ABSTRACT
Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
Subject(s)
Animals , Male , Cytokines , Metabolism , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Gastrointestinal Microbiome , Houttuynia , Chemistry , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Inflammation , Drug Therapy , Pathology , Influenza A Virus, H1N1 Subtype , Virulence , Intestinal Mucosa , Metabolism , Microbiology , Pathology , Lung , Metabolism , Pathology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Pathology , Plant Extracts , Chemistry , Polysaccharides , Chemistry , Pharmacology , Therapeutic Uses , Toll-Like Receptors , Metabolism , Zonula Occludens-1 Protein , MetabolismABSTRACT
<p><b>BACKGROUND</b>A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.</p><p><b>METHODS</b>Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1 x 10(5), 1 x 10(6) human breast cancer stem-like cells, and 1 x 10(6) parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1 x 10(6) MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Our results demonstrated that cells in implanted human bones of group B, which received 1 x 10(6) cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P = 0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest.</p><p><b>CONCLUSIONS</b>In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.</p>
Subject(s)
Animals , Female , Humans , Mice , Bone Neoplasms , Breast Neoplasms , Pathology , CD24 Antigen , Cell Line, Tumor , Disease Models, Animal , Hepatocyte Growth Factor , Pharmacology , Hyaluronan Receptors , Immunohistochemistry , Neoplastic Stem Cells , Pathology , Osteopontin , Phenotype , Receptors, CXCR4ABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic potential of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, and to analyze TRAIL-induced apoptosis in Jurkat cells.</p><p><b>METHODS</b>Expression of TRAIL receptors (DR4 and DR5) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Cytotoxic effects were determined by colony formation assay and a cell counting kit. The effects of recombinant TRAIL on apoptosis of Jurkat cells were determined by DNA fragmentation (DNA ladder) and PI staining. Changes in mitochondrial membrane potential were detected with JC-1 fluorescence.</p><p><b>RESULTS</b>TRAIL inhibited the proliferation and induced internucleosomal DNA fragmentation (characteristic of apoptosis) and loss of mitochondrial membrane potential.</p><p><b>CONCLUSION</b>Recombinant soluble TRAIL can be used as a therapy for cancer.</p>