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1.
Artigo em Inglês | MEDLINE | ID: mdl-34623538

RESUMO

An obligately anaerobic, Gram-stain-positive, non-motile, non-spore-forming and rod-shaped strain AGMB00832T was isolated from swine faeces. Phylogenetic analysis based on the 16S rRNA gene, together with the housekeeping genes, gyrB and rpoD, revealed that strain AGMB00832T belonged to the genus Faecalicatena and was most closely related to Faecalicatena orotica KCTC 15331T. In biochemical analysis, strain AGMB00832T was shown to be negative for catalase, oxidase and urease. Furthermore, the isolate was positive for ß-glucosidase, ß-glucuronidase, glutamic acid decarboxylase, proline arylamidase, acid phosphatase and naphthol-AS-BI-phosphohydrolase. The major cellular fatty acids (> 10%) of the isolate were C14:0, C16:0 and C18:1ω11t DMA. Based on the whole genome sequence analysis, the DNA G + C content of strain AGMB00832T was 44.2 mol%, and the genome size and numbers of rRNA and tRNA genes were 5,175,159 bp, 11 and 53, respectively. The average nucleotide identity and digital DNA-DNA hybridization values between strain AGMB00832T and related strains were ≤ 77.4 and 22.5%, respectively. Furthermore, the genome analysis revealed the presence of genes for alkaline shock protein 23 and cation/proton antiporters, which may facilitate growth of strain AGMB00832T in alkaline culture condition. On the basis of polyphasic taxonomic approach, strain AGMB00832T represents a novel species within the genus Faecalicatena, for which the name Faecalicatena faecalis sp. nov. is proposed. The type strain is AGMB00832T (= KCTC 15946T = NBRC 114613T).

2.
J Clin Med ; 10(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34640312

RESUMO

This prospective randomized controlled trial evaluated the safety and efficacy of real-time feedback-controlled dosimetry (RFD)-guided selective retina therapy (SRT) in chronic central serous chorioretinopathy (CSC). Forty-four participants with chronic CSC were included and randomly assigned to the control group or SRT group. The SRT laser system with RFD-guidance was applied to cover the entire leakage area. If SRF remained at the 6-week follow-up visit, re-treatment and rescue SRT was performed for the SRT group and crossover group, respectively. The rate of complete resolution of subretinal fluid (SRF), mean SRF height, and mean retinal sensitivity were compared between the two groups at 6-weeks post-treatment. The complete SRF resolution rate in all SRT-treated eyes was evaluated at 12-weeks post-treatment. The rate of complete SRF resolution was significantly higher in the SRT group (63.6%) than in the control group (23.8%) at 6-weeks post-treatment (p = 0.020). The mean SRF height at 6 weeks after SRT was significantly lower in the SRT group (p = 0.041). Overall, SRT-treated eyes showed complete SRF resolution in 70.3% of eyes at 12-weeks post-treatment. RFD-guided SRT was safe and effective to remove SRF in chronic CSC patients during the 3-month follow-up period.

3.
Tissue Eng Regen Med ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674182

RESUMO

Cancer is one of the major diseases that threaten human life worldwide. Despite advances in cancer treatment techniques, such as radiation therapy, chemotherapy, targeted therapy, and immunotherapy, it is still difficult to cure cancer because of the resistance mechanism of cancer cells. Current understanding of tumor biology has revealed that resistance to these anticancer therapies is due to the tumor microenvironment (TME) represented by hypoxia, acidity, dense extracellular matrix, and immunosuppression. This review demonstrates the latest strategies for effective cancer treatment using functional nanoparticles that can modulate the TME. Indeed, preclinical studies have shown that functional nanoparticles can effectively modulate the TME to treat refractory cancer. This strategy of using TMEs with controllable functional nanoparticles is expected to maximize cancer treatment efficiency in the future by combining it with various modern cancer therapeutics.

4.
Toxicol Res ; 37(4): 395-403, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34631496

RESUMO

In the last decade, several advancements have been made in omics technologies and they have been applied extensively in diverse research areas. Especially in toxicological research, omics technology can efficiently and accurately generate relevant data on the molecular dynamics associated with adverse outcomes. Toxicomics is defined as the combination of toxicology and omics technologies and encompasses toxicogenomics, toxicoproteomics, and toxicometabolomics. This paper reviews the trend of applying omics technologies to evaluate cadmium (Cd) toxicity in zebrafish (D. rerio). Cd is a toxic heavy metal posing several environmental concerns; however, it is being used widely in everyday life. Zebrafish embryos and larvae are employed as standard models for many toxicity tests because they share 71.4% genetic homology with humans. This study summarizes the toxicity of Cd on the nerves, liver, heart, skeleton, etc. of zebrafish and introduces detailed omics techniques to understand the results of the toxicomic studies. Finally, the trend of toxicity evaluation in the zebrafish model of Cd based on omics technology is presented.

5.
Proteomics ; : e2100125, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596327

RESUMO

Akkermansia muciniphila is a prominent mucin-degrading bacterium that acts as a keystone species in regulating the human gut microbiota. Despite recently increasing research into this bacterium and its relevance to human health, a high-resolution database of its functional proteins remains scarce. Here, we provide a proteomic overview of A. muciniphila grown in different nutrient conditions ranging from defined to complex. Of 2318 protein-coding genes in the genome, we identified 841 (40%) that were expressed at the protein level. Overall, proteins involved in energy production and carbohydrate metabolism indicate that A. muciniphila relies mainly on the Embden-Meyerhof-Parnas pathway, and produces short-chain fatty acids through anaerobic fermentation in a nutrient-specific manner. Moreover, this bacterium possesses a broad repertoire of glycosyl hydrolases, together with putative peptidases and sulfatases, to cleave O-glycosylated mucin. Of them, putative mucin-degrading enzymes (Amuc_1220, Amuc_1120, Amuc_0052, Amuc_0480, and Amuc_0060) are highly abundant in the mucin-supplemented media. Furthermore, A. muciniphila uses mucin-derived monosaccharides as sources of energy and cell wall biogenesis. Our dataset provides nutrient-dependent global proteomes of A. muciniphila ATCC BAA-835 to offer insights into its metabolic functions that shape the composition of the human gut microbiota via mucin degradation.

6.
Ophthalmologica ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649253

RESUMO

PURPOSE: To evaluate the efficacy of selective retina therapy (SRT), used in conjunction with real-time feedback dosimetry (RFD), in the treatment of bevacizumab-resistant chronic central serous chorioretinopathy (CSC). PATIENTS AND METHODS: In this retrospective cohort study, 22 eyes of 22 patients with anti-VEGF-resistant chronic CSC, showing focal or diffuse foveal leakages on fundus fluorescein angiography (FFA), were included. After evaluation of the test spots at temporal arcades, SRT (wavelength, 527 nm; pulse repetition rate, 100 Hz; ramping over maximal 15 micropulses; and spot diameter, 200 µm) using RFD was applied to the leakage sites observed on FFA. Changes in the mean best-corrected visual acuity (BCVA), central macular thickness (CMT), and subretinal fluid (SRF) height were evaluated at baseline and at 1, 3, 6, 9, and 12 months following treatment. RESULTS: SRF completely resolved in 81.8% (18/22 eyes) cases at 12-months post-treatment. The mean BCVA (logMAR) improved from 0.49 ± 0.29 at baseline to 0.43 ± 0.36 at 12 months (p = 0.067). The mean BCVA gain was 0.06 logMAR, equivalent to 3 ETDRS letters. The CMT significantly decreased from 323 ± 85.6 µm at baseline to 221.5 ± 60.4 µm at 12 months (p < 0.001). The mean SRF height also significantly decreased from 174.6 ± 86.4 µm at baseline to 35.1 ± 75.4 µm at 12 months (p < 0.001). CONCLUSION: SRT showed favorable visual and anatomical outcomes in patients with bevacizumab-resistant chronic CSC.

7.
J Agric Food Chem ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34672564

RESUMO

Identification of chemical markers in food additives and dietary supplements is crucial for quantitative assessment and standardization of their quality and efficacy. Arthrospira platensis, formerly Spirulina platensis and known colloquially as spirulina, has been widely investigated for its various biological effects, including anti-inflammation, antihypertension, antioxidant, and antiatherosclerosis. In this study, we utilized an approach involving a combination of bioassay-guided fractionation, synthesis, mass spectral molecular networking, principal component analysis (PCA), and correlation analysis to identify measurable chemical markers in spirulina products that can be used to evaluate the efficacy of commercial products in downregulating the expression level of the proinflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα). Consequently, we found that the apocarotenoids 3-hydroxy-ß-ionone (1) and apo-13-zeaxanthinones (2a/2b) significantly repressed expression of IL-1ß (9.5 ± 1.5 and 28.7 ± 0.6%, respectively) and IL-6 (10.1 ± 0.7 and 6.1 ± 0.4%, respectively) at 10 µg/mL (p < 0.05) using RAW 264.7 mouse macrophages. Notably, this is the first report of the isolation of these apocarotenoids from spirulina and their in vitro anti-inflammatory properties. Finally, we propose the use of our approach as a convenient way to establish markers in other dietary supplements.

8.
Sci Total Environ ; : 151046, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34673059

RESUMO

While wastewater has been found to harbor SARS-CoV-2, the persistence of SARSCoV-2 in stormwater and potential transmission is poorly understood. It is plausible that the virus is detectable in stormwater samples where human-originated fecal contamination may have occurred from sources like sanitary sewer overflows, leaky wastewater pipes, and non-human animal waste. Because of these potential contamination pathways, it is possible that stormwater could serve as an environmental reservoir and transmission pathway for SARS-CoV-2. The objectives of this study are: 1) determine whether the presence of SARS-CoV-2 could be detected in stormwater via RT-ddPCR (reverse transcription-digital droplet PCR); 2) quantify human-specific fecal contamination using microbial source tracking; and 3) examine whether rainfall characteristics influence virus concentrations. To accomplish these objectives, we investigated whether SARS-CoV-2 could be detected from 10 storm sewer outfalls each draining a single, dominant land use in Columbus, Xenia, and Springboro, Ohio. Of the 25 samples collected in 2020, at minimum one SARS-CoV-2 target gene (N2 [US-CDC and CN-CDC], and E) was detected in 22 samples (88%). A single significant correlation (p = 0.001), between antecedent dry period and the USCDC N2 gene, was found between target gene concentrations and rainfall characteristics. Grouped by city, two significant relationships emerged showing cities had different levels of the SARS-CoV-2 E gene. Given the differences in scale, the county-level COVID-19 confirmed cases COVID-19 rates were not significantly correlated with stormwater outfall-scale SARS-CoV-2 gene concentrations. Countywide COVID-19 data did not accurately portray neighborhood-scale confirmed COVID-19 case rates. Potential hazards may arise when human fecal contamination is present in stormwater and facilitates future investigation on the threat of viral outbreaks via surfaces waters where fecal contamination may have occurred. Future studies should investigate whether humans are able to contract SARS-CoV-2 from surface waters and the factors that may affect viral longevity and transmission.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34590994

RESUMO

A novel bacterial isolate designated as strain AGMB01083T was isolated from Korean cow faeces deposited in the National Institute of Animal Science (Wanju, Republic of Korea). The bacterium is obligate anaerobic, Gram-strain-positive, and motile. Cells are straight or curved rod-shaped, flagella and spores are observed. Growth occurs between 20-40 °C (temperature optimum of 35 °C), at pH 7-9 (pH optimum of 7), and in the presence of 0.5-1.0 % (w/v) NaCl. Based on the 16S rRNA gene sequence analysis, the strain belongs to the genus Anaerosporobacter and is most closely related to A. mobilis HY-37-4T (=KCTC5027T, similarity, 95.7 %). The DNA G+C content is 36.2 mol%, determined by the whole-genome sequence. The average nucleotide identity value between strain AGMB01083T and strain A. mobilis HY-37-4T is 75.5 %, below the interspecies identity threshold value. The major cellular fatty acids (>10 %) of strain AGMB01083T are C16 : 0, C16 : 0 dimethyl acetal (DMA), and C16 : 0 3-OH. Based on the phylogenetic, phenotypic, biochemical, chemotaxonomic, and genomic characterization, strain AGMB01083T is proposed to be a novel species, named Anaerosporobacter faecicola, in the genus Anaerosporobacter. The type strain is AGMB01083T (=KCTC 15857T=NBRC 114517T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Bovinos , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes , Filogenia , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA
10.
J Cell Mol Med ; 25(19): 9295-9305, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34469037

RESUMO

Uveitis caused by herpes simplex virus (HSV)-1 is characterized by increased intraocular pressure (IOP) in the presence of anterior chamber inflammation. Despite their clinical significance, the pathogenic changes associated with HSV-1 infection in trabecular meshwork (TM) cells, the key cell type regulating IOP, have not been completely elucidated. In this study, cytokine array analyses showed a significant stepwise increase in monocyte chemoattractant protein (MCP)-1 expression upon HSV-1 infection in TM cells (p < 0.05). HSV-1 infection led to downregulation of fibrogenic molecules (fibronectin, α-smooth muscle actin, connective tissue growth factor and TGF-ß1). Notably, HSV-1 infection caused a significant increase in actin stress fibres, with a twofold increase in active RhoA, which was enhanced by treatment with TGF-ß1 and inhibited by treatment with the Rho-kinase inhibitor, Y-27632. TM cells treated with MCP-1 exhibited a dose-dependent increase in actin stress fibres compared to untreated TM cells. Our study suggests that HSV-1 infection in TM cells increases cell contractile activity rather than fibrotic changes in the extracellular matrix (ECM) components. Taken together, these observations demonstrate the enhanced expression of MCP-1 and TM cell contractile activity upon HSV-1 infection and events with potential implications for the pathobiology of abrupt IOP elevation in HSV-1 anterior uveitis.

11.
J Clin Med ; 10(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34575341

RESUMO

PURPOSE: The aim of this study is to investigate the structure-function characteristics and vision-related quality of life (VR-QoL) in uveitic glaucoma (UG) compared with open-angle glaucoma (OAG). METHOD: The study included 69 patients with UG and 138 patients with primary open angle glaucoma, normal-tension glaucoma. A 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was used to evaluate the patients' VR-QoL. The retinal nerve fiber layer thickness (RNFLT) was measured using optical coherence tomography, and the integrated visual field (IVF) was determined using the best location method. RESULTS: There were no significant differences in the binocular IVF and mean deviation (MD) of the affected eye between the OAG and UG group, whereas the average RNFLT was significant thinner in the OAG group (p = 0.008). The patients with UG showed a significantly lower composite score and five subscales of the VFQ-25, compared with those with OAG (p < 0.05, for all, general linear model). Multivariate linear regression analyses showed that the composite score showed the strongest associations with the whole IVF (ß = 1.240, p < 0.001) in the OAG group, whereas in the UG group, a significant association was seen only with the inferior VF of the affected eye (ß = 0.596, p = 0.038). CONCLUSIONS: The eyes with UG exhibited distinctive structure-function characteristics and worse VR-QoL that differentiated them from OAG eyes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34542393

RESUMO

An obligately anaerobic, non-motile, Gram-negative and rod-shaped strain (AGMB03916T) was isolated from faeces of a 2-week-old piglet raised at the National Institute of Animal Science in Wanju, Republic of Korea. Growth of strain AGMB03916T occurred at 30-45 °C (optimum, 37 °C), at pH 6-9 (optimum, pH 8) and in the presence of 0.5-1.0 % (w/v) NaCl. Based on the results of 16S rRNA gene sequence analyses, strain AGMB03916T was closely related to two validly published species of the genus Phocaeicola, Phocaeicola plebeius and Phocaeicola coprocola. The 16S rRNA gene sequence similarity of strain AGMB03916T compared to P. plebeius M12T (=KCTC 5793T) and P. coprocola M16T (=KCTC 5443T) were 96.3 and 95.0 %, respectively. The genomic DNA G+C content of strain AGMB03916T was 46.4 mol%. The average nucleotide identity values between strain AGMB03916T and the reference strains were 74.9-78.5 %. Cells were able to utilize d-glucose, lactose, sucrose, maltose, salicin, aesculin hydrolysis, cellobiose and raffinose. The major end product of metabolism was acetate. The major cellular fatty acids (>10 %) of the isolate were iso-C15 : 0, anteiso-C15 : 0, C16 : 0, C16 : 0 3-OH and summed feature 11 (iso-C17 : 0 3-OH and/or C18 : 2 DMA). On the basis of the genotypic, biochemical, chemotaxonomic, phenotypic and phylogenetic data, strain AGMB03916T represents a novel species of the genus Phocaeicola, for which the name Phocaeicola faecicola sp. nov. is proposed. The type strain is AGMB03916T (=KCTC 25014T=GDMCC 1.2574T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Suínos , Vitamina K 2
13.
Antonie Van Leeuwenhoek ; 114(11): 1867-1875, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34491487

RESUMO

A novel, strictly anaerobic, gram-negative, segmented filamentous bacterium strain AGMB03513T, was isolated from the faeces of a 5-month-old pig. Phylogenetic analysis based on the 16S rRNA gene indicated that the isolate was a member of the family Lachnospiraceae, and the closest strain was Anaerostipes butyraticus. Strain AGMB03513T formed a lineage within the genus Anaerostipes and was closely related to A. butyraticus DSM 22094 T (= KCTC 15125 T, 95.8%), Anaerostipes hadrus DSM 3319 T (= KCTC 15606 T, 95.5%), Anaerostipes caccae DSM 14662 T (= KCTC 15019 T, 94.0%), and Anaerostipes rhamnosivorans DSM 26241 T (= KCTC 15316 T, 93.4%). Strain AGMB03513T grew at temperatures between 30 and 45 °C, within a pH range of 7.0-9.0, and in medium containing up to 1.5% NaCl. Cells were found to utilise D-glucose, D-mannitol, D-lactose, D-saccharose, D-maltose, D-xylose, L-arabinose, D-mannose, and D-sorbitol, and acetate was identified as the major end product of metabolism. The major components of the cellular fatty acids were C12:0, C16:0, and C18:0. In addition, the bacterium contained meso-diaminopimelic acid in the cell wall. According to the comparative analysis of the whole genome sequence, the DNA G + C content of strain AGMB03513 was 37.0 mol%. In addition, Average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridisation (dDDH) values were obtained in comparisons of strain AGMB03513T with reference strains of species in the genus Anaerostipes. ANI values were found to be between 71.0 and 75.7%, AAI values between 66.6 and 73.2%, and dDDH values between 19.5 and 21.4%. All the data were below the threshold range for species determination. Based on phenotypic, phylogenetic, biochemical, chemotaxonomic, and genomic characteristics, we considered it reasonable to assign a novel species status to strain AGMB03513T, for which we propose the name Anaerostipes faecalis sp. nov. The type strain is AGMB03513T (= KCTC 25020 T = NBRC 114896 T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Animais , Técnicas de Tipagem Bacteriana , Clostridiales , DNA Bacteriano/genética , Ácidos Graxos/análise , Fezes , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Suínos
14.
J Nutr Biochem ; 99: 108852, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34525389

RESUMO

This study aimed to develop a well-characterized mouse model of alcoholic hepatitis (AH) regression. Male C57BL/6J mice were fed a Lieber-DeCarli (LD) control diet or LD containing 5% ethanol for ten days followed by one binge, which is the chronic-binge model of AH developed by the National Institute on Alcohol Abuse and Alcoholism. To determine AH regression, mice previously exposed to ethanol were put on LD control diet and metabolic and inflammatory features were monitored weekly for three weeks. Serum alcohol, total cholesterol, and alanine transaminase levels were increased in ethanol-fed mice, which declined to those of no ethanol controls within one and three weeks after ethanol withdrawal, respectively. Serum malondialdehyde was increased with ethanol feeding, but it was restored to no ethanol control levels within one week. Ethanol-induced changes in the hepatic expression of genes involved in lipogenesis, fatty acid oxidation, ethanol metabolism, and antioxidant response were restored to those of no ethanol controls after 3 weeks of ethanol withdrawal. Also, ethanol-induced hepatic inflammation was gradually decreased during the 3 weeks of ethanol withdrawal. Hepatic nicotinamide adenine dinucleotide (NAD+) levels and the expression of enzymes involved in the NAD+ salvage pathway were decreased by ethanol feeding, which was mitigated after ethanol withdrawal. Ethanol significantly lowered hepatic sirtuin 1 expression, but its levels were restored with ethanol cessation. This study established a mouse model of AH regression, which can be used as a preclinical model to study the potential of dietary bioactives or therapeutic agents on AH regression.

15.
Sci Total Environ ; 801: 149757, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34467932

RESUMO

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 129 million confirm cases. Many health authorities around the world have implemented wastewater-based epidemiology as a rapid and complementary tool for the COVID-19 surveillance system and more recently for variants of concern emergence tracking. In this study, three SARS-CoV-2 target genes (N1 and N2 gene regions, and E gene) were quantified from wastewater influent samples (n = 250) obtained from the capital city and 7 other cities in various size in central Ohio from July 2020 to January 2021. To determine human-specific fecal strength in wastewater samples more accurately, two human fecal viruses (PMMoV and crAssphage) were quantified to normalize the SARS-CoV-2 gene concentrations in wastewater. To estimate the trend of new case numbers from SARS-CoV-2 gene levels, different statistical models were built and evaluated. From the longitudinal data, SARS-CoV-2 gene concentrations in wastewater strongly correlated with daily new confirmed COVID-19 cases (average Spearman's r = 0.70, p < 0.05), with the N2 gene region being the best predictor of the trend of confirmed cases. Moreover, average daily case numbers can help reduce the noise and variation from the clinical data. Among the models tested, the quadratic polynomial model performed best in correlating and predicting COVID-19 cases from the wastewater surveillance data, which can be used to track the effectiveness of vaccination in the later stage of the pandemic. Interestingly, neither of the normalization methods using PMMoV or crAssphage significantly enhanced the correlation with new case numbers, nor improved the estimation models. Viral sequencing showed that shifts in strain-defining variants of SARS-CoV-2 in wastewater samples matched those in clinical isolates from the same time periods. The findings from this study support that wastewater surveillance is effective in COVID-19 trend tracking and provide sentinel warning of variant emergence and transmission within various types of communities.

16.
Adv Mater ; 33(38): e2101216, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34342046

RESUMO

Conductive metal-organic frameworks (cMOFs) are emerging materials for various applications due to their high surface area, high porosity, and electrical conductivity. However, it is still challenging to develop cMOFs having high surface reactivity and durability. Here, highly active and stable cMOF are presented via the confinement of bimetallic nanoparticles (BNPs) in the pores of a 2D cMOF, where the confinement is guided by dipolar-interaction-induced site-specific nucleation. Heterogeneous metal precursors are bound to the pores of 2D cMOFs by dipolar interactions, and the subsequent reduction produces ultrasmall (≈1.54 nm) and well-dispersed PtRu NPs confined in the pores of the cMOF. PtRu-NP-decorated cMOFs exhibit significantly enhanced chemiresistive NO2 sensing performances, owing to the bimetallic synergies of PtRu NPs and the high surface area and porosity of cMOF. The approach paves the way for the synthesis of highly active and conductive porous materials via bimetallic and/or multimetallic NP loading.

17.
J Pathol ; 255(3): 319-329, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34374436

RESUMO

Epigenetic regulation in macrophages plays a crucial role in the inflammatory response of cells. We investigated the role of macrophage histone deacetylase 4 (HDAC4) in diet-induced obesity and non-alcoholic steatohepatitis using macrophage-specific Hdac4 knockout mice (Hdac4MKO ). Hdac4 floxed control (Hdac4fl/fl ) and Hdac4MKO mice were fed a regular chow diet or an obesogenic high-fat/high-sucrose/high-cholesterol (HF/HS/HC) diet for 12 weeks. The loss of macrophage Hdac4, compared with Hdac4fl/fl control, aggravated the diet-induced inflammation in the liver and white adipose tissue only in male mice. Splenic monocytes isolated from male mice fed the HF/HS/HC diet showed increased lipopolysaccharide (LPS) sensitivity and decreased Ly6C-/Ly6C+ ratios in male Hdac4MKO mice, but not in females. Bone marrow-derived macrophages (BMMs) from male Hdac4MKO mice had a lesser efferocytotic capacity but higher proinflammatory gene expression upon LPS stimulation than male Hdac4fl/fl mice. However, female Hdac4MKO BMMs exhibited the opposite responses. The induction of estrogen receptor α (ERα, Esr1) expression by LPS was less in male but more in female Hdac4MKO BMMs than Hdac4fl/fl BMMs. Moreover, overexpression of human HDAC4 decreased basal expression of Esr1 and abolished its induction by LPS. Inhibition of ERα increased Hdac4 with induction of inflammatory genes, whereas activation of ERα decreased Hdac4 with reduction of inflammatory genes in male and female Hdac4fl/fl BMMs treated with LPS. However, regardless of the inhibition or activation of ERα, proinflammatory genes were induced by LPS more in male Hdac4MKO BMMs than Hdac4fl/fl cells, whereas cells in females showed opposite responses. In conclusion, this study suggests that the lack of macrophage Hdac4 aggravates hepatic and white adipose inflammation in male mice with diet-induced obesity and non-alcoholic steatohepatitis, and not in female mice. HDAC4 and ERα appear to counteract each other, but ERα may not be a major player in sex-dependent inflammatory responses in macrophages deficient in HDAC4. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

18.
Environ Int ; 157: 106802, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34358914

RESUMO

Limited studies on multi-omics have been conducted to comprehensively investigate the molecular mechanism underlying the developmental neurotoxicity of perfluorooctanesulfonic acid (PFOS). In this study, the locomotor behavior of zebrafish larvae was assessed under the exposure to 0.1-20 µM PFOS based on its reported neurobehavioral effect. After the number of zebrafish larvae was optimized for proteomics and metabolomics studies, three kinds of omics (i.e., transcriptomics, proteomics, and metabolomics) were carried out with zebrafish larvae exposed to 0.1, 1, 5, and 10 µM PFOS. More importantly, a data-driven integration of multi-omics was performed to elucidate the toxicity mechanism involved in developmental neurotoxicity. In a concentration-dependent manner, exposure to PFOS provoked hyperactivity and hypoactivity under light and dark conditions, respectively. Individual omics revealed that PFOS exposure caused perturbations in the pathways of neurological function, oxidative stress, and energy metabolism. Integrated omics implied that there were decisive pathways for axonal deformation, neuroinflammatory stimulation, and dysregulation of calcium ion signaling, which are more clearly specified for neurotoxicity. Overall, our findings broaden the molecular understanding of the developmental neurotoxicity of PFOS, for which multi-omics and integrated omics analyses are efficient for discovering the significant molecular pathways related to developmental neurotoxicity in zebrafish.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/toxicidade , Animais , Embrião não Mamífero , Fluorcarbonetos/toxicidade , Larva , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
19.
BMJ Open ; 11(8): e046828, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380719

RESUMO

INTRODUCTION: Hands play a part in the transmission of infections. Handwashing with soap sufficiently reduces the level of hand contamination and the spread of infections. As soap is not usually available due to cost, ash is often used as a zero-cost alternative to soap in the rural settings of developing countries. However, there is limited evidence on the effectiveness of ash to reduce microbial contamination of hands. This study is, therefore, designed to assess the effect of ash on microbial contamination of hands in the rural settings of northwest Ethiopia. METHODS AND ANALYSIS: A two-arm clustered-randomised controlled trial will be employed. A total of 11 clusters per arm will be selected using simple random sampling technique. A total of 220 mothers or caregivers of under-5 children will be included in each arm. After providing health education on effective handwashing process, we will ask study subjects to do the usual activities. We will then take swab samples from the dominant hand before washing. After swabbing, participants will be asked to wash their hands with water only and with ash by following effective handwashing procedures. We will again take swab samples from the dominant hand after washing and drying. Finally, we will compare each intervention arm against the control. A generalised estimating equation (GEE) with robust SE estimation will be used to account the cluster nature of data. ETHICS AND DISSEMINATION: Results will be published in peer-reviewed journal and presented at international conferences. The protocol is approved by the Institutional Review Board of the University of Gondar, Ethiopia. TRIAL REGISTRATION NUMBER: Pan African Clinical Trial Registry; PACTR202011855730652.


Assuntos
Desinfecção das Mãos , Mãos , Criança , Etiópia , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , População Rural , Sabões
20.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360584

RESUMO

Trichostatin A (TSA) is a representative histone deacetylase (HDAC) inhibitor that modulates epigenetic gene expression by regulation of chromatin remodeling in cells. To investigate whether the regulation of chromatin de-condensation by TSA can affect the increase in the efficiency of Cas9 protein-gRNA ribonucleoprotein (RNP) indel formation from plant cells, genome editing efficiency using lettuce and tobacco protoplasts was examined after several concentrations of TSA treatments (0, 0.1, 1 and 10 µM). RNP delivery from protoplasts was conducted by conventional polyethylene glycol (PEG) transfection protocols. Interestingly, the indel frequency of the SOC1 gene from TSA treatments was about 3.3 to 3.8 times higher than DMSO treatment in lettuce protoplasts. The TSA-mediated increase of indel frequency of the SOC1 gene in lettuce protoplasts occurred in a concentration-dependent manner, although there was not much difference. Similar to lettuce, TSA also increased the indel frequency by 1.5 to 1.8 times in a concentration-dependent manner during PDS genome editing using tobacco protoplasts. The MNase test clearly showed that chromatin accessibility with TSA treatments was higher than that of DMSO treatment. Additionally, TSA treatment significantly increased the level of histone H3 and H4 acetylation from lettuce protoplasts. The qRT-PCR analysis showed that expression of cell division-related genes (LsCYCD1-1, LsCYCD3-2, LsCYCD6-1, and LsCYCU4-1) was increased by TSA treatment. These findings could contribute to increasing the efficiency of CRISPR/Cas9-mediated genome editing. Furthermore, this could be applied for the development of useful genome-edited crops using the CRISPR/Cas9 system with plant protoplasts.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Ácidos Hidroxâmicos/farmacologia , Alface/metabolismo , Proteínas de Plantas/metabolismo , Protoplastos/metabolismo , Tabaco/metabolismo , Divisão Celular , Genoma de Planta , Alface/efeitos dos fármacos , Alface/genética , Alface/crescimento & desenvolvimento , Células Vegetais , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Inibidores da Síntese de Proteínas/farmacologia , Protoplastos/efeitos dos fármacos , Tabaco/efeitos dos fármacos , Tabaco/genética , Tabaco/crescimento & desenvolvimento
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