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1.
Brief Bioinform ; 25(5)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39293802

RESUMO

Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis-expression quantitative loci (sb-cis-eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb-cis-eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes.


Assuntos
Locos de Características Quantitativas , Humanos , Masculino , Feminino , Povo Asiático/genética , Transcriptoma , China , Cromossomos Humanos X/genética , Caracteres Sexuais , Genética Populacional , Regulação da Expressão Gênica , Perfilação da Expressão Gênica/métodos
2.
Anal Chem ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325964

RESUMO

The detection of endogenous phenolic compounds (EPs) in food is of great significance in elucidating their bioactivity and health effects. Here, a novel bifunctional vanillic acid-Cu (VA-Cu) nanozyme with peroxidase-like and laccase-like activities was successfully prepared. The peroxidase mimic behavior of VA-Cu nanozyme can catalyze 3,3',5,5'-tetramethylbenzidine (TMB) to generate oxidized TMB (oxTMB). Owing to the high reducing power of EPs, this process can be inhibited, and the degree of inhibition increases with the increase of reaction time. Additionally, owing to the outstanding laccase mimic behavior of the VA-Cu, it can facilitate the oxidation of various EPs, resulting in the formation of colored quinone imines, and the degree of catalysis increases with the increase of reaction time. Based on the interesting experimental phenomena mentioned above, a six-channel nanozyme sensor array (2 enzyme-mimic activities × 3 time points = 6 sensing channels) was constructed, successfully achieving discriminant analysis of nine EPs. In addition, the combination of artificial neural network (ANN) algorithms and sensor arrays has successfully achieved accurate identification and prediction of nine EPs in black tea, honey, and grape juice. Finally, a portable method for identifying EPs in food has been proposed by combining it with a smartphone.

3.
Int J Biol Macromol ; 280(Pt 3): 135877, 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39317290

RESUMO

Phanerochaete chrysosporium were immobilized in magnetic Fe3O4 nanoparticles and calcium alginate to form MC microspheres. The obtained MC microsphere was characterized by SEM, EDS, XRD, BET, VSM and TGA. The results indicated that MC microsphere was a three-dimensional structure with relatively large specific surface area and good porosity. MC microspheres had excellent magnetic recovery performance and thermal stability. The characteristics and performance of MC microspheres on adsorption of Cu2+ were evaluated based on batch adsorption experiments. The maximum adsorption capacity of Cu2+ by MC microspheres was 35.07 mg g-1 at pH of 5.0, temperature of 35 °C and adsorption time of 8 h. MC microspheres can still effectively adsorb Cu2+ at 400 mg L-1. Integrating simulation results from pseudo-second-order kinetic model, Intra-particle diffusion model and Freundlich model, the process was mainly dominated by chemical adsorption, and it is a multi-molecular layer adsorption. The results of XPS and FTIR showed that complexation, ion replacement, and reduction are important mechanisms for adsorption of Cu2+ on MC microspheres. -OH and C-O/C=O mainly complexes with Cu2+ in the biosorption process. After five adsorption-desorption cycles, the adsorption efficiency can still reach 32.40 %. Therefore, MC microspheres are a potential adsorbent that can achieve effective recovery.

4.
Int J Antimicrob Agents ; : 107338, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293773

RESUMO

Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like Klebsiella pneumoniae present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of K. pneumoniae to colistin in vitro and to validate the synergistic therapeutic effect in vivo. The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro concurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the AI-2 factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on Galleria mellonella and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone. These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant K. pneumoniae-associated infections.

5.
Front Med (Lausanne) ; 11: 1408342, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39188880

RESUMO

Background: Surgical patients often experience intraoperative hypothermia or hyperthermia. However, the relationship of intraoperative hypothermia and hyperthermia with postoperative pulmonary infection (PPI) and surgical site infection (SSI) is unclear. Here, we conducted a retrospective cohort study to address these issues. Methods: Adult patients who underwent major non-cardiac surgery under general anesthesia were eligible for the study and were recruited. Three indices of core body temperature under hypothermia (<36°C) and hyperthermia (>37.3°C) were calculated as mentioned in the following: absolute value (0C), duration of exposure (min), and area under the curve (AUC,°C× min). The outcomes were in-hospital PPI and SSI. The risk-adjusted association of intraoperative hypothermia and hyperthermia with PPI and SSI was determined. Results: The absolute value (the nadir value of hypothermia and the peak value of hyperthermia) was not associated with PPI and SSI. PPI was associated with (1) duration: hypothermia >90 min [adjusted odds ratio (aOR): 1.425, 95% confidence interval (CI): 1.131-1.796] and hyperthermia >75 min (aOR: 1.395, 95%CI: 1.208-1.612) and (2) AUC: hypothermia >3,198 (aOR: 1.390, 95%CI: 1.128-1.731) and hyperthermia >7,945 (aOR: 2.045, 95%CI: 1.138-3.676). SSI was associated with (1) duration: hypothermia > 195 min (aOR: 2.900, 95%CI: 1.703-4.937) and hyperthermia >75 min (aOR: 1.395, 95%CI: 1.208-1.612) and (2) AUC: hypothermia >6,946 (aOR: 2.665, 95%CI: 1.618-4.390), hyperthermia >7,945 (aOR: 2.619, 95%CI: 1.625-4.220). Interactions were not observed between hyperthermia and hypothermia on the outcomes. Conclusions: It was observed that intraoperative hypothermia and hyperthermia are associated with postoperative pulmonary infection and surgical site infection in major non-cardiac surgery.

6.
Biomed Pharmacother ; 178: 117223, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39094541

RESUMO

Hyperuricemia is with growing incidence and of high risk to develop into gout and other metabolic diseases. The key enzyme catalyzing uric acid synthesis, xanthine oxidoreductase (XOR) is a vital target for anti-hyperuricemic drugs, while XOR inhibitors characterized as both potent and safe are currently in urgent need. In this study, a novel small molecule compound, CC15009, was identified as a specific XOR inhibitor. CC15009 exerted strongest in vitro XOR inhibitory activity among current XOR inhibitors. It also showed favorable dose-dependent uric acid-lowering effects in two different XOR substrate-induced hyperuricemic mouse models, which was significantly superior than the current first-line drug, allopurinol. Mechanically, the direct binding of CC15009 against XOR was confirmed by molecular docking and SPR analysis. The inhibition mode was competitive and reversible. Besides, the potential antioxidant activity of CC15009 was indicated by its strong inhibitory activity against the oxidized isoform of XOR, which reduced ROS generation as the byproduct. Regarding the safety concerns of current XOR inhibitors, especially in cardiovascular risks, the safety of CC15009 was comprehensively evaluated. No significant abnormality was observed in the acute, subacute toxicity tests and mini-AMES test. Notably, there was no obvious inhibition of CC15009 against cardiac ion channels, including hERG, Nav1.5, Cav1.2 at the concentration of 30 µM, indicating its lower cardiovascular risk. Taken together, our results supported CC15009 as a candidate of high efficacy and safety profile to treat hyperuricemia through direct XOR inhibition.


Assuntos
Inibidores Enzimáticos , Hiperuricemia , Ácido Úrico , Xantina Desidrogenase , Animais , Humanos , Masculino , Camundongos , Alopurinol/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Hiperuricemia/tratamento farmacológico , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Ácido Úrico/sangue , Xantina Desidrogenase/antagonistas & inibidores , Xantina Desidrogenase/metabolismo
7.
Acta Pharmacol Sin ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152295

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15 (5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15 was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15 significantly reduced Aß accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15 and the necessity of the CaMKIIα/Fos for FO-4-15 was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15 and mGluR1 was displayed by Ca2+ flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15 was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15 may hold promise as a potential treatment for Alzheimer's disease.

8.
BMC Biol ; 22(1): 169, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135045

RESUMO

BACKGROUND: Numerous insect species undertake long-distance migrations on an enormous scale, with great implications for ecosystems. Given that take-off is the point where it all starts, whether and how the external light and internal circadian rhythm are involved in regulating the take-off behaviour remains largely unknown. Herein, we explore this issue in a migratory pest, Cnaphalocrocis medinalis, via behavioural observations and RNAi experiments. RESULTS: The results showed that C. medinalis moths took off under conditions where the light intensity gradually weakened to 0.1 lx during the afternoon or evening, and the take-off proportions under full spectrum or blue light were significantly higher than that under red and green light. The ultraviolet-A/blue light-sensitive type 1 cryptochrome gene (Cmedcry1) was significantly higher in take-off moths than that of non-take-off moths. In contrast, the expression of the light-insensitive CRY2 (Cmedcry2) and circadian genes (Cmedtim and Cmedper) showed no significant differences. After silencing Cmedcry1, the take-off proportion significantly decreased. Thus, Cmedcry1 is involved in the decrease in light intensity induced take-off behaviour in C. medinalis. CONCLUSIONS: This study can help further explain the molecular mechanisms behind insect migration, especially light perception and signal transmission during take-off phases.


Assuntos
Criptocromos , Proteínas de Insetos , Mariposas , Animais , Migração Animal , Ritmo Circadiano , Criptocromos/genética , Criptocromos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Luz , Mariposas/fisiologia , Interferência de RNA
9.
Sci Rep ; 14(1): 15114, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956155

RESUMO

Wheat straw returning is a common agronomic measure in the farmland. Understanding organic carbon transformation is of great significance for carbon budget under the premise of widespread distribution of cadmium (Cd) contaminated soils. An incubation experiment was conducted to assess the influence of Cd contamination on the decomposition and accumulation of total organic carbon (TOC) as well as the composition and abundance of bacterial communities in eight soil types with wheat straw addition. The results showed that inhibition of Cd contamination on microbially mediated organic carbon decomposition was affected by soil types. The lower cumulative C mineralization and higher TOC content could be observed in the acidic soils relative to that in the alkaline soils. The content of Cd in soil exhibits different effects on the inhibition in decomposition of TOC. The high dosage level of Cd had stronger inhibitory impact due to its high toxicity. The decomposition of TOC was restricted by a reduction in soil bacterial abundance and weakening of bacterial activities. Redundancy analysis (RDA) indicated that Proteobacteria and Gemmatimonadetes were abundant in alkaline Cd-contaminated soils with wheat straw addition, while Bacteroidetes dominated cumulative C mineralization in acidic Cd-contamination soils. Moreover, the abundance of predicted functional bacteria indicated that high-dose Cd-contamination and acid environment all inhibited the decomposition of TOC. The present study suggested that pH played an important role on carbon dynamics in the Cd-contaminated soils with wheat straw addition.


Assuntos
Cádmio , Carbono , Microbiologia do Solo , Poluentes do Solo , Solo , Triticum , Cádmio/metabolismo , Cádmio/análise , Triticum/metabolismo , Triticum/química , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Carbono/metabolismo , Carbono/análise , Solo/química , Bactérias/metabolismo , Biodegradação Ambiental , Concentração de Íons de Hidrogênio
10.
Biosens Bioelectron ; 262: 116529, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38950518

RESUMO

In the food industry, sulfides are commonly used as preservatives and flavor regulators. However, long-term excessive intake of sulfides can lead to serious health problems. Therefore, developing efficient sulfide detection methods is particularly important. Here, we have effectively synthesized a novel bifunctional copper hydroxide nitrate (Cu2(OH)3NO3) nanozyme with outstanding peroxidase-like and laccase-like behaviors in basic deep eutectic solvents (DES). Because the various types of sulfides have diverse regulatory effects on the two catalytic behaviors of Cu2(OH)3NO3, a two channel nanozyme sensor array based on the peroxidase-like and laccase-like behaviors of Cu2(OH)3NO3 was constructed and successfully used for the identification of six kinds of sulfides (Na2S, Na2S2O3, Na2SO3, Na2SO4, NaHSO3, and Na2S2O8). Remarkably, the sensor array has achieved successful discrimination among six sulfides present in wine, egg, and milk samples. Finally, the sensor array has successfully distinguished and differentiated three actual samples (wine, egg, and milk). This study is of great significance in promoting the efficient construction of array units and improving the effective identification of sulfides in complex food samples.


Assuntos
Técnicas Biossensoriais , Cobre , Análise de Alimentos , Sulfetos , Sulfetos/química , Cobre/química , Técnicas Biossensoriais/métodos , Análise de Alimentos/instrumentação , Nitratos/análise , Nitratos/química , Leite/química , Vinho/análise , Animais , Hidróxidos/química , Nanoestruturas/química
11.
Mol Biol Evol ; 41(7)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38995236

RESUMO

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin, genomic makeup, and genetic interaction with surrounding populations are not well understood. To decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from 4 ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from the Uyghurs in terms of their overall genomic makeup, although the 2 populations were closely related in genetics, and both showed a substantial admixture of western and eastern peoples. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those living or along the old Silk Road.


Assuntos
Povo Asiático , Humanos , Masculino , Feminino , Povo Asiático/genética , China , Genoma Humano , Sequenciamento Completo do Genoma , População da Ásia Central
12.
Sci Rep ; 14(1): 17200, 2024 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060323

RESUMO

Nutrition is a limiting feature of species evolution. The differences in nutritional requirements are the evolutionary result of differential adaptations to environmental changes, explaining differences in their ecological traits. Cnaphalocrocis medinalis and Cnaphalocrocis exigua, two related species of rice leaffolders, have similar morphology and feeding properties but different migration and overwintering behaviors. However, it is unclear whether they have evolved adult nutritional differentiation traits to coexist. To explore this issue, this study examined the effects of carbohydrates and amino acids on their reproductive and demographic parameters. The findings indicate that carbohydrate intake prolonged the longevity and population growth of two rice leaffolders, but amino acid intake promoted egg hatching only. However, nutrient deficiency made it impossible for C. medinalis to reproduce successfully and survive, but it did not affect C. exigua. The population expansion and survival of migratory C. medinalis relied on adult nutritional intake. Conversely, the nutrients necessary for C. exigua overwintering activity mostly came from the storage of larvae. The difference in nutritional requirements for population growth and survival between the two rice leaffolders partially explained their differences in migration and overwintering.


Assuntos
Oryza , Animais , Oryza/crescimento & desenvolvimento , Aminoácidos/metabolismo , Crescimento Demográfico , Necessidades Nutricionais , Mariposas/fisiologia , Mariposas/crescimento & desenvolvimento , Larva/fisiologia , Feminino , Longevidade/fisiologia , Masculino , Especificidade da Espécie
13.
Biomed Pharmacother ; 177: 117103, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39018870

RESUMO

Alzheimer's disease (AD), the major cause of dementia, is a multifactoral progressive neurodegenerative disorder that currently affects over 43 million people worldwide. The interaction betweengenetic and environmental factors decides pathogenesis and pathological development. The chemical drugs designed for clinical applications on AD have not reached the expected preventive effect so far.Here, we obtained a new evodiamine (Evo) derivative, LE-42, which exhibited lower cytotoxicity in SH-SY5Y cells and HepaG2 cells than that of Evo. The LD50 of LE-42 in SH-SY5Y cells and HepaG2 cells was increased by 9 folds and 14 folds than Evo, respectively. The LE-42 also exhibited much more potent effects on anti-oxidation and anti-cytotoxicity of AßOs than Evo. The LE-42 significantly improved the working memory, spatial learning, and memory of the 3×Tg AD mice, and the pharmacodynamic dose of LE-42 on AD mice was increased by 500 folds than that of Evo. LE-42 significantly improved the Tau hyperphosphorylation, a typical pathological feature in 3×Tg AD mice. The LE-42 restored the JAK2/STAT3 pathway's dysfunction and upregulated the expression of GluN1, GluA2, SYN, and PSD95, subsequentially improving the synaptic integrity in 3×Tg mice. The activation of the JAK2/STAT3 axis by LE-42 was a possible mechanism for a therapeutic effect on the AD mice.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Quinazolinas , Sinapses , Animais , Quinazolinas/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Camundongos , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/patologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Humanos , Camundongos Transgênicos , Modelos Animais de Doenças , Masculino , Fator de Transcrição STAT3/metabolismo , Proteínas tau/metabolismo , Janus Quinase 2/metabolismo , Linhagem Celular Tumoral , Fosforilação/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL
14.
J Asian Nat Prod Res ; : 1-11, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38945152

RESUMO

Histone deacetylase 6 (HDAC6) was a potential target for Alzheimer's disease (AD). In this study, a series of novel oxyevodiamine-based HDAC6 inhibitors with a variety of linker moieties were designed, synthesized and evaluated. Compound 12 with a benzyl linker was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC50 value of 6.2 nM and was more than 200 fold selectivity over HDAC1. It also had lower cytotoxicity and higher anti-H2O2 activity in vitro comparing with other derivatives. Compound 12 might be a good lead as novel HDAC6 inhibitor for the treatment of AD.

15.
Front Vet Sci ; 11: 1401909, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872795

RESUMO

Aims: The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)-induced immune stress. Methods: Two hundred and forty one-day-old male Arbor Acres chicks were randomly divided into four groups (saline, LPS, saline + AEE and LPS + AEE) with six replicates of ten broilers each. The saline group and LPS group were fed the normal diet, while the other two groups received normal diet plus 0.1 g/kg AEE. Broilers in the LPS and LPS + AEE groups were injected intraperitoneally with 0.5 mg/kg B.W LPS in saline for seven consecutive days beginning at 14 days of age, while broilers in the saline and saline + AEE groups were injected with saline only. Results: The results showed that AEE improved the ileal morphology and increased the ratio of villus height to crypt depth of immune-stressed broilers. LPS-induced immune stress significantly reduced the expression of the genes for the tight junction proteins occludin, zonula occludens-1 (ZO-1), claudin-1 and claudin-2, in the ileum, while AEE significantly up-regulated the expression of these genes. Compared with the saline group, the LPS-treated chickens showed significantly increased mRNA expression of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), cyclooxygenase-2 (COX-2), and microsomal Prostaglandin E Synthesase-1 (mPGES-1) in the ileum, while they were significantly decreased by AEE supplementation. In addition, analysis of the ileal bacterial composition showed that compared with saline and LPS + AEE groups, the proportion of Firmicutes and Lactobacillus in the LPS group was lower, while the proportion of Proteobacteria and Escherichia-Shigella was higher. Similarly, Line Discriminant Analysis Effect Size (LEfSe) analysis showed that compared with the LPS group, Brevibacillus was dominant in the saline group, while the LPS + AEE group was rich in Rhizobium, Lachnoclostridium, Ruminococcaceae, Faecalibacterium, Negativibacillus, Oscillospiraceae, and Flavonifractor. Conclusion: These results indicate that dietary supplementation with 0.1 g/kg AEE could protect the intestinal health by improving the intestinal villus morphology, enhancing the expression of tight junction genes and alleviating inflammation to resist the immune stress caused by LPS stimulation in broilers, and the mechanism may involve COX-2-related signal transduction and improved intestinal microbiota composition.

16.
Front Microbiol ; 15: 1396663, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873155

RESUMO

Klebsiella pneumoniae (K. pneumoniae) infection and the rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. Polymyxin E (colistin), a group of cationic antimicrobial polypeptides, is currently one of the last resort treatment options against carbapenem-resistant Gram-negative pathogens. The effectiveness of colistin has been compromised due to its intensive use. This study found that fingolimod (FLD), a natural product derivative, exhibited a significant synergistic bactericidal effect on K. pneumoniae when combined with colistin, both in vitro and in vivo. The checkerboard method was employed to assess the in vitro synergistic effect of FLD with colistin. FLD enhanced the susceptibility of bacteria to colistin and lowered effectively minimum inhibitory concentrations (MIC) when compared to colistin MIC, and the fractional inhibitory concentrations (FIC) value was less than 0.3. The time-kill curve demonstrated that the combination treatment of FLD and colistin had significant bactericidal efficacy. The in vitro concurrent administration of colistin and FLD resulted in heightening membrane permeability, compromising cell integrity, diminishing membrane fluidity, and perturbing membrane homeostasis. They also induced alterations in membrane potential, levels of reactive oxygen species, and adenosine triphosphate synthesis, ultimately culminating in bacterial death. Moreover, the combination of FLD with colistin significantly influenced fatty acid metabolism. In the mouse infection model, the survival rate of mice injected with K. pneumoniae was significantly improved to 67% and pathological damage was significantly relieved with combination treatment of FLD and colistin when compared with colistin treatment. This study highlights the potential of FLD in combining with colistin for treating infections caused by MDR isolates of K. pneumoniae.

18.
Poult Sci ; 103(7): 103825, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772090

RESUMO

This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal microbiota of broilers raised under stressful high density (HD) stocking conditions compared with normal density broilers (ND). A total of 432 one-day-old AA+ male broilers were randomly divided into 4 groups: normal density (ND, 14 broilers /m2), high density (HD, 22 broilers /m2), ND + AEE, and HD + AEE. The results of the study revealed a significant decrease in the growth performance of broiler chickens as a result of HD stress (P < 0.05). The total antioxidant capacity (T-AOC) in serum demonstrated a significant decrease (P < 0.05) at both 28 and 35 d. Conversely, the serum level of malondialdehyde (MDA) exhibited a significant increase (P < 0.05). Dietary supplementation of AEE resulted in a significant elevation (P < 0.05) of serum GSH-PX, SOD and T-AOC activity at both 28 and 35 d. Moreover, exposure to HD stress resulted in a considerable reduction in the height of intestinal villi and mRNA expression of tight junction proteins in the jejunum, along with, a significant elevation in the mRNA expression of inflammatory cytokines (P < 0.05). However, the administration of AEE reversed the adverse effects of HD-induced stress on villus height and suppressed the mRNA expression of the pro-inflammatory genes, COX-2 and mPGES-1. Additionally, the exposure to HD stress resulted in a substantial reduction in the α-diversity of cecal microbiota and disruption in the equilibrium of intestinal microbial composition, with a notable decrease in the relative abundance of Bacteroides and Faecalibacterium (P < 0.05). In contrast, the addition of AEE to the feed resulted in a notable increase in the relative abundance of Phascolarctobacterium and enhanced microbial diversity (P < 0.05). The inclusion of AEE in the diet has been demonstrated to enhance intestinal integrity and growth performance of broilers by effectively mitigating disruptions in gut microbiota induced by HD stress.


Assuntos
Ração Animal , Antioxidantes , Aspirina , Ceco , Galinhas , Dieta , Suplementos Nutricionais , Eugenol , Microbioma Gastrointestinal , Animais , Galinhas/crescimento & desenvolvimento , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Antioxidantes/metabolismo , Dieta/veterinária , Ceco/microbiologia , Ceco/efeitos dos fármacos , Aspirina/administração & dosagem , Aspirina/farmacologia , Aspirina/análogos & derivados , Ração Animal/análise , Suplementos Nutricionais/análise , Eugenol/análogos & derivados , Eugenol/administração & dosagem , Eugenol/farmacologia , Distribuição Aleatória , Criação de Animais Domésticos , Inflamação/veterinária , Inflamação/induzido quimicamente
19.
Sci Rep ; 14(1): 10082, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698242

RESUMO

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. However, effective diagnostic, therapeutic and prognostic biomarkers are still lacking. Our research group previously revealed through high-throughput sequencing that the serum exosomes miR-133a-3p, miR-206, and miR-549a-3p differ significantly in severe TBI (sTBI), mild or moderate TBI (mTBI), and control groups. However, convincing experimental evidence is lacking. To solve this problem, we used qPCR in this study to further verify the expression levels of serum exosomes miR-133a-3p, miR-206 and miR-549a-3p in TBI patients. The results showed that the serum exosomes miR-206 and miR-549a-3p showed good predictive value as biomarkers of TBI. In addition, in order to further verify whether serum exosomes miR-206 and miR-549a-3p can be used as potential biomarkers in patients with TBI and to understand the mechanism of their possible effects, we further determined the contents of SOD, BDNF, VEGF, VEGI, NSE and S100ß in the serum of TBI patients. The results showed that, serum exosomes miR-206 and miR-549a-3p showed good correlation with BDNF, NSE and S100ß. In conclusion, serum exosomes miR-206 and miR-549a-3p have the potential to serve as potential biomarkers in patients with TBI.


Assuntos
Biomarcadores , Lesões Encefálicas Traumáticas , Exossomos , MicroRNAs , Humanos , MicroRNAs/sangue , MicroRNAs/genética , Exossomos/metabolismo , Exossomos/genética , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/genética , Biomarcadores/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Estudos de Casos e Controles
20.
Ecotoxicol Environ Saf ; 278: 116406, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728941

RESUMO

Cadmium contamination inevitably affects the microbially mediated transformation of nitrogen in soils with wheat straw return. The responses of nitrogen functional microorganisms to cadmium in acidic and alkaline soils under wheat straw returned are still unclear. In this study, quantitative polymerase chain reaction (qPCR) and sequencing of nitrifying and denitrifying bacteria were performed to investigate the effects of wheat straw application on nitrogen conversion in different Cd-contaminated soils during an incubation experiment. Results showed that the presence of Cd decreased the abundance of hao gene catalyzing nitrification and norB gene catalyzing denitrification process, resulting the accumulation of NH4+-N and reduction of NO3--N in the acidic soils. Additionally, Cd-contamination stimulates the nitrification catalyzed by bacterial amoA gene and thus reduced the NH4+-N content in the alkaline soils. Meanwhile, Cd dominated the decrease of NO3--N content by promoting denitrification process catalyzed by nirS gene. Among all nitrifying and denitrifying microorganisms, Nitrosospira are tolerant to Cd stress under alkaline condition but sensitive to acidic condition, which dominantly harbored hao gene in the acidic soils and bacterial amoA gene in the alkaline soils. This study aimed to provide reasonable information for the rational adoption of wheat straw returning strategies to realize nitrogen regulation in Cd-contaminated farmland soil.


Assuntos
Cádmio , Desnitrificação , Nitrificação , Microbiologia do Solo , Poluentes do Solo , Triticum , Cádmio/análise , Cádmio/metabolismo , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Nitrogênio/metabolismo , Solo/química , Bactérias/metabolismo , Bactérias/genética , Ciclo do Nitrogênio
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