RESUMEN
Transcriptome sequencing was employed to mine the simple sequence repeat(SSR) locus information of Saposhnikovia divaricata and design specific primers, which aimed to provide a basis for the research on the genetic diversity of S. divaricata germplasm resources. The seed purity, 1 000-seed weight, germination rate, and seed vigor were determined. MISA was used to obtain the SSR locus information from 12 606 unigene longer than 1 kb in the transcriptome database. Forty-three pairs of SSR primers designed in Primer 3 were used to analyze the polymorphism of 28 S. divaricata samples of different sources. The results showed that there were differences in the seed purity, 1 000-seed weight, germination rate, vigor, and seed length and width among S. divaricata samples of different sources. Particularly, the germination rate and seed vigor had significant differences, and HB-ZJK1, NMG-CF4, NMG-BT, NMG-HLE1, and NMG-CF2 had significantly higher 1 000-seed weight, germination rate, and seed vigor than the samples of other sources. Among the 86 233 unigene, 12 606(14.62%) unigene contained 15 958 SSR loci, with one SSR locus every 5 009 bp on average. The SSR loci were mainly single nucleotide and dinucleotide repeats, which were dominated by G/C and TC/AG, respectively. All the primers were screened by using 28 S. divaricata sample from different habitats, and the primers corresponding to the amplification products with clear bands and stable polymorphism were obtained. The clustering results of the biological characteristics and genetic diversity of the 28 S. divaricata samples were basically consistent, and the samples of the same origin(HB-AG1, HB-AG2, HB-ZJK1, and HB-ZJK2) generally gathered together and had close genetic relationship. The SSRs in S. divaricata transcriptome has high frequency, rich types, and high polymorphism, which provides candidate molecular markers for the germplasm identification, genetic map construction, and molecular-assisted breeding.
Asunto(s)
Apiaceae , Transcriptoma , Polimorfismo Genético , Repeticiones de Microsatélite/genética , Apiaceae/genética , Etiquetas de Secuencia ExpresadaRESUMEN
Vascular remodeling plays a vital role in hypertensive diseases and is an important target for hypertension treatment. Irisin, a newly discovered myokine and adipokine, has been found to have beneficial effects on various cardiovascular diseases. However, the pharmacological effect of irisin in antagonizing hypertension-induced vascular remodeling is not well understood. In the present study, we investigated the protection and mechanisms of irisin against hypertension and vascular remodeling induced by angiotensin II (Ang II). Adult male mice of wild-type, FNDC5 (irisin-precursor) knockout, and FNDC5 overexpression were used to develop hypertension by challenging them with Ang II subcutaneously in the back using a microosmotic pump for 4 weeks. Similar to the attenuation of irisin on Ang II-induced VSMCs remodeling, endogenous FNDC5 ablation exacerbated, and exogenous FNDC5 overexpression alleviated Ang II-induced hypertension and vascular remodeling. Aortic RNA sequencing showed that irisin deficiency exacerbated intracellular calcium imbalance and increased vasoconstriction, which was parallel to the deterioration in both ER calcium dysmetabolism and ER stress. FNDC5 overexpression/exogenous irisin supplementation protected VSMCs from Ang II-induced remodeling by improving endoplasmic reticulum (ER) homeostasis. This improvement includes inhibiting Ca2+ release from the ER and promoting the re-absorption of Ca2+ into the ER, thus relieving Ca2+-dependent ER stress. Furthermore, irisin was confirmed to bind to its receptors, αV/ß5 integrins, to further activate the AMPK pathway and inhibit the p38 pathway, leading to vasoprotection in Ang II-insulted VSMCs. These results indicate that irisin protects against hypertension and vascular remodeling in Ang II-challenged mice by restoring calcium homeostasis and attenuating ER stress in VSMCs via activating AMPK and suppressing p38 signaling.
Asunto(s)
Angiotensina II , Hipertensión , Ratones , Masculino , Animales , Angiotensina II/metabolismo , Fibronectinas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Remodelación Vascular , Calcio/metabolismo , Músculo Liso Vascular/metabolismo , Estrés del Retículo EndoplásmicoRESUMEN
In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.