Bitter taste receptors: Key target to understand the effects of polyphenols on glucose and body weight homeostasis. Pathophysiological and pharmacological implications.

Experimental and clinical research has reported beneficial effects of polyphenol intake on high prevalent diseases such as type 2 diabetes and obesity. These phytochemicals are ligands of taste 2 receptors (T2Rs) that have been recently located in a variety of organs and extra-oral tissues. Therefore, the interaction between polyphenol and T2Rs in brain structures can play a direct effect on appetite/satiety regulation and food intake. T2Rs are also expressed along the digestive tract, and their interaction with polyphenols can induce the release of gastrointestinal hormones (e.g., ghrelin, GLP-1, CCK) influencing appetite, gastrointestinal functionally, and glycemia control. Intestinal microbiota can also influence on network effects of polyphenols-T2Rs interaction and vice versa, impacting innate immune responses and consequently on gut functionally. Furthermore, polyphenols binding to T2Rs present important effects on adipose tissue metabolism. Interestingly, T2R polymorphism could, at least partially, explain the inter-individual variability of the effects of polyphenols on glucose and body weight homeostasis. Together, these factors can contribute to understand the beneficial effects of polyphenol-rich diets but also might aid in identifying new pharmacological pathway targets for the treatment of diabetes and obesity.

Effect of moderate beer consumption (with and without ethanol) on cardiovascular health in postmenopausal women.

BACKGROUND: The main aim of this 2-year non-randomized parallel controlled clinical pilot trial was to evaluate the long-term effect of a moderate daily intake of beer (with and without alcohol) on cardiovascular health in postmenopausal women. A total of 34 participants were grouped into three study arms: 16 were administered alcoholic beer, 6 consumed non-alcoholic beer, and 12 were in the control group. Changes in glucose metabolism, lipid profile, liver enzymes, anthropometric measurements, body composition, and blood pressure variables were monitored. Data on medical history, diet, and exercise were collected, and gustatory capacities were determined. RESULTS: Moderate consumption of beer, both alcoholic and non-alcoholic, seemed to have positive effects on biochemical indicators of cardiovascular health in postmenopausal women, with 660 mL day-1 of non-alcoholic beer reducing low-density lipoprotein cholesterol blood levels, and 330 mL day-1 of alcoholic beer increasing high-density lipoprotein cholesterol. The evolution of changes in android and gynoid fat percentage and their ratio differed significantly between study groups, which was attributable to either the interventions or the disparity between groups regarding the time elapsed since menopause onset. Iso-α-acids recognition threshold could be involved in intervention group election, whereas the sensory phenotypes studied were not associated with alcohol drinking frequency. CONCLUSIONS: Moderate beer consumption was found to improve the lipid profile of postmenopausal women, although their effects in preventing cardiometabolic alterations deserve further research (trial registration number: ISRCTN13825020; https://doi.org/10.1186/ISRCTN13825020). © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer.

BACKGROUND: RNA modifications are important regulators of transcript activity and an increasingly emerging body of data suggests that the epitranscriptome and its associated enzymes are altered in human tumors. METHODS: Combining data mining and conventional experimental procedures, NSUN7 methylation and expression status was assessed in liver cancer cell lines and primary tumors. Loss-of-function and transfection-mediated recovery experiments coupled with RNA bisulfite sequencing and proteomics determined the activity of NSUN7 in downstream targets and drug sensitivity. RESULTS: In this study, the initial screening for genetic and epigenetic defects of 5-methylcytosine RNA methyltransferases in transformed cell lines, identified that the NOL1/NOP2/Sun domain family member 7 (NSUN7) undergoes promoter CpG island hypermethylation-associated with transcriptional silencing in a cancer-specific manner. NSUN7 epigenetic inactivation was common in liver malignant cells and we coupled bisulfite conversion of cellular RNA with next-generation sequencing (bsRNA-seq) to find the RNA targets of this poorly characterized putative RNA methyltransferase. Using knock-out and restoration-of-function models, we observed that the mRNA of the coiled-coil domain containing 9B (CCDC9B) gene required NSUN7-mediated methylation for transcript stability. Most importantly, proteomic analyses determined that CCDC9B loss impaired protein levels of its partner, the MYC-regulator Influenza Virus NS1A Binding Protein (IVNS1ABP), creating sensitivity to bromodomain inhibitors in liver cancer cells exhibiting NSUN7 epigenetic silencing. The DNA methylation-associated loss of NSUN7 was also observed in primary liver tumors where it was associated with poor overall survival. Interestingly, NSUN7 unmethylated status was enriched in the immune active subclass of liver tumors. CONCLUSION: The 5-methylcytosine RNA methyltransferase NSUN7 undergoes epigenetic inactivation in liver cancer that prevents correct mRNA methylation. Furthermore, NSUN7 DNA methylation-associated silencing is associated with clinical outcome and distinct therapeutic vulnerability.

Inter-individual characteristics on basic taste recognition thresholds in a college-aged cohort: potential predictive factors.

Studying nutritional status from the perspective of taste sensitivity, rather than only dietary patterns, may provide new insights into the role of taste receptor signaling in the development of metabolic-associated diseases. In this cross-sectional study, we investigated the possible influence of sociodemographic (sex and smoking habit) and clinical variables (dental cavities, missing teeth, sinusitis, rhinitis, body mass index and metabolic high prevalence family antecedent diseases) on tastant (sucrose, monosodium glutamate, sodium chloride, citric acid, quinine, sinigrin, phenylthiocarbamide) recognition thresholds (RTs) in a college-aged cohort (n = 397). Predictive models for the tastant RTs were generated and a higher sucrose RT was found in females than in males, while sinusitis and rhinitis explained sucrose and sodium chloride RTs. Smoking habit was not an important predictive factor of taste sensitivity, although its long-term influence on RTs remains unclear. Additionally, a positive correlation was found between all the tastant RTs studied. Although results did not show a clear pattern, the statistical approach employed should prove useful in future studies of predictors of taste sensitivity.

Effect of moderate beer consumption (with and without ethanol) on osteoporosis in early postmenopausal women: Results of a pilot parallel clinical trial.

Introduction: Osteoporosis is a chronic progressive bone disease characterized by low bone mineral density (BMD) and micro-architectural deterioration of bone tissue, leading to an increase in bone fragility and the risk of fractures. A well-known risk factor for bone loss is postmenopausal status. Beer may have a protective effect against osteoporosis associated with its content of silicon, polyphenols, iso-α-acids and ethanol, and its moderate consumption may therefore help to reduce bone loss in postmenopausal women. Methods: Accordingly, a 2-year controlled clinical intervention study was conducted to evaluate if a moderate daily intake of beer with (AB) or without alcohol (NAB) could have beneficial effects on bone tissue. A total of 31 postmenopausal women were assigned to three study groups: 15 were administered AB (330 mL/day) and six, NAB (660 mL/day), whereas, the 10 in the control group refrained from consuming alcohol, NAB, and hop-related products. At baseline and subsequent assessment visits, samples of plasma and urine were taken to analyze biochemical parameters, and data on medical history, diet, and exercise were collected. BMD and the trabecular bone score (TBS) were determined by dual-energy X-ray absorptiometry. Markers of bone formation (bone alkaline phosphatase [BAP] and N-propeptide of type I collagen [PINP]) and bone resorption (N-telopeptide of type I collagen [NTX] and C-telopeptide of type I collagen [CTX]) were determined annually. Results: Bone formation markers had increased in the AB and NAB groups compared to the control after the 2-year intervention. However, the evolution of BMD and TBS did not differ among the three groups throughout the study period. Discussion: Therefore, according to the findings of this pilot study, moderate beer intake does not seem to have a protective effect against bone loss in early post-menopausal women.

Association of phenylthiocarbamide perception with anthropometric variables and intake and liking for bitter vegetables.

Phenylthiocarbamide (PTC) sensitivity, a sensory trait mediated by the bitter taste receptor 38 (TAS2R38), has been described as a promising biomarker of health status or disease risk. The aim of this cross-sectional study was to evaluate the influence of PTC phenotypes on (1) individual anthropometric and clinical history variables; (2) other basic taste recognition thresholds (RTs), and (3) the hedonic perception and habitual intake of Brassicaceae vegetables in a young adult population (18.9 ± 1.7 years old). The PTC phenotype was determined by the quantitative measure of the PTC recognition threshold (non-tasters, 24.1%; tasters, 52.3%; and super tasters, 23.6%). No significant differences in smoking habits, oral and nasal disorders, family antecedents of diseases related to metabolic syndrome, and Brassicaceae vegetable hedonic perception and consumption were found between the PTC phenotype groups. The average BMI of super-taster females and males was significantly lower compared to non-tasters. In addition, the PTC taster status was a predictor of lower scores for other basic taste RTs. Overall, the defined PTC super-taster cohort could be differentiated from the non-tasters by variables related to weight control such as BMI and sucrose RT.

Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells.

Dyslipidemia, metabolic disorders and/or obesity are postulated as risk factors for pancreatic ductal adenocarcinoma (PDAC). The majority of patients with these metabolic alterations have low density lipoproteins (LDLs) with increased susceptibility to become aggregated in the extracellular matrix (ECM). LDL aggregation can be efficiently inhibited by low-density lipoprotein receptor-related protein 1 (LRP1)-based peptides. The objectives of this work were: (i) to determine if aggregated LDLs affect the intracellular cholesteryl ester (CE)/free cholesterol (FC) ratio and/or the tumor pancreatic cell proliferation, using sphingomyelinase-modified LDL particles (Aggregated LDL, AgLDL); and (ii) to test whether LRP1-based peptides, highly efficient against LDL aggregation, can interfere in these processes. For this, we exposed human pancreatic cancer cell lines (PANC-1, RWP-1 and Capan-1) to native (nLDL) or AgLDLs in the absence or presence of LRP1-based peptides (DP3) or irrelevant peptides (IP321). Results of thin-layer chromatography (TLC) following lipid extraction indicate that AgLDLs induce a higher intracellular CE/FC ratio than nLDL, and that DP3 but not IP321 counteracts this effect. AgLDLs also increase PANC-1 cell proliferation, which is inhibited by the DP3 peptide. Our results indicate that AgLDL-induced intracellular CE accumulation plays a crucial role in the proliferation of pancreatic tumor cell lines. Peptides with anti-LDL aggregation properties may thus exhibit anti-tumor effects.

The transcribed ultraconserved region uc.160+ enhances processing and A-to-I editing of the miR-376 cluster: hypermethylation improves glioma prognosis.

Transcribed ultraconserved regions (T-UCRs) are noncoding RNAs derived from DNA sequences that are entirely conserved across species. Their expression is altered in many tumor types, and, although a role for T-UCRs as regulators of gene expression has been proposed, their functions remain largely unknown. Herein, we describe the epigenetic silencing of the uc.160+ T-UCR in gliomas and mechanistically define a novel RNA-RNA regulatory network in which uc.160+ modulates the biogenesis of several members of the miR-376 cluster. This includes the positive regulation of primary microRNA (pri-miRNA) cleavage and an enhanced A-to-I editing on its mature sequence. As a consequence, the expression of uc.160+ affects the downstream, miR-376-regulated genes, including the transcriptional coregulators RING1 and YY1-binding protein (RYBP) and forkhead box P2 (FOXP2). Finally, we elucidate the clinical impact of our findings, showing that hypermethylation of the uc.160+ CpG island is an independent prognostic factor associated with better overall survival in lower-grade gliomas, highlighting the importance of T-UCRs in cancer pathophysiology.

Epigenetic Profiling and Response to CD19 Chimeric Antigen Receptor T-Cell Therapy in B-Cell Malignancies.

BACKGROUND: Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance of epigenetic changes in cancer immunology prompted us to determine the impact of the DNA methylation profiles of CART19 cells on the clinical course. METHODS: We recruited 114 patients with B-cell malignancies, comprising 77 patients with acute lymphoblastic leukemia and 37 patients with non-Hodgkin lymphoma who were treated with CART19 cells. Using a comprehensive DNA methylation microarray, we determined the epigenomic changes that occur in the patient T cells upon transduction of the CAR vector. The effects of the identified DNA methylation sites on clinical response, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, event-free survival, and overall survival were assessed. All statistical tests were 2-sided. RESULTS: We identified 984 genomic sites with differential DNA methylation between CAR-untransduced and CAR-transduced T cells before infusion into the patient. Eighteen of these distinct epigenetic loci were associated with complete response (CR), adjusting by multiple testing. Using the sites linked to CR, an epigenetic signature, referred to hereafter as the EPICART signature, was established in the initial discovery cohort (n = 79), which was associated with CR (Fisher exact test, P < .001) and enhanced event-free survival (hazard ratio [HR] = 0.36; 95% confidence interval [CI] = 0.19 to 0.70; P = .002; log-rank P = .003) and overall survival (HR = 0.45; 95% CI = 0.20 to 0.99; P = .047; log-rank P = .04;). Most important, the EPICART profile maintained its clinical course predictive value in the validation cohort (n = 35), where it was associated with CR (Fisher exact test, P < .001) and enhanced overall survival (HR = 0.31; 95% CI = 0.11 to 0.84; P = .02; log-rank P = .02). CONCLUSIONS: We show that the DNA methylation landscape of patient CART19 cells influences the efficacy of the cellular immunotherapy treatment in patients with B-cell malignancy.

Consumption of peanut products improves memory and stress response in healthy adults from the ARISTOTLE study: A 6-month randomized controlled trial.

BACKGROUND: Peanuts are rich in bioactive compounds that may have a positive impact on memory and stress response. OBJECTIVE: To evaluate the effect of regular consumption of peanut products on cognitive functions and stress response in healthy young adults. DESIGN: A three-arm parallel-group randomized controlled trial was conducted in 63 healthy young adults that consumed 25 g/day of skin roasted peanuts (SRP, n = 21), 32 g/d of peanut butter (PB, n = 23) or 32 g/d of a control butter made from peanut oil (free of phenolic compounds and fiber) (CB, n = 19) for six months. Polyphenol intake, cognitive functions, and anxiety and depression scores were evaluated using validated tests. Fecal short-chain fatty acids (SCFAs) and plasma and fecal fatty acids were assessed by chromatographic methods. Urinary cortisol was quantified by an enzymatic method. RESULTS: Comparing the two interventions with the control, a significant reduction in anxiety scores was observed in the SRP compared to the CB group. After the intervention, consumers of SRP and PB had an improved immediate memory (p = 0.046 and p = 0.011). Lower anxiety scores were associated with SRP and PB (p < 0.001 and p = 0.002, respectively) and lower depression scores with SRP, PB and CB (p = 0.007, p = 0.003 and p = 0.032, respectively). Memory functions and stress response were significantly correlated with polyphenol intake, fecal SCFAs, plasma and fecal very long chain saturated fatty acids (VLCSFAs). CONCLUSIONS: Regular peanut and peanut butter consumption may enhance memory function and stress response in a healthy young population. These effects seem to be associated with the intake of peanut polyphenols, increased levels of fecal SCFAs, and unexpectedly, VLCSFAs, which were also present in the control product.

Accuracy of Virtually Planned Maxillary Distraction in Cleft Patients - An Evaluative Study.

INTRODUCTION: Maxillary distraction may be used to treat severe maxillary hypoplasia in cleft lip and palate (CLP) patients. Three-dimensional (3D) planning has been shown to increase the accuracy of distraction and reduce operative time and complications. The aim of the study was to measure the accuracy of internal maxillary distraction after 3D planning in CLP patients, to add evidence to validate the virtual osteotomy and distraction procedure. MATERIALS AND METHODS: Eleven CLP patients with severe maxillary hypoplasia underwent maxillary distraction using internal distractors. Virtual planning was used to design the osteotomies, the distractor position, and the distraction vector. Cutting and positioning guides transferred this information to the surgical procedure. Four to six month postoperative computed tomography-scan was done before distractor removal; anatomical reference points were compared to the virtual planning to determine accuracy. RESULTS: A high accuracy (point dislocation <1.5 mm) was found in 90% of the points of the surface of the maxilla; the majority of the zygomatic screws were placed within a distance of 0.8-1 mm from their planned position. DISCUSSION: The high accuracy achieved through virtual planning promotes optimal distractor placement; a customized distraction vector has a direct effect on the final position of the maxilla.

Moderate Consumption of Beer (with and without Ethanol) and Menopausal Symptoms: Results from a Parallel Clinical Trial in Postmenopausal Women.

The menopausal transition can be a challenging period for women's health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms (p-value AB vs. Control: 0.009; p-value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.

Effect of physiological factors, pathologies, and acquired habits on the sweet taste threshold: A systematic review and meta-analysis.

Sweet taste perception is a key factor in the establishment of the food pattern with nonstatic thresholds. Indeed, taste sensitivity can be influenced by physiological factors (age and sex), pathologies (obesity and type 2 diabetes mellitus), and acquired habits (tobacco and alcohol consumption). In order to elucidate how these variables influence the sucrose detection threshold (DT) and recognition threshold (RT), a systematic review and meta-analysis of the relevant literature were performed. After a comprehensive search in the PubMed and Scopus databases, a total of 48 studies were qualitatively considered, and 44 were meta-analyzed. The factors of aging (standard mean difference [SMD]: -0.46; 95% confidence interval (CI), -0.74 to -0.19; I2 : 73%; Tau2 : 0.18) and type 2 diabetes mellitus (SMD: 0.30; 95% CI, 0.06 to 0.55; I2 : 0%; Tau2 : 0.00) were found to significantly increase the sucrose RT, whereas the DT only increased in subjects with a higher body mass index (SMD: 0.58; 95% CI, 0.35 to 0.82; I2 : 0%; Tau2 : 0.00). No effects of sex and tobacco smoking were found, and associations with alcohol consumption could not be assessed, as it was included as a variable in only one study. Feasible mechanisms underlying changes in sucrose thresholds include the modulation of hormones involved in energy and body weight homeostasis, taste bud abundance, taste brain signaling, and the gut-brain axis. The present work provides insights into the variables that should be considered when assessing sweet taste sensitivity, discusses the mechanisms underlying differences in sweet taste, and highlights the need for further research in the field of personalized nutrition.

Effects of the Non-Alcoholic Fraction of Beer on Abdominal Fat, Osteoporosis, and Body Hydration in Women.

Several studies have shown that binge drinking of alcoholic beverages leads to non-desirable outcomes, which have become a serious threat to public health. However, the bioactive compounds in some alcohol-containing beverages might mitigate the negative effects of alcohol. In beer, the variety and concentration of bioactive compounds in the non-alcoholic fraction suggests that its consumption at moderate levels may not only be harmless but could also positively contribute to an improvement of certain physiological states and be also useful in the prevention of different chronic diseases. The present review focuses on the effects of non-alcoholic components of beer on abdominal fat, osteoporosis, and body hydration in women, conditions selected for their relevance to health and aging. Although beer drinking is commonly believed to cause abdominal fat deposition, the available literature indicates this outcome is inconsistent in women. Additionally, the non-alcoholic beer fraction might improve bone health in postmenopausal women, and the effects of beer on body hydration, although still unconfirmed seem promising. Most of the health benefits of beer are due to its bioactive compounds, mainly polyphenols, which are the most studied. As alcohol-free beer also contains these compounds, it may well offer a healthy alternative to beer consumers.

Vegetable and Fruit Consumption and Prognosis Among Cancer Survivors: A Systematic Review and Meta-Analysis of Cohort Studies.

The number of cancer survivors is growing rapidly worldwide, especially long-term survivors. Although a healthy diet with a high vegetable and fruit consumption is a key factor in primary cancer prevention, there is a lack of specific dietary recommendations for cancer survivors, except in the case of breast cancer [World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) report]. We have therefore carried out a systematic review and meta-analysis of cohort studies reporting on the associations between vegetable and fruit intake with cancer recurrence and mortality and all-cause mortality in cancer patients. After a comprehensive search of PubMed and Scopus databases, the results of 28 selected articles were analyzed. A high vegetable intake before diagnosis was inversely associated with overall mortality in survivors of head and neck (HR: 0.75; 95% CI: 0.65, 0.87) and ovarian cancer (HR: 0.78; 95% CI: 0.66, 0.91). In ovarian cancer patients, prediagnosis fruit intake was also inversely associated with all-cause mortality (HR: 0.82; 95% CI: 0.70, 0.96). The evidence was insufficient for survivors of other cancers, although these associations generally tended to be protective. Therefore, more studies are needed to clarify the association between vegetable and fruit consumption and the prognosis of these different types of cancer. To date, the general recommendation to consume ≥5 servings of vegetables and fruit per day (∼400 g/d) could underestimate the needs of cancer survivors, particularly those with ovarian tumors, in which the recommendation could increase to ∼600 g/d (i.e., 300 g/d of vegetables and 300 g/d of fruit).

The use of 3D additive manufacturing technology in autogenous dental transplantation.

BACKGROUND: In medicine and dentistry, 3D technology allows the virtual planning and printing of surgical replicas of anatomical structures that can facilitate certain transplant procedures. In dentistry, 3D technology is useful in autogenous tooth transplantation. CASE PRESENTATION: We present a clinical case of an ectopic mandibular second premolar, describing the preoperative planning with dental replicas and the autotransplantation surgery. 3D prints of the surgical replica of the tooth to be transplanted was made using an Objet30 Prime® Printer, PolyJet. Clinical controls performed at 3, 6 and 12 months indicated the satisfactory evolution of the transplanted tooth. CONCLUSION: 3D additive manufacturing technology allows the preparation of a new recipient socket with the aid of a surgical replica of the tooth to be transplanted, thus minimizing handling and extraoral time.

The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition.

One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that the oncofetal HMGA2 gene is aberrantly reexpressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 is abundantly present in the cytoplasm, where it interacts with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. Notably, downregulation of RPSAP52 impairs the balance between the oncogene LIN28B and the tumor suppressor let-7 family of miRNAs, inhibits cellular proliferation and migration in vitro and slows down tumor growth in vivo. In addition, high levels of RPSAP52 in patient samples associate with a worse prognosis in sarcomas. Overall, we reveal the roles of a transcribed pseudogene that may display properties of an oncofetal master regulator in human cancers.

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program.

Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease.