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1.
Food Chem ; 335: 127663, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32738540

RESUMO

Dissecting the functions of high molecular weight glutenin subunits (HMW-GSs) is helpful for improving wheat quality via breeding. In this study, we used a wheat mutant AS273 in which HMW-GS 1Dy12 was silenced to investigate the silencing mechanism of 1Dy12 and its effects on gluten accumulation and flour-processing quality. Results suggested that the expression of 1Dy12 in AS273 was decreased by one fifth during grain development; a stop codon produced by a base mutation (C/T) led to truncated translation; the absence of 1Dy12 stimulated the accumulation of low molecular weight glutenin subunits (LMW-GSs), gliadins, and glutenin macropolymers, and was resulted in larger protein bodies; AS273 had an inferior flour-processing performance. Based on the outputs achieved in this study it is concluded that 1Dy12 makes important contributions to bread, sponge cake and biscuit-processing quality.


Assuntos
Pão , Glutens/genética , Glutens/metabolismo , Triticum/genética , Triticum/metabolismo , Pão/análise , Códon de Terminação , Eletroforese em Gel de Poliacrilamida , Farinha , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Gliadina/metabolismo , Peso Molecular , Mutação , Proteínas de Armazenamento de Sementes/genética , Proteínas de Armazenamento de Sementes/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Triticum/crescimento & desenvolvimento
2.
Sci Total Environ ; 751: 141725, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33181981

RESUMO

Trace elements (TEs) in water are crucial parameters for assessing water quality. However, detailed studies are limited on TEs in the hydrological system of the Tibetan plateau (TP). Here, we sampled snow, river water, and groundwater in Yulong Snow Mountain (Mt. Yulong) region, southeast TP, in 2016 and analyzed the concentrations of nine TEs (namely Al, Mn, Fe, Cr, Ni, Cu, Zn, As, and Pb). In snow, the average concentrations of Fe, Zn, and Al were >10 µg/L, whereas other elements, including Cr, Ni, Cu, As, Hg, and Pb, exhibited average concentrations <1 µg/L. The concentrations of Al, Mn, Fe, Zn, and As were higher in rivers than in snow. According to enrichment factors (EFs), Zn concentration in snow was highly influenced by anthropogenic activities, whereas Mn, Fe, Cr, and As were uninfluenced. River and lake/reservoir water near human settlements were affected by anthropogenic activities. However, groundwater around Mt. Yulong is not contaminated yet. The increasing EFs in Mt. Yulong snowpit are consistent with those of southern TP snowpits, suggesting that the area has been affected by anthropogenic activities both from local emissions and long-distance transport of pollutants from South Asia. A conceptual model was proposed to show TEs in the water cycle. Although water quality is good overall in Mt. Yulong region, threats to the water environment still exit due to increasing anthropogenic activities and climate warming. The accelerated ablation of cryosphere due to climate warming could be a source of TEs in rivers and groundwater, which should be paid attention to in the future.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33140453

RESUMO

RATIONALE: The screening for illegal adulteration of glucocorticoids (GCs) in cosmetics is challenging due to the vast variety of potential GCs that are present to improve the declared effects. An effective analytical method to screen illegally added GCs in cosmetics is vital to protect consumers. METHODS: An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method using precursor ion scanning (PIS) acquisition mode was developed to screen GCs in cosmetics. 47 GCs were investigated to identify common GCs product ions formed by collision-induced dissociation. Cosmetic samples spiked with GCs were extracted using solid-phase extraction. RESULTS: Four common positive product ions, m/z 121, 135, 147, and 171, were selected for PIS analysis. Limits of detection (LOD) were established for all 47 GCs. The method was validated on spiked samples to ensure its effectiveness in terms of sensitivity and selectivity. Sixty samples were analyzed. Seven GCs were detected in six samples. CONCLUSIONS: An effective screening method using UPLC/MS/MS with PIS acquisition mode was developed and successfully applied to screen for targeted and untargeted GCs in cosmetic samples.

4.
J Autoimmun ; : 102562, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33168359

RESUMO

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.

5.
Dev Comp Immunol ; : 103913, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137394

RESUMO

Protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase, a highly conserved enzyme widely expressed in eukaryotic cells, which accounts for a majority of the serine/threonine phosphatase activity in cells implicated in regulation of immune signaling pathways and antiviral response. However, most of studies about PP2A have been conducted in mammals but few in crustaceans. In this study, two subunits of PP2A (named as CqPP2Ab and CqPP2Ac) were characterized to be involved in white spot syndrome virus (WSSV) infection in the haematopoietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus. The open reading frame (ORF) of CqPP2Ab was 1341 bp encoding 446 amino acids with seven WD40 domains, and the ORF of CqPP2Ac was 930 bp encoding 309 amino acids with a PP2Ac domain. Tissue distribution analysis showed that the mRNA transcript of CqPP2Ab and CqPP2Ac were both widely expressed in all the tested tissues with the highest expression in hemocyte, followed by high expression in Hpt. The gene expressions of CqPP2Ab and CqPP2Ac were both significantly down-regulated at 6 h post WSSV infection (6 hpi) in Hpt cells. Importantly, the expression of viral immediate early gene IE1 and late viral gene envelope protein VP28 were both significantly increased post WSSV infection after gene silencing of CqPP2Ab or CqPP2Ac in Hpt cells, suggesting that CqPP2Ab and CqPP2Ac could inhibit WSSV infection in Hpt cells, probably by increasing the antimicrobial substances expression in consideration to the significantly reduced expression of anti-lipopolysaccharide factor, crustin, and lysozyme after gene silencing of CqPP2Ab or CqPP2Ac, respectively. These findings provide a new light on the mechanism of WSSV infection and the antiviral response in crustaceans.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33203825

RESUMO

Polyhydroxyalkanoates (PHA) are a family of microbial polyesters that are used as biodegradable plastics in replacement of conventional plastics for various applications. However, the high production cost is the barrier for PHA market expansion. This study aimed to utilize food waste as low-cost feedstock to produce poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) by Haloferax mediterranei . The effects of acetate (Ac), propionate (Pr), butyrate (Bu), and the short-chain carboxylates derived from food waste were examined on the microbial growth and PHBV production. Results showed that a mixture of carboxylates provided a 55% higher PHBV yield than glucose. The food-waste-derived nutrients achieved the yields of 0.41 to 0.54 g PHBV/g Ac from initial loadings of 450 mg/L to 1800 mg/L Ac of total carboxylates. And the consumption of individual carboxylate varied between different compositions of the carbon source. The present study demonstrates the potential of using food waste as feedstock to produce PHBV by Haloferax mediterranei , which can provide economic benefits to the current PHA industry. Meanwhile, it will also help promote organic waste reduction in landfills and waste management in general.

8.
J Chromatogr A ; 1634: 461671, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33166891

RESUMO

A rapid, simple and generic analytical method has been developed for the analysis of veterinary drugs in pork by a quadrupole time-of-flight mass spectrometry (Q-TOF MS). This method allows for the simultaneous identification, screening and quantitation of 141 veterinary drug residues and metabolites from eighteen different classes. After extraction with acetonitrile/water and clean-up with C18 cartridges, the samples were analyzed by HPLC-Q-TOF MS. Validation of this method consisted of confirmation of identity, selectivity, linearity, limit of detection (LOD), lowest limit of quantification (LLOQ), matrix effect, recovery, precision and applicability of the method. Identification of the analytes was based on accurate mass measurements. The characteristic fragments were obtained by collisional experiments for a more reliable identification. The procedure was then applied to real pork samples. Sulfamethazine was detected in one sample and its metabolites were successfully found in one single run. This approach proved to be satisfactory for routine analysis.

9.
BMC Cancer ; 20(1): 1120, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213397

RESUMO

BACKGROUND: Previous research results on the predictive factors of neoadjuvant chemotherapy (NCT) efficacy in breast cancer are inconsistent, suggesting that the ability of a single factor to predict efficacy is insufficient. Combining multiple potential efficacy-related factors to build a model may improve the accuracy of prediction. This study intends to explore the clinical and biological factors in breast cancer patients receiving NCT and to establish a nomogram that can predict the pathologic complete response (pCR) rate of NCT. METHODS: We selected 165 breast cancer patients receiving NCT from July 2017 to May 2019. Using pretreatment biopsy materials, immunohistochemical studies to assess estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression. The correlation between biological markers and pCR was analyzed. These predictors were used to develop a binary logistic regression model with cross-validation and to show the established predictive model with a nomogram. RESULTS: The nomogram for pCR based on lymphovascular invasion, anemia (hemoglobin≤120 g/L), ER, Ki67 expression levels and NCT regimen had good discrimination performance (area under the curve [AUC], 0.758; 95% confidence interval [CI], 0.675-0.841) and calibration coordination. According to the Hosmer-Lemeshow test, the calibration chart showed satisfactory agreement between the predicted and observed probabilities. The final prediction accuracy of cross-validation was 76%. CONCLUSIONS: We developed a nomogram based on multiple clinical and biological covariations that can provide an early prediction of NCT response and can help to quickly assess the individual benefits of NCT.

10.
Cell ; 183(4): 890-904.e29, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33157037

RESUMO

The Eastern Eurasian Steppe was home to historic empires of nomadic pastoralists, including the Xiongnu and the Mongols. However, little is known about the region's population history. Here, we reveal its dynamic genetic history by analyzing new genome-wide data for 214 ancient individuals spanning 6,000 years. We identify a pastoralist expansion into Mongolia ca. 3000 BCE, and by the Late Bronze Age, Mongolian populations were biogeographically structured into three distinct groups, all practicing dairy pastoralism regardless of ancestry. The Xiongnu emerged from the mixing of these populations and those from surrounding regions. By comparison, the Mongols exhibit much higher eastern Eurasian ancestry, resembling present-day Mongolic-speaking populations. Our results illuminate the complex interplay between genetic, sociopolitical, and cultural changes on the Eastern Steppe.

11.
Exp Gerontol ; : 111142, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33130112

RESUMO

BACKGROUND: In this study, the ovariectomized rat model was used to explore the impact of menopause on rats' dorsal lingual epithelium; at the same time, the curative effects of Remifemin and estradiol were also observed. METHODS: 28 adult female Sprague-Dawley rats were divided into four groups randomly, including sham-operated group (SHAM), an ovariectomized group (OVX), an ovariectomized treated with estradiol (OVX + E), an ovariectomized treated with Remifemin (OVX + iCR). Variation and possible mechanisms were studied via morphology, immunohistochemistry and electron microscope. RESULTS: The results showed that the dorsal lingual epithelium became thinner significantly in the apex part in OVX group, as well as the levels of proliferating cell nuclear antigen (PCNA) and the epidermal growth factor (EGF) were lower than that in other three groups. However, they could reverse close to normal after estradiol and Remifemin treatment respectively. CONCLUSION: The thinning in the apex of dorsal lingual epithelium might be due to the reduced proliferation in the germinal layer led by the abating of estrogen level, instead of apoptosis. This might play an important role in the pathogenesis of the menopause female tongue burning sensation. Remifemin had certain curative effect on the dorsal lingual mucosa, but a little more inferior than estrogen.

12.
BMJ Open ; 10(11): e034775, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154042

RESUMO

OBJECTIVES: To estimate the prevalence, ethnic differences and associated risk factors of myopic maculopathy in Han and Uygur adults in Xinjiang, China. DESIGN AND SETTING: A cross-sectional study with multistage, stratified cluster sampling method was conducted in Xinjiang, China. PARTICIPANTS: A total of 4023 Han and Uygur participants aged 40 years and older were eligible for the study. OUTCOME MEASURES: The association between myopic maculopathy and its risk factors was screened using the generalised estimating equation (GEE) model. We also investigated whether ethnic differences exist between Han and Uygur populations affected by myopic maculopathy. Myopic maculopathy was defined in accordance with International Photographic Classification and Grading System for Myopic Maculopathy. RESULTS: A total of 3044 subjects (5946 eyes) were included in our study (1736 Han and 1308 Uygur individuals). The participants consisted of 1256 (41.3%) men and 1788 (58.7%) women. The average age was 52.2±9.4 years, and the mean spherical equivalent (SE) was -0.18±2.31 dioptre (D). Myopic maculopathy was detected in 198 eyes of 138 participants. The age-adjusted prevalence of myopic maculopathy reached 5.8% (95% CI 4.8 to 6.8). In the GEE model, myopic maculopathy was significantly associated with old age (per year; OR: 1.16; 95% CI 1.13 to 1.19; p<0.001) and myopic SE (per -1 D; OR: 1.48; 95% CI 1.40 to 1.56; p<0.001). No ethnic differences were detected between Han (98, 5.7%) and Uygur population (40, 3.1%) in terms of the prevalence of myopic maculopathy (OR=0.89; 95% CI 0.53 to 1.48; p=0.64). Neither urbanisation (p=0.38) nor the level of education (p=0.92) was associated with myopic maculopathy. CONCLUSIONS: A high age-adjusted prevalence of myopic maculopathy was observed in Han and Uygur populations in Xinjiang, China. Old age and high degree of myopic refraction were independent risk factors for myopic maculopathy. No ethnic differences were detected in Han and Uygur populations affected by myopic maculopathy.

13.
Virol Sin ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33156486

RESUMO

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. The median age of the studied cohort was 59.83 ± 12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. The ratios of interferon gamma (IFN-γ)-secreting cells to total CD4+ and CD8+ cells were normal as 24.68% ± 9.60% and 66.41% ± 14.87% respectively. However, the number of IFN-γ-secreting NK cells diminished (58.03% ± 11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (Mean value neutralisation antibodies titers = 157.2, P = 0.05). No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS, and the cytopathic effect was lacking. But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages. Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARS-CoV-2 infection.

14.
Sensors (Basel) ; 20(22)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182697

RESUMO

To realize the blind estimation of binary phase shift keying (BPSK) signal, this paper describe a new relational expression among the state of Duffing oscillator excited by BPSK signal, the pseudo-random code of BPSK signal, and the difference frequency between the to-be-detect signal and internal drive force signal of Duffing oscillator. Two output characteristics of Duffing oscillators excited by BPSK signals named implied periodicity and pilot frequency array synchronization are presented according to the different chaotic states of Duffing oscillator. Then two blind estimation methods for the carrier frequency and pseudo-random sequence of the BPSK signal are proposed based on these two characteristics, respectively. These methods are shown to have a significant effect on the parameter estimation of BPSK signals with no prior knowledge, even at very low signal-to-noise ratios (SNRs).

16.
Food Funct ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175932

RESUMO

Osteoarthritis (OA) is a complicated pathological condition affecting thousands of people around world, many with substantial unmet medical care needs and without any effective therapies. Previous study has indicated that glucagon-like peptide-1 (GLP-1) is involved in the pathological progress of osteoarthritis; however, the role of dipeptidase-4 (DPP4), which regulates the degradation of GLP-1, still remains unclear in osteoarthritis. Herein, after comparing normal mouse cartilage tissues with OA mouse cartilage tissues by histological analysis, we found out that DPP4 was highly expressed in OA cartilage tissues. To investigate the role of DPP4 in osteoarthritis, the apoptosis and senescence of chondrocytes were found to be decreased in vitro when DPP4 was downregulated by siRNA in chondrocytes. Further study showed that the inhibition of DPP4 by procyanidins, a grape seed extract, attenuated apoptosis and senescence of chondrocytes in vitro. Furthermore, the results showed that DPP4 inhibition protects cartilage by activating Sirt1, which has been reported to be associated with many pathophysiological processes, particularly in age-related diseases, such as neurodegenerative disorders and osteoarthritis. In addition, animal experiment results demonstrated that procyanidins were capable of ameliorating the progression of osteoarthritis through the inhibition of DPP4. This study provides a competitive target for the therapeutic treatment of osteoarthritis, and procyanidins were shown to be a potential medicine for the restoration of the effects of osteoarthritis.

17.
Magn Reson Med ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179826

RESUMO

PURPOSE: The aim of this work is to shed light on the issue of reproducibility in MR image reconstruction in the context of a challenge. Participants had to recreate the results of "Advances in sensitivity encoding with arbitrary k-space trajectories" by Pruessmann et al. METHODS: The task of the challenge was to reconstruct radially acquired multicoil k-space data (brain/heart) following the method in the original paper, reproducing its key figures. Results were compared to consolidated reference implementations created after the challenge, accounting for the two most common programming languages used in the submissions (Matlab/Python). RESULTS: Visually, differences between submissions were small. Pixel-wise differences originated from image orientation, assumed field-of-view, or resolution. The reference implementations were in good agreement, both visually and in terms of image similarity metrics. DISCUSSION AND CONCLUSION: While the description level of the published algorithm enabled participants to reproduce CG-SENSE in general, details of the implementation varied, for example, density compensation or Tikhonov regularization. Implicit assumptions about the data lead to further differences, emphasizing the importance of sufficient metadata accompanying open datasets. Defining reproducibility quantitatively turned out to be nontrivial for this image reconstruction challenge, in the absence of ground-truth results. Typical similarity measures like NMSE of SSIM were misled by image intensity scaling and outlier pixels. Thus, to facilitate reproducibility, researchers are encouraged to publish code and data alongside the original paper. Future methodological papers on MR image reconstruction might benefit from the consolidated reference implementations of CG-SENSE presented here, as a benchmark for methods comparison.

18.
J Biophotonics ; : e202000349, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179837

RESUMO

3-photon microscopy (3PM) excited at the 1700-nm window enables deep-tissue imaging in vivo, especially in brain. PC rod soliton source has previously been exclusively used as the excitation source, which is rather costly and difficult to align. Here we demonstrate a novel nonlinear optical technique to build femtosecond laser source at the 1700-nm window, based on self-phase modulation (SPM) in a short span of large-mode-area (LMA) fiber. The spectral broadening experienced by the pump pulse leads to the generation of a red-shifted sidelobe at 1603 nm. After spectral filtering, this sidelobe corresponds to 170-fs, 167-nJ pulses at 1603 nm. Using this SPM source, we further demonstrate deep-brain 3PM to a depth of 1500 µm below the mouse brain surface in vivo. Our SPM femtosecond laser source thus provides a cost effective and easy-to-align alternative excitation source to the PC rod soliton source. This article is protected by copyright. All rights reserved.

19.
J Genet Genomics ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33187879

RESUMO

The TaQ alleles as one of the AP2-like transcription factors in common wheat (Triticum aestivum) play an important role in the evolution of spike characteristics from wild and domesticated emmer to modern wheat cultivars. Its loss-of-function mutant not only changed threshability and spike architecture but also affected plant height, flowering time, and floret structure. However, the comprehensive functions of TaAQ and TaDq genes in wheat have not been fully elucidated yet. Here, CRISPR/SpCas9 was used to edit wheat TaAQ and TaDq. We obtained homozygous plants in the T1 generation with loss of function of only TaAQ or TaDq and simultaneous loss of function of TaAQ and TaDq to analyze the effect of these genes on wheat spikes and floret shapes. The results demonstrated that the TaAQ-edited plants and the TaAQ and TaDq simultaneously-edited plants were nearly similar in spike architecture, whereas the TaDq-edited plants were different from the wild-type ones only in plant height. Moreover, the TaAQ-edited plants or the TaAQ and TaDq simultaneously-edited plants were more brittle than the wild-type and the TaDq-edited plants. Based on the expression profiling, we postulated that the VRN1, FUL2, SEP2, SEP5, and SEP6 genes might affect the number of spikelets and florets per spike in wheat by regulating the expression of TaQ. Combining the results of this report and previous reports, we conceived a regulatory network of wheat traits, including plant height, spike shape, and floral organs, which were influenced by AP2-like family genes. The results achieved in this study will help us to understand the regulating mechanisms of TaAQ and TaDq alleles on wheat floral organs and inflorescence development.

20.
Front Cell Infect Microbiol ; 10: 572849, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194811

RESUMO

Overuse or abuse of antibiotics has undoubtedly accelerated the increasing prevalence of global antibiotic resistance crisis, and thus, people have been trying to explore approaches to decrease dosage of antibiotics or find new antibacterial agents for many years. Antimicrobial peptides (AMPs) are the ideal candidates that could kill pathogens and multidrug-resistant bacteria either alone or in combination with conventional antibiotics. In the study, the antimicrobial efficacy of mud crab Scylla paramamosain AMPs Sphistin and Sph12-38 in combination with eight selected antibiotics was evaluated using a clinical pathogen, Pseudomonas aeruginosa. It was interesting to note that the in vitro combination of rifampicin and azithromycin with Sphistin and Sph12-38 showed significant synergistic activity against P. aeruginosa. Moreover, an in vivo study was carried out using a mouse model challenged with P. aeruginosa, and the result showed that the combination of Sph12-38 with either rifampicin or azithromycin could significantly promote the healing of wounds and had the healing time shortened to 4-5 days compared with 7-8 days in control. The underlying mechanism might be due to the binding of Sphistin and Sph12-38 with P. aeruginosa lipopolysaccharides (LPS) and subsequent promotion of the intracellular uptake of rifampicin and azithromycin. Taken together, the significant synergistic antibacterial effect on P. aeruginosa in vitro and in vivo conferred by the combination of low dose of Sphistin and Sph12-38 with low dose of rifampicin and azithromycin would be beneficial for the control of antibiotic resistance and effective treatment of P. aeruginosa-infected diseases in the future.

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