Accurate network pharmacology and novel ingredients formula of herbal targeting estrogen signaling for psoriasis intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: As a common chronic inflammatory skin disease, psoriasis is incompletely understood and brings a lot of distress to patients. The estrogen signaling pathway has been implicated in its pathogenesis, making it a potential therapeutic target. Si Cao Formula (SCF) has demonstrated promise in treating psoriasis clinically. However, its molecular mechanisms concerning psoriasis remain largely unexplored. AIM OF THE STUDY: To elucidate the underlying mechanisms of the action of SCF on psoriasis. MATERIALS AND METHODS: Active ingredients were identified by LC-MS/MS. After the treatment with SCF, the exploration of differentially expressed proteins (DEPs) were conducted using tandem mass tag (TMT)-based quantitative proteomics analysis. By GO/KEGG, WikiPathways and network pharmacology, core signaling pathway and protein targets were explored. Consequently, major signaling pathway and protein targets were validated by RT-qPCR, immunoblotting and immunofluorescence. Based on Lipinski's Rule of Five rules and molecular docking, 8 active compounds were identified that acted on the core targets. RESULTS: 41 compounds of SCF and 848 specific targets of these compounds were identified. There were 570 DEPs between IMQ (Imiquimod) and IMQ + SCF group, including 279 up-regulated and 304 down-regulated proteins. GO/KEGG, WikiPathways and network pharmacology revealed estrogen signaling pathway as the paramount pathways, through which SCF functioned on psoriasis. We further show novel ingredients formula of SCF contributes to estrogen signaling intervention, including liquiritin, parvisoflavone B, glycycoumarin, 8-prenylluteone, licochalcone A, licochalcone B, oxymatrine, and 13-Hydroxylupanine, where targeting MAP2K1, ILK, HDAC1 and PRKACA, respectively. Molecular docking proves that they have good binding properties. CONCLUSION: Our results provide an in-depth view of psoriasis pathogenesis and herbal intervention, which expands our understanding of the systemic pharmacology to reveal the multiple ingredients and multiple targets of SCF and focus on one pathway (estrogen signaling pathway) may be a novel therapeutic strategy for psoriasis treatment of herbal medicine.

Mechanisms of JinHong Formula on treating sepsis explored by randomized controlled trial combined with network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: JinHong Formula (JHF) was derived from the famous Rhubarb and Moutan Decoction which was prescribed for appendicitis. It was originally recorded in the classic of "Jingui Yaolve" written by Zhang Zhongjing. It is a kind of traditional Chinese medicine, widely used in the treatment of inflammation. However, the clinical effect of JHF for sepsis and its comprehensive mechanism in sepsis remained largely unknown. RESEARCH PURPOSE: The aim of our study was to evaluate the clinical effect of JHF in the treatment of sepsis, and to explore its mechanism from the perspective of network pharmacology. RESEARCH METHODS: The single-center randomized clinical trial was conducted to assess the effect of JHF in the treatment of sepsis. Additionally, we used the Chinese herbal medicine pharmacology database and analysis platform to identify the active components and therapeutic target of JHF. Numerous well-known disease target databases have been used to screen therapeutic target proteins for sepsis. Furthermore, we have established a Protein-Protein Interaction (PPI) network and carried out Gene Onotology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis. In order to conclude which active compounds from JHF may be responsible for signaling pathway, we performed network analysis. RESEARCH RESULTS: The study included 114 patients. By comparing participants with and without JHF, the results suggested that JHF significantly reduced all-cause mortality on 28 and 60 days after intervention, and improved Sequential Organ Failure Assessment (SOFA) on 7th day after intervention as well as. JHF had an effect of anti-inflammatories and antioxidants (SOD). By using network pharmacological analysis, we identified 72 active components and 426 target genes of JHF, and successfully constructed a "JHF-compound target-sepsis" network. 116 mentioned targets revealed by GO/KEGG enrichment analysis played a significant role in the inflammatory reaction and immunoregulation via interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathway. Moreover, the analysis of "pathway target-active component" revealed that Sennidin A, Rheidin A, Rheidin B, Rheidin C, (E)-4-Phenyl-3-Buten-2-One, Osmanthuside H, Esculetin, and Caffeicacid were responsible for IL-17, TNF signaling pathways. CONCLUSION: JHF contains potential active substance of anti-inflammatory and antioxidant. These active compounds may come into play through IL-17 and TNF signaling pathways. For sepsis, JHF may be a promising and effective treatment strategy.

Artificial Intelligence-Assisted Microcatheter Shaping for Intracranial Aneurysm Coiling: A Preliminary Study.

BACKGROUND: To evaluate the efficacy of artificial intelligence (AI) technology-assisted microcatheter shaping for coil embolization of intracranial aneurysms. METHODS: From June 2019 to May 2021, 30 aneurysms in 24 patients were treated with coiling embolization using computer software-assisted microcatheter shaping at our institution. All patients underwent digital subtraction angiography (DSA) before coiling embolization. After three-dimensional (3D) rotational angiography, digital imaging and communications in medicine (DICOM) data were extracted and imported into computer software based on an AI algorithm. 3D images of the parent artery and aneurysm were constructed with the software and data including the central axis of the parent artery, aneurysm location, aneurysm size, and 3D structure were automatically obtained. The optimal microcatheter path was calculated and the shape of the mandrel was automatically generated. Surgeons shaped the mandrel and microcatheter following the AI-generated template and completed the endovascular procedure. RESULTS: All patients successfully completed the endovascular procedure without perioperative complications. The microcatheters shaped as per the AI template accurately entered the aneurysm sacs in 1 attempt; 15 aneurysms required no microguidewire assistance in catheterizing the aneurysm sac and 15 did. The stability of the microcatheters during the procedures was satisfactory. No rebound incidence was observed and no reshaping was necessary. CONCLUSIONS: The AI-assisted microcatheter shaping technology provides a new method to generate the optimal shape for the mandrel and microcatheter during endovascular procedures. The technology facilitates microcatheter accuracy and stability during coiling embolization and provides technical support for surgeons.

Efficacy and Safety of Willis Covered Stent for Treatment of Complex Vascular Diseases of the Internal Carotid Artery.

BACKGROUND: Willis covered stents are used in clinical practice for some complex cerebrovascular diseases. However, the performance of the Willis covered stent requires further investigation. In this study, we investigate the safety and efficacy of Willis covered stents for the treatment of complex vascular diseases of the internal carotid artery (ICA). METHODS: Thirteen patients with complex ICA diseases treated with the Willis covered stent system at our institution from October 2016 to January 2018 were analyzed retrospectively. Follow-up observation and digital subtraction angiography (DSA) examination were conducted at about 6-10 months after the treatment. RESULTS: The complex vascular diseases of the ICA were successfully treated in 12 patients. The technical success rate was 92.3%. Pathologically, 13 lesions included blood blister-like aneurysm (n = 7), traumatic pseudoaneurysm (n = 1), traumatic carotid artery rupture (n = 1), and aneurysm with arteriovenous fistula (n = 4). Thirteen patients with complex vascular diseases of the ICA were treated with 15 Willis covered stents. The release sites of Willis covered stents were the C7 (n = 2), C6 (n = 1), C5 and/or C4 (n = 9), and the C2 (n = 3) segment of the ICA. DSA performed immediately after stent deployment revealed that complete occlusion of the lesion was achieved in 11 patients and endoleak was observed in 2 patients. Of the 11 patients, postoperative DSA examination indicated that the lesions were occluded completely. Among 2 patients, who had a second stent implantation at the break of the ICA, the traumatic ICA rupture was essentially completely obstructed in 1 patient. The endoleak remained in 1 patient with carotid cavernous sinus fistula because the placement of the second stent system was difficult with his ICA tortuosity. No recurrence of aneurysms, hemorrhagia, and other lesions was observed, and the patients' parent arteries were patent without stenosis. No procedure-related complications or deaths occurred during follow-up. CONCLUSIONS: For the treatment of complex vascular diseases in the ICA, Willis covered stent implantation is safe and effective. However, longer follow-up, large-sample controlled studies, and multicenter studies are needed for further confirmation.