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1.
Blood ; 144(6): 646-656, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38843478

RESUMO

ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.


Assuntos
Aminopiridinas , Morfolinas , Oxazinas , Púrpura Trombocitopênica Idiopática , Piridinas , Pirimidinas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Idoso , Oxazinas/uso terapêutico , Oxazinas/efeitos adversos , Idoso de 80 Anos ou mais , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Morfolinas/uso terapêutico , Morfolinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Quinase Syk/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Contagem de Plaquetas , Estudos Prospectivos
2.
Glia ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39188024

RESUMO

Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca2+ activation increased the 18F-FDG uptake, but this effect was not found when the study was performed in knock out mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2-/-) nor in floxed mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1ΔGFAP). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca2+ activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38490245

RESUMO

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38741198

RESUMO

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

5.
Pediatr Dev Pathol ; 27(4): 340-347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468551

RESUMO

Rectosigmoid solitary juvenile polyps are benign lesions, relatively frequent in childhood. The clinical debut of a pediatric polyp with bleeding is relatively frequent, but there are very few reports of rectal prolapse of polyps. We present the case of a 7-year-old female patient with no previous history who presented with rectal prolapse of a polyp with acute bleeding. An urgent endoscopic examination was performed and 2 rectosigmoid polypoid lesions were found and resected. The anatomopathological study showed that these were 2 hamartomatous polyps with mild dysplasia. The patient is asymptomatic and is being followed up. The literature concerning rectal prolapse of polyps in the pediatric population is scarce. In a pediatric patient with a rectal prolapse, this entity should be considered in the differential diagnosis.


Assuntos
Hemorragia Gastrointestinal , Prolapso Retal , Humanos , Prolapso Retal/diagnóstico , Prolapso Retal/patologia , Prolapso Retal/etiologia , Feminino , Criança , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/patologia , Pólipos Intestinais/patologia , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/complicações , Diagnóstico Diferencial
6.
World J Surg ; 2024 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304983

RESUMO

BACKGROUND: Groin hernia repair (GHR) is a performed procedure worldwide, with approximately 20 million surgeries carried out each year. Despite being less common in females, there is a lack of research on how sex influences the outcomes of GHR. This systematic review and meta-analysis aim to assess how patient sex impacts results in GHR. METHODS: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. We searched for studies up to October 2023 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The studies included focused on sex outcomes for both robotic and open GHR procedures. Data extraction and quality assessment were conducted using the Risk of Bias in Non-Randomized Studies - Of Interventions tool. Our statistical analysis was performed using the metafor package in RStudio. RESULTS: After screening a total of 3917 articles, we identified 29 studies that met our criteria, comprising a total of 1,236,694 patients. Among them, 98,641 (7.98%) patients were females. Our findings showed that females had higher rates of hernia recurrence (RR 1.28), chronic pain (RR 1.52), and surgical site infections (SSIs) (RR 1.46) compared to males. Females showed a lower tendency to undergo minimally invasive surgery (MIS) with a relative risk of 0.82 (95% CI 0.69-0.97; p = 0.02). CONCLUSION: Females tend to face higher rates of complications after GHR such as an elevated risk of chronic pain, recurrence, and surgical site infections (SSI). Moreover, they undergo fewer MIS options compared to males. These results underscore the importance of research to enhance outcomes for women undergoing GHR.

7.
Appl Microbiol Biotechnol ; 108(1): 375, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878165

RESUMO

The selection of oleaginous bacteria, potentially applicable to biotechnological approaches, is usually carried out by different expensive and time-consuming techniques. In this study, we used Oil Red O (ORO) as an useful dye for staining of neutral lipids (triacylglycerols and wax esters) on thin-layer chromatography plates. ORO could detect minimal quantities of both compounds (detection limit, 0.0025 mg of tripalmitin or 0.005 mg of cetylpalmitate). In addition, we developed a specific, rapid, and inexpensive screening methodology to detect triacylglycerol-accumulating microorganisms grown on the agar plate. This staining methodology detected 9/13 strains with a triacylglycerol content higher than 20% by cellular dry weight. ORO did not stain polyhydroxyalkanoates-producing bacteria. The four oleaginous strains not detected by this screening methodology exhibited a mucoid morphology of their colonies. Apparently, an extracellular polymeric substance produced by these strains hampered the entry of the lipophilic dye into cells. The utilization of the developed screening methodology would allow selecting of oleaginous bacteria in a simpler and faster way than techniques usually used nowadays, based on unspecific staining protocols and spectrophotometric or chromatographic methods. Furthermore, the use of ORO as a staining reagent would easily characterize the neutral lipids accumulated by microorganisms as reserve compounds. KEY POINTS: • Oil Red O staining is specific for triacylglycerols • Oil Red O staining is useful to detect oleaginous bacteria • Fast and inexpensive staining to isolate oleaginous bacteria from the environment.


Assuntos
Compostos Azo , Bactérias , Coloração e Rotulagem , Triglicerídeos , Cromatografia em Camada Fina , Coloração e Rotulagem/métodos , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/química , Compostos Azo/metabolismo , Compostos Azo/química , Triglicerídeos/metabolismo , Triglicerídeos/análise , Técnicas Bacteriológicas/métodos
8.
Cryobiology ; 116: 104947, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39084504

RESUMO

Grapevine (Vitis vinifera L.) crops are continuously exposed to biotic and abiotic stresses, which can cause genetic and epigenetic alterations. To determine the possible effects of grapevine cryopreservation on the regulation of DNA demethylase genes, this work studied the expression of DNA demethylase genes in cryopreserved and post-cryopreserved grapevine tissues. V. vinifera DNA demethylases were characterized by in silico analysis, and gene expression quantification was conducted by RT‒qPCR. Three DNA demethylase sequences were found: VIT_13s0074g00450 (VvDMT), VIT_08s0007g03920 (VvROS1), and VIT_06s0061g01270 (VvDML3). Phylogenetic analysis revealed that the sequences from V. vinifera and A. thaliana had a common ancestry. In the promoters of responsive elements to transcription factors such as AP-2, Myb, bZIP, TBP, and GATA, the conserved domains RRM DME and Perm CXXC were detected. These responsive elements play roles in the response to abiotic stress and the regulation of cell growth. These data helped us characterize the V. vinifera DNA demethylase genes. Gene expression analysis indicated that plant vitrification solution 2 (PVS2) treatment does not alter the expression of DNA demethylase genes. The expression levels of VvDMT and VvROS1 increased in response to cryopreservation by vitrification. Furthermore, in post-cryopreservation, VvROS1 was highly induced, and VvDML3 was repressed in all the treatment groups. Gene expression differences between different treatments and tissues may play roles in controlling methylation patterns during gene regulation in tissues stressed by cryopreservation procedures and in the post-cryopreservation period during plant growth and development.


Assuntos
Criopreservação , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Vitis , Vitis/genética , Vitis/crescimento & desenvolvimento , Criopreservação/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Sementes/genética , Sementes/crescimento & desenvolvimento , Desmetilação do DNA , Zigoto/metabolismo , Metilação de DNA , Crioprotetores/farmacologia
9.
Pediatr Dermatol ; 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39246031

RESUMO

We report on a 13-year-old boy diagnosed with hypohidrotic ectodermal dysplasia (HED) due to a pathogenic variant in ectodysplasin A (EDA). He exhibited multiple whitish, millimetric papules clustered on the nasal ala, forehead, temporal, and zygomatic arch areas. Histological examination revealed numerous hyperplastic sebaceous lobules within the upper dermis. The occurrence of sebaceous papules in this distribution among HED patients has rarely been reported. An association with the blockage of the Wnt/ß-catenin pathway due to EDA malfunction has been speculated.

10.
Pediatr Dermatol ; 41(2): 315-317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37827858

RESUMO

A healthy 2-year-old girl presented with multiple asymptomatic subcutaneous nodules on both legs. Histologically demonstrated calcium deposition within the dermis and subcutaneous tissue consistent with calcinosis cutis. Laboratory abnormalities, underlying genetic conditions, and potential triggering factors were ruled out. The lesions resolved over an 18-month period without treatment, emphasizing the importance of the wait-and-see approach in idiopathic cases of calcinosis cutis.


Assuntos
Calcinose Cutânea , Calcinose , Dermatopatias , Neoplasias Cutâneas , Feminino , Humanos , Pré-Escolar , Calcinose/diagnóstico , Calcinose/patologia , Gordura Subcutânea/patologia , Dermatopatias/diagnóstico , Dermatopatias/patologia
11.
J Sci Food Agric ; 104(10): 5860-5868, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38385790

RESUMO

BACKGROUND: Avocado fruit is rich in xanthophylls, which have been related to positive effects on human health. Xanthophyl acetyltransferases (XATs) are enzymes catalyzing the esterification of carboxylic acids to the hydroxyl group of the xanthophyll molecule. This esterification is thought to increase the lipophilic nature of the xanthophyll and its stability in a lipophilic environment. Studies on XATs in fruits are very scarce, and no studies had been carried out in avocado fruit during postharvest. The objective of this work was to investigate the changes in the expression of genes encoding XAT, during avocado fruit ripening. RESULTS: Avocado fruits were obtained from a local market and stored at 15 °C for 8 days. The fruit respiration rate, ethylene production, and fruit peel's color space parameters (L*, a*, b*) were measured during storage. Fruit mesocarp samples were taken after 1, 3, 5, and 7 days of storage and frozen with liquid nitrogen. Total RNA was extracted from fruit mesocarp, and the quantification of the two genes designated as COGE_ID: 936743791 and COGE_ID: 936800185 encoding XATs was performed with real-time quantitative reverse transcription polymerase chain reaction using actin as a reference gene. The presence of a climacteric peak and large changes in color were recorded during postharvest. The two genes studied showed a large expression after 3 days of fruit storage. CONCLUSIONS: We conclude that during the last stages of ripening in avocado fruit there was an active esterification of xanthophylls with carboxylic acids, which suggests the presence of esterified xanthophylls in the fruit mesocarp. © 2024 Society of Chemical Industry.


Assuntos
Frutas , Regulação da Expressão Gênica de Plantas , Persea , Proteínas de Plantas , Persea/genética , Persea/crescimento & desenvolvimento , Persea/metabolismo , Persea/química , Persea/enzimologia , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Frutas/enzimologia , Frutas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Armazenamento de Alimentos , Xantofilas/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo
12.
Rev Esp Enferm Dig ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39364705

RESUMO

Meckel's Diverticulum (MD) originates from the incomplete obliteration of the omphalomesenteric duct during the seventh week of gestation. The classic clinical description of MD follows the "rule of two: 2% of the population, 2 inches in length, 2 feet from the ileocecal valve, a 2:1 ratio between males and females, and presentation at two years of age. This study evaluates to what extent the "rule of two" applies to a Spanish pediatric cohort.

13.
Pediatr Res ; 94(3): 1180-1188, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37069223

RESUMO

BACKGROUND: Small for gestational age (SGA) perform a postnatal catch-up growth to recover their genetic trajectory. We studied the postnatal catch-up growth pattern of fetuses born with an appropriate-for-gestational-age (AGA) weight but with fetal growth deceleration (FGD) to explore whether they catch up. METHODS: Nine hundred and sixty-six newborns at Villalba University General Hospital (HUGV), were followed from 34 to 37 weeks to birth. Z-scores, adjusted for sex and age, of weight, length, and BMI at 3, 6, 9, and 12 months were calculated. We define catch-up as an increase in z-score greater than 0.67 SD in the growth curves. RESULTS: AGA FGD had lower mean weight and length than AGA non-FGD at all time points; BMI was lower until 3 months. AGA FGD had a lower weight, length, and BMI z-score (until 9, 6 months, and at birth, respectively) than AGA non-FGD. AGA FGD newborns had a significantly increased likelihood of weight catch-up at 3 months (OR 1.79; 95% CI: 1.16, 2.78; p = 0.009) and BMI in all investigated periods (OR 1.90; 95% CI 1.30, 2.78; p < 0.001 at 3 months), compared to AGA non-FGD newborns. CONCLUSIONS: AGA FGD newborns perform catch-up growth, especially in weight and BMI, in the first year of life, compared to AGA non-FGD. IMPACT: Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a lower weight and height, during the first year of life, compared to AGA non-FGD. Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a higher likelihood of weight catch-up in the first 3 months of life and of BMI in the first year compared to AGA non-FGD. AGA FGD experienced early weight and BMI catch-up, especially in the first 3 months of life, like SGA. This finding should be considered in the future follow-up.


Assuntos
Estatura , Peso Fetal , Gravidez , Feminino , Recém-Nascido , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Retardo do Crescimento Fetal , Idade Gestacional
14.
Am J Bot ; 110(5): e16170, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37070636

RESUMO

PREMISE: Domestication of plant species results in phenotypic modifications and changes in biotic interactions. Most studies have compared antagonistic plant-herbivore interactions of domesticated plants and their wild relatives, but little attention has been given to how domestication influences plant-pollinator interactions. Floral attributes and interactions of floral visitors were compared between sister taxa of the genus Cucurbita (Cucurbitaceae), the domesticated C. moschata, C. argyrosperma ssp. argyrosperma and its wild progenitor C. argyrosperma ssp. sororia in the place of origin. METHODS: We conducted univariate and multivariate analyses to compare floral morphological traits and analyzed floral reward (nectar and pollen) quantity and quality between flowers of wild and domesticated Cucurbita taxa. Staminate and pistillate flowers of all three taxa were video recorded, and visitation and behavior of floral visitors were registered and analyzed. RESULTS: Most floral morphological characteristics of flowers of domesticated taxa were larger in both staminate and pistillate flowers. Staminate and pistillate flowers presented distinct correlations between floral traits and integration indices between domesticated and wild species. Additionally, pollen quantity and protein to lipid ratio were greater in domesticated species. Cucurbit pollen specialists, Eucera spp., had the highest probability of visit for all Cucurbita taxa. CONCLUSIONS: We provide evidence that floral traits of domesticated and wild Cucurbita species experienced different selection pressures. Domesticated Cucurbita species may have more resources invested towards floral traits, thereby increasing attractiveness to pollinators and potentially plant reproductive success. Wild ancestor plant populations should be conserved in their centers of origin to preserve plant-pollinator interactions.


Assuntos
Cucurbita , Abelhas , Animais , Cucurbita/genética , Polinização , Domesticação , Plantas , Reprodução , Flores/anatomia & histologia
15.
Appl Microbiol Biotechnol ; 107(17): 5503-5516, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37439834

RESUMO

In actinomycetes, the acyl-CoA carboxylases, including the so-called acetyl-CoA carboxylases (ACCs), are biotin-dependent enzymes that exhibit broad substrate specificity and diverse domain and subunit arrangements. Bioinformatic analyses of the Rhodococcus jostii RHA1 genome found that this microorganism contains a vast arrange of putative acyl-CoA carboxylases domains and subunits. From the thirteen putative carboxyltransferase domains, only the carboxyltransferase subunit RO01202 and the carboxyltransferase domain present in the multidomain protein RO04222 are highly similar to well-known essential ACC subunits from other actinobacteria. Mutant strains in each of these genes showed that none of these enzymes is essential for R. jostii growth in rich or in minimal media with high nitrogen concentration, presumably because of their partial overlapping activities. A mutant strain in the ro04222 gene showed a decrease in triacylglycerol and mycolic acids accumulation in rich and minimal medium, highlighting the relevance of this multidomain ACC in the biosynthesis of these lipids. On the other hand, RO01202, a carboxyltransferase domain of a putative ACC complex, whose biotin carboxylase and biotin carboxyl carrier protein domain were not yet identified, was found to be essential for R. jostii growth only in minimal medium with low nitrogen concentration. The results of this study have identified a new component of the TAG-accumulating machinery in the oleaginous R. jostii RHA1. While non-essential for growth and TAG biosynthesis in RHA1, the activity of RO04222 significantly contributes to lipogenesis during single-cell oil production. Furthermore, this study highlights the high functional diversity of ACCs in actinobacteria, particularly regarding their essentiality under different environmental conditions. KEY POINTS: • R. jostii possess a remarkable heterogeneity in their acyl-carboxylase complexes. • RO04222 is a multidomain acetyl-CoA carboxylase involved in lipid accumulation. • RO01202 is an essential carboxyltransferase only at low nitrogen conditions.


Assuntos
Carboxil e Carbamoil Transferases , Rhodococcus , Triglicerídeos/metabolismo , Rhodococcus/genética , Rhodococcus/metabolismo , Carboxil e Carbamoil Transferases/metabolismo , Nitrogênio/metabolismo
16.
Cryobiology ; 110: 56-68, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36528080

RESUMO

Cryopreservation has the potential for long-term germplasm storage. The metabolic pathways and gene regulation involved in cryopreservation procedures are still not well documented. Hence, the genetic expression profile was evaluated using RNA-Seq in zygotic embryos of grapevines subjected to cryopreservation by vitrification. Sequencing was performed on the Illumina NextSeq 500. The average alignment of reads was 96% against the reference genome. The expression profiles showed 229 genes differentially expressed (186 repressed and 46 induced). The main biological processes showing upregulated enrichment were related to nucleosome assembly, while downregulated processes were related to organ growth. The most highly repressed processes were associated with the organization of the cell wall and membrane components. The unnamed protein product and 17.3 kDa class II heat shock protein (HSP) were highly induced, while ATPase subunit 1 and expansin-A1 were repressed. The response to the cooling and warming process during cryopreservation probably indicates that the changes occurring in transcription may be related to epigenetics. In addition, the cell exhibits an increase in the reserve of nutrients while seeking to survive modestly using available energy and pausing the plant's development. Additionally, energy containment occurred to cope with the stress caused by the treatment where deactivation of components of the cell membrane was observed, possibly due to changes in fluidity caused by alterations in temperature.


Assuntos
Criopreservação , Transcriptoma , Criopreservação/métodos , Temperatura Baixa , Vitrificação , Transição de Fase
17.
Planta Med ; 89(4): 364-376, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36130709

RESUMO

Numerous preclinical studies provide evidence that curcumin, a polyphenolic phytochemical extracted from Curcuma longa (turmeric) has neuroprotective, anti-inflammatory and antioxidant properties against various neurological disorders. Curcumin neuroprotective effects have been reported in different animal models of epilepsy, but its potential effect attenuating brain glucose hypometabolism, considered as an early marker of epileptogenesis that occurs during the silent period following status epilepticus (SE), still has not been addressed. To this end, we used the lithium-pilocarpine rat model to induce SE. Curcumin was administered orally (300 mg/kg/day, for 17 days). Brain glucose metabolism was evaluated in vivo by 2-deoxy-2-[18F]Fluoro-D-Glucose ([18F]FDG) positron emission tomography (PET). In addition, hippocampal integrity, neurodegeneration, microglia-mediated neuroinflammation, and reactive astrogliosis were evaluated as markers of brain damage. SE resulted in brain glucose hypometabolism accompanied by body weight (BW) loss, hippocampal neuronal damage, and neuroinflammation. Curcumin did not reduce the latency time to the SE onset, nor the mortality rate associated with SE. Nevertheless, it reduced the number of seizures, and in the surviving rats, curcumin protected BW and attenuated the short-term glucose brain hypometabolism as well as the signs of neuronal damage and neuroinflammation induced by the SE. Overall, our results support the potential adaptogen-like effects of curcumin attenuating key features of SE-induced brain damage.


Assuntos
Curcumina , Estado Epiléptico , Ratos , Animais , Curcumina/farmacologia , Curcumina/metabolismo , Ratos Sprague-Dawley , Doenças Neuroinflamatórias , Encéfalo , Hipocampo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Glucose/farmacologia , Pilocarpina/metabolismo , Pilocarpina/farmacologia , Modelos Animais de Doenças
18.
J Integr Neurosci ; 22(3): 75, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37258443

RESUMO

BACKGROUND: Epilepsy is one of the most common neurologic diseases, and around 30% of all epilepsies, particularly the temporal lobe epilepsy (TLE), are highly refractory to current pharmacological treatments. Abnormal synchronic neuronal activity, brain glucose metabolism alterations, neurodegeneration and neuroinflammation are features of epilepsy. Further, neuroinflammation has been shown to contribute to dysregulation of neuronal excitability and the progression of epileptogenesis. Flufenamic acid (FLU), a non-steroidal anti-inflammatory drug, is also characterized by its wide properties as a dose-dependent ion channel modulator. In this context, in vitro studies have shown that it abolishes seizure-like events in neocortical slices stimulated with a gamma-aminobutyric acid A (GABAA) receptor blocker. However, little is known about its effects in animal models. Thus, our goal was to assess the efficacy and safety of a relatively high dose of FLU in the lithium-pilocarpine rat model of status epilepticus (SE). This animal model reproduces many behavioral and neurobiological features of TLE such as short-term brain hypometabolism, severe hippocampal neurodegeneration and inflammation reflected by a marked reactive astrogliosis. METHODS: FLU (100 mg/kg, i.p.) was administered to adult male rats, 150 min before SE induced by pilocarpine. Three days after the SE, brain glucose metabolism was assessed by 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) positron emission tomography (PET). Markers of hippocampal integrity, neurodegeneration and reactive astrogliosis were also evaluated. RESULTS: FLU neither prevented the occurrence of the SE nor affected brain glucose hypometabolism as assessed by [18F]FDG PET. Regarding the neurohistochemical studies, FLU neither prevented neuronal damage nor hippocampal reactive astrogliosis. On the contrary, FLU increased the mortality rate and negatively affected body weight in the rats that survived the SE. CONCLUSIONS: Our results do not support an acute anticonvulsant effect of a single dose of FLU. Besides, FLU did not show short-term neuroprotective or anti-inflammatory effects in the rat lithium-pilocarpine model of SE. Moreover, at the dose administered, FLU resulted in deleterious effects.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Estado Epiléptico , Ratos , Masculino , Animais , Lítio/efeitos adversos , Pilocarpina/efeitos adversos , Ácido Flufenâmico/metabolismo , Ácido Flufenâmico/farmacologia , Ácido Flufenâmico/uso terapêutico , Ratos Sprague-Dawley , Fluordesoxiglucose F18/metabolismo , Fluordesoxiglucose F18/farmacologia , Fluordesoxiglucose F18/uso terapêutico , Gliose/metabolismo , Doenças Neuroinflamatórias , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/metabolismo , Epilepsia/metabolismo , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Hipocampo/metabolismo , Glucose/metabolismo , Anti-Inflamatórios/efeitos adversos , Modelos Animais de Doenças
19.
Ultraschall Med ; 44(2): e118-e125, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34820795

RESUMO

PURPOSE: High-frequency ultrasound allows the accurate identification of neurofibromas in neurofibromatosis type 1 (NF1). This study aimed to analyze the ultrasound features of neurofibromas in children with NF1, to establish a classification based on the clinical and sonographic patterns of the different types of neurofibromas, and to evaluate the interobserver correlation coefficient (κ) of this classification. MATERIALS AND METHODS: In this prospective, single referral center observational study, clinical and ultrasound findings of neurofibromas in children diagnosed with NF 1 were analyzed. To identify the ultrasound patterns, a cluster analysis allowing the inclusion of both clinical and ultrasound data was designed. The κ coefficient was calculated using 9 external evaluators. RESULTS: 265 ultrasound scans were performed on a total of 242 neurofibromas from 108 children diagnosed with NF1. Cluster analysis allowed the identification of 9 patterns (Snedecor's F, P < 0.001) classified as "classic" cutaneous neurofibroma, blue-red neurofibroma, pseudoatrophic neurofibroma, nodular subcutaneous neurofibroma, diffuse subcutaneous neurofibroma, congenital cutaneous neurofibroma, congenital plexiform neurofibroma, congenital diffuse and plexiform neurofibroma, and subfascial neurofibroma. The κ coefficient of the interobserver ratings was 0.82. CONCLUSION: Patterns identified in the cluster analysis allow neurofibromas to be classified with a very high interobserver correlation.


Assuntos
Neurofibroma Plexiforme , Neurofibroma , Neurofibromatose 1 , Criança , Humanos , Neurofibromatose 1/diagnóstico por imagem , Neurofibroma Plexiforme/diagnóstico por imagem , Estudos Prospectivos , Neurofibroma/diagnóstico por imagem , Análise por Conglomerados
20.
Sensors (Basel) ; 23(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36679427

RESUMO

Football is a very demanding sport which requires players to exert maximum effort, producing fatigue and eventually injuries. Thermography can be used to detect fatigue and prevent its consequences through thermal asymmetries in the bilateral body areas; however, its adequacy for elite footballers has not been widely studied. Therefore, the objective of the present investigation was to determine the suitability of thermography to detect fatigue in male football players. For this reason, twenty participants were gathered into a pair of subgroups (low [<0.2 °C] vs. high thermal asymmetry [≥0.2 °C]) based on a thermography session of the lower limbs (thighs, calves, and hamstrings). After the thermography session, players performed CMJs before and after an RSA test (6 × 30 m/20″). A mixed two-way analysis of variance and Bonferroni post hoc pairwise comparisons were undertaken to analyse the results. No significant differences (p > 0.05) were found in any of the RSA test variables between low and high thermal asymmetry groups for thighs and calves. On the other hand, the low thermal asymmetry hamstring group reported a smaller percentage difference in sprints for the first sprint (%Diff) and a larger percentage difference in sprints two and three with respect to the best sprint (%Best). For CMJs, the low thermal asymmetry hamstring group reported significantly higher values post-RSA test, indicating better performance. Accordingly, thermography can provide information about performance in CMJ and RSA tests through hamstring asymmetries over 0.2 °C. Meanwhile, larger asymmetries than 0.2 °C in calves and thighs do not seem to be related to performance in these tests; therefore, coaches should consider if it is optimal to align players with high hamstring asymmetries.


Assuntos
Desempenho Atlético , Futebol Americano , Corrida , Futebol , Humanos , Masculino , Termografia , Fadiga
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