Involvement of miRNAs in the differentiation of human glioblastoma multiforme stem-like cells

Glioblastoma multiforme (GBM)-initiating cells (GICs) represent a tumor subpopulation with neural stem cell-like properties that is responsible for the development, progression and therapeutic resistance of human GBM. We have recently shown that blockade of NFκB pathway promotes terminal differentiation and senescence of GICs both in vitro and in vivo, indicating that induction of differentiation may be a potential therapeutic strategy for GBM. MicroRNAs have been implicated in the pathogenesis of GBM, but a high-throughput analysis of their role in GIC differentiation has not been reported. We have established human GIC cell lines that can be efficiently differentiated into cells expressing astrocytic and neuronal lineage markers. Using this in vitro system, a microarray-based high-throughput analysis to determine global expression changes of microRNAs during differentiation of GICs was performed. A number of changes in the levels of microRNAs were detected in differentiating GICs, including over-expression of hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222, and down-regulation of hsa-miR-93 and hsa-miR-106a. Functional studies showed that miR-21 over-expression in GICs induced comparable cell differentiation features and targeted SPRY1 mRNA, which encodes for a negative regulator of neural stem-cell differentiation. In addition, miR-221 and miR-222 inhibition in differentiated cells restored the expression of stem cell markers while reducing differentiation markers. Finally, miR-29a and miR-29b targeted MCL1 mRNA in GICs and increased apoptosis. Our study uncovers the microRNA dynamic expression changes occurring during differentiation of GICs, and identifies miR-21 and miR-221/222 as key regulators of this process

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Wear Debris Characterization and Corresponding Biological Response: Artificial Hip and Knee Joints

Wear debris, of deferent sizes, shapes and quantities, generated in artificial hip and knees is largely confined to the bone and joint interface. This debris interacts with periprosthetic tissue and may cause aseptic loosening. The purpose of this review is to summarize and collate findings of the recent demonstrations on debris characterization and their biological response that influences the occurrence in implant migration. A systematic review of peer-reviewed literature is performed, based on inclusion and exclusion criteria addressing mainly debris isolation, characterization, and biologic responses. Results show that debris characterization largely depends on their appropriate and accurate isolation protocol. The particles are found to be non-uniform in size and non-homogeneously distributed into the periprosthetic tissues. In addition, the sizes, shapes, and volumes of the particles are influenced by the types of joints, bearing geometry, material combination, and lubricant. Phagocytosis of wear debris is size dependent; high doses of submicron-sized particles induce significant level of secretion of bone resorbing factors. However, articles on wear debris from engineered surfaces (patterned and coated) are lacking. The findings suggest considering debris morphology as an important parameter to evaluate joint simulator and newly developed implant materials

Effectiveness of the modified computed tomography severity index in patients with severe acute pancreatitis [Eficacia del índice de gravedad tomográfico modificado en enfermos con pancreatitis aguda grave]

Introduction: Acute pancreatitis (AP) is a very important cause of morbidity and mortality in Mexico. In 2001 AP was the 17th cause of death. Since 1994, the computed tomography (CT) scan was accepted for the screening of the severity (a) according to the Computed Tomography Severity Index (CTSI). In 2004 Mortele et al., developed a new tomography classification, Modified Computed Tomography Severity Index (MCTSI) including pancreatic and extra pancreatic disease, obtaining a very good correlation with those with organ failure. This study proposes compare the tomography classifications as indicators of severity. Methods: Cross-sectional study. Were included 30 patients with acute pancreatitis; APACHE II ≥8, non improvement with medical treatment and with initial mild pancreatitis, with addition of signs of complication in the first 72 hours of evolution, under CT scan, CTSIM and CTSI were compared. Statistical analysis using X2 test was calculated, kappa concordance coefficient (k) for the severity classifications. Results: AP prevalence was 51.07%.Of the 30 patients including, 19 man with mean age of 39.0 years (18-58 years), and 11 woman, with mean age of 50.9 years (22-82 years). The main causes were biliary pancreatitis in 16 cases (53.3%), and the second was alcohol, 8 cases (26.7%). The kappa concordance coefficient for both tomography scans was 0.48 (p ≤ 0.003). For the CTSIM and CTSI sensitivity was 61% vs. 38%, specificity 66% vs. 100% and positive predictive value of 81% vs. 100%, respectively. Conclusions: The CTSIM is more useful for the screening in patients with severe acute pancreatitis than CTSI

Effectiveness of the modified computed tomography severity index in patients with severe acute pancreatitis [Eficacia del índice de gravedad tomogrZapotitlánfico modificado en enfermos con pancreatitis aguda grave]

Introduction: Acute pancreatitis (AP) is a very important cause of morbidity and mortality in Mexico. In 2001 AP was the 17th cause of death. Since 1994, the computed tomography (CT) scan was accepted for the screening of the severity (a) according to the Computed Tomography Severity Index (CTSI). In 2004 Mortele et al., developed a new tomography classification, Modified Computed Tomography Severity Index (MCTSI) including pancreatic and extra pancreatic disease, obtaining a very good correlation with those with organ failure. This study proposes compare the tomography classifications as indicators of severity. Methods: Cross-sectional study. Were included 30 patients with acute pancreatitis; APACHE II ?8, non improvement with medical treatment and with initial mild pancreatitis, with addition of signs of complication in the first 72 hours of evolution, under CT scan, CTSIM and CTSI were compared. Statistical analysis using X2 test was calculated, kappa concordance coefficient (k) for the severity classifications. Results: AP prevalence was 51.07%.Of the 30 patients including, 19 man with mean age of 39.0 years (18-58 years), and 11 woman, with mean age of 50.9 years (22-82 years). The main causes were biliary pancreatitis in 16 cases (53.3%), and the second was alcohol, 8 cases (26.7%). The kappa concordance coefficient for both tomography scans was 0.48 (p ? 0.003). For the CTSIM and CTSI sensitivity was 61% vs. 38%, specificity 66% vs. 100% and positive predictive value of 81% vs. 100%, respectively. Conclusions: The CTSIM is more useful for the screening in patients with severe acute pancreatitis than CTSI

Vitamin D Deficiency in Mexican Pregnant Women: Is Supplementation with ≤400 IU/day Enough?

Controversy remains surrounding vitamin D routine supplementation in healthy pregnancy, and the doses are unclear. The aim of this study was to describe maternal vitamin D status throughout pregnancy in a group of Mexican women and evaluate the effect of frequently prescribed doses of vitamin D3 on longitudinal 25-OH-D concentrations, adjusting for obesity, season, and other factors. We conducted a cohort study (Instituto Nacional de Perinatología-INPer) (2017–2020)) of healthy pregnant women without complications. Pregestational overweight/obesity (body mass index ≥ 25), vitamin D3 supplementation (prescribed by physician; 0–250, 250–400, and >400 IU/day), and serum 25-OH-D concentrations (ELISA) were evaluated in each trimester of pregnancy. Vitamin D deficiency or insufficiency was computed (<20 and <30 ng/mL, respectively). We studied 141 adult women; 58.5% had pregestational obesity or overweight. In the first trimester, 45.8% of the women were supplemented with vitamin D3; 51.4% had vitamin D insufficiency and 37.3%, deficiency. In the third trimester, 75.4% of the women were supplemented, and 20% of them still had deficiency. The final general mixed linear model showed that 25-OH-D significantly increased throughout pregnancy (p < 0.001); the highest increase was observed in the third trimester in women with doses >400 IU/day of vitamin D3 (+4 ng/mL, 95% CI: 1.72–8.11 ng/mL). In winter/autumn, 25-OH-D concentrations were also lower (p ≤ 0.05). In this group of pregnant Mexican women, the prevalence of vitamin D deficiency and insufficiency was high. A higher increase in 25-OH-D concentrations during pregnancy was observed when the women were supplemented with >400 IU/day. Common supplementation doses of 250–400 IU/day were insufficient for achieving an adequate maternal vitamin D status

Involvement of miRNAs in the differentiation of human glioblastoma multiforme stem-like cells

Glioblastoma multiforme (GBM)-initiating cells (GICs) represent a tumor subpopulation with neural stem cell-like properties that is responsible for the development, progression and therapeutic resistance of human GBM. We have recently shown that blockade of NFκB pathway promotes terminal differentiation and senescence of GICs both in vitro and in vivo, indicating that induction of differentiation may be a potential therapeutic strategy for GBM. MicroRNAs have been implicated in the pathogenesis of GBM, but a high-throughput analysis of their role in GIC differentiation has not been reported. We have established human GIC cell lines that can be efficiently differentiated into cells expressing astrocytic and neuronal lineage markers. Using this in vitro system, a microarray-based high-throughput analysis to determine global expression changes of microRNAs during differentiation of GICs was performed. A number of changes in the levels of microRNAs were detected in differentiating GICs, including over-expression of hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222, and down-regulation of hsa-miR-93 and hsa-miR-106a. Functional studies showed that miR-21 over-expression in GICs induced comparable cell differentiation features and targeted SPRY1 mRNA, which encodes for a negative regulator of neural stem-cell differentiation. In addition, miR-221 and miR-222 inhibition in differentiated cells restored the expression of stem cell markers while reducing differentiation markers. Finally, miR-29a and miR-29b targeted MCL1 mRNA in GICs and increased apoptosis. Our study uncovers the microRNA dynamic expression changes occurring during differentiation of GICs, and identifies miR-21 and miR-221/222 as key regulators of this process