Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast‐cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic ...glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow‐cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose‐deprived conditions. Fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7‐related metabolic pathways is a viable therapeutic strategy.
Synopsis
Transcriptomic and metabolomic profiling of primary brain tumor cells demonstrate that functionally different glioblastoma (GBM) cell subpopulations depend on distinct metabolic pathways for their growth and survival. More invasive slow cycling tumor cells rely on oxidative phosphorylation and lipid metabolism, suggesting targetable candidates for the inhibition of treatment‐resistant tumors.
Patient‐derived GBM cells contain fast‐cycling cells (FCCs) relying on aerobic glycolysis and slow‐cycling cells (SCCs) depending on mitochondrial oxidative phosphorylation in vivo.
SCCs show increased resistance, invasion, and metabolic gene signatures characteristic of recurrent tumors.
SCCs show increased levels of metabolites and components involved in lipid metabolism, storage, and transport.
Block of FABP7‐dependent exogenous fatty acid uptake decreases resistance of SCCs to chemotherapy and glucose deprivation.
Oxidative phosphorylation and lipid metabolism specify distinct energetic set‐up of invasive brain tumor cells.
To develop a predictive model for successful cervical ripening in women that undergo induction of labour by means of a vaginal prostaglandin slow-release delivery system (Propess®). Prospective ...observational study on 204 women that required induction of labour between February 2019 and May 2020 at "La Mancha Centro" hospital in Alcázar de San Juan, Spain. The main variable studied was effective cervical ripening (Bishop score > 6). Using multivariate analysis and binary logistic regression, we created three initial predictive models (model A: Bishop Score + Ultrasound cervical length + clinical variables (estimated fetal weight, premature rupture of membranes and body mass index)); model B: Ultrasound cervical lenght + clinical variables; and model C: Bishop score + clinical variables) to predict effective cervical ripening. All three predictive models obtained (A, B and C) presented good predictive capabilities, with an area under the ROC curve ≥ 0.76. Predictive model C, composed of the variables: gestational age (OR 1.55, 95% CI 1.18-2.03, p = 0.002), premature rupture of membranes (OR 3.21 95% CI 1.34-7.70, p = 0.09) body mass index (OR 0.93, 95% CI 0.87-0.98, p = 0.012), estimated fetal weight (OR 0.99, 95% CI 0.99-1.00, p = 0.068) and Bishop score (OR 1.49 95% CI 1.18-1.81, p = 0.001), is presented as the model of choice with an area under the ROC curve of 0.76 (95% CI 0.70-0.83, p < 0.001). A predictive model composed of the variables: gestational age, premature rupture of membranes, body mass index, estimated fetal weight and Bishop score upon admission presents good capabilities in predicting successful cervical ripening following administration of prostaglandins. This tool could be useful in making clinical decisions with regard to induction of labour.
The combination of high-performance thermoplastic poly(ether ether ketone) (PEEK) with inorganic fullerene-like tungsten disulfide (IF-WS2) nanoparticles offers an attractive way to combine the ...merits of organic and inorganic materials into novel polymer nanocomposite materials. Here, we report the processing of novel PEEK/IF-WS2 nanocomposites, which overcome the nanoparticle agglomerate formation and provide PEEK−particle interactions. The IF-WS2 nanoparticles do not require exfoliation or modification, making it possible to obtain stronger, lighter materials without the complexity and processing cost associated with these treatments. The nanocomposites were fabricated by melt blending, after a predispersion step based on ball milling and mechanical treatments in organic solvent, which leads to the dispersion of individually IF-WS2 nanoparticles in the PEEK matrix as confirmed by scanning electron microscopy. In order to determine the performance of the PEEK/IF-WS2 nanocomposites for potential critical applications, particularly for the aircraft industry, we have extensively investigated these materials with a wide range of structural, thermal, and mechanical techniques using time-resolved synchrotron X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, dynamic-mechanical analysis, and tensile and impact tests as well as thermal measurements. Modulus, tensile strengh, thermal stability, and thermal conductivity of PEEK exhibited remarkable improvement with the addition of IF-WS2.
Glioblastoma is the most lethal brain cancer in adults, with no known cure. This cancer is characterized by a pronounced genetic heterogeneity, but aberrant activation of receptor tyrosine kinase ...signaling is among the most frequent molecular alterations in glioblastoma. Somatic mutations of fibroblast growth factor receptors (
) are rare in these cancers, but many studies have documented that signaling through FGFRs impacts glioblastoma progression and patient survival. Small-molecule inhibitors of FGFR tyrosine kinases are currently being trialed, underlining the therapeutic potential of blocking this signaling pathway. Nevertheless, a comprehensive overview of the state of the art of the literature on FGFRs in glioblastoma is lacking. Here, we review the evidence for the biological functions of FGFRs in glioblastoma, as well as pharmacological approaches to targeting these receptors.
Recent studies suggest that the beneficial properties provided by sourdough fermentation may be translated to the development of new GF products that could improve their technological and nutritional ...properties. The main objective of this manuscript is to review the current evidence regarding the elaboration of GF baked goods, and to present the latest knowledge about the so-called sourdough biotechnology. A bibliographic search of articles published in the last 12 years has been carried out. It is common to use additives, such as hydrocolloids, proteins, enzymes, and emulsifiers, to technologically improve GF products. Sourdough is a mixture of flour and water fermented by an ecosystem of lactic acid bacteria (LAB) and yeasts that provide technological and nutritional improvements to the bakery products. LAB-synthesized biopolymers can mimic gluten molecules. Sourdough biotechnology is an ecological and cost-effective technology with great potential in the field of GF products. Further research is necessary to optimize the process and select species of microorganisms robust enough to be competitive in any circumstance.
Radial glia-like (RGL) stem cells persist in the adult mammalian hippocampus, where they generate new neurons and astrocytes throughout life. The process of adult neurogenesis is well documented, but ...cell-autonomous factors regulating neuronal and astroglial differentiation are incompletely understood. Here, we evaluate the functions of the transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) in adult hippocampal RGL cells using a conditional-inducible mouse model. We find that ZEB1 is necessary for self-renewal of active RGL cells. Genetic deletion of Zeb1 causes a shift toward symmetric cell division that consumes the RGL cell and generates pro-neuronal progenies, resulting in an increase of newborn neurons and a decrease of newly generated astrocytes. We identify ZEB1 as positive regulator of the ets-domain transcription factor ETV5 that is critical for asymmetric division.
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•The stem cell transcription factor, ZEB1, demarcates active from quiescent RGL cells•ZEB1 drives the self-renewal of RGL cells by promoting asymmetric cell division•Loss of Zeb1 causes increased neurogenesis and decreased astrogliogenesis•ZEB1 induces Etv5 expression to regulate asymmetric cell division
Gupta et al. show that the stem cell transcription factor, ZEB1, labels activated hippocampal stem cells and regulates their self-renewal and astroglial fate specification. Mechanistically, ZEB1 promotes asymmetric cell divisions and induces the expression of ETV5, a transcriptional regulator of asymmetric divisions and astroglial lineage commitment.
Background: Overweight and obesity differ in their repercussions on the health and health-related quality of life (HRQoL) of patients. The objective of this study was to compare physical activity ...levels and dietary habits before admission and HRQoL at discharge between patients with obesity and overweight. Methods: A cross-sectional study was undertaken among participants in a clinical trial on education for healthy eating and physical activity, enrolling non-diabetic patients admitted to Internal Medicine Departments. These were classified by body mass index (BMI) as having overweight (25–29.9 Kg/m2) or obesity (≥30 kg/m2). Data were gathered on sociodemographic characteristics, clinical variables (medication for anxiety/depression, Charlson Comorbidity Index, length of hospital stay), physical exercise and diet (International Physical Activity and Pardo Questionnaires), and HRQoL (EQ-5D-5L). The study included 98 patients with overweight (58.2% males) and 177 with obesity (52% males). Results: In comparison to patients with obesity, those with overweight obtained better results for regular physical exercise (p = 0.007), healthy diet (p = 0.004), and “emotional eating” (p = 0.017). No between-group difference was found in HqoL scores. Conclusion: Patients with overweight and obesity differ in healthy dietary and physical exercise behaviors. Greater efforts are warranted to prevent an increase in the BMI of patients, paying special attention to their state of mind.
Purpose
To develop a predictive model for risk of cesarean section in pregnant women after induction of labor.
Methods
A retrospective cohort study was conducted of 861 induced labors during 2009, ...2010, and 2011 at Hospital “La Mancha-Centro” in Alcázar de San Juan, Spain. Multivariate analysis was used with binary logistic regression and areas under the ROC curves to determine predictive ability. Two predictive models were created: model A predicts the outcome at the time the woman is admitted to the hospital (before the decision to of the method of induction); and model B predicts the outcome at the time the woman is definitely admitted to the labor room.
Results
The predictive factors in the final model were: maternal height, body mass index, nulliparity, Bishop score, gestational age, macrosomia, gender of fetus, and the gynecologist’s overall cesarean section rate. The predictive ability of model A was 0.77 95 % confidence interval (CI) 0.73–0.80 and model B was 0.79 (95 % CI 0.76–0.83). The predictive ability for pregnant women with previous cesarean section with model A was 0.79 (95 % CI 0.64–0.94) and with model B was 0.80 (95 % CI 0.64–0.96). For a probability of estimated cesarean section ≥80 %, the models A and B presented a positive likelihood ratio (+LR) for cesarean section of 22 and 20, respectively. Also, for a likelihood of estimated cesarean section ≤10 %, the models A and B presented a +LR for vaginal delivery of 13 and 6, respectively.
Conclusion
These predictive models have a good discriminative ability, both overall and for all subgroups studied. This tool can be useful in clinical practice, especially for pregnant women with previous cesarean section and diabetes.
Purpose: To evaluate the effect and safety of vaginal dinoprostone in pregnant women with PROM who undergo induction of labor (IoL). Materials and Methods: Prospective observational study conducted ...at La Mancha Centro hospital from 1 February 2019, to 30 August 2020. Obstetric and neonatal variables of 94 pregnant women with PROM who underwent IoL with vaginal dinoprostone were analyzed, and the results were compared with 330 patients without PROM who also underwent IoL. Bivariate and multivariate analyses were performed using binary and multiple linear regression. Results: A total of 424 women were included in this study. A greater response to cervical ripening (Bishop score > 6) with PGE2 was observed in the PROM group (odds ratio (OR) 2.73, 95% confidence interval (CI) 1.50−4.99, p = 0.001), as well as a shorter total duration of IoL (mean difference (MD) 2823.37 min (min), 95% CI 1257.30−4389.43, p < 0.001). Cesarean sections were performed in 28.7% (n = 27) of patients in the PROM group vs. 34.2% (n = 113) of patients in the non-PROM group, with no significant differences (OR 0.87%, 95% CI 0.47−1.60, p = 0.652). There were no significant differences in changes in the cardiotocographic record (CTG), postpartum hemorrhage (PPH), uterine rupture, or adverse neonatal outcomes between the two groups. Conclusions: The use of vaginal dinoprostone in pregnant women undergoing IoL with PROM is safe for the mother and the fetus, shortens the total delivery time, and does not increase the risk of cesarean section compared with pregnant women undergoing IoL without PROM.
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