The mechanism of Zhenzhu Pills treating intracerebral hemorrhage secondary injury based on network pharmacology and molecular docking.

BACKGROUND: Intracerebral hemorrhage (ICH) secondary injury is serious and affects patient's prognosis. The Zhenzhu Pills used to treat subacute ICH in Tibet has shown to have a certain curative effect. Network pharmacology and molecular docking technology are employed to explore the potential mechanism of Zhenzhu Pills. The components and potential targets of Zhenzhu Pills were screened from the Traditional Chinese Medicine Systems Pharmacology database. The Gene Expression Omnibus Series 24265 was used to screen differentially expressed genes between perihematomal tissue and normal brain. METHODS: The herbs-components-targets network was established, with weighted eigenvalue to identify the core components and targets of Zhenzhu Pills treatment of ICH secondary injury. Targets' bioinformatics enrichment was proceeded by gene ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. Finally, molecular docking was used to identify the hydrogen bonding activity between the key components and action targets. RESULTS: Five herbal drugs were screened from Traditional Chinese Medicine Systems Pharmacology database, with a total of 48 components and 234 targets. The Gene Expression Omnibus Series 24265 dataset was evaluated and 920 differentially expressed genes were identified. A total of 29 intersection targets of Zhenzhu Pills were explored in the treatment of ICH secondary injury. Drugs-components-targets network analysis showed that the pivotal targets were prostaglandin G/H synthase 2, interleukin 6, heme oxygenase-1, vascular endothelial growth factor, and vascular cell adhesion molecule 1, and the core components were quercetin, luteolin, and kaempferol. Gene ontology and KEGG pathway enrichment analysis showed that biological processes such as cell chemotaxis, wound healing, leukocyte migration, and regulation of body fluid levels played an important role in the secondary injury of ICH. The results of KEGG pathway analysis were mainly related to advanced glycation end products-receptor for advanced glycation end products signal pathway and tumor necrosis factor signal pathway. Molecular docking of 3 flavonoids with 5 core targets with the results also showed active hydrogen bonding. CONCLUSIONS: This study provides insights into the potential mechanisms of Zhenzhu Pills in the treatment of secondary injuries resulting from ICH and highlights specific components, targets, and molecular pathways involved in this therapeutic effect. These possible therapeutic mechanisms include inhibiting inflammation, edema, oxidative stress, and so on.

Analysis of Changes in KPS Scores and Imaging Signs in Deep Brain Gliomas by DWI Combined with Intraoperative Ultrasound Resection.

Objective: This study investigates the efficacy of DWI combined with intraoperative ultrasound for deep brain glioma treatment, analyzing changes in Karnofsky performance status (KPS) scores and imaging signs. Objectives include elucidating the approach's advantages, addressing knowledge gaps, and contributing insights into its effectiveness for enhancing deep brain glioma management. Methods: In this retrospective study, we analyzed a total of 346 patients with deep brain glioma who underwent surgical treatment at our hospital from July 2015 to January 2022. After applying inclusion and exclusion criteria, 310 patients were selected and categorized into a control group (n = 150) and an observation group (n = 160) based on different auxiliary techniques of surgical treatment. The degree of resection and Karnofsky performance status (KPS) scores were assessed at 1 day preoperatively, 1 week, and 1 month postoperatively for both groups. Additionally, we conducted a comprehensive analysis of DWI and ultrasound imaging signs among patients with different grades of deep brain glioma. The study duration covered the specified period, and statistical analyses were performed to evaluate the outcomes. Results: In our study, the observation group demonstrated significantly improved resection degrees, with a total resection rate of 82.50% compared to the control group's 65.33%. Preoperative Karnofsky performance status scores showed no significant difference between groups (P > .05), but postoperative scores at 1 week and 1 month were significantly higher in the observation group (P < .05). Intraoperative ultrasound and DWI revealed distinct imaging signs differentiating low-grade and high-grade patients. These results highlight the efficacy of DWI combined with intraoperative ultrasound resection in enhancing resection outcomes and influencing postoperative Karnofsky performance status. Conclusions: DWI combined with intraoperative ultrasonic resection in deep brain glioma has a significant effect, with specific imaging signs, which can effectively improve the total resection rate and KPS score, and is worthy of clinical promotion. DWI combined with intraoperative ultrasound has important clinical significance in the resection of deep brain gliomas. The better resection results and improved postoperative Karnofsky performance-status score that we observed suggest a possible benefit in patient outcomes, which could influence treatment strategies. The precise imaging signs identified by this method provide valuable guidance for targeted and effective tumor resection.

Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

Platycodin D inhibits glioblastoma cell proliferation, migration, and invasion by regulating DEPDC1B-mediated epithelial-to-mesenchymal transition.

BACKGROUND: Platycodin D (PD) is a potent bioactive constituent in the medicinal herb Platycodon grandiflorum. It has shown anticancer properties, particularly against glioblastoma (GB) and other human malignancies. DEPDC1B (DEP domain-containing protein 1B) is an oncogene associated with epithelial-mesenchymal transition (EMT). It is highly expressed in GB and correlated with tumor grade and patient prognosis. In this study, we investigated whether the antiglioma effect of PD was associated with downregulation of DEPDC1B. METHODS: Gene expression and clinical data were obtained from the China Glioma Genome Atlas and The Cancer Genome Atlas databases for glioma samples. In vitro experiments were conducted using Cell Counting Kit-8 and Transwell assays to assess the impact of PD on the proliferation, migration, and invasion of GB cells. mRNA and protein expression was evaluated using real-time polymerase chain reaction and western blotting, respectively. RESULTS: PD exerted inhibitory effects on the proliferation and motility of GB cells. PD downregulated DEPDC1B protein as well as several markers associated with EMT, namely N-cadherin, vimentin, and Snail. The suppressive effects of PD were enhanced when DEPDC1B was knocked down in GB cells, while overexpression of DEPDC1B in cells reversed the inhibitory effects of PD. CONCLUSION: PD exerts an antiglioma effect by regulating DEPDC1B-mediated EMT.

Platycodin D suppresses proliferation, migration, and invasion of human glioblastoma cells through regulation of Skp2.

BACKGROUND: Platycodin D (PD) is a major bioactive component of Platycodon grandiflorum, a medicinal herb that is widely used in China, and is effective against various human cancers, including glioblastoma multiforme (GBM). S phase kinase-related protein 2 (Skp2) is oncogenic and overexpressed in various human tumors. It is highly expressed in GBM and its expression is correlated with tumor growth, drug resistance and poor prognosis. In this study, we investigated whether inhibition of glioma progression by PD is mediated by decreasing expression of Skp2. METHODS: Cell Counting Kit-8 (CCK-8) and Transwell assays were used to determine the effects of PD on GBM cell proliferation, migration, and invasion in vitro. mRNA and protein expression were determined by real time polymerase chain reaction (RT-PCR) and western blotting, respectively. The U87 xenograft model was used to verify the anti-glioma effect of PD in vivo. Expression levels of Skp2 protein were analyzed by immunofluorescence staining. RESULTS: PD suppressed proliferation and motility of GBM cells in vitro. The expression of Skp2 in U87 and U251 cells was significantly reduced by PD. PD mainly decreased the cytoplasmic expression of Skp2 in glioma cells. Skp2 protein expression was downregulated by PD, resulting in upregulation of its downstream targets, p21and p27. The inhibitory effect of PD was enhanced by Skp2 knockdown in GBM cells and reversed in cells with Skp2 overexpression. CONCLUSION: PD suppresses glioma development by regulation of Skp2 in GBM cells.

Network pharmacology-based screening of the active ingredients and mechanisms of evodiae fructus anti-glioblastoma multiforme.

BACKGROUND: Evodiae fructus has been shown to have anti-glioblastoma multiforme (GBM) effects. However, its anti-GBM active components and mechanism remain unclear. In this study, the active components of evodiae fructus were screened by network pharmacology to explore the possible molecular mechanism of resistance to GBM. MATERIALS AND METHODS: The main active ingredients of evodiae fructus were derived from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Batch-traditional Chinese medicine (TCM). TCMSP and Swiss absorption, distribution, metabolism and elimination (ADME) predict genetic targets for ingredients that meet pharmacological criteria. GBM-related targets were obtained from DisGeNet, GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and TCGA. A Venn diagram was used to obtain the common targets of evodiae fructus and GBM. Protein-protein interaction (PPI) networks and component-disease target networks were constructed using Cytoscape 3.8.1 software for visualization. GBM gene differential expression was visualized by VolcaNoseR, and potential targets were enriched by Gene Ontology (GO) function and annotated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway by SRplot. Molecular docking verification was conducted using AutoDock Vina software. RESULTS: According to the screening conditions, 24 active components and 80 drug targets were obtained. The PPI network contains 80 proteins. The molecular docking verification showed the molecular docking affinity of the core active compounds in evodiae fructus with CASP3, JUN, EGFR, and AKT1. CONCLUSIONS: This study preliminarily identified the various molecular targets and multiple pathways of evodiae fructus against GBM.

Recent Insights Into the Protective Mechanisms of Paeoniflorin in Neurological, Cardiovascular, and Renal Diseases.

ABSTRACT: The monoterpene glycoside paeoniflorin (PF) is the principal active constituent of the traditional Chinese herbal medicines, Radix Paeoniae Alba and Radix Paeoniae Rubra, which have been used for millennia to treat cardiovascular diseases (eg, hypertension, bleeding, and atherosclerosis) and neurological ailments (eg, headaches, vertigo, dementia, and pain). Recent evidence has revealed that PF exerts inhibitory effects on inflammation, fibrosis, and apoptosis by targeting several intracellular signaling cascades. In this review, we address the current knowledge about the pharmacokinetic properties of PF and its molecular mechanisms of action. We also present results from recent preclinical studies supporting the utility of PF for the treatment of pain, cerebral ischemic injury, and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, new evidence suggests a general protective role of PF in heart attack, diabetic kidney, and atherosclerosis. Mechanistically, PF exerts multiple anti-inflammatory actions by targeting toll-like receptor-mediated signaling in both parenchymal and immune cells (in particular, macrophages and dendritic cells). A better understanding of the molecular actions of PF may lead to the expansion of its therapeutic uses.