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1.
Poult Sci ; 102(1): 102304, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36436371

RESUMO

H9N2 subtype avian influenza (AI) is an infectious disease associated with immunosuppression in poultry. Here, the regulation function of PA-X protein was determined on the host innate immune response of H9N2-infected chicken bone marrow-derived DCs (chBM-DCs). Based on 2 mutated viruses expressing PA-X protein (rTX) or deficient PA-X protein (rTX-FS), and the established culture system of chBM-DCs, results showed PA-X protein inhibited viral replication in chBM-DCs but not in non-immune chicken cells (DF-1). Moreover, PA-X protein downregulated the expression of phenotypic markers (CD40, CD86, and MHCII) and proinflammatory cytokine (IL-12 and IL-1ß) of chBM-DCs. The mixed lymphocyte reaction between chBM-DCs and chicken T cells showed PA-X protein significantly decreased H9N2-infected chBM-DCs to induce T cell proliferation, implying a suppression of the DC-induced downstream T cell response. Taken together, these findings indicated that PA-X protein is a key viral protein to help H9N2 subtype AIVs escape the innate immunity of chBM-DCs.

2.
Chem Commun (Camb) ; 58(93): 13023, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36367129

RESUMO

Retraction of 'CoH-catalyzed radical hydroalkylation of alkenes with 1,3-dicarbonyls' by Meihui Guan et al., Chem. Commun., 2022, 58, 5265-5268, https://doi.org/10.1039/D2CC01382G.

3.
Entropy (Basel) ; 24(11)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36421495

RESUMO

The black widow spider optimization algorithm (BWOA) had the problems of slow convergence speed and easily to falling into local optimum mode. To address these problems, this paper proposes a multi-strategy black widow spider optimization algorithm (IBWOA). First, Gauss chaotic mapping is introduced to initialize the population to ensure the diversity of the algorithm at the initial stage. Then, the sine cosine strategy is introduced to perturb the individuals during iteration to improve the global search ability of the algorithm. In addition, the elite opposition-based learning strategy is introduced to improve convergence speed of algorithm. Finally, the mutation method of the differential evolution algorithm is integrated to reorganize the individuals with poor fitness values. Through the analysis of the optimization results of 13 benchmark test functions and a part of CEC2017 test functions, the effectiveness and rationality of each improved strategy are verified. Moreover, it shows that the proposed algorithm has significant improvement in solution accuracy, performance and convergence speed compared with other algorithms. Furthermore, the IBWOA algorithm is used to solve six practical constrained engineering problems. The results show that the IBWOA has excellent optimization ability and scalability.

4.
Front Microbiol ; 13: 962614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439793

RESUMO

South China tigers (Panthera tigris amoyensis, SC) are the most threatened tiger subspecies in the world. All the living SCs are captive in zoos or reserves and depend on artificial feeding. The composition of the gut microbiome plays an important role in sustaining the health of the host. A comprehensive understanding of the composition and development of the microbial community of SC is helpful to improve the feeding of captive SC. In this study, we collected 47 fecal samples, 37 of which were from SC of three developmental stages, 5 from adult Amur tigers (Am), and 5 from adult Bengal tigers (Bg), which were all housed in the same zoo. We investigated the diversity, richness, and composition of the bacterial microbiomes and we found that the gut microbiome of SC is strongly affected by host aging. The composition of the gut microbiome of juvenile SC experienced dramatic changes from 5 months old to 1 year old, and it showed much less difference when compared to the samples of 1 year old and the subadult. No significant differences were observed between the samples of subadult and the adult groups. The predominant phylum of 5-month-old SC is Fusobacteriota (33.99%) when the juvenile tigers were older than 5 months, and Firmicutes, but not Fusobacteriota, became the predominant phylum of bacteria in their gut. The gut microbiome of SC, Am, and Bg is possibly affected by their genetic variation; however, the core microbiome of these three subspecies is the same. Our data suggest that the gut microbiome of SC undergoes a developmental progression: a developmental phase (cub), a transitional phase (subadult), and a stable phase (adult). These results expand our understanding of the role of age in the development of the gut microbiome of SC.

5.
Phytother Res ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447359

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by ß-amyloid (Aß) plaques, neurofibrillary tangles, neuronal cell loss, and oxidative stress. Further deposition of Aß in the brain induces oxidative stress, neuroinflammation, and memory dysfunction. Hawthorn (Crataegus pinnatifida Bge.) leaf, a known traditional Chinese medicine, is commonly used for the treatment of hyperlipidemia, heart palpitations, forgetfulness, and tinnitus, and its main bioactive components are Hawthorn Leaf Flavonoids (HLF). In this study, we investigated the neuroprotective effects of the HLF on the Aß25-35 (bilateral hippocampus injection) rat model of AD. The results showed that the oral administration of HLF at a dose of 50, 100, and 200 mg/kg for 30 days significantly ameliorated neuronal cell damage and memory deficits, and markedly increased the enzyme activities of superoxide dismutase and catalase, and the content of glutathione whereas it decreased the malondialdehyde content in the Aß25-35 rat model of AD as well as suppressed the activation of astrocytes. In addition, HLF up-regulated Nrf-2, NQO-1, and HO-1 protein expressions. Also, it reduced neuroinflammation by inhibiting activation of astrocytes. In summary, these results indicated that HLF decreased the oxidative stress via activating Nrf-2/antioxidant response element signaling pathways, and may suggest as a potential candidate for AD therapeutic agent.

6.
Virulence ; 13(1): 1928-1942, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36271710

RESUMO

PA-X protein arises from a ribosomal frameshift in the PA of influenza A virus (IAV). However, the immune regulatory effect of the PA-X protein of H1N1 viruses on the nasal mucosal system remains unclear. Here, a PA-X deficient H1N1 rPR8 viral strain (rPR8-△PAX) was generated and its pathogenicity was determined. The results showed that PA-X was a pro-virulence factor in mice. Furthermore, it reduced the ability of H1N1 viruses to infect dendritic cells (DCs), the regulator of the mucosal immune system, but not non-immune cells (DF-1 and Calu-3). Following intranasal infection of mice, CCL20, a chemokine that monitors the recruitment of submucosal DCs, was downregulated by PA-X, resulting in an inhibition of the recruitment of CD11b+ DCs to submucosa. It also attenuated the migration of CCR7+ DCs to cervical lymph nodes and inhibited DC maturation with low MHC II and CD40 expression. Moreover, PA-X suppressed the maturation of phenotypic markers (CD80, CD86, CD40, and MHC II) and the levels of secreted pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) while enhancing endocytosis and levels of anti-inflammatory IL-10 in vitro, suggesting an impaired maturation of DCs that the key step for the activation of downstream immune responses. These findings suggested that the PA-X protein played a critical role in escaping the immune response of nasal mucosal DCs for increasing the virulence of H1N1 viruses.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Camundongos , Animais , Virulência , Proteínas não Estruturais Virais , Fatores de Virulência/metabolismo , Células Dendríticas
7.
J Cell Mol Med ; 26(22): 5657-5669, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36282889

RESUMO

The study aimed to investigate the mechanism by which cancer-associated fibroblasts (CAFs) are activated by cancer cells and construct a risk model to predict the prognosis of patients with pancreatic cancer (PC) after surgery. Pancreatic stellate cells were isolated from human pancreatic tissue and co-cultured with cancer cells to verify their crosstalk. Liquid chromatography-tandem mass spectrometry was used to detect proteins secreted by cancer cells. The online tools Gene Expression Profiling Interactive Analysis, UALCAN, and the Human Protein Atlas were used to analyse gene expression in PC. Expression data from the cancer genome atlas and the clinical samples were used to develop a training receiver operating characteristic (ROC) model and an external validation ROC model, respectively. We identified that cancer cells promote the activation of inflammatory CAFs (iCAF) through secretory proteins, which promote PC metastasis. Six candidate proteins secreted by cancer cells were identified which promote iCAF formation. These proteins were highly expressed in tumours and were associated with a poor prognosis in patients with PC. Moreover, a 6-gene model was constructed to predict death risk in patients at 1, 2 and 3 years after surgery. The training areas under the ROC curves (AUC) of 1-, 2- and 3-year death risks were 0.780, 0.792 and 0. 825, respectively. The externally validated AUC of death at 3 years post-surgery was 0.728. In conclusion, cancer cell-secreted proteins play a vital role in iCAF formation, and the 6-gene model may be a potential marker for predicting whether PC patients will benefit from surgery.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Pancreáticas , Humanos , Fibroblastos Associados a Câncer/metabolismo , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/metabolismo
8.
Bioinformatics ; 38(22): 5100-5107, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36205562

RESUMO

MOTIVATION: The interaction between drugs and targets (DTI) in human body plays a crucial role in biomedical science and applications. As millions of papers come out every year in the biomedical domain, automatically discovering DTI knowledge from biomedical literature, which are usually triplets about drugs, targets and their interaction, becomes an urgent demand in the industry. Existing methods of discovering biological knowledge are mainly extractive approaches that often require detailed annotations (e.g. all mentions of biological entities, relations between every two entity mentions, etc.). However, it is difficult and costly to obtain sufficient annotations due to the requirement of expert knowledge from biomedical domains. RESULTS: To overcome these difficulties, we explore an end-to-end solution for this task by using generative approaches. We regard the DTI triplets as a sequence and use a Transformer-based model to directly generate them without using the detailed annotations of entities and relations. Further, we propose a semi-supervised method, which leverages the aforementioned end-to-end model to filter unlabeled literature and label them. Experimental results show that our method significantly outperforms extractive baselines on DTI discovery. We also create a dataset, KD-DTI, to advance this task and release it to the community. AVAILABILITY AND IMPLEMENTATION: Our code and data are available at https://github.com/bert-nmt/BERT-DTI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Publicações , Software , Humanos , Interações Medicamentosas
9.
Mediators Inflamm ; 2022: 1153300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262548

RESUMO

Regulatory T cells (Tregs) and M2c macrophages have been shown to exert potentially synergistic therapeutic effects in animals with adriamycin-induced nephropathy (AN), a model chronic proteinuric renal disease. M2c macrophages may protect against renal injury by promoting an increase in the number of Tregs in the renal draining lymph nodes of AN mice, but how they do so is unclear. In this study, we used an AN mouse model to analyze how M2c macrophages induce the migration of Tregs. Using flow cytometry, we found that M2c macrophages promoted the migration of Tregs from the peripheral blood to the spleen, thymus, kidney, and renal draining lymph nodes. At the same time, M2c macrophages significantly upregulated chemokine receptors and adhesion molecule in Tregs, including CCR4, CCR5, CCR7, CXCR5, and CD62L. Treating AN mice with monoclonal anti-CD62L antibody inhibited the migration of M2c macrophages and Tregs to the spleen, thymus, kidney, and renal draining lymph nodes. Taken together, our results suggest that M2c macrophages upregulate CD62L in Tregs and thereby promote their migration to inflammatory sites, where they exert renoprotective effects. These insights may aid the development of treatments against chronic kidney disease.


Assuntos
Doxorrubicina , Insuficiência Renal Crônica , Camundongos , Animais , Doxorrubicina/toxicidade , Receptores CCR7 , Macrófagos , Linfócitos T Reguladores , Insuficiência Renal Crônica/patologia
10.
Antioxidants (Basel) ; 11(10)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36290735

RESUMO

Melatonin, an indoleamine synthesized in the pineal gland of mammals, is a natural bioactive compound with powerful antioxidant and anti-inflammatory properties. Here, we evaluated whether melatonin has the capacity to moderate the oxidative stress of dendritic cells (DCs) for inflammatory control in an acute lung injury (ALI) model. Our findings showed that melatonin remarkably inhibited total nitric oxide synthase (T-NOS) activity, nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, and lipid peroxidation (MDA detection) levels in both an LPS-induced murine ALI model and LPS-induced DCs. Meanwhile, the reduced glutathione (GSH) level and the GSH/GSSG ratio were recovered. In addition, antioxidant enzymes, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were increased in these processes. Moreover, melatonin also inhibited the LPS-induced secretions of IL-1ß, IL-6, and TGF-ß in vivo and in vitro. Finally, we found that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) axis was required in the inhibition of LPS-induced oxidative stress in DCs by melatonin. Altogether, these data indicate that melatonin strongly suppresses the LPS-induced oxidative stress in DCs, which is a promising DC-targeted strategy via inflammatory control for ALI treatment.

11.
Nat Commun ; 13(1): 6288, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271046

RESUMO

Influenza A virus (IAV) polymerase protein PB2 has been shown to partially inhibit the host immune response by blocking the induction of interferons (IFNs). However, the IAV PB2 protein that regulates the downstream signaling pathway of IFNs is not well characterized. Here, we report that IAV PB2 protein reduces cellular sensitivity to IFNs, suppressing the activation of STAT1/STAT2 and ISGs. Furthermore, IAV PB2 protein targets mammalian JAK1 at lysine 859 and 860 for ubiquitination and degradation. Notably, the H5 subtype of highly pathogenic avian influenza virus with I283M/K526R mutations on PB2 increases the ability to degrade mammalian JAK1 and exhibits higher replicate efficiency in mammalian (but not avian) cells and mouse lung tissues, and causes greater mortality in infected mice. Altogether, these data describe a negative regulatory mechanism involving PB2-JAK1 and provide insights into an evasion strategy from host antiviral immunity employed by IAV.


Assuntos
Antivirais , Vírus da Influenza A , Animais , Camundongos , Imunidade Inata , Vírus da Influenza A/genética , Interferons , Lisina , Mamíferos , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Janus Quinase 1/metabolismo
12.
J Fungi (Basel) ; 8(10)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36294622

RESUMO

The aim of this study was to investigate the effects of purified ß-glucosidases from Issatchenkia terricola SLY-4, Pichia kudriavzevii F2-24, and Metschnikowia pulcherrima HX-13 (named as SLY-4E, F2-24E, and HX-13E, respectively) on the flavor complexity and typicality of wines. Cabernet Sauvignon wines were fermented by Saccharomycescerevisiae with the addition of SLY-4E, F2-24E, and HX-13E; the fermentation process and characteristics of wines were analyzed. The addition of SLY-4E, F2-24E, and HX-13E into must improved the contents of terpenes, higher alcohols, and esters, and decreased the contents of C6 compounds and fatty acids, which enhanced the fruity, floral, and taste aspects, reducing the unpleasant green of wines with no significant difference in their appearance. ß-glucosidases from different yeast species produced different aroma compound profiles which presented different flavor and quality. F2-24EW had the best effect on flavor and quality of wine followed by SLY-4EW and HX-13EW. These research results can provide references for the use of ß-glucosidases from non-Saccharomyces yeasts to improve the flavor complexity, typicality, and quality of wines.

13.
Entropy (Basel) ; 24(9)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36141066

RESUMO

Attention mechanisms can improve the performance of neural networks, but the recent attention networks bring a greater computational overhead while improving network performance. How to maintain model performance while reducing complexity is a hot research topic. In this paper, a lightweight Mixture Attention (MA) module is proposed to improve network performance and reduce the complexity of the model. Firstly, the MA module uses multi-branch architecture to process the input feature map in order to extract the multi-scale feature information of the input image. Secondly, in order to reduce the number of parameters, each branch uses group convolution independently, and the feature maps extracted by different branches are fused along the channel dimension. Finally, the fused feature maps are processed using the channel attention module to extract statistical information on the channels. The proposed method is efficient yet effective, e.g., the network parameters and computational cost are reduced by 9.86% and 7.83%, respectively, and the Top-1 performance is improved by 1.99% compared with ResNet50. Experimental results on common-used benchmarks, including CIFAR-10 for classification and PASCAL-VOC for object detection, demonstrate that the proposed MA outperforms the current SOTA methods significantly by achieving higher accuracy while having lower model complexity.

14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(9): 819-824, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36082713

RESUMO

Objective To investigate the effects of microRNA-152 (miR-152) targeting at angiotensin II type 1 receptor (AGTR1) on the epithelial mesenchymal transition (EMT) and renin-angiotensin system (RAS) of HCCLM3 human hepatocellular carcinoma cells. Methods The cultured HCCLM3 cells were divided into untransfected group (untreated), negative control group (transfection negative control sequence) and miR-152 group (transfected miR-152 mimic). The expressions of miR-152, angiotensin converting enzyme (ACE), angiotensin II (AngII) and angiotensin II type 1 receptor (AGTR1) mRNAs were detected by real-time fluorescence quantitative PCR. Cell invasion and migration were detected by TranswellTM assay. The expression of vimentin, N-cadherin, E-cadherin and AGTR1 were tested by western blot. The targeting relationship between miR-152 and AGTR1 were examined by double luciferase reporter assay. Results Compared with the untransfected group or the negative control group, the expression levels of miR-152 and E-cadherin protein in the miR-152 group significantly increased, while the expression levels of ACE, AngII, AGTR1 mRNA, the number of invaded cells, the number of migrating cells, and the protein expression levels of vimentin, N-cadherin, and AGTR1 decreased significantly. The results of double luciferase reporter gene assay confirmed that miR-152 can target binding with AGTR1. Conclusion miR-152 may inhibit EMT and RAS of HCCLM3 cells by targeting down-regulation of AGTR1 expression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , RNA Mensageiro/genética , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Renina-Angiotensina/genética , Vimentina/genética , Vimentina/metabolismo
15.
Zhongguo Zhen Jiu ; 42(9): 1017-23, 2022 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-36075598

RESUMO

OBJECTIVE: To investigate the effect and mechanism of acupoint injection with 0.1% vitamin C+vitamin B complex solution (VC+VBCo) at "Tiantu" (CV 22), "Quchi" (LI 11) and "Zusanli" (ST 36) in mouse model of pneumonia induced by influenza A virus (A/PR/8/34 [H1N1], PR8). METHODS: Sixty male ICR mice were randomized into 6 groups, i.e. control group, model group, acupoint injection group, intraperitoneal injection group, non-target point group and ribavirin group, 10 mice in each one. Except the control group, the pneumonia models were induced by slow nasal dripping PR8 virus in the other groups. On the 2nd day of experiment, VC+VBCo solution, 40 µL was injected at "Tiantu" (CV 22), "Quchi" (LI 11, left) and "Zusanli" (ST 36, left) in the acupoint injection group; VC+VBCo solution, 120 µL was injected intraperitoneally in the intraperitoneal injection group; VC+VBCo solution, 40 µL was injected at non-target acupoints (0.5 cm away from "Tiantu" [CV 22] to the left side, "Quchi" [LI 11, left] and "Zusanli" [ST 36, left]) in the non-target point group; and ribavirin solution, 120 µL was injected intraperitoneally in the ribavirin group. The intervention was delivered once daily, for consecutive 7 days. Three parallel experiments were undertaken. The mean death rate and survival time were assessed in each group, the body mass and lung index were compared among groups. Using HE staining, the morphology of lung tissue was observed; and with real-time fluorescence quantitative PCR, viral load in lung tissue was detected. The concentrations of inflammatory factors (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-10) were detected in lung tissue of each group using ELISA; and those of oxidative stress markers (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malondialdehyde [MDA]) were detected with chemiluminescence method. RESULTS: Compared with the control group, the body mass was decreased and lung index was increased in the model group (P<0.01). In comparison with the model group, body mass was increased in the acupoint injection group (P<0.05), lung index was reduced in the acupoint injection group the and ribavirin group (P<0.05); the mean death rate was decreased and the mean survival time prolonged in the mice of the acupoint injection group (P<0.01, P<0.05); and the mean death rate was reduced in the mice of the ribavirin group (P<0.05). In the model group, the alveolar structure was not integral, the alveolar septum was thickened, inflammatory cells were infiltrated and red blood cells exudated seriously (P<0.01). Compared with the model group, in the acupoint injection group and the ribavirin group, the alveolar structure was integral, the thickened alveolar septum was alleviated; and the infiltration of inflammatory cells and the exudation of red blood cells were reduced remarkably. The viral load was reduced in the mice of the ribavirin group when compared with the model group (P<0.01). Compared with the control group, the concentrations of TNF-α, IL-1ß and MDA in lung tissue were increased and those of IL-10, SOD and GSH-Px were reduced in the model group (P<0.01). In the acupoint injection group and the ribavirin group, the concentrations of TNF-α, IL-1ß and MDA were reduced in lung tissue and those of IL-10, SOD and GSH-Px were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION: Acupoint injection with VC+VBCo solution may alleviate inflammatory responses and oxidative stress in lung tissue of the PR8-induced pneumonia mice, improve survival rate and prolong the survival time in the case of no effect of the viral load.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Pneumonia , Pontos de Acupuntura , Animais , Interleucina-10 , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ribavirina/uso terapêutico , Superóxido Dismutase , Fator de Necrose Tumoral alfa
16.
Neuroscience ; 505: 91-110, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36116555

RESUMO

Melatonin (MT) has been reported to control and prevent Alzheimer's disease (AD) in the clinic; however, the effect and mechanism of MT on AD have not been specifically described. Therefore, the main purpose of this meta-analysis was to explore the effect and mechanism of MT on AD models by studying behavioural indicators and pathological features. Seven databases were searched and 583 articles were retrieved. Finally, nine studies (13 analyses, 294 animals) were included according to pre-set criteria. Three authors independently judged the selected literature and the methodological quality. Meta-analysis showed that MT markedly ameliorated the learning ability by reducing the escape latency, and the memory deficit was significantly corrected by increasing the dwell time in the target quadrant and crossings over the platform location in the Morris Water Maze (MWM). Among the pathological features, subgroup analysis found that MT may ease the symptoms of AD mainly by reducing the deposition of Aß40 and Aß42 in the cortex. In addition, MT exerted a superior effect on ameliorating the learning ability of senescence-related and metabolic AD models, and corrected the memory deficit of the toxin-induced AD model. The study was registered at PROSPERO (CRD42021226594).


Assuntos
Doença de Alzheimer , Melatonina , Animais , Doença de Alzheimer/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , Modelos Animais de Doenças , Transtornos da Memória , Cognição , Aprendizagem em Labirinto , Peptídeos beta-Amiloides/metabolismo
17.
Brief Bioinform ; 23(6)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36136367

RESUMO

Well understanding protein function and structure in computational biology helps in the understanding of human beings. To face the limited proteins that are annotated structurally and functionally, the scientific community embraces the self-supervised pre-training methods from large amounts of unlabeled protein sequences for protein embedding learning. However, the protein is usually represented by individual amino acids with limited vocabulary size (e.g. 20 type proteins), without considering the strong local semantics existing in protein sequences. In this work, we propose a novel pre-training modeling approach SPRoBERTa. We first present an unsupervised protein tokenizer to learn protein representations with local fragment pattern. Then, a novel framework for deep pre-training model is introduced to learn protein embeddings. After pre-training, our method can be easily fine-tuned for different protein tasks, including amino acid-level prediction task (e.g. secondary structure prediction), amino acid pair-level prediction task (e.g. contact prediction) and also protein-level prediction task (remote homology prediction, protein function prediction). Experiments show that our approach achieves significant improvements in all tasks and outperforms the previous methods. We also provide detailed ablation studies and analysis for our protein tokenizer and training framework.


Assuntos
Biologia Computacional , Proteínas , Humanos , Proteínas/química , Biologia Computacional/métodos , Sequência de Aminoácidos , Estrutura Secundária de Proteína , Aminoácidos
18.
Brief Bioinform ; 23(6)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36156661

RESUMO

Pre-trained language models have attracted increasing attention in the biomedical domain, inspired by their great success in the general natural language domain. Among the two main branches of pre-trained language models in the general language domain, i.e. BERT (and its variants) and GPT (and its variants), the first one has been extensively studied in the biomedical domain, such as BioBERT and PubMedBERT. While they have achieved great success on a variety of discriminative downstream biomedical tasks, the lack of generation ability constrains their application scope. In this paper, we propose BioGPT, a domain-specific generative Transformer language model pre-trained on large-scale biomedical literature. We evaluate BioGPT on six biomedical natural language processing tasks and demonstrate that our model outperforms previous models on most tasks. Especially, we get 44.98%, 38.42% and 40.76% F1 score on BC5CDR, KD-DTI and DDI end-to-end relation extraction tasks, respectively, and 78.2% accuracy on PubMedQA, creating a new record. Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fluent descriptions for biomedical terms.


Assuntos
Mineração de Dados , Processamento de Linguagem Natural
19.
Front Microbiol ; 13: 947112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090063

RESUMO

Severe influenza A virus infection leads to overwhelming inflammatory responses and cellular apoptosis, which causes lung injury and contributes to high mortality and morbidity. The gut microbiome altered in response to the infection might influence the disease progression and the treatment outcome. Cangma Huadu (CMHD) granules, an in-hospital preparation of traditional Chinese medicine, have been shown to be favorable in the clinical treatment of influenza. However, the effects and mechanisms of CMHD granules on severe influenza pneumonia and its mechanisms are not well-known. In this study, a lethal influenza A (H1N1) A/Puerto Rico/8/34 virus (PR8)-infected mice model was established, and the 16S ribosomal RNA (16S rRNA) V3-V4 region sequencing of the intestinal microbiome was conducted. We revealed that the oral administration of CMHD granules protects mice against higher mortality, enhanced weight loss, overwhelmed interferon-γ concentration, lung viral titers, and severe lung pathological injury in PR8-infected mice. CMHD granules' administration downregulated the levels of interleukin (IL)-1ß, tumor necrosis factor-α, and malondialdehyde, while it upregulated the levels of IL-10, superoxide dismutase, and glutathione peroxidase. Subsequently, it decreased the protein ratio of B-cell lymphoma-2/Bcl-2-associated X and the expression of cleaved caspase-3. The diversity and compositions of the gut microbes were altered profoundly after the administration of CMHD granules in PR8-infected mice. A higher abundance of Bifidobacterium, Parasutterella, Bacteroides, and Faecalibaculum was observed in the CMHD group, and a higher abundance of Lactobacillus and Turicibacter was observed in the positive drug Ribavirin group. The linear discriminant analysis effect size also revealed a higher proportion of Bacteroides and Bifidobacterium_pseudolongum characterized in the CMHD group. These results demonstrated that CMHD granules are a promising strategy for managing severe influenza and attenuating severe lung damage via reducing viral titer, inflammatory responses, and oxidative stress. The mechanisms are involved in repressed Bcl-2-regulated apoptosis and altered composition and diversity of the gut microbiome.

20.
J Gastrointest Oncol ; 13(4): 1805-1817, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092341

RESUMO

Background: Although studies have reported that certain sleep characteristics, such as sleep duration and sleep apnea, are linked to the risk of colorectal cancer (CRC), this link remains contentious because of the limited evidence from individual studies. Furthermore, evidence indicated that shift work involving circadian disruption as a probable human carcinogen. This systematic review and meta-analysis aimed to examine the associations between sleep duration, sleep apnea, and shift work with the risk of colorectal neoplasms, including CRC and colorectal adenoma (CRA). Methods: We conducted a comprehensive literature search in PubMed, Embase, and Web of Science databases. The inclusion criteria were determined using PICOS principles. Observational studies reporting associations of sleep duration, sleep apnea, or shift work with risk of CRC or CRA were included. We assessed the risk of bias on the basis of the Newcastle-Ottawa Scale. Results: A total of 18 observational studies were included. Of these studies, nine studies reported the effect of sleep duration on risk of colorectal neoplasms, five reported the effect of sleep apnea, and six reported the effect of shift work. The relative risk (RR) for colorectal neoplasms was 1.06 [95% confidence interval (CI): 0.94, 1.20] in the short sleep duration group compared with the moderate sleep duration group. Long sleep duration was associated with an increased risk of colorectal neoplasms (RR: 1.33, 95% CI: 1.07, 1.65). The pooled results showed that sleep apnea was associated with an increased risk of colorectal neoplasms (RR: 1.75, 95% CI: 1.56, 1.97). Furthermore, results showed that the association between shift work and the risk of colorectal neoplasms was not significant (RR: 1.06, 95% CI: 0.95, 1.17). No publication bias was observed in all the analyses (all P>0.05). The sensitivity analysis showed that no individual study substantially influenced the pooled RRs for colorectal neoplasms and CRC. Conclusions: Our findings suggest the significant positive association of long sleep duration and sleep apnea with risk of colorectal neoplasms and CRC. Given that sleep characteristics may be a potentially modifiable risk factor for colorectal neoplasms, further understanding of its role in carcinogenesis will provide valuable insight for cancer prevention.

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