We investigated the anti-inflammatory activities of argirein and rhein on inflammatory edema in rat paw which was caused by complete adjuvant, compared with ibuprofen. We hypothesized that the adjuvant-induced inflammation is attributed to upregulation of activating transcript factor 6 (ATF6; a chaperone for endoplasmic reticulum (ER) stress), p66Shc (an adaptive protein modulating oxidative stress), and NADPH oxidase subunits p22phox and gp91phox in the inflamed tissues. Biomarkers were measured in the rat paw in association with monitoring swellings. The primary inflammatory edema of the injected paw occurred rapidly and sustained over a couple of days, and the secondary inflammation developed 2 weeks later. The inflammatory edema was accompanied by upregulation of cytokines including ATF6, p66Shc, p22phox, gp91phox, and MMP-2 and an increase in ratio of p-Akt/Akt in the afflicted paw. These were suppressed by either argirein and rhein or ibuprofen. These findings indicate that ER stress, upregulated p66Shc, and phosphorylated Akt are actively implicated in the inflammatory zone caused by adjuvant injection. These biomarkers were causal factors responsible for inflammation of the afflicted paw and were suppressed by a supermolecule argirein and rhein, and the anti-inflammatory activities of the two compounds were comparable to that of ibuprofen.
Lung cancer is the leading cause of cancer-related deaths for both men and women. Early diagnosis of lung cancer has a 5-year survival rate of 48.8%, however, nearly 35% of stage I patients relapses after surgical resection, thus portending a poor prognosis. Therefore, detecting lung cancer in early stage and further identifying the high-risk patients would allow the opportunity to provide adjuvant therapy and possibly increase survival. There is considerable evidence that the immune system produces an autoantibody response to neoplastic cells. The detection of such autoantibodies has been shown to have diagnostic and prognostic value. Here we took advantage of the high-throughput Luminex technique to multiplex a total of 14 tumor-associated autoantigens to detect the autoantibody from the patients sera. The 14 antigens were expressed by in vitro transcription/translation system with HaloTag at N-terminus. The fusion proteins were then covalently immobilized onto the Luminex microspheres conjugated by the halo-link ligand, thus eliminating the protein purification procedure. Sera samples from cancer patients and healthy controls were interacted with the microsphere-antigen complex to measure the autoantibodies. We have developed a quick multiplex detection system for measuring autoantibody signature from patient sera with minimal cross-reaction. A panel of seven autoantibody biomarkers has generated an AUC>80% in distinguishing the lung cancers from healthy controls. This study is the first report by combining Luminex platform and HaloTag technology to detect humoral immune response in cancer patients. Due to the flexibility of the Luminex technology, this approach can be applied to others conditions such as infectious, neurological, and metabolic diseases. One can envision that this multiplex Luminex system as well as the panel of seven biomarkers could be used to screen the high-risk population with subsequent CT test based on the blood test result.
Background Thyroid cancer (TC) is considered as the fastest growing malignancy in the human endocrine system, particularly papillary thyroid cancer (PTC). MicroRNAs (miRs) serve as a role in promoting or suppressing tumors in various types of malignant tumor including PTC. This study aims to explore whether microRNA-26a-5p (miR-26a-5p) could affect the proliferation, invasion and metastasis ability of PTC cells by regulating Wnt5a. Materials and methods The expression of miR-26a-5p was examined by qRT-PCR in PTC tissue samples (58 cases, mean age 53 years old) and PTC cell lines (K1 and BCPAP). Cell proliferation, invasion and migration were tested with CCK8 assay, colony formation assay, transwell invasion assay and wound healing assay, respectively. Luciferase reporting experiment was used to verify that Wnt5a is a molecular target of miR-26a-5p. The relationship between miR-26a-5p and Wnt5a was analyzed by qRT-PCR and Western blot and was further proved by Pearson’s correlation analysis. Animal (24 nude mice) experiments were used to demonstrate that miR-26a-5p inhibits tumor growth by targeting Wnt5a. Results The expression of miR-26a-5p declined in PTC tissues ( P <0.01). The expression of miR-26a-5 was also significantly down-regulated in PTC tissues with advanced TNM stages ( P <0.01) and lymph node metastasis ( P <0.01) compared with normal thyroid tissues. Compared with normal human thyroid cell line Nthy-ori 3-1, the expression of miR-26a-5p in K1 cells and BCPAP cells were nearly 4.02-fold ( P <0.01) and 2.51-fold ( P <0.01) reduced. Up regulation of miR-26a-5p inhibited proliferation, colony formation, invasion and migration of PTC cells. MiR-26a-5p negatively regulated Wnt5a expression ( r =−0.887, P <0.01), yet Wnt5a overexpression reversed the tumor-suppressive effect of miR-26a-5p in PTC. Animal experiments further verified that miR-26a-5p inhibited PTC growth by targeting Wnt5a. Conclusion Overexpression of miR-26a-5p depresses proliferation, invasion, metastasis of PTC via Wnt5a. Therefore, miR-26a-5p may represent a potentially effective target gene for PTC.
BackgroundCisplatin (DDP)-based chemotherapy is the mainstay of first-line therapy for lung cancer. However, their efficacy is often limited by the existence or development of chemoresistance. The aim of this study was to find and investigate the function of miRNAs in cisplatin (DDP)-resistant non-small cell lung cancer (NSCLC) A549 cell.MethodsQuantitative real-time PCR assay was employed to compare the differences of miRNA expression in both cisplatin-resistant A549 (A549/DDP) cell and the parental A549 cell. The dysregulated miRNAs were then corrected by transfecting oligonucleotides into A549/DDP cells. The cellular sensitivity to cisplatin, cell apoptosis and migration were conducted by MTT, flow cytometry and cell wound healing assay, respectively.ResultsBoth miR-589 and miR-1244 were significantly down-regulated in A549/DDP cell compared to the parental A549, while the expression of miR-182 and miR-224 were increased in A549/DDP cell (P < 0.05). Importantly, transfection of the cisplatin-resistant cells with either miR-589 or miR-1244 resulted in an increased sensitivity to cisplatin, indicating that the dysregulated miRNA may play an important role in chemotherapy resistance in cancer cell. The rescued expression of miRNA also reduced cell invasion and increased apoptosis of A549/DDP cell.ConclusionThe study indicates a crucial role of miR-1244 in the progress of cisplatin resistance of A549. Further understanding of miR-1244-mediated signaling pathways may promote the clinical use of miR-1244 in lung cancer therapy.
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