Transcriptome and HPLC Analysis Reveal the Regulatory Mechanisms of Aurantio-Obtusin in Space Environment-Induced Senna obtusifolia Lines

Senna obtusifolia is a famous medicinal plant that is widely used in Asian countries. Its seed plays an important role in the treatment of many diseases because it contains various anthraquinones and flavonoids. Our previous studies have indicated that three space environment-induced S. obtusifolia lines (SP-lines) i.e., QC10, QC29, and QC46, have higher seed yield and aurantio-obtusin (AO) content. However, the underlying mechanism of higher AO content in SP-lines is still unknown. Herein, transcriptome sequencing and HPLC were employed to analyze the differences between SP-lines and ground control (GC3) and elucidate the regulatory mechanisms of AO accumulation in SP-lines. The results show that 4002 differentially expressed genes (DEGs) were identified in SP-lines versus (vs.) GC3. DEGs in the QC10 vs. GC3, QC29 vs. GC3, and QC46 vs. GC3 comparisons were classified into 28, 36, and 81 GO terms and involved in 63, 74, and 107 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. KEGG pathway and gene expression analysis revealed that DEGs involved in anthraquinone pathways were significantly elevated in QC10 and QC46. Integrating the results of GO annotation, KEGG enrichment, and gene expression analysis, we propose that the elevated genes such as DAHPS, DHQS, and MenB enhance the metabolic flux in the anthraquinone pathway and promote AO content in QC10 and QC46. Taken together, this study elucidated the mechanism of AO content in SP-lines and provides valuable genetic information for S. obtusifolia. In addition, to the best of our knowledge, this study presents the first transcriptome analysis of environment-induced medicinal plants and paves the way to select elite S. obtusifolia varieties in the future

Remediation of deterioration in microbial structure in continuous Pinellia ternata cropping soil by crop rotation

Pinellia ternata is a traditional Chinese herb that suffers from continuous cropping (CC), which significantly decreases both yield and quality. The influence of CC on microbiome in P. ternata rhizosphere and the effects of remediation on microbiota by rotational cropping (CR) were assessed by Illumina high-throughput sequencing technology. CC tends to decrease the Îą-diversities along with cultivation time, whereas CR tends to increase them. Differentially abundant analysis showed that microbial structure was important in maintaining the health status of P. ternata rhizosphere. Results suggested that CC soils were mainly enriched for Pseudomonas, Rhizobium, and Streptophyta operational taxonomic units (OTUs), while the CR soils were mainly enriched for Rhizobium, Pseudomonas, Flavobacterium, Sphingomonas, Rhizobacter, and Arthrobacter OTUs. On the basis of the community dissimilarities, we grouped all sample replicates into three post hoc clusters in which soils were defined as healthy, health-suppressed, and health-depressed soils. The three soil types represented different soil physicochemical properties. The activities of the microbiome features, including ammonia oxidizer, sulfate reducer, nitrite reducer, dehalogenation, xylan degrader, sulfide oxidizer, nitrogen fixation, atrazine metabolism, chitin degradation, degraded aromatic hydrocarbons, and chlorophenol degradation, were also considerably different among the three soils.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Novel harmine derivatives as potent acetylcholinesterase and amyloid beta aggregation dual inhibitors for management of Alzheimer’s disease

AbstractIn this study, a series of potential ligands for the treatment of AD were synthesised and characterised as novel harmine derivatives modified at position 9 with benzyl piperazinyl. In vitro studies revealed that the majority of the derivatives exhibited moderate to potent inhibition against hAChE and Aβ1 − 42 aggregation. Notably, compounds 13 and 17d displayed potent drug − likeness and ADMET properties, demonstrating remarkable inhibitory activities towards AChE (IC50 = 58.76 nM and 89.38 nM, respectively) as well as Aβ aggregation (IC50 = 9.31 μM and 13.82 μM, respectively). More importantly, compounds 13 and 17d showed exceptional neuroprotective effects against Aβ1 − 42−induced SH − SY5Y damage, while maintaining low toxicity in SH − SY5Y cells. Further exploration of the mechanism through kinetic studies and molecular modelling confirmed that compound 13 could interact with both the CAS and the PAS of AChE. These findings suggested that harmine derivatives hold great potential as dual − targeted candidates for treating AD

SmGRAS1 and SmGRAS2 Regulate the Biosynthesis of Tanshinones and Phenolic Acids in Salvia miltiorrhiza

Salvia miltiorrhiza is one of the most widely used traditional Chinese medicinal plants because of its excellent performance in treating heart diseases. Tanshinones and phenolic acids are two important classes of effective metabolites, and their biosynthesis has attracted widespread interest. Here, we functionally characterized SmGRAS1 and SmGRAS2, two GRAS family transcription factors from S. miltiorrhiza. SmGRAS1/2 were highly expressed in the root periderm, where tanshinones mainly accumulated in S. miltiorrhiza. Overexpression of SmGRAS1/2 upregulated tanshinones accumulation and downregulated GA, phenolic acids contents, and root biomass. However, antisense expression of SmGRAS1/2 reduced the tanshinones accumulation and increased the GA, phenolic acids contents, and root biomass. The expression patterns of biosynthesis genes were consistent with the changes in compounds accumulation. GA treatment increased tanshinones, phenolic acids, and GA contents in the overexpression lines, and restored the root growth inhibited by overexpressing SmGRAS1/2. Subsequently, yeast one-hybrid, dual-luciferase, and electrophoretic mobility shift assays (EMSA) showed SmGRAS1 promoted tanshinones biosynthesis by directly binding to the GARE motif in the SmKSL1 promoter and activating its expression. Yeast two-hybrid assays showed SmGRAS1 interacted physically with SmGRAS2. Taken together, the results revealed that SmGRAS1/2 acted as repressors in root growth and phenolic acids biosynthesis but as positive regulators in tanshinones biosynthesis. Overall, our findings revealed the potential value of SmGRAS1/2 in genetically engineering changes in secondary metabolism. &nbsp;</p

Identification of seeds based on molecular markers and secondary metabolites in Senna obtusifolia and Senna occidentalis

Abstract Background Senna obtusifolia and Senna occidentalis (Leguminosae), whose seeds have similar appearance and chemical constituents, are easily confused in using their seeds. To elucidate the similarities and differences between S. obtusifolia seeds and S. occidentalis seeds, three molecular markers and high performance liquid chromatography (HPLC) were employed to evaluate the seeds characteristics of these two medicinal herbs. Results The results showed that selected 3 ISSR and 7 SCoT primers could distinguish S. obtusifolia seeds from S. occidentalis seeds based on the specific band and UPGMA dendrogram. ITS2 sequence indicated that the intra-specific similarity of 20 S. obtusifolia and 16 S. occidentalis was 99.79 and 100.0%, respectively, while the inter-specific similarity between S . obtusifolia and S. occidentalis was 89.58%. Although phylogenetic analysis revealed that these two species had a close relationship, they were assigned to different branches. HPLC fingerprint results showed that seeds of S. obtusifolia and S. occidentalis shared some secondary metabolites, but aurantio-obtusin was not detected in S. occidentalis seeds which could differentiate S. obtusifolia seeds from S. occidentalis seeds. Conclusions The present study not only compared the seeds characters of S. obtusifolia and S. occidentalis from molecular and secondary metabolites levels, but also provided a convenient method to identify S. obtusifolia seeds and S. occidentalis seeds effectively

14-Thienyl Methylene Matrine (YYJ18), the Derivative from Matrine, Induces Apoptosis of Human Nasopharyngeal Carcinoma Cells by Targeting MAPK and PI3K/Akt Pathways in Vitro

Background/Aims: Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck cancer with the highest incidence in South China. Previous studies have proved that matrine, a main alkaloid isolated from Sophora flavescens Ait, has antitumor activity against NPC. However, the effect is not so pronounced and the underlying mechanism remains largely unclear. Here we investigated whether 14-thienyl methylene matrine (YYJ18) that was derived from matrine could exert more effective suppression activity on NPC, along with the underlying mechanism. Methods: NPC cell lines CNE1, CNE2 and HONE1 were treated with YYJ18. Cell proliferation and apoptosis were determined by MTT assay and flow cytometry. Activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways were determined by Western blotting and quantitative RT-PCR. Results: YYJ18 remarkably inhibited proliferation and induced apoptosis of all three NPC cell lines in a dose-dependent manner, especially in CNE2 cells. Furthermore, YYJ18 treatment significantly suppressed phosphorylation of p38 in CNE2 cells, but upregulated phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt. Next, alterations in downstream signaling were found, including activation of BCL2-associated X protein (Bax), caspase-3 and inactivation of B-cell CLL/lymphoma 2 (Bcl-2). Conclusion: We demonstrate the potent inhibitory effects of 14-thienyl methylene matrine on NPC cells for the first time, which could be mediated by modulation of MAPK and PI3K/Akt pathways

Le Courrier

27 novembre 18361836/11/27 (N328)

Biodegradable Nanoglobular Magnetic Resonance Imaging Contrast Agent Constructed with Host–Guest Self-Assembly for Tumor-Targeted Imaging

Gadolinium-based macromolecular magnetic resonance imaging (MRI) contrast agents (CAs) have attracted increasing interest in tumor diagnosis. However, their practical application is potentially limited because the long-term retention of gadolinium ion in vivo will induce toxicity. Here, a nanoglobular MRI contrast agent (CA) PAMAM-PG-<i>g</i>-s-s-DOTA­(Gd) + FA was designed and synthesized on the basis of the facile host–guest interaction between β-cyclodextrin and adamantane, which initiated the self-assembly of poly­(glycerol) (PG) separately conjugated with gadolinium chelates by disulfide bonds and folic acid (FA) molecule onto the surface of poly­(amidoamine) (PAMAM) dendrimer, finally realizing the biodegradability and targeting specificity. The nanoglobular CA has a higher longitudinal relaxivity (<i>r</i>₁) than commercial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), showing a value of 8.39 mM^–1 s^–1 at 0.5 T, and presents favorable biocompatibility on the observations of cytotoxicity and tissue toxicity. Furthermore, MRI on cells and tumor-bearing mice both demonstrate the obvious targeting specificity, on the basis of which the effective contrast enhancement at tumor location was obtained. In addition, this CA exhibits the ability of cleavage to form free small-molecule gadolinium chelates and can realize minimal gadolinium retention in main organs and tissues after tumor detection. These results suggest that the biodegradable nanoglobular PAMAM-PG-<i>g</i>-s-s-DOTA­(Gd) + FA can be a safe and efficient MRI CA for tumor diagnosis

Balancing the pre-aggregation and crystallization kinetics enables high efficiency slot-die coated organic solar cells with reduced non-radiative recombination losses

Slot-die coating being compatible with the roll-to-roll technique has been regarded as a promising tool for upscaling the manufacturing of organic solar cells (OSCs). However, there has been a significant gap between the efficiencies of the state-of-the-art spin-coated devices and the scalable processed devices. The active layer morphology is crucial to achieve high efficiency in OSCs, which depends on the conditions of film fabrication. To figure out and optimize the slot-die coating process, a deeper understanding of the film formation kinetics is important. Herein, in situ measurements of the slot-die coating process based on the PM7:IT4F system are demonstrated to illustrate the aggregation and crystallization evolution at various die temperatures and substrate temperatures. OSCs with a high power conversion efficiency of 13.2% are achieved at 60 °C die temperature/60 °C substrate temperature due to the improved exciton dissociation, charge transport and suppressed non-radiative charge recombination. The optimized morphology is attributed to the balanced polymer pre-aggregation and small molecule crystallization kinetics. The unsuitable die temperature leads to overlarge phase separation and consequently inefficient exciton dissociation while the improper substrate temperature results in weak crystallization and the following shrunken carrier lifetime with strong non-radiative combination. This work provides fundamental understanding on the correlations among processing methodology, solution pre-aggregation, morphology formation kinetics, device physics and device performance and affords guidance for device optimization in scalable manufacturing