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1.
Plant Biotechnol J ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593377

RESUMO

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

2.
ACS Nano ; 18(17): 11103-11119, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38623806

RESUMO

In recent years, carbon nanotubes have emerged as a widely used nanomaterial, but their human exposure has become a significant concern. In our former study, we reported that pulmonary exposure of multiwalled carbon nanotubes (MWCNTs) promoted tumor metastasis of breast cancer; macrophages were key effectors of MWCNTs and contributed to the metastasis-promoting procedure in breast cancer, but the underlying molecular mechanisms remain to be explored. As a follow-up study, we herein demonstrated that MWCNT exposure in breast cancer cells and macrophage coculture systems promoted metastasis of breast cancer cells both in vitro and in vivo; macrophages were skewed into M2 polarization by MWCNT exposure. LncRNA NBR2 was screened out to be significantly decreased in MWCNTs-stimulated macrophages through RNA-seq; depletion of NBR2 led to the acquisition of M2 phenotypes in macrophages by activating multiple M2-related pathways. Specifically, NBR2 was found to positively regulate the downstream gene TBX1 through H3k27ac activation. TBX1 silence rescued NBR2-induced impairment of M2 polarization in IL-4 & IL-13-stimulated macrophages. Moreover, NBR2 overexpression mitigated the enhancing effects of MWCNT-exposed macrophages on breast cancer metastasis. This study uncovered the molecular mechanisms underlying breast cancer metastasis induced by MWCNT exposure.


Assuntos
Neoplasias da Mama , Macrófagos , Nanotubos de Carbono , Nanotubos de Carbono/química , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Humanos , Feminino , Camundongos , Animais , Proteínas com Domínio T/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Metástase Neoplásica , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral
3.
J Exp Clin Cancer Res ; 43(1): 90, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523299

RESUMO

BACKGROUND: Ropivacaine, a local anesthetic, exhibits anti-tumor effects in various cancer types. However, its specific functions and the molecular mechanisms involved in breast cancer cell stemness remain elusive. METHODS: The effects of ropivacaine on breast cancer stemness were investigated by in vitro and in vivo assays (i.e., FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft model). RNA-seq, bioinformatics analysis, Western blot, Luciferase reporter assay, and CHIP assay were used to explore the mechanistic roles of ropivacaine subsequently. RESULTS: Our study showed that ropivacaine remarkably suppressed stem cells-like properties of breast cancer cells both in vitro and in vivo. RNA-seq analysis identified GGT1 as the downstream target gene responding to ropivacaine. High GGT1 levels are positively associated with a poor prognosis in breast cancer. Ropivacaine inhibited GGT1 expression by interacting with the catalytic domain of AKT1 directly to impair its kinase activity with resultant inactivation of NF-κB. Interestingly, NF-κB can bind to the promoter region of GGT1. KEGG and GSEA analysis indicated silence of GGT1 inhibited activation of NF-κB signaling pathway. Depletion of GGT1 diminished stem phenotypes of breast cancer cells, indicating the formation of NF-κB /AKT1/GGT1/NF-κB positive feedback loop in the regulation of ropivacaine-repressed stemness in breast cancer cells. CONCLUSION: Our finding revealed that local anesthetic ropivacaine attenuated breast cancer stemness through AKT1/GGT1/NF-κB signaling pathway, suggesting the potential clinical value of ropivacaine in breast cancer treatment.


Assuntos
Neoplasias da Mama , NF-kappa B , Humanos , Feminino , NF-kappa B/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ropivacaina/farmacologia , Ropivacaina/uso terapêutico , Anestésicos Locais/farmacologia , Anestésicos Locais/uso terapêutico , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo
4.
Prev Med Rep ; 39: 102662, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38426040

RESUMO

Objective: Current cost-effectiveness analyses of amblyopia screening are mainly from western countries. It remains unclear whether it is cost-effective to implement a preschool amblyopia screening programme in China. Our study aimed to evaluate the cost-effectiveness of a hypothetical kindergarten-based amblyopia screening versus non-screening among 3-year-old children. Methods: We developed a decision tree combined with a Markov model to compare the cost and effectiveness of screening versus non-screening for 3-year-old children from a third-party payment perspective. The primary outcomes were quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Costs were obtained from expert opinions in different regions of China. Transition probabilities and health utilities were mainly based on published literature and open sources. Sensitivity analyses were performed to assess the impact of parameters' uncertainty on results. Results: Base-case analysis demonstrated that the ICER of screening versus non-screening was $17,466/QALY, well below the WTP threshold ($38,223/QALY) for China. One-way sensitivity analysis showed that the prevalence of amblyopia, the transition probability per year from untreated amblyopia to healthy, and the discount rate were the top three factors. The likelihood of cost-effectiveness of screening compared with non-screening was 92.56%, according to probabilistic sensitivity analysis. Scenario analysis also indicated that ICER was lower than the WTP threshold even if the time horizon was shortened or the screening was delayed to the age of 4 or 5. Conclusions: Amblyopia screening could be considered a cost-effective strategy compared to non-screening for 3-year-old children in China. Screening for children at the age of 4 or 5 may even yield better results.

5.
Mol Nutr Food Res ; 68(6): e2300443, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456781

RESUMO

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Masculino , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos , Glucose/farmacologia , Metilaminas , Colina/farmacologia
6.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338776

RESUMO

Rice effective panicle is a major trait for grain yield and is affected by both the genetic tiller numbers and the early tillering vigor (ETV) traits to survive environmental adversities. The mechanism behind tiller bud formation has been well described, while the genes and the molecular mechanism underlying rice-regulating ETV traits are unclear. In this study, the candidate genes in regulating ETV traits have been sought by quantitative trait locus (QTL) mapping and bulk-segregation analysis by resequencing method (BSA-seq) conjoint analysis using rice backcross inbred line (BIL) populations, which were cultivated as late-season rice of double-cropping rice systems. By QTL mapping, seven QTLs were detected on chromosomes 1, 3, 4, and 9, with the logarithm of the odds (LOD) values ranging from 3.52 to 7.57 and explained 3.23% to 12.98% of the observed phenotypic variance. By BSA-seq analysis, seven QTLs on chromosomes 1, 2, 4, 5, 7, and 9 were identified using single-nucleotide polymorphism (SNP) and insertions/deletions (InDel) index algorithm and Euclidean distance (ED) algorithm. The overlapping QTL resulting from QTL mapping and BSA-seq analysis was shown in a 1.39 Mb interval on chromosome 4. In the overlap interval, six genes, including the functional unknown genes Os04g0455650, Os04g0470901, Os04g0500600, and ethylene-insensitive 3 (Os04g0456900), sialyltransferase family domain containing protein (Os04g0506800), and ATOZI1 (Os04g0497300), showed the differential expression between ETV rice lines and late tillering vigor (LTV) rice lines and have a missense base mutation in the genomic DNA sequences of the parents. We speculate that the six genes are the candidate genes regulating the ETV trait in rice, which provides a research basis for revealing the molecular mechanism behind the ETV traits in rice.


Assuntos
Oryza , Locos de Características Quantitativas , Oryza/genética , Estações do Ano , Mapeamento Cromossômico/métodos , Fenótipo
7.
ACS Omega ; 8(39): 36245-36252, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37810641

RESUMO

As an important member of the graphene family, vertical graphene (VG) has broad applications like field emission, energy storage, and sensors owing to its fascinating physical and chemical properties. Among various fabrication methods for VG, plasma enhanced chemical vapor deposition (PECVD) is most employed because of the fast growth rate at relatively low temperature for the high-quality VG. However, to date, relations between growth manner of VG and growth parameters such as growth temperature, dosage of gaseous carbon source, and electric power to generate plasma are still less known, which in turn hinder the massive production of VG for further applications. In this study, the growth behavior of VG was studied as functions of temperature, plasma power, and gas composition (or chamber pressure). It was found that the growth behavior of VG is sensitive to the growth conditions mentioned above. Although conditions with high growth temperature, large flow rate of mixed gas of methane and carrier gases, and high plasma power may be helpful for the fast growth of VG, brunching of VG is simultaneously enhanced, which in turn decreases the vertical growth nature of VG. High-quality VG can be achieved by optimizing the growth parameters. It was revealed that the vertical growth nature of VG is governed by the electric field at the interfacial layer between VG and the substrate, for which its strength is influenced by the density of plasma. These findings are important for the general understanding of the VG growth and provided a feasible way for the controllable fabrication of VG using the remote PECVD method which is usually believed to be unsuitable for the fabrication of VG.

8.
Oncogene ; 42(41): 3062-3074, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37634009

RESUMO

Gastric cancer (GC) is characterized by its vigorous chemoresistance to current therapies, which is attributed to the highly heterogeneous and immature phenotype of cancer stem cells (CSCs) during tumor initiation and progression. The secretory WNT2 ligand regulates multiple cancer pathways and has been demonstrated to be a potential therapeutic target for gastrointestinal tumors; however, its role involved in gastric CSCs (GCSCs) remains unclear. Here, we found that overexpression of WNT2 enhanced stemness properties to promote chemoresistance and tumorigenicity in GCSCs. Mechanistically, WNT2 was positively regulated by its transcription factor SOX4, and in turn, SOX4 was upregulated by the canonical WNT2/FZD8/ß-catenin signaling pathway to form an auto-regulatory positive feedback loop, resulting in the maintenance of GCSCs self-renewal and tumorigenicity. Furthermore, simultaneous overexpression of both WNT2 and SOX4 was correlated with poor survival and reduced responsiveness to chemotherapy in clinical GC specimens. Blocking WNT2 using a specific monoclonal antibody significantly disrupted the WNT2-SOX4 positive feedback loop in GCSCs and enhanced the chemotherapeutic efficacy when synergized with the chemo-drugs 5-fluorouracil and oxaliplatin in a GCSC-derived mouse xenograft model. Overall, this study identified a novel WNT2-SOX4 positive feedback loop as a mechanism for GCSCs-induced chemo-drugs resistance and suggested that the WNT2-SOX4 axis may be a potential therapeutic target for gastric cancer treatment.

9.
Mar Drugs ; 21(7)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37504941

RESUMO

Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer's disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against H2O2/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3ß and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Humanos , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/metabolismo , Fosfatidilserinas/farmacologia , Fosfatidilserinas/química , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Neurônios , Hipocampo
10.
Comput Biol Med ; 162: 107057, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37271112

RESUMO

Medical ultrasound technology has garnered significant attention in recent years, with Ultrasound-guided regional anesthesia (UGRA) and carpal tunnel diagnosis (CTS) being two notable examples. Instance segmentation, based on deep learning approaches, is a promising choice to support the analysis of ultrasound data. However, many instance segmentation models cannot achieve the requirement of ultrasound technology e.g. real-time. Moreover, fully supervised instance segmentation models require large numbers of images and corresponding mask annotations for training, which can be time-consuming and labor-intensive in the case of medical ultrasound data. This paper proposes a novel weakly supervised framework, CoarseInst, to achieve real-time instance segmentation of ultrasound images with only box annotations. CoarseInst not only improves the network structure, but also proposes a two-stage "coarse-to-fine" training strategy. Specifically, median nerves are used as the target application for UGRA and CTS. CoarseInst consists of two stages, with pseudo mask labels generated in the coarse mask generation stage for self-training. An object enhancement block is incorporated to mitigate the performance loss caused by parameter reduction in this stage. Additionally, we introduce a pair of loss functions, the amplification loss, and the deflation loss, that work together to generate the masks. A center area mask searching algorithm is also proposed to generate labels for the deflation loss. In the self-training stage, a novel self-feature similarity loss is designed to generate more precise masks. Experimental results on a practical ultrasound dataset demonstrate that CoarseInst could achieve better performance than some state-of-the-art fully supervised works.


Assuntos
Trabalho de Parto , Nervo Mediano , Gravidez , Feminino , Humanos , Nervo Mediano/diagnóstico por imagem , Ultrassonografia , Algoritmos , Extremidade Superior , Processamento de Imagem Assistida por Computador
11.
Mar Drugs ; 21(6)2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37367679

RESUMO

The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.


Assuntos
Epilepsia , Ácidos Graxos Ômega-3 , Feminino , Gravidez , Camundongos , Animais , Pentilenotetrazol/toxicidade , Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-3/farmacologia , Dieta , Fosfolipídeos , Suplementos Nutricionais , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle
13.
J Sci Food Agric ; 103(11): 5529-5538, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37069483

RESUMO

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.


Assuntos
Aterosclerose , Ácidos e Sais Biliares , Camundongos , Animais , Ácidos e Sais Biliares/metabolismo , Camundongos Knockout , Colesterol , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL
14.
J Agric Food Chem ; 71(18): 6908-6919, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37098125

RESUMO

Homeostasis of reactive oxygen species is required to maintain sperm maturation and capacitation. Docosahexaenoic acid (DHA) is accumulated in testicles and spermatozoa and has the ability to manipulate the redox status. The effects of dietary n-3 polyunsaturated fatty acid (n-3 PUFA) deficiency from early life to adulthood on the physiological and functional properties of males under the redox imbalance of testicular tissue deserve attention. The consecutive injection of hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) for 15 days to induce oxidative stress in testicular tissue was used to elucidate the consequences of testicular n-3 PUFA deficiency. The results indicated that reactive oxygen species treatment in adult male mice with DHA deficiency in the testis could reduce spermatogenesis and disrupt sex hormone production, as well as trigger testicular lipid peroxidation and tissue damage. N-3 PUFA deficiency from early life to adulthood resulted in higher susceptibility to testicular dysfunction in the germinal function of supplying germ cells and the endocrine role of secreting hormones through the mechanism of aggravating mitochondria-mediated apoptosis and destruction of blood testicular barrier under oxidative stress, which might provide a basis for humans to reduce susceptibility to chronic disease and maintain reproductive health in adulthood through dietary interventions of n-3 PUFAs.


Assuntos
Ácidos Graxos Ômega-3 , Humanos , Camundongos , Masculino , Animais , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio/farmacologia , Sêmen , Testículo , Ácidos Docosa-Hexaenoicos/farmacologia
15.
J Agric Food Chem ; 71(8): 3681-3693, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36790098

RESUMO

Based on the structural features of both succinate dehydrogenase inhibitors (SDHIs) and targeted covalent inhibitors, a series of N-phenylpropiolamides containing a Michael acceptor moiety were designed to find new antifungal compounds. Nineteen compounds showed potent inhibition activity in vitro on nine species of plant pathogenic fungi. Compounds 9 and 13 showed higher activity on most of the fungi than the standard drug azoxystrobin. Compound 13 could completely inhibit Physalospora piricola infection on apples at 200 µg/mL concentration over 7 days and showed high safety to seed germination and seedling growth of plants at ≤100 µg/mL concentration. The action mechanism showed that 13 is an SDH inhibitor with a median inhibitory concentration, IC50, value of 0.55 µg/mL, comparable with that of the positive drug boscalid. Molecular docking studies revealed that 13 can bind well to the ubiquinone-binding region of SDH by hydrogen bonds and undergoes π-alkyl interaction and π-cation interaction. At the cellular level, 1 as the parent compound could destruct the mycelial structure of P. piricola and partly dissolve the cell wall and/or membrane. Structure-activity relationship analysis showed that the acetenyl group should be a structure determinant for the activity, and the substitution pattern of the phenyl ring can significantly impact the activity. Thus, N-phenylpropiolamide emerged as a novel and promising lead scaffold for the development of new SDHIs for plant protection.


Assuntos
Fungicidas Industriais , Xylariales , Antifúngicos/farmacologia , Antifúngicos/química , Simulação de Acoplamento Molecular , Ácido Succínico , Succinato Desidrogenase , Relação Estrutura-Atividade , Fungos/metabolismo , Succinatos , Xylariales/metabolismo , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química
16.
Food Funct ; 14(5): 2349-2361, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36843452

RESUMO

Previous studies have found that eicosapentaenoic acid-enriched phospholipids (EPA-PLs) alleviated glucose and lipid metabolism, which was accompanied by an increase of cluster of differentiation 36 (CD36). However, the effects of EPA-PLs on glucose and lipid metabolism in the case of CD36 mutation are unclear. Thus, spontaneously hypertensive rats/NCrl (SHR) were used as a CD36 mutation model to determine the effects of dietary 2% EPA-PLs for 4 weeks on glucose and lipid metabolism. The results showed that the intervention of EPA-PLs significantly alleviated the abnormal increase of serum free fatty acid levels and glycerol levels in SHRs. Moreover, the administration of EPA-PLs decreased the triglyceride levels and cholesterol levels by 31.1% and 37.9%, respectively, in the liver. Dietary EPA-PLs had no effect on epididymal fat weight, but EPA-PLs inhibited adipocyte hypertrophy in SHRs. Further mechanistic research found that EPA-PL pretreatment significantly reduced triacylglycerol catabolism and increased fatty acid ß-oxidation. Additionally, the administration of EPA-PLs decreased the area under the curve of the intraperitoneal glucose tolerance test and fasting serum insulin levels by activating the IRS/PI3K/AKT signaling pathway. Furthermore, EPA-PL pretreatment significantly increased the CD36 gene expression in the liver tissues, adipose tissues and muscle tissues even in the case of CD36 mutation. These results indicated that EPA-PLs alleviate glucose and lipid metabolism in the case of CD36 mutation, which provides a precise nutrition strategy for people with CD36 mutation.


Assuntos
Glucose , Metabolismo dos Lipídeos , Ratos , Animais , Glucose/metabolismo , Ratos Endogâmicos SHR , Fosfolipídeos/metabolismo , Ácido Eicosapentaenoico/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo
17.
Mol Nutr Food Res ; 67(8): e2200825, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36815232

RESUMO

Blood-brain barrier (BBB) impairment is related to the development of Alzheimer's disease (AD), which is dependent not only on tight junction but also on transcytosis of brain endothelial cells (BECs) in the BBB. Aging induces the decrease of ligand-specific receptor-mediated transcytosis (RMT) and the increase of non-specific caveolar transcytosis in BECs, which lead to the entry into parenchyma of neurotoxic proteins and the smaller therapeutic index in central nervous system drug delivery, further provoking neurodegenerative disease. A previous study suggests that sea-derived Antarctic krill oil (AKO) exhibits synergistic effects with land-derived nobiletin (NOB) and theanine (THE) on ameliorating memory and cognitive deficiency in SAMP8 mice. However, it is still unclear whether BBB change is involved. Hence, the effects of AKO combined with NOB and THE on aging-induced BBB impairment, including tight junction between BECs, ligand-specific RMT, and non-specific caveolar transcytosis in BECs, are investigated. The results suggest that AKO exhibits synergistic effects with NOB and THE on regulating ligand-specific RMT in BBB by inhibiting alkaline phosphatase (ALPL). The study provides a potential strategy candidate or targeted dietary patterns to prevent and treat AD by improving the BBB function.


Assuntos
Doença de Alzheimer , Euphausiacea , Doenças Neurodegenerativas , Camundongos , Animais , Barreira Hematoencefálica , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/farmacologia , Fosfatase Alcalina/uso terapêutico , Ligantes , Células Endoteliais/metabolismo , Doenças Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Transcitose , Proteínas de Transporte/metabolismo , Doença de Alzheimer/metabolismo
18.
Pest Manag Sci ; 79(5): 1721-1730, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36606406

RESUMO

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite, which transmits various pathogens to humans, livestock and wild animals. Hexokinase (HK) is a key regulatory enzyme of the glycolytic pathway in the organisms. However, little is known about hexokinase and its functions in ticks. RESULTS: The open reading frame of the H. longicornis HK (HlHK) gene was 1425 bp and encoded a protein of 474 amino acids, containing conserved domains for glucose, glucose 6-phosphate, and adenosine triphosphate. The expression of HlHK gene was detected at different developmental stages and in different tissues of unfed female ticks. Enzyme-linked immunosorbent assay revealed that both HK protein- and DNA-based vaccines increased the antibody levels of the immunized animals. A vaccination trail on rabbits against H. longicornis infestation indicated that the rHlHK protein and HlHK DNA vaccines reduced the number of attached female ticks by 9% and 12%, egg mass weight by 36% and 34%, and egg hatching rate by 41% and 17%, respectively. Overall, protein vaccination conferred 65.6% protection against adult female ticks, whereas the DNA vaccine conferred 51.8% protection. CONCLUSION: This is the first report of the molecular characterization of the HK protein and sequencing of the HK gene from H. longicornis. Positive results from vaccination trials on rabbits of the recombinant HK protein and HK DNA suggest that these novel anti-tick vaccines potentially can be used as viable tick control tools for the management of the Asian longhorned tick. Additionally, inhibition of glucose metabolism may be a new strategy for tick control. © 2023 Society of Chemical Industry.


Assuntos
Ixodidae , Carrapatos , Vacinas de DNA , Humanos , Animais , Feminino , Coelhos , Vacinas de DNA/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Ixodidae/genética
19.
Mar Drugs ; 21(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36662212

RESUMO

It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional ß-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA ß-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA ß-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet ß-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.


Assuntos
Ácidos Graxos Ômega-3 , Insulinas , Camundongos , Animais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Estreptozocina/toxicidade , Ácidos Graxos Insaturados , Ácidos Graxos , Inflamação/tratamento farmacológico , Pâncreas , Suplementos Nutricionais , Apoptose , Estresse Oxidativo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia
20.
Food Chem ; 405(Pt A): 134872, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36371831

RESUMO

As an oxycarotenoid with strong antioxidant properties, astaxanthin can considerably boost pigmentation and improve the nutritional value of eggs. The purpose of this study was to elucidate the comparative effects of different chemical structures of astaxanthin including free astaxanthin, monoester-enriched astaxanthin and diester-enriched astaxanthin on the nutritional enhancement of eggs within 20 days. The results showed that supplementation of free astaxanthin to laying hens was more effective in accumulating astaxanthin in egg yolks than supplementation with esterified astaxanthin. The retention rate of free astaxanthin was approximately 12.0 % at the plateau phase in egg yolk, while that of monoester-enriched and diester-enriched astaxanthin were 4.0 % and 2.5 %, respectively. Free astaxanthin possessed a high retention rate and pigmentation effect compared with esterified astaxanthin, which might provide a basis for astaxanthin enhancement in eggs and potential application in nutritional functional foods.


Assuntos
Galinhas , Gema de Ovo , Animais , Feminino , Gema de Ovo/química , Ração Animal/análise , Dieta , Ovos
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