Meta-analysis of studies comparing adjuvant dexamethasone to glycerol to improve clinical outcome of bacterial meningitis.

BACKGROUND: Neurological complications are a problematic factor in acute bacterial meningitis; hence, its prevention is the key to ensure the success of meningitis treatment. Glycerol and dexamethasone are both applied in this regard. Oral glycerol is an appropriate alternative instead of intravenous dexamethasone because it does not have problems related to intravenous injection, the high cost, and drug complications. The main objective of this study was to compare the efficacy of adjuvant dexamethasone versus glycerol in order to improve the clinical outcome of bacterial meningitis. MATERIALS AND METHODS: We conducted a search on the available resources including PubMed, Ovid, Elsevier, Cochrane, and another search engines such as Google till 2014. All clinical trials that were performed in the field of comparing the effectiveness of the two drugs and met the inclusion criteria were gathered and after extraction the relative risk (RR) values, the pooled RR was calculated. The main outcome was neurological complications. Meta-analysis of the data was performed in Stata version 11.2 using both fixed and random effect models, weighting each study by inverse of variance. RESULTS: In 5 comparative studies (1,340 patients), the rate of neurological complications of glycerol compared to that of dexamethasone was 1.02 [95% confidence interval (CI), 0.98 compared to 1.12]. The rate of neurological complications of dexamethasone compared to dexamethasone + glycerol was 1 (95% CI, 0.97 compared to 1.03), dexamethasone compared to placebo was 0.99 (95% CI, 0.97 compared to 1.03), glycerol compared to glycerol + dexamethasone was 0.98 (95% CI, 0.94 compared to 1.02), and glycerol compared to placebo was 0.97 (95% CI, 0.94 compared to 1.01). In these studies, no difference was reported between dexamethasone and glycerol in terms of reducing neurological complications. CONCLUSION: Although there were some weak evidences for the nonstatistical significant effect of glycerol in the prevention of neurologic complication after meningitis, there was no difference between glycerol and dexamethasone.

Analysis of EMT induction in a non-invasive breast cancer cell line by mesenchymal stem cell supernatant: Study of 2D and 3D microfluidic based aggregate formation and migration ability, and cytoskeleton remodeling.

AIMS: The process of Epithelial-to-mesenchymal transition (EMT) as a phenotypic invasive shift and the factors affecting it, are under extensive research. Application of supernatants of human adipose-derived mesenchymal stem cells (hADMSCs) on non-invasive cancer cells is a well known method of in vitro induction of EMT like process. While previous researches have focused on the effects of hADMSCs supernatant on the biochemical signaling pathways of the cells through expression of different proteins and genes, we investigated pro-carcinogic alterations of physico-mechanical cues in terms of changes in cell motility and aggregated formation in 3D microenvironments, and cytoskeletal actin-myosin content and fiber arrangement. MAIN METHODS: MCF-7 cancer cells were treated by the supernatant from 48 hour-starved hADMSCs, and their vimentin/E-cadherin expressions were evaluated. The invasive potential of treated and non-treated cells was measured and compared through aggregate formation and migration capability. Furthermore, alterations in cell and nucleus morphologies were studied, and F-actin and myosin-II alterations in terms of content and arrangement were investigated. KEY FINDINGS: Results indicated that application of hADMSCs supernatant enhanced vimentin expression as the biomarker of EMT, and induced pro-carcinogenic effects on non-invasive cancer cells through increased invasive potential by higher cell motility and reduced aggregate formation, rearrangement of actin structure and generation of more stress fibers, together with increased myosin II that lead to enhanced cell motility and traction force. SIGNIFICANCE: Our results indicated that in vitro induction of EMT through mesenchymal supernatant influenced biophysical features of cancer cells through cytoskeletal remodeling that emphasizes the interconnection of chemical and physical signaling pathways during cancer progress and invasion. Results give a better insight to EMT as a biological process and the synergy between biochemical and biophysical parameters that contribute to this process, and eventually assist in improving cancer treatment strategies.

Mechanics of actin filaments in cancer onset and progress.

Cancer, as a major cause of mortality, is highly related to alterations in the structure and behavior of cells of cancerous tissues. The invasive nature of cancer cells is correlated with their increased traction force, high deformability and altered cell adhesion. These changes are directly attributed to the remodeling of cell cytoskeleton mostly in actin structure. While microtubules and intermediate filaments are mostly involved in mechanical properties of cytoskeleton, actin fibers actively contribute to not only mechanical properties, but also other aspects. Hence study of actin mechanics assists in a deeper understanding of cancer related events. Here, with a biomechanical perspective, we describe the cytoskeleton changes in cancer onset and progress in fiber and protein levels, with focus on actin structure in terms of content and arrangement. Cytoskeleton remodeling and particularly alterations in the content and arrangement of actin structure, highly influence cell mechanical properties, force generation and adhesion potentials.