Brunonianines D-F, three new C19-diterpenoid alkaloids from the Delphinium brunonianum, with therapeutic effect on ovarian cancer in vitro and in vivo.

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.

Chemical constituents of Rubia tibetica Hook. f. from Tibetan medicine and cytotoxic activity evaluation.

Two unprecedented quinone compounds Rubiaxylm A (1) and Rubiaxylm B (2), along with fifteen known anthraquinones (3-17) were isolated and characterized from the roots of Rubia tibetica in Tibetan medicine. Their structures were identified through comprehensive analyses of 1D/2D NMR as well as HR-ESIMS data. Furthermore, all separated compounds were evaluated for their cytotoxic activity on A549, Caco-2, MDA-MB-231 and Skov-3 cell lines. In particular, compound 2 effectively inhibited MDA-MB-231 cells with an IC50 value of 8.15 ± 0.20 µM. Subsequently, the anti-tumor mechanism of 2 was investigated by flow cytometry, JC-1 staining, cell scratching and cell colony. These results indicated that compound 2 could inhibit the proliferation of MDA-MB-231 cells by arresting cells in the G1 phase.

Brunonianines A-C, C20-diterpenoid alkaloids with cyano group from Delphinium brunonianum Royle.

Cyano tends to have better biological activity, but it is rarely reported in natural products, especially in the C20-diterpene alkaloids. Herein, three unprecedented C20-diterpenoid alkaloids, brunonianines A-C (1-3), possessing rare cyano functional group as well as an atisine backbone constructed from a phenethyl substituent and a tetrahydropyran ring, along with four C19-alkaloids (4-7) and one amide alkaloids (8), were isolated from the whole plant of Delphinium brunonianum Royle. Compounds 1-3 are also the first atisine type diterpenoid alkaloids with cyano group obtained from nature. The structures of the previously undescribed compounds were elucidated by HR-ESI-MS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations and single-crystal X-ray diffraction. Reasonable speculations have also been made regarding the biogenic synthetic pathways of compounds 1-3. In addition, the inhibitory activity of all compounds was also tested against four tumor lines: A549, Caco-2, H460 and Skov-3, where compound 2 (IC50 2.20 ± 0.21 µM) showed better inhibitory activity against Skov-3 cells than the hydroxycamptothecin. Using flow cytometry, cell staining, migration and invasion analysis, and Western blot, compound 2 was found to arrest cells in the G2/M phase and was able to effectively inhibit cell motility to achieve potent anti-tumor effects. In addition, compound 2 can effectively induce apoptosis by activating the Bax/Bcl-2/Caspase-3 signaling pathway.

Effects of bundle-care interventions on pressure ulcers in patients with stroke: A meta-analysis.

We conducted a meta-analysis to assess the effects of bundle-care interventions on pressure ulcers in patients with stroke to provide a basis for clinical work. Randomised controlled trials on the effects of bundle-care interventions in patients with stroke were identified using computerised searches of the PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, VIP and Wanfang databases, from the time of inception of each database to July 2023, supplemented by manual literature searches. Two researchers independently retrieved and screened the articles, extracted the data and evaluated the quality of the included studies. After reaching consensus, meta-analysis was performed using RevMan 5.4. Twenty-four papers were included, involving 3330 patients of whom 1679 were in the intervention group and 1651 were in the control group. The results showed that, compared with standard care, bundle-care interventions significantly reduced the incidence of pressure ulcers (3.28% vs. 14.84%, odds ratio [OR]: 0.19, 95% confidence interval [CI]: 0.14-0.26, p < 0.001), and aspiration (5.60% vs. 18.84%, OR: 0.25, 95% CI: 0.17-0.39, p < 0.001), and improved patient satisfaction with nursing care (96.59% vs. 84.43%, OR. 5.45, 95% CI: 3.76-7.90, p < 0.001). Current evidence suggests that care bundles are significantly better than conventional nursing measures in preventing pressure ulcers and aspiration, and improving patient satisfaction with nursing care in patients with stroke, and are worthy of clinical promotion and application.

[Relationship between multi-gene proteins in colorectal carcinoma complicated with chronic schistosomiasis: an immunohistochemical study by using tissue microarray techniques].

OBJECTIVE: To investigate the relationship between p53, COX-2, Bax, c-myc genes and colorectal carcinoma complicated with chronic schistosomiasis. METHODS: One hundred and sixty patients with colorectal carcinoma were selected and divided into two groups; a schistosomiasis group (colorectal carcinoma complicated with chronic schistosomiasis, n = 80) and a non-schistosomiasis group (colorectal carcinoma uncomplicated with chronic schistosomiasis, n = 80). The tissue microarray techniques and immunohistochemistry method were used in all the patients to detect the expressions of p53, COX-2, Bax and c-myc proteins. RESULTS: The positive rate and level of p53 protein expression in the schistosomiasis group were lower than those in the non-schistosomiasis group, but there were no significant differences between the two groups (both P > 0.05). The COX-2 protein in both groups was positive, but the positive expression level of COX-2 in the schistosomiasis group was higher than that in the nonschistosomiasis group, and there was a significant difference between the two groups (P < 0.01). The positive rate and level of Bax protein expression were not significantly different between the two groups (both P > 0.05). The positive rate of c-myc expression in the schistosomiasis group was higher than that in the non-schistosomiasis group, with a significant difference (P < 0.01), but the positive expression level was lower than that in the non-schistosomiasis group, and there was a significant difference between the two groups (P < 0.01). CONCLUSIONS: Schistosome infection may impact on the deficiency of p53 of human colorectal cancer cells. It may promote the excessive expression of COX-2 protein, which is an indirect carcinogenic factor. The expression of Bax gene has no correlation with schistosome infection. The schistosome chronic infection may cause a persistent low level expression of c-myc gene.