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1.
Sci Rep ; 11(1): 19783, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611209

RESUMO

Deep learning networks have been successfully applied to transfer functions so that the models can be adapted from the source domain to different target domains. This study uses multiple convolutional neural networks to decode the electroencephalogram (EEG) of stroke patients to design effective motor imagery (MI) brain-computer interface (BCI) system. This study has introduced 'fine-tune' to transfer model parameters and reduced training time. The performance of the proposed framework is evaluated by the abilities of the models for two-class MI recognition. The results show that the best framework is the combination of the EEGNet and 'fine-tune' transferred model. The average classification accuracy of the proposed model for 11 subjects is 66.36%, and the algorithm complexity is much lower than other models.These good performance indicate that the EEGNet model has great potential for MI stroke rehabilitation based on BCI system. It also successfully demonstrated the efficiency of transfer learning for improving the performance of EEG-based stroke rehabilitation for the BCI system.

2.
World J Gastroenterol ; 27(36): 6128-6141, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34629824

RESUMO

BACKGROUND: Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines. AIM: To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs). METHODS: Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared. RESULTS: Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group (P = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, P = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups. CONCLUSION: Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Primárias Múltiplas , Tumores do Estroma Gastrointestinal/terapia , Humanos , Índice Mitótico , Prognóstico , Pontuação de Propensão
3.
Hum Vaccin Immunother ; : 1-5, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623220

RESUMO

To evaluate whether two-dose of varicella vaccine would provide a better protection to children from varicella than one-dose, we conducted a 1:3 matched case-control study in children in Qingdao, China. A total of 509 varicella cases aged 6-11 y were collected from the China Information System for Disease Control and Prevention (CISDCP). And 1,527 controls, who did not suffer from varicella, were selected and matched with cases by age and class. The varicella vaccine effectiveness (VE) and corresponding 95% confidence interval (95% CI) were calculated. The vaccination coverage rate of one-dose varicella vaccine in the cases was 52.9%, while for the controls was 59.1%. And the two-dose vaccination rate in the cases and controls were 4.3% and 14.5%, respectively. A statistically significant difference was found in the immunization history between the cases and controls (P < .001).The overall varicella VE was 56.1% (95% CI: 45.0%-64.9%), and the VE of two-dose vaccination (81.6%, 95% CI: 70.5%-88.4%) was substantially higher than that of one-dose vaccination (44.7%, 95% CI: 31.6%-55.4%). For less than 2 y, 2-4 y, 4-6 y, and more than 6 y after only one-dose vaccination, the varicella VE were 96.6% (95% CI: 75.0%-99.5%), 81.2% (95% CI: 55.6%-92.0%), 60.8% (95% CI: 46.8%-70.2%), and 18.0% (95% CI: 4.3%-35.6%), respectively. The varicella VE gradually decreased over time (P for trend < 0.001). It is recommended that the coverage of varicella vaccine should be increased and two-dose of varicella vaccine should be included in the National Immunization Program of China.

4.
Sci Rep ; 11(1): 19478, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593870

RESUMO

Immunomodulation is an ability of several particular probiotics. However, it still remains unclear whether the immunomodulatory effects of specific probiotics vary for different antigen presentation models with the same antigen. To investigate this matter, six groups of BALB/c mice (n = 10) were exposed to one of two antigen presentation models: ovalbumin (OVA) by injection alone, or injection plus intranasal administration. Moreover, the mice were fed distilled water or Lactobacillus casei Shirota fermented beverage (LcSFB) at low (2.5 × 109 CFU/kg body weight) or high doses (5 × 109 CFU/kg body weight) by gavage for 8 weeks. LcSFB enhanced the proliferation of splenocytes, production of OVA-specific immunoglobulin (Ig)-G and IgA, and the ratio of T-helper (Th)-2/Th1 cytokines in mice injected with OVA. Conversely, in the mice treated with OVA by injection plus intranasal administration, LcSFB attenuated the immune responses against OVA by reducing the proliferation of splenocytes, levels of OVA-specific IgE, IgG, and IgM, and ratio of Th2/Th1 cytokines. Moreover, LcSFB increased the percentage of regulatory T cells in the injection plus intranasal administration group. Taken together, this work indicates the immunoregulatory effects of LcSFB depend on how the antigen is presented. Therefore, the use of probiotics to boost the immune system must be carefully considered.

5.
FASEB J ; 35(11): e21856, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34606651

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is a severe central nervous system (CNS) autoimmune disease that primarily damages the optic nerves and spinal cord. Group 2 innate lymphoid cells (ILC2) are potent producers of type 2 cytokines that orchestrate immune and inflammatory responses. However, the role of ILC2 in CNS autoimmune diseases remains unknown. In patients with NMOSD, we identified a significant reduction of ILC2 in peripheral blood, which was correlated with disease severity. Using a mouse model of NMOSD induced by intracerebral injection of NMOSD-IgG with complement, we found CNS infiltration of ILC2 mainly expressing interleukin (IL)-5 and IL-13. The depletion of ILC2 led to increased CNS lesion volume, reduced CNS glucose metabolism, and augmented astrocyte injury and demyelination. The exacerbated NMOSD pathology was accompanied by increased accumulation of Iba1+ cells and complement activity in CNS lesions. In addition, the expansion of ILC2 using IL-33 attenuated NMO pathology. Collectively, these findings suggest a beneficial role of ILC2 in NMOSD, which deserves further investigation for future design of immune therapies to treat patients with NMOSD.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34608727

RESUMO

Plants use secondary metabolites such as polyphenols for chemical defense against pathogens and herbivores. Despite their importance in plant pathogen interactions and tolerance to diseases, it remains challenging to detect polyphenols in complex plant tissues. Here, we create molecular sensors for plant polyphenol imaging that are based on near-infrared (NIR) fluorescent single wall carbon nanotubes (SWCNTs). We identified polyethylene glycol- phospholipids that render (6,5)-SWCNTs sensitive ( K d  = 90 nM) to plant polyphenols (tannins, flavonoids, …), which red-shift (up to 20 nm) and quench their emission (~1000 nm). These sensors report changes in total polyphenol level after herbivore or pathogen challenge in crop plant systems (Soybean  Glycine max ) and leaf tissue extracts ( Tococa spp).  We furthermore demonstrate remote chemical imaging of pathogen-induced polyphenol release from roots of soybean seedlings over the time course of 24h. This approach allows  in situ  visualization and understanding of the chemical plant defense in real time and paves the way for plant phenotyping for optimized polyphenol secretion.

7.
Sensors (Basel) ; 21(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34640802

RESUMO

Due to the high mortality of many cancers and their related diseases, the prediction and prognosis techniques of cancers are being extensively studied to assist doctors in making diagnoses. Many machine-learning-based cancer predictors have been put forward, but many of them have failed to become widely utilised due to some crucial problems. For example, most methods require too much training data, which is not always applicable to institutes, and the complicated genetic mutual effects of cancers are generally ignored in many proposed methods. Moreover, a majority of these assist models are actually not safe to use, as they are generally built on black-box machine learners that lack references from related field knowledge. We observe that few machine-learning-based cancer predictors are capable of employing prior knowledge (PrK) to mitigate these issues. Therefore, in this paper, we propose a generalisable informed machine learning architecture named the Informed Attentive Predictor (IAP) to make PrK available to the predictor's decision-making phases and apply it to the field of cancer prediction. Specifically, we make several implementations of the IAP and evaluate its performance on six TCGA datasets to demonstrate the effectiveness of our architecture as an assist system framework for actual clinical usage. The experimental results show a noticeable improvement in IAP models on accuracies, f1-scores and recall rates compared to their non-IAP counterparts (i.e., basic predictors).


Assuntos
Neoplasias , Humanos , Aprendizado de Máquina , Neoplasias/diagnóstico , Prognóstico
8.
Comput Biol Med ; 138: 104914, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34638021

RESUMO

Electrocardiogram (ECG) and phonocardiogram (PCG) are both noninvasive and convenient tools that can capture abnormal heart states caused by coronary artery disease (CAD). However, it is very challenging to detect CAD relying on ECG or PCG alone due to low diagnostic sensitivity. Recently, several studies have attempted to combine ECG and PCG signals for diagnosing heart abnormalities, but only conventional manual features have been used. Considering the strong feature extraction capabilities of deep learning, this paper develops a multi-input convolutional neural network (CNN) framework that integrates time, frequency, and time-frequency domain deep features of ECG and PCG for CAD detection. Simultaneously recorded ECG and PCG signals from 195 subjects are used. The proposed framework consists of 1-D and 2-D CNN models and uses signals, spectrum images, and time-frequency images of ECG and PCG as inputs. The framework combining multi-domain deep features of two-modal signals is very effective in classifying non-CAD and CAD subjects, achieving an accuracy, sensitivity, and specificity of 96.51%, 99.37%, and 90.08%, respectively. The comparison with existing studies demonstrates that our method is very competitive in CAD detection. The proposed approach is very promising in assisting the real-world CAD diagnosis, especially under general medical conditions.

9.
Front Public Health ; 9: 747787, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650953

RESUMO

Background: Vaccines have been contributing to eradicate or drastically reduce the incidence of common diseases. Simultaneously, vaccine hesitancy is considered among the top ten global health threats. The COVID-19 pandemic has caused a tremendous impact on health, economics, and society worldwide, while also reinforcing faulty beliefs about the necessity of vaccine programs as a whole. This study aims to synthesise evidence on the impact of the COVID-19 pandemic on vaccine hesitancy. Methods: A scoping review of literature between 1 January 2020 and 1 August 2021 was performed. Results: COVID-19 vaccine acceptance decreased from more than 70 to <50% in 8 months starting from January 2020. Healthcare professionals demonstrate higher rates of vaccine receptivity than the public, which was more influenced by (social) media. The circulation of misinformation was associated with increased fear of side effects related to COVID-19 vaccines. Regarding other vaccines coverage, parents' intentions to vaccinate their children against influenza increased 15.8% during the COVID-19 pandemic so far. Nonetheless, the number of vaccines administered decreased, influenced by factors like fear of being exposed to the virus at healthcare facilities and restrictions. Conclusions: Several efforts should be undertaken to improve vaccine acceptance and coverage now and beyond the pandemic to optimal population protection.


Assuntos
COVID-19 , Vacinas contra Influenza , Vacinas contra COVID-19 , Criança , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
10.
Blood Purif ; : 1-6, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649238

RESUMO

INTRODUCTION: Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) are recent prognostic biomarkers associated with inflammation. Increased erythropoiesis resistance index (ERI) may predict the risk of all-cause and cardiovascular mortality in hemodialysis (HD) patients. However, the roles of NLR and PLR in erythropoietin (EPO) responsiveness remain unclear in HD patients. This study aims to investigate the relationship between NLR and PLR and EPO responsiveness in maintenance HD patients. METHODS: A total of 299 HD patients were included in this survey. Laboratory data and demographic details were collected. EPO responsiveness was evaluated by ERI. Pearson correlation analysis and logistic regressions were conducted to evaluate the factors that may be associated with EPO responsiveness. RESULTS: The EPO responsiveness was positively related to ferritin and negatively related to serum albumin, lymphocytes, and hemoglobin. A multivariate linear regression revealed that only NLR (standardized ß = 0.13, p = 0.024) but not PLR (standardized ß = 0.107, p = 0.063) was correlated with a higher ERI. CONCLUSION: A higher NLR level was shown to be a cheaper method to predict worse EPO responsiveness in HD patients.

11.
J Microbiol Biotechnol ; 31(1)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34489377

RESUMO

The genus Streptomyces is intensively studied due to its excellent ability to produce secondary metabolites with diverse bioactivities. In particular, adequate precursors of secondary metabolites as well as sophisticated post modification systems make some high-yield industrialstrains of Streptomyces the promising chassis for the heterologous production of natural products. However, lack of efficient genetic tools for the manipulation of industrial strains, especially the episomal vector independent tools suitable for large DNA fragment deletion, makes it difficult to remold the metabolic pathways and streamline the genomes in these strains. In this respect, we developed an efficient deletion system independent of the episomal vector for large DNA fragment deletion. Based on this system, four large segments of DNA, ranging in length from 10 kb to 200 kb, were knocked out successfully from three industrial Streptomyces strains without any marker left. Notably, compared to the classical deletion system used in Streptomyces, this deletion system takes about 25% less time in our cases. This work provides a very effective tool for further genetic engineering of the industrial Streptomyces.

12.
Adv Sci (Weinh) ; : e2102027, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473427

RESUMO

The organic passivated carbon nanotube (CNT)/silicon (Si) solar cell is a new type of low-cost, high-efficiency solar cell, with challenges concerning the stability of the organic layer used for passivation. In this work, the stability of the organic layer is studied with respect to the internal and external (humidity) water content and additionally long-term stability for low moisture environments. It is found that the organic passivated CNT/Si complex interface is not stable, despite both the organic passivation layer and CNTs being stable on their own and is due to the CNTs providing an additional path for water molecules to the interface. With the use of a simple encapsulation, a record power conversion efficiency of 22% is achieved and a stable photovoltaic performance is demonstrated. This work provides a new direction for the development of high-performance/low-cost photovoltaics in the future and will stimulate the use of nanotubes materials for solar cells applications.

13.
Dis Markers ; 2021: 6482665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512815

RESUMO

Diabetic retinopathy (DR) is a common chronic fundus disease, which has four different kinds of microvessel structure and microvascular lesions: microaneurysms (MAs), hemorrhages (HEs), hard exudates, and soft exudates. Accurate detection and counting of them are a basic but important work. The manual annotation of these lesions is a labor-intensive task in clinical analysis. To solve the problem, we proposed a novel segmentation method for different lesions in DR. Our method is based on a convolutional neural network and can be divided into encoder module, attention module, and decoder module, so we refer it as EAD-Net. After normalization and augmentation, the fundus images were sent to the EAD-Net for automated feature extraction and pixel-wise label prediction. Given the evaluation metrics based on the matching degree between detected candidates and ground truth lesions, our method achieved sensitivity of 92.77%, specificity of 99.98%, and accuracy of 99.97% on the e_ophtha_EX dataset and comparable AUPR (Area under Precision-Recall curve) scores on IDRiD dataset. Moreover, the results on the local dataset also show that our EAD-Net has better performance than original U-net in most metrics, especially in the sensitivity and F1-score, with nearly ten percent improvement. The proposed EAD-Net is a novel method based on clinical DR diagnosis. It has satisfactory results on the segmentation of four different kinds of lesions. These effective segmentations have important clinical significance in the monitoring and diagnosis of DR.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34519195

RESUMO

Low-dimensional organic-inorganic hybrid perovskites have attracted much interest owing to their superior solar conversion performance, environmental stability, and excitonic properties compared to their three-dimensional (3D) counterparts. Among reduced-dimensional perovskites, guanidinium-based perovskites crystallize in layered one-dimensional (1D) and two-dimensional (2D). Here, our studies demonstrate how the dimensionality of the hybrid perovskite influences the chemical and physical properties under different pressures (i.e., bond distance, angle, vdW distance). Comprehensive studies show that 1D GuaPbI3 does not undergo a phase transition even up to high pressures (∼13 GPa) and its band gap monotonically reduces with pressure. In contrast, 2D Gua2PbI4 exhibits an early phase transition at 5.5 GPa and its band gap follow nonmonotonic pressure response associated with phase transition as well as other bond angle changes. Computational simulations reveal that the phase transition is related to the structural deformation and rotation of PbI6 octahedra in 2D Gua2PbI4 owing to a larger degree of freedom of deformation. The soft lattice allows them to uptake large pressures, which renders structural phase transitions possible. Overall the results offer the first insights into how layered perovskites with different dimensionality respond to structural changes driven by pressure.

15.
Int J Med Sci ; 18(15): 3395-3402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522166

RESUMO

Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.


Assuntos
COVID-19/diagnóstico por imagem , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , COVID-19/sangue , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Contagem de Linfócitos , Oxigênio/uso terapêutico , Prognóstico
16.
Mol Med Rep ; 24(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34515326

RESUMO

Stroke is one of the main causes of disease­related mortality worldwide. Buyang Huanwu Decoction (BHD) has been used to protect against stroke and stroke­induced disability for several years in China. Studies have shown that BHD can relieve neuronal damage in rats with cerebral ischemia/reperfusion (I/R) injury. However, the mechanism remains unclear. A middle cerebral artery occlusion and reperfusion (MCAO­R) model was used in the present study. The animals were treated with BHD (5, 10 and 20 g/kg) or rapamycin. Infarct size and modified neurological severity score were calculated on day 5 following MCAO­R surgery. Cellular changes around the ischemic penumbra were revealed by hematoxylin and eosin and Nissl staining. The protein expression levels of nestin, brain­derived neurotrophic factor (BDNF), doublecortin on the X chromosome (DCX) and autophagy­related proteins (beclin 1, LC3­II and p62) in the peri­ischemic area of the brain were detected. The results demonstrated that post­surgical treatment with BHD reduced the brain infarct size and improved neurological deficits in MCAO­R rats. BHD protected against MCAO­R­induced neuronal impairment and promoted neurogenesis, increased the protein expression of nestin, BDNF and DCX and markedly enhanced autophagy by increasing beclin 1 and LC3­II and decreasing p62. Meanwhile, BHD promoted the expression of sirtuin 1 (SIRT1), an important regulator of autophagy. In conclusion, the present study suggested that post­surgical treatment with BHD could protect rat brains from I/R injury, potentially through the SIRT1/autophagy pathway.

17.
ACS Synth Biol ; 10(9): 2359-2370, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34469126

RESUMO

Cyclohexanone monooxygenases (CHMO) consume molecular oxygen and NADPH to catalyze the valuable oxidation of cyclic ketones. However, CHMO usage is restricted by poor stability and stringent specificity for NADPH. Efforts to engineer CHMO have been limited by the sensitivity of the enzyme to perturbations in conformational dynamics and long-range interactions that cannot be predicted. We demonstrate an aerobic, high-throughput growth selection platform in Escherichia coli for oxygenase evolution based on NADH redox balance. We applied this NADH-dependent selection to alter the cofactor specificity of CHMO to accept NADH, a less expensive cofactor than NADPH. We first identified the variant CHMO DTNP (S208D-K326T-K349N-L143P) with a ∼1200-fold relative cofactor specificity switch from NADPH to NADH compared to the wild type through semirational design. Molecular modeling suggests CHMO DTNP activity is driven by cooperative fine-tuning of cofactor contacts. Additional evolution of CHMO DTNP through random mutagenesis yielded the variant CHMO DTNPY with a ∼2900-fold relative specificity switch compared to the wild type afforded by an additional distal mutation, H163Y. These results highlight the difficulty in engineering functionally innovative variants from static models and rational designs, and the need for high throughput selection methods. Our introduced tools for oxygenase engineering accelerate the advancements of characteristics essential for industrial feasibility.

18.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4314-4322, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581034

RESUMO

Bolbostemma paniculatum is a commonly used Chinese medicinal material effective in clearing heat, removing toxin, eliminating phlegm, and alleviating swelling. The anti-tumor activity it possesses makes it a research hotspot. At present, 76 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids, anthraquinones, organic acids, etc., with anti-tumor, antiviral, and immunosuppressive pharmacological activities. This study reviewed the research on the chemical constituents and pharmacological effects of B. paniculatum over the past 20 years, aiming to provide a scientific basis for the research on the pharmacodynamic material basis and promote the development and utilization of B. paniculatum.


Assuntos
Cucurbitaceae , Medicamentos de Ervas Chinesas , Triterpenos , Medicamentos de Ervas Chinesas/farmacologia , Edema
19.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4480-4487, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581053

RESUMO

This study investigated the mechanism of improving impaired glucose tolerance(IGT) of rats by Huanglian Wendan Decoction from the perspective of the skeletal muscle Nod-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/interleukin-1ß(IL-1ß), interleukin-18(IL-18) pathway. Healthy male SD rats were fed with the diet containing 45% fat for 20 weeks, accompanied by a high-temperature and high-humidity environment and an inactive lifestyle, for the establishment of the IGT rat model. The rats were divided into the blank control group, model control group, metformin hydrochloride group(positive drug group, 0.05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group(7.8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks, the obesity and glycemic indexes of all the rats were measured. The fasting serum insulin(FINS) level was determined by ELISA, with the insulin sensitivity index(ISI) and insulin resistance index(IRI) calculated. The mRNA and protein expression le-vels of nuclear factor kappaB(NF-κB), NLRP3, caspase-1, IL-1ß and IL-18 in skeletal muscle tissue were detected by real-time polymerase chain reaction(PCR), Western blot and immunofluorescence. Compared with the blank control group, the model control group witnessed significantly increased mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1ß and IL-18. As revealed by the comparison with the model control group, Huanglian Wendan Decoction could effectively regulate the obesity status, reduce body weight, correct the abnormal levels of 2-hour plasma glucose(2 hPG), insulin resistance index(IRI), insulin sensitivity index(ISI), and lower the mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1ß and IL-18 in the skeletal muscle tissue of IGT rats. Combined with previous studies, the above results showed that the occurrence and development of IGT was closely related to inflammatory response and the classic pyroptosis pathway in skeletal muscle, such as NLRP3/caspase-1/IL-1ß, IL-18. It is inferred that the mechanism of Huanglian Wendan Decoction was to alleviate insulin resistance(IR) and then reverse the course of IGT lies in the regulation of the abnormal insulin receptor signaling pathway based on the NLRP3 inflammasome pathway.


Assuntos
Intolerância à Glucose , Interleucina-18 , Animais , Caspase 1/genética , Medicamentos de Ervas Chinesas , Interleucina-18/genética , Interleucina-1beta , Masculino , Músculo Esquelético , NF-kappa B/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Ratos , Ratos Sprague-Dawley
20.
Eur J Pharmacol ; 910: 174442, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34492285

RESUMO

The aim of this study was to analyze the active components of Schisandra chinensis on liver injury and its mechanism in mice by network pharmacology. The active components of S. chinensis were found through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and their corresponding targets were predicted. The targets of liver injury were searched through Therapeutic Targets Database (TTD), DisGeNET and drugbank databases, and the Venn diagram was constructed to obtain the action targets. The "drug-active component-target" network and protein-protein interaction network (PPI) were constructed by using STRING database and Cytoscape software, and the key targets were further screened by the enrichment analysis of relevant KEGG pathways. Finally, a CCl4-induced mouse liver injury model was established to verify the efficacy and related targets of S. chinensis and clarify its mechanism. Eight active components and 56 related targets of S. chinensis were screened out based on their oral bioavailability (OB) and drug likeness (DL). Five targets of S. chinensis related to liver injury were found by using the Venn diagram. The key targets, namely Ptgs2 and Nos2 genes, were further screened out by constructing a PPI network, and Schisandrol B (SCB) was considered the key component most closely related to the liver injury in S. chinensis. The results indicate that SCB may play a role in the treatment of the CCl4-induced liver injury by down-regulating the expression of iNOS and COX-2, and regulating the expression of NF-κB and IL-17 signaling pathway to inhibit the expression of proinflammatory factors.

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