Rare oxoisoaporphine alkaloids from Menispermum dauricum with potential anti-inflammatory activity.

Eleven alkaloids including four previously undescribed oxoisoaporphine alkaloids, menisoxoisoaporphines A-D (1-4), four known analogues (5-8), and three aporphine alkaloids (9-11), were isolated and identified from the rhizomes of Menispermum dauricum. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. Among them, compounds 1 and 4 were the first samples of oxoisoaporphine with C-6 isopentylamino moiety, and 2 was a rare C-4 methylation product of oxoisoaporphine alkaloid. The in vitro anti-inflammatory activity of compounds 1-11 was performed by evaluating the inhibition of NO level in LPS-induced RAW264.7 macrophages. Among them, compound 4 exhibited the most potent NO inhibition activity with an IC50 value of 1.95 ± 0.33 µM. The key structure-activity relationships of those oxoisoaporphine alkaloids for anti-inflammatory effects have been summarized.

Triterpenoids from the fruits of Melia toosendan Sieb. et Zucc. with α-glucosidase inhibitory activities.

Four previously unreported tirucallane-type triterpenoids (1-4), together with four known analogues (5-8), were isolated from the fruits of Melia toosendan Sieb. et Zucc. Their planar structures were comprehensively elucidated by detailed analyses of HRESIMS, 1D and 2D NMR spectra data. The relative configurations of 1-4 were determined by NOESY experiments. The comparison of experimental and calculated electronic circular dichroism (ECD) spectra led to the establishment of the absolute configurations of new compounds. All isolated triterpenoids were evaluated for their α-glucosidase inhibitory activities in vitro. Compounds 4 and 5 showed moderate α-glucosidase inhibitory activities with IC50 values of 120.3 ± 5.8 and 104.9 ± 7.1 µM, respectively.

Effect of vegetation utilization on runoff and sediment production on grain-for-green slopes in the wind-water erosion crisscross region.

To effectively utilize the vegetation on grain-for-green slopes in the wind-water erosion crisscross region, it is necessary to determine the reasonable vegetation utilization intensity. We set up runoff plots on slopes which were not cultivated and were closed for many years in the Liudaogou catchment, a typical catchment in wind-water erosion crisscross region of the Loess Plateau. With artificial simulated rainfall experiments, the characteristics of runoff and sediment yield on slopes (10°, 20° and 30°) under different utilization intensity of vegetation were studied to select the reasonable utilization intensity. The results showed that the runoff rate in the process of rainfall simulation could be divided into two periods: rapidly increasing in the initial period and slow increasing or quasi-steady state in the middle and late periods. The variation of erosion rate during the rainfall was dependent on the slope. The utilization intensity had a significant effect on the runoff yield, which increased with the increasing utilization intensities. The slope gradient had a significant effect on the sediment yield, with the variation of sediment yield with slope gradient being: 20°>30°>10°. Compared with the unused (natural) plots, the relative runoff and sediment increased with increasing utilization intensities. Predicted based on the rainfall data, annual soil erosion amount on the slope would be basically lower than the tolerance level of soil loss when the vegetation cover on the slope surface reached 25% in 15 years after abandoning reclamation. More attention should be paid to the restoration and management of vegetation on the slope of 20° in this area.

Cancer-associated fibroblasts in a human HEp-2 established laryngeal xenografted tumor are not derived from cancer cells through epithelial-mesenchymal transition, phenotypically activated but karyotypically normal.

Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression and even initiation. However, the origins of CAFs in various cancer types remain controversial, and one of the important hypothesized origins is through epithelial-mesenchymal transition (EMT) from cancer cells. In this study, we investigated whether the HEp-2 laryngeal cancer cells are able to generate CAFs via EMT during tumor formation, which is now still unknown. The laryngeal xenografted tumor model was established by inoculating the HEp-2 laryngeal cancer cell line in nude mice. Primary cultured CAFs from the tumor nodules and matched normal fibroblasts (NFs) from the adjacent connective tissues were subcultured, purified, and verified by immunofluorescence. Migration, invasion, and proliferation potentials were compared between the CAFs and NFs. A co-culture of CAFs with HEp-2 cells and a co-injection of CAFs with HEp-2 cells in nude mice were performed to examine the cancer-promoting potential of CAFs to further verify their identity. Karyotypic analyses of the CAFs, NFs, and HEp-2 cells were conducted. A co-culture of NFs with HEp-2 cells was also performed to examine the expression of activated markers of CAFs. A pathological examination confirmed that the laryngeal xenografted tumor model was successfully established, containing abundant CAFs. Immunocytochemical staining verified the purities and identities of the CAFs and NFs. Although the CAFs manifested higher migration, invasion, proliferation, and cancer-promoting capacities compared with the NFs, an analysis of chromosomes revealed that both the CAFs and NFs showed typical normal mouse karyotypes. In addition, the NFs co-cultured with HEp-2 cells did not show induced expressions of activated markers of CAFs. Our findings reveal that the CAFs in the HEp-2 established laryngeal xenografted tumor are not of laryngeal cancer origin but of mouse origin, indicating that the HEp-2 laryngeal cancer cells cannot generate their own CAFs via EMT in this model.

Interleukin-23 as a potential therapeutic target for rheumatoid arthritis.

Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA). Increasing evidence has revealed the importance of IL-23, which closely resembles IL-12 structurally and immunologically, in linking innate and adaptive immunity. IL-23, a newly identified heterodimeric pro-inflammatory cytokine, is composed of a p40 subunit in common with IL-12 and a unique p19 subunit. Recent evidence suggests that IL-23, rather than IL-12, is the crucial factor in the pathogenesis of various immune-mediated disorders. In addition, recent studies have explored the role of IL-23 in patients with RA. An elevated expression of IL-23 has been demonstrated in the synovial fibroblasts and plasma of patients with RA. Moreover, an association between IL-23 and IL-23R polymorphisms with susceptibility to RA has been reported. Therefore, the targeting of IL-23 or the IL-23 receptor has been proposed as a potential therapeutic approach for RA. In this review we will discuss the biological features of IL-23, and summarize recent advances in our understanding of the role of IL-23 in the pathogenesis and treatment of RA.

[Correlation between the vascular endothelial growth factor C expression and lymph node metastasis in human nasopharyngeal carcinoma].

OBJECTIVE: To detect the expression of vessel endothelial growth factor C (VEGF-C) and microlymphatic vessel density (MLVD) and probe the relationship between lymphangiogenesis and lymph node micrometastasis in nasopharyngeal carcinoma. METHODS: The expression of VEGF-C, was evaluated in 58 cases with nasopharyngeal carcinoma and 20 samples of nasopharyngitis tissues by immunohistochemical staining SP methods. The MLVD in tumor was counted by immunostaining with the specific antibody lymphatic vessel endothelial hyaluronic acid receptor 1 and analyzed with clinicopathologic parameters. RESULTS: The positive rate of VEGF-C was 84.5% and 15.0% respectively in nasopharyngeal carcinoma and nasopharyngitis tissues, there was significant difference between them (chi2 = 32.309, P <0.01). The microlymphatic vessel density was (28.6 +/- 6.2) pieces per field and (10.5 +/- 3.0) pieces per field respectively in nasopharyngeal carcinoma and nasopharyngitis tissues, there was significant difference between them (t = 12.491, P <0.01). The expression of VEGF-C and the MLVD were significantly higher in nasopharyngeal carcinoma and in lymph node metastasis group than in no-metastasis group. The expression of VEGF-C was positively correlated with MLVD (t =3.512, P <0.01), lymph node metastasis (chi2 =7.715, P <0.01, r =0.712) and clinical stage (chi2 =4.250, P <0.05, r =0.481). CONCLUSIONS: In nasopharyngeal carcinoma, the expression rate of VEGF-C was high. VEGF-C expression was positively correlated with MLVD and lymph node metastasis and tumor staging. It was explained that VEGF-C attached itself to the emergence and infiltration and transfer of NPC. There was close correlation between the expression of VEGF-C and MLVD. It was explained that the expression of VEGF-C in NPC was correlated to neoplasm lymphangiogenesis and that VEGF-C played a vital role in the progression of NPC. VEGF-C was likely to a potential target of anticancer therapy.