Bone marrow niche is a major contributing factor in leukemia development and drug resistance in acute myeloid leukemia (AML) patients. Although mimicking leukemic bone marrow niche relies on two-dimensional (2D) culture conditions, it cannot recapitulate complex bone marrow structure that causes introduction of different three-dimensional (3D) scaffolds. Simultaneously, microfluidic platform by perfusing medium culture mimic interstitial fluid flow, along with 3D scaffold would help for mimicking bone marrow microenvironment. In this study TF-1 cells were cocultured with bone marrow mesenchymal stem cells (BM-MSCs) in 2D and 3D microfluidic devices. Phenotype maintenance during cell culture and proliferation rate was assayed and confirmed by cell cycle analysis. Morphology of cells in 2D and 3D culture conditions was demonstrated by scanning electron microscopy. After these experiments, drug screening was performed by applying azacitidine and cytarabine and cytotoxicity assay and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for B cell lymphoma 2 (BCL2) were done to compare drug resistance in 2D and 3D culture conditions. Our result shows leukemic cells in 3D microfluidic device retaining their phenotype and proliferation rate was significantly higher in 3D culture condition in comparison to 2D culture condition (p < 0.05), which was confirmed by cell cycle analysis. Cytotoxicity assay also illustrated drug resistance in 3D culture condition and qRT-PCR demonstrated higher BCL2 expression in 3D microfluidic device in contrast to 2D microfluidic device (p < 0.05). On balance, mimicking bone marrow niche would help the target therapy and specify the role of niche in development of leukemia in AML patients.
Platelets play a critical role in wound healing and hemostasis, as well as in repairing bone fracture. The impact of platelets on inflammation and inflammatory diseases has been appreciated. It has been demonstrated that inflammation and oxidative stress are intimately involved in the pathogenesis of osteoporosis. Degranulation of platelets, anuclear cell fragments, leads to the release of different growth factors and chemoattractants affecting bone metabolism. The net effect is, however, not fully understood. The current review is aimed to examine available studies on the impact of platelets on bone health. We searched data from Scopus, PubMed and Web of Science using keywords such as platelets, osteoblasts, osteoclasts, bone, antiplatelet drugs, bone formation, and bone resorption. As hypothesis of the review is emerging, a small number of in vivo and in vitro studies are found. Based on the available data, platelets and platelet-derived numerous immune and inflammatory agents can be viewed as targets for therapeutic and/or preventive measures in osteoporosis.
High uptakes of USPIO nanoparticles in the liver and spleen and their fast clearance from other tissues suggest that these nanoparticles labeled with a β-emitter radioisotope could be suitable as treatment agents for spleen and liver malignancies only if the organ tolerance dose is not exceeded.
Objectives: Oral lichen planus (OLP) is a chronic, immunologically mediated, mucocutaneous disorder. A wide range of topical and systemic therapies have been used in the treatment of OLP. The efficacy of IMOD (an Iranian new immunomodulator drug, containing selenium, carotene, and flavonoids) in the management of oral lichen planus was evaluated. Study design: In a before-after clinical trial study, thirty patients (21 women and 9 men; age range 35-66 years with 112 lesions) with lichen planus were enrolled. The study covered a three-month period of therapy by IMOD (400 mg/day) and a three-month follow-up period after drug cessation. Outcome measures include soreness relief based on the "nu-meric scale", and clinical improvement of lesion size and score. Saliva levels of TNF-α was analysed at the baseline and after treatment by ELISA. Statistical analysis of Wilcoxon and paired student's t-test were used. Results: Approximately 85% of patients showed partial to complete improvement and remained symptom free after drug cessation. There was no significant difference in mean saliva TNF-α level before and after the treatment. Conclusion: These results suggest that IMOD seems to be an effective alternative treatment for OLP and TNF-α may not be a good indicator for monitoring therapeutic response of OLP.
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