Abstract: Background: Degenerative diseases are a medical, social, and economic problem worldwide. The most significant factors predisposing the development of degenerative changes in intervertebral discs are a low density and poor biosynthetic potential of the cells. Therefore, stem cell therapy in this case should show high clinical efficiency. Methods: The research aim was to evaluate the regenerative potential of cryopreserved mesenchymal stem cells (MSCs) upon degenerative changes in intervertebral discs. Rats with simulated degenerative damage of the intervertebral disc Co6–Co7 were administrated with 0.5 × 106 of either native or cryopreserved cells on a collagen sponge to the defect area. The results of experiments were histomorphometrically evaluated on the 30th, 60th, and 90th days after treatment. Results: The restoration of tears, clefts, and collagen fiber fragmentations was noted on the 60th and 90th day after administration of native and cryopreserved MSCs respectively. An increase in fibrochondrocyte density got ahead of the annulus fibrosus height recovery. In the control group without treatment the regeneration was hardly observed. Conclusion: The use of MSCs promotes the restoration of the degenerated intervertebral disc. Cryopreserved MSCs have a “lag” therapeutic effect at the early stages, but show similar results to the native analogue on the 90th day after administration.
Abstract: Background: The interplay between Epstein-Barr virus infection, malaria, and endemic Burkitt’s Lymphoma is not well understood. Reports show diminished EBV-specific Th1 responses in children living in malaria endemic areas and deficiency of EBNA1-specific IFN-γ T cell responses in children with endemic Burkitt’s Lymphoma (eBL). This study, therefore, examined some factors involved in the loss of EBNA-1-specific T cell responses in eBL. Methods: T-cell subset frequencies, activation, and IFN-γ- or IL-4-specific responses were analyzed by flow-cytometry. Plasma cytokine levels were measured by ELISA. Results: CD4+ and CD8+ cells in age- and sex-matched healthy controls (n = 3) expressed more IFN-γ in response to all immunostimulants than in pediatric endemic BL (eBL) patients (n = 4). In healthy controls, IFN-γ expression was higher than IL-4 expression, whereas in eBL patients the expression of IL-4 by CD4+ cells to EBNA-1 was slightly higher than IFN-γ. Moreover, the blood levels of TNF-α was significantly lower (p = 0.004) while IL-10 was significantly higher (p = 0.038), in eBL patients (n = 21) compared to controls (n = 16). Additionally, the frequency of CD4+CD25hi+ T cells was higher in both age-matched acute uncomplicated malaria (n = 26) and eBL (n = 14) patients compared to healthy controls (n = 19; p = 0.000 and p = 0.027, respectively). Conclusion: The data suggest that reduced Th1 response in eBL might be due to increased levels of IL-10 and T reg cells.
Abstract: Nanomedicine helps to fight diseases at the cellular and molecular level by utilizing unique properties of quasi-atomic particles at a size scale ranging from 1 to 100 nm. Nanoparticles are used in therapeutic and diagnostic approaches, referred to as theranostics. The aim of this review is to illustrate the application of general principles of nanotechnology to select examples of life sciences, molecular medicine and bio-assays. Critical aspects relating to those examples are discussed.
Abstract: HGF/c-Met system has covered, in the past two decades, multiple areas of research, from basic cell biology to clinical trials. This research topic witnessed a good deal of scientific interest and progress. [...]
Abstract: Accumulating evidence suggests that ubiquitin E3 ligases are involved in cancer development as their mutations correlate with genomic instability and genetic susceptibility to cancer. Despite significant findings of cancer-driving mutations in the BRCA1 gene, estrogen receptor (ER)-positive breast cancers progress upon treatment with DNA damaging-cytotoxic therapies. In order to understand the underlying mechanism by which ER-positive breast cancer cells develop resistance to DNA damaging agents, we employed an estrogen receptor agonist, Erb-041, to increase the activity of ERβ and negatively regulate the expression and function of the estrogen receptor α (ERα) in MCF-7 breast cancer cells. Upon Erb-041-mediated ERα down-regulation, the transcription of an ERα downstream effector, BCA2 (Breast Cancer Associated gene 2), correspondingly decreased. The ubiquitination of chromatin-bound BCA2 was induced by ultraviolet C (UVC) irradiation but suppressed by Erb-041 pretreatment, resulting in a blunted DNA damage response. Upon BCA2 silencing, DNA double-stranded breaks increased with Rad51 up-regulation and ataxia telangiectasia mutated (ATM) activation. Mechanistically, UV-induced BCA2 ubiquitination and chromatin binding were found to promote DNA damage response and repair via the interaction of BCA2 with ATM, γH2AX and Rad51. Taken together, this study suggests that Erb-041 potentiates BCA2 dissociation from chromatin and co-localization with Rad51, resulting in inhibition of homologous recombination repair.
Abstract: The hepatocyte growth factor (HGF): MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents—either as therapeutic proteins or small molecules that target the HGF/MET pathway—have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed.