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2.
Sci Total Environ ; 914: 169851, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38185165

RESUMEN

The release of rare earth elements (REEs) from mining wastes and their applications has significant environmental implications, necessitating the development of effective prevention and reclamation strategies. The mobility of REEs in groundwater due to microorganisms has garnered considerable attention. In this study, a La(III) resistant actinobacterium, Micromonospora saelicesensis KLBMP 9669, was isolated from REE enrichment soil in GuiZhou, China, and evaluated for its ability to adsorb and biomineralize La(III). The findings demonstrated that M. saelicesensis KLBMP 9669 immobilized La(III) through the physical and chemical interactions, with immobilization being influenced by the initial La(III) concentration, biomass, and pH. The adsorption kinetics followed a pseudo-second-order rate model, and the adsorption isotherm conformed to the Langmuir model. La(III) adsorption capacity of this strain was 90 mg/g, and removal rate was 94 %. Scanning electron microscope (SEM) coupled with energy dispersive X-ray spectrometer (EDS) analysis revealed the coexistence of La(III) with C, N, O, and P. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) investigations further indicated that carboxyl, amino, carbonyl, and phosphate groups on the mycelial surface may participate in lanthanum adsorption. Transmission electron microscopy (TEM) revealed that La(III) accumulation throughout the M. saelicesensis KLBMP 9669, with some granular deposits on the mycelial surface. Selected area electron diffraction (SAED) confirmed the presence of LaPO4 crystals on the M. saelicesensis KLBMP 9669 biomass after a prolonged period of La(III) accumulation. This post-sorption nano-crystallization on the M. saelicesensis KLBMP 9669 mycelial surface is expected to play a crucial role in limiting the bioimmobilization of REEs in geological repositories.


Asunto(s)
Metales de Tierras Raras , Micromonospora , Contaminantes Químicos del Agua , Fósforo , Biomineralización , Minerales , Adsorción , Cinética , Espectroscopía Infrarroja por Transformada de Fourier , Concentración de Iones de Hidrógeno , Contaminantes Químicos del Agua/química
3.
J Med Food ; 27(2): 110-122, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38181190

RESUMEN

The objective of this study was to examine the impact and underlying mechanisms of pelargonidin-3-galactoside (Pg3gal) produced from purple sweet potatoes on colonic inflammation induced by dextran sulfate sodium (DSS) in a murine model of ulcerative colitis (UC). C57BL/6J mice were categorized into four groups (n = 6 per group): DSS+Pg3gal, control, control+Pg3gal, and DSS. Colitis was induced by providing free access to 3% DSS for 10 days. The DSS+Pg3gal model mice received DSS concurrently with intragastric Pg3gal (25 mg/kg). The health of the mice was carefully monitored on a regular basis, and scores for the Disease Activity Index (DAI) were documented. A histological assessment was conducted using hematoxylin and eosin staining to evaluate the extent of mucosal injury present. The expression levels of IL-6, NLRP3, ASC, cleaved-Caspase-1, TNF-α, N-GSDMS, and cleaved-IL-1ß proteins were evaluated by Western blot analysis. The process of 16S rRNA sequencing was carried out to examine the composition and relative abundance of gut microbiotas within the intestines of the mice. The DAI results revealed that Pg3gal significantly attenuated the DSS-induced UC in mice. In addition, it successfully alleviated the decline in colon size, improved the condition of colonic tissue, and significantly inhibited the production of proinflammatory cytokines, such as IL-6, IL-1ß, and TNF-α, in the colon tissues. Additionally, Pg3gal modulated the DSS-induced imbalanced gut microbiota, as evidenced by decreased Proteobacteria and Deferribacteres and simultaneous elevation in Firmicutes, Bacteroidetes, and Verrucomicrobia. In summary, Pg3gal alleviated DSS-induced UC by inhibiting pyroptosis in intestinal epithelial cells and enhancing the structural integrity of the gut microbiota.


Asunto(s)
Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Ipomoea batatas , Animales , Ratones , Sulfato de Dextran/efectos adversos , Colon/patología , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Antocianinas/metabolismo , ARN Ribosómico 16S , Piroptosis , Ratones Endogámicos C57BL , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Intestinos/patología , Modelos Animales de Enfermedad
4.
J Agric Food Chem ; 72(1): 245-258, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38148374

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) has become a major global health problem with no approved pharmacological treatment for this disease. Thus, it is urgent to develop effective therapeutic targets for clinical intervention. Here, we show for the first time that ZFP30, a member of the KRAB-ZFP family, is significantly increased in NAFLD models. ZFP30 silencing ameliorates free fatty acid (FFA)-induced lipid accumulation; in contrast, the ZFP30 overexpression exacerbates the triglyceride accumulation and steatosis in hepatocytes. Further investigation revealed that the effects of ZFP30 on hepatic lipid accumulation were mainly attributed to the PPARα downregulation in the NAFLD model. Mechanistically, ZFP30 directly binded to the promoter of PPARα and recruited KAP1 to suppress its transcription. Moreover, chlorogenic acid (CGA) reversed the upregulation of ZFP30 in NAFLD, promoting the PPARα expression, resulting in enhanced fatty acid oxidation and alleviated hepatic steatosis. Collectively, our study indicates ZFP30 as a potential target for NAFLD treatment.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ácido Clorogénico/farmacología , Ácido Clorogénico/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Hígado/metabolismo , Metabolismo de los Lípidos , Ácidos Grasos no Esterificados/metabolismo , Ratones Endogámicos C57BL , Dieta Alta en Grasa
5.
J Agric Food Chem ; 71(51): 20585-20601, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38101321

RESUMEN

Soil salinity is an important limiting factor in agricultural production. Rhizospheric fungi can potentially enhance crop salinity tolerance, but the precise role of signaling substances is still to be systematically elucidated. A rhizospheric fungus identified as Paecilomyces vaniformisi was found to enhance the salinity tolerance of rice seedlings. In this study, a novel polysaccharide (PPL2b) was isolated from P. vaniformisi and identified as consisting of Manp, Glcp, GalpA, and Galp. In a further study, PPL2b showed significant activity in alleviating salinity stress-induced growth inhibition in rice seedlings. The results indicated that under salinity stress, PPL2b enhances seed germination, plant growth (height and biomass), and biochemical parameters (soluble sugar and protein contents). Additionally, PPL2b regulates genes such as SOS1 and SKOR to decrease K+ efflux and increase Na+ efflux. PPL2b increased the expression and activity of genes related to antioxidant enzymes and nonenzyme substances in salinity-induced oxidative stress. Further study indicated that PPL2b plays a crucial role in regulating osmotic substances, such as proline and betaine, in maintaining the osmotic balance. It also modulates plant hormones to promote rice seedling growth and enhance their tolerance to soil salinity. The variables interacted and were divided into two groups (PC1 77.39% and PC2 18.77%) based on their relative values. Therefore, these findings indicate that PPL2b from P. vaniformisi can alleviate the inhibitory effects of salinity stress on root development, osmotic adjustment, ion balance, oxidative stress balance, and growth of rice seedlings. Furthermore, it suggests that polysaccharides produced by rhizospheric fungi could be utilized to enhance crop tolerance to salinity.


Asunto(s)
Oryza , Paecilomyces , Plantones , Oryza/metabolismo , Salinidad , Polisacáridos/metabolismo , Suelo/química , Estrés Fisiológico
6.
Front Plant Sci ; 14: 1206820, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37780526

RESUMEN

Soil acidity is a serious problem in agricultural lands as it directly affects the soil, crop production, and human health. Soil acidification in agricultural lands occurs due to the release of protons (H+) from the transforming reactions of various carbon, nitrogen, and sulfur-containing compounds. The use of biochar (BC) has emerged as an excellent tool to manage soil acidity owing to its alkaline nature and its appreciable ability to improve the soil's physical, chemical, and biological properties. The application of BC to acidic soils improves soil pH, soil organic matter (SOM), cation exchange capacity (CEC), nutrient uptake, microbial activity and diversity, and enzyme activities which mitigate the adverse impacts of acidity on plants. Further, BC application also reduce the concentration of H+ and Al3+ ions and other toxic metals which mitigate the soil acidity and supports plant growth. Similarly, soil salinity (SS) is also a serious concern across the globe and it has a direct impact on global production and food security. Due to its appreciable liming potential BC is also an important amendment to mitigate the adverse impacts of SS. The addition of BC to saline soils improves nutrient homeostasis, nutrient uptake, SOM, CEC, soil microbial activity, enzymatic activity, and water uptake and reduces the accumulation of toxic ions sodium (Na+ and chloride (Cl-). All these BC-mediated changes support plant growth by improving antioxidant activity, photosynthesis efficiency, stomata working, and decrease oxidative damage in plants. Thus, in the present review, we discussed the various mechanisms through which BC improves the soil properties and microbial and enzymatic activities to counter acidity and salinity problems. The present review will increase the existing knowledge about the role of BC to mitigate soil acidity and salinity problems. This will also provide new suggestions to readers on how this knowledge can be used to ameliorate acidic and saline soils.

7.
Artículo en Inglés | MEDLINE | ID: mdl-37486345

RESUMEN

A Gram-positive, aerobic actinomycete, designated strain KLBMP 9356T, was isolated from weathered potash tailings soil sampled in Xuzhou, Jiangsu Province, PR China. The colonies were cream-coloured, convex and rounded. The optimal growth conditions of strain KLBMP 9356T were 1 % (w/v) NaCl, 28 °C and pH 7. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain KLBMP 9356T showed the highest similarity to Nocardioides zhouii CGMCC 1.11084T (98.9 %) and Nocardioides glacieisoli CGMCC 1.11097T (98.7 %). Results from two tree-making algorithms supported the position that strain KLBMP 9356T forms a stable clade with N. zhouii CGMCC 1.11084T and N. glacieisoli CGMCC 1.11097T. Strain KLBMP 9356T exhibited low digital DNA-DNA hybridization values with N. zhouii CGMCC 1.11084T (27.6 %) and N. glacieisoli CGMCC 1.11097T (31.4 %). The average nucleotide identity values between strain KLBMP 9356T and N. zhouii CGMCC 1.11084T and N. glacieisoli CGMCC 1.11097T were 83.8% and 85.9%, respectively. The peptidoglycan in the cell wall of the novel strain was ll-2,6-diaminopimelic acid and the predominant menaquinone was MK-8(H4). The major fatty acids (>10 %) were C17:1ω8c and C18:1ω9c. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, lyso-phospatidylglycerol and phosphatidylinositol. The genomic DNA G+C content was 71.6 mol%. Based on its morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 9356T represents a novel species of the genus Nocardioides, for which the name Nocardioides potassii sp. nov. is proposed. The type strain is KLBMP 9356T (=CGMCC 4.7738T=NBRC 115493T).


Asunto(s)
Ácidos Grasos , Fosfolípidos , Ácidos Grasos/química , Fosfolípidos/química , Nocardioides , Suelo , Filogenia , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Análisis de Secuencia de ADN , Microbiología del Suelo , Vitamina K 2/química
8.
J Agric Food Chem ; 71(19): 7451-7458, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37146254

RESUMEN

3-Phenylpropionic acid (3PPA) and its derivative 3-phenylpropyl acetate (3PPAAc) are important aromatic compounds with broad applications in the cosmetics and food industries. In this study, we constructed a plasmid-free 3PPA-producing Escherichia coli strain and designed a novel 3PPAAc biosynthetic pathway. A module containing tyrosine ammonia lyase and enoate reductase, evaluated under the control of different promoters, was combined with phenylalanine-overproducing strain E. coli ATCC31884, enabling the plasmid-free de novo production of 218.16 ± 43.62 mg L-1 3PPA. The feasibility of the pathway was proved by screening four heterologous alcohol acetyltransferases, which catalyzed the transformation of 3-phenylpropyl alcohol into 3PPAAc. Afterward, 94.59 ± 16.25 mg L-1 3PPAAc was achieved in the engineered E. coli strain. Overall, we have not only demonstrated the potential of de novo synthesis of 3PPAAc in microbes for the first time but also provided a platform for the future of biosynthesis of other aromatic compounds.


Asunto(s)
Escherichia coli , Fenilpropionatos , Escherichia coli/genética , Escherichia coli/metabolismo , Ingeniería Metabólica , Fenilpropionatos/metabolismo
9.
Artículo en Inglés | MEDLINE | ID: mdl-37191981

RESUMEN

Strain KLBMP 9083T, a novel actinobacterium, was isolated from weathered soils collected from a karst area in Anshun, Guizhou Province, PR China. The taxonomic position of strain KLBMP 9083T was studied using the polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain KLBMP 9083T formed a stabilized monophyletic clade with its closest relative strain Antribacter gilvus CGMCC 1.13856T (98.4 % 16S rRNA gene sequence similarity). The peptidoglycan hydrolysates contained alanine, glutamic acid, threonine and lysine. The polar lipids were composed of diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an unidentified phosphoglycolipid, an unidentified phospholipid and an unidentified glycolipid. The predominant menaquinones were MK-9(H8) (87.1 %), MK-9(H6) (7.3 %) and MK-9(H4) (5.6 %). The major fatty acids (>10 %) were anteiso-C15 : 0 and iso-C15 : 0. The genomic DNA G+C content was 72.3 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between strain KLBMP 9083T and A. gilvus CGMCC 1.13856T were 23.4 and 79.9 %, respectively. On the basis of morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 9083T represents a novel species of the genus Antribacter, for which the name Antribacter soli sp. nov. is proposed. The type strain is KLBMP 9083T (=CGMCC 4.7737T=NBRC 115577T).


Asunto(s)
Actinobacteria , Actinomycetales , Ácidos Grasos/química , Suelo , Filogenia , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Análisis de Secuencia de ADN , Fosfolípidos , Vitamina K 2
10.
Phytother Res ; 37(7): 2965-2978, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36879546

RESUMEN

Acute lung injury (ALI) caused by acute bacterial infection remains a common life-threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti-inflammatory, anti-cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)-induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP-infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF-κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c-Jun N-terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD-like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr-alleviated ALI via inhibiting pro-inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP-induced ALI.


Asunto(s)
Lesión Pulmonar Aguda , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Klebsiella pneumoniae/metabolismo , Inflamasomas , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Antraquinonas/farmacología , Antraquinonas/uso terapéutico , Pulmón , Citocinas/metabolismo , Lipopolisacáridos/farmacología
11.
Chemosphere ; 318: 137909, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36681195

RESUMEN

Toxic substances in the environment disturb the adsorption of pollutants in plants but little is known about the underlying mechanisms of these processes. This study evaluated the PAH adsorption by Phragmites australis under NAs stress. Results showed that Naphthenic acids (NAs) significantly decreased the adsorption of PAHs and had higher selectivity for type and structure. P. australis root cell growth and mitosis were significantly affected by NAs, which was accompanied by serious disturbances in mitochondrial function. The physiological evaluation showed the NAs could increase Reactive Oxygen Species (ROS) accumulation by around 16-fold and cause damage to the root cell normal redox equilibrium. The levels of three key related antioxidants, PLA, CAT and POD, decreased significantly to 35-50% under NAs stress and were dependent upon NAs concentration. Furthermore, NAs could significantly change the concentration and species of root exudates of P. ausralis. Autotoxic substances, including alcohol and amines, increased by 28.63% and 23.96, respectively. Sixteen compounds were identified and assumed as potential biomarkers. Galactonic, glyceric, and octadecanoic acid had the general effect of activating PAH in soil. The global view of the metabolic pathway suggests that NAs influenced the citric acid cycle, fatty acid synthesis, amino acid metabolism and the phenylpropanoid pathway. Detection data results indicated that the energy products cause hypoxia and oxidative stress, which are the main processes under the NAs. Furthermore, verification of these processes was fulfilled through gene expression and biomarkers quantification. Our results provide novel metabolic insights into the mechanisms of PAHs adsorption by P. australis under NAs disturbance, suggesting that monitoring NAs in phytoremediation applications is necessary.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Adsorción , Poaceae/metabolismo , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/metabolismo
12.
IEEE/ACM Trans Comput Biol Bioinform ; 20(2): 1137-1146, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35503837

RESUMEN

The imaging genetics approach generates large amount of high dimensional and multi-modal data, providing complementary information for comprehensive study of Schizophrenia, a complex mental disease. However, at the same time, the variety of these data in structures, resolutions, and formats makes their integrative study a forbidding task. In this paper, we propose a novel model called Joint Sparse Collaborative Regression (JSCoReg), which can extract class-specific features from different health conditions/disease classes. We first evaluate the performance of feature selection in terms of Receiver operating characteristic curve and the area under the ROC curve in the simulation experiment. We demonstrate that the JSCoReg model can achieve higher accuracy compared with similar models including Joint Sparse Canonical Correlation Analysis and Sparse Collaborative Regression. We then applied the JSCoReg model to the analysis of schizophrenia dataset collected from the Mind Clinical Imaging Consortium. The JSCoReg enables us to better identify biomarkers associated with schizophrenia, which are verified to be both biologically and statistically significant.


Asunto(s)
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/genética , Algoritmos , Imagen por Resonancia Magnética/métodos , Simulación por Computador , Curva ROC , Encéfalo
13.
Precis Clin Med ; 6(4): pbad031, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38163004

RESUMEN

Inflammatory bowel diseases (IBD) are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence. Although the pathomechanism of IBD has been extensively investigated, several aspects of its pathogenesis remain unclear. Long non-coding RNAs (lncRNAs) are transcripts with more than 200 nucleotides in length that have potential protein-coding functions. LncRNAs play important roles in biological processes such as epigenetic modification, transcriptional regulation and post-transcriptional regulation. In this review, we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment, as well as their potential roles as immune regulators, diagnostic biomarkers and therapeutic targets or agents for IBD.

14.
Mol Ther Oncolytics ; 26: 314-329, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36090477

RESUMEN

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both in vitro and in vivo. Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation in vivo. In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

15.
Mol Biomed ; 3(1): 22, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35854035

RESUMEN

CRISPR-Cas systems are an immune defense mechanism that is widespread in archaea and bacteria against invasive phages or foreign genetic elements. In the last decade, CRISPR-Cas systems have been a leading gene-editing tool for agriculture (plant engineering), biotechnology, and human health (e.g., diagnosis and treatment of cancers and genetic diseases), benefitted from unprecedented discoveries of basic bacterial research. However, the functional complexity of CRISPR systems is far beyond the original scope of immune defense. CRISPR-Cas systems are implicated in influencing the expression of physiology and virulence genes and subsequently altering the formation of bacterial biofilm, drug resistance, invasive potency as well as bacterial own physiological characteristics. Moreover, increasing evidence supports that bacterial CRISPR-Cas systems might intriguingly influence mammalian immune responses through targeting endogenous genes, especially those relating to virulence; however, unfortunately, their underlying mechanisms are largely unclear. Nevertheless, the interaction between bacterial CRISPR-Cas systems and eukaryotic cells is complex with numerous mysteries that necessitate further investigation efforts. Here, we summarize the non-canonical functions of CRISPR-Cas that potentially impact bacterial physiology, pathogenicity, antimicrobial resistance, and thereby altering the courses of mammalian immune responses.

16.
Microbiol Spectr ; 10(1): e0199921, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-35196814

RESUMEN

A human host exploits stresses such as acidic/alkaline pH, antifungal drugs, and reactive oxygen species to kill microbial pathogens such as the fungus Aspergillus fumigatus. However, A. fumigatus is resistant to these stresses in vitro. Therefore, what accounts for the potent antifungal activity of the human host? In this observation, we show that simultaneous exposure to acidic pH and oxidative stresses is much more potent than the individual stresses themselves and that this combinatorial stress kills A. fumigatus synergistically in vitro. Interestingly, A. fumigatus is resistant to the combination of alkaline pH and oxidative stress. Quantitative real-time PCR analyses showed that acidic/alkaline pH stress can mediate oxidative stress responses in A. fumigatus by regulating the expression of catalase-encoding genes. We further show that A. fumigatus is sensitive to the combination of acidic/alkaline stress and azole drug stress. Transcriptome analysis revealed that the sensitivity of A. fumigatus to azole drugs under acidic/alkaline conditions may be related to changes in genetic stability, sphingolipid metabolism, lipid metabolism, and amino acid metabolism. Collectively, our findings suggest that combinatorial stress represents a powerful fungicidal mechanism employed by hosts against pathogens, which suggests novel approaches to potentiate antifungal therapy. IMPORTANCE The human host combats fungal infections via phagocytic cells that recognize and kill fungal pathogens. Immune cells combat Aspergillus fumigatus infections with a potent mixture of chemicals, including reactive oxygen species, acidic/alkaline stress, and antifungal drugs. However, A. fumigatus is relatively resistant to these stresses in vitro. In this observation, we show that it is the combination of acidic/alkaline pH and oxidative or azole stress that kills A. fumigatus so effectively, and we define the molecular mechanisms that underlie this potency. Our findings suggest that combinatorial stress is a powerful fungicidal mechanism employed by hosts, which suggests novel approaches to potentiate antifungal therapy. This study provides a platform for future studies that will address the combinatorial impacts of various environmental stresses on A. fumigatus and other pathogenic microbes.


Asunto(s)
Ácidos/farmacología , Álcalis/farmacología , Antifúngicos/farmacología , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/metabolismo , Azoles/farmacología , Aspergilosis/microbiología , Aspergillus fumigatus/genética , Azoles/metabolismo , Catalasa/genética , Catalasa/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Especies Reactivas de Oxígeno/metabolismo
17.
J Glob Antimicrob Resist ; 28: 226-232, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35041999

RESUMEN

OBJECTIVES: Linezolid-dependent growth has contributed to wide dissemination of Staphylococcus epidermidis in hospitals. This study aimed to characterise linezolid-resistant coagulase-negative staphylococci (CoNS) isolates and the possibility of linezolid dependence in China. METHODS: Phenotypic and genotypic resistance of 13 CoNS isolates were investigated by antimicrobial susceptibility testing and PCR. Similarity of isolates was determined by pulsed-field gel electrophoresis (PFGE). Characterisation of the cfr-carrying plasmid was performed by S1 nuclease PFGE, Southern blotting and whole-genome sequencing (WGS). A maximum likelihood phylogenetic tree was constructed for phylogenetic analysis. Growth curve analysis was performed with and without linezolid to determinate the possible contribution of linezolid dependence to linezolid-resistant CoNS dissemination. RESULTS: Thirteen CoNS isolates showed linezolid MICs of 8 mg/L to >256 mg/L, typed into three PFGE profiles. Southern blotting and WGS indicated that the cfr gene was located on a 39.5-kb plasmid with 99% identity to cfr-harbouring plasmids pSR01, pLRSA417 and pH29-46. The cfr gene was flanked by two copies of an IS256-like element ISEnfa4 family transposase, indicating the transferability of linezolid resistance conferred by the cfr gene. Comparative phylogenetic analysis revealed that Staphylococcus capitis XZ03 shared high similarity with linezolid-resistant S. capitis isolates in Huashan Hospital, Shanghai. Thirteen CoNS isolates did not exhibit linezolid dependence on exposure from 8-32 mg/L. CONCLUSION: The endemic CoNS clone carrying the cfr gene in our hospital showed high-level linezolid resistance, threatening linezolid use. Linezolid-dependent growth under linezolid selective pressure was not observed, indicating that it may not yet be a common phenotype in Staphylococcus spp.


Asunto(s)
Coagulasa , Infecciones Estafilocócicas , Antibacterianos/farmacología , China/epidemiología , Coagulasa/genética , Humanos , Linezolid/farmacología , Fenotipo , Filogenia , Plásmidos/genética , Infecciones Estafilocócicas/epidemiología , Staphylococcus
18.
IEEE Trans Neural Netw Learn Syst ; 33(9): 4285-4299, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33587718

RESUMEN

With the rapid evolution of wireless mobile devices, there emerges an increased need to design effective collaboration mechanisms between intelligent agents to gradually approach the final collective objective by continuously learning from the environment based on their individual observations. In this regard, independent reinforcement learning (IRL) is often deployed in multiagent collaboration to alleviate the problem of a nonstationary learning environment. However, behavioral strategies of intelligent agents in IRL can be formulated only upon their local individual observations of the global environment, and appropriate communication mechanisms must be introduced to reduce their behavioral localities. In this article, we address the problem of communication between intelligent agents in IRL by jointly adopting mechanisms with two different scales. For the large scale, we introduce the stigmergy mechanism as an indirect communication bridge between independent learning agents, and carefully design a mathematical method to indicate the impact of digital pheromone. For the small scale, we propose a conflict-avoidance mechanism between adjacent agents by implementing an additionally embedded neural network to provide more opportunities for participants with higher action priorities. In addition, we present a federal training method to effectively optimize the neural network of each agent in a decentralized manner. Finally, we establish a simulation scenario in which a number of mobile agents in a certain area move automatically to form a specified target shape. Extensive simulations demonstrate the effectiveness of our proposed method.

19.
J Healthc Eng ; 2021: 2334332, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34760139

RESUMEN

The neuropsychological characteristics inside the brain are still not sufficiently understood in previous Gestalt psychological analyses. In particular, the extraction and analysis of human brain consciousness information itself have not received enough attention for the time being. In this paper, we aim to investigate the features of EEG signals from different conscious thoughts. Specifically, we try to extract the physiologically meaningful features of the brain responding to different contours and shapes in images in Gestalt cognitive tests by combining persistent homology analysis with electroencephalogram (EEG). The experimental results show that more brain regions in the frontal lobe are involved when the subject perceives the random and disordered combination of images compared to the ordered Gestalt images. Meanwhile, the persistence entropy of EEG data evoked by random sequence diagram (RSD) is significantly different from that evoked by the ordered Gestalt (GST) images in several frequency bands, which indicate that the human cognition of the shape and contour of images can be separated to some extent through topological analysis. This implies the feasibility to digitize the neural signals while preserving the whole and local features of the original signals, which are further verified by our extensive experiments. In general, this paper evaluates and quantifies cognitively related neural correlates by persistent homology features of EEG signals, which provides an approach to realizing the digitization of neural signals. Preliminary verification of the analyzability of human consciousness signals provides reliable research ideas and directions for the realization of feature extraction and analysis of human brain consciousness cognition.


Asunto(s)
Encéfalo , Electroencefalografía , Encéfalo/diagnóstico por imagen , Cognición , Estado de Conciencia , Entropía , Humanos
20.
Int J Mol Sci ; 22(21)2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34768852

RESUMEN

Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.


Asunto(s)
Antocianinas/farmacología , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacos , Mitofagia/efectos de los fármacos , Piroptosis/efectos de los fármacos , Animales , Antocianinas/análisis , Antocianinas/química , Línea Celular , ADN Mitocondrial/genética , Modelos Animales de Enfermedad , Femenino , Inflamación/tratamiento farmacológico , Ipomoea batatas/química , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/patogenicidad , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/prevención & control , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/microbiología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo
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