Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Radix Paeoniae Rubra Against Glioma.

Glioma has a high mortality and can hardly be completely cured. Radix Paeoniae Rubra (RPR) is a prevalent component in traditional Chinese medicine used for tumor treatments. We explored the mechanism of RPR in treating glioma using network pharmacology and experiments. A network pharmacology approach was used to screen active ingredients, targets of RPR and glioma. We then constructed a herb-active ingredient-target-pathway network and conducted protein-protein interaction (PPI) network analysis, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was also performed. Using CCK-8, colony formation, and xenograft experiments, we evaluated the effect of RPR on glioma. The involved pathway and proteins were identified by Western blot. From public databases, we identified nine active RPR ingredients and 40 overlapping targets among 109 RPR targets and 1360 glioma-associated targets. The PPI analysis revealed ten targets, such as AKT1, TP53, and VEGFA, which were identified as hub genes. The results from GO and KEGG analysis highlighted the involvement of the PI3K/AKT pathway. A herb-active ingredient-target-pathway network was constructed. By docking molecular structures, six suitable conformations have been identified. The RPR extract demonstrated anti-tumor properties by inhibiting glioma cell proliferation in vitro and in vivo, likely achieved by suppressing the phosphorylation of the PI3K/AKT signaling pathway. RPR concurrently downregulated the phosphorylation level of AKT1 and the protein expression level of VEGFA, while upregulating the expression of P53 in the U251 cell line. Utilizing network pharmacology and molecular docking, our study not only predicted the impact of RPR on glioma but also delineated the herb-active ingredient-target-pathway network. Experimentally, we confirmed that RPR may exert its anti-tumor properties by inhibiting the phosphorylation of the PI3K/AKT pathway, including AKT1, and by regulating the expression levels of VEGFA and P53.

Antagonistic RALF peptides control an intergeneric hybridization barrier on Brassicaceae stigmas.

Pollen-pistil interactions establish interspecific/intergeneric pre-zygotic hybridization barriers in plants. The rejection of undesired pollen at the stigma is crucial to avoid outcrossing but can be overcome with the support of mentor pollen. The mechanisms underlying this hybridization barrier are largely unknown. Here, in Arabidopsis, we demonstrate that receptor-like kinases FERONIA/CURVY1/ANJEA/HERCULES RECEPTOR KINASE 1 and cell wall proteins LRX3/4/5 interact on papilla cell surfaces with autocrine stigmatic RALF1/22/23/33 peptide ligands (sRALFs) to establish a lock that blocks the penetration of undesired pollen tubes. Compatible pollen-derived RALF10/11/12/13/25/26/30 peptides (pRALFs) act as a key, outcompeting sRALFs and enabling pollen tube penetration. By treating Arabidopsis stigmas with synthetic pRALFs, we unlock the barrier, facilitating pollen tube penetration from distantly related Brassicaceae species and resulting in interspecific/intergeneric hybrid embryo formation. Therefore, we uncover a "lock-and-key" system governing the hybridization breadth of interspecific/intergeneric crosses in Brassicaceae. Manipulating this system holds promise for facilitating broad hybridization in crops.

Primary motor area-related injury of anterior central gyrus in Parkinson's disease with dyskinesia: A study based on MRS and Q-space.

INTRODUCTION: By using magnetic resonance spectroscopy (MRS) and Q-Space imaging technology, this research analyzes the imaging characteristics of white matter fibers in the primary motor cortex and posterior limbs of the subcortical internal capsule in parkinsonian patients with motor disorders. The correlation among the changes in axonal function and structure in the cerebral cortex and subcortical cortex and motor disorder is further revealed. METHODS: First, motor function and clinical condition of 20 patients with Parkinson's disease is assessed the third section of the Unified Parkinson's Scale and H&Y Parkinson's Clinical Staging Scale. Magnetic resonance (MR) scanning is performed with 1H-MRS. Secondly, the range maps of N-acetylaspartic acid (NAA), Choline (Cho), and Creatine (Cr) in the region of interest (the primary motor area of anterior central cortex gyrus, i.e. M1 region) are obtained, and the ratios of NAA/Cr and Cho are calculated. Third, Q-Space MR diffusion imaging technique is used to collect Q-Space images, and a Dsi-studio workstation is used to post-process the images. The fraction anisotropic (FA), generalized fraction anisotropic (GFA), and apparent diffusion coefficient (ADC) parameters of Q-Space in the primary motor cortex and the region of interest in the posterior limb of the internal capsule are obtained. Finally, the parameters of MRS and Q-Space in the experimental group and the control group are further analyzed by SPSS statistical software. RESULTS: After assessing with Parkinson's score scale, there is obvious motor dysfunction in the experimental group. The average clinical stage of H&Y is 3.0 ± 0.31. In the analysis of MRS data, the ratio of NAA/Cr in the primary motor area of the anterior central gyrus in the experimental group is significantly lower than that in the control group (P < 0.05). In the ADC map obtained by Q-Space imaging technique, the ADC value in the primary motor area of the anterior central gyrus in the experimental group is higher than that in the control group (P < 0.05), and the difference is statistically significant (P < 0.05). There is no significant difference between the experimental group and the control group (P > 0.05) in FA and GFA values of the posterior limb of capsule to characterize the characteristics of white matter fibers. CONCLUSIONS: In parkinsonian patients with motor dysfunction, there are apparent functional and structural changes in the primary motor area neurons and peripheral white matter of the anterior central gyrus, and no obvious damage to the axonal structure of the descending fibers in the cortex.

RALF peptide signaling controls the polytubey block in Arabidopsis.

Fertilization of an egg by multiple sperm (polyspermy) leads to lethal genome imbalance and chromosome segregation defects. In Arabidopsis thaliana, the block to polyspermy is facilitated by a mechanism that prevents polytubey (the arrival of multiple pollen tubes to one ovule). We show here that FERONIA, ANJEA, and HERCULES RECEPTOR KINASE 1 receptor-like kinases located at the septum interact with pollen tube-specific RALF6, 7, 16, 36, and 37 peptide ligands to establish this polytubey block. The same combination of RALF (rapid alkalinization factor) peptides and receptor complexes controls pollen tube reception and rupture inside the targeted ovule. Pollen tube rupture releases the polytubey block at the septum, which allows the emergence of secondary pollen tubes upon fertilization failure. Thus, orchestrated steps in the fertilization process in Arabidopsis are coordinated by the same signaling components to guarantee and optimize reproductive success.