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Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.
الملخص
Objective: To develop an efficient preparative method for the separation of Gelsemium alkaloids from Gelsemium elegans. Methods: High-speed counter-current chromatography (HSCCC) with several two-phase solvent systems was investigated for the separation of Gelsemium alkaloids. The purity and structure identification of the purified compounds were performed with HPLC and NMR spectra, respectively. Results: In a single operation, 206.6 mg of crude alkaloid sample was separated to yield 28.7 mg of koumine, 24.9 mg of gelsemine, 26.9 mg of humantenine, and 7.2 mg of gelsevirine, with the purities of 97.8%, 95.4%, 97.4%, and 93.5%, respectively. Conclusion: A preparative HSCCC method is successfully established for the separation of four Gelsemium alkaloids from G. elegans with a modified two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-0.5% triethylamine-H2O (3:5:3:4).
الملخص
<p><b>OBJECTIVE</b>To study the frequency distribution of single nucleotide polymorphisms (SNPs) in two genes associated with incomplete Kawasaki disease (KD) (rs1569723 in CD40 gene and rs2736340 in BLK gene), and to investigate its association with the genetic susceptibility and clinical phenotypes of incomplete KD.</p><p><b>METHODS</b>A total of 184 children with incomplete KD and 203 normal children were recruited to carry out a case-control study. The genotypes of SNPs in CD40 gene and BLK gene were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequency distribution of genotypes was compared between the KD and control groups. The association between gene polymorphisms and clinical features of incomplete KD was analyzed.</p><p><b>RESULTS</b>There were no significant differences in genotype (AA, AC, CC) and allele frequencies in CD40 SNP rs1569723 between the KD and control groups. There were significant differences in the frequency distribution of three genotypes (TT, CT, CC) in BLK SNP rs2736340 between the KD and control groups (P=0.031), and the KD group had a significantly higher frequency of T allele than the control group (P=0.007). There were significant differences in the incidence of conjunctival hyperaemia among the patients with different genotypes (rs1569723 in CD40 gene) (P=0.036). The SNP rs2736340 in BLK gene was associated with the extremity changes in KD patients (P=0.017).</p><p><b>CONCLUSIONS</b>The SNP rs2736340 in BLK gene is associated with the susceptibility to incomplete KD, and the SNP rs1569723 in CD40 gene and SNP rs2736340 in BLK gene are associated with some of clinical phenotypes of incomplete KD.</p>
الموضوعات
Child , Child, Preschool , Female , Humans , Infant , Male , CD40 Antigens , Genetics , Genetic Predisposition to Disease , Mucocutaneous Lymph Node Syndrome , Genetics , Polymorphism, Single Nucleotideالملخص
<p><b>OBJECTIVE</b>To review the central role of leukemia stem cells (LSCs) in drug resistance and metastasis, aiming to provide key insights into leukemogenic pathology and developing novel therapeutic strategies against the relapse of leukemia.</p><p><b>DATA SOURCES</b>The data used in this review were obtained mainly from the studies reported in PubMed using the key terms "tumor-initiating cells", "leukemia stem cells", "drug resistance" and "metastasis".</p><p><b>STUDY SELECTION</b>Relevant articles on studies of leukemia stem cells were selected.</p><p><b>RESULTS</b>Increasing numbers of studies have suggested the importance of cancer stem cells (CSCs) in the initiation and maintenance of cancer, especially in leukemia. This review has summarized the origin, characteristics, isolation and identification of LSCs. It highlights the crucial role of LSCs in drug resistance and metastasis of leukemia by illustrating possible mechanisms and aims to provide novel therapeutic strategies for LSCs-targeted treatment.</p><p><b>CONCLUSION</b>LSCs play a crucial role in drug resistance and metastasis of leukemia and new promising LSCs-targeted therapies warrant investigation in both experimental models and clinical practice.</p>
الموضوعات
Animals , Humans , Drug Resistance, Neoplasm , Physiology , Leukemia , Pathology , Models, Biological , Neoplasm Metastasis , Pathology , Neoplastic Stem Cells , Metabolism , Pathology , Physiologyالملخص
<p><b>BACKGROUND</b>CC chemokine receptor 3 (CCR3), expressed on some inflammatory cells, is a member of the chemokine receptor family. Its ligand is eotaxin/CCL11. In this research, we studied the expression and function of CCR3 induced by interleukin-2 (IL-2) and interleukin-4 (IL-4) on human germinal centre (GC) B cells.</p><p><b>METHODS</b>Cells isolated from human tonsils were stimulated with IL-2 or/and IL-4 followed by bonding with eotaxin/CCL11. Flow cytometry was used to detect expression of CCR3 on GC B cells and apoptosis of GC B cells. Real time quantitative reverse transcription polymerase chain reaction and Northern blot assays were used to analyse the CCR3 mRNA expressed in the GC B cells. Chemotaxis and adhesion assays were used to determine the effect of eotaxin/CCL11 ligand bonded to CCR3 on GC B cells.</p><p><b>RESULTS</b>There was no CCR3 expression on human freshly isolated GC B cells. The combination IL-2 and IL-4 could upregulate CCR3 mRNA and protein expression on GC B cells. Eotaxin could not induce GC B cell chemotaxis and adhesion but triggered apoptosis of GC B cells.</p><p><b>CONCLUSION</b>IL-2 and IL-4 together induced expression of CCR3 on GC B cells, and the receptor acted as a death receptor.</p>
الموضوعات
Humans , Apoptosis , B-Lymphocytes , Metabolism , Pathology , Cell Adhesion , Chemotaxis, Leukocyte , Germinal Center , Metabolism , Pathology , Interleukin-2 , Pharmacology , Interleukin-4 , Pharmacology , RNA, Messenger , Receptors, CCR3 , Receptors, Chemokine , Geneticsالملخص
<p><b>OBJECTIVE</b>To investigate the optimal margin in nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) 4 cm or less in diameter.</p><p><b>METHODS</b>Eighty-two kidneys with RCC 4 cm or less in diameter resected by radical nephrectomy were prospectively studied. The kidney samples were sectioned at 3 mm interval and examined for multicentricity. On each layer of tissue sectioned, parenchyma margin of 15 mm beyond pseudocapsule was continuously sectioned and examined for completeness of pseudocapsule and extra-pseudocapsule cancer lesion. The farthest distance between extra-pseudocapsule lesion and primary tumor was measured. PCNA expression was detected in 41 patients by using standard SP immunohistochemistry technique.</p><p><b>RESULTS</b>The diameter of 82 primary tumors was 3.4 +/- 0.8 cm (range 1.5 - 4.0 cm). Of these, 31.7% (26/82) were found without intact pseudocapsule and 17.1% (14/82) with positive cancer lesions beyond pseudocapsule. The average distance between extra-pseudocapsule cancer lesion and primary tumor was 0.5 +/- 1.3 mm (range 0 - 5.0 mm), with a confidential interval (CI) of 95% (0.11, 0.94). Statistically, the one side percentile P(95) was 4.9 mm, P(97.5) was 5.0 mm and P(100) was 5.0 mm. The mean PCNA index in the 41 patients with RCC was (29.5 +/- 17.6)%, which was (49.6 +/- 21.5)% in the group with extra-pseudocapsule cancer lesions and (24.6 +/- 12.7)% in the group without (t = 3.162, P = 0.013). The ratio of strong expression was 5/8 in the group with extra-pseudocapsule cancer lesions, and 18.2% (6/33) in the group without the lesions (chi(2) = 6.442, P = 0.011). Logistic regression analysis showed that completeness of pseudocapsule and PCNA index were significant predictors of extra-pseudocapsule cancer lesions (P = 0.019).</p><p><b>CONCLUSIONS</b>These data suggest that when NSS is performed in RCC 4 cm or less in diameter, a margin of more than 5 mm of adjacent parenchyma should be excised with the tumor. Enucleation alone was associated with a significant risk of incomplete excision, and therefore liable for local recurrence. Tumors with incomplete pseudocapsule and(or) high PCNA indices are more likely to have extra-pseudocapsule cancer lesions, so intensive follow-up is necessary after NSS.</p>