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1.
Cell ; 187(9): 2269-2287.e16, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38608703

RESUMO

Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic BRCA2 mutations predispose to these changes. An analogous SBS signature, again without biallelic BRCA2 inactivation, accompanies MGO accumulation and DNA damage in Kras-driven, Brca2-mutant murine pancreatic cancers and human breast cancers. MGO triggers BRCA2 proteolysis, temporarily disabling BRCA2's tumor suppressive functions in DNA repair and replication, causing functional haploinsufficiency. Intermittent MGO exposure incites episodic SBS mutations without permanent BRCA2 inactivation. Thus, a metabolic mechanism wherein MGO-induced BRCA2 haploinsufficiency transiently bypasses Knudson's two-hit requirement could link glycolysis activation by oncogenes, metabolic disorders, or dietary challenges to mutational signatures implicated in cancer evolution.


Assuntos
Proteína BRCA2 , Neoplasias da Mama , Glicólise , Aldeído Pirúvico , Animais , Proteína BRCA2/metabolismo , Proteína BRCA2/genética , Camundongos , Humanos , Feminino , Aldeído Pirúvico/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Haploinsuficiência , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Mutação , Dano ao DNA , Reparo do DNA , Linhagem Celular Tumoral
2.
Cytokine ; 177: 156541, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38368696

RESUMO

OBJECTIVES: Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients. METHODS AND RESULTS: Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls. CONCLUSIONS: The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.


Assuntos
Hepatite Autoimune , Transplante de Fígado , Animais , Humanos , Feminino , Adulto , Masculino , Fator de Necrose Tumoral alfa , Fígado/patologia , Autoanticorpos , Transdução de Sinais
3.
Neuropsychol Rev ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285291

RESUMO

Autism is more frequently diagnosed in males, with evidence suggesting that females are more likely to be misdiagnosed or underdiagnosed. Possibly, the male/female ratio imbalance relates to phenotypic and camouflaging differences between genders. Here, we performed a comprehensive approach to phenotypic and camouflaging research in autism addressed in two studies. First (Study 1 - Phenotypic Differences in Autism), we conducted a systematic review and meta-analysis of gender differences in autism phenotype. The electronic datasets Pubmed, Scopus, Web of Science, and PsychInfo were searched. We included 67 articles that compared females and males in autism core symptoms, and in cognitive, socioemotional, and behavioural phenotypes. Autistic males exhibited more severe symptoms and social interaction difficulties on standard clinical measures than females, who, in turn, exhibited more cognitive and behavioural difficulties. Considering the hypothesis of camouflaging possibly underlying these differences, we then conducted a meta-analysis of gender differences in camouflaging (Study 2 - Camouflaging Differences in Autism). The same datasets as the first study were searched. Ten studies were included. Females used more compensation and masking camouflage strategies than males. The results support the argument of a bias in clinical procedures towards males and the importance of considering a 'female autism phenotype'-potentially involving camouflaging-in the diagnostic process.

4.
Arch Biochem Biophys ; 753: 109914, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290597

RESUMO

The mitochondrial outer membrane protein porin 1 (Por1), the yeast orthologue of mammalian voltage-dependent anion channel (VDAC), is the major permeability pathway for the flux of metabolites and ions between cytosol and mitochondria. In yeast, several Por1 phosphorylation sites have been identified. Protein phosphorylation is a major modification regulating a variety of biological activities, but the potential biological roles of Por1 phosphorylation remains unaddressed. In this work, we analysed 10 experimentally observed phosphorylation sites in yeast Por1 using bioinformatics tools. Two of the residues, T100 and S133, predicted to reduce and increase pore permeability, respectively, were validated using biological assays. In accordance, Por1T100D reduced mitochondrial respiration, while Por1S133E phosphomimetic mutant increased it. Por1T100A expression also improved respiratory growth, while Por1S133A caused defects in all growth conditions tested, notably in fermenting media. In conclusion, we found phosphorylation has the potential to modulate Por1, causing a marked effect on mitochondrial function. It can also impact on cell morphology and growth both in respiratory and, unpredictably, also in fermenting conditions, expanding our knowledge on the role of Por1 in cell physiology.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Animais , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fosforilação , Canais de Ânion Dependentes de Voltagem/metabolismo , Mitocôndrias/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Mamíferos/metabolismo
5.
Gynecol Oncol ; 182: 99-107, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38262245

RESUMO

BACKGROUND: POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior. OBJECTIVES: To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models. RESULTS: This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I2 = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I2 = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I2 = 68%, 18 studies). CONCLUSION: POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.


Assuntos
Carcinoma Endometrioide , DNA Polimerase II , Neoplasias do Endométrio , Mutação , Gradação de Tumores , Proteínas de Ligação a Poli-ADP-Ribose , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , DNA Polimerase II/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Prognóstico , Intervalo Livre de Progressão
6.
Cephalalgia ; 44(4): 3331024241247845, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38676534

RESUMO

BACKGROUND: Cluster headache is a primary headache disorder characterized by bouts with circadian and circannual patterns. The CLOCK gene has a central role in regulating circadian rhythms. Here, we investigate the circannual CLOCK expression in a population of cluster headache patients in comparison to matched controls. METHODS: Patients with cluster headache were sampled two to four times over at least one year, both in or outside bouts, one week after each solstice and equinox. The expression of CLOCK was measured by quantitative real-time polymerase chain reaction (RT-PCR) in the peripheral blood. RESULTS: This study included 50 patients and 58 matched controls. Among the patient population, composed of 42/50 males (84%) with an average age of 44.6 years, 45/50 (90%) suffered from episodic cluster headache. Two to four samples were collected from each patient adding up to 161 samples, 36 (22.3%) of which were collected within a bout. CLOCK expression for cluster headache patients was considerably different from that of the control population in winter (p-value mean = 0.006283), spring (p-value mean = 0.000006) and summer (p-value mean = 0.000064), but not in autumn (p-value mean = 0.262272). For each season transition, the variations in CLOCK expression were more pronounced in the control group than in the cluster headache population. No statistically significant differences were found between bout and non-bout samples. No individual factors (age, sex, circadian chronotype, smoking and coffee habits or history of migraine) were related to CLOCK expression. CONCLUSIONS: We observed that CLOCK expression in cluster headache patients fluctuates less throughout the year than in the control population. Bout activity and lifestyle factors do not seem to influence CLOCK expression.


Assuntos
Proteínas CLOCK , Cefaleia Histamínica , Humanos , Cefaleia Histamínica/genética , Masculino , Feminino , Adulto , Proteínas CLOCK/genética , Proteínas CLOCK/biossíntese , Pessoa de Meia-Idade , Ritmo Circadiano , Estações do Ano
7.
Br J Nutr ; : 1-13, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772907

RESUMO

This cross-sectional study aims to describe and compare energy, nutrient intake and food consumption according to eating location and by age groups using data from the National Food, Nutrition and Physical Activity Survey (IAN-AF 2015/2016). Dietary intake was estimated by two non-consecutive days of food diaries (children)/24-h recalls (other age groups), and four eating location categories were defined according to the proportion of meals consumed at out-of-home locations: Home (at least 80 % of meals at home), Other Homes, School or Work and Restaurants and Other Places. The majority of meals (69·1 %) were consumed at home. Meals were also often taken at school by children and adolescents and in restaurants and similar outlets by adults and elderly. Children and adolescents in the School or Work category ate more fruit, vegetables and pulses and cereals and starchy tubers, whereas adults in this category ate more red and processed meats, sugar-sweetened beverages and sweets. Compared with Home category, Restaurants and Other Places was associated with worse diet adequacies among children (ß = -1·0; 95 % CI = -2·0, -0·04), adolescents: (ß = -2·4; 95 % CI = -3·2, -1·5) and adults (ß = -1·3; 95 % CI = -1·6, -1·0) reflecting higher intakes of energy, fat, trans-fatty acids and SFA, and Na. The elderly consumed more free sugars and fat when eating out of home in general. Overall, findings reflect important variation in nutrient profiles by eating location, with meals taken at school or work contributing to higher consumption of nutrient-dense foods and those taken in restaurants and other similar settings implying higher consumption of energy-dense foods.

8.
Eur J Pediatr ; 183(8): 3327-3336, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38730194

RESUMO

To evaluate the influence of early nutritional intake on the growth pattern of very preterm infants. This was an observational study including 109 newborns (< 32 weeks gestational age). Perinatal morbidities, nutritional therapy (first four weeks of life), and weight, length, and head circumference (HC) growth at term-equivalent age were evaluated. Growth restriction was defined as a difference > 1.2 SD between the birth and term age measurements. Growth restriction at term-equivalent age: 52.3% (weight), 42.9% (length), and 22% (HC). Morbidities were positively correlated with nutrition therapy and negatively correlated with the total energy provision: protein ratio. The duration of parenteral nutrition, the time to reach full enteral feedings, and the total energy provision: protein ratio were significantly correlated. Nutrient intake influenced weight, length, and HC growth, and cumulative energy deficit was significantly associated with HC growth restriction.   Conclusion: Perinatal morbidities interfere with nutritional therapy and early nutrient intake, leading to insufficient energy and energy provision: protein ratio for growth. What is Known: • The intake of macronutrients early in life, mainly protein, is important for the optimal growth of pretem infants. • The severity of morbidities and low gestational ages impact the nutritional management of preterm infants. What is New: • The number of morbidities, reflecting the severity of the neonatal clinical course, had a detrimental effect on the nutritional therapy and nutrients intake. • The inadequate energy provision per gram of protein ratio was significantly associated with growth restriction in all growth measures at the second week of life, persisting for head circumference up to the fourth week, highlighting the importance of its measurement, as it could be a precocious sign of development risk.


Assuntos
Proteínas Alimentares , Ingestão de Energia , Humanos , Recém-Nascido , Feminino , Masculino , Proteínas Alimentares/administração & dosagem , Nutrição Parenteral/métodos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido Prematuro/crescimento & desenvolvimento , Idade Gestacional , Doenças do Prematuro/etiologia
9.
Climacteric ; 27(4): 340-350, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38978340

RESUMO

Many women seek treatment to improve menopausal vasomotor symptoms (VMS). The selection of women most likely to benefit from menopause hormone therapy (MHT) is crucial in clinical practice. There is general agreement that women younger than 60 years or who initiate MHT within the first 10 years of menopause, with no contraindications, have greater benefits considering symptomatic relief and additional advantages. This group may have the advantage of protection from osteoporosis and from other chronic diseases that affect postmenopausal women, namely cardiovascular disease (CVD). Cumulating evidence supports MHT for symptomatic women. However, inadequate use according to the needs of symptomatic women led to a burden of suffering worldwide. In recent years, the emergent use of non-regulated body-identical hormones (non-rBHT) can expose patients to potential harms. These hormone preparations are not regulated through the same tests of safety, efficacy or dosing consistency as regulated-BHT (r-BHT). The POESIT (Portugal + Spain + Italy) recommendations highlight the use of 17ß-estradiol (E2) and micronized progesterone (P4) as the real r-BHT. In addition, the group emphasizes as an example the data from the REPLENISH study with 1 mg E2/100 mg P4. The combination of the two hormones in one convenient pill showed a clear reduction or elimination of hot flashes and an improvement in sleep quality and, consequently, quality of life. At the same time, this combination has shown high rates of amenorrhea and no significant impact on lipid, glucose or coagulation parameters. Both the REPLENISH study and a real-life retrospective study pointed to the possibility of a lower risk of venous thromboembolism (VTE) with this formulation than with other combinations.


Assuntos
Estradiol , Terapia de Reposição de Estrogênios , Fogachos , Menopausa , Progesterona , Humanos , Feminino , Fogachos/tratamento farmacológico , Estradiol/administração & dosagem , Progesterona/administração & dosagem , Progesterona/uso terapêutico , Terapia de Reposição de Estrogênios/métodos , Pessoa de Meia-Idade , Qualidade de Vida , Espanha , Itália
10.
Appetite ; 198: 107377, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38679064

RESUMO

Most instruments measuring nutrition literacy evaluate theoretical knowledge, not necessarily reflecting skills relevant to food choices. We aimed to develop and validate a photograph-based instrument to assess nutrition literacy (NUTLY) among adults in Portugal. NUTLY assesses the ability to distinguish foods with different nutritional profiles; from each of several combinations of three photographs (two foods with similar contents and one with higher content) participants are asked to identify the food with the highest energy/sodium content. The NUTLY version with 79 combinations, obtained after experts/lay people evaluations, was applied to a sample representing different age, gender and education groups (n = 329). Dimensionality was evaluated through latent trait models. Combinations with negative or with positive small factor loadings were excluded after critical assessment. Internal consistency was measured using Cronbach's alpha and construct validity by comparing NUTLY scores with those obtained in the Medical Term Recognition Test and the Newest Vital Sign (NVS), and across education and training in nutrition/health groups. The cut-off to distinguish adequate/inadequate nutrition literacy was defined through ROC analysis using the Youden index criterion, after performing a Latent class analysis which identified a two-class model to have the best goodness of fit. Test-retest reliability was assessed after one month (n = 158). The final NUTLY scale was unidimensional and included 48 combinations (energy: 33; sodium: 15; α = 0.74). Mean scores (±standard deviation) were highest among nutritionists (39.9 ± 4.4), followed by health professionals (38.5 ± 4.1) and declined with decreasing education (p < 0.001). Those with adequate nutrition literacy according to NVS showed higher NUTLY scores (37.9 ± 4.3 vs. 33.9 ± 6.9, p < 0.001). Adequate nutrition literacy was defined as a NUTLY score≥35 (sensitivity: 89.3%; specificity: 93.7%). Test-retest reliability was high (ICC = 0.77). NUTLY is a valid and reliable nutrition literacy measurement tool.


Assuntos
Letramento em Saúde , Fotografação , Humanos , Feminino , Masculino , Adulto , Reprodutibilidade dos Testes , Portugal , Pessoa de Meia-Idade , Adulto Jovem , Conhecimentos, Atitudes e Prática em Saúde , Idoso , Inquéritos e Questionários/normas , Adolescente
11.
An Acad Bras Cienc ; 96(3): e20230634, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985029

RESUMO

The demand for low-cost and time-efficient biomonitoring and ecological assessment strategies has increased due to threats to biodiversity. We evaluated the ability of surrogates (genera and biovolume classes) to access information provided by diatom species. Moreover, we investigated whether the relative importance of spatial and environment on diatom communities identified at the genus or classified at biovolume classes reflects the ecological responses at the species. We used biotic, environmental, and spatial data from Pampa streams. We employed Procrustes analysis to detect whether the spatial variation of communities at the species level was represented by the surrogates and variation partitioning to evaluate the relative importance of spatial and environment. We found high congruence between the surrogates and diatom species communities. Furthermore, whilst both spatial and environment were important to explain species composition, only the environment was important for both surrogates. We suggest that the use of genus-level determinations can provide information about the environmental relationships of species, whereas biovolume classes may be useful to detect changes in diatom communities. These results are a first step to seek for strategies aiming to simplify biological monitoring and assessments at pampean streams, especially considering the demand for the identification of organisms at the species.


Assuntos
Biodiversidade , Diatomáceas , Monitoramento Ambiental , Rios , Diatomáceas/classificação , Diatomáceas/crescimento & desenvolvimento , Brasil , Rios/química , Monitoramento Ambiental/métodos , Monitoramento Biológico/métodos
12.
J Clin Nurs ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323737

RESUMO

AIM: To analyse the content of the nursing diagnosis ineffective peripheral tissue perfusion in patients with diabetic foot. DESIGN: A methodological study with a quantitative approach was performed. METHODS: The analysis was performed between January and May 2021 by 34 nurses with clinical/theoretical/research experience with diabetes or nursing diagnoses. These nurses evaluated the relevance, clarity and precision of 12 diagnosis-specific etiological factors, 22 clinical indicators and their conceptual and operational definitions. FINDINGS: All 12 etiological factors analysed were considered relevant to diagnostic identification. However, five showed inconsistencies regarding the clarity or precision of the operational definitions, requiring adjustments. Regarding the 22 clinical indicators evaluated, all of them presented a Content Validity Index (CVI) that was statistically significant. However, in the indicators, the colour does not return to lowered limb after 1 min of leg elevation, and cold foot had Content Validity Index (CVI) <0.9 regarding relevance and accuracy of operational definitions. CONCLUSIONS: Twelve etiological factors and 22 clinical indicators were validated. Thus, this study revealed new and relevant aspects characterising peripheral perfusion in patients with diabetic foot that have not yet been clinically validated. IMPLICATIONS FOR NURSING PRACTICE: This study contributes to support the professional practice of nurses through the early identification of etiological factors and clinical indicators in persons with diabetic foot. As a proposal, we suggest the inclusion of new defining characteristics and related factors for the nursing diagnosis ineffective peripheral tissue perfusion in the NANDA-I taxonomy. IMPACT: The research highlights new and relevant aspects such as etiological factors and clinical indicators to characterise peripheral perfusion in patients with diabetic foot. Based on these findings, clinical validation is recommended to confirm the relevance of the proposed elements in the population studied for greater reliability and improved diagnostic assessment for the professional practice of nurses. REPORTING METHOD: EQUATOR guidelines were adhered to using the GRRAS checklist for reporting reliability and agreement studies. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

13.
Alzheimers Dement ; 20(7): 4792-4802, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38865440

RESUMO

INTRODUCTION: The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non-hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain. METHODS: We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non-hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses. RESULTS: Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty-eight percent of the sample had non-hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07), female sex (OR = 1.68, 95% CI = 1.11-2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02-4.35). DISCUSSION: Two-thirds of patients from a memory clinic cohort had non-hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population. HIGHLIGHTS: The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non-hemorrhagic markers. The prevalence of non-hemorrhagic CAA markers in memory clinic patients is unknown. Two-thirds of patients in our memory clinic presented non-hemorrhagic CAA markers. The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers. The hemorrhagic risk of patients presenting these type of markers remains unclear.


Assuntos
Biomarcadores , Angiopatia Amiloide Cerebral , Disfunção Cognitiva , Imageamento por Ressonância Magnética , Humanos , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/complicações , Feminino , Masculino , Idoso , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Transtornos da Memória/etiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Idoso de 80 Anos ou mais
14.
Nutr Health ; : 2601060241248716, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38650585

RESUMO

Aim: To assess the effect of cashew nut flour on the hematological parameters of children living with HIV-AIDS. Method: A 32-week randomized, blind clinical trial conducted at a specialized outpatient clinic. Children aged 2-12 years were allocated to intervention groups (IGs) (n = 11) receiving 12 g/day of cashew nut flour and control groups (CGs) (n = 9) receiving 12 g/day of carboxymethyl cellulose. Parameters of erythrocytes, leukocytes, platelets, and lipid profiles were evaluated. Results: In the IG, the elevation and reduction of leukocyte and lipid profile biomarkers, respectively, were not statistically significant (p > 0.05). A clinically and statistically significant increase in mean corpuscular hemoglobin concentration was observed in the CG (p = 0.018), with a large effect size (Cohen's d = 0.9). There were no statistically significant changes in platelet counts among participants (p = 0.18). The effect size for white blood cell count, low-density lipoprotein cholesterol, very low-density lipoprotein, and triglycerides was moderate in the IG compared to the CG. Conclusion: Cashew nut flour supplementation may increase levels of leukocytes and lipid profile parameters in children living with HIV. Brazilian Clinical Trials Registry (REBEC): U1111.1276.6591.

15.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255965

RESUMO

Stroke is a major cause of death and disability worldwide. Endovascular thrombectomy has been impactful in decreasing mortality. However, many clinical results continue to show suboptimal functional outcomes despite high recanalization rates. This gap in recanalization and symptomatic improvement suggests a need for adjunctive therapies in post-thrombectomy care. With greater insight into ischemia-reperfusion injury, recent preclinical testing of neuroprotective agents has shifted towards preventing oxidative stress through upregulation of antioxidants and downstream effectors, with positive results. Advances in multiple neuroprotective therapies, including uric acid, activated protein C, nerinetide, otaplimastat, imatinib, verapamil, butylphthalide, edaravone, nelonemdaz, ApTOLL, regional hypothermia, remote ischemic conditioning, normobaric oxygen, and especially nuclear factor erythroid 2-related factor 2, have promising evidence for improving stroke care. Sedation and blood pressure management in endovascular thrombectomy also play crucial roles in improved stroke outcomes. A hand-in-hand approach with both endovascular therapy and neuroprotection may be the key to targeting disability due to stroke.


Assuntos
AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/terapia , Neuroproteção , Acidente Vascular Cerebral/terapia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Assistência Odontológica
16.
Int J Mol Sci ; 25(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732233

RESUMO

Donepezil (DNPZ) is a cholinesterase inhibitor used for the management of Alzheimer's disease (AD) and is dependent on membrane transporters such as ABCG2 to actively cross brain barriers and reach its target site of action in the brain. Located in the brain ventricles, the choroid plexus (CP) forms an interface between the cerebrospinal fluid (CSF) and the bloodstream, known as the blood-CSF barrier (BCSFB). Historically, the BCSFB has received little attention as a potential pathway for drug delivery to the central nervous system (CNS). Nonetheless, this barrier is presently viewed as a dynamic transport interface that limits the traffic of molecules into and out of the CNS through the presence of membrane transporters, with parallel activity with the BBB. The localization and expression of drug transporters in brain barriers represent a huge obstacle for drug delivery to the brain and a major challenge for the development of therapeutic approaches to CNS disorders. The widespread interest in understanding how circadian clocks modulate many processes that define drug delivery in order to predict the variability in drug safety and efficacy is the next bridge to improve effective treatment. In this context, this study aims at characterizing the circadian expression of ABCG2 and DNPZ circadian transport profile using an in vitro model of the BCSFB. We found that ABCG2 displays a circadian pattern and DNPZ is transported in a circadian way across this barrier. This study will strongly impact on the capacity to modulate the BCSFB in order to control the penetration of DNPZ into the brain and improve therapeutic strategies for the treatment of AD according to the time of the day.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Barreira Hematoencefálica , Donepezila , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Barreira Hematoencefálica/metabolismo , Animais , Humanos , Encéfalo/metabolismo , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/farmacologia , Transporte Biológico , Plexo Corióideo/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Camundongos , Ritmo Circadiano , Proteínas de Neoplasias
17.
Int J Mol Sci ; 25(6)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38542189

RESUMO

The encapsulation of retinol within silica microparticles has emerged as a promising opportunity in the realm of cosmetic and pharmaceutical formulations, driven by the need to reinforce the photoprotection and oxidation stability of retinol. This work examines the process of encapsulating retinol into silica microparticles. The association efficiency, microparticle size, molecular structure, morphology, oxidation, and release profile, as well as biocompatibility and skin sensitization, were evaluated. Results showed that 0.03% of retinol and 9% of emulsifier leads to an association efficiency higher than 99% and a particle size with an average of 5.2 µm. FTIR results indicate that there is an association of retinol with the silica microparticles, and some may be on the surface. Microscopy indicates that when association happens, there is less aggregation of the particles. Oxidation occurs in two different phases, the first related to the retinol on the surface and the second to the associated retinol. In addition, a burst release of up to 3 h (30% free retinol, 17% associated retinol) was observed, as well as a sustained release of 44% of retinol up to 24 h. Encapsulation allowed an increase in the minimal skin cytotoxic concentrations of retinol from 0.04 µg/mL to 1.25 mg/mL without skin sensitization. Overall, retinol is protected when associated with silica microparticles, being safe to use in cosmetics and dermatology.


Assuntos
Retinoides , Saccharum , Preparações de Ação Retardada , Vitamina A , Dióxido de Silício/química , Tamanho da Partícula
18.
J Environ Manage ; 367: 121991, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39094409

RESUMO

The Equatorial South Atlantic region, spanning over 1700 km, is currently undergoing extensive exploitation through various activities such as oil extraction, desalination plants, marine mineral explorations, and wind power for green hydrogen production. This undoubtedly also contributes to the exacerbation of pre-existing chronic environmental impacts. This study aims to investigate the concentrations of 60 substances, categorized as Persistent Organic Pollutants (POPs) and Contaminants of Emerging Concern (CECs) from various classes including: polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), as well as Pyrethroids (PPs), Triazines (TPs) and Organophosphates (OPPs) pesticides in consumable fish, shellfish, and crabs. The bivalve (Mytella charruana), crab (Ucides cordatus), and catfish (Sciades herzbergii) samples were collected in areas of ecological, environmental and economic importance. This data was used to estimate concentrations in the organisms, and to calculate cancer and human health risk. The most prevalent pollutant classes in the organisms were OCPs, followed by TPs and PPs. Shellfish and fish samples had more compounds indicating health risks, when compared to crabs. The substances causing cancer risks varied across organisms and study areas. The heightened cancer risks linked to specific compounds in various species highlight the urgent need to address persistent pollutants to prevent long-term health impacts on both humans and wildlife. Compounds such as PPs, TPs, and OPPs pose significant risks of neurotoxicity and endocrine disruption. This study underscores the interconnectedness of environmental and human health in coastal ecosystems, calling for continuous monitoring and adaptive management strategies to protect these fragile environments and the communities that rely on them.


Assuntos
Organismos Aquáticos , Animais , Neoplasias , Poluentes Químicos da Água/análise , Bifenilos Policlorados/análise , Praguicidas/análise , Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Humanos , Peixes , Hidrocarbonetos Clorados/análise , Braquiúros
19.
Molecules ; 29(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38792264

RESUMO

The study aimed to utilize MoO3 catalysts, produced on a pilot scale via combustion reaction, to produce biodiesel from residual oil. Optimization of the process was conducted using a 23 experimental design. Structural characterization of the catalysts was performed through X-ray diffraction, fluorescence, Raman spectroscopy, and particle size distribution analyses. At the same time, thermal properties were examined via thermogravimetry and differential thermal analysis. Catalytic performance was assessed following process optimization. α-MoO3 exhibited a monophasic structure with orthorhombic phase, whereas α/h-MoO3 showed a biphasic structure. α-MoO3 had a larger crystallite size and higher crystallinity, with thermal stability observed up to certain temperatures. X-ray fluorescence confirmed molybdenum oxide predominance in the catalysts, with traces of iron oxide. Particle size distribution analyses revealed polymodal distributions attributed to structural differences. Both catalysts demonstrated activity under all conditions tested, with ester conversions ranging from 93% to 99%. The single-phase catalyst had a long life cycle and was reusable for six biodiesel production cycles. The experimental design proved to be predictive and significant, with the type of catalyst being the most influential variable. Optimal conditions included α-MoO3 catalyst, oil/alcohol ratio of 1/15, and a reaction time of 60 min, resulting in high biodiesel conversion rates and showcasing the viability of MoO3 catalysts in residual oil biodiesel production.

20.
J Sci Food Agric ; 104(11): 6541-6552, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38520251

RESUMO

BACKGROUND: Aquaponic systems are sustainable processes of managing water and nutrients for food production. An innovate nutrient-efficient catfish-based (Clarias gariepinus) aquaponics system was implemented for producing two cultivars of two leafy vegetables largely consumed worldwide: lamb's lettuce (Valerianella locusta var. Favor and Valerianella locusta var. de Hollande) and arugula (Eruca vesicaria var. sativa and Eruca sativa). Different growing treatments (4 × 2 factorial design) were applied to plants of each cultivar, grown at two light intensities (120 and 400 µmol m-2 s-1). During growth, several morphological characteristics (root length, plant height, leaf number, foliage diameter and biggest leaf length) were measured. At harvest, plants were weighed and examined qualitatively in terms of greenness and health status. Additionally, leaf extracts were obtained and used to determine total phenolic contents, antioxidant capacities, and levels of cytotoxicity to Caco-2 intestinal model cells. RESULTS: After a 5-week growth period, both lamb's lettuce cultivars presented high levels of greenness and health status, at both light intensities, particularly the var. de Hollande that also showed higher average performance in terms of plant morphology. In turn, arugula cultivars showed lower levels of greenness and health status, especially the cultivar E. vesicaria var. sativa submitted to direct sunlight during growth. In addition, plant specimens submitted to higher levels of light intensity showed higher contents in antioxidants/polyphenols. Cultivars with a higher content in antioxidants/polyphenols led to higher Caco-2 cell viability. CONCLUSION: For successful industrial implementation of the aquaponics technology, different and optimized acclimatizing conditions must be applied to different plant species and cultivars. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Peixes-Gato , Lactuca , Luz , Folhas de Planta , Animais , Humanos , Peixes-Gato/crescimento & desenvolvimento , Peixes-Gato/metabolismo , Lactuca/crescimento & desenvolvimento , Lactuca/química , Lactuca/efeitos da radiação , Lactuca/metabolismo , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Células CACO-2 , Antioxidantes/metabolismo , Antioxidantes/análise , Fenóis/metabolismo , Fenóis/análise
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