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1.
Food Chem ; 462: 141020, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39216377

RESUMEN

The effects of preharvest methyl jasmonate (MeJA) spray application on the physicochemical quality, metabolism of phenolics, and cell wall components in raspberries were investigated during a 10-day cold storage period. MeJA spray reduced firmness loss, decay incidence, and weight loss, while maintained higher levels of soluble solids content, ascorbic acid, anthocyanins and flavonoids in raspberries. Furthermore, MeJA application resulted in increased total pectin and protopectin levels, as well as lowered water-soluble pectin, and activities of pectin methyl esterase, polygalacturonase and cellulase enzymes. Additionally, MeJA treatment upregulated the phenylpropanoid pathway, leading to higher endogenous phenolics and activities of phenylalanine-ammonia lyase and shikimate dehydrogenase. In conclusion, preharvest MeJA spray application could be adopted to enhance the storage potential of cold-stored raspberries for 10 days by maintaining higher firmness, assuring better physicochemical quality, and increasing phenolic metabolism, while reducing cell wall hydrolysis.


Asunto(s)
Acetatos , Antioxidantes , Pared Celular , Ciclopentanos , Almacenamiento de Alimentos , Frutas , Oxilipinas , Fenoles , Rubus , Oxilipinas/farmacología , Oxilipinas/metabolismo , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos , Pared Celular/química , Ciclopentanos/farmacología , Ciclopentanos/metabolismo , Fenoles/metabolismo , Antioxidantes/metabolismo , Acetatos/farmacología , Acetatos/metabolismo , Frutas/metabolismo , Frutas/química , Frutas/efectos de los fármacos , Rubus/metabolismo , Rubus/química , Conservación de Alimentos/métodos , Frío , Proteínas de Plantas/metabolismo
2.
Cell Stem Cell ; 31(9): 1241-1243, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39241753

RESUMEN

While the placenta regulates nutritional exchange between mother and fetus, Yu et al. reveal that human placental development is itself nutrient-sensitive. They elucidate entwined metabolic and epigenetic transitions driving syncytialization and pinpoint a requirement for the metabolite acetyl-CoA, which is sensitive to glucose metabolism.


Asunto(s)
Acetilcoenzima A , Placenta , Placentación , Humanos , Embarazo , Femenino , Acetilcoenzima A/metabolismo , Placenta/metabolismo , Acetatos/metabolismo , Acetatos/farmacología , Animales , Glucosa/metabolismo , Epigénesis Genética
3.
Sci Rep ; 14(1): 20576, 2024 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-39242697

RESUMEN

Rosa damascena Mill., commonly known as the King Flower, is a fragrant and important species of the Rosaceae family. It is widely used in the perfumery and pharmaceutical industries. The scent and color of the flowers are significant characteristics of this ornamental plant. This study aimed to investigate the relative expression of MYB1, CCD1, FLS, PAL, CER1, GT1, ANS and PAR genes under two growth stages (S1 and S2) in two morphs. The CCD1 gene pathway is highly correlated with the biosynthesis of volatile compounds. The results showed that the overexpression of MYB1, one of the important transcription factors in the production of fragrance and color, in the Hot pink morph of sample S2 increased the expression of PAR, PAL, FLS, RhGT1, CCD1, ANS, CER1, and GGPPS. The methyl jasmonate (MeJA) stimulant had a positive and cumulative effect on gene expression in most genes, such as FLS in ACC.26 of the S2 sample, RhGT1, MYB1, CCD1, PAR, ANS, CER1, and PAL in ACC.1. To further study, a comprehensive analysis was performed to evaluate the relationship between the principal volatile compounds and colors. Our data suggest that the rose with pink flowers had a higher accumulation content of flavonoids and anthocyanin. To separate essential oil compounds, GC/MS analysis identified 26 compounds in four samples. The highest amount of geraniol, one of the main components of damask rose, was found in the Hot pink flower, 23.54%, under the influence of the MeJA hormone.


Asunto(s)
Flores , Regulación de la Expresión Génica de las Plantas , Odorantes , Rosa , Rosa/genética , Rosa/metabolismo , Flores/genética , Flores/metabolismo , Odorantes/análisis , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxilipinas/metabolismo , Oxilipinas/farmacología , Compuestos Orgánicos Volátiles/metabolismo , Genes de Plantas , Ciclopentanos/metabolismo , Ciclopentanos/farmacología , Pigmentación/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Acetatos/farmacología , Acetatos/metabolismo , Color
4.
Physiol Plant ; 176(5): e14488, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39228009

RESUMEN

As a commonly used medicinal plant, the flavonoid metabolites of Blumea balsamifera and their association with genes are still elusive. In this study, the total flavonoid content (TFC), flavonoid metabolites and biosynthetic gene expression patterns of B. balsamifera after application of exogenous methyl jasmonate (MeJA) were scrutinized. The different concentrations of exogenous MeJA increased the TFC of B. balsamifera leaves after 48 h of exposure, and there was a positive correlation between TFC and the elicitor concentration. A total of 48 flavonoid metabolites, falling into 10 structural classes, were identified, among which flavones and flavanones were predominant. After screening candidate genes by transcriptome mining, the comprehensive analysis of gene expression level and TFC suggested that FLS and MYB may be key genes that regulate the TFC in B. balsamifera leaves under exogenous MeJA treatment. This study lays a foundation for elucidating flavonoids of B. balsamifera, and navigates the breeding of flavonoid-rich B. balsamifera varieties.


Asunto(s)
Acetatos , Ciclopentanos , Flavonoides , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Metaboloma , Oxilipinas , Hojas de la Planta , Oxilipinas/farmacología , Oxilipinas/metabolismo , Ciclopentanos/farmacología , Ciclopentanos/metabolismo , Acetatos/farmacología , Flavonoides/metabolismo , Metaboloma/efectos de los fármacos , Metaboloma/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Asparagaceae/genética , Asparagaceae/metabolismo , Asparagaceae/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo
5.
Proc Natl Acad Sci U S A ; 121(37): e2322217121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39240965

RESUMEN

Root exudates are known signaling agents that influence legume root nodulation, but the molecular mechanisms for nonflavonoid molecules remain largely unexplored. The number of soybean root nodules during the initial growth phase shows substantial discrepancies at distinct developmental junctures. Using a combination of metabolomics analyses on root exudates and nodulation experiments, we identify a pivotal role for certain root exudates during the rapid growth phase in promoting nodulation. Phenoxyacetic acid (POA) was found to activate the expression of GmGA2ox10 and thereby facilitate rhizobial infection and the formation of infection threads. Furthermore, POA exerts regulatory control on the miR172c-NNC1 module to foster nodule primordia development and consequently increase nodule numbers. These findings collectively highlight the important role of POA in enhancing nodulation during the accelerated growth phase of soybeans.


Asunto(s)
Glycine max , Nodulación de la Raíz de la Planta , Simbiosis , Glycine max/crecimiento & desarrollo , Glycine max/metabolismo , Glycine max/microbiología , Glycine max/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Nódulos de las Raíces de las Plantas/metabolismo , Nódulos de las Raíces de las Plantas/microbiología , Nódulos de las Raíces de las Plantas/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/microbiología , Raíces de Plantas/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , MicroARNs/metabolismo , MicroARNs/genética , Acetatos/metabolismo , Acetatos/farmacología
6.
J Environ Manage ; 369: 122336, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39243422

RESUMEN

Nutrient imbalances, such as high boron (B) stress, occur within, as well as across, agricultural systems worldwide and have become an important abiotic factor that reduces soil fertility and inhibits plant growth. Sugar beet is a B-loving crop and is better suited to be grown in high B environments, but the methods and mechanisms regarding the enhancement of high-B stress tolerance traits are not clear. The main objective of this research was to elucidate the effects of the alone and/or combined foliar spraying of zinc sulfate (ZnSO4) and methyl jasmonate (MeJA) on the growth parameters, tolerance, and photochemical performance of sugar beet under high-B stress. Results demonstrated that the photosynthetic performance was inhibited under high-B stress, with a reduction of 11.33% in the net photosynthetic rate (Pn) and an increase of 25.30% in the tolerance index. The application of ZnSO4, MeJA, and their combination enhanced sugar beet's adaptability to high-B stress, with an increase in Pn of 9.22%, 4.49%, and 2.85%, respectively, whereas the tolerance index was elevated by 15.33%, 8.21%, and 5.19%, respectively. All three ameliorative treatments resulted in increased photochemical efficiency (Fv/Fm) and the photosynthetic performance index (PIABS) of PSII. Additionally, they enhanced the light energy absorption (ABS/RC) and trapping capacity (DIO/RC), reduced the thermal energy dissipation (TRO/RC), and facilitated the QA to QB transfer in the electron transport chain (ETC) of PSII, which collectively improved the photochemical performance. Therefore, spraying both ZnSO4 and MeJA can better alleviate high-B stress and promote the growth of sugar beet, but the combined spraying effect of ZnSO4 and MeJA is lower than that of individual spraying. This study provides a reference basis for enhancing the ability of sugar beet and other plants to tolerate high-B stress and for sugar beet cultivation in high B areas.


Asunto(s)
Acetatos , Beta vulgaris , Boro , Ciclopentanos , Oxilipinas , Fotosíntesis , Hojas de la Planta , Zinc , Beta vulgaris/efectos de los fármacos , Beta vulgaris/crecimiento & desarrollo , Beta vulgaris/efectos de la radiación , Ciclopentanos/farmacología , Fotosíntesis/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Acetatos/farmacología , Estrés Fisiológico
7.
Drug Des Devel Ther ; 18: 3987-4001, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39258274

RESUMEN

Cytomegalovirus (CMV) infection is arguably the most important infectious complication that negatively affects the outcome of solid organ transplantation. For decades, CMV management after transplantation has relied on antiviral drugs that inhibit viral DNA polymerase (ganciclovir, foscarnet, and cidofovir). However, their use has been complicated by myelosuppression, nephrotoxicity, and selection of drug-resistant viruses. During the past few years, the therapeutic armamentarium for the management of CMV in solid organ transplant recipients has expanded with the approval of letermovir for CMV prophylaxis in high-risk CMV D+/R- kidney recipients, and maribavir for the treatment of refractory and resistant CMV infection. Both drugs offer significant improvement when compared to standard anti-CMV therapies; letermovir was as efficacious for CMV prevention, whereas maribavir was more effective in treating refractory and resistant CMV infections. Both letermovir and maribavir have favorable safety profiles compared to CMV DNA polymerase inhibitors, without the risk of neutropenia and leukopenia associated with ganciclovir and renal toxicities associated with foscarnet and cidofovir. Moreover, letermovir and maribavir are orally bioavailable, which allows convenient outpatient treatment. However, letermovir and maribavir have a significant drug interaction potential in solid organ transplant recipients, resulting in higher levels of calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus). Both letermovir and maribavir are CMV-specific and do not have clinical efficacy against other herpes viruses. Thus, there is a need for additional antiviral drugs to prevent herpes simplex and other herpes viruses when clinically indicated. This article provides a comprehensive review of the clinical data supporting the use of letermovir and maribavir in clinical practice. The author provides perspectives on the role of these newly approved drugs in the current management landscape of CMV infection in solid organ transplantation.


Asunto(s)
Acetatos , Antivirales , Infecciones por Citomegalovirus , Trasplante de Órganos , Quinazolinas , Ribonucleósidos , Humanos , Infecciones por Citomegalovirus/tratamiento farmacológico , Antivirales/uso terapéutico , Antivirales/efectos adversos , Antivirales/farmacología , Ribonucleósidos/uso terapéutico , Ribonucleósidos/efectos adversos , Ribonucleósidos/farmacología , Trasplante de Órganos/efectos adversos , Acetatos/uso terapéutico , Acetatos/efectos adversos , Acetatos/farmacología , Quinazolinas/uso terapéutico , Quinazolinas/farmacología , Bencimidazoles/uso terapéutico , Bencimidazoles/efectos adversos , Bencimidazoles/farmacología , Citomegalovirus/efectos de los fármacos , Diclororribofuranosil Benzoimidazol/análogos & derivados
8.
BMC Plant Biol ; 24(1): 847, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251901

RESUMEN

BACKGROUND: Camellia nitidissima is a rare, prized camellia species with golden-yellow flowers. It has a high ornamental, medicinal, and economic value. Previous studies have shown substantial flavonol accumulation in C. nitidissima petals during flower formation. However, the mechanisms underlying the golden flower formation in C. nitidissima remain largely unknown. RESULTS: We performed an integrative analysis of the transcriptome, proteome, and metabolome of the petals at five flower developmental stages to construct the regulatory network underlying golden flower formation in C. nitidissima. Metabolome analysis revealed the presence of 323 flavonoids, and two flavonols, quercetin glycosides and kaempferol glycosides, were highly accumulated in the golden petals. Transcriptome and proteome sequencing suggested that the flavonol biosynthesis-related genes and proteins upregulated and the anthocyanin and proanthocyanidin biosynthesis-related genes and proteins downregulated in the golden petal stage. Further investigation revealed the involvement of MYBs and bHLHs in flavonoid biosynthesis. Expression analysis showed that flavonol synthase 2 (CnFLS2) was highly expressed in the petals, and its expression positively correlated with flavonol content at all flower developmental stages. Transient overexpression of CnFLS2 in the petals increased flavonol content. Furthermore, correlation analysis showed that the jasmonate (JA) pathways positively correlated with flavonol biosynthesis, and exogenous methyl jasmonate (MeJA) treatment promoted CnFLS2 expression and flavonol accumulation. CONCLUSIONS: Our findings showed that the JA-CnFLS2 module regulates flavonol biosynthesis during golden petal formation in C. nitidissima.


Asunto(s)
Camellia , Flavonoles , Flores , Proteínas de Plantas , Camellia/genética , Camellia/metabolismo , Camellia/crecimiento & desarrollo , Flores/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Flavonoles/metabolismo , Flavonoles/biosíntesis , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas , Ciclopentanos/metabolismo , Transcriptoma , Pigmentación/genética , Oxilipinas/metabolismo , Acetatos/metabolismo , Acetatos/farmacología , Proteoma/metabolismo , Metaboloma , Multiómica , Oxidorreductasas
9.
BMC Microbiol ; 24(1): 317, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223475

RESUMEN

BACKGROUND: Rusted root rot is one of the most common root diseases in Panax ginseng, and Cylindrocarpon destructans is one of the main pathogenic fungus. The objective of this study was to screen and explore the extracts of biocontrol bacteria isolated from ginseng rhizosphere soil against Cylindrocarpon destructans. RESULTS: Bacterial strains Bacillus amyloliquefaciens YY8 and Enterobacteriacea YY115 were isolated and found to exhibit in vitro antifungal activity against C. destructans. A combination of crude protein extract from B. amyloliquefaciens YY8 and ethyl acetate extract from Enterobacteriacea YY115 in a 6:4 ratio exhibited the strongest antifungal activity against C. destructans. Measurements of electrical conductivity, protein content, and nucleic acid content in suspension cultures of C. destructans treated with a mixture extracts indicated that the extracts disrupted the cell membranes of rusted root rot mycelia, resulting in the leakage of electrolytes, proteins, and nucleic acids from the cells, and ultimately inhibiting the growth of C. destructans. The combined extracts suppressed the infection of ginseng roots discs by C. destructans effectively. CONCLUSION: The extracts obtained from the two bacterial strains effectively inhibited C. destructans in P. ginseng. It can provide scientific basis for the development of new biological control pesticides, reduce the use of chemical pesticides, and promote the sustainable development of agriculture.


Asunto(s)
Bacillus amyloliquefaciens , Enterobacteriaceae , Panax , Enfermedades de las Plantas , Raíces de Plantas , Panax/microbiología , Panax/química , Bacillus amyloliquefaciens/metabolismo , Bacillus amyloliquefaciens/química , Bacillus amyloliquefaciens/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Raíces de Plantas/microbiología , Enterobacteriaceae/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Microbiología del Suelo , Rizosfera , Acetatos/farmacología , Ascomicetos/efectos de los fármacos , Ascomicetos/química , Antifúngicos/farmacología , Antifúngicos/metabolismo , Agentes de Control Biológico/farmacología
10.
Sci Rep ; 14(1): 19937, 2024 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-39198657

RESUMEN

Trifloxystrobin (TFS) is a widely used strobilurin class fungicide. Ginkgo biloba L. has gained popularity due to its recognized medicinal and antioxidant properties. The aim of this study was to determine whether Ginkgo biloba L. extract (Gbex) has a protective role against TFS-induced phytotoxicity, genotoxicity and oxidative damage in A. cepa. Different groups were formed from Allium cepa L. bulbs subjected to tap water (control), 200 mg/L Gbex (Gbex1), 400 mg/L Gbex (Gbex2), 0.8 g/L TFS solution (TFS), 200 mg/L Gbex + 0.8 g/L TFS (TFS + Gbex1) and 400 mg/L Gbex + 0.8 g/L TFS (TFS + Gbex2), respectively. The phenolic composition of Gbex and alterations in the morphological, physiological, biochemical, genotoxicity and anatomical parameters were evaluated. Rutin, protocatechuic acid, catechin, gallic acid, taxifolin, p-coumaric acid, caffeic acid, epicatechin, syringic acid and quercetin were the most prevalent phenolic substances in Gbex. Rooting percentage, root elongation, weight gain, chlorophyll a and chlorophyll b decreased by approximately 50%, 85%, 77%, 55% and 70%, respectively, as a result of TFS treatment compared to the control. In the TFS group, the mitotic index fell by 28% compared to the control group, but chromosomal abnormalities, micronuclei frequency and tail DNA percentage increased. Fragment, vagrant chromosome, sticky chromosome, uneven chromatin distribution, bridge, vacuole-containing nucleus, reverse polarization and irregular mitosis were the chromosomal abnormalities observed in the TFS group. The levels of proline (2.17-fold) and malondialdehyde (2.71-fold), as well as the activities of catalase (2.75-fold) and superoxide dismutase (2.03-fold) were increased by TFS in comparison to the control. TFS-provoked meristematic disorders were damaged epidermis and cortex cells, flattened cell nucleus and thickened cortex cell wall. Gbex combined with TFS relieved all these TFS-induced stress signs in a dose-dependent manner. This investigation showed that Gbex can play protective role in A. cepa against the phytotoxicity, genotoxicity and oxidative damage caused by TFS. The results demonstrated that Gbex had this antioxidant and antigenotoxic potential owing to its high phenolic content.


Asunto(s)
Acetatos , Ginkgo biloba , Cebollas , Estrés Oxidativo , Extractos Vegetales , Estrobilurinas , Extractos Vegetales/farmacología , Cebollas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Acetatos/farmacología , Metacrilatos/toxicidad , Antioxidantes/farmacología , Antioxidantes/metabolismo , Daño del ADN/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Iminas/farmacología , Iminas/toxicidad
11.
Int J Mol Sci ; 25(16)2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39201671

RESUMEN

Diabetic nephropathy, a leading cause of end-stage renal disease, accounts for significant morbidity and mortality. It is characterized by microinflammation in the glomeruli and myofibroblast activation in the tubulointerstitium. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is shown to possess anti-inflammatory and anti-fibrotic properties, implying its renal-protective potential. This study investigates which type of component can reduce the damage caused by diabetic nephropathy in a single setting. The ethyl acetate (EtOAc) layer was demonstrated to provoke peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ activities in renal mesangial cells by dual luciferase reporter assay. In a high glucose (HG)-cultured mesangial cell model, the EtOAc layer substantially inhibited HG-induced elevations of interleukin-1ß, transforming growth factor-ß1 (TGF-ß1), and fibronectin, whereas down-regulated PPAR-γ was restored. In addition, among the extracts of S. miltiorrhiza, the EtOAc layer effectively mitigated TGF-ß1-stimulated myofibroblast activation. The EtOAc layer also showed a potent ability to attenuate renal hypertrophy, proteinuria, and fibrotic severity by repressing diabetes-induced proinflammatory factor, extracellular matrix accumulation, and PPAR-γ reduction in the STZ-induced diabetes mouse model. Our findings, both in vitro and in vivo, indicate the potential of the EtOAc layer from S. miltiorrhiza for future drug development targeting diabetic nephropathy.


Asunto(s)
Acetatos , Diabetes Mellitus Experimental , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Fibrosis , PPAR gamma , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , PPAR gamma/metabolismo , Acetatos/química , Acetatos/farmacología , Masculino , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Fibronectinas/metabolismo , Ratones Endogámicos C57BL , PPAR alfa/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Glucosa/metabolismo
12.
Mol Med ; 30(1): 130, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39182021

RESUMEN

BACKGROUND: Vascular calcification is a common vascular lesion associated with high morbidity and mortality from cardiovascular events. Antibiotics can disrupt the gut microbiota (GM) and have been shown to exacerbate or attenuate several human diseases. However, whether antibiotic-induced GM disruption affects vascular calcification remains unclear. METHODS: Antibiotic cocktail (ABX) treatment was utilized to test the potential effects of antibiotics on vascular calcification. The effects of antibiotics on GM and serum short-chain fatty acids (SCFAs) in vascular calcification mice were analyzed using 16 S rRNA gene sequencing and targeted metabolomics, respectively. Further, the effects of acetate, propionate and butyrate on vascular calcification were evaluated. Finally, the potential mechanism by which acetate inhibits osteogenic transformation of VSMCs was explored by proteomics. RESULTS: ABX and vancomycin exacerbated vascular calcification. 16 S rRNA gene sequencing and targeted metabolomics analyses showed that ABX and vancomycin treatments resulted in decreased abundance of Bacteroidetes in the fecal microbiota of the mice and decreased serum levels of SCFAs. In addition, supplementation with acetate was found to reduce calcium salt deposition in the aorta of mice and inhibit osteogenic transformation in VSMCs. Finally, using proteomics, we found that the inhibition of osteogenic transformation of VSMCs by acetate may be related to glutathione metabolism and ubiquitin-mediated proteolysis. After adding the glutathione inhibitor Buthionine sulfoximine (BSO) and the ubiquitination inhibitor MG132, we found that the inhibitory effect of acetate on VSMC osteogenic differentiation was weakened by the intervention of BSO, but MG132 had no effect. CONCLUSION: ABX exacerbates vascular calcification, possibly by depleting the abundance of Bacteroidetes and SCFAs in the intestine. Supplementation with acetate has the potential to alleviate vascular calcification, which may be an important target for future treatment of vascular calcification.


Asunto(s)
Acetatos , Antibacterianos , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Calcificación Vascular , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Calcificación Vascular/metabolismo , Calcificación Vascular/etiología , Calcificación Vascular/tratamiento farmacológico , Ratones , Ácidos Grasos Volátiles/metabolismo , Acetatos/farmacología , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Masculino , Osteogénesis/efectos de los fármacos , ARN Ribosómico 16S/genética , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Vancomicina/efectos adversos , Vancomicina/farmacología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos
13.
BMC Plant Biol ; 24(1): 807, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39187785

RESUMEN

Cadmium (Cd) is a biologically non-essential heavy metal, a major soil pollutant, and extremely harmful to plants. The phytohormone methyl jasmonate (MeJA) plays an important role in plant heavy-metal resistance. However, the understanding of the effects of MeJA supply level on alleviating Cd toxicity in plants is limited. Here, we investigated how MeJA regulated the development of physiological processes and cell wall modification in Cosmos bipinnatus. We found that low concentrations of MeJA increased the dry weight of seedlings under 120 µM Cd stress by reducing the transport of Cd from roots to shoots. Moreover, a threshold concentration of exogenous MeJA increased the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in plant roots, the concentration of Cd in the root cell wall, and the contents of pectin and hemicellulose 1 polysaccharides, through converting Cd into pectin-bound forms. These results suggested that MeJA mitigated Cd toxicity by modulating root cell wall polysaccharide and functional group composition, especially through pectin polysaccharides binding to Cd, with effects on Cd transport capacity, specific chemical forms of Cd, and homeostatic antioxidant systems in C. bipinnatus.


Asunto(s)
Acetatos , Cadmio , Ciclopentanos , Oxilipinas , Reguladores del Crecimiento de las Plantas , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Acetatos/farmacología , Cadmio/toxicidad , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Contaminantes del Suelo/toxicidad , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Antioxidantes/metabolismo , Superóxido Dismutasa/metabolismo
14.
Cell Metab ; 36(9): 1998-2014.e15, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39163862

RESUMEN

Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the molecular mechanisms remain poorly understood. This study investigated how sleep disturbances contribute to metabolic imbalance and cognition impairment using a chronic sleep fragmentation (SF) mouse model. SF mice exhibited impaired cognition, glucose metabolism, and insulin sensitivity compared with controls. We identified increased acetate levels in hypothalamic astrocytes as a defensive response in SF mice. Through acetate infusion or astrocyte-specific Acss1 deletion to elevate acetate levels, we observed mitigated metabolic and cognitive impairments in SF mice. Mechanistically, acetate binds and activates pyruvate carboxylase, thereby restoring glycolysis and the tricarboxylic acid cycle. Among individuals most commonly affected by SF, patients with obstructive sleep apnea exhibited elevated acetate levels when coupled with type 2 diabetes. Our study uncovers the protective effect of acetate against sleep-induced metabolic and cognitive impairments.


Asunto(s)
Acetatos , Cognición , Ratones Endogámicos C57BL , Privación de Sueño , Animales , Acetatos/metabolismo , Acetatos/farmacología , Ratones , Masculino , Privación de Sueño/metabolismo , Humanos , Astrocitos/metabolismo , Disfunción Cognitiva/metabolismo
15.
Bioorg Chem ; 152: 107727, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39167872

RESUMEN

Inflammation management presents a critical challenge in modern medicine, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a widely used therapeutic option. However, their efficacy is often accompanied by significant gastrointestinal adverse effects, necessitating the exploration of safer alternatives, particularly through the investigation of cyclooxygenase-2 (COX-2) inhibitors. This study endeavors to address this imperative through the synthesis and evaluation of pyrazoline-phenoxyacetic acid derivatives. Among the synthesized compounds, 6a and 6c emerged as promising candidates, demonstrating potent COX-2 inhibition with IC50 values of 0.03 µM for both and selectivity index = 365.4 and 196.9, respectively. Furthermore, these compounds exhibited efficacy in mitigating formalin-induced edema in male Wistar rats, accompanied by favorable safety profiles upon histological examination of vital organs. Comprehensive safety assessments, including evaluation of creatinine, AST, and ALT enzymatic as well as troponin T and creatine kinase-MB levels, further reinforce the promising attributes of the synthetic candidates. Molecular docking studies endorsed by molecular dynamic simulations corroborate the biological findings, elucidating significant protein-ligand interactions at COX-2 active sites indicative of therapeutic potential.


Asunto(s)
Antiinflamatorios no Esteroideos , Inhibidores de la Ciclooxigenasa 2 , Ciclooxigenasa 2 , Edema , Ratas Wistar , Animales , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/química , Masculino , Ciclooxigenasa 2/metabolismo , Edema/tratamiento farmacológico , Edema/inducido químicamente , Ratas , Relación Estructura-Actividad , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Estructura Molecular , Acetatos/química , Acetatos/farmacología , Acetatos/síntesis química , Simulación del Acoplamiento Molecular , Humanos , Relación Dosis-Respuesta a Droga , Formaldehído , Farmacóforo
16.
Plant Physiol Biochem ; 215: 108953, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151367

RESUMEN

Bioactive secondary metabolites from fungi, including Trichoderma, are an excellent source of plant biostimulants. Although production of novel biostimulants from known microbes is critical, challenging them may produce novel bioactive compounds. With this hypothesis, the study used live Fusarium chlamydosporum (FOL7) culture as the inducer during T. harzianum (IF63) growth in broth. Plate assays and gas chromatography-mass spectrometry (GC-MS) analysis were used to characterise the metabolites. Microscopy, pot experiments and, biochemical estimations of the defence-related enzymes in tomato plants established the biostimulant activity of the induced Trichoderma metabolites. Fungal crude metabolites (FCM) obtained from IF63+FOL7 extracts (TF.ex) showed increased antimicrobial activity. TF.ex at 50 µg mL-1, inhibited the FOL7 growth by 68.33% compared to the Trichoderma alone extract. Scanning electron microscopy (SEM) revealed morphological disruption of FOL7 mycelia by TF.ex. GC-MS analysis of the extracts revealed the presence of approximately 64 compounds, of which at least 13 were detected explicitly in TF.ex. Methyl (3-oxo-2-pentylcyclopentyl) acetate (Methyl dihydrojasmonate), a lipid functionally related to jasmonic acid, was the major metabolite (∼21%) present in TF.ex. Tomato seed dressing with TF.ex promoted plant growth and induced systemic resistance against FOL7 compared to alone Trichoderma and Fusarium extracts. The TF.ex treatment increased the superoxide dismutase (33%) and catalase activity by 2.5-fold in tomato plants. The study concludes that fungal secondary metabolites may be modulated by providing appropriate challenges to produce effective metabolite-based biostimulants for agricultural applications.


Asunto(s)
Acetatos , Ciclopentanos , Fusarium , Oxilipinas , Enfermedades de las Plantas , Solanum lycopersicum , Trichoderma , Solanum lycopersicum/microbiología , Solanum lycopersicum/metabolismo , Ciclopentanos/metabolismo , Ciclopentanos/farmacología , Oxilipinas/metabolismo , Acetatos/metabolismo , Acetatos/farmacología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Resistencia a la Enfermedad/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Hypocreales
17.
J Med Chem ; 67(15): 12855-12867, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39077778

RESUMEN

The overexpression of HER2 is pivotal in the initiation and progression of breast cancer. Developing HER2-targeted radiotracers is crucial for noninvasive assessment of HER2 expression, patient selection for HER2-targeted therapy, monitoring treatment response, and identifying resistance. Here, we reported a nonsite-specific coupled radiotracer, 68Ga-NOTA-SNA004-His6, and a site-specific coupled radiotracer, 68Ga-NODAGA-SNA004-GSC, based on a novel HER2 nanobody, SNA004. Both radiotracers exhibited high affinity, specific targeting, and rapid clearance in vitro and in vivo. Additionally, these tracers and trastuzumab showed noncompetitive binding to HER2. Compared to 68Ga-NOTA-SNA004-His6, 68Ga-NODAGA-SNA004-GSC demonstrated significantly reduced renal and liver uptake. PET/CT imaging with 68Ga-NODAGA-SNA004-GSC sensitively detected the responsiveness of various tumor models to trastuzumab and its antibody-drug conjugates (ADCs). Overall, the site-specific coupled radiotracer 68Ga-NODAGA-SNA004-GSC offered significant advantages in biodistribution and signal-to-noise ratio, making it a valuable tool for monitoring HER2 expression levels before, during, and after trastuzumab and ADC treatment.


Asunto(s)
Radioisótopos de Galio , Compuestos Heterocíclicos con 1 Anillo , Inmunoconjugados , Receptor ErbB-2 , Anticuerpos de Dominio Único , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Humanos , Inmunoconjugados/química , Inmunoconjugados/farmacocinética , Inmunoconjugados/farmacología , Animales , Radioisótopos de Galio/química , Femenino , Compuestos Heterocíclicos con 1 Anillo/química , Anticuerpos de Dominio Único/química , Ratones , Distribución Tisular , Línea Celular Tumoral , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Acetatos/química , Acetatos/farmacología , Radiofármacos/química , Ratones Desnudos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos
18.
Food Chem ; 459: 140360, 2024 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38991443

RESUMEN

Methyl jasmonate (MJ) has potential to regulate fruit ripening and quality. 'Yoho' and 'Jiro' persimmons were sprayed with MJ (0, 2, 4, and 6 mM), four weeks before anticipated harvest to evaluate its effects on fruit colour and bioactive compounds. Preharvest MJ application significantly improved fruit colour with increased a*, b*, chroma, and colour index. The MJ 6 mM application had significantly enhanced soluble solids content (SSC), reduced total chlorophyll content in peel and pulp, and soluble and total tannins in persimmons. MJ treatments exhibited higher contents of total phenolics, flavonoids, carotenoids, and antioxidant activities. Additionally, MJ treatments enhanced the activities of shikimate dehydrogenase (SKDH), phenylalanine ammonia-lyase (PAL), catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and lipoxygenase (LOX) enzymes. Overall, pre-harvest MJ application at 6 mM four weeks before anticipated harvest could be useful for advancing colour and improving bioactive compounds in 'Yoho' and 'Jiro' persimmons.


Asunto(s)
Acetatos , Antioxidantes , Color , Ciclopentanos , Diospyros , Frutas , Oxilipinas , Oxilipinas/farmacología , Oxilipinas/metabolismo , Antioxidantes/metabolismo , Ciclopentanos/farmacología , Ciclopentanos/metabolismo , Frutas/química , Frutas/crecimiento & desarrollo , Frutas/metabolismo , Frutas/efectos de los fármacos , Acetatos/farmacología , Acetatos/metabolismo , Diospyros/química , Diospyros/crecimiento & desarrollo , Diospyros/metabolismo , Proteínas de Plantas/metabolismo , Fenoles/metabolismo , Fenoles/análisis , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Flavonoides/análisis , Flavonoides/metabolismo , Superóxido Dismutasa/metabolismo , Clorofila/metabolismo , Clorofila/análisis , Carotenoides/metabolismo , Carotenoides/análisis
19.
Pestic Biochem Physiol ; 203: 106005, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39084800

RESUMEN

Odorant-binding proteins (OBPs) play key roles in host plant location by insects, and can accordingly serve as important targets for the development of attractants. In this study, we detected the high expression of SlitOBP34 in male antennae of Spodoptera litura. Subsequently, the fluorescence competitive binding experiments displayed that the SlitOBP34 protein has binding affinity for different ligands. Then, protein-ligand interaction analyses found the presence of six amino acid residues may serve as key recognition sites. Further electroantennographic and biobehavioral assessments revealed that the electrophysiological responses of male antennae were evoked in response to stimulation with the six identified host volatiles, and that these volatiles attracted male moths to varying extents. Notably, low concentrations of benzaldehyde, 1-hexanol, and cis-3-hexenyl acetate were found to have significant attractant effects on male moths, thereby identifying these three host volatiles as potential candidates for the development of male attractants. These findings advance our current understanding of the olfactory-encoded mechanisms of host plants selection in S. litura and have enabled us to develop novel adult attractants for controlling the pest in the future.


Asunto(s)
Antenas de Artrópodos , Proteínas de Insectos , Receptores Odorantes , Spodoptera , Compuestos Orgánicos Volátiles , Animales , Spodoptera/efectos de los fármacos , Masculino , Receptores Odorantes/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Compuestos Orgánicos Volátiles/metabolismo , Compuestos Orgánicos Volátiles/farmacología , Antenas de Artrópodos/metabolismo , Hexanoles/farmacología , Hexanoles/metabolismo , Acetatos/metabolismo , Acetatos/farmacología , Benzaldehídos
20.
Int Immunopharmacol ; 139: 112700, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39018685

RESUMEN

BACKGROUNDS & AIM: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats. MATERIALS AND METHODS: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1ß (IL-1ß), and cleaved caspase-3 immuno-expressions were also evaluated. RESULTS: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1ß and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1ß), and apoptotic (caspase-3) parameters. CONCLUSION: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1ß signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects.


Asunto(s)
Acetatos , Ciclofosfamida , Ciclopropanos , Interleucina-1beta , Antagonistas de Leucotrieno , Proteína con Dominio Pirina 3 de la Familia NLR , Placenta , Quinolinas , Ratas Wistar , Transducción de Señal , Sulfuros , Animales , Femenino , Embarazo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Ciclofosfamida/toxicidad , Ciclofosfamida/efectos adversos , Quinolinas/farmacología , Quinolinas/uso terapéutico , Acetatos/uso terapéutico , Acetatos/farmacología , Interleucina-1beta/metabolismo , Placenta/efectos de los fármacos , Placenta/patología , Placenta/metabolismo , Antagonistas de Leucotrieno/farmacología , Antagonistas de Leucotrieno/uso terapéutico , Transducción de Señal/efectos de los fármacos , Ratas , Factor de Crecimiento Placentario/metabolismo , Estrés Oxidativo/efectos de los fármacos , Inflamasomas/metabolismo , Apoptosis/efectos de los fármacos
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