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1.
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.

2.
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.

3.
Perioper Med (Lond) ; 13(1): 39, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38735977

RESUMO

BACKGROUND: Postoperative acute kidney injury (AKI) is a common and costly complication after non-cardiac surgery. Patients with or without diabetes could develop hyperglycemia before surgery, and preoperative hyperglycemia was closely associated with postoperative poor outcomes, but the association between preoperative fasting blood glucose level and postoperative AKI is still unclear. METHODS: Data from patients undergoing non-cardiac surgery in Chongqing University Cancer Hospital from January 1, 2017, to May 31, 2023, were collected, preoperative glucose value and perioperative variables were extracted, the primary exposure of interest was preoperative glucose value, and the outcome was postoperative AKI. RESULTS: Data from 39,986 patients were included in the final analysis, 741(1.9%) patients developed AKI, 134(5.6%) in the cohort with DM, and 607(1.6%) in the cohort without DM(OR 1.312, 95% CI 1.028-1.675, P = 0.029). A significant non-linear association between preoperative glucose and AKI exists in the cohort without DM after covariable adjustment (P = 0.000), and every 1 mmol/L increment of preoperative glucose level increased OR by 15% (adjusted OR 1.150, 95% CI 1.078-1.227, P = 0.000), the optimal cut-point of preoperative fasting glucose level to predict AKI was 5.39 mmol/L (adjusted OR 1.802, 95%CI 1.513-2.146, P = 0.000). However, in the cohort with DM, the relation between preoperative glucose and postoperative AKI was not significant after adjusting by covariables (P = 0.437). No significance exists between both cohorts in the risk of AKI over the range of preoperative glucose values. CONCLUSION: A preoperative fasting glucose value of 5.39 mmol/L can predict postoperative acute kidney injury after non-cardiac surgery in patients without diagnosed diabetes, but it is not related to AKI in patients with the diagnosis.

4.
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
5.
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
6.
Poult Sci ; 103(7): 103825, 2024 May 11.
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.

7.
Plant Mol Biol ; 114(3): 44, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630172

RESUMO

Albino tea cultivars have high economic value because their young leaves contain enhanced free amino acids that improve the quality and properties of tea. Zhonghuang 1 (ZH1) and Zhonghuang 2 (ZH2) are two such cultivars widely planted in China; however, the environmental factors and molecular mechanisms regulating their yellow-leaf phenotype remain unclear. In this study, we demonstrated that both ZH1 and ZH2 are light- and temperature-sensitive. Under natural sunlight and low-temperature conditions, their young shoots were yellow with decreased chlorophyll and an abnormal chloroplast ultrastructure. Conversely, young shoots were green with increased chlorophyll and a normal chloroplast ultrastructure under shading and high-temperature conditions. RNA-seq analysis was performed for high light and low light conditions, and pairwise comparisons identified genes exhibiting different light responses between albino and green-leaf cultivars, including transcription factors, cytochrome P450 genes, and heat shock proteins. Weighted gene coexpression network analyses of RNA-seq data identified the modules related to chlorophyll differences between cultivars. Genes involved in chloroplast biogenesis and development, light signaling, and JA biosynthesis and signaling were typically downregulated in albino cultivars, accompanied by a decrease in JA-ILE content in ZH2 during the albino period. Furthermore, we identified the hub genes that may regulate the yellow-leaf phenotype of ZH1 and ZH2, including CsGDC1, CsALB4, CsGUN4, and a TPR gene (TEA010575.1), which were related to chloroplast biogenesis. This study provides new insights into the molecular mechanisms underlying leaf color formation in albino tea cultivars.


Assuntos
Albinismo , Perfilação da Expressão Gênica , Temperatura , Temperatura Baixa , Clorofila
8.
J Asian Nat Prod Res ; : 1-8, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619479

RESUMO

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment.

9.
PLoS One ; 19(4): e0299054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574027

RESUMO

Wheat straw returning is widely practiced in agriculture; therefore, it is critical to determine the physicochemical and bacterial indicators in soil for the organic carbon storage, accumulative C mineralization, total nitrogen improvement, and nitrogen mineralization in various soil types after wheat straw returning. This study evaluated the influenced indicators of wheat straw addition on soil organic carbon and nitrogen transformation in diverse soil types. For this purpose, an incubation experiment was conducted to analyze the carbon and nitrogen transformation in soil from eight Chinese provinces treated with the same dry weight of wheat straw. The results indicated that the primary physicochemical and bacterial indicators that predict the carbon and nitrogen transformations in the acidic and alkaline soils were different. Of all the natural physicochemical properties of soil, cation exchange capacity and clay content were significantly correlated with organic carbon, mineralized carbon, total nitrogen, and mineralized nitrogen in the alkaline soil. In the acidic soil, the initial C/N ratio of soil was the most significant indicator of carbon and nitrogen transformation. From the perspective of the carbon- and nitrogen-relating bacterial communities, Proteobacteria were largely responsible for the accumulative C mineralization in both types of soil. Furthermore, Proteobacteria strongly regulated the organic carbon storage in the acidic soil after wheat straw addition, whereas Gemmatimonadetes was the main predicted indicator in the alkaline soil. Additionally, total nitrogen and mineralized nitrogen levels were largely explained by Bifidobacterium and Luteimonas in the alkaline soil and by Nitrospira and Bdellovibrio in the acidic soil. Soil physicochemical and biological properties significantly influence soil carbon and nitrogen transformation, which should be considered crucial indicators to guide the rational regulation of straw return in several areas.


Assuntos
Carbono , Solo , Solo/química , Triticum , Nitrogênio/análise , Agricultura/métodos , Bactérias , Proteobactérias , Fertilizantes
11.
Food Chem ; 450: 139326, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615530

RESUMO

Although nanozymes sensor arrays have the potential to recognize multiple target substances simultaneously, they currently rarely identify phenolic acids in food due to limited catalytic performance and complex preparation conditions of nanozymes. Here, inspired by the structure of polyphenol oxidase, we have successfully prepared a novel gallic acid-Cu (GA-Cu) nanozyme with laccase-like activity. Due to the different catalytic efficiency of GA-Cu nanozymes towards six common phenolic acids, a three-channel colorimetric sensor array was constructed using reaction kinetics as the sensing unit to achieve high-throughput detection and identification of six phenolic acids within a concentration range from 1 to 100 µM. This method avoids the creation of numerous sensing units. Notably, the successful discrimination of six phenolic acids in samples of juice, beer, and wine has been achieved by the sensor array. Finally, aided by smartphones, a portable technique has been devised for the detection of phenolic acids.


Assuntos
Colorimetria , Ácido Gálico , Hidroxibenzoatos , Vinho , Hidroxibenzoatos/química , Hidroxibenzoatos/análise , Colorimetria/métodos , Vinho/análise , Ácido Gálico/química , Ácido Gálico/análise , Cerveja/análise , Cobre/química , Cobre/análise , Sucos de Frutas e Vegetais/análise , Catálise , Nanoestruturas/química , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Análise de Alimentos/instrumentação , Análise de Alimentos/métodos
12.
BMC Biol ; 22(1): 59, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38475771

RESUMO

BACKGROUND: Hmong-Mien (HM) speakers are linguistically related and live primarily in China, but little is known about their ancestral origins or the evolutionary mechanism shaping their genomic diversity. In particular, the lack of whole-genome sequencing data on the Yao population has prevented a full investigation of the origins and evolutionary history of HM speakers. As such, their origins are debatable. RESULTS: Here, we made a deep sequencing effort of 80 Yao genomes, and our analysis together with 28 East Asian populations and 968 ancient Asian genomes suggested that there is a strong genetic basis for the formation of the HM language family. We estimated that the most recent common ancestor dates to 5800 years ago, while the genetic divergence between the HM and Tai-Kadai speakers was estimated to be 8200 years ago. We proposed that HM speakers originated from the Yangtze River Basin and spread with agricultural civilization. We identified highly differentiated variants between HM and Han Chinese, in particular, a deafness-related missense variant (rs72474224) in the GJB2 gene is in a higher frequency in HM speakers than in others. CONCLUSIONS: Our results indicated complex gene flow and medically relevant variants involved in the HM speakers' evolution history.


Assuntos
Conexina 26 , Pool Gênico , Genética Populacional , Humanos , Povo Asiático , China , Genômica
13.
Biomed Pharmacother ; 173: 116400, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484560

RESUMO

Hyperlipidemia caused by abnormal lipid metabolism has reached epidemic proportions. This phenomenon is also common in companion animals. Previous studies showed that AEE significantly improves abnormal blood lipids in hyperlipidemia rats and mice, but its mechanism is still not clear enough. In this study, the mechanism and potential key pathways of AEE on improving hyperlipidemia in mice were investigated through the transcriptome and proteome study of ApoE-/- mice liver and the verification study on high-fat HepG2 cells. The results showed that AEE significantly decreased the serum TC and LDL-C levels of hyperlipidemia ApoE-/- mice, and significantly increased the enzyme activity of CYP7A1. After AEE intervention, the results of mice liver transcriptome and proteome showed that differential genes and proteins were enriched in lipid metabolism-related pathways. The results of RT-qPCR showed that AEE significantly regulated the expression of genes related to lipid metabolism in mice liver tissue. AEE significantly upregulated the protein expression of CYP7A1 in hyperlipidemia ApoE-/- mice liver tissue. The results in vitro showed that AEE significantly decreased the levels of TC and TG, and improved lipid deposition in high-fat HepG2 cells. AEE significantly increased the expression of CYP7A1 protein in high-fat HepG2 cells. AEE regulates the expression of genes related to lipid metabolism in high-fat HepG2 cells, mainly by FXR-SHP-CYP7A1 and FGF19-TFEB-CYP7A1 pathways. To sum up, AEE can significantly improve the hyperlipidemia status of ApoE-/- mice and the lipid deposition of high-fat HepG2 cells, and its main pathway is probably the bile acid metabolism-related pathway centered on CYP7A1.


Assuntos
Hiperlipidemias , Camundongos , Ratos , Animais , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Proteômica , Proteoma/metabolismo , Dieta Hiperlipídica/efeitos adversos , Lipídeos , Metabolismo dos Lipídeos/genética , Perfilação da Expressão Gênica , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Fígado/metabolismo
14.
Plants (Basel) ; 13(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38498446

RESUMO

Odorant-binding proteins (OBPs) play important roles in the insect olfactory system since they bind external odor molecules to trigger insect olfactory responses. Previous studies have identified some plant-derived volatiles that attract the pervasive insect pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), such as phenylacetaldehyde, benzyl acetate, 1-heptanol, and hexanal. To characterize the roles of CmedOBPs in the recognition of these four volatiles, we analyzed the binding abilities of selected CmedOBPs to each of the four compounds, as well as the expression patterns of CmedOBPs in different developmental stages of C. medinalis adult. Antennaes of C. medinalis adults were sensitive to the studied plant volatile combinations. Expression levels of multiple CmedOBPs were significantly increased in the antennae of 2-day-old adults after exposure to volatiles. CmedOBP1, CmedOBP6, CmedPBP1, CmedPBP2, and CmedGOBP2 were significantly up-regulated in the antennae of volatile-stimulated female and male adults when compared to untreated controls. Fluorescence competition assays confirmed that CmedOBP1 could strongly bind 1-heptanol, hexanal, and phenylacetaldehyde; CmedOBP15 strongly bound benzyl acetate and phenylacetaldehyde; and CmedOBP26 could weakly bind 1-heptanol. This study lays a theoretical foundation for further analysis of the mechanisms by which plant volatiles can attract C. medinalis. It also provides a technical basis for the future development of efficient plant volatile attractants of C. medinalis.

15.
Molecules ; 29(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474606

RESUMO

Metalloenzymes are ubiquitously present in the human body and are relevant to a variety of diseases. However, the development of metalloenzyme inhibitors is limited by low specificity and poor drug-likeness associated with metal-binding fragments (MBFs). A generalized drug discovery strategy was established, which is characterized by the property characterization of zinc-dependent metalloenzyme inhibitors (ZnMIs). Fifteen potential Zn2+-binding fragments (ZnBFs) were identified, and a customized pharmacophore feature was defined based on these ZnBFs. The customized feature was set as a required feature and applied to a search for novel inhibitors for histone deacetylase 1 (HDAC1). Ten potential HDAC1 inhibitors were recognized, and one of them (compound 9) was a known potent HDAC1 inhibitor. The results demonstrated the effectiveness of our strategy to identify novel inhibitors for zinc-dependent metalloenzymes.


Assuntos
Inibidores de Histona Desacetilases , Metaloproteínas , Humanos , Inibidores de Histona Desacetilases/farmacologia , Metaloproteínas/química , Descoberta de Drogas , Zinco , Histona Desacetilase 1
16.
Adv Sci (Weinh) ; 11(15): e2306472, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342606

RESUMO

Myofibrillogenesis regulator-1 (MR-1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR-1 on the development and metastasis of non-small cell lung cancer (NSCLC). MR-1 is upregulated in NSCLC and positively associated with poor prognosis. The overexpression of MR-1 promotes the metastasis of NSCLC cells by stabilizing the expression of Notch3-ICD (NICD3) in the cytoplasm through enrichment analysis, in vitro and in vivo experimental researches. And Notch3 signaling can upregulate many genes related to metastasis. The stabilizing effect of MR-1 on NICD3 is achieved through the mono-ubiquitin lysosomal pathway and the specific E3 ubiquitin ligase is Itchy homolog (ITCH). There is a certain interaction between MR-1 and NICD3. Elevated MR-1 can affect the level of ITCH phosphorylation, reduce its E3 enzyme activity, and thus lead to reduce the ubiquitination and degradation of NICD3. Interference with the interaction between MR-1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR-1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Neoplasias Pulmonares/genética , Lisossomos/metabolismo , Desenvolvimento Muscular , Ubiquitina , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
17.
Toxics ; 12(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38393218

RESUMO

Resveratrol (RSV), a polyphenol, is known to have a wide range of pharmacological properties in vitro. RSV may have therapeutic value for various neurodegenerative diseases via neuroprotective effects. However, it is not yet clear whether RSV can induce intestinal-brain interactions. It is assumed that the intestinal cells may secrete some factors after being stimulated by other substances. These secreted factors may activate nerve cells through gut-brain interaction, such as exosomes. In this study, it was discovered that Caco-2 cells treated with RSV secrete exosomes to activate SH-SY5Y neuronal cells. The results showed that secreted factors from RSV-treated Caco-2 cells activated SH-SY5Y. The exosomes of RSV-treated Caco-2 cells activated SH-SY5Y cells, which was manifested in the lengthening of the nerve filaments of SH-SY5Y cells. The exosomes were characterized using transmission electron microscopy and sequenced using the Illumina NovaSeq 6000 sequencer. The results showed that the miRNA expression profile of exosomes after RSV treatment changed, and twenty-six kinds of miRNAs were identified which expressed differentially between the control group and the RSV-treated group. Among them, three miRNAs were selected as candidate genes for inducing SH-SY5Y neural cell activation. Three miRNA mimics could activate SH-SY5Y neurons. These results suggested that the miRNA in intestinal exocrine cells treated with RSV may play an important role in the activation of SH-SY5Y neurons.

18.
Int J Mol Sci ; 25(4)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38396823

RESUMO

Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE had excellent thromboprophylaxis and inhibition of platelet aggregation. This study aimed to investigate the effect of AEE on the liver of thrombosed rats to reveal its mechanism of thromboprophylaxis. Therefore, a multi-omics approach was used to analyze the liver. Transcriptome results showed 132 differentially expressed genes (DEGs) in the AEE group compared to the model group. Proteome results showed that 159 differentially expressed proteins (DEPs) were identified in the AEE group compared to the model group. Six proteins including fibrinogen alpha chain (Fga), fibrinogen gamma chain (Fgg), fibrinogen beta chain (Fgb), orosomucoid 1 (Orm1), hemopexin (Hpx), and kininogen-2 (Kng2) were selected for parallel reaction monitoring (PRM) analysis. The results showed that the expression of all six proteins was upregulated in the model group compared with the control group. In turn, AEE reversed the upregulation trend of these proteins to some degree. Metabolome results showed that 17 metabolites were upregulated and 38 were downregulated in the model group compared to the control group. AEE could reverse the expression of these metabolites to some degree and make them back to normal levels. The metabolites were mainly involved in metabolic pathways, including linoleic acid metabolism, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. Comprehensive analyses showed that AEE could prevent thrombosis by inhibiting platelet activation, decreasing inflammation, and regulating amino acid and energy metabolism. In conclusion, AEE can have a positive effect on thrombosis-related diseases.


Assuntos
Aspirina/análogos & derivados , Eugenol/análogos & derivados , Trombose , Tromboembolia Venosa , Ratos , Animais , Eugenol/farmacologia , Eugenol/uso terapêutico , Eugenol/metabolismo , Anticoagulantes/farmacologia , Multiômica , Tromboembolia Venosa/tratamento farmacológico , Aspirina/uso terapêutico , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Trombose/metabolismo , Fígado/metabolismo , Fibrinogênio/metabolismo , Orosomucoide/metabolismo
19.
Sci Total Environ ; 921: 171048, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387590

RESUMO

Quantification of nitrogen (N) cycling genes contributes to our best understanding of N transformation processes. The application of organic amendment (OA) is widely recognized as an effective measure to improve N management and soil fertility in various ecosystems. However, our understanding of N-cycling gene abundances in response to OA application remains deficient. We performed a meta-analysis embracing 124 sets of observation data to study the impact of OA application on the main N-cycling gene abundances, including nifH, amoA, nirS, nirK and nosZ. We found that the significantly positive response of N-cycling gene abundances to OA application was attributed to the rotation cropping system (by 6.45 %-104.20 %) in the field experiment (by 19.43 %-52.56 %), OA application alone (by 8.29 %-111.70 %) especially manure addition (by 33.43 %-98.70 %), application dose of OAs within 10-20 t ha-1 (by 45.33 %-381.90 %), fertilization duration <5 years (by 43.69 %-112.63 %), C/N of OA <25 (by 37.87 %-160.90 %), SOC lower than 1.2 % (by 41.44 %-157.89 %) and application to alkaline soil (by 32.24 %-134.40 %). Moreover, soil organic carbon (SOC) and pH were the most essential regulators associated with N-cycling gene abundances with OA application. Identification of key driving factors of the abundance of N-cycling functional genes will help remedy strategies for managing OAs in ecosystems.


Assuntos
Ecossistema , Solo , Carbono , Ciclo do Nitrogênio/genética , Nitrogênio , Microbiologia do Solo , Fertilizantes/análise
20.
Int J Biol Macromol ; 261(Pt 2): 129878, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309394

RESUMO

In order to investigate the structural characteristics and immunomodulatory effects of Poria cocos polysaccharides, a water-soluble homogeneous polysaccharide (PCP-2) was isolated by water extraction and alcohol precipitation and further purified by Cellulose DEAE-52 and Sephacryl S-100HR column chromatography. PCP-2 is a heteropolysaccharide composed of glucose, galactose, mannose, and fucose in a molar ratio of 42.0: 35.0: 13.9: 9.1. It exhibits a narrow molecular weight distribution at 2.35 kDa with a branching degree of 37.1 %. The main chain types of PCP-2 include 1,3-ß-D-Glc and 1,6-ß-D-Glc as the backbone glucans and 1,6-α-D-Gal as the backbone heterogalactan. In vitro experiments demonstrate that PCP-2 directly stimulate RAW264.7 cell proliferation and secretion of inflammatory factors such as NO and TNF-α. In cyclophosphamide (CTX)-induced mice, it promotes the development of thymus and spleen immune organs, elevates the blood levels of IgG, IgA, IgM and CD3+CD4+ T cells, increases the intestinal villus height/ crypt depth ratio and improves gut barrier dysfunctions. These findings suggest that PCP-2 is a natural fungal polysaccharide with broad spectrum of immunoenhancing effects, which can significantly ameliorate the immunocompromised state.


Assuntos
Polissacarídeos Fúngicos , Poria , Wolfiporia , Camundongos , Animais , Wolfiporia/química , Água , Polissacarídeos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Fator de Necrose Tumoral alfa , Poria/química
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