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1.
Biochem Pharmacol ; : 116192, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583811

RESUMO

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.

2.
Curr Opin Lipidol ; 35(1): 25-32, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37788374

RESUMO

PURPOSE OF REVIEW: Cardiovascular diseases (CVD) pose a significant public health challenge, contributing to 422 million disability-adjusted life years in 2021. The role of high-density lipoproteins (HDL) and alcohol consumption, one of their major modifiable determinants, remains controversial. The objective of this review is to provide a comprehensive narrative overview of HDL functionality and its predictive value for CVD in relation to patterns of alcohol consumption. RECENT FINDINGS: HDL phenotypes beyond HDL-cholesterol (HDL-c) such as distribution of HDL subspecies, HDL particle abundance, and reverse cholesterol transport capacity are promising indicators of atherosclerotic CVD risk. Low-to-moderate alcohol consumption seems to improve HDL functionality and reduce the incidence of CVD among primarily middle-aged men and postmenopausal women. Advancements in our understanding of HDL biogenesis, structure, and function hold promise for improving HDL-related measures and their predictive value for cardiovascular health. SUMMARY: Low-to-moderate alcohol consumption appears to not only increase HDL-c concentration found in the HDL fraction of plasma but also enhance HDL functionality, providing insights into the underlying mechanisms linking alcohol exposure and cardiovascular health benefits. However, rigorous, well designed intervention trials of alcohol consumption on hard cardiovascular outcomes are needed to identify robust causal associations of HDL phenotypes and alcohol consumption with cardiovascular risk.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Lipoproteínas HDL , Consumo de Bebidas Alcoólicas/efeitos adversos , HDL-Colesterol , Doenças Cardiovasculares/epidemiologia
3.
Animals (Basel) ; 13(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38136835

RESUMO

The quadratus lumborum (QL) block is an ultrasound-guided locoregional anesthesia technique which aims to provide analgesia to the abdomen. The main objective of this study was to assess a modified ultrasound-guided dorsal QL block in cat cadavers. For this purpose, a volume of 0.4 mL kg-1 of a mixture of iopromide and methylene blue was administered between the psoas minor muscle and the vertebral body (VB) of the first lumbar vertebra, and its distribution was assessed in thirteen cat cadavers. We hypothesized that this injection point would be feasible, offering a more cranial distribution of the injectate and a more consistent staining of the truncus sympathicus. The study was divided into two phases. Phase 1 consisted of an anatomical study (three cadavers were dissected). Phase 2 consisted of the ultrasound-guided administration of the injectate and the assessment of its distribution by computed tomography and anatomical dissection. The results showed a consistent distribution of contrast media within five (4-8) VBs from T10 to L5. Methylene blue stained three (2-6) rami ventrales, affecting T11 (10%), T12 (20%), T13 (60%), L1 (85%), L2 (95%) and L3 (65%). The truncus sympathicus was dyed in all cadavers with a spread of five (3-7) VBs. Finally, the splanchnicus major nerve was stained in all cadavers (100%). These results suggest that this technique could provide analgesia to the abdominal viscera and the abdominal wall, probably with the exception of the cranial aspects of the abdominal wall.

4.
J Sci Food Agric ; 103(15): 7506-7516, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37402233

RESUMO

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.


Assuntos
Cerveja , Etanol , Feminino , Humanos , Consumo de Bebidas Alcoólicas , Cerveja/análise , HDL-Colesterol , Pós-Menopausa
5.
Animals (Basel) ; 13(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37444012

RESUMO

The QL block is a high-level locoregional anesthesia technique, which aims to provide analgesia to the abdomen. Several approaches of the QL block have been studied to find out which one allows a greater distribution of the injectate. The aim of this study is to compare the traditional interfascial QL block (IQL) with a new latero-ventral approach (LVQL). We hypothesize that this new approach could be safer and easier to perform, since the injectate is administered more superficially and further away from vital structures. Our second objective is to assess whether a higher volume of injectate (0.6 mL/kg) could reach the ventral branches of the last thoracic nerves, leading to a blockade of the cranial abdomen. Six thawed canine cadavers (12 hemiabdomens) were used for this purpose. Both approaches were performed in all cadavers. A combination of methylene blue/iopromide was administered to each hemiabdomen, randomly assigned to the LVQL or IQL. No differences were found regarding the ease of perform the LVQL with respect to IQL. The results show that both techniques reached the ventral branches from L1 to L3, although only the IQL consistently stained the sympathetic trunk (5/6 IQL vs. 1/6 LVQL). The use of a higher volume did not enhance a more cranial distribution of the injectate.

6.
Mol Cancer ; 22(1): 83, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173708

RESUMO

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.


Assuntos
Neoplasias Hepáticas , Metiltransferases , Humanos , 5-Metilcitosina , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Proteômica , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/genética
8.
Clin Case Rep ; 11(5): e7159, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37215960

RESUMO

This study describes a case of a 20-day-old male fighting bull with bilateral clinical anophthalmia and brachygnathia superior whose dam was 12.5 years old and was mistakenly dewormed with ivermectin intramuscularly in the first third of gestation in a livestock farm. A macroscopic examination of the carcass was performed, with a special focus on the ocular components. Eyeball remains were found in both orbits and a histopathological examination was performed on them. Antibodies by serological study against bovine herpes virus-1, respiratory syncytial virus and bovine viral diarrhea virus for both the cow and the calf were not detected. The calf had small orbits and inside them a white and brown mass of soft consistency. Microscopically, abundant muscular and adipose tissue was observed, alongside nervous structures and vestiges of ocular structures with stratified epithelium and abundant connective tissue with glands. No evidence that this congenital bilateral anophthalmia had infectious or hereditary origin was found. By contrast, the malformation could be related to the treatment with ivermectin during the first month of gestation.

9.
Genes Nutr ; 18(1): 7, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37076809

RESUMO

The predominant source of alcohol in the diet is alcoholic beverages, including beer, wine, spirits and liquors, sweet wine, and ciders. Self-reported alcohol intakes are likely to be influenced by measurement error, thus affecting the accuracy and precision of currently established epidemiological associations between alcohol itself, alcoholic beverage consumption, and health or disease. Therefore, a more objective assessment of alcohol intake would be very valuable, which may be established through biomarkers of food intake (BFIs). Several direct and indirect alcohol intake biomarkers have been proposed in forensic and clinical contexts to assess recent or longer-term intakes. Protocols for performing systematic reviews in this field, as well as for assessing the validity of candidate BFIs, have been developed within the Food Biomarker Alliance (FoodBAll) project. The aim of this systematic review is to list and validate biomarkers of ethanol intake per se excluding markers of abuse, but including biomarkers related to common categories of alcoholic beverages. Validation of the proposed candidate biomarker(s) for alcohol itself and for each alcoholic beverage was done according to the published guideline for biomarker reviews. In conclusion, common biomarkers of alcohol intake, e.g., as ethyl glucuronide, ethyl sulfate, fatty acid ethyl esters, and phosphatidyl ethanol, show considerable inter-individual response, especially at low to moderate intakes, and need further development and improved validation, while BFIs for beer and wine are highly promising and may help in more accurate intake assessments for these specific beverages.

10.
Front Nutr ; 9: 1014140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36458171

RESUMO

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.

11.
Food Funct ; 13(24): 12664-12673, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36454091

RESUMO

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.


Assuntos
Cloreto de Sódio , Limiar Gustativo , Masculino , Feminino , Humanos , Adulto Jovem , Estudos Transversais , Percepção Gustatória , Sacarose , Paladar
12.
Artigo em Inglês | MEDLINE | ID: mdl-36231171

RESUMO

This study investigated the long-term effect (six-months) of a Pain Neuroscience Education (PNE) program on pain perception, quality of life, kinesiophobia and catastrophism in older adults with multimorbidity and chronic pain. Fifty participants (n = 50) were randomly assigned to the pain education therapy group (PET; n = 24) and control group (CG; n = 26). The PET group received six sessions (i.e., once a week, 50 min) about neurophysiology of pain while the CG carried on with their usual life. Perception of pain through the visual analogue scale (VAS), quality of life (EQ-5D questionnaire), kinesiophobia (TSK-11) and catastrophism (PCS) were assessed after six months since the last PNE session. Statistically significant differences on VAS (t(48) = 44, p = 0.01, ES = 0.42 [0.13, 0.65]) was found in favor to PET group. No other statistically significant differences were found. This study found that the application of a PNE intervention in an isolated form was able to significantly reduce pain perception with low effect size in the long-term (six months after intervention) in elderly people with chronic pain.


Assuntos
Dor Crônica , Idoso , Dor Crônica/terapia , Humanos , Medição da Dor , Percepção da Dor , Modalidades de Fisioterapia , Qualidade de Vida
13.
Front Vet Sci ; 9: 887746, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990257

RESUMO

Ultrasonographic assessment of the renal size can provide useful clinical information, in combination with other ultrasonographic parameters. The aims of this study were to establish the agreement between the ultrasonographic and radiographic measurements of the kidneys (K) and vertebral bodies (L5 and L6), to establish an ultrasonographic measurement of kidney-to-vertebral body (L5 and L6) ratio to estimate the renal size in cats, and to assess the impact of age, body weight, sex, and gonadal status on the ultrasonographic measurements of the kidneys, vertebral bodies, and ratios. The vertebral bodies of L5 and L6 were chosen as they were easy to identify with ultrasonography (US) using the lumbosacral junction as a landmark, and they are not usually affected by vertebral anomalies. A total of 60 cats (19 intact males, 12 neutered males, 17 intact females, and 12 neutered females) were included in the study. The cats were divided into three age groups (<7 months, 7 months-7 years, and >7 years), two body weight categories (≤ 3.5 kg and >3.5 kg), and two sex and gonadal status groups (male and female, and intact and neutered, respectively). Measurements of the renal and vertebral body length were performed on the radiographic and ultrasonographic images. Two different ratios were obtained, namely, K/L5 and K/L6. There was no significant difference between the length of both kidneys and the length of the vertebral bodies of L5 and L6 on ultrasonographic or radiographic images. There was a good agreement between ultrasonographic and radiographic measurements of both kidneys and vertebral bodies. In conclusion, the kidney length to L6 length ratio obtained was 1.81 ± 0.20 (1.76-1.86), which was useful for evaluating the size of the feline kidney and was not influenced by the age, body weight, sex, or gonadal status.

14.
Genes Nutr ; 17(1): 12, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35896963

RESUMO

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.

15.
Cancers (Basel) ; 14(4)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35205638

RESUMO

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.

16.
Mol Ther Nucleic Acids ; 27: 621-644, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35036070

RESUMO

Noncoding RNAs play regulatory roles in physiopathology, but their involvement in neurodevelopmental diseases is poorly understood. Rett syndrome is a severe, progressive neurodevelopmental disorder linked to loss-of-function mutations of the MeCP2 gene for which no cure is yet available. Analysis of the noncoding RNA profile corresponding to the brain-abundant circular RNA (circRNA) and transcribed-ultraconserved region (T-UCR) populations in a mouse model of the disease reveals widespread dysregulation and enrichment in glutamatergic excitatory signaling and microtubule cytoskeleton pathways of the corresponding host genes. Proteomic analysis of hippocampal samples from affected individuals confirms abnormal levels of several cytoskeleton-related proteins together with key alterations in neurotransmission. Importantly, the glutamate receptor GRIA3 gene displays altered biogenesis in affected individuals and in vitro human cells and is influenced by expression of two ultraconserved RNAs. We also describe post-transcriptional regulation of SIRT2 by circRNAs, which modulates acetylation and total protein levels of GluR-1. As a consequence, both regulatory mechanisms converge on the biogenesis of AMPA receptors, with an effect on neuronal differentiation. In both cases, the noncoding RNAs antagonize MeCP2-directed regulation. Our findings indicate that noncoding transcripts may contribute to key alterations in Rett syndrome and are not only useful tools for revealing dysregulated processes but also molecules of biomarker value.

17.
Mol Oncol ; 16(3): 648-664, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34665919

RESUMO

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.


Assuntos
Metilação de DNA , Glioma , MicroRNAs , Sequência Conservada/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Glioma/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo
18.
J Natl Cancer Inst ; 114(3): 436-445, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-34581788

RESUMO

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.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos , Epigênese Genética , Humanos , Imunoterapia Adotiva/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/genética
19.
Int J Food Sci Nutr ; 73(2): 184-194, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34425722

RESUMO

This study aims to evaluate whether sous-vide cooking better preserves the (poly)phenol content and profile of red and white cardoon stalks versus traditional boiling, both before and after simulated oral-gastro-intestinal digestion. Thirty one (poly)phenols were quantified in red and white cardoon by HPLC-MS/MS, phenolic acids being >95%, and 5-caffeoylquinic and 1,5-dicaffeoylquinic acids the major ones. Although both varieties showed a similar profile, raw red cardoon had 1.7-fold higher (poly)phenol content than raw white cardoon. Culinary treatments decreased (poly)phenol content, but sous-vide cooked cardoon had a greater content than the boiled one, suggesting a protective effect. After gastrointestinal digestion, (poly)phenol bioaccessibility of boiled and sous-vide cooked cardoon (52.6-90.5%) was higher than that of raw samples (0.2-0.7%), although sous-vide system no longer played a protective effect compared to boiling. In summary, red cardoon was a richer source of bioaccessible (poly)phenols than white cardoon, even sous-vide cooked or boiled.


Assuntos
Cynara , Culinária , Fenol , Fenóis/análise , Espectrometria de Massas em Tandem
20.
Clin Nutr ; 40(11): 5556-5567, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34656952

RESUMO

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.


Assuntos
Arachis , Cognição , Dieta/métodos , Memória de Curto Prazo , Estresse Fisiológico , Adolescente , Adulto , Ansiedade/etiologia , Ansiedade/prevenção & controle , Depressão/etiologia , Depressão/prevenção & controle , Inquéritos sobre Dietas , Ingestão de Alimentos , Ácidos Graxos/metabolismo , Ácidos Graxos Voláteis/sangue , Fezes/química , Feminino , Voluntários Saudáveis , Humanos , Hidrocortisona/urina , Masculino , Polifenóis/análise , Adulto Jovem
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