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1.
Hypertension ; 81(3): 541-551, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38164755

RESUMEN

BACKGROUND: KDM6A (Lysine-Specific Demethylase 6A) is a specific demethylase for histone 3 lysine (K) 27 trimethylation (H3K27me3). The purpose of this study is to investigate whether KDM6A in renal tubule cells plays a role in the regulation of kidney function and blood pressure. METHODS: We first crossed Ksp-Cre+/- and KDM6Aflox/flox mice for generating inducible kidney-specific deletion of KDM6A gene. RESULTS: Notably, conditional knockout of KDM6A gene in renal tubule cells (KDM6A-cKO) increased H3K27me3 levels which leads to a decrease in Na excretion and elevation of blood pressure. Further analysis showed that the expression of NKCC2 (Na-K-2Cl cotransporter 2) and NCC (Na-Cl cotransporters) was upregulated which contributes to impaired Na excretion in KDM6A-cKO mice. The expression of AQP2 (aquaporin 2) was also increased in KDM6A-cKO mice, which may facilitate water reabsorption in KDM6A-cKO mice. The expression of Klotho was downregulated while expression of aging markers including p53, p21, and p16 was upregulated in kidneys of KDM6A-cKO mice, indicating that deletion of KDM6A in the renal tubule cells promotes kidney aging. Interestingly, KDM6A-cKO mice developed salt-sensitive hypertension which can be rescued by treatment with Klotho. KDM6A deficiency induced salt-sensitive hypertension likely through downregulation of the Klotho/ERK (extracellular signal-regulated kinase) signaling and upregulation of the WNK (with-no-lysine kinase) signaling. CONCLUSIONS: This study provides the first evidence that KDM6A plays an essential role in maintaining normal tubular function and blood pressure. Renal tubule cell specific KDM6A deficiency causes hypertension due to increased H3K27me3 levels and the resultant downregulation of Klotho gene expression which disrupts the Klotho/ERK/NCC/NKCC2 signaling.


Asunto(s)
Histona Demetilasas , Hipertensión , Proteínas Serina-Treonina Quinasas , Animales , Ratones , Acuaporina 2/metabolismo , Presión Sanguínea/fisiología , Histonas/metabolismo , Hipertensión/genética , Hipertensión/metabolismo , Riñón/metabolismo , Lisina/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Sodio/metabolismo , Cloruro de Sodio/metabolismo , Histona Demetilasas/metabolismo
2.
Nat Prod Res ; 37(4): 651-656, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35506313

RESUMEN

Extracts from plants used in Chinese medicine can be good sources of fungicides for agricultural applications. In this study, we separated and identified antifungal compounds from four traditional Chinese medicine extracts and evaluated their antifungal activities in vitro and in vivo. In vitro, honokiol extracted from Artemisia argyi showed broad-spectrum antimicrobial and mycelial inhibitory activity with EC50 in the range 3.56 - 33.85 µg/mL against eight plant pathogens. q-PCR indicated that honokiol might induce cell cancerisation and inhibit cellular respiration, which provided significant insights into honokiol function in tobacco resistance to molecular mechanisms of the phytopathogenic fungus Phytophthora nicotianae. In vivo, honokiol significantly decreased the rate of fungal infection in eggplants, potatoes, grapes, cherry tomatoes, and cucumbers, and enhanced disease resistance in tobacco. Overall, our results indicate that honokiol has the potential to control a variety of fungal and oomycete diseases, and A. argyi could be a source of honokiol.


Asunto(s)
Artemisia , Lignanos , Antifúngicos/farmacología , Lignanos/farmacología , Extractos Vegetales/farmacología
3.
Microb Biotechnol ; 16(1): 139-147, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36415948

RESUMEN

Aspergillus genus is a key component in fermentation and food processing. However, sterigmatocystin (STE)-a mycotoxin produced by several species of Aspergillus-limits the use of some Aspergillus species (such as Aspergillus versicolor, Aspergillus inflatus, and Aspergillus parasiticus) because of its toxicity and carcinogenicity. Here, we engineered an STE-free Aspergillus versicolor strain based on genome mining techniques. We sequenced and assembled the Aspergillus versicolor D5 genome (34.52 Mb), in which we identified 16 scaffolds and 54 biosynthetic gene clusters (BGCs). We silenced cytochrome P450 coding genes STC17 and STC27 by insertional inactivation. The production of STE in the Δstc17 mutant strain was increased by 282% but no STE was detected in the Δstc27 mutant. Metabolites of Δstc27 mutant exhibited growth-promoting effect on plants. Our study makes significant progress in improving the application of some Aspergillus strains by restricting their production of toxic and carcinogenic compounds.


Asunto(s)
Aspergillus , Esterigmatocistina , Esterigmatocistina/metabolismo , Aspergillus/genética , Aspergillus/metabolismo , Metabolismo Secundario , Fermentación
4.
Ecotoxicol Environ Saf ; 247: 114273, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36356529

RESUMEN

Sterigmatocystin (STE) is a common hepatotoxic and nephrotoxic contaminant in cereals, however, its phytotoxicity and mechanisms are poorly understood. Here, the phytotoxic mechanisms of STE were investigated via the metabolomics of Amaranthus retroflexus L. A total of 140 and 113 differential metabolites were detected in the leaves and stems, respectively, among which amino acids, lipids, and phenolic compounds were significantly perturbed. Valine, leucine, isoleucine, and lysine biosynthesis were affected by STE. These metabolic responses revealed that STE might be toxic to plants by altering the plasma membrane and inducing oxidative damage, which was verified by measuring the relative electrical conductivity and quantification of reactive oxygen species. The elevated amino acids, as well as the decreased of D-sedoheptuiose-7-phosphate indicated increased proteolysis and carbohydrate metabolism restriction. Furthermore, the IAA level also decreased. This study provides a better understanding of the impacts of STE on the public health, environment and food security.


Asunto(s)
Alcaloides , Amaranthus , Toxinas Biológicas , Esterigmatocistina , Metabolómica , Aminoácidos
5.
Front Microbiol ; 13: 940156, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36081807

RESUMEN

Tobacco bacterial wilt caused by Ralstonia solanacearum is one of the most devastating diseases. Microbial keystone taxa were proposed as promising targets in plant disease control. In this study, we obtained an antagonistic Bacillus isolate EM-1 from bacterial wilt-suppressive soil, and it was considered rhizosphere-resident bacteria based on high (100%) 16S rRNA gene similarity to sequences derived from high-throughput amplicon sequencing. According to 16S rRNA gene sequencing and MLSA, strain EM-1 was identified as Bacillus velezensis. This strain could inhibit the growth of R. solanacearum, reduce the colonization of R. solanacearum in tobacco roots, and decrease the incidence of bacterial wilt disease. In addition, strain EM-1 also showed a strong inhibitory effect on other phytopathogens, such as Alternaria alternata and Phytophthora nicotianae, indicating a wide antagonistic spectrum. The antimicrobial ability of EM-1 can be attributed to its volatile, lipopeptide and polyketide metabolites. Iturin A (C14, C15, and C16) was the main lipopeptide, and macrolactin A and macrolactin W were the main polyketides in the fermentation broth of EM-1, while heptanone and its derivatives were dominant among the volatile organic compounds. Among them, heptanones and macrolactins, but not iturins, might be the main potential antibacterial substances. Complete genome sequencing was performed, and the biosynthetic gene clusters responsible for iturin A and macrolactin were identified. Moreover, strain EM-1 can also induce plant resistance by increasing the activity of CAT and PPO in tobacco. These results indicated that EM-1 can serve as a biocontrol Bacillus strain for tobacco bacterial wilt control. This study provides a better insight into the strategy of exploring biocontrol agent based on rhizosphere microbiome.

6.
Curr Microbiol ; 79(9): 249, 2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35834051

RESUMEN

Bacillus altitudinis is a widely distributed soil bacterium that has various functional activities, including remediation of contaminated soil, degradation of herbicides, and enhancement of plant growth. B. altitudinis GQYP101 was isolated from the rhizosphere soil of Lycium barbarum L. and demonstrated potential as a plant growth-promoting bacterium. In this work, strain GQYP101 could solubilize phosphorus, and increased the stem diameter, maximum leaf area, and fresh weight of corn in a pot experiment. Nitrogen and phosphorus contents of corn seedlings (aerial part) increased by 100% and 47.9%, respectively, after application of strain GQYP101. Concurrently, nitrogen and phosphorus contents of corn root also increased, by 55.40% and 20.3%, respectively. Furthermore, rhizosphere soil nutrients were altered and the content of available phosphorus increased by 73.2% after application of strain GQYP101. The mechanism by which strain GQYP101 improved plant growth was further investigated by whole genome sequence analysis. Strain GQYP101 comprises a circular chromosome and a linear plasmid. Some key genes of strain GQYP101 were identified that were related to phosphate solubilization, alkaline phosphatase, chemotaxis, and motility. The findings of this study may provide a theoretical basis for strain GQYP101 to enhance crop yield as microbial fertilizer.


Asunto(s)
Microbiota , Rizosfera , Bacillus , Bacterias/metabolismo , Nitrógeno , Fosfatos/metabolismo , Fósforo , Plantones , Suelo/química , Microbiología del Suelo , Zea mays/metabolismo
7.
Bioresour Technol ; 350: 126913, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35231600

RESUMEN

This study investigated the effects of adding biocontrol microbes on metabolites and pathogenic microorganisms during mushroom residue composting and the relationships of metabolite changes with microbes and material transformation. The results showed that the addition of Bacillus subtilis (BS) and Trichoderma harzianum (TH) with mushroom residue promoted the conversion of organic carbon and nitrogen. The abundance of pathogenic microbes was increased in biocontrol microbial treatments. BS or TH treatments increased the levels of amino acids, carbohydrates, and bacteriostatic alkaloid metabolites. Network analysis revealed that the main microorganisms significantly related to alkaloid metabolites were Rhabdanaerobium, Atopostipes, Planifilum and Ureibacillus. The increased bacterial abundance and decreased NO3--N and TOC were closely related to the increases in amino acid and alkaloid metabolites after biocontrol agent treatments. Generally, adding biocontrol microbes is an effective way to increase the levels of antibacterial metabolites, but there is a risk of increasing the abundance of pathogenic microbes.


Asunto(s)
Agaricales , Alcaloides , Compostaje , Microbiota , Aminoácidos , Estiércol , Aceites de Plantas , Suelo
8.
Adv Sci (Weinh) ; 9(15): e2104034, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35315252

RESUMEN

Generation of kidney organoids using autologous kidney stem cells represents an attractive strategy for treating and potentially replacing the failing kidneys. However, whether adult mammalian kidney stem cells have regenerative capacity remains unknown. Here, previously unidentified adult kidney Sca1+ Oct4+ stem/progenitor cells are isolated. Interestingly, culturing these cells leads to generation of kidney-like structures. First, the assembly of self-organizing 3D kidney-like structures is observed. These kidney organoids contain podocytes, proximal tubules, and endothelial cells that form networks of capillary loop-like structures. Second, the differentiation of kidney stem cells into functionally mature tubules and self-organizing kidney-shaped structures in monolayer culture that selectively endocytoses dextran, is shown. Finally, the de novo generation of an entire self-organizing nephron from monolayer cultures is observed. Mechanistically, it is demonstrated that Sirt2-mediated canonical Wnt/ß-catenin signaling is critical for the development of kidney organoids. Thus, the first evidence is provided that the adult mouse kidney stem cells are capable of de novo generating kidney organoids.


Asunto(s)
Células Madre Pluripotentes , Podocitos , Animales , Células Endoteliales , Riñón , Mamíferos , Ratones , Sirtuina 2 , beta Catenina
9.
Phytochemistry ; 197: 113125, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35157922

RESUMEN

The filamentous fungi Fusarium sp. are well-known for their ability to produce abundant specialised metabolites with attractive chemical structures and bioactivities. In this study, chemical analyses of the endophyte F. equiseti D39 led to the isolation and identification of two pairs of undescribed 3-decalinoyltetramic acids (3DTAs) E/Z diastereomers, decalintetracids A and B. Their structures were elucidated by comprehensive spectroscopic analysis and quantum-chemical calculations. Although 3DTAs were commonly reported from fungi, decalintetracid A possessed an unprecedented tricyclo [7.2.1.02,7] dodecane skeleton, which added the diversity of these fungal metabolites. In addition, decalintetracid B was featured by a unique 6/6/5 ring system core. A plausible biosynthetic pathway for decalintetracids A and B was proposed. Both compounds exhibited phytotoxicity toward Amaranthus retroflexus L. and Amaranthus hybrid, indicating their potential as natural herbicides.


Asunto(s)
Alcaloides , Fusarium , Alcaloides/metabolismo , Endófitos , Fusarium/química , Pirrolidinonas
10.
Bioresour Technol ; 340: 125668, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34339999

RESUMEN

This study evaluated the effects of biocontrol Bacillus and fermenting bacteria addition on the microbial community, metabolic functions and antibiotic resistance genes (ARGs) of new prickly ash seed oil meal (PSOM)-biochar composting. The results showed that the addition of Bacillus subtilis and fermentation bacteria significantly increased the NH4+-N, bacterial abundance and fungal diversity of compost while decreasing the relative abundances (RAs) of carbon metabolism genes in mature compost. NH4+-N was significantly correlated with microbial abundance and diversity, and its increase was closely related to microbial amino acid metabolism. The addition of biocontrol and fermenting bacteria changed the RAs of ARGs, which was caused by changes in the potential hosts Proteobacteria, Bacteroidota and Firmicutes in the compost. Consequently, adding Bacillus and fermenting bacteria into PSOM to make composting was suggested as an effective method to promote nutrient transformation, regulate microbial activity and decrease RAs of tetracycline and vancomycin ARGs.


Asunto(s)
Bacillus , Compostaje , Microbiota , Antibacterianos/farmacología , Bacillus/genética , Bacillus subtilis , Carbón Orgánico , Farmacorresistencia Microbiana , Fermentación , Genes Bacterianos , Estiércol , Aceites de Plantas
11.
Front Plant Sci ; 12: 655673, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33959142

RESUMEN

Recent studies have observed differing microbiomes between disease-suppressive and disease-conducive soils. However, it remains unclear whether the microbial keystone taxa in suppressive soil are critical for the suppression of diseases. Bacterial wilt is a common soil-borne disease caused by Ralstonia solanacearum that affects tobacco plants. In this study, two contrasting tobacco fields with bacterial wilt disease incidences of 0% (disease suppressive) and 100% (disease conducive) were observed. Through amplicon sequencing, as expected, a high abundance of Ralstonia was found in the disease-conducive soil, while large amounts of potential beneficial bacteria were found in the disease-suppressive soil. In the fungal community, an abundance of the Fusarium genus, which contains species that cause Fusarium wilt, showed a positive correlation (p < 0.001) with the abundance of Ralstonia. Network analysis revealed that the healthy plants had more complex bacterial networks than the diseased plants. A total of 9 and 13 bacterial keystone taxa were identified from the disease-suppressive soil and healthy root, respectively. Accumulated abundance of these bacterial keystones showed a negative correlation (p < 0.001) with the abundance of Ralstonia. To complement network analysis, culturable strains were isolated, and three species belonging to Pseudomonas showed high 16S rRNA gene similarity (98.4-100%) with keystone taxa. These strains displayed strong inhibition on pathogens and reduced the incidence of bacterial wilt disease in greenhouse condition. This study highlighted the importance of keystone species in the protection of crops against pathogen infection and proposed an approach to obtain beneficial bacteria through identifying keystone species, avoiding large-scale bacterial isolation and cultivation.

12.
Front Plant Sci ; 12: 738611, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-36406638

RESUMEN

Bacterial communities in the rhizosphere play an important role in sustaining plant growth and the health of diverse soils. Recent studies have demonstrated that microbial keystone taxa in the rhizosphere microbial community are extremely critical for the suppression of diseases. However, the mechanisms involved in disease suppression by keystone species remain unclear. The present study assessed the effects of three Pseudomonas strains, which were identified as keystone species in our previous study, on the growth performance and root-associated bacterial community of tobacco plants. A high relative abundance of Ralstonia was found in the non-inoculated group, while a large Azospira population was observed in all groups inoculated with the three Pseudomonas strains. Correspondingly, the activities of the defense-related enzymes and the expression levels of the defense signaling marker genes of the plant were increased after inoculation with the Pseudomonas strains. Moreover, the correlation analyses showed that the relative abundance of Azospira, the activity of superoxide dismutase, catalase, and polyphenol oxidase, and the expression of H1N1, ACC Oxidase, and PR1 a/c had a significantly negative (p<0.05) relationship with the abundance of Ralstonia. This further revealed that the keystone species, such as Pseudomonas spp., can suppress bacterial wilt disease by enhancing the systemic resistance of tobacco plants.

13.
Front Microbiol ; 11: 584174, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33101258

RESUMEN

Paenibacillus polymyxa is an important member of the plant growth-promoting rhizobacteria. P. polymyxa YC0136 inoculation had beneficial effect on growth promotion and biological control of tobacco (Nicotiana tabacum L.) under field conditions. This study aimed to reveal the growth-promoting mechanisms of strain YC0136. In growth-promotion assays, tobacco plant height was increased by 8.42% and 8.25% at 60 and 90 days, respectively, after inoculation with strain YC0136. Strain YC0136 also promoted the accumulation of tobacco biomass in varying degrees. Following inoculation with strain YC0136, 3,525 and 4,368 tobacco genes were up-regulated and down-regulated, respectively. Strain YC0136 induced the expression of plant hormone-related genes in tobacco, including auxin, cytokinin, and gibberellin, as well as transcription factors related to stress resistance such as WRKY and MYB. In addition, strain YC0136 induced the up-regulation of genes in the phenylpropanoid biosynthesis pathway by 1.51-4.59 times. Interaction with tobacco also induced gene expression changes in strain YC0136, with 286 and 223 genes up-regulated and down-regulated, respectively. Tobacco interaction induced up-regulation of the ilvB gene related to auxin biosynthesis in strain YC0136 by 1.72 times and induced expression of some nutrient transport genes. This study contributes to our understanding of the growth-promoting mechanisms of strain YC0136 on tobacco and provides a theoretical basis for the application of P. polymyxa YC0136 as a biological fertilizer.

14.
J Agric Food Chem ; 68(40): 11207-11214, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-32915561

RESUMEN

Fungi have been proved as promising and prolific sources of functional secondary metabolites with potent agricultural applications. In this study, 14 xanthone derivatives (1-14), including six new ones, versicones I-N (1-4, 7, 11), and a biogenetically related derivative (15), were isolated from the alga-derived fungus Aspergillus versicolor D5. Their structures were elucidated by comprehensive spectroscopic methods. Versicone L (4) exhibited a broad antifungal spectrum and prominent inhibitory effects on Botrytis cinerea at a minimum inhibitory concentration (MIC) of 152 µM, 7-fold stronger than that of the positive control, carbendazim (MIC = 1.05 × 103 µM). Dihydrosterigmatocystin (13) showed strong antifungal activity toward B. cinerea at MIC = 38.3 µM, almost 30-fold stronger than that of carbendazim. Meanwhile, 13 exhibited potent herbicidal activity toward Amaranthus retroflexus L. with an MIC of 24.5 µM, approximately 4-fold stronger than that of the positive control, glyphosate (MIC = 94.7 µM). Additionally, 13 also displayed remarkable activity against other weeds belonging to Amaranth sp. Analysis of the structure-herbicidal activity relationship indicated that the bifuranic ring played an important role in xanthone phytotoxicity and the presence of a double bond in the furan ring could decrease phytotoxicity. This study indicated that xanthones can be served as promising candidates for lead compounds of agrochemicals.


Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Aspergillus/química , Herbicidas/química , Herbicidas/farmacología , Xantonas/química , Xantonas/farmacología , Amaranthus/efectos de los fármacos , Amaranthus/crecimiento & desarrollo , Aspergillus/aislamiento & purificación , Botrytis/efectos de los fármacos , Botrytis/crecimiento & desarrollo , China , Chlorophyta/microbiología , Pruebas de Sensibilidad Microbiana , Estructura Molecular
15.
Hypertension ; 75(5): 1233-1241, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32223380

RESUMEN

KL (klotho) levels decline with age, which is an important mechanistic driver of aging. KL gene deficiency is associated with hypertension. The purpose of this study is to investigate the potential role of H3K27me3 (histone 3 lysine [K] 27 trimethylation) in the regulation of KL gene expression and examine the related molecular pathways that may drive kidney cell aging. Kidneys were collected from 6-month-old WT (wild type; young WT), 30-month-old WT (aged WT), and 6- (young) and 20-month-old (aged) KL mutant mice, respectively. We demonstrated that the H3K27me3 level was increased in kidneys of aged WT and KL mutant mice versus young WT mice. Elevation of H3K27me3 levels was likely due to downregulation of the H3K27 (histone H3 Lys 27)-specific demethylase JMJD3 (the Jumonji domain containing-3) in the aged kidneys. Inhibition of PRC2 (polycomb repressive complex C2; histone trimethyltransferase) decreased the H3K27me3 levels leading to an increase in the expression of KL in cultured primary renal tubule cells assessed by Western blot and KL promoter activity assays. The chromatin immunoprecipitation qPCR assay revealed that H3K27me3 was physically associated with the KL promoter region. Furthermore, aging impaired the SGK1 (serum- and glucocorticoid-induced protein kinase 1)/FOXO3a (the forkhead box class O 3a) signaling leading to upregulation of p53 and p16 (aging markers) in the kidney of aged WT mice. KL may regulate the SGK1/FOXO3 signaling, which was decreased due to KL deficiency. Thus, aging-associated downregulation of KL gene expression may be partly attributed to upregulation of H3K27me3 levels. Downregulation of KL may impair the SGK1/FOXO3 signaling contributing to kidney cell aging.


Asunto(s)
Envejecimiento/genética , Regulación de la Expresión Génica/genética , Glucuronidasa/genética , Código de Histonas , Histonas/genética , Túbulos Renales/metabolismo , Envejecimiento/metabolismo , Animales , Western Blotting , Núcleo Celular/metabolismo , Células Cultivadas , Inmunoprecipitación de Cromatina , Proteína Potenciadora del Homólogo Zeste 2/biosíntesis , Proteína Potenciadora del Homólogo Zeste 2/genética , Inducción Enzimática , Proteína Forkhead Box O3/metabolismo , Glucuronidasa/biosíntesis , Glucuronidasa/deficiencia , Histonas/metabolismo , Proteínas Inmediatas-Precoces/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo , Riñón/crecimiento & desarrollo , Túbulos Renales/citología , Proteínas Klotho , Masculino , Metilación , Ratones , Regiones Promotoras Genéticas , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
16.
J Mol Cell Cardiol ; 138: 66-74, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31758962

RESUMEN

There is controversy regarding whether excess FGF23 causes left ventricular hypertrophy (LVH) directly through activation of fibroblast growth factor receptor 4 (FGFR4) in cardiomyocytes or indirectly through reductions in soluble Klotho (sK). We investigated the respective roles of myocardial FGFR4 and sKL in mediating FGF23-induced LVH using mouse genetic and pharmacological approaches. To investigate a direct role of myocardial FGFR4 in mediating the cardiotoxic effects of excess circulating FGF23, we administered rFGF23 to mice with cardiac-specific loss of FGFR4 (FGFR4 heart-cKO). We tested a model of sKL deficiency, hypertension and LVH created by the conditional deletion of FGFR1 in the renal distal tubule (FGFR1DT cKO mice). The cardioprotective effects of sKL in both mouse models was assessed by the systemic administration of recombinant sKL. We confirmed that FGF23 treatment activates PLCγ in the heart and induces LVH in the absence of membrane α-Klotho. Conditional deletion of FGFR4 in the myocardium prevented rFGF23-induced LVH in mice, establishing direct cardiotoxicity of FGF23 through activation of FGFR4. Recombinant sKL administration prevented LVH, but not HTN, in FGFR1DT cKO mice, consistent with direct cardioprotective effects. Co-administration of recombinant sKL with FGF23 in culture inhibited rFGF23-induced p-PLCγ signaling. Thus, FGF23 ability to include LVH represents a balance between FGF23 direct cardiac activation of FGFR4 and the modulating effects of circulating sKL to alter FGF23-dependent myocardial signaling pathways.


Asunto(s)
Factores de Crecimiento de Fibroblastos/metabolismo , Glucuronidasa/metabolismo , Hipertrofia Ventricular Izquierda/metabolismo , Miocardio/metabolismo , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Animales , Citoprotección , Factor-23 de Crecimiento de Fibroblastos , Eliminación de Gen , Células HEK293 , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Túbulos Renales Distales/patología , Proteínas Klotho , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Solubilidad
17.
Biomolecules ; 9(10)2019 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-31640228

RESUMEN

This study explored the chemical compositions of garlic essential oil, the inhibitory activity of garlic essential oil and diallyl disulfide (DADS) against Phytophthora nicotianae, and the effects on mycelial plasma membrane permeability and P. nicotianae inhibition. In total, 29 compounds were detected in garlic essential oil, of which 26 were detected by gas chromatography‒mass spectrometry (GC-MS) and 21 by headspace solid-phase microextraction (HS-SPME) GC-MS. DADS (60.12% and 19.09%) and trisulfide di-2-propenyl (14.18% and 17.98%) were the major components identified by HS-SPME GC-MS and GC-MS analysis, respectively. Half-inhibitory concentration (Ec50, antagonism) and minimum inhibitory concentration (MIC, fumigation) of DADS against P. nicotianae were 150.83 µL/L and 20 µL/L, respectively, while Ec50 of garlic essential oil was 1108.25 µL/L. Mycelial membrane permeability gradually increased in a concentration-dependent manner, and cell death increased at 450 µL/L DADS. Furthermore, DADS treatment significantly reduced the incidence of tobacco black shank and the number of P. nicotianae pathogens in rhizosphere soil. DADS also promoted root development of tobacco seedlings at low concentrations, which was inhibited at high concentrations. Therefore, DADS may play an important role in the antifungal effect against P. nicotianae by destroying mycelial cell membrane integrity, causing an increase in cell membrane permeability, and leading to cell death.


Asunto(s)
Compuestos Alílicos/farmacología , Antifúngicos/farmacología , Disulfuros/farmacología , Ajo/química , Aceites Volátiles/farmacología , Phytophthora/efectos de los fármacos , Componentes Aéreos de las Plantas/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad , Nicotiana/efectos de los fármacos , Nicotiana/microbiología
18.
Adv Exp Med Biol ; 1155: 543-553, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31468430

RESUMEN

Taurine transporter (TauT) has been identified as a target gene of p53 tumor suppressor. TauT is also found to be overexpressed in variety type of human cancers, such as leukemia. This study showed that expression of TauT was upregulated by c-Myc and c-Jun oncogenes. To explore whether blocking of TauT inhibits tumor development, the RNA interference (RNAi) and immune targeting approaches were tested in tumor cells in vitro and in p53 mutant mice in vivo. Knockdown of TauT expression by RNAi resulted in cell cycle G2 arrest and suppressed human breast cancer MCF-7 cells proliferation determined by colonies production and cell migration assays. Knockdown of TauT also rendered MCF-7 cells more susceptible to chemotherapeutic drug-induced apoptosis. An antibody specifically against TauT blocked taurine uptake and induced cell cycle G2 arrest leading to cell death of variety type of tumor cells without affecting the viability of normal mammalian cells. TauT peptide vaccination significantly increased median lifespan (1.5-fold) of the p53 null mice and rescued p53+/- mice by extending the median lifespan from 315 days to 621 days. Furthermore, single dose treatment of tumor-bearing (thymic lymphoma) p53 null mice with TauT peptide reduced tumor size by about 50% and significantly prolonged survival of these mice from average 7 days (after observing the thymic lymphoma) to 21 days. This finding demonstrates that a novel TauT peptide vaccine can delay, inhibit, and/or treat p53 mutation related spontaneous tumorigenesis in vivo. Therefore, TauT peptide may be used as a universal cancer vaccine to prevent and/or treat patients with p53 mutation-mediated cancers.


Asunto(s)
Vacunas contra el Cáncer , Inmunoterapia , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Interferencia de ARN , Proteína p53 Supresora de Tumor/genética , Animales , Anticuerpos Monoclonales/farmacología , Puntos de Control del Ciclo Celular , Técnicas de Silenciamiento del Gen , Genes jun , Genes myc , Humanos , Células MCF-7 , Ratones , Ratones Noqueados , Terapia Molecular Dirigida , Mutación , Taurina , Vacunas de Subunidad
19.
Front Microbiol ; 10: 1285, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31231352

RESUMEN

Two novel 3-decalinoyltetramic acid (3DTA) derivatives, namely fusarisetins C and D (1 and 2), and four known derivatives (3-6) were isolated from the marine-derived fungus Fusarium equiseti D39. Their structures were determined by spectroscopic data, vibrational circular dichroism (VCD) calculations, and X-ray crystallography. Compound 2 was identified as the first fusarisetin to possess an unprecedented carbon skeleton with a tetracyclic ring system comprised of a decalin moiety (6/6) and a tetramic acid moiety. A plausible biosynthetic pathway for the isolated compounds was proposed. All 3DTAs derivatives exhibited a potent phytotoxicity, and 5 also displayed a remarkable anti-phytopathogenic activity superior to the positive control resulting in damage of the cell membrane of Pseudomonas syringae and ensuing leakage of the intracellular components. Here, the phytotoxicity of fusarisetins has been reported for the first time. The OSMAC fermentation optimization approach to give 5 was performed by varying the culture media and salinities. The results showed that potato liquid medium with 1% salinity is the most favorable condition for the production of 5.

20.
Artículo en Inglés | MEDLINE | ID: mdl-30834364

RESUMEN

Bacillus velezensis DSYZ is a plant growth-promoting rhizobacterium with the capacity to control fungal pathogens. It was isolated from the rhizosphere soil of garlic. Here, we present the complete genome sequence of B. velezensis DSYZ. Several gene clusters that are related to the biosynthesis of antimicrobial compounds were predicted.

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