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1.
Nature ; 615(7953): 652-659, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36890232

RESUMO

Increasing the proportion of locally produced plant protein in currently meat-rich diets could substantially reduce greenhouse gas emissions and loss of biodiversity1. However, plant protein production is hampered by the lack of a cool-season legume equivalent to soybean in agronomic value2. Faba bean (Vicia faba L.) has a high yield potential and is well suited for cultivation in temperate regions, but genomic resources are scarce. Here, we report a high-quality chromosome-scale assembly of the faba bean genome and show that it has expanded to a massive 13 Gb in size through an imbalance between the rates of amplification and elimination of retrotransposons and satellite repeats. Genes and recombination events are evenly dispersed across chromosomes and the gene space is remarkably compact considering the genome size, although with substantial copy number variation driven by tandem duplication. Demonstrating practical application of the genome sequence, we develop a targeted genotyping assay and use high-resolution genome-wide association analysis to dissect the genetic basis of seed size and hilum colour. The resources presented constitute a genomics-based breeding platform for faba bean, enabling breeders and geneticists to accelerate the improvement of sustainable protein production across the Mediterranean, subtropical and northern temperate agroecological zones.


Assuntos
Produtos Agrícolas , Diploide , Variação Genética , Genoma de Planta , Genômica , Melhoramento Vegetal , Proteínas de Plantas , Vicia faba , Cromossomos de Plantas/genética , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Variações do Número de Cópias de DNA/genética , DNA Satélite/genética , Amplificação de Genes/genética , Genes de Plantas/genética , Variação Genética/genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Geografia , Melhoramento Vegetal/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Recombinação Genética , Retroelementos/genética , Sementes/anatomia & histologia , Sementes/genética , Vicia faba/anatomia & histologia , Vicia faba/genética , Vicia faba/metabolismo
2.
Biol Proced Online ; 26(1): 18, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898416

RESUMO

BACKGROUND: The lack of standardized protocols for isolating extracellular vesicles (EVs), especially from biobank-stored blood plasma, translates to limitations for the study of new biomarkers. This study examines whether a combination of current isolation methods could enhance the specificity and purity of isolated EVs for diagnosis and personalized medicine purposes. RESULTS: EVs were isolated from healthy human plasma stored for one year by ultracentrifugation (UC), size exclusion chromatography (SEC), or SEC and UC combined (SEC + UC). The EV isolates were then characterized by transmission electron microscopy imaging, nanoparticle tracking analysis (NTA) and western blotting. Proteomic procedures were used to analyze protein contents. The presence of EV markers in all isolates was confirmed by western blotting yet this analysis revealed higher albumin expression in EVs-UC, suggesting plasma protein contamination. Proteomic analysis identified 542 proteins, SEC + UC yielding the most complex proteome at 364 proteins. Through gene ontology enrichment, we observed differences in the cellular components of EVs and plasma in that SEC + UC isolates featured higher proportions of EV proteins than those derived from the other two methods. Analysis of proteins unique to each isolation method served to identify 181 unique proteins for the combined approach, including those normally appearing in low concentrations in plasma. This indicates that with this combined method, it is possible to detect less abundant plasma proteins by proteomics in the resultant isolates. CONCLUSIONS: Our findings reveal that the SEC + UC approach yields highly pure and diverse EVs suitable for comprehensive proteomic analysis with applications for the detection of new biomarkers in biobank-stored plasma samples.

3.
Psychol Med ; 54(7): 1329-1338, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37987188

RESUMO

BACKGROUND: Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change. METHODS: This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories. RESULTS: The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed. CONCLUSIONS: FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Seguimentos , Estudos Retrospectivos , Estudos Prospectivos , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnóstico
4.
Psychol Med ; : 1-10, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813601

RESUMO

BACKGROUND: Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood. METHODS: Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications. RESULTS: There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose-response relationship was observed between levels of CA and severity of outcome domains. CONCLUSION: Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.

5.
Psychol Med ; : 1-9, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38505954

RESUMO

BACKGROUND: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). METHODS: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. RESULTS: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. CONCLUSIONS: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.

6.
Psychol Med ; 54(7): 1339-1349, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38014924

RESUMO

BACKGROUND: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. METHODS: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. RESULTS: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. CONCLUSIONS: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.


Assuntos
Disfunção Cognitiva , Transtornos Psicóticos , Esquizofrenia , Gravidez , Feminino , Humanos , Transtornos Psicóticos/diagnóstico , Esquizofrenia/complicações , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Imageamento por Ressonância Magnética
7.
Eur J Pediatr ; 183(9): 3757-3766, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38858227

RESUMO

In 2016, the Spanish Research Group on Bronchopulmonary Dysplasia (BPD) (GEIDIS) established a national registry with participation of 66 hospitals to collect information on clinical characteristics and long-term outcomes of BPD infants into adulthood. The aim of this observational study is to examine forced spirometry data in early childhood and to assess their correlation with the respiratory support required at 36 weeks postmenstrual age (PMA). The study analyzed data from preterm infants with BPD born between January 2016 and December 2017 who underwent forced spirometry at 5-7 years of age. Statistical analyses were conducted to investigate the relationships between spirometry results, perinatal factors, and the required respiratory support at 36 weeks PMA. The study involved 143 patients with a median gestational age (GA) of 27.3 weeks (range 25.7-28.7) and a median weight of 880 g (range 740-1135). Abnormal spirometry results were observed in 39.2% (56) of the patients. Among patients diagnosed with BPD type 3, those requiring over 30% oxygen at 36 weeks PMA exhibited an increased risk of abnormal spirometry results (OR 4.48; 95% CI 1.11-18.13) compared to those requiring positive pressure with less than 30% oxygen. In addition, this subgroup had a higher risk of developing a restrictive-mixed pattern compared to those with BPD type 1 (OR 10.65; 95% CI 2.06-54.98) and BPD type 2 (OR 6.76; 95% CI 1.09-42.06). No significant differences were found in the incidence of an obstructive pattern between BPD types.      Conclusion: The requirement of more than 30% oxygen at 36 weeks PMA serves as a risk indicator for pulmonary function impairment in school-aged children with BPD. These findings suggest persistent airway and parenchymal injury in this specific patient population, and highlight the importance of careful monitoring to evaluate their long-term effects on lung function. What is Known: • Premature patients with bronchopulmonary dysplasia (BPD) may present abnormalities in pulmonary function tests during school age. However, the predictive accuracy of consensus BPD severity classification remains uncertain. What is New: • The requirement of more than 30% oxygen at 36 weeks postmenstrual age (PMA) indicates a potential risk of pulmonary function impairment in school-aged children with BPD. Additionally, a significant correlation has been observed between a restrictive-mixed pattern with exposure to mechanical ventilation and the development of severe forms of BPD.


Assuntos
Displasia Broncopulmonar , Sistema de Registros , Espirometria , Humanos , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/epidemiologia , Masculino , Feminino , Espanha/epidemiologia , Recém-Nascido , Criança , Pré-Escolar , Recém-Nascido Prematuro , Idade Gestacional , Pulmão/fisiopatologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-39090439

RESUMO

PURPOSE: Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. METHODS: A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. RESULTS: The total scores on the measures of cognition and social exclusion were strongly associated (ß = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). CONCLUSION: The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38772974

RESUMO

PURPOSE: People with psychotic disorders have high levels of social exclusion; however, little is known about its early predictors. We present a long-term observational cohort study aimed at examining early risk factors for later social exclusion. METHODS: A total of 243 subjects were assessed at their first psychotic episode for early risk factors including sociodemographic variables, familial risk of major mental disorders, perinatal complications, childhood factors, and adolescent factors and re-assessed after a mean follow-up of 21 years for 12 social exclusion domains: leisure activities, housing, work, income, neighborhood deprivation, educational attainment, physical and mental health, family and social support, legal competence, and discrimination. The ability of risk factors to predict social exclusion was examined using hierarchical linear regression. RESULTS: Overall social exclusion was independently predicted by low parental socio-economic status, length of follow-up, familial risk of schizophrenia, obstetric complications, neurodevelopmental delay, poor childhood adjustment, childhood adversity, poor adolescent social networks, poor adolescent adjustment, and low premorbid IQ. The model explained 58.2% of the variance in total social exclusion score. Each social exclusion domain was predicted by a different set of variables, which explained between 17.8 and 57.0% of their variance, although low socio-economic status, familial risk of schizophrenia, obstetric complications, childhood adversity, and poor social networks predicted most of the social exclusion domains. CONCLUSION: Early risk factors strongly predicted later social exclusion. A multifaceted approach to preventing later social exclusion is crucial in people with a first episode of psychosis and early risk factors of social exclusion.

10.
Clin Oral Investig ; 28(5): 255, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630185

RESUMO

OBJECTIVES: To evaluate the trueness of the digital maxillary occlusal records in comparison with the conventional records for the fabrication of complete-arch implant-supported fixed prostheses. MATERIALS AND METHODS: This randomized controlled clinical trial followed the recommendations of the CONSORT statement. Twenty participants who used a mandibular interim complete-arch fixed prosthesis and conventional complete maxillary dentures were included in the study. The participants were randomized into two types of maxillary occlusal records: conventional (COR) and digital (DOR) (TRIOS; Shape A/S). After fabricating the prostheses, the distribution and number of occlusal contact points, and the time taken to obtain the maxillary occlusal record and work model were evaluated. Descriptive analysis was used to evaluate the distribution of occlusal contact points. The Wilcoxon test was employed for assessing the number of occlusal contact points, while the Mann-Whitney U test was used for the time taken to obtain the working casts and the maxillary occlusal record and occlusal adjustment times (p < 0.05). RESULTS: There was a similarity in the jaw relation recording methods regarding the distribution of occlusal contact points. There was no difference in the number of occlusal contact points between the anterior (p = 0.439) and posterior (p = 0.227) teeth. No relationship was observed between the distribution and number of occlusal contact points (COR, p = 0.288; DOR, p = 0.183). DOR required less occlusal and clinical adjustment time, on the other hand more laboratory and total workflow time than COR (p < 0.001). CONCLUSION: The DOR may be an option for obtaining the functional space necessary for the assembly of teeth in complete-arch implant-supported fixed prostheses; however, it requires more working time. CLINICAL RELEVANCE: The digital occlusal recording method can be used to assess the interocclusal space for the virtual tooth setup of a complete-arch implant-supported fixed prosthesis.


Assuntos
Implantes Dentários , Humanos , Prótese Total , Registro da Relação Maxilomandibular , Laboratórios , Mandíbula
11.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38396674

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is associated with high mortality rates. Approximately 80% of cases occur in cirrhotic livers, posing a significant challenge for appropriate therapeutic management. Adequate screening programs in high-risk groups are essential for early-stage detection. The extent of extrahepatic tumor spread and hepatic functional reserve are recognized as two of the most influential prognostic factors. In this retrospective multicenter study, we utilized machine learning (ML) methods to analyze predictors of mortality at the time of diagnosis in a total of 208 patients. The eXtreme gradient boosting (XGB) method achieved the highest values in identifying key prognostic factors for HCC at diagnosis. The etiology of HCC was found to be the variable most strongly associated with a poorer prognosis. The widely used Barcelona Clinic Liver Cancer (BCLC) classification in our setting demonstrated superiority over the TNM classification. Although alpha-fetoprotein (AFP) remains the most commonly used biological marker, elevated levels did not correlate with reduced survival. Our findings suggest the need to explore new prognostic biomarkers for individualized management of these patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizado de Máquina , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/química , Biomarcadores Tumorais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
12.
J Fish Biol ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113396

RESUMO

Batch spawner fishes develop successive clutches of oocytes which allows them to participate in many reproductive cycles during their adult life (iteroparous) and spawn in multiple events within each breeding cycle. Here, ovarian follicular development was morpho-functionally analyzed in females of the iteroparous batch spawner fish Gymnocorymbus ternetzi. To obtain better insights into the reproductive morpho-physiology in batch spawners, the objective of this research was to analyze the dynamics of the follicular development, with its hormonal regulation between two active reproduction events. We found that over 16 days, follicles progressed asynchronously to chromatin nucleolus, Primary and Secondary growth stages of oogenesis with progressive secretion of 17ß-estradiol (E2). During the end of secondary growth, the increase in 17α,20ß-dihydroxy-4-pregnen-3-one (17,20ß-p) was measured relative to the maturation process of the ovarian follicles (e.g., nuclear migration and its rupture during the resumption of meiosis). Interestingly, an additional increase in E2 was observed after fish reproduction, probably related to the recruitment of new batch follicles for secondary growth. We also measured the high values of multiple condition factor post-reproduction measurements, reflecting more energy invested during the pre-reproductive process. We also quantified high concentrations of 17,20ß-p, probably related to the recruitment of a new batch of oogonia to meiosis, presumably secreted by post-ovulatory follicles, after fish reproduction. We finally found that fish without exposure to reproductive stimulus developed a regression phase at day 24, characterized by massive follicle atresia, that allow them to recycle energy and constitutive materials of the follicles invested during oogenesis for another reproductive cycle.

13.
Int J Mol Sci ; 25(14)2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39063180

RESUMO

T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), present significant challenges to treatment due to their aggressive nature and chemoresistance. Chemotherapies remain a mainstay for their management, but the aggressiveness of these cancers and their associated toxicities pose limitations. Immunepotent CRP (ICRP), a bovine dialyzable leukocyte extract, has shown promise in inducing cytotoxicity against various cancer types, including hematological cancers. In this study, we investigated the combined effect of ICRP with a panel of chemotherapies on cell line models of T-ALL and T-LBL (CEM and L5178Y-R cells, respectively) and its impact on immune system cells (peripheral blood mononuclear cells, splenic and bone marrow cells). Our findings demonstrate that combining ICRP with chemotherapies enhances cytotoxicity against tumoral T-cell lymphoblasts. ICRP + Cyclophosphamide (CTX) cytotoxicity is induced through a caspase-, reactive oxygen species (ROS)-, and calcium-dependent mechanism involving the loss of mitochondrial membrane potential, an increase in ROS production, and caspase activation. Low doses of ICRP in combination with CTX spare non-tumoral immune cells, overcome the bone marrow-induced resistance to CTX cell death, and improves the CTX antitumor effect in vivo in syngeneic Balb/c mice challenged with L5178Y-R. This led to a reduction in tumor volume and a decrease in Ki-67 proliferation marker expression and the granulocyte/lymphocyte ratio. These results set the basis for further research into the clinical application of ICRP in combination with chemotherapeutic regimens for improving outcomes in T-cell malignancies.


Assuntos
Ciclofosfamida , Espécies Reativas de Oxigênio , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Ciclofosfamida/farmacologia , Sinergismo Farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Apoptose/efeitos dos fármacos , Bovinos , Morte Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Camundongos Endogâmicos BALB C , Proliferação de Células/efeitos dos fármacos
14.
Int J Mol Sci ; 25(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39063123

RESUMO

Prolonged exposure to HIV-1 transactivator of transcription (Tat) protein dysregulates monoamine transmission, a physiological change implicated as a key factor in promoting neurocognitive disorders among people living with HIV. We have demonstrated that in vivo expression of Tat in Tat transgenic mice decreases dopamine uptake through both dopamine transporter (DAT) and norepinephrine transporter (NET) in the prefrontal cortex. Further, our novel allosteric inhibitor of monoamine transporters, SRI-32743, has been shown to attenuate Tat-inhibited dopamine transport through DAT and alleviates Tat-potentiated cognitive impairments. The current study reports the pharmacological profiles of SRI-32743 in basal and Tat-induced inhibition of human NET (hNET) function. SRI-32743 exhibited less affinity for hNET binding than desipramine, a classical NET inhibitor, but displayed similar potency for inhibiting hDAT and hNET activity. SRI-32743 concentration-dependently increased hNET affinity for [3H]DA uptake but preserved the Vmax of dopamine transport. SRI-32743 slowed the cocaine-mediated dissociation of [3H]Nisoxetine binding and reduced both [3H]DA and [3H]MPP+ efflux but did not affect d-amphetamine-mediated [3H]DA release through hNET. Finally, we determined that SRI-32743 attenuated a recombinant Tat1-86-induced decrease in [3H]DA uptake via hNET. Our findings demonstrated that SRI-32743 allosterically disrupts the recombinant Tat1-86-hNET interaction, suggesting a potential treatment for HIV-infected individuals with concurrent cocaine abuse.


Assuntos
Cocaína , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Produtos do Gene tat do Vírus da Imunodeficiência Humana , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química , Cocaína/farmacologia , Cocaína/metabolismo , Humanos , HIV-1/metabolismo , HIV-1/efeitos dos fármacos , Quinazolinas/farmacologia , Quinazolinas/química , Animais , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Ligação Proteica , Camundongos
15.
Dent Traumatol ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041919

RESUMO

Bodybuilding and cross-training exercises bring health benefits. However, orofacial injuries can occur during practice. This study aimed to map, analyze, interpret, and synthesize data from studies on the main orofacial injuries resulting from bodybuilding and cross-training practices. This scoping review followed the Joanna Briggs Institute and PRISMA-ScR methods, with high-sensitivity searches in PubMed, Web of Science, Scopus, ScienceDirect, Embase, Virtual Health Library and the Google Scholar. Original scientific articles published up to May 2024 were included, which evaluated the presence of self-reported or professionally diagnosed orofacial injuries by bodybuilding and cross-training practitioners aged 18 years or older. Literature reviews, editorials, and guidelines were excluded. Tables and figures were used to map and summarize the results. Out of 30.485 potentially eligible articles, four were included. The main orofacial injuries identified in both bodybuilding and cross-training practitioners were dental damage (n = 4), temporomandibular joint (TMJ) disorders (n = 3), and traumas to oral soft tissues (n = 2) and facial soft tissues (n = 2). Dental damage and TMJ disorders were the most prevalent conditions among bodybuilding and cross-training practitioners. Therefore, dental damage and TMJ disorders were the most prevalent conditions among bodybuilding and cross-training practitioners. However, further prospective studies with more in-depth methodological designs and fewer biases are necessary.

16.
Int J Psychol ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38852955

RESUMO

This research investigates discrimination against suspected Islamic terrorists based on tolerance for the use of torture. This research is justified by the need to identify how intergroup and ideological factors combine to express discrimination. Two experimental studies were conducted with a between-subjects design. Study 1 (N = 282) analysed the terrorist threat against the ingroup and the nationality of torturers with respect to support for torture against suspected Islamic terrorists. Study 2 (N = 165) analysed the interaction among terrorist threat against the ingroup and perceived threat (realistic and symbolic) as moderators in the relationship between RWA and discrimination. Study 1 indicated that support for torture was greater when the victims of terrorist acts and the torturers belonged to the ingroup. Study 2 indicated that the perceived threat encourages support for the use of torture, regardless of the levels of RWA. Taken together, these results elucidate the psychosocial processes that are present in the hostility towards social minorities from predominantly Muslim countries and in the strengthening of xenophobic political positions.

17.
Neuroophthalmology ; 48(4): 294-298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933747

RESUMO

Millard-Gubler syndrome is a pontine syndrome caused by a lesion in the lower pons region. It is characterised by ipsilateral facial paralysis and VI paresis and contralateral brachiocrural palsy. We present the case of a female patient, G4P2A1, at 21 weeks of gestation, with preeclampsia, complaints of blurred vision, diplopia, and right hemiparesis, in whom a clinical diagnosis of Millard-Gubler syndrome was made. Neuroimaging showed an intraparenchymal haemorrhage towards the central portion of the bulbopontine junction. An extensive aetiological study was carried out to determine the cause of the hypertensive disorder syndrome during pregnancy. The patient improved satisfactorily from the neurological deficit after delivery of an early stillbirth.

18.
Int J Dent Hyg ; 22(3): 758-768, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38439218

RESUMO

OBJECTIVE: This scoping review aimed (1) to map, analyse, interpret and synthesize data from in situ studies on which substances were added to acidic beverages to reduce the erosive potential on tooth enamel and (2) to establish the level of evidence of the effectiveness of adding substances to acidic beverages to reduce the erosive potential on tooth enamel. DESIGN: This is a scoping review, according to the methods from the Joanna Briggs Institute and PRISMA-ScR, with high-sensitivity searches in the databases PubMed (MEDLINE), Virtual Health Library, Embase (Elsevier), Scopus (Elsevier), Web of Science and ScienceDirect (Elsevier). In situ studies published in English until December 2022 were included. Studies that did not report a control group were excluded. To map and summarize the results, tables and figures were used. RESULTS: From 895 potentially eligible articles, nine were included. Blackcurrant juices (n = 5) with the addition of calcium (n = 3) or xanthan gum (n = 2) formulations were the most tested in terms of reducing the erosive potential of the beverages on tooth enamel. The profilometer was the equipment of choice (n = 8) for evaluating the loss of enamel structure after the experimental tests. CONCLUSIONS: Calcium and xanthan gum are among the most tested by in situ studies, offering promising results in reducing the erosive potential of fruit juices and carbonated and energy drinks.


Assuntos
Bebidas , Esmalte Dentário , Erosão Dentária , Humanos , Erosão Dentária/prevenção & controle , Erosão Dentária/etiologia , Esmalte Dentário/efeitos dos fármacos , Bebidas/efeitos adversos , Ácidos/efeitos adversos , Concentração de Íons de Hidrogênio , Cálcio/análise , Cálcio/uso terapêutico , Sucos de Frutas e Vegetais/efeitos adversos
19.
Angew Chem Int Ed Engl ; 63(4): e202315146, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-37953459

RESUMO

The chiral-induced spin selectivity effect (CISS) is a breakthrough phenomenon that has revolutionized the field of electrocatalysis. We report the first study on the electron spin-dependent electrocatalysis for the oxygen reduction reaction, ORR, using iron phthalocyanine, FePc, a well-known molecular catalyst for this reaction. The FePc complex belongs to the non-precious catalysts group, whose active site, FeN4, emulates catalytic centers of biocatalysts such as Cytochrome c. This study presents an experimental platform involving FePc self-assembled to a gold electrode surface using chiral peptides (L and D enantiomers), i.e., chiro-self-assembled FePc systems (CSAFePc). The chiral peptides behave as spin filters axial ligands of the FePc. One of the main findings is that the peptides' handedness and length in CSAFePc can optimize the kinetics and thermodynamic factors governing ORR. Moreover, the D-enantiomer promotes the highest electrocatalytic activity of FePc for ORR, shifting the onset potential up to 1.01 V vs. RHE in an alkaline medium, a potential close to the reversible potential of the O2 /H2 O couple. Therefore, this work has exciting implications for developing highly efficient and bioinspired catalysts, considering that, in biological organisms, biocatalysts that promote O2 reduction to water comprise L-enantiomers.

20.
Curr Issues Mol Biol ; 45(6): 5164-5179, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37367077

RESUMO

This study analyzed the chemical composition of Cymbopogon citratus essential oil from Puebla, México, assessed its antioxidant activity, and evaluated in silico protein-compound interactions related to central nervous system (CNS) physiology. GC-MS analysis identified myrcene (8.76%), Z-geranial (27.58%), and E-geranial (38.62%) as the main components, with 45 other compounds present, which depends on the region and growing conditions. DPPH and Folin-Ciocalteu assays using the leaves extract show a promising antioxidant effect (EC50 = 48.5 µL EO/mL), reducing reactive oxygen species. The bioinformatic tool SwissTargetPrediction (STP) shows 10 proteins as potential targets associated with CNS physiology. Moreover, protein-protein interaction diagrams suggest that muscarinic and dopamine receptors are related to each other through a third party. Molecular docking reveals that Z-geranial has higher binding energy than M1 commercial blocker and blocks M2, but not M4 muscarinic acetylcholine receptors, whereas ß-pinene and myrcene block M1, M2, and M4 receptors. These actions may positively affect cardiovascular activity, memory, Alzheimer's disease, and schizophrenia. This study highlights the significance of understanding natural product interactions with physiological systems to uncover potential therapeutic agents and advanced knowledge on their benefits for human health.

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