expected to be used to treat the fungal infections related to C. glabrata in poultry to improve production performance.


Assuntos
Candida glabrata , Medicamentos de Ervas Chinesas , Animais , Antibacterianos/farmacologia , Doenças das Aves/tratamento farmacológico , Doenças das Aves/microbiologia , Candida glabrata/classificação , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Columbidae/microbiologia , Medicamentos de Ervas Chinesas/farmacologia , Testes de Sensibilidade Microbiana/veterinária
11.
Pest Manag Sci ; 77(2): 805-816, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32909651

RESUMO

BACKGROUND: Anoplophora glabripennis (Coleoptera: Cerambycidae) is a major quarantine pest in forestry. It is widely distributed throughout many regions such as Asia, Europe, and North America, and has enormous destructive potential for forests. The larvae of A. glabripennis overwinter in a dormant state with strong cold tolerance, and whether the larvae survive winter determines the population density in the following year. However, the molecular mechanisms of this process are not clear. RESULTS: RNA sequencing (RNA-Seq) analysis of A. glabripennis larvae at five overwintering stages identified 6876 differentially expressed genes (DEGs). Among these, 46 functional genes that might respond to low temperature were identified. Weighted gene co-expression network analysis revealed that the MEturquoise module was correlated with the overwintering process. The STPK, PP2A, DGAT, and HSF genes were identified as hub genes using visualization of gene network. In addition, four genes related to sugar transport, gluconeogenesis and glycosylation were screened, which may be involved in the metabolic regulation of overwintering larvae. The protein-protein interaction network indicated that ribosomal protein and ATP synthase may play an important role in connecting with other proteins. The expression levels of fifteen hub genes were further validated by quantitative RT-PCR, and the results were consistent with RNA-Seq. CONCLUSION: This study demonstrates key genes that may reveal the molecular mechanism of overwintering in A. glabripennis larvae. The genes may be the potential targets to prevent larvae from surviving the cold winter by developing new biological agents using genetic engineering.


Assuntos
Besouros , Animais , Ásia , Besouros/genética , Europa (Continente) , Larva/genética , América do Norte
12.
IEEE J Biomed Health Inform ; 25(1): 59-68, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32340970

RESUMO

Functional electrical stimulation (FES) provides an effective way for foot drop (FD) correction. To overcome the redundant and blind stimulation problems in the state-of-the-art methods, this study proposes a closed-loop scheme for an adaptive electromyography (EMG)-modulated stimulation profile. The developed method detects real-time angular velocity during walking. It provides feedbacks to a long short-term memory (LSTM) neural network for predicting synchronous tibialis anterior (TA) EMG. Based on the prediction, it modulates the stimulation intensity, taking into account of the subject-specific dead zone and saturation of the electrically evoked activation. The proposed method is tested on ten able-bodied participants and six FD subjects as proof of concept. The experimental results show that the proposed method can successfully induce the dorsiflexion of the ankle joint, and generate an activation pattern similar to a natural gait, with the mean Correlation Coefficient of 0.9021. Thus, the proposed method has the potential to help patients to retrieve normal gait.


Assuntos
Terapia por Estimulação Elétrica , Transtornos Neurológicos da Marcha , Neuropatias Fibulares , Estimulação Elétrica , Eletromiografia , Marcha , Humanos , Estudo de Prova de Conceito
13.
Plant Physiol Biochem ; 157: 195-210, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33120111

RESUMO

In nature, many different factors cause plants to present variegated leaves. The purpose of this study was to reveal the changes in the green and albino leaves of Hydrangea macrophylla 'Maculata'. It was found that in the albino zone, the leaves became thinner, the chloroplast structure disappeared, and a large number of leucoplasts replaced chloroplasts. In addition, the albino zone of the leaves contained almost no chlorophyll and showed no function related to transforming and utilizing light energy, and more intense oxidative stress was observed in the albino zone of the leaves than in the green zone. RNA-seq analysis showed that the chlorophyll synthesis pathway of the albino zone of leaves was blocked. Upregulated expression of the hydrangea ringspot virus (HdRSV) coat protein (CP) gene was detected in albino tissue by RT-qPCR. Finally, combined UPLC-MS/MS and RNA-seq analyses revealed metabolic changes involving multiple pathways in albino leaf tissue, centered on the TCA cycle. We hypothesize that HdRSV may alter energy metabolism in the albino zone of leaves, including increased lipid metabolism, reduced sugar metabolism, and increased synthesis of amino acids and the viral capsid protein from ribosomes.


Assuntos
Hydrangea/metabolismo , Hydrangea/virologia , Metaboloma , Folhas de Planta/metabolismo , Vírus de Plantas/patogenicidade , Transcriptoma , Cromatografia Líquida , Ciclo do Ácido Cítrico , Folhas de Planta/virologia , RNA-Seq , Espectrometria de Massas em Tandem
14.
Appl Opt ; 59(27): 8111-8117, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32976389

RESUMO

A new broadband tunable metamaterial absorber based on different radii of vanadium dioxide (VO2) rings loaded on the dielectric layer is designed. According to the insulator-to-metal phase transition characteristics of VO2 under thermal excitation, the dynamic adjustment of the absorption by the external temperature is achieved. The simulation results demonstrate that when VO2 is in its metal phase at high temperature, an absorption greater than 90% in the bandwidth range of 2.64-7 THz can be obtained and its relative bandwidth is reached to 90.5%. However, the absorption rate in the same frequency range is always lower than 2.3% when VO2 is in the insulator phase at low temperature, which means that the absorber can be used as a perfect reflector. The maximum tunable range of the proposed absorber can be realized from below 2.3% to nearly 100%. We further analyze and discuss the equivalent impedance and electric field distribution of the absorber and clarify the adjustment mechanism of the absorption performance of the VO2 ring. In addition, a multireflection interference theory is also investigated to quantitatively explain the physical absorption mechanism. Such a tunable broadband absorber based on temperature control has great potential to be applied to sensors, thermophotovoltaics, and wireless communication.

15.
Poult Sci ; 99(9): 4530-4538, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32867997

RESUMO

In this study, a strain of Trichosporon was isolated from white pseudomembranes and ulcers formed on mucous membranes of pigeon bursas and was identified through gene sequencing. Bacteriostatic actions of Acorus gramineus, Sophora flavescens, Polygonum hydropiper, and Chinese herbal mixture on this species were explored in vitro, and the minimum inhibitory concentration of herbal medicines against Trichosporon was determined through microdilution method. Therapeutic effects of herbal medicines on chickens infected by Trichosporon were studied, whose results showed that minimum inhibitory concentration of A. gramineus was 32 µg/µL, that of S. flavescens was 2 µg/µL, that of P. hydropiper was 120 µg/µL, and that of Chinese herbal mixture was 36 µg/µL. Antibacterial effects of S. flavescens were the best. In accordance with animal experiments, therapeutic effects of Chinese herbal medicines on infected chickens were better than those of fluconazole. The mortality rate of the Chinese herbal medicine treatment group was 33.33%, that of the fluconazole treatment group was 46.67%, and that of the Chinese medicine protection group was 23.33%. The longer the time of Chinese medicine treatments was, the better the treatment effects would be. Glutamic oxaloacetylase values of the serum and liver in the Chinese herbal medicine treatment group were both significantly lower than those of the nontreatment group. From the results, it can be seen that A. gramineus, S. flavescens, P. hydropiper, and Chinese herbal mixture have certain inhibitory effects on Trichosporon spp. Chinese herbal medicine protections in advance could reduce Trichosporon infections.


Assuntos
Galinhas , Medicamentos de Ervas Chinesas , Trichosporon , Tricosporonose , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Testes de Sensibilidade Microbiana/veterinária , Trichosporon/efeitos dos fármacos , Tricosporonose/tratamento farmacológico , Tricosporonose/veterinária
16.
Poult Sci ; 99(9): 4598-4606, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32868004

RESUMO

To investigate the impact of total flavonoids of Epimedium (TFE) on the development of follicles of laying hens, 3 types of follicles including primary, prehierarchical, and preovulatory follicles were selected to obtain the follicular granulosa cells cultured in vitro. First, extraction of TFE was conducted by alcohol-soluble and ultrasonic methods. The effects of TFE on activity and proliferation of follicular granulosa cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and measuring the expression of proliferating cell nuclear antigen mRNA through real-time quantitative polymerase chain reaction, and the expression of the follicle-stimulating hormone receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, and cytochrome P450 family 11 subfamily A member 1 mRNA was detected to study the functions of TFE affecting the differentiation and hormone secretion by granulosa cells. The results showed that TFE significantly improved the proliferation of 3 types of granulosa cells and promoted the differentiation of granulosa cells and accelerated the conversion of primary follicles to prehierarchical follicles. Total flavonoids of Epimedium played an important role in promoting progesterone secretion by prehierarchical and preovulatory granulosa cells. The results indicated that TFE could promote proliferation and differentiation of follicular granulosa cells and improve hormone secretion and follicle development, which provided reference data for TFE used as a feed additive or safe Chinese veterinary medicine to promote the laying rate.


Assuntos
Diferenciação Celular , Galinhas , Epimedium , Flavonoides , Células da Granulosa , Animais , Diferenciação Celular/efeitos dos fármacos , Galinhas/crescimento & desenvolvimento , Epimedium/química , Feminino , Flavonoides/farmacologia , Células da Granulosa/citologia , Células da Granulosa/efeitos dos fármacos
17.
Int J Med Sci ; 17(9): 1246-1256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547320

RESUMO

Sorafenib is the standard systemic treatment for advanced hepatocellular carcinoma (HCC), and improving its therapeutic effects is crucial for addressing cancer aggression. We previously reported that epalrestat, an aldo-keto reductase 1B10 inhibitor, enhanced sorafenib's inhibitory effects on HCC xenograft in nude mice. This study aimed to elucidate the mechanism of epalrestat's anti-tumour enhancing effects on sorafenib. HepG2 cells were treated with sorafenib, epalrestat, and their combination. Cell proliferation was assessed with Cell Counting Kit-8 and colony formation assays. AKR1B10 supernate concentration and enzyme activity were detected by ELISA assay and the decrease of optical density of NADPH at 340 nm. Cell cycle and apoptosis analyses were performed with flow cytometry. Western blots clarified the molecular mechanism underlying effects on cell cycle, apoptosis, and autophagy. The anti-tumour mechanism was then validated in vivo through TUNEL and immunohistochemistry staining of HCC xenograft sections. Epalrestat combined with sorafenib inhibited HepG2 cellular proliferation in vitro, arrested the cell cycle at G0/G1, and promoted apoptosis and autophagy. Treatment with a specific mTOR activator MHY-1485 increased mTOR phosphorylation, while suppressing apoptosis and autophagy. Consistent with in vitro results, data from the HCC-xenograft nude mouse model also indicated that combined treatment inhibited the mTOR pathway and promoted apoptosis and autophagy. In conclusion, epalrestat heightens sorafenib's anti-cancer effects via blocking the mTOR pathway, thus inducing cell cycle arrest, apoptosis, and autophagy.


Assuntos
Membro B10 da Família 1 de alfa-Ceto Redutase/metabolismo , Rodanina/análogos & derivados , Sorafenibe/farmacologia , Tiazolidinas/farmacologia , Membro B10 da Família 1 de alfa-Ceto Redutase/genética , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Western Blotting , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Células Hep G2 , Xenoenxertos , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Rodanina/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
18.
Science ; 369(6499): 77-81, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32376603

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Betacoronavirus/isolamento & purificação , COVID-19 , Vacinas contra COVID-19 , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Relação Dose-Resposta Imunológica , Feminino , Imunogenicidade da Vacina , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Projetos Piloto , Pneumonia Viral/virologia , Ratos , Ratos Wistar , SARS-CoV-2 , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Células Vero , Carga Viral , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
19.
Transpl Int ; 33(9): 1040-1045, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32357275

RESUMO

To summarize measures for the prevention and control of the 2019 novel coronavirus disease (COVID-19) in the department of kidney transplantation. We retrospectively analyzed the clinical data of outpatients and inpatients in the department of kidney transplantation from January 20 to March 1, 2020, and followed up the in-home kidney transplant recipients and those waiting for kidney transplantation through the Internet platform. Our department had formulated detailed prevention and control measures, mainly including kidney transplant outpatient management, kidney transplantation ward management, management of kidney transplant surgery, dialysis management of patients waiting for kidney transplantation, personal protection of medical staff, and follow-up management of discharged patients after kidney transplantation. During the epidemic period, there were no COVID-19 cases among 68 outpatient examined kidney transplant recipients, 32 hospitalized kidney transplant recipients, 19 patients waiting for kidney transplantation in hospital, and 30 medical staff. There were no COVID-19 cases among 160 follow-up recipients after kidney transplantation and 60 patients waiting for kidney transplantation. During the epidemic period, we implemented strict prevention and control measures and adjusted working methods and procedures to ensure safe and orderly work of the department.


Assuntos
COVID-19/prevenção & controle , Transplante de Rim , Adulto , COVID-19/epidemiologia , COVID-19/transmissão , China/epidemiologia , Feminino , Hospitalização , Humanos , Transplante de Rim/efeitos adversos , Masculino , Corpo Clínico Hospitalar , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Isolamento de Pacientes , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Transplantados
20.
Poult Sci ; 99(5): 2757-2765, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359613

RESUMO

In the present study, for the purpose of investigating the effects of the total flavonoids of Epimedium (TFE) in regard to preventing the development of atrophied oviducts and follicles induced by forced molting, 300-day-old Hy-Line Brown layer hens were divided into 3 study groups as follows: the control (CON) group was the normal group, without forced molting and TFE treatments; the TFE1 group was treated by adding a 1‰ TFE treatment after forced molting; and the TFE0 group was not treated by TFE after forced molting. During this study's experimental process, the egg production rates were recorded each day. In addition, the hens were randomly chosen to be weighed every 4 D and also randomly selected to be sacrificed every 7 D. Then, sample tissues of albumen-secreting part and uterus from the fallopian tube of the layer hens were collected for PCR and hematoxylin-eosin staining tests. The results showed that the body weights, number of follicles, and weights and sizes of the fallopian tube for the TFE1 and TFE0 groups were significantly reduced when compared with those of the control group on the 15th D of the experiment. Furthermore, at the end of study, it was found that the egg production rates, weights of the fallopian tube, and ovarian follicles of TFE1 had recovered to normal levels. At the same time, the serum estrogen and the expressions of the progesterone receptor and estrogen receptor mRNA in fallopian tube were higher than those observed for the TFE0 group. The results of this study provided valuable evidence that TFE could improve the development of atrophied oviducts and increase the egg laying rates, thereby making it a potential multicomponent natural drug for egg production in the future.


Assuntos
Proteínas Aviárias/metabolismo , Galinhas/metabolismo , Epimedium/química , Tubas Uterinas/efeitos dos fármacos , Flavonoides/metabolismo , Folículo Ovariano/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Animais , Estrogênios/metabolismo , Tubas Uterinas/crescimento & desenvolvimento , Feminino , Flavonoides/administração & dosagem , Muda , Folículo Ovariano/crescimento & desenvolvimento , RNA Mensageiro/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
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