Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by poor survival rates and lack of effective therapies. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally through specific pairing with target messenger RNAs (mRNAs). Extracellular vesicles (EVs), a heterogeneous group of cell-derived vesicles, transport miRNAs, mRNAs and intracellular proteins, and have been shown to promote horizontal malignancy into adjacent tissue, as well as resistance to conventional therapies. Furthermore, GB-derived EVs have distinct miRNA contents and are able to penetrate the blood–brain barrier. Numerous studies have attempted to identify EV-associated miRNA biomarkers in serum/plasma and cerebrospinal fluid, but their collective findings fail to identify reliable biomarkers that can be applied in clinical settings. However, EVs carrying specific miRNAs or miRNA inhibitors have great potential as therapeutic nanotools in GB, and several studies have investigated this possibility on in vitro and in vivo models. In this review, we discuss the role of EVs and their miRNA content in GB progression and resistance to therapy, with emphasis on their potential as diagnostic, prognostic and disease monitoring biomarkers and as nanocarriers for gene therapy.
BackgroundThe epidermal growth factor receptor (EGFR) mutation status assessment has become increasingly important given the significant impact of tyrosine kinase inhibitors in lung cancer management.Our aim was to compare real life operational characteristics for three EGFR mutation assays - two targeted approaches and a next generation sequencing (NGS) technique.MethodsEGFR mutation status was assessed for lung adenocarcinoma samples (formalin fixed- paraffin embedded samples) using qPCR, SNaPshot and NGS (Ion Torrent™) techniques.ResultsA total of 15 high clinical significance mutations were identified by at least one technique from the total of 64 samples. All mutations were identified by the TaqMan qPCR technique while SNaPshot in conjunction with fragment analysis identified 11 EGFR mutations. The NGS approach followed by an automatic analysis using the default calling parameters identified 10 mutations from the SNaPshot/qPCR panel and other three insertions, five point mutations and 58 silent variants; manual data review identified all 15 high significance mutations.ConclusionsPerformance was similar for high tumor content samples but careful data analysis and post hoc variant calling filter alterations were necessary in order to obtain robust results from low tumor content samples by NGS. NGS is able to generate a comprehensive mutational profile albeit at a higher cost and workload. Result interpretation should take into account not only general run parameters such as mean read depth but also relative coverage and read distribution; currently there is an acute need to define firm recommendations/standards concerning NGS data interpretation and quality control.
Introduction: Neonatal early onset sepsis assessment is based on the history of pregnancy and delivery and nonspecific clinical signs. None of the biomarkers currently in use for clinical practice has adequate prognostic value, so it is not possible to clearly distinguish neonates with culture-proven sepsis from those with only risk factors or clinical suspicion. Endocan is an endothelial mediator involved in the inflammatory response that is present in low concentrations in the serum of healthy subjects, and in much higher concentrations in patients with SIRS and septic shock. The purpose of this study is to evaluate the utility of serum endocan serum levels as a biomarker for the diagnosis of neonatal early onset sepsis (EOS). Methodology: Serum endocan concentration was measured in newborns with clinical suspicion of EOS admitted to the Neonatal Intensive Care Unit on day 1, 3 and 7. Results: Serum endocan levels were significantly increased in septic compared to non-septic neonates in the early stages of sepsis (2.43 ± 0.95 vs. 1.77 ± 0.57, p = 0.004), continued to rise up to 72 hours from onset and then decreased by the seventh day under treatment. Conclusions: These results suggest a potential role for endocan as an early marker for diagnosis and follow-up in neonatal EOS. Studies on a larger number of cases are needed in order to establish the practical utility of this molecule as a diagnostic tool for clinical practice.
Introduction: Endocan is a specific endothelial mediator involved in the inflammatory response. Its role in the diagnosis of sepsis has been studied in adult patients and late onset neonatal sepsis. The clinical signs of early onset sepsis (EOS) are nonspecific and routinely used biomarkers, such as C-reactive protein and procalcitonin, have low sensitivity, specificity and positive predictive value. Endocan could be useful as a biomarker for diagnosis of EOS, but at present normal range values for this molecule have not been reported. The aim of this study is to establish the normal values range for serum endocan in term and preterm newborns without risk factors for EOS and to characterize the variation pattern of its levels at different postnatal moments. Methodology: Mean endocan serum concentration (ESC) was measured in term and preterm newborns without clinical suspicion of EOS at different moments from birth. Results: ESC (ng/mL) in term newborns was 1.74+/-0.13 on day 1 and 2.02+/-0.41 on day 3 respectively, (p=0.09). In preterm newborns ESC (ng/mL) was 2.02+/-0.11 and 1.97+/-0.18, (p=0.8) for day 1 and 3 respectively. ESC was not significantly influenced by sex, mode of delivery, evidence of fetal distress or presence of minor birth trauma. Conclusions: ESC (ng/mL) between the first and third day of life in either term or preterm infants don’t appear to be significantly influenced by factors that are associated with elevation of inflammatory markers, thus using this biomarker for the diagnosis of EOS might reduce the false positive results.
Mycobacteria culture remains the cornerstone of tuberculosis diagnosis. Naturally contaminated samples need pre-inoculation processing but some economically challenged medical facilities may benefit from a simpler and cheaper sputum decontamination procedure. The aim of this study was to test a simple decontamination method lacking a centrifugation step to be used in conjunction with the culture on Löwenstein-Jensen medium. A total of 7446 sputum samples collected from 3229 patients were microscopically examined and then cultured on Löwestein-Jensen medium using a simplified Petroff method. All positive cultures were confirmed by direct microscopic examination and biochemical identification. Culture and microscopic status and time to positivity were recorded. Mean and median times to culture and contamination rate were similar as compared to classical Löwenstein-Jensen culture method. Overall results suggest that the described modified of Petroff method may be used with adequate results in resource poor settings as the method does not require an aerosol safe centrifuge and relies on cheap, stable and readily available reagents.
Ketoprofen a non-steroidal anti-inflammatory drug was intercalated into Mg-Al hydrotalcites lamella as an inorganic host by different methods. The intercalation compounds were examined by X-ray diffraction (XRD), FTIR spectroscopy, differential thermal analysis and thermo gravimetric analysis. The XRD patterns of the samples the diffraction peaks are typical to those of well crystallized solids with the hydrotalcite structure. The FTIR spectroscopy and thermogravimetric (DTG) analysis point out the presence of the organic compound in the network structure of the synthesized hydrotalcites.
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