[Mechanism of aqueous extract of Strychni Semen in improving pain in rats with rheumatoid arthritis based on TLR4/TNF-α/MMP-9 signaling pathway].

This study aims to explore the mechanism of aqueous extract of Strychni Semen(SA) in relieving pain in the rat model of rheumatoid arthritis(RA) via Toll-like receptor 4(TLR4)/tumor necrosis factor-α(TNF-α)/matrix metalloproteinase-9(MMP-9) signaling pathway. Firstly, the main chemical components of Strychni Semen were searched against TCMSP, TCMID, ETCM, and related literature, and the main targets of the chemical components were retrieved from TargetNet and SwissTargetPrediction. The main targets of RA and pain were searched against GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). Venny 2.1.0 was used to obtain the common targets shared by Strychni Semen, RA, and pain, and STRING and Cytoscape 3.6.1 were used to build the protein-protein interaction network. Then, molecular docking was carried out in AutoDock Vina. Finally, the rat model of type Ⅱ collagen-induced arthritis(CIA) was established. The up-down method and acetone method were employed to examine the mechanical pain threshold and cold pain threshold of rats, and the pain-relieving effect of SA on CIA rats was evaluated comprehensively. Hematoxylin-eosin(HE) staining was employed to evaluate the histopathological changes of joints in CIA rats. The expression levels of key target proteins was determined by immunohistochemistry and Western blot, and the mRNA levels of key targets were determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). The results of network prediction showed that Strychni Semen may act on the TLR4/TNF-α/MMP-9 signaling pathway to exert the pain-relieving effect. The results of molecular docking showed that brucine, the main active component of SA, had strong binding ability to TLR4, TNF-α, and MMP-9. The results of animal experiments showed that SA improved the mechanical and cold pain sensitivity(P<0.05, P<0.01) and reduced the joint histopathological score of CIA rats(P<0.01). In addition, medium and high doses of SA down-regulated the protein and mRNA levels of TNF-α, TLR4, and MMP-9(P<0.05,P<0.01). In conclusion, SA alleviated the mechanical pain sensitivity, cold pain sensitivity, and joint histopathological changes in CIA rats by inhibiting the over activation of TLR4/TNF-α/MMP-9 signaling pathway.

[Anti-rheumatoid arthritis mechanism of Sophorae Tonkinesis Radix et Rhizoma based on network pharmacology and experimental verification].

Based on the network pharmacology, molecular docking, and animal experiment, this study explored the anti-rheumatoid arthritis(RA) mechanism of Sophorae Tonkinesis Radix et Rhizoma(STRR). The active components of STRR were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicine Integrative Database(TCMID), and previous research, main targets of STRR from TCMSP and SwissTargetPrediction, and targets of RA from GeneCards, DrugBank, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). The common targets of the two were screened by Venny 2.1.0. Cytoscape 3.6.0 was used to generate the "component-target" network, and STRING and Cytoscape were used to construct the protein-protein interaction(PPI) network. DAVID 6.8 was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and AutoDock Vina for molecular docking. Finally, collagen-induced rheumatoid arthritis(CIA) mouse model was constructed, and the expression of core target proteins was detected by Western blot. A total of 27 active components, including quercetin, genistein, kaempferol, subprogenin C, and daidzein, and 154 anti-RA targets, such as signal transducer and activator of transcription 3(STAT3), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), AP-1 transcription factor subunit(JUN), and interleukin 6(IL6), of STRR were screened out. It was preliminarily indicated that STRR may regulate phosphatidylinositol-3-kinase-protein kinase B(PI3 K-AKT) signaling pathway and TNF signaling pathway to modulate the positive regulation of RNA polymerase Ⅱ promoter transcription, inflammatory response, and other biological processes, thus exerting the anti-RA effect. The results of molecular docking showed that the main active components in STRR had high binding affinity to the core targets. Animal experiment suggested that the water extract of STRR can significantly reduce the levels of p-STAT3, p-MAPK1, and TNF. This study demonstrated the multi-component, multi-target and multi-pathway synergistic effect of STRR in the treatment of RA, laying an experimental basis for clinical application of this medicine.

[Effect of neutrophil extracellular traps on ischemic stroke and intervention of traditional Chinese medicine].

Ischemic stroke is the leading cause of death and disability in adults in China. Recent studies have shown that neutrophil extracellular traps play a crucial role in occurrence and development of ischemic stroke. This paper reviewed the literatures on NETs since the discovery of NETs more than a decade ago, and summarized the composition of NETs, the effects of NETs on stroke, the intervention targets of NETs, and the effects of traditional Chinese medicine on NETs. NETs are an important cause of brain injury after stroke. Platelets, peptidylarginine deiminase 4, reactive oxygen species and histones are the targets to regulate NET formation in stroke. There are few researches on traditional Chinese medicine targeting NETs for stroke. Studies on the intervention of traditional Chinese medicine mainly target on neutrophils, which are the main components of NETs, and platelets, which induce the formation of NETs. The paper provided a comprehensive overview of current studies of NETs in ischemic stroke, so as to provide new ideas for the treatment and drug development of ischemic stroke.

Benzoxazole-Linked Ultrastable Covalent Organic Frameworks for Photocatalysis.

The structural uniqueness of covalent organic frameworks (COFs) has brought these new materials great potential for advanced applications. One of the key aspects yet to be developed is how to improve the robustness of covalently linked reticular frameworks. In order to make the best use of π-conjugated structures, we develop herein a "killing two birds with one stone" strategy and construct a series of ultrastable benzoxazole-based COFs (denoted as LZU-190, LZU-191, and LZU-192) as metal-free photocatalysts. Benefiting from the formation of benzoxazole rings through reversible/irreversible cascade reactions, the synthesized COFs exhibit permanent stability in the presence of strong acid (9 M HCl), strong base (9 M NaOH), and sunlight. Meanwhile, reticulation of the benzoxazole moiety into the π-conjugated COF frameworks decreases the optical band gap and therefore increases the capability for visible-light absorption. As a result, the excellent photoactivity and unprecedented recyclability of LZU-190 (for at least 20 catalytic runs, each with a product yield of 99%) have been illustrated in the visible-light-driven oxidative hydroxylation of arylboronic acids to phenols. This contribution represents the first report on the photocatalytic application of benzoxazole-based structures, which not only sheds new light on the exploration of robust organophotocatalysts from small molecules to extended frameworks but also offers in-depth understanding of the structure-activity relationship toward practical applications of COF materials.

Effects of intensity of arm training on hemiplegic upper extremity motor recovery in stroke patients: a randomized controlled trial.

OBJECTIVE: To investigate the effects of different intensities of arm rehabilitation training on the functional recovery of hemiplegic upper extremity. DESIGN: A randomized controlled trial. INTERVENTIONS: Thirty-two stroke patients meeting the enrolment criteria were randomly divided into three groups: group A (n = 11), group B (n = 10) and group C (n = 11). Each group received arm training for 1 hour, 2 hours and 3 hours a day respectively, 5 days per week, for a period of six weeks. MAIN MEASURES: Motor function was assessed by Fugl-Meyer Assessment, Action Research Arm Test and Barthel Index, carried out before treatment, two weeks, four weeks and six weeks after treatment. RESULTS: When comparing the three groups, the Fugl-Meyer Assessment improvement was more significant in group C (20.50 ± 7.84) than that in group A (11.90 ± 6.52 ) and group B (13.80 ± 6.41) after four weeks of treatment (P < 0.05). The Action Research Arm Test score improvement was more significant in group C (7.30 ± 2.95) than in group A (3.30 ± 2.91 ) (P < 0.05). After six weeks of treatment, the Fugl-Meyer Assessment and Action Research Arm Test score improvements were more significant in group C (24.50 ± 7.96, 10.90 ± 3.60) and group B (19.70 ± 7.09, 8.70 ± 4.62) than in group A (13.00 ± 6.38, 5.30 ± 3.40) (P < 0.05). There were no significant differences of Barthel Index among the three groups (P > 0.05). In each group, Fugl-Meyer Assessment, Action Research Arm Test and Barthel Index scores increased significantly after six weeks of treatment (P < 0.05). CONCLUSIONS: An increase in the intensity of arm training might improve the motor function of the arm after stroke.