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Métodos Terapéuticos y Terapias MTCI
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1.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38612877

RESUMEN

Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.


Asunto(s)
Hedera , Ácido Oleanólico/análogos & derivados , Saponinas , Glicosiltransferasas/genética
2.
Int J Nanomedicine ; 19: 2359-2375, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476276

RESUMEN

Background: Molybdenum diselenide (MoSe2), as a nano near-infrared absorber, has been widely studied in the field of photothermal therapy of cancer. However, there is little research on its application in the treatment of human choriocarcinoma. Methods and Results: In this paper, a new type of carbon-coated MoSe2 (MEC) nanoparticles was prepared by a one-step hydrothermal method. The chemical characterization including SEM, TEM, EDS, XRD, FT-IR, TGA, Roman, and XPS showed that MEC was successfully synthesized. MEC exhibited a high photothermal conversion efficiency (50.97%) and extraordinary photothermal stability under laser irradiation. The cell experiment results showed that MEC had good biocompatibility on normal cells while significant photothermal effect on human choriocarcinoma (JEG-3) cells, achieving a good anticancer effect. The level of reactive oxygen species (ROS) in JEG-3 cells was significantly increased under the combination of MEC nanoparticles and near-infrared radiation. MEC nanoparticles could induce apoptosis of JEG-3 cells in combination with near-infrared radiation. Finally, transcriptomic analysis verified that MEC combined with laser radiation could inhibit DNA replication and induce apoptosis, thus improving its therapeutic effect on human choriocarcinoma. Conclusion: MEC nanoparticles exert an excellent photothermal effect and may become an important candidate drug for the treatment of human choriocarcinoma.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Humanos , Fototerapia , Línea Celular Tumoral , Espectroscopía Infrarroja por Transformada de Fourier , Nanopartículas/química
3.
Genes (Basel) ; 15(1)2024 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-38254968

RESUMEN

In traditional Chinese medicine, Angelica dahurica is a valuable herb with numerous therapeutic applications for a range of ailments. There have not yet been any articles on the methodical assessment and choice of the best reference genes for A. dahurica gene expression studies. Real-time quantitative PCR (RT-qPCR) is widely employed as the predominant method for investigating gene expression. In order to ensure the precise determination of target gene expression outcomes in RT-qPCR analysis, it is imperative to employ stable reference genes. In this study, a total of 11 candidate reference genes including SAND family protein (SAND), polypyrimidine tract-binding protein (PTBP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), TIP41-like protein (TIP41), cyclophilin 2 (CYP2), elongation factor 1 α (EF1α), ubiquitin-protein ligase 9 (UBC9), tubulin ß-6 (TUB6), thioredoxin-like protein YLS8 (YLS8), and tubulin-α (TUBA) were selected from the transcriptome of A. dahurica. Subsequently, three statistical algorithms (geNorm, NormFinder, and BestKeeper) were employed to assess the stability of their expression patterns across seven distinct stimulus treatments. The outcomes obtained from these analyses were subsequently amalgamated into a comprehensive ranking using RefFinder. Additionally, one target gene, phenylalanine ammonia-lyase (PAL), was used to confirm the effectiveness of the selected reference genes. According to the findings of this study, the two most stable reference genes for normalizing the expression of genes in A. dahurica are TIP41 and UBC9. Overall, our research has determined the appropriate reference genes for RT-qPCR in A. dahurica and provides a crucial foundation for gene screening and identifying genes associated with the biosynthesis of active ingredients in A. dahurica.


Asunto(s)
Angelica , Angelica/genética , Tubulina (Proteína) , Actinas , Reacción en Cadena en Tiempo Real de la Polimerasa , Estrés Fisiológico
4.
Phys Chem Chem Phys ; 25(42): 29289-29302, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37876253

RESUMEN

Bacterial DNA phosphorothioate (PT) modification provides a specific anchoring site for sulfur-binding proteins (SBDs). Besides, their recognition patterns include phosphate links and bases neighboring the PT-modified site, thereby bringing about genome sequence-dependent properties in PT-related epigenetics. Here, we analyze the contributions of the DNA backbone (phosphates and deoxyribose) and bases bound with two SBD proteins in Streptomyces pristinaespiralis and coelicolor (SBDSco and SBDSpr). The chalcogen-hydrophobic interactions remained constantly at the anchoring site while the adjacent bases formed conditional and distinctive non-covalent interactions. More importantly, SBD/PT-DNA interactions were not limited within the traditional "4-bp core" range from 5'-I to 3'-III but extended to upstream 5'-II and 5'-III bases and even 5''-I to 5''-III at the non-PT-modified complementary strand. From the epigenetic viewpoint, bases 3'-II, 5''-I, and 5''-III of SBDSpr and 3'-II, 5''-II, and 5''-III of SBDSco present remarkable differentiations in the molecular recognitions. From the protein viewpoint, H102 in SBDSpr and R191 in SBDSco contribute significantly while proline residues at the PT-bound site are strictly conserved for the PT-chalcogen bond. The mutual and make-up mutations are proposed to alter the SBD/PT-DNA recognition pattern, besides additional chiral phosphorothioate modifications on phosphates 5'-II, 5'-II, 3'-I, and 3'-II.


Asunto(s)
Calcógenos , ADN , ADN/química , ADN Bacteriano/química , Proteínas Bacterianas/metabolismo , Fosfatos/química
5.
Front Plant Sci ; 13: 973665, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36119590

RESUMEN

Drought restricts the growth of alpine grassland vegetation. This study aimed to explore a new technical system to improve the drought resistance of forage grass. Qinghai cold-land Poa pratensis seedlings were used in the drought stress experiment. A combination of abscisic acid (ABA) and polyacrylamide (PAM) were used to affect the growth, leaf physiology, soil enzyme activity, and rhizosphere microbial diversity of P. pratensis. The fresh leaf weight and root surface area were significantly increased after ABA-PAM combined treatment, while root length was significantly reduced. Besides, the leaf catalase (CAT) and superoxide dismutase (SOD) enzyme activity, proline and chlorophyll content, increased after the treatment, while malondialdehyde (MDA) content decreased. The treatment also increased sucrase, urease, and alkaline protease activities in rhizosphere soil, while decreasing acid phosphatase and neutral phosphatase enzyme activities. ABA-PAM combined treatment enhanced the rhizosphere microbial community and forage drought resistance by altering the abundance of various dominant microorganisms in the rhizosphere soil. The relative abundances of Actinobacteria, Chloroflexi, and Acidobacteria decreased, while Proteobacteria, Firmicutes, and Ascomycota increased. Unlike the relative abundance of Gibberella that decreased significantly, Komagataeibacter, Lactobacillus, Pichia, and Dekkera were significantly increased. Single-factor collinearity network analysis revealed a close relationship between the different rhizosphere microbial communities of forage grass, after ABA-PAM treatment. This study implies that ABA-PAM combined treatment can improve the drought resistance of forages. Therefore, it provides a theoretical and practical basis for restoring drought-induced grassland degradation.

6.
Dis Markers ; 2022: 9082576, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35692879

RESUMEN

Information regarding the function of Melilotus officinalis (L.) Pall. in skeletal muscles is still unknown. In this study, we explored the possible regulatory targets of M. (L.) Pall. that affects the repair patterns in chronic muscle injury. We analyzed the potential target genes and chemical composition of M. (L.) Pall. and constructed a "drug-component-disease target genes" network analysis. Five active ingredients and 87 corresponding targets were obtained. Muscle-tendon junction (MTJ) cells were used to perform receptor-ligand marker analysis using the CellphoneDB algorithm. Targets of M. (L.) Pall. were screened further for the cellular ligand-receptor protein action on MTJs. Enrichment analysis suggests that those protein-associated ligand receptors may be associated with a range of intercellular signaling pathways. Molecular docking validation was then performed. Five proteins (CCL2, VEGFA, MMP2, MET, and EGFR) may be regulated by the active ingredient luteolin and scoparone. Finally, molecular dynamics simulations revealed that luteolin can stably target binding to MMP2. M. (L.) Pall. influences skeletal muscle repair patterns by affecting the fibroblast interactions in the muscle-tendon junctions through the active ingredients luteolin and scoparone.


Asunto(s)
Medicamentos Herbarios Chinos , Melilotus , Humanos , Ligandos , Luteolina , Metaloproteinasa 2 de la Matriz , Melilotus/química , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Músculo Esquelético
7.
Int J Mol Sci ; 23(3)2022 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-35163190

RESUMEN

WRKYs, a large family of transcription factors, are involved in plant response to biotic and abiotic stresses, but the role of them in tomato resistance to Oidium neolycopersici is still unclear. In this study, we evaluate the role of WRKYs in powdery mildew-resistant wild tomato (Solanum habrochaites) LA1777 defense against O. neolycopersici strain lz (On-lz) using a combination of omics, classical plant pathology- and cell biology-based approaches. A total of 27 WRKYs, belonging to group I, II, and III, were identified as differentially expressed genes in LA1777 against On-lz. It was found that expression of ShWRKY41 was increased after Pseudomonas syringae pv. tomato (Pst) DC3000, On-lz and Botrytiscinerea B05 inoculation or ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) treatment. GUS staining of ShWRKY41 promoter indicated that the expression of ShWRKY41 could be induced by SA and ethylene. Furthermore, ShWRKY41 gene silencing reduced the resistance to On-lz infection by decreasing the generation of H2O2 and HR in LA1777 seedlings. Overall, our research suggests that ShWRKY41 plays a positive role in defense activation and host resistance to O. neolycopersici in wild tomato (S. habrochaites) LA1777.


Asunto(s)
Resistencia a la Enfermedad/genética , Solanum/genética , Factores de Transcripción/genética , Proteínas de Arabidopsis/genética , Ascomicetos/genética , Ascomicetos/patogenicidad , Hongos/genética , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Plantas/metabolismo , Plantones/metabolismo
8.
J Sci Food Agric ; 101(10): 4350-4360, 2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-33420734

RESUMEN

BACKGROUND: Melt crystallization is typically recognized as a highly efficient and green method for oil fractionation. This work concentrated on novel layer melt crystallization for preparing desirable olein and stearin products from palm oil and the evaluation of fraction quality. Layer melt crystallization was performed at various temperatures and the effects on fractions were evaluated using iodine value (IV), solid fat content (SFC) and melting point. The lipid composition, thermal and crystallization properties, and phase behaviors of the final optimized fractions were determined using gas chromatography, high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry and differential scanning calorimetry. RESULTS: Increasing crystallization tube temperatures under the same jacket temperature increased the melting point and SFC, while decreasing the IV of the olein product. Opposite results were observed for the stearin product. Major fatty acids in fractions were determined as palmitic acid and oleic acid. 1,2-Dioleoyl-3-palmitoylglycerol and 1,3-dipalmitoyl-2-oleoylglycerol were identified as the main triacylglycerols in olein and stearin fractions, respectively. A critical effect of crystallization temperature on co-crystallization of oleins and stearins was revealed. A transition from plate-like crystal growth to spherulitic growth with spontaneous nucleation was indicated in palm oil and stearin fractions with increasing crystallization temperature. As for olein fractions, a temperature increase resulted in heterogeneous nucleation from instantaneous nucleation. CONCLUSIONS: Novel layer melt crystallization was successfully applied and optimized for fractionating palm oil. The composition and property changes of obtained fractions were analyzed and explained at both macroscopic and microscopic levels. © 2021 Society of Chemical Industry.


Asunto(s)
Lípidos/química , Ácido Oléico/química , Aceite de Palma/química , Ácidos Esteáricos/química , Rastreo Diferencial de Calorimetría , Cromatografía Líquida de Alta Presión , Cristalización , Espectrometría de Masas , Temperatura
9.
Int J Pharm ; 487(1-2): 250-9, 2015 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-25899285

RESUMEN

Teniposide (VM-26) is a semisynthetic derivative of podophyllotoxin effective for the treatment of many types of tumors. However, the poor water solubility and adverse effects restrict its clinical use. Our study aimed to develop a novel phospholipid complex albumin nanoparticle (VM-E80-AN) to reduce the systemic toxicity and enhance antitumor activity of VM-26. Egg yolk lecithin E80 and human serum albumin (HSA) were used as the main excipients to replace Cremophor EL in the commercial formulation. The physicochemical properties of VM-E80-AN were characterized to optimize the formulation. Cell and animal studies were further carried out to estimate its tumor inhibition efficacy, biodistribution, and toxicity. Comparison between VM-26 solution and VM-E80-AN showed that VM-E80-AN significantly reduced the toxicity of VM-26 and enhanced the anticancer efficacy of the drug. Thus, VM-E80-AN represents a safe and promising formulation of teniposide for clinical application.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Tenipósido/administración & dosificación , Tenipósido/farmacología , Albúminas , Animales , Antineoplásicos Fitogénicos/efectos adversos , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Excipientes , Humanos , Lecitinas , Masculino , Ratones , Ratones Endogámicos C57BL , Nanopartículas , Ratas , Ratas Wistar , Tenipósido/efectos adversos , Distribución Tisular , Ensayos Antitumor por Modelo de Xenoinjerto
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