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MAIN CONCLUSION: We generated transplastomic tobacco lines that stably express a human Basic Fibroblast Growth Factor (hFGFb) in their chloroplasts stroma and purified a biologically active recombinant hFGFb. MAIN: The use of plants as biofactories presents as an attractive technology with the potential to efficiently produce high-value human recombinant proteins in a cost-effective manner. Plastid genome transformation stands out for its possibility to accumulate recombinant proteins at elevated levels. Of particular interest are recombinant growth factors, given their applications in animal cell culture and regenerative medicine. In this study, we produced recombinant human Fibroblast Growth Factor (rhFGFb), a crucial protein required for animal cell culture, in tobacco chloroplasts. We successfully generated two independent transplastomic lines that are homoplasmic and accumulate rhFGFb in their leaves. Furthermore, the produced rhFGFb demonstrated its biological activity by inducing proliferation in HEK293T cell lines. These results collectively underscore plastid genome transformation as a promising plant-based bioreactor for rhFGFb production.

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OBJECTIVE: The present study aimed to evaluate the association between muscle mass variation, estimated by different equations, during hospitalization with the energy and protein intake and clinical and nutrition outcomes of patients using nutrition support. METHODS: A prospective observational study with patients older than 18 years in use of enteral and/or parenteral nutrition therapy and monitored by the Nutritional Therapy Committee between December 14, 2021, and December 14, 2022. Data were collected from the electronic records and were applied in 11 equations to estimate the four different portions of muscle mass of patients receiving nutrition support at the beginning and the end of hospitalization. RESULTS: A total of 261 patients were evaluated, with a median age of 61.0 (49.0-69.75) years, and 106 were women (40.6%). According to the nutrition diagnosis, several participants had severe malnutrition (39.5%). The most muscle mass estimation equations indicated a reduction of muscle mass during hospitalization. All patients presented negative energy and protein balances during hospitalization, but greater protein intake increased the lean soft tissue. Also, the greater the number of infections, metabolic complications, and scheduled diet interruption, the greater was the chance of losing muscle mass. CONCLUSION: There can be an association between the variation in muscle mass and energy and protein intake during hospitalization of patients using nutrition support. In addition, variation in muscle mass was associated with complications from nutrition support. The results emphasize the importance of anthropometric measurements to estimate muscle mass when other methods are not available.

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Gastrointestinal protist (GP) and soil-transmitted helminth (STH) infections cause significant morbidity among children in poor-resource settings of tropical and sub-tropical countries including Colombia. Few prospective transversal studies investigating how GP and STH infections affect growth development and nutritional status during childhood have been conducted in this country, none of them in the Antioquia Department. This microscopy-based study estimated the prevalence of GP and helminth (including STH) infections in faecal samples from schoolchildren (n = 384) collected during April-May 2019 in three municipalities of the Antioquia Department. Demographic, epidemiological, and household data were elicited through face-to-face interviews. Parasite detection was carried out by direct microscopic examination of both fresh smears and concentrated faecal material. Children (aged 6-15 years) also had their haemoglobin (Hb) levels, height and weight data collected, and BMI estimated. Data were analysed using bivariate and multivariate logistic regression analysis. Overall, 60.7 % (233/384) of schoolchildren were infected by at least one intestinal parasitic species. Among GPs, Blastocystis sp. was the most common species found (47.7 %, 95 % CI: 42.6-52.8), followed by G. duodenalis (15.9 %, 95 % CI: 12.4-19.9). Cryptosporidium spp. and Cyclospora cayetanensis were sporadically identified (0.3 %, 95 % CI: 0.1-1.4 each). Among helminths, the most prevalent species found were Trichuris trichiura (6.0 %, 95 % CI: 3.8-8.9) and Enterobius vermicularis (1.0 %, 95 % CI: 0.3-2.6). Hookworms, Ascaris lumbricoides, and Strongyloides stercoralis were found at prevalence rates <1 %. Underweight, overweigh, or obese schoolchildren had 1.2 times greater chance of being infected with intestinal parasites than their counterparts with a healthy weight (P-value: 0.015). Variables significantly associated with an increased likelihood of being infected by intestinal parasites include living in a household with unfinished flouring, not wearing shoes, being in close proximity to rodents, and having improper waste disposal. Relatively simple interventional measures directed towards the improvement of household conditions, access to sanitary toilets, and promoting shoe wearing can significantly reduce childhood infections by GP and helminths in the Antioquia Department.

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We report the draft genome sequences of four Morganella morganii strains isolated from the stools of four patients diagnosed with colorectal cancer (CRC) in Medellín, Colombia. These genomes represent an important addition to the limited number of genomes of M. morganii strains originating from CRC patients currently available.

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PURPOSE: Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients' overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS. MATERIALS AND METHODS: IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS. RESULTS: Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B-like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor-positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS. CONCLUSION: NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

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CONTEXT: Reduced muscle mass is linked to poor outcomes in both inpatients and outpatients, highlighting the importance of muscle mass assessment in clinical practice. However, laboratory methods to assess muscle mass are not yet feasible for routine use in clinical practice because of limited availability and high costs. OBJECTIVE: This work aims to review the literature on muscle mass prediction by anthropometric equations in adults or older people. DATA SOURCES: The following databases were searched for observational studies published until June 2022: MEDLINE, Embase, Scopus, SPORTDiscus, and Web of Science. DATA EXTRACTION: Of 6437 articles initially identified, 63 met the inclusion criteria for this review. Four independent reviewers, working in pairs, selected and extracted data from those articles. DATA ANALYSIS: Two studies reported new equations for prediction of skeletal muscle mass: 10 equations for free-fat mass and lean soft tissue, 22 for appendicular lean mass, 7 for upper-body muscle mass, and 7 for lower-body muscle mass. Twenty-one studies validated previously proposed equations. This systematic review shows there are numerous equations in the literature for muscle mass prediction, and most are validated for healthy adults. However, many equations were not always accurate and validated in all groups, especially people with obesity, undernourished people, and older people. Moreover, in some studies, it was unclear if fat-free mass or lean soft tissue had been assessed because of an imprecise description of muscle mass terminology. CONCLUSION: This systematic review identified several feasible, practical, and low-cost equations for muscle mass prediction, some of which have excellent accuracy in healthy adults, older people, women, and athletes. Malnourished individuals and people with obesity were understudied in the literature, as were older people, for whom there are only equations for appendicular lean mass. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021257200.

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We designed a controlled trial protocol that seeks to contribute to cognitive science by studying the effect of thought training on children's executive functions. The study design is a cluster randomized controlled trial, with intra-subject and inter-subject evaluation, with two parallel groups: an experimental group and a TAU control group. With three measures, pre-test, post-test, and follow-up after three months. The participants will be children aged 9 to 11. The allocation will be randomized by groups and not individually. The sample will be a minimum of 44 participants. The primary measures will be neuropsychological tests to assess executive functions. Secondary measures will be a computational thinking test, neuropsychological tests to assess metacognition and attention, and an acceptability scale. The experimental group will participate in the COGNI-MACHINE computational thinking training designed by the first author. The training frequency will be twice a week in 60 min sessions for 12 weeks. The TAU control group will receive computer science classes as usual during the same time as the experimental group. The evaluators taking the measurements will be blinded to the assignment. The investigators in charge of the intervention will be blinded to the results of the evaluations.

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Research shows many positive effects from physical exercise. The present study examined the impact of a structured physical exercise program compared to treatment as usual on the gross motor skills of children diagnosed with autism spectrum disorder (ASD). Participants included 20 children, from 4 to 7 years old, who were assigned to two groups; an experimental group (n = 10) who received a structured physical exercise program for 60-min sessions, three times a week for eight weeks, and a control group (n = 10) who received conventional physiotherapy. Gross motor skills were assessed with the Abbreviated Development Scale -3 before and after the physical exercise program. The experimental group exhibited significant improvements in gross motor skills compared to the control group. This study suggests that structured physical exercise programs can improve gross motor skills in children with ASD.

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BACKGROUND: The purpose of this systematic review is to synthesize the existing literature reporting the effects of computerized cognitive trainings on the executive functions of children with ADHD. METHOD: A systematic review was carried out following the PRISMA statement; the primary sources used were five electronic databases (Scopus, Science Direct, Pubmed, Springer, Taylor & Francis). RESULTS: 20 articles met the eligibility criteria, data on the training characteristics and the effects on executive functions were extracted, followed by an analysis of bias and the methodological quality of the studies. The results of the studies were widely heterogeneous, largely associated with the variety of training programs and the measurement instruments used. The most studied executive functions were working memory and inhibitory control. Some of the studies reported that the intervention led to significant effects on working memory and attention (N = 7), and improvements in inhibitory control (N = 5) and planning (N = 4) were also reported. At the same time, others did not report the effects of the intervention on these processes. The assessment of the quality of the evidence showed important risk biases among the reviewed studies. CONCLUSION: Some training based on computer systems showed positive effects on the executive functions of working memory, attention, and inhibitory control in children with ADHD. However, other training sessions did not show significant effects. In general, the evidence shows mixed results, a high diversity of measurement instruments, and high risks of bias between the studies. Therefore, the evidence has not been consistent about the general benefits of computerized training on the executive functions of children with ADHD.

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Blastocystis sp. is among the most frequent intestinal protists identified in humans globally. However, characterization of Blastocystis subtype diversity in humans is ongoing. We report here the identification of novel Blastocystis subtype ST41 in a Colombian patient undergoing colorectal cancer screening involving colonoscopy and fecal testing (microscopy, culture, PCR). The full-length ssu rRNA gene sequence of the protist was generated using MinION long-read sequencing technology. The validity of the novel subtype was confirmed via phylogenetic and pairwise distance analyses of the full-length ST41 sequence and all other valid subtypes. The study provides reference material essential for conducting subsequent experimental studies.

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Hypothalamic circuits compute systemic information to control metabolism. Astrocytes residing within the hypothalamus directly sense nutrients and hormones, integrating metabolic information, and modulating neuronal responses. Nevertheless, the role of the astrocytic circadian clock on the control of energy balance remains unclear. We used mice with a targeted ablation of the core-clock gene Bmal1 within Gfap-expressing astrocytes to gain insight on the role played by this transcription factor in astrocytes. While this mutation does not substantially affect the phenotype in mice fed normo-caloric diet, under high-fat diet we unmasked a thermogenic phenotype consisting of increased energy expenditure, and catabolism in brown adipose and overall metabolic improvement consisting of better glycemia control, and body composition. Transcriptomic analysis in the ventromedial hypothalamus revealed an enhanced response to moderate cellular stress, including ER-stress response, unfolded protein response and autophagy. We identified Xbp1 and Atf1 as two key transcription factors enhancing cellular stress responses. Therefore, we unveiled a previously unknown role of the astrocytic circadian clock modulating energy balance through the regulation of cellular stress responses within the VMH.

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BACKGROUND: Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown. RESULTS: Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features. CONCLUSIONS: These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.

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Abandonment of agricultural lands promotes the global expansion of secondary forests, which are critical for preserving biodiversity and ecosystem functions and services. Such roles largely depend, however, on two essential successional attributes, trajectory and recovery rate, which are expected to depend on landscape-scale forest cover in nonlinear ways. Using a multi-scale approach and a large vegetation dataset (843 plots, 3511 tree species) from 22 secondary forest chronosequences distributed across the Neotropics, we show that successional trajectories of woody plant species richness, stem density and basal area are less predictable in landscapes (4 km radius) with intermediate (40-60%) forest cover than in landscapes with high (greater than 60%) forest cover. This supports theory suggesting that high spatial and environmental heterogeneity in intermediately deforested landscapes can increase the variation of key ecological factors for forest recovery (e.g. seed dispersal and seedling recruitment), increasing the uncertainty of successional trajectories. Regarding the recovery rate, only species richness is positively related to forest cover in relatively small (1 km radius) landscapes. These findings highlight the importance of using a spatially explicit landscape approach in restoration initiatives and suggest that these initiatives can be more effective in more forested landscapes, especially if implemented across spatial extents of 1-4 km radius.

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Down syndrome is the main genetic cause of intellectual disability. Many studies describe the clinical characteristics of DS patients; however, few have investigated the clinical profile of mothers who have children with DS. Advanced maternal age (≥ 35 years old) is a risk factor for DS. Although there is an overall increase in pregnancies among women with advanced maternal age, there is still a lack of awareness of the increased risk of aneuploidy. Here, we reported the clinical and epidemiological profile of DS children and their mothers in a public reference hospital in the State of Rio de Janeiro, Brazil. For data collection, we performed a face-to-face interview guided by a structured questionnaire with closed-ended questions. A total of 344 individuals, 172 mothers and their DS children, were included in this study. Our results show that 56% of the mothers sampled were ≥ 35 years of age at childbirth. Although 98% of them received prenatal care, only 4% obtained a prenatal diagnosis of DS. Most mothers reported not drinking alcohol or smoking cigarettes during pregnancy. Furthermore, 91% of women took prenatal vitamins and supplements; however, 47% were not aware of their benefits for a healthy pregnancy. Given the strict correlation between advanced maternal age and DS, prenatal care should include genetic counseling for women over 35 years of age. This study highlights the importance of prenatal care and the urgent need for better DS screening allowing for immediate postnatal care, positively impacting the life expectancy of these patients.

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This article presents a systematic review of studies on cognitive training programs based on artificial cognitive systems and digital technologies and their effect on executive functions. The aim has been to identify which populations have been studied, the characteristics of the implemented programs, the types of implemented cognitive systems and digital technologies, the evaluated executive functions, and the key findings of these studies. The review has been carried out following the PRISMA protocol; five databases have been selected from which 1889 records were extracted. The articles were filtered following established criteria, to give a final selection of 264 articles that have been used for the purposes of this study in the analysis phase. The findings showed that the most studied populations were school-age children and the elderly. The most studied executive functions were working memory and attentional processes, followed by inhibitory control and processing speed. Many programs were commercial, customizable, gamified, and based on classic tasks. Some more recent initiatives have begun to incorporate user-machine interfaces, robotics, and virtual reality, although studies on their effects remain scarce. The studies recognize multiple benefits of computerized neuropsychological stimulation and rehabilitation programs for executive functions in different age groups, but there is a lack of studies in specific population sectors and with more rigorous research designs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13369-022-07292-5.

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BACKGROUND: Spent coffee grounds (SCGs) are a good source of chlorogenic acid (CGA), which can be hydrolyzed to quinic acid (QA) and caffeic acid (CA). These molecules have antioxidant and neuroprotective capacities, benefiting human health. The hydrolysis of CGA can be done by biotechnological processes, such as solid-state fermentation (SSF). This work evaluated the use of SSF with Aspergillus sp. for the joint release of the three molecules from SCGs. RESULTS: Hydroalcoholic extraction of the total phenolic compounds (TPCs) from SCGs was optimized, obtaining 28.9 ± 1.97 g gallic acid equivalent (GAE) kg-1 SCGs using 0.67 L ethanol per 1 L, a 1:9 solid/liquid ratio, and a 63 min extraction time. Subsequently, SSF was performed for 30 days, achieving the maximum yields for CGA, QA, and TPCs on the 16th day: 7.12 ± 0.01 g kg-1 , 4.68 ± 0.11 g kg-1 , and 54.96 ± 0.49 g GAE kg-1 respectively. CA reached its maximum value on the 23rd day, at 4.94 ± 0.04 g kg-1 . The maximum antioxidant capacity was 635.7 mmol Trolox equivalents kg-1 on the 14th day. Compared with unfermented SCGs extracts, TPCs and CGA increase their maximum values 2.3-fold, 18.6-fold for CA, 14.2 for QA, and 6.4-fold for antioxidant capacity. Additionally, different extracts' profiles were obtained throughout the SSF process, allowing us to adjust the type of enriched extract to be produced based on the SSF time. CONCLUSION: SSF represents an alternative to produce extracts with different compositions and, consequently, different antioxidant capacities, which is a potentially attractive fermentation process for different applications. © 2022 Society of Chemical Industry.

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Introduction: The use of computational systems has ventured into different healthcare areas, such as rehabilitation and stimulation of cognitive processes. To this date, it is possible to identify some reviews collecting studies on the efficacy and effects of those programs in groups such as older adults, children, and teenagers; there is a lack of academic literature giving an account of young and middle-aged adults. Objective: To identify empirical studies that measured the feasibility and effect of computer-based stimulation and rehabilitation programs for cognitive functions in young and middle-aged adults. Materials and methods: The PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) extension was used as a base for a scoping review, as suggested by Cochrane Collaboration. Five databases -Science Direct, Scopus, Springer, PubMed, and Taylor & Francis- were used to trace information. The data registry and synthesis of the results was carried out independently by two reviewers. Results: 896 registries were found between 2015 and 2022, of which 91 met the eligibility principles, which evaluated the effects of programs based on computational systems on executive functions on young and middle-aged adults. Conclusion: Most of the interventions based on computational systems showed to be feasible and had moderate to significant effects on executive functions in young and middle-aged adults.

Introducción: El uso de los sistemas computacionales ha incursionado de forma notable en diferentes áreas de la salud, como la rehabilitación y estimulación de los procesos cognitivos. Si bien a la fecha se pueden identificar algunas revisiones que recopilan estudios sobre la eficacia y efectos de estos programas en grupos como adultos mayores, niños y adolescentes, existe poca literatura orientada a la adultez joven y la adultez media. Objetivo: Identificar estudios empíricos que midieron la viabilidad y el efecto de los programas de estimulación y rehabilitación de las funciones ejecutivas basados en computadora en la población adulta joven y media. Materiales y métodos: Se realizó revisión de alcance basado en la extensión PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extensión for Scoping Reviews) sugerido por Cochrane Collaboration. Para el rastreo de información se seleccionaron cinco bases de datos: Science Direct, Scopus, Springer, PubMed y Taylor & Francis. El proceso de registro de datos y la síntesis de los resultados fue realizada por dos revisores de forma independiente. Resultados: Se encontraron 896 registros desde el 2015 al 2022, de los cuales 91 cumplieron los principios de elegibilidad, en los que se evaluaron los efectos de programas basados en sistemas computacionales sobre las funciones ejecutivas en adultos jóvenes y adultos medios. Conclusión: La mayoría de las intervenciones basadas en sistemas computacionales mostraron ser viables y tener efectos favorables de moderados a significativos sobre las funciones ejecutivas de adultos jóvenes y medios.

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Systematic modeling of the enzymatic hydrolysis of milk proteins is needed to assist the study and production of partially hydrolyzed milk. The enzymatic hydrolysis of milk proteins was characterized and evaluated as a function of the temperature and protease concentration using Alcalase, Neutrase and Protamex. Modeling was based on the combination of two empirical models formed by a logarithmic and a polynomial equation to correlate the kinetic constants and the operating conditions. The logarithmic equation fitted with high accuracy to the experimental hydrolysis curves with the three proteases (R2 > 0.99). The kinetic constants were correlated with the operating conditions (R2 > 0.97) using polynomial equations. The temperature and protease concentration significantly affected the initial rate of hydrolysis, i.e., the kinetic constant a, while the kinetic constant b was not significantly affected. The values for the kinetic constant a were predicted according to the operating conditions and they were strongly correlated with the experimental data (R2 = 0.95). The model allowed for a high-quality prediction of the hydrolysis curves of milk proteins. This modeling tool can be used in future research to test the correlation between the degree of hydrolysis and the functional properties of milk hydrolysates.

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The recurrence of Glioblastoma is partly attributed to the highly resistant subpopulation of glioma stem cells. A novel therapeutic approach focuses on restoring apoptotic programs in these cancer stem cells, as they are often deregulated. BH3-mimetics, targeting anti-apoptotic Bcl-2 family members, are emerging as promising compounds to sensitize cancer cells to antineoplastic treatments. Herein, we determined that the most abundantly expressed anti-apoptotic Bcl-2 family members, Bcl-xL and Mcl-1, are the most relevant in regulating patient-derived glioma stem cell survival. We exposed these cells to routinely used chemotherapeutic drugs and BH3-mimetics (ABT-263, WEHI-539, and S63845). We observed that the combination of BH3-mimetics targeting Bcl-xL with chemotherapeutic agents caused a marked increase in cell death and that this sensitivity to Bcl-xL inhibition correlated with Noxa expression levels. Interestingly, whereas co-targeting Bcl-xL and Mcl-1 led to massive cell death in all tested cell lines, down-regulation of Noxa promoted cell survival only in cell lines expressing higher levels of this BH3-only. Therefore, in glioma stem cells, the efficacy of Bcl-xL inhibition is closely associated with Mcl-1 activity and Noxa expression. Hence, a potentially effective strategy would consist of combining Bcl-xL inhibitors with chemotherapeutic agents capable of inducing Noxa, taking advantage of this pro-apoptotic factor.

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