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1.
Clin Nucl Med ; 49(8): e392-e393, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38967509

RESUMO

ABSTRACT: Metastatic insulinomas can cause recurrent hypoglycemia requiring continuous IV glucose infusion. Various medical and chemotherapeutic treatment options are used to reduce the patient's risk of death due to hypoglycemia. Treatment-resistant hepatic metastatic insulinomas may benefit clinically from 90Y transarterial radioembolization therapy. In this case, we present a case of liver metastatic insulinoma that achieved clinical improvement after 2 cycles of 90Y microspheres transarterial radioembolization, and the presence of active metastases was demonstrated with 68Ga-NODAGA-exendin-4 PET/CT imaging.


Assuntos
Embolização Terapêutica , Exenatida , Radioisótopos de Gálio , Hipoglicemia , Insulinoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Ítrio , Humanos , Insulinoma/diagnóstico por imagem , Radioisótopos de Ítrio/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Acetatos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/radioterapia , Masculino , Metástase Neoplásica , Pessoa de Meia-Idade
2.
Planta ; 260(2): 47, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970694

RESUMO

MAIN CONCLUSION: Transcription of PagMYB147 was induced in poplar infected by Melampsora magnusiana, and a decline in its expression levels increases the host's susceptibility, whereas its overexpression promotes resistance to rust disease. Poplars are valuable tree species with diverse industrial and silvicultural applications. The R2R3-MYB subfamily of transcription factors plays a crucial role in response to biotic stresses. However, the functional studies on poplar R2R3-MYB genes in resistance to leaf rust disease are still insufficient. We identified 191 putative R2R3-MYB genes in the Populus trichocarpa genome. A phylogenetic analysis grouped poplar R2R3-MYBs and Arabidopsis R2R3-MYBs into 33 subgroups. We detected 12 tandem duplication events and 148 segmental duplication events, with the latter likely being the main contributor to the expansion of poplar R2R3-MYB genes. The promoter regions of these genes contained numerous cis-acting regulatory elements associated with response to stress and phytohormones. Analyses of RNA-Seq data identified a multiple R2R3-MYB genes response to Melampsora magnusiana (Mmag). Among them, PagMYB147 was significantly up-regulated under Mmag inoculation, salicylic acid (SA) and methyl jasmonate (MeJA) treatment, and its encoded product was primarily localized to the cell nucleus. Silencing of PagMYB147 exacerbated the severity of Mmag infection, likely because of decreased reactive oxygen species (ROS) production and phenylalanine ammonia-lyase (PAL) enzyme activity, and up-regulation of genes related to ROS scavenging and down-regulation of genes related to PAL, SA and JA signaling pathway. In contrast, plants overexpressing PagMYB147 showed the opposite ROS accumulation, PAL enzyme activity, SA and JA-related gene expressions, and improved Mmag resistance. Our findings suggest that PagMYB147 acts as a positive regulatory factor, affecting resistance in poplar to Mmag by its involvement in the regulation of ROS homeostasis, SA and JA signaling pathway.


Assuntos
Basidiomycota , Ciclopentanos , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Filogenia , Doenças das Plantas , Proteínas de Plantas , Populus , Fatores de Transcrição , Populus/genética , Populus/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Basidiomycota/fisiologia , Resistência à Doença/genética , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Oxilipinas/metabolismo , Oxilipinas/farmacologia , Estudo de Associação Genômica Ampla , Reguladores de Crescimento de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Acetatos/farmacologia , Arabidopsis/genética , Arabidopsis/microbiologia
3.
Physiol Plant ; 176(4): e14434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38981863

RESUMO

Anthocyanin is a type of plant secondary metabolite beneficial to human health. The anthocyanin content of vegetable and fruit crops signifies their nutritional quality. However, the molecular mechanism of anthocyanin accumulation, especially tissue-specific accumulation, in Caitai, as well as in other Brassica rapa varieties, remains elusive. In the present study, taking advantage of three kinds of Caitai cultivars with diverse colour traits between leaves and stems, we conducted a comparative transcriptome analysis and identified the molecular pathway of anthocyanin biosynthesis in Caitai leaves and stems, respectively. Our further investigations demonstrate that bHLH42, which is robustly induced by MeJA, closely correlates with tissue-specific accumulation of anthocyanins in Caitai; bHLH42 upregulates the expression of flavonoid/anthocyanin biosynthetic pathway genes to activate anthocyanin biosynthesis pathway, importantly, overexpression of bHLH42 significantly improves the anthocyanin content of Caitai. Our analysis convincingly suggests that bHLH42 induced by jasmonic acid signalling plays a crucial role in tissue-specific accumulation of anthocyanins in Caitai.


Assuntos
Acetatos , Antocianinas , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Ciclopentanos , Flavonoides , Regulação da Expressão Gênica de Plantas , Oxilipinas , Proteínas de Plantas , Antocianinas/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Flavonoides/metabolismo , Acetatos/metabolismo , Acetatos/farmacologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Folhas de Planta/metabolismo , Folhas de Planta/genética , Reguladores de Crescimento de Plantas/metabolismo
4.
Methods Mol Biol ; 2827: 109-143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985266

RESUMO

Plant growth regulators are routinely added to in vitro culture media to foster the growth and differentiation of the cells, tissues, and organs. However, while the literature on usage of the more common auxins, cytokinins, gibberellins, abscisic acid, and ethylene is vast, other compounds that also have shown a growth-regulating activity have not been studied as frequently. Such substances are also capable of modulating the responses of plant cells and tissues in vitro by regulating their growth, differentiation, and regeneration competence, but also by enhancing their responses toward biotic and abiotic stress agents and improving the production of secondary metabolites of interest. This chapter will discuss the in vitro effects of several of such less frequently added plant growth regulators, including brassinosteroids (BRS), strigolactones (SLs), phytosulfokines (PSKs), methyl jasmonate, salicylic acid (SA), sodium nitroprusside (SNP), hydrogen sulfite, various plant growth retardants and inhibitors (e.g., ancymidol, uniconazole, flurprimidol, paclobutrazol), and polyamines.


Assuntos
Reguladores de Crescimento de Plantas , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Técnicas de Cultura de Tecidos/métodos , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Desenvolvimento Vegetal/efeitos dos fármacos , Plantas/metabolismo , Plantas/efeitos dos fármacos , Lactonas/farmacologia , Lactonas/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo , Acetatos/farmacologia , Acetatos/metabolismo
5.
BMC Plant Biol ; 24(1): 549, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872078

RESUMO

Ginseng (Panax ginseng C. A. Mey.) is an important and valuable medicinal plant species used in traditional Chinese medicine, and its metabolite ginsenoside is the primary active ingredient. The FAR1/FHY3 gene family members play critical roles in plant growth and development as well as participate in a variety of physiological processes, including plant development and signaling of hormones. Studies have indicated that methyl jasmonate treatment of ginseng adventitious roots resulted in a significant increase in the content of protopanaxadiol ginsenosides. Therefore, it is highly significant to screen the FAR1/FHY3 gene family members in ginseng and preliminarily investigate their expression patterns in response to methyl jasmonic acid signaling. In this study, we screened and identified the FAR1/FHY3 family genes in the ginseng transcriptome databases. And then, we analyzed their gene structure and phylogeny, chromosomal localization and expression patterns, and promoter cis-acting elements, and made GO functional annotations on the members of this family. After that, we treated the ginseng adventitious roots with 200 mM methyl jasmonate and investigated the trend of the expression of four genes containing the largest number of methyl jasmonate cis-acting elements at different treatment times. All four genes were able to respond to methyl jasmonate, the most significant change was in the PgFAR40 gene. This study provides data support for subsequent studies of this family member in ginseng and provides experimental reference for subsequent validation of the function of this family member under methyl jasmonic acid signaling.


Assuntos
Acetatos , Ciclopentanos , Regulação da Expressão Gênica de Plantas , Família Multigênica , Oxilipinas , Panax , Filogenia , Proteínas de Plantas , Oxilipinas/farmacologia , Ciclopentanos/farmacologia , Panax/genética , Panax/metabolismo , Panax/efeitos dos fármacos , Acetatos/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Perfilação da Expressão Gênica , Genes de Plantas , Ginsenosídeos
6.
Appl Microbiol Biotechnol ; 108(1): 372, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874789

RESUMO

Methanol is a promising feedstock for the bio-based economy as it can be derived from organic waste streams or produced electrochemically from CO2. Acetate production from CO2 in microbial electrosynthesis (MES) has been widely studied, while more valuable compounds such as butyrate are currently attracting attention. In this study, methanol was used as a co-substrate with CO2 to enhance butyrate production in MES. Feeding with CO2 and methanol resulted in the highest butyrate production rates and titres of 0.36 ± 0.01 g L-1 d-1 and 8.6 ± 0.2 g L-1, respectively, outperforming reactors with only CO2 feeding (0.20 ± 0.03 g L-1 d-1 and 5.2 ± 0.1 g L-1, respectively). Methanol acted as electron donor and as carbon source, both of which contributed ca. 50% of the carbon in the products. Eubacterium was the dominant genus with 52.6 ± 2.5% relative abundance. Thus, we demonstrate attractive route for the use of the C1 substrates, CO2 and methanol, to produce mainly butyrate. KEY POINTS: • Butyrate was the main product from methanol and CO2 in MES • Methanol acted as both carbon and electron source in MES • Eubacterium dominating microbial culture was enriched in MES.


Assuntos
Butiratos , Dióxido de Carbono , Metanol , Metanol/metabolismo , Dióxido de Carbono/metabolismo , Butiratos/metabolismo , Reatores Biológicos/microbiologia , Carbono/metabolismo , Acetatos/metabolismo
7.
Sci Rep ; 14(1): 13729, 2024 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877134

RESUMO

The aim of this study was to investigate the fertility of "Huajin 6" and the effect of exogenous methyl jasmonate on its fertility. In this study, "Huajin 6", "Huajin 6" treated with methyl jasmonate and "Damaohua" were used as the research objects, the stamen phenotypes and the shape of pollen grains were observed, pollen viability and stigma receptivity were measured. The results showed that the pistil structure and function were normal, and although the stamen anthers did not dehisce, they were still capable of producing pollen with a certain amount of vigor. Methyl jasmonate could promote the opening of the flowers of "Huajin 6" and improve the development of pollen grains to a certain extent, but it could not promote anthers dehiscence of "Huajin 6". This study can provide theoretical guidance for the cultivation of new honeysuckle varieties using "Huajin 6".


Assuntos
Ciclopentanos , Fertilidade , Flores , Oxilipinas , Pólen , Oxilipinas/farmacologia , Fertilidade/efeitos dos fármacos , Ciclopentanos/farmacologia , Acetatos/farmacologia , Lonicera/fisiologia , Lonicera/efeitos dos fármacos , Polinização
8.
J Transl Med ; 22(1): 570, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879538

RESUMO

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.


Assuntos
Acetatos , Microbioma Gastrointestinal , Lesão Pulmonar , Infecções por Orthomyxoviridae , Junções Íntimas , Animais , Junções Íntimas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Acetatos/metabolismo , Humanos , Infecções por Orthomyxoviridae/complicações , Camundongos Endogâmicos C57BL , Vírus da Influenza A , Transplante de Microbiota Fecal , Receptores Acoplados a Proteínas G/metabolismo , Camundongos , Células Epiteliais/metabolismo , Disbiose , Ácidos Graxos Voláteis/metabolismo
9.
Food Res Int ; 190: 114636, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945625

RESUMO

There has been growing interest in the use of mixed cultures comprised of Oenococcus oeni and Saccharomyces cerevisiae to produce wine with local style and typicality. This study has investigated the influence of the inoculation protocol of O. oeni on the fermentation kinetics and aromatic profile of Chardonnay wine. The one selected autochthonous O. oeni strain (ZX-1) inoculated at different stages of the alcoholic fermentation process successfully completed malolactic fermentation (MLF). Co-inoculum of S. cerevisiae and O. oeni enabled simultaneous alcoholic fermentation and MLF, leading to at least a 30 % reduction in the total fermentation time when compared to the sequential inoculation process, which was attributed to the lower ethanol stress. Meanwhile, co-inoculum stimulated the accumulation of volatile aroma compounds in Chardonnay wine. In particular, the mixed modality where the O. oeni strain ZX-1 was inoculated 48 h after S. cerevisiae allowed higher levels of terpenes, acetates, short-chain, and medium-chain fatty acid ethyl esters to be produced, which may result in the enhanced floral and fruity attributes of wine. Aroma reconstitution and omission models analysis revealed that the accumulation of linalool, geraniol, isoamyl acetate, ethyl hexanoate, and ethyl caprylate during the mixed fermentation process enhanced the stone fruit, tropical fruit, and citrus aromas in Chardonnay wine. Therefore, the simultaneous fermentation of S. cerevisiae and autochthonous O. oeni ZX-1 has a positive effect on MLF and contributes to producing wines with distinctive style.


Assuntos
Fermentação , Odorantes , Oenococcus , Saccharomyces cerevisiae , Vinho , Vinho/microbiologia , Vinho/análise , Saccharomyces cerevisiae/metabolismo , Oenococcus/metabolismo , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Etanol/metabolismo , Acetatos/metabolismo , Terpenos/metabolismo , Microbiologia de Alimentos
10.
Molecules ; 29(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38930986

RESUMO

In this study, hybrid skeleton material ZIF-8@ZIF-67 was synthesized by the epitaxial growth method and then was utilized as a carrier for encapsulating Pseudomonas fluorescens lipase (PFL) through the co-precipitation method, resulting in the preparation of immobilized lipase (PFL@ZIF-8@ZIF-67). Subsequently, it was further treated with glutaraldehyde to improve protein immobilization yield. Under optimal immobilization conditions, the specific hydrolytic activity of PFL@ZIF-8@ZIF-67 was 20.4 times higher than that of the free PFL. The prepared biocatalyst was characterized and analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). Additionally, the thermal stability of PFL@ZIF-8@ZIF-67 at 50 °C was significantly improved compared to the free PFL. After 7 weeks at room temperature, PFL@ZIF-8@ZIF-67 retained 78% of the transesterification activity, while the free enzyme was only 29%. Finally, PFL@ZIF-8@ZIF-67 was applied to the neryl acetate preparation in a solvent-free system, and the yield of neryl acetate reached 99% after 3 h of reaction. After 10 repetitions, the yields of neryl acetate catalyzed by PFL@ZIF-8@ZIF-67 and the free PFL were 80% and 43%, respectively.


Assuntos
Enzimas Imobilizadas , Lipase , Pseudomonas fluorescens , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Pseudomonas fluorescens/enzimologia , Lipase/química , Lipase/metabolismo , Esterificação , Estabilidade Enzimática , Zeolitas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Acetatos/química , Difração de Raios X , Biocatálise , Imidazóis
11.
Mol Med Rep ; 30(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38904207

RESUMO

Montelukast and zafirlukast, cysteinyl leukotriene receptor antagonists (LTRAs), trigger apoptosis and inhibit cell proliferation of triple­negative breast cancer MDA­MB­231 cells. By contrast, only zafirlukast induces G0/G1 cell cycle arrest. The present study compared the effects of these drugs on proteins regulating cell proliferation, apoptosis, autophagy, and endoplasmic reticulum (ER) and oxidative stress using reverse transcription­quantitative PCR, western blotting and flow cytometry. The expression of proliferating markers, Ki­67 and proliferating cell nuclear antigen, was decreased by both drugs. Zafirlukast, but not montelukast, decreased the expression of cyclin D1 and CDK4, disrupting progression from G1 to S phase. Zafirlukast also increased the expression of p27, a cell cycle inhibitor. Both drugs decreased the expression of anti­apoptotic protein Bcl­2 and ERK1/2 phosphorylation, and increased levels of the autophagy marker LC3­II and DNA damage markers, including cleaved PARP­1, phosphorylated (p)­ATM and p­histone H2AX. The number of caspase 3/7­positive cells was greater in montelukast­treated cells compared with zafirlukast­treated cells. Montelukast induced higher levels of the ER stress marker CHOP compared with zafirlukast. Montelukast activated PERK, activating transcription factor 6 (ATF6) and inositol­requiring enzyme type 1 (IRE1) pathways, while zafirlukast only stimulated ATF6 and IRE1 pathways. GSK2606414, a PERK inhibitor, decreased apoptosis mediated by montelukast, but did not affect zafirlukast­induced cell death. The knockdown of CHOP by small interfering RNA reduced apoptosis triggered by montelukast and zafirlukast. In conclusion, the effects on cell cycle regulator proteins may contribute to cell cycle arrest caused by zafirlukast. The greater apoptotic effects of montelukast may be caused by the higher levels of activated caspase enzymes and the activation of three pathways of ER stress: PERK, ATF6, and IRE1.


Assuntos
Acetatos , Apoptose , Autofagia , Ciclopropanos , Dano ao DNA , Estresse do Retículo Endoplasmático , Indóis , Quinolinas , Sulfetos , Sulfonamidas , Humanos , Sulfetos/farmacologia , Ciclopropanos/farmacologia , Quinolinas/farmacologia , Apoptose/efeitos dos fármacos , Acetatos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Linhagem Celular Tumoral , Autofagia/efeitos dos fármacos , Sulfonamidas/farmacologia , Indóis/farmacologia , Feminino , Dano ao DNA/efeitos dos fármacos , Fenilcarbamatos/farmacologia , Compostos de Tosil/farmacologia , Proliferação de Células/efeitos dos fármacos , eIF-2 Quinase/metabolismo , eIF-2 Quinase/genética , Endorribonucleases/metabolismo , Endorribonucleases/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Fator de Transcrição CHOP/metabolismo , Fator de Transcrição CHOP/genética , Ciclo Celular/efeitos dos fármacos , Antagonistas de Leucotrienos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética
12.
Front Immunol ; 15: 1279043, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840916

RESUMO

Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1-/- mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic Schistosoma mansoni infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of Schistosoma mansoni to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.


Assuntos
Acetatos , Ciclopropanos , Modelos Animais de Doenças , Camundongos Knockout , Quinolinas , Receptores de Leucotrienos , Esquistossomose mansoni , Sulfetos , Animais , Receptores de Leucotrienos/metabolismo , Camundongos , Ciclopropanos/uso terapêutico , Ciclopropanos/farmacologia , Acetatos/uso terapêutico , Acetatos/farmacologia , Sulfetos/uso terapêutico , Sulfetos/farmacologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Quinolinas/uso terapêutico , Quinolinas/farmacologia , Feminino , Schistosoma mansoni/imunologia , Doença Crônica , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/uso terapêutico , Fígado/parasitologia , Fígado/patologia , Fígado/metabolismo , Fígado/imunologia , Camundongos Endogâmicos C57BL , Praziquantel/uso terapêutico , Praziquantel/farmacologia , Linfócitos T Reguladores/imunologia
13.
Sci Rep ; 14(1): 14582, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918455

RESUMO

Volatile organic compounds (VOCs) are metabolites pivotal in determining the aroma of various products. A well-known VOC producer of industrial importance is Saccharomyces cerevisiae, partially responsible for flavor of beers and wines. We identified VOCs in beers produced by yeast strains characterized by improved aroma obtained in UV-induced mutagenesis. We observed significant increase in concentration of compounds in strains: 1214uv16 (2-phenylethyl acetate, 2- phenylethanol), 1214uv31 (2-ethyl henxan-1-ol), 1214uv33 (ethyl decanoate, caryophyllene). We observed decrease in production of 2-phenyethyl acetate in strain 1214uv33. Analysis of intracellular metabolites based on 1H NMR revealed that intracellular phenylalanine concentration was not changed in strains producing more phenylalanine related VOCs (1214uv16 and 1214uv33), so regulation of this pathway seems to be more sophisticated than is currently assumed. Metabolome analysis surprisingly showed the presence of 3-hydroxyisobutyrate, a product of valine degradation, which is considered to be absent in S. cerevisiae. Our results show that our knowledge of yeast metabolism including VOC production has gaps regarding synthesis pathways for individual metabolites and regulation mechanisms. Detailed analysis of 1214uv16 and 1214uv33 may enhance our knowledge of the regulatory mechanisms of VOC synthesis in yeast, and analysis of strain 1214uv31 may reveal the pathway of 2-ethyl henxan-1-ol biosynthesis.


Assuntos
Cerveja , Metaboloma , Mutação , Saccharomyces cerevisiae , Compostos Orgânicos Voláteis , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Cerveja/análise , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Odorantes/análise , Álcool Feniletílico/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/análise , Fermentação , Fenilalanina/metabolismo , Fenilalanina/análise , Metabolômica/métodos , Acetatos
14.
Environ Int ; 189: 108785, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823155

RESUMO

Sex and thyroid hormones are critical for male reproductive health. However, the associations between haloacetic acid (HAA) exposure - a known endocrine disruptor - and sex and thyroid hormones in humans remains unclear. We thus recruited 502 male participants seeking fertility evaluation from a reproductive center. We measured concentrations of sex and thyroid hormones in a single blood sample and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in repeated urine samples. Multivariable linear regression models were constructed to evaluate the associations between HAA concentrations and hormone measurements. After adjusting for potential confounders and urinary creatinine concentrations, urinary concentrations of TCAA were inversely associated with serum levels of sex hormone-binding globulin (SHBG), testosterone (T), T/luteinizing hormone ratio (T/LH), and thyroid stimulating hormone (TSH) (all P for trend < 0.10). Compared with participants in the lowest quartile of TCAA concentrations, those in the highest quartile had reduced serum levels of SHGB by 14.2 % (95% CI: -26.7, -3.0 %), T by 11.1 % (95% CI: -21.7, -1.3 %), T/LH by 21.0 % (95% CI: -36.7, -7.1 %), and TSH by 19.1 % (95% CI: -39.7, -1.5 %). Additionally, we observed inverse associations between continuous measurements of urinary HAAs and serum levels of free T, bioactive T, and estradiol. Our findings suggest that male HAA exposure may be associated with disrupted sex and thyroid function.


Assuntos
Hormônios Tireóideos , Humanos , Masculino , Adulto , Hormônios Tireóideos/sangue , Testosterona/sangue , Testosterona/urina , Disruptores Endócrinos/urina , Disruptores Endócrinos/sangue , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/metabolismo , Adulto Jovem , Ácido Tricloroacético/urina , Ácido Tricloroacético/sangue , Hormônio Luteinizante/sangue , Tireotropina/sangue , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Pessoa de Meia-Idade , Hormônios Esteroides Gonadais/sangue , Hormônios Esteroides Gonadais/urina , Acetatos
15.
Nutrients ; 16(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892659

RESUMO

CONTEXT: Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting. OBJECTIVE: Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases. DATA SOURCES: A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction. DATA ANALYSIS: It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion. CONCLUSIONS: The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.


Assuntos
Ácidos Graxos Voláteis , Fezes , Síndrome do Intestino Irritável , Síndrome do Intestino Irritável/dietoterapia , Síndrome do Intestino Irritável/terapia , Humanos , Fezes/química , Fezes/microbiologia , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , Transplante de Microbiota Fecal , Probióticos , Propionatos/metabolismo , Propionatos/análise , Ensaios Clínicos Controlados Aleatórios como Assunto , Acetatos/análise , Feminino , Microbioma Gastrointestinal , Biomarcadores/análise , Masculino , Adulto , Estudos de Casos e Controles
16.
Plant Mol Biol ; 114(3): 70, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842600

RESUMO

Melon (Cucumis melo L.) is an important horticultural and economic crop. ETHYLENE RESPONSE FACTOR1 (ERF1) plays an important role in regulating plant development, and the resistance to multiple biotic and abiotic stresses. In this study, developmental biology, molecular biology and biochemical assays were performed to explore the biological function of CmERF1 in melon. Abundant transcripts of CmERF1 were found in ovary at green-yellow bud (GYB) and rapid enlargement (ORE) stages. In CmERF1 promoter, the cis-regulatory elements for indoleacetic acid (IAA), methyl jasmonate (MeJA), salicylic acid (SA), abscisic acid (ABA), gibberellic acid (GA), light and low temperature responses were found. CmERF1 could be significantly induced by ethylene, IAA, MeJA, SA, ABA, and respond to continuous light and low temperature stresses in melon. Ectopic expression of CmERF1 increased the length of siliqua and carpopodium, and expanded the size of leaves in Arabidopsis. Knockdown of CmERF1 led to smaller ovary at anthesis, mature fruit and leaves in melon. In CmERF1-RNAi #2 plants, 75 genes were differently expressed compared with control, and the promoter regions of 28 differential expression genes (DEGs) contained the GCC-box (AGCCGCC) or DRE (A/GCCGAC) cis-acting elements of CmERF1. A homolog of cell division cycle protein 48 (CmCDC48) was proved to be the direct target of CmERF1 by the yeast one-hybrid assay and dual-luciferase (LUC) reporter (DLR) system. These results indicated that CmERF1 was able to promote the growth of fruits and leaves, and involved in multiple hormones and environmental signaling pathways in melon.


Assuntos
Cucumis melo , Ciclopentanos , Frutas , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas , Folhas de Planta , Proteínas de Plantas , Plantas Geneticamente Modificadas , Cucumis melo/genética , Cucumis melo/crescimento & desenvolvimento , Cucumis melo/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Regiões Promotoras Genéticas , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Acetatos/farmacologia , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia
17.
Nat Commun ; 15(1): 5424, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926344

RESUMO

Anaerobic, acetogenic bacteria are well known for their ability to convert various one-carbon compounds, promising feedstocks for a future, sustainable biotechnology, to products such as acetate and biofuels. The model acetogen Acetobacterium woodii can grow on CO2, formate or methanol, but not on carbon monoxide, an important industrial waste product. Since hydrogenases are targets of CO inhibition, here, we genetically delete the two [FeFe] hydrogenases HydA2 and HydBA in A. woodii. We show that the ∆hydBA/hydA2 mutant indeed grows on CO and produces acetate, but only after a long adaptation period. SNP analyzes of CO-adapted cells reveal a mutation in the HycB2 subunit of the HydA2/HydB2/HydB3/Fdh-containing hydrogen-dependent CO2 reductase (HDCR). We observe an increase in ferredoxin-dependent CO2 reduction and vice versa by the HDCR in the absence of the HydA2 module and speculate that this is caused by the mutation in HycB2. In addition, the CO-adapted ∆hydBA/hydA2 mutant growing on formate has a final biomass twice of that of the wild type.


Assuntos
Acetobacterium , Proteínas de Bactérias , Monóxido de Carbono , Formiatos , Acetobacterium/genética , Acetobacterium/metabolismo , Acetobacterium/crescimento & desenvolvimento , Formiatos/metabolismo , Monóxido de Carbono/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Hidrogenase/metabolismo , Hidrogenase/genética , Mutação , Dióxido de Carbono/metabolismo , Transporte de Elétrons , Biomassa , Acetatos/metabolismo , Polimorfismo de Nucleotídeo Único
18.
Science ; 384(6703): 1453-1460, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38870272

RESUMO

Insects detect and discriminate a diverse array of chemicals using odorant receptors (ORs), which are ligand-gated ion channels comprising a divergent odorant-sensing OR and a conserved odorant receptor co-receptor (Orco). In this work, we report structures of the ApOR5-Orco heterocomplex from the pea aphid Acyrthosiphon pisum alone and bound to its known activating ligand, geranyl acetate. In these structures, three ApOrco subunits serve as scaffold components that cannot bind the ligand and remain relatively unchanged. Upon ligand binding, the pore-forming helix S7b of ApOR5 shifts outward from the central pore axis, causing an asymmetrical pore opening for ion influx. Our study provides insights into odorant recognition and channel gating of the OR-Orco heterocomplex and offers structural resources to support development of innovative insecticides and repellents for pest control.


Assuntos
Acetatos , Afídeos , Proteínas de Insetos , Receptores Odorantes , Receptores Odorantes/química , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Animais , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Afídeos/química , Acetatos/química , Acetatos/metabolismo , Ligantes , Terpenos/química , Terpenos/metabolismo , Odorantes/análise , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Ativação do Canal Iônico , Microscopia Crioeletrônica , Monoterpenos Acíclicos
19.
Biomolecules ; 14(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38927108

RESUMO

(1) Background: Phytochemicals are crucial antioxidants that play a significant role in preventing cancer. (2) Methods: We explored the use of methyl jasmonate (MeJA) in the in vitro cultivation of D. morbifera adventitious roots (DMAR) and evaluated its impact on secondary metabolite production in DMAR, optimizing concentration and exposure time for cost-effectiveness. We also assessed its anti-inflammatory and anti-lung cancer activities and related gene expression levels. (3) Results: MeJA treatment significantly increased the production of the phenolic compound 3,5-Di-caffeoylquinic acid (3,5-DCQA). The maximum 3,5-DCQA production was achieved with a MeJA treatment at 40 µM for 36 h. MeJA-DMARE displayed exceptional anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-induced RAW 264.7 cells. Moreover, it downregulated the mRNA expression of key inflammation-related cytokines. Additionally, MeJA-DMARE exhibited anti-lung cancer activity by promoting ROS production in A549 lung cancer cells and inhibiting its migration. It also modulated apoptosis in lung cancer cells via the Bcl-2 and p38 MAPK pathways. (4) Conclusions: MeJA-treated DMARE with increased 3,5-DCQA production holds significant promise as a sustainable and novel material for pharmaceutical applications thanks to its potent antioxidant, anti-inflammatory, and anti-lung cancer properties.


Assuntos
Acetatos , Anti-Inflamatórios , Ciclopentanos , Neoplasias Pulmonares , Oxilipinas , Raízes de Plantas , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Acetatos/farmacologia , Acetatos/química , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Células RAW 264.7 , Raízes de Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico/metabolismo , Apoptose/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Células A549 , Sapindaceae/química
20.
Biomolecules ; 14(6)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38927118

RESUMO

Ginseng (Panax ginseng C. A. Meyer) is an ancient and valuable Chinese herbal medicine, and ginsenoside, as the main active ingredient of ginseng, has received wide attention because of its various pharmacological active effects. Cytochrome P450 is the largest family of enzymes in plant metabolism and is involved in the biosynthesis of terpenoids, alkaloids, lipids, and other primary and secondary plant metabolites. It is significant to explore more PgCYP450 genes with unknown functions and reveal their roles in ginsenoside synthesis. In this study, based on the five PgCYP450 genes screened in the pre-laboratory, through the correlation analysis with the content of ginsenosides and the analysis of the interactions network of the key enzyme genes for ginsenoside synthesis, we screened out those highly correlated with ginsenosides, PgCYP309, as the target gene from among the five PgCYP450 genes. Methyl jasmonate-induced treatment of ginseng adventitious roots showed that the PgCYP309 gene responded to methyl jasmonate induction and was involved in the synthesis of ginsenosides. The PgCYP309 gene was cloned and the overexpression vector pBI121-PgCYP309 and the interference vector pART27-PgCYP309 were constructed. Transformation of ginseng adventitious roots by the Agrobacterium fermentum-mediated method and successful induction of transgenic ginseng hairy roots were achieved. The transformation rate of ginseng hairy roots with overexpression of the PgCYP309 gene was 22.7%, and the transformation rate of ginseng hairy roots with interference of the PgCYP309 gene was 40%. Analysis of ginseng saponin content and relative gene expression levels in positive ginseng hairy root asexual lines revealed a significant increase in PPD, PPT, and PPT-type monomeric saponins Re and Rg2. The relative expression levels of PgCYP309 and PgCYP716A53v2 genes were also significantly increased. PgCYP309 gene promotes the synthesis of ginsenosides, and it was preliminarily verified that PgCYP309 gene can promote the synthesis of dammarane-type ginsenosides.


Assuntos
Sistema Enzimático do Citocromo P-450 , Ginsenosídeos , Panax , Panax/genética , Panax/metabolismo , Panax/enzimologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Ginsenosídeos/metabolismo , Ginsenosídeos/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Acetatos/farmacologia , Acetatos/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo
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