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1.
Mol Inform ; 43(3): e202300270, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38235949

RESUMO

Transporters play an indispensable role in facilitating the transport of nutrients, signaling molecules and the elimination of metabolites and toxins in human cells. Contemporary computational methods have been employed in the prediction of transporter inhibitors. However, these methods often focus on isolated endpoints, overlooking the interactions between transporters and lacking good interpretation. In this study, we integrated a comprehensive dataset and constructed models to assess the inhibitory effects on seven transporters. Both conventional machine learning and multi-task deep learning methods were employed. The results demonstrated that the MLT-GAT model achieved superior performance with an average AUC value of 0.882. It is noteworthy that our model excels not only in prediction performance but also in achieving robust interpretability, aided by GNN-Explainer. It provided valuable insights into transporter inhibition. The reliability of our model's predictions positioned it as a promising and valuable tool in the field of transporter inhibition research. Related data and code are available at https://gitee.com/wutiantian99/transporter_code.git.


Assuntos
Aprendizado de Máquina , Humanos , Reprodutibilidade dos Testes
2.
J Cheminform ; 16(1): 4, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183072

RESUMO

Evaluation of chemical drug-likeness is essential for the discovery of high-quality drug candidates while avoiding unwarranted biological and clinical trial costs. A high-quality drug candidate should have promising drug-like properties, including pharmacological activity, suitable physicochemical and ADMET properties. Hence, in silico prediction of chemical drug-likeness has been proposed while being a challenging task. Although several prediction models have been developed to assess chemical drug-likeness, they have such drawbacks as sample dependence and poor interpretability. In this study, we developed a novel strategy, named DBPP-Predictor, to predict chemical drug-likeness based on property profile representation by integrating physicochemical and ADMET properties. The results demonstrated that DBPP-Predictor exhibited considerable generalization capability with AUC (area under the curve) values from 0.817 to 0.913 on external validation sets. In terms of application feasibility analysis, the results indicated that DBPP-Predictor not only demonstrated consistent and reasonable scoring performance on different data sets, but also was able to guide structural optimization. Moreover, it offered a new drug-likeness assessment perspective, without significant linear correlation with existing methods. We also developed a free standalone software for users to make drug-likeness prediction and property profile visualization for their compounds of interest. In summary, our DBPP-Predictor provided a valuable tool for the prediction of chemical drug-likeness, helping to identify appropriate drug candidates for further development.

3.
Int J Biol Macromol ; 257(Pt 2): 127527, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37866558

RESUMO

Adhesion to gastrointestinal tract is crucial for bifidobacteria to exert their probiotic effects. Our previous work found that bile salts significantly enhance the adhesion ability of Bifidobacterium longum BBMN68 to HT-29 cells. In this study, trypsin-shaving and LC-MS/MS-based surface proteomics were employed to identify surface proteins involved in bile stress response. Among the 829 differentially expressed proteins, 56 up-regulated proteins with a fold change >1.5 were subjected to further analysis. Notably, the minor pilin subunit FimB was 4.98-fold up-regulated in response to bile stress. In silico analysis and RT-PCR confirmed that gene fimB, fimA and srtC were co-transcribed and contributed to the biosynthesis of sortase-dependent pili Pil1. Moreover, scanning electron microscopy and immunogold electron microscopy assays showed increased abundance and length of Pil1 on BBMN68 under bile stress. As the major pilin subunit FimA serves as adhesion component of Pil1, an inhibition assay using anti-FimA antibodies further confirmed the critical role of Pil1 in mediating the adhesion of BBMN68 to HT-29 cells under bile stress. Our findings suggest that the up-regulation of Pil1 in response to bile stress enhances the adhesion of BBMN68 to intestinal epithelial cells, highlighting a novel mechanism of gut persistence in B. longum strains.


Assuntos
Bifidobacterium longum , Humanos , Bifidobacterium longum/genética , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/farmacologia , Bile , Regulação para Cima , Células HT29 , Cromatografia Líquida , Espectrometria de Massas em Tandem
4.
Comput Biol Med ; 168: 107746, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039896

RESUMO

Cancer is a highly complex disease characterized by genetic and phenotypic heterogeneity among individuals. In the era of precision medicine, understanding the genetic basis of these individual differences is crucial for developing new drugs and achieving personalized treatment. Despite the increasing abundance of cancer genomics data, predicting the relationship between cancer samples and drug sensitivity remains challenging. In this study, we developed an explainable graph neural network framework for predicting cancer drug sensitivity (XGraphCDS) based on comparative learning by integrating cancer gene expression information and drug chemical structure knowledge. Specifically, XGraphCDS consists of a unified heterogeneous network and multiple sub-networks, with molecular graphs representing drugs and gene enrichment scores representing cell lines. Experimental results showed that XGraphCDS consistently outperformed most state-of-the-art baselines (R2 = 0.863, AUC = 0.858). We also constructed a separate in vivo prediction model by using transfer learning strategies with in vitro experimental data and achieved good predictive power (AUC = 0.808). Simultaneously, our framework is interpretable, providing insights into resistance mechanisms alongside accurate predictions. The excellent performance of XGraphCDS highlights its immense potential in aiding the development of selective anti-tumor drugs and personalized dosing strategies in the field of precision medicine.


Assuntos
Antineoplásicos , Aprendizado Profundo , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Redes Neurais de Computação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Genômica/métodos
5.
Int J Biol Macromol ; 258(Pt 2): 129054, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159708

RESUMO

Hydrogel-based flexible wearable sensors have garnered significant attention in recent years. However, the use of hydrogel, a biomaterial known for its high toughness, environmental friendliness, and frost resistance, poses a considerable challenge. In this study, we propose a stepwise construction and multiple non-covalent interaction matching strategy to successfully prepare dynamically physically crosslinked multifunctional conductive hydrogels. These hydrogels self-assembled to form a rigid crosslinked network through intermolecular hydrogen bonding and metal ion coordination chelation. Furthermore, the freeze-thawing process promoted the formation of poly(vinyl alcohol) microcrystalline domains within the amorphous hydrogel network system, resulting in exceptional mechanical properties, including a tensile strength (2.09 ± 0.01 MPa) and elongation at break of 562 ± 12 %. It can lift 10,000 times its own weight. Additionally, these hydrogels exhibit excellent resistance to swelling and maintain good toughness even at temperatures as low as -60 °C. As a wearable strain sensor with remarkable sensing ability (GF = 1.46), it can be effectively utilized in water and underwater environments. Moreover, it demonstrates excellent antimicrobial properties against Escherichia coli (Gram-negative bacteria). Leveraging its impressive sensing ability, we combine signal recognition with a deep learning model by incorporating Morse code for encryption and decryption, enabling information transmission.


Assuntos
Quitosana , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Escherichia coli , Hidrogéis , Álcool de Polivinil
6.
Chemosphere ; 345: 140530, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890791

RESUMO

A template-free pyrolysis route has been developed using condensation-assembly precursors made of trimethoxyboroxane (TMB) and melamine (M) to cater the requirements of an industrial real-world environment. The precursors contain abundant B-N bonds and exhibit a high level of interconnectivity, resulting in 3D-PBN with enhanced mechanical properties and the ability to be easily customized in terms of shape. Moreover, 3D-PBN demonstrates rapid adsorption kinetics and excellent reusability, efficiently removing up to 270% of its own weight of fuel within 30 s and being readily regenerated through simple calcination. Even after undergoing 50 cycles, the mechanical properties remain at a remarkable 80%, while the adsorption performance exceed 95%. Furthermore, a comprehensive analysis of thermal behavior from precursor to 3D-PBN has been conducted, leading to the proposal of a molecular-scale evolution process comprising four major steps. This understanding enables us to control the phase reaction and regulate the composition of the products, which is crucial for determining the characteristics of the final product.


Assuntos
Compostos de Boro , Porosidade , Compostos de Boro/química
7.
Int J Biol Macromol ; 246: 125700, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37414312

RESUMO

The rapid spread of multidrug-resistant pathogens with the low efficacy of common antibiotics for humans and animals in its clinical therapeutics are a global health concern. Therefore, there is a need to develop new treatment strategies to control them clinically. The study aimed to evaluate the effects of Plantaricin Bio-LP1 bacteriocin produced from Lactiplantibacillus plantarum NWAFU-BIO-BS29 to alleviate the inflammation caused by multidrug-resistance Escherichia Coli (MDR-E. coli) infection in BALB/c mice-model. The focus was given on aspects linked to the mechanism of the immune response. Results indicated that Bio-LP1 had highly promising effects on partially ameliorating MDR-E. coli infection by reducing the inflammatory response through inhibiting the overexpression of proinflammatory-cytokines such as secretion of tumor necrosis factor (TNF-α) and interleukin (IL-6 and IL-ß) and strongly regulated theTLR4 signaling-pathway. Additionally, avoided the villous destruct, colon length shortening, loss of intestinal barrier integrity, and increased disease activity index. Furthermore, significantly increased the relative abundance of beneficial-intestinal-bacteria including Ligilactobacillus, Enterorhabdus, Pervotellaceae, etc. Finally, improved the intestinal mucosal barrier to alleviate the pathological damages and promote the production of short-chain fatty acids (SCFAs) a source of energy for the proliferation. In conclusion, plantaricin Bio-LP1 bacteriocin can be considered a safe alternative to antibiotics against MDR-E. coli-induced intestinal inflammation.


Assuntos
Bacteriocinas , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli , Escherichia coli , Lactobacillaceae , Animais , Camundongos , Bacteriocinas/administração & dosagem , Bacteriocinas/isolamento & purificação , Bacteriocinas/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/prevenção & controle , Microbioma Gastrointestinal , Inflamação/prevenção & controle , Intestinos/metabolismo , Intestinos/microbiologia , Lactobacillaceae/química , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Ácidos Graxos Voláteis/análise
8.
Mol Inform ; 42(7): e2200284, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37195875

RESUMO

Drug-induced liver injury (DILI) is one of the major causes of drug withdrawals, acute liver injury and blackbox warnings. Clinical diagnosis of DILI is a huge challenge due to the complex pathogenesis and lack of specific biomarkers. In recent years, machine learning methods have been used for DILI risk assessment, but the model generalization does not perform satisfactorily. In this study, we constructed a large DILI data set and proposed an integration strategy based on hybrid representations for DILI prediction (HR-DILI). Benefited from feature integration, the hybrid graph neural network models outperformed single representation-based models, among which hybrid-GraphSAGE showed balanced performance in cross-validation with AUC (area under the curve) as 0.804±0.019. In the external validation set, HR-DILI improved the AUC by 6.4 %-35.9 % compared to the base model with a single representation. Compared with published DILI prediction models, HR-DILI had better and balanced performance. The performance of local models for natural products and synthetic compounds were also explored. Furthermore, eight key descriptors and six structural alerts associated with DILI were analyzed to increase the interpretability of the models. The improved performance of HR-DILI indicated that it would provide reliable guidance for DILI risk assessment.


Assuntos
Produtos Biológicos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Modelos Biológicos , Redes Neurais de Computação , Aprendizado de Máquina
9.
PLoS One ; 18(5): e0286138, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37253032

RESUMO

Magnetic reconnection is a process that can rapidly convert magnetic field energy into plasma thermal energy and kinetic energy, and it is also an important energy conversion mechanism in space physics, astrophysics and plasma physics. Research related to analytical solutions for time-dependent three-dimensional magnetic reconnection is extremely difficult. For decades, several mathematical descriptions have been developed regarding different reconnection mechanisms, in which the equations based on magnetohydrodynamics theory outside the reconnection diffusion region are widely accepted. However, the equation set cannot be analytically solved unless specified constraints are imposed or the equations are reduced. Based on previous analytical methods for kinematic stationary reconnection, here the analytical solutions for time-dependent kinematic three-dimensional magnetic reconnection are discussed. In contrast to the counter-rotating plasma flows that existed in steady-state reconnection, it is found that spiral plasma flows, which have never been reported before, can be generated if the magnetic field changes exponentially with time. These analyses reveal new scenarios for time-dependent kinematic three-dimensional magnetic reconnection, and the deduced analytical solutions could improve our understanding of the dynamics involved in reconnection processes, as well as the interactions between the magnetic field and plasma flows during magnetic reconnection.


Assuntos
Campos Magnéticos , Física , Fenômenos Biomecânicos , Fenômenos Físicos , Difusão
10.
Insects ; 14(4)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37103198

RESUMO

Ecdysteroid hormones are key regulators of insect development and metamorphosis. Ecdysone-inducible E75, a major component of insect ecdysone signaling pathway, has been well characterized in holometabolous insects, however, barely in hemimetabolous species. In this study, a total of four full-length E75 cDNAs from the English grain aphid, Sitobion avenae, were identified, cloned, and characterized. The four SaE75 cDNAs contained 3048, 2625, 2505, and 2179 bp open reading frames (ORF), encoding 1015, 874, 856, and 835 amino acids, respectively. Temporal expression profiles showed that SaE75 expression was low in adult stages, while high in pseudo embryo and nymphal stages. SaE75 was differentially expressed between winged and wingless morphs. RNAi-mediated suppression of SaE75 led to substantial biological impacts, including mortality and molting defects. As for the pleiotropic effects on downstream ecdysone pathway genes, SaHr3 (hormone receptor like in 46) was significantly up-regulated, while Sabr-c (broad-complex core protein gene) and Saftz-f1 (transcription factor 1) were significantly down-regulated. These combined results not only shed light on the regulatory role of E75 in the ecdysone signaling pathway, but also provide a potential novel target for the long-term sustainable management of S. avenae, a devastating global grain pest.

11.
Foods ; 11(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36496574

RESUMO

Lactic acid bacteria are one of the bioresources that can promote the host's health and have potential therapeutic applications. This study aimed to evaluate the probiotic properties of novel Lactiplantibacillus plantarum NWAFU-BISO-BS29 isolated in vitro from traditional Chinese fermented milk, assess its safety, and study its interaction with the gut microbiota using a BALB/c mouse model. The findings reveal that this strain had a high tolerance to gastric acidity (64.4%) and bile salts (19.83-87.92%) with remarkable auto-aggregation and co-aggregation abilities (33.01-83.96%), respectively. Furthermore, it lowered the cholesterol levels in dead cells (44.02%) and live cells (34.95%) and produced short-chain fatty acids (SCFAs). Likewise, it showed good antioxidant properties and strong antipathogen activity against Escherichia coli and Staphylococcus aureus with inhibition zones at 21 and 25 mm, respectively. The safety assessment results indicate that all of the virulence factor genes were not detected in the whole DNA; additionally, no hemolysis or resistance to antibiotics commonly used in food and feed was observed. Interestingly, the 16S rRNA gene sequencing of the mouse gut microbiota showed a marked alteration in the microbial composition of the administrated group, with a noticeable increase in Firmicutes, Patescibacteria, Campylobacterota, Deferribacterota, Proteobacteria, and Cyanobacteria at the phylum level. The modulation of gut microbial diversity significantly improved the production of SCFCs due to the abundance of lactobacillus genera, which was consistent with the functional gene predictive analysis and is believed to have health-promoting properties. Based on these results, our novel strain is considered a safe and good probiotic and could hold high potential to be used as a starter culture or to safely supplement functional foods as a probiotic and may provide new insights into therapeutic interventions.

12.
3 Biotech ; 12(12): 337, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36340806

RESUMO

Lactic acid bacteria (LAB) are believed to have health-promoting properties to the host and can be used in therapeutics interventions; intriguingly, they have the property to produce bio-preservatives substances. Therefore, this study aimed to mine probiotics and evaluate their safety, functional properties, and cholesterol-lowering capability. Seven potential probiotic strains were compared from 56 LAB strains isolated from traditional Chinese fermented milk. The results showed that all tested strains are tolerant to gastric acidity (45.5-83.26) and bile salts (11.92-92.91%) and have antibacterial activity against Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922. Likewise, it lowered the cholesterol levels in vitro by live cells (26.57-45.76%) and dead cells (29.53-50.97%) with remarkable aggregation ability (13.8-43.71%). Antioxidant properties and produce short chain fatty acids (SCFAs) were strain-dependent features. Upon assessment of the safety, Enterococcus faecium NWAFU-BIO-AS14 exhibited virulence factors genes (VFs) of (mur-2ed, odc, and tet(K)) and + hemolysis activity. While Enterococcus faecium NWAFU-BIO-A-B24 and Limosilactobacillus fermentum NWAFU-BIO-B-S6 have VFs of (odc, vanC2, and ant(6)-Ia). Limosilactobacillus fermentum NWAFU-BIO-D-B2 has only (odc). Thus, they are not considered as safe probiotics. In contrast, Lactiplantibacillus plantarum NWAFU-BIO-BS29, Companilactobacillus crustorum NWAFU-BIO-AS16, and Lactobacillus gallinarum NWAFU-BIO-D-S7 are the safest and best strains, respectively, due to the absence of 16 VFs and their sensitivity to antibiotics such as kanamycin, erythromycin, tetracycline, gentamycin, vancomycin, streptomycin, chloramphenicol, and ampicillin. Accordingly, these strains have a high potentiality to be used as starter cultures or safely applied as perfect probiotics in functionals food and feed. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03403-z.

13.
J Appl Toxicol ; 42(10): 1639-1650, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35429013

RESUMO

In recent years, drug-induced nephrotoxicity has been one of the main reasons for the failure of drug development. Early prediction of the nephrotoxicity for drug candidates is critical to the success of clinical trials. Therefore, it is very important to construct an effective model that can predict the potential nephrotoxicity of compounds. Machine learning methods have been widely used to predict the physicochemical properties, biological activities, and safety assessment of compounds. In this study, we manually collected 777 valid drug data and constructed a total of 72 classification models using nine types of molecular fingerprints combined with different machine learning algorithms. From experimental literature and the US FDA Drugs Database, some marketed drugs were screened for external validation of the models. Finally, three models exhibited good performance in the prediction of nephrotoxicity of both chemical drugs and Chinese herbal medicines. The best model was the support vector machine algorithm combined with CDK graph only fingerprint. Furthermore, the applicability domain of the models was analyzed according to the OECD principles, and we also used the SARpy and information gain methods to find eight substructures that might cause nephrotoxicity, so as to attract attention in the future drug discovery.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Aprendizado de Máquina , Algoritmos , Simulação por Computador , Descoberta de Drogas , Humanos , Máquina de Vetores de Suporte
14.
J Cheminform ; 14(1): 16, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35292114

RESUMO

The Janus kinase (JAK) family plays a pivotal role in most cytokine-mediated inflammatory and autoimmune responses via JAK/STAT signaling, and administration of JAK inhibitors is a promising therapeutic strategy for several diseases including COVID-19. However, to screen and design selective JAK inhibitors is a daunting task due to the extremely high homology among four JAK isoforms. In this study, we aimed to simultaneously predict pIC50 values of compounds for all JAK subtypes by constructing an interpretable GNN multitask regression model. The final model performance was positive, with R2 values of 0.96, 0.79 and 0.78 on the training, validation and test sets, respectively. Meanwhile, we calculated and visualized atom weights, followed by the rank sum tests and local mean comparisons to obtain key atoms and substructures that could be fine-tuned to design selective JAK inhibitors. Several successful case studies have demonstrated that our approach is feasible and our model could learn the interactions between proteins and small molecules well, which could provide practitioners with a novel way to discover and design JAK inhibitors with selectivity.

15.
ACS Omega ; 6(41): 27233-27238, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34693143

RESUMO

Graph neural networks (GNNs) constitute a class of deep learning methods for graph data. They have wide applications in chemistry and biology, such as molecular property prediction, reaction prediction, and drug-target interaction prediction. Despite the interest, GNN-based modeling is challenging as it requires graph data preprocessing and modeling in addition to programming and deep learning. Here, we present Deep Graph Library (DGL)-LifeSci, an open-source package for deep learning on graphs in life science. Deep Graph Library (DGL)-LifeSci is a python toolkit based on RDKit, PyTorch, and Deep Graph Library (DGL). DGL-LifeSci allows GNN-based modeling on custom datasets for molecular property prediction, reaction prediction, and molecule generation. With its command-line interfaces, users can perform modeling without any background in programming and deep learning. We test the command-line interfaces using standard benchmarks MoleculeNet, USPTO, and ZINC. Compared with previous implementations, DGL-LifeSci achieves a speed up by up to 6×. For modeling flexibility, DGL-LifeSci provides well-optimized modules for various stages of the modeling pipeline. In addition, DGL-LifeSci provides pretrained models for reproducing the test experiment results and applying models without training. The code is distributed under an Apache-2.0 License and is freely accessible at https://github.com/awslabs/dgl-lifesci.

16.
Int J Food Microbiol ; 355: 109336, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34352499

RESUMO

Foodborne disease caused by antibiotic resistant Salmonella is quite difficult to deal with. In order to further explore the antibiotic resistance associated with gene transfer among foodborne Salmonella, several wild-type Salmonella strains were used as donors and recipients, respectively, to investigate how extended spectrum ß-lactamases (ESBLs) encoding genes co-transfer with transposable elements to transmit antibiotic resistance. Antibiotic susceptibility was determined by agar dilution method, the transposase encoding gene was detected via PCR combined with DNA sequencing, S1 nuclease and pulsed field gel electrophoresis (S1-PFGE), and southern-blot. Illumina HiSeq 4000 platform and Nanopore MinION long-read sequencing technology were used to determine the antibiotic resistance encoding genes (ARGs) and their surrounding gene environment. The results indicated that the conjugation frequency was from ×10-4 to ×10-5 per recipient cell. A 185,608-bp-long DNA fragment and two short backbone protein encoding regions in pG19 in the donor fused with part genes in pS3 in the recipient during conjugation, the size of this fusion plasmid is as same as that of pG19. Cefoxitin resistance of the transconjugant was mediated by a tnpA21-related blaDHA-1 transfer. Resistance of Salmonella to ceftriaxone, cefoperazone and ceftiofur was mediated by a tnpU1548 related blaTEM-1B and blaCTX-M-3 transfer. The study indicated that transposase synergy and plasmid selective fusion act as important roles for foodborne Salmonella gathering ARGs. The consistent size of the plasmid before and after fusion suggested the invisibility and complexity of bacterial conjugation without DNA sequencing, the fact reminded us that the rampant transmission of antibiotic-resistance encoding genes would pose tremendous threat to food safety.


Assuntos
Farmacorresistência Bacteriana , Plasmídeos , Salmonella , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Transferência Genética Horizontal/genética , Plasmídeos/genética , Salmonella/efeitos dos fármacos , Salmonella/genética
17.
Probiotics Antimicrob Proteins ; 13(6): 1632-1643, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33851347

RESUMO

The beneficial effects of probiotics on ameliorating ulcerative colitis (UC) have attracted much attention in recent years. Nevertheless, the number of these identified probiotics is still limited. In addition, the adhesion abilities of probiotics are considered to be a key determinant for probiotic efficacy. However, the relationship between the adhesion abilities of probiotics and their role in ameliorating UC has been poorly studied to date. This study measured the adhesion abilities of four Lactobacillus strains to Caco-2 cells and their anti-adhesion effects on Caco-2 cells against pathogenic bacteria, as well as their application in ameliorating the symptoms of dextran sulfate sodium-induced UC, and further illustrated the relationship between these two potential probiotic properties of probiotics and their beneficial effects on UC. Results suggested that the adhesion abilities of the four tested Lactobacillus strains exists highly strain-specific and the mechanisms of their anti-adhesion effect on Caco-2 cells against Escherichia coli may be different. Moreover, all these strains had promising effects on ameliorating UC by reducing inflammatory response and improving the intestinal mucosal barrier function, as well as promoting the production of SCFAs. In conclusion, the four tested Lactobacillus strains can be considered as alternative dietary supplements in alleviating UC. In addition, it could be concluded that there is no significant correlation between the adhesion abilities of probiotics and their role in ameliorating UC, which further illustrated that the adhesion properties of probiotics in vitro may not be suitable as the key criterion for screening potential strains with UC-alleviating effects.


Assuntos
Aderência Bacteriana , Colite , Escherichia coli , Lactobacillus , Probióticos , Animais , Células CACO-2 , Colite/induzido quimicamente , Colite/terapia , Sulfato de Dextrana , Escherichia coli/patogenicidade , Humanos , Camundongos
18.
Int J Biol Macromol ; 164: 2162-2176, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32791267

RESUMO

Bacteriocins are a subclass of antibacterial peptides considered to be the most promising alternative to antibiotics. A large number of unknown bacteriocins are hidden in lactic acid bacteria. In this study, by combining the genome with LC-MS/MS, 14 novel bacteriocins produced by Lactobacillus rhamnosus LS-8 were detected. Moreover, these bacteriocins were successfully cloned via plasmid pET-28a(+) and pET-30a(+) and heterologously expressed in Escherichia coli BL21. Escherichia coli ATCC25922 and Staphylococcus aureus ATCC25923 were used to confirm their antibacterial activity. Subsequently, the four bacteriocins (pH 25, S68, S81, and S137) with the strongest antibacterial ability were selected, and their expression conditions were optimized. Purification was performed by cation exchange chromatography and high performance liquid chromatography, and the active parts were collected and analyzed by mass spectrometry. The mass spectrometry analysis revealed that peptide coverage was >71.39%. The MICs of the four bacteriocins against four pathogenic bacteria ranged from 5.38 to 19.84 µg/mL. In addition, these bacteriocins significantly inhibited the growth of four standard pathogenic bacteria. They also exhibited broad-spectrum bacteriostasis on Gram-positive and Gram-negative bacteria. Therefore, these new bacteriocins have great potential in the study of alternative antibiotics.


Assuntos
Bacteriocinas/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Cromatografia Líquida/métodos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Plasmídeos/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos
19.
J Food Sci ; 85(5): 1523-1535, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32282078

RESUMO

Bacteriocins are defined as ribosomally synthesized antibacterial peptides/proteins that either kill or inhibit the growth of other bacteria. In the present study, the physicochemical properties, mode of action, and potential use in food preservation of a novel bacteriocin BM1122 from Lactobacillus crustorum MN047 were studied. It exhibited a broad inhibitory spectrum against selected Gram-positive and Gram-negative bacteria. Kinetic curves revealed efficient time-dependent bactericidal activity. Moreover, BM1122 possessed low hemolytic activity and good thermal stability between 60 and 120 °C. It was resistant to a wide range of pH (2 to 11) and proteinases. The scanning and transmission electron microscopy showed that BM1122 led to plasmolysis of Staphylococcus aureus and pore formation in Escherichia coli. Flow cytometric analysis demonstrated that BM1122 destroyed cell membrane integrity. Additionally, BM1122 could also inhibit biofilm formation and disturb the normal cell cycles of S. aureus and E. coli. Finally, BM1122 may enhance the inhibition of S. aureus and E. coli on beef meat stored at 4 °C for a duration of 10 days. These findings indicated that BM1122 had the potential for use as a natural preservative in the food industry. PRACTICAL APPLICATION: Fresh raw meats are highly perishable products. Bacteriocin BM1122 with a broad antibacterial spectrum can inhibit the growth of microorganisms in beef meat during refrigerated storage.


Assuntos
Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Lactobacillus/química , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Bacteriocinas/química , Bacteriocinas/metabolismo , Bovinos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Conservação de Alimentos , Lactobacillus/metabolismo , Carne Vermelha/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
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