FTY720 increases paclitaxel efficacy in cisplatin-resistant oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma has high recurrence and cisplatin resistance. As cancer stem cells, autophagy, and sphingolipids have been appointed as associated with chemotherapy resistance, we tested combined treatments targeting autophagy and/or sphingolipid metabolism with paclitaxel using cisplatin-resistant oral squamous cell carcinoma cells. METHODS: Cisplatin-resistant oral squamous cell carcinoma cells were maintained under exposition to FTY720 and chloroquine combined with paclitaxel and submitted to viability, clonogenicity, and spheres formation assays. The xenograft tumor model using cisplatin-resistant CAL27 cells was adopted to examine the drug combinations' potential antitumoral efficacy. Using an animal model, sphingolipids profiles from plasma and tissue samples were obtained by liquid chromatography coupled to mass spectrometry to identify potential lipids associated with drug response. RESULTS AND DISCUSSION: Our results showed higher autophagic flux in cisplatin-resistant Ooral squamous cell carcinoma (CAL27 and SCC9) cells than in parental cells. The combinations of an autophagy inhibitor (chloroquine) or an autophagy inducer/sphingosine kinase 1 antagonist (FTY720) with paclitaxel (PTX) had a synergistic antitumor effect. Treated CisR cells lost clonogenicity and tumor sphere abilities and reduced proteins associated with proliferation, survival, and cancer stem cells. FTY720 plus PTX had higher antitumor efficacy than PTX against CAL27 CisR xenograft tumor formation. Additionally, increases in glucosylceramide, dehydroglucosylceramide, and sphingomyelin were presented in responsive tumors. CONCLUSION: FTY720 sensitizes cisplatin-resistant oral squamous cell carcinoma cells for paclitaxel.

Myrciaria dubia "camu camu" flour as a magnetoprotector in male mouse infertility.

Possible adverse effects of extremely low frequency magnetic fields (ELF-MF) are linked to a decrease of antioxidant defenses and the production of free radicals. The increase of free radicals affects the mitochondrial functionality inducing apoptosis, which affects the phosphorylation and generation of key ATP in fertilization. Myrciaria dubia, known as "camu camu," is a fruit with high levels of ascorbic acid, which exerts an important antioxidant function in the prevention of premature cell damage. In this study, the effect of Myrciaria dubia flour on oxidative damage produced by ELF-MF (610 µT) was evaluated by detecting the activity of endogenous mitochondrial oxidoreductase enzymes in a complete sperm cycle of mice. We found that the MF caused a significant (P < 0.05) decrease in sperm quality, whereas the groups supplied with Myrciaria dubia flour (50 and 75 mg/kg of body mass) in ELF-MF exposure showed a significant recovery (P < 0.05) in parameters of viability, percentage of plasma membrane integrity and mitochondrial activity, and index of epidymal sperm. This suggests that Myrciaria dubia flour would have an antioxidant activity that counteracts the damaging effects of ELF-MF in spermatogenesis and could be used as a natural ELF-MF protector. Bioelectromagnetics. 40:91-103, 2019. © 2019 Bioelectromagnetics Society.

A robust nonlinear observer for real-time attitude estimation using low-cost MEMS inertial sensors.

This paper deals with the attitude estimation of a rigid body equipped with angular velocity sensors and reference vector sensors. A quaternion-based nonlinear observer is proposed in order to fuse all information sources and to obtain an accurate estimation of the attitude. It is shown that the observer error dynamics can be separated into two passive subsystems connected in "feedback". Then, this property is used to show that the error dynamics is input-to-state stable when the measurement disturbance is seen as an input and the error as the state. These results allow one to affirm that the observer is "robustly stable". The proposed observer is evaluated in real-time with the design and implementation of an Attitude and Heading Reference System (AHRS) based on low-cost MEMS (Micro-Electro-Mechanical Systems) Inertial Measure Unit (IMU) and magnetic sensors and a 16-bit microcontroller. The resulting estimates are compared with a high precision motion system to demonstrate its performance.

Retrospective analysis of outcomes for pediatric acute lymphoblastic leukemia in South American centers.

Introduction: Acute lymphoblastic Leukemia (ALL) is the most common pediatric malignancy. While the survival rate for childhood ALL exceeds 90% in high-income countries, the estimated survival in low-and middle-income countries ranges from 22-79%, depending on the region and local resources. Methods: This study retrospectively reviewed demographic, biological, and clinical parameters of children under 18 years of age with newly diagnosed ALL presenting between 2013-2017 across five pediatric centers in 4 countries in South America. Survival analyses were estimated using the Kaplan-Meier method. Results: Across the five centers, 752 patients were analyzed (Bolivia [N=9], Ecuador [N=221], Paraguay [N=197], Peru [N=325]) and 92.1% (n=690) patients were diagnosed with B-cell and 7.5% (n= 56) with T-cell ALL. The median age was 5.5 years old (IQR 7.29). At diagnosis, 47.8% of patients were categorized as standard and 51.9% as high risk per their institutional regimen. Advanced diagnostics availability varied between modalities. MRD was evaluated in 69.1% of patients; molecular testing was available for ETV6-RUNX, BCR-ABL1, TCF3-PBX1, and KMT2A-rearranged ALL in 75-81% of patients; however, karyotyping and evaluation for iAMP21 were only performed in 42-61% of patients. Central nervous system (CNS) involvement was evaluated at diagnosis in 57.3% (n=429) patients; of these, 93.7% (n=402) were CNS 1, 1.6% (n=7) were CNS 2, 0.7% (n=11) were CNS3, 1.9% (n=8) had cranial nerve palsy, and 2.1% (n=9) results unavailable. Chemotherapy delays >2 weeks were reported in 56.0% (n=421) patients during treatment. Delays were attributed to infection in 63.2% (n=265), drug-related toxicities in 47.3% (n=198), and resource constraints, including lack of bed availability in 23.2% (n=97) of patients. The 3-year Abandonment-sensitive EFS and OS were 61.0±1.9% and 67.2±1.8%, respectively. The 3-year EFS and OS were 71.0±1.8% and 79.6±1.7%, respectively. Discussion: This work reveals opportunities to improve survival, including addressing severe infections, treatment interruptions, and modifications due to drug shortages. In 2018, healthcare professionals across South America established the Pediatric Oncology Latin America (POLA) group in collaboration with St. Jude Children's Research Hospital. POLA collaborators developed an evidence-based, consensus-derived, adapted treatment guideline, informed by preliminary results of this evaluation, to serve as the new standard of care for pediatric ALL in participating institutions.

TNF-α detection using gold nanoparticles as a surface-enhanced Raman spectroscopy substrate.

Background: TNF-α is a cytokine involved in inflammation. Surface-enhanced Raman spectroscopy (SERS) could be useful in its detection. Aim: Identify the TNF-α in an aqueous solution, using gold nanoparticles (AuNPs) as a SERS substrate. Materials & methods: Raman and SERS spectra were obtained from TNF-α samples, combined with AuNPs, with decreasing concentrations of TNF-α. The samples were analyzed using optical transmission spectroscopy, dynamic light scattering, and transmission electron microscopy. Results: Transmission electron microscopy/dynamic light scattering determined a change in the average diameter of the TNF-α/AuNPs (∼9.6 nm). Raman bands obtained were associated with aromatic amino acid side chains. We observe Raman signals for TNF-α concentrations as low as 0.125 pg/ml. Conclusion: TNF-α signal at physiological concentrations was determined with SERS.

Dataset on water-glycerol flow in a horizontal pipeline with and without leaks.

The dataset presented in this article was collected in a laboratory flow circuit, which was designed to investigate high-viscosity flows. The data set is composed of 1200 s (equivalent to 12,000 samples) of mass flow and pressure measurements taken at five points along the pipeline. The first 300 s were recorded when the flow in the loop was composed only of glycerol. The remaining data were acquired when the flow was composed of a water-glycerol mixture. During the data acquisition, two extractions were produced. The research reported in [1] uses 160 s of the data provided here. This article explains in detail the experimental set-up and the principal instruments used for obtaining the dataset. The dataset is in the form of seven columns: Time, Mass Flow, Pressure 1, Pressure 2, Pressure 3, Pressure 4, Pressure 5, in supplementary Excel and Matlab files.

Aroma-retention capacities of functional whey protein aggregates: Study of a strawberry aroma in solutions and in fat-free yogurts.

The aroma-retention capacity of functional whey protein aggregates (WPA) was compared to that of native whey protein isolate (WPI) in aqueous solutions and in fat-free yogurts. The retention of aroma compounds, constituting a model strawberry aroma, was evaluated by calculating gas-matrix partition coefficients using headspace gas chromatography (HS-GC). The retention capacity of WPA differed from the one of WPI for three out of seven aroma compounds detected in HS-GC. Incorporating WPA in fat-free yogurts tended to decrease the release of hydrophobic aroma compounds such as 2-nonanone or methyl-cinnamate. The magnitude of the differences between the partition coefficients of yogurts enriched in WPI or WPA was lower than in aqueous solutions, which is likely to be due to the higher complexity of the food matrix and potential interactions with other ingredients. Overall, the different aroma-retention capacities of native WPI and functional WPA are likely to lead to unbalanced aroma, especially in fat-free dairy products.

Exposure to arsenic and lead in children from Salamanca México, effects on telomeric lengthening and mitochondrial DNA.

Levels of urinary arsenic and levels of lead in blood were measured in children attending elementary schools located in an industrial zone in Salamanca, México. Its possible effects using telomere length and mitochondrial DNA copy number as biomarkers of genomic disequilibrium by oxidative stress were studied. Eighty-eight children (6-15 years old) were included and urine samples were collected for quantification of arsenic, while lead was measured in blood samples using inductively coupled plasma mass spectrometry (ICP-MS). DNA was isolated from peripheral blood and relative telomere length and the mitochondrial DNA copy number were determined by real-time PCR. The geometric mean of urinary arsenic was 54.16 µg/L (11.7-141.1 µg/L). Ninety-eight percent of the children were above 15 µg/L (biomonitoring equivalent value). With respect to the concentration of lead in blood, the mean was 3.78 µg/dL (LOD-22.61), where 24.5% of the participants had equal or above the reference value (5 µg/dL; Mexican Official Norm NOM-199-SSA1-2000, 2017). A positive association between urinary arsenic and telomere length was found (ß = 0.161; 95% CI: 0.12; 0.301; P = 0.034), while lead blood concentrations were negatively associated with mitochondrial DNA copy number (ß = - 0.198; 95% CI: - 2.81; - 0.17; P = 0.019), after adjusting by age, sex, and total white blood cell count. Differences in the mitochondrial DNA content were observed in children with lead blood levels from 2.5 µg/dL, (P ≤ 0.001), suggesting an effect at lead exposure levels considered acceptable (< 5 µg/dL). In conclusion, children living in an industrial area in Salamanca showed an exposure to arsenic and lead and an impact on telomere length and mitochondrial DNA content associated with arsenic and lead exposure, respectively.

Impact of potato cultivation and cattle farming on physicochemical parameters and enzymatic activities of Neotropical high Andean Páramo ecosystem soils.

The Andean Páramos are high mountain ecosystems whose soils are essential for the management of South American water resources, but research on anthropic impacts to these soils is currently minimal and insufficient. The objective of this study was to evaluate the impacts of potato (Solanum tuberosum) cultivation and livestock on the physicochemical parameters and enzymatic activities that determine the soil quality of the Neotropical high Andean Páramo ecosystem in the Nevados National Natural Park (Nevados NNP) in Colombia. It was hypothesised that sites with potato crops and livestock farming would exhibit significant changes in soil physicochemical parameters and enzymatic activities compared with Páramo sites that have been conserved without agriculture. Samples were collected from soils under potato cultivation, livestock and Páramo (subject to the lowest degree of human intervention possible), on three farms in the El Bosque District at three different altitudes (Buenos Aires, El Edén and La Secreta) during two seasons (dry and rainy). The results showed that none of the physical parameters under study presented statistically significant differences due to the type of use (livestock, potato crop or Páramo), season of sampling (dry or rainy season) or altitude (different farms). The chemical parameters that statistically significantly differed due to land use were organic carbon, cation exchange capacity, calcium, potassium, and ammonium and those that showed statistically significant differences associated with the sampling timing were organic carbon, nitrogen, cation exchange capacity, total carbon, C/N and nitrate. Additionally, there were differences in organic carbon due to the altitude of the farms. With respect to enzymatic activities, those of ß-glucosidase, phosphodiesterase and urease significantly decreased in soils under potato cultivation and livestock relative to those of Páramo, but those of acid phosphatase and protease increased significantly under potato cropping and livestock. The activities of ß-glucosidase, acid phosphatase, alkaline phosphatase, phosphodiesterase and protease were higher during the dry season than the rainy season, and the activities of ß-glucosidase, acid phosphatase and urease decreased statistically in the lower-altitude farm (La Secreta). These decreases in enzymatic activities are attributable to changes in the organic carbon of the soil. This study provides a novel insight on the relationships between land use and the physicochemical parameters and enzymatic activities of Páramo soils (which have been minimally studied to date) at different altitudes and during different seasons. The results suggest that changes in agricultural practices should be implemented to maintain the organic carbon of soil and, therefore, its enzymatic activities.

Association of Leukocyte Telomere Length and Mitochondrial DNA Copy Number in Children from Salamanca, Mexico.

AIM: The purpose of this study was to determine if there is a correlation between telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) in children. METHODS: Leukocyte TL and mtDNAcn were measured by real-time PCR in 98 Mexican children 6-12 years of age from Salamanca, México. RESULTS: A positive association was found between TL and mtDNAcn after a natural log transformation (Pearson correlation r = 0.72; p < 0.0001). No correlation between age and body mass index (BMI) biomarkers was found, and no differences according to sex were observed. After adjustment for these variables, a linear regression model showed an association between TL and mtDNAcn (ß = 0.739, 95% confidence interval 0.594; 0.885, p < 0.0001). CONCLUSIONS: A strong positive correlation between TL and mtDNAcn was found in the study population; age, sex, and BMI seemed to have no effect on this correlation.

Effect of management (ecological and conventional) on functional groups of soil microorganisms in coffee agroecosystems with different resilience to climate variability, Colombia

The effect of management (ecological and conventional) on functional groups of microorganisms of soil in agroecosystems with different resilience scores reported to climate variability in Anolaima, Colombia was evaluated. Were found clustering associated with management and cellulolytic bacteria and fungi abundances. No differences found in diversity of phosphate solubilizing or nitrogen-fixing microorganisms, related to management. The diversity of microbial functional groups was affected by the climatic condition of sampling season. Management was relevant in relationships between resilience scores to climate variability and cellulolytic microorganisms; in ecological agroecosystems, biodiversity knowledge, agroecological main structure, and the participation of farmers in organizations were important.

Assessment of cellulolytic microorganisms in soils of Nevados Park, Colombia.

A systematized survey was conducted to find soil-borne microbes that degrade cellulose in soils from unique ecosystems, such as the Superpáramo, Páramo, and the High Andean Forest in the Nevados National Natural Park (NNNP), Colombia. These high mountain ecosystems represent extreme environments, such as high levels of solar radiation, low atmospheric pressure, and extreme daily changes in temperature. Cellulolytic activity of the microorganisms was evaluated using qualitative tests, such as growth in selective media followed by staining with congo red and iodine, and quantitative tests to determine the activity of endoglucanase, ß-glucosidase, exoglucanase, and total cellulase. Microorganisms were identified using molecular markers, such as the 16S rRNA gene for bacteria and the internal transcribed spacer region (ITS) of ribosomal DNA for fungi. Multivariate statistical analysis (MVA) was used to select microorganisms with high cellulolytic capacity. A total of 108 microorganisms were isolated from the soils and, in general, the enzymatic activities of fungi were higher than those of bacteria. Our results also found that none of the organisms studied were able to degrade all the components of the cellulose and it is therefore suggested that a combination of bacteria and/or fungi with various enzymatic activities be used to obtain high total cellulolytic activity. This study gives an overview of the potential microorganism that could be used for cellulose degradation in various biotechnological applications and for sustainable agricultural waste treatment.

Assessment of cellulolytic microorganisms in soils of Nevados Park, Colombia

A systematized survey was conducted to find soil-borne microbes that degrade cellulose in soils from unique ecosystems, such as the Superpáramo, Páramo, and the High Andean Forest in the Nevados National Natural Park (NNNP), Colombia. These high mountain ecosystems represent extreme environments, such as high levels of solar radiation, low atmospheric pressure, and extreme daily changes in temperature. Cellulolytic activity of the microorganisms was evaluated using qualitative tests, such as growth in selective media followed by staining with congo red and iodine, and quantitative tests to determine the activity of endoglucanase, β-glucosidase, exoglucanase, and total cellulase. Microorganisms were identified using molecular markers, such as the 16S rRNA gene for bacteria and the internal transcribed spacer region (ITS) of ribosomal DNA for fungi. Multivariate statistical analysis (MVA) was used to select microorganisms with high cellulolytic capacity. A total of 108 microorganisms were isolated from the soils and, in general, the enzymatic activities of fungi were higher than those of bacteria. Our results also found that none of the organisms studied were able to degrade all the components of the cellulose and it is therefore suggested that a combination of bacteria and/or fungi with various enzymatic activities be used to obtain high total cellulolytic activity. This study gives an overview of the potential microorganism that could be used for cellulose degradation in various biotechnological applications and for sustainable agricultural waste treatment.