RESUMO

Introducción: Diversas investigaciones han establecido la relación entre temperatura y duración del embarazo, la exposición a temperaturas altas durante el embarazo plantea interrogantes en especial el papel que esta juega frente a los partos prematuros y partos de bajo peso, es indispensable determinar si las temperaturas altas o bajas tienen un comportamiento protector o de riesgo sobre el feto durante la gestación en regiones tropicales. Objetivo: describir la relación entre la exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos del departamento del Guaviare-Colombia. Metodología: Estudio tipo observacional, analítico, retrospectivo de corte transversal que busco determinar la relación entre exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos, el universo estuvo conformado por 10.137 nacidos vivos, de los cuales 9.932 cumplieron los criterios de inclusión. Se determinó Odds Ratio para estimar la asociación entre las variables. Resultados: Dentro de la semana de retraso 3 el estar expuesto a temperaturas máximas percentil 90 es un factor protector para la ganancia ponderal de peso OR < 1, la exposición a temperaturas mínimas percentil 10 se asoció como factor protector para el parto prematuro en la semana de retraso 1 y 2 OR < 1.Conclusión: A pesar del beneficio de las altas y bajas temperaturas durante el embarazo en la ganancia ponderal de peso y disminución del parto prematuro, es recomendable prevenir la exposición a temperaturas extremas durante el periodo de gestación[AU]

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Introduction: Various investigations have established the relationship between temperature and duration of pregnancy. Exposure to high temperatures during pregnancy raises questions, especially the role it plays in premature births and low-weight births. It is essential to determine whether high temperatures or low have a protective or risky behavior on the fetus during pregnancy in tropical regions.Objective: to describe the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns in the department of Guaviare-Colombia.Methodology:Observational, analytical, retrospective cross-sectional study that sought to determine the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns. The universe was made up of 10,137 births. alive, of which 9,932 met the inclusion criteria. Odds Ratio was determined to estimate the association between the variables.Results:Within the 3rd week of delay, being exposed to maximum temperatures at the 90th percentile is a protective factor for weight gain OR < 1, exposure to minimum temperatures at the 10th percentile was associated as a protective factor for premature birth in the week. of delay 1 and 2 OR < 1. Conclusion: Despite the benefit of high and low temperatures during pregnancy in weight gain and reduction in premature birth, it is advisable to prevent exposure to extreme temperatures during the gestation period[AU]

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Introdução: Várias investigações estabeleceram a relação entre temperatura e duração da gravidez. A exposição a altas temperaturas durante a gravidez levanta questões, especialmente o papel que desempenha nos partos prematuros e nos nascimentos de baixo peso. É essencial determinar se as temperaturas altas ou baixas têm um comportamento protetor ou de risco para o feto durante a gravidez em regiões tropicais. Objetivo:descrever a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos no departamento de Guaviare-Colômbia. Metodologia: Estudo observacional, analítico, retrospectivo e transversal que buscou determinar a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos. O universo foi composto por 10.137 nascimentos. vivos, dos quais 9.932 preencheram os critérios de inclusão. O Odds Ratio foi determinado para estimar a associação entre as variáveis. Resultados:Na 3ª semana de atraso, a exposição a temperaturas máximas no percentil 90 é fator de proteção para ganho de peso OR < 1, a exposição a temperaturas mínimas no percentil 10 foi associada como fator de proteção para parto prematuro na semana. de atraso 1 e 2 OR < 1.Conclusão:Apesar do benefício das altas e baixas temperaturas durante a gravidez no ganho de peso e redução do parto prematuro, é aconselhável evitar a exposição a temperaturas extremas durante o período de gestação[AU]

Assuntos

Humanos , Feminino , Gravidez , Recém-Nascido de muito Baixo Peso , Parto , Colômbia

RESUMO

Sciadonus alphacrucis Melo, Gomes, Møller & Nielsen, 2022 is a rare deep-sea species, previously known from only two specimens collected off São Paulo State, southeastern Brazil, in the western South Atlantic. Herein, we report a new specimen of S. alphacrucis collected on the continental slope off Santa Catarina State, southern Brazil, thereby extending its known distribution by 420 km. Additionally, we provide the new meristic and morphometric data, the molecular identification using sequences of the cytochrome c oxidase subunit I (COI), an updated distribution map, and a discussion of troglomorphic traits.

Assuntos

Código de Barras de DNA Taxonômico , Complexo IV da Cadeia de Transporte de Elétrons , Animais , Brasil , Complexo IV da Cadeia de Transporte de Elétrons/genética , Oceano Atlântico , Filogenia , Distribuição Animal , Feminino , Masculino , Peixes/genética , Peixes/classificação

RESUMO

In 2023, cholera affected approximately 1 million people and caused more than 5000 deaths globally, predominantly in low-income and conflict settings. In recent years, the number of new cholera outbreaks has grown rapidly. Further, ongoing cholera outbreaks have been exacerbated by conflict, climate change, and poor infrastructure, resulting in prolonged crises. As a result, the demand for treatment and intervention is quickly outpacing existing resource availability. Prior to improved water and sanitation systems, cholera, a disease primarily transmitted via contaminated water sources, also routinely ravaged high-income countries. Crumbling infrastructure and climate change are now putting new locations at risk - even in high-income countries. Thus, understanding the transmission and prevention of cholera is critical. Combating cholera requires multiple interventions, the two most common being behavioral education and water treatment. Two-dose oral cholera vaccination (OCV) is often used as a complement to these interventions. Due to limited supply, countries have recently switched to single-dose vaccines (OCV1). One challenge lies in understanding where to allocate OCV1 in a timely manner, especially in settings lacking well-resourced public health surveillance systems. As cholera occurs and propagates in such locations, timely, accurate, and openly accessible outbreak data are typically inaccessible for disease modeling and subsequent decision-making. In this study, we demonstrated the value of open-access data to rapidly estimate cholera transmission and vaccine effectiveness. Specifically, we obtained non-machine readable (NMR) epidemic curves for recent cholera outbreaks in two countries, Haiti and Cameroon, from figures published in situation and disease outbreak news reports. We used computational digitization techniques to derive weekly counts of cholera cases, resulting in nominal differences when compared against the reported cumulative case counts (i.e., a relative error rate of 5.67% in Haiti and 0.54% in Cameroon). Given these digitized time series, we leveraged EpiEstim-an open-source modeling platform-to derive rapid estimates of time-varying disease transmission via the effective reproduction number ( R t ). To compare OCV1 effectiveness in the two considered countries, we additionally used VaxEstim, a recent extension of EpiEstim that facilitates the estimation of vaccine effectiveness via the relation among three inputs: the basic reproduction number ( R 0 ), R t , and vaccine coverage. Here, with Haiti and Cameroon as case studies, we demonstrated the first implementation of VaxEstim in low-resource settings. Importantly, we are the first to use VaxEstim with digitized data rather than traditional epidemic surveillance data. In the initial phase of the outbreak, weekly rolling average estimates of R t were elevated in both countries: 2.60 in Haiti [95% credible interval: 2.42-2.79] and 1.90 in Cameroon [1.14-2.95]. These values are largely consistent with previous estimates of R 0 in Haiti, where average values have ranged from 1.06 to 3.72, and in Cameroon, where average values have ranged from 1.10 to 3.50. In both Haiti and Cameroon, this initial period of high transmission preceded a longer period during which R t oscillated around the critical threshold of 1. Our results derived from VaxEstim suggest that Haiti had higher OCV1 effectiveness than Cameroon (75.32% effective [54.00-86.39%] vs. 54.88% [18.94-84.90%]). These estimates of OCV1 effectiveness are generally aligned with those derived from field studies conducted in other countries. Thus, our case study reinforces the validity of VaxEstim as an alternative to costly, time-consuming field studies of OCV1 effectiveness. Indeed, prior work in South Sudan, Bangladesh, and the Democratic Republic of the Congo reported OCV1 effectiveness ranging from approximately 40% to 80%. This work underscores the value of combining NMR sources of outbreak case data with computational techniques and the utility of VaxEstim for rapid, inexpensive estimation of vaccine effectiveness in data-poor outbreak settings.

RESUMO

[This corrects the article DOI: 10.3389/fmicb.2022.843170.].

RESUMO

In mammal's pineal glands, ATP interacts with the high-affinity P2Y1 and the low-affinity P2X7 receptors. ATP released from sympathetic nerve terminals potentiates noradrenaline-induced serotonin N-acetyltransferase (Snat) transcription, N-acetylserotonin (NAS), and melatonin (MLT) synthesis. Circulating melatonin impairs the expression of adhesion molecules in endothelial cells, blocking the migration of leukocytes. Acute defence response induced by pathogen- and danger/damage-associated molecular patterns (PAMPs and DAMPs) triggers the NF-κB pathway in pinealocytes and blocks the transcription of Snat. Therefore, the darkness hormone is not released, and neutrophils and monocytes migrate to the lesion sites. ATP released in high amounts from apoptotic and death cells was considered a DAMP, and the blockage of P2X7 receptors was tested as a new class of drugs for treating brain damage. However, this is not a simple equation. High ATP injected in a lateral ventricle blocked MLT, but not NAS, synthesis as it impairs the transcription of acetyl serotonin N-methyltransferase. NAS is released in the plasma and the cerebral spinal fluid. NAS also blocks the rolling and adhesion of leukocytes to endothelial cells. Otherwise, it is metabolised specifically in each brain area to provide the requested concentration of MLT as a neuroprotector. As observed in physiological conditions, high extracellular ATP, different from the other DAMPs, reports the environmental light/dark cycle rhythm because NAS substitutes MLT as the nocturnal chemical indicator, the darkness hormone. Thus, blocking the P2X7R should not be considered a universal therapy for improving acute strokes, as MLT and ATP are partners in health and disease.

RESUMO

INTRODUCTION: The study aimed to assess the psychometric quality of the Peer Mental Health Stigmatization Scale - Revised (PMHSS-R), by examining its factorial structure among young adults in Ireland and Argentina. METHOD: A total of 429 participants aged between 18 and 25 years old were recruited (n = 187 Ireland, n = 242 Argentina). The PMHSS-R was completed by Irish participants and was translated, pilot-studied, and subsequently completed by Argentinian participants. RESULTS: A Confirmatory Factor Analysis demonstrated optimal factor loadings for an eight-item solution and acceptable internal consistency for both scale dimensions in the Argentinian sample. Satisfactory levels of partial scalar invariance were achieved between countries, indicating that the scale measures mental health stigma consistently across cultures. DISCUSSION AND CONCLUSIONS: Our findings highlight the PMHSS-R as a cross-culturally valid and reliable psychometric instrument to evaluate interventions targeting stigma. In conclusion, the PMHSS-R can be used in cross-cultural research to compare levels of mental health stigma and investigate the interplay between stigma and other psychologically relevant constructs between different countries and cultural contexts.

RESUMO

Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.

Assuntos

Neoplasias da Mama , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Proteína Supressora de Tumor p53 , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Brasil/epidemiologia , Adulto , Proteína Supressora de Tumor p53/genética , Pessoa de Meia-Idade , Testes Genéticos/métodos , Saúde Pública , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/epidemiologia , Idoso

RESUMO

OBJECTIVES: Whole-grain pearl millet is a nutritious cereal source of dietary fiber, vitamins, minerals, and bioactive compounds. It offers health benefits such as glycemic control and satiety. Extrusion cooking for diverse formulations, including beverages, can alter its chemical composition, impacting the nutritional value. This study aimed to evaluate the sensory acceptability of an extruded millet flour beverage and its acute effects on glycemic index (GI), glycemic and insulinemic response, food intake, and subjective appetite sensations in euglycemic and eutrophic adults. METHODS: This is an acute, single-blind, randomized, controlled, cross-over clinical study comprising 14 euglycemic and eutrophic adults. Initially, beverages based on whole extruded millet flour were developed, and sensorially and chemically analyzed. Next, a clinical trial was conducted with participants undergoing four sessions and consuming one of the following options: extruded millet beverage, a maltodextrin control beverage, or a glucose solution administered in two separate sessions. Blood glucose, insulin, and appetite responses were assessed over a 2-h period, in addition to determining the GI of the beverages and analyzing food intake in the 24 h following each session. RESULTS: The extruded millet flour strawberry-flavored beverage had the best sensory acceptance and was classified as having as high GI. Consumption of the extruded millet beverage showed similar glycemic and insulinemic responses, as well as appetite control and food intake of the subjects, when compared with consumption of the maltodextrin control beverage. CONCLUSIONS: Intake of the extruded millet beverage maintained glycemic and insulinemic responses, appetite control, and food intake in euglycemic and eutrophic subjects.

Assuntos

Apetite , Bebidas , Glicemia , Estudos Cross-Over , Farinha , Índice Glicêmico , Insulina , Pennisetum , Humanos , Adulto , Masculino , Método Simples-Cego , Feminino , Apetite/efeitos dos fármacos , Farinha/análise , Bebidas/análise , Insulina/sangue , Glicemia/análise , Controle Glicêmico/métodos , Ingestão de Alimentos/fisiologia , Pessoa de Meia-Idade , Adulto Jovem , Grãos Integrais , Fibras na Dieta/administração & dosagem , Fibras na Dieta/análise

RESUMO

The irreproducibility in scientific research has become a critical issue. Despite the essential role of rigorous methodology in constructing a scientific article, more than half of publications, on average, are considered non-reproducible. The implications of this irreproducibility extend to reliability problems, hindering progress in technological production and resulting in substantial financial losses. In the context of laboratory animal research, this work emphasizes the importance of choosing an appropriate experimental model within the 3R's principle (Refine, Reduce, Replace). This study specifically addresses a deficiency in data specification in scientific articles, revealing inadequacies in the description of crucial details, such as environmental conditions, diet, and experimental procedures. For this purpose, 124 articles from journals with relevant impact factors were analyzed, conducting a survey of data considered important for the reproducibility of studies. Important flaws in the presentation of data were identified in most of the articles evaluated. The results of this study highlight the need to improve the description of essential information, standardizing studies, and ensuring the reproducibility of experiments in areas such as metabolism, immunity, hormones, stress, among others, to enhance the reliability and reproduction of experimental results, aligning with international guidelines such as ARRIVE and PREPARE.

RESUMO

Candida auris is an emerging multidrug-resistant and opportunistic pathogenic yeast. Whole-genome sequencing analysis has defined five major clades, each from a distinct geographic region. The current study aimed to examine the genome of the C. auris 20-1498 strain, which is the first isolate of this fungus identified in Mexico. Based on whole-genome sequencing, the draft genome was found to contain 70 contigs. It had a total genome size of 12.86 Mbp, an N50 value of 1.6 Mbp, and an average guanine-cytosine (GC) content of 45.5%. Genome annotation revealed a total of 5432 genes encoding 5515 proteins. According to the genomic analysis, the C. auris 20-1498 strain belongs to clade IV (containing strains endemic to South America). Of the two genes (ERG11 and FKS1) associated with drug resistance in C. auris, a mutation was detected in K143R, a gene located in a mutation hotspot of ERG11 (lanosterol 14-α-demethylase), an antifungal drug target. The focus on whole-genome sequencing and the identification of mutations linked to the drug resistance of fungi could lead to the discovery of new therapeutic targets and new antifungal compounds.

RESUMO

Thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2) is an intercellular signal produced mainly by neurons. Among the multiple pharmacological effects of TRH, that on food intake is not well understood. We review studies demonstrating that peripheral injection of TRH generally produces a transient anorexic effect, discuss the pathways that might initiate this effect, and explain its short half-life. In addition, central administration of TRH can produce anorexic or orexigenic effects, depending on the site of injection, that are likely due to interaction with TRH receptor 1. Anorexic effects are most notable when TRH is injected into the hypothalamus and the nucleus accumbens, while the orexigenic effect has only been detected by injection into the brain stem. Functional evidence points to TRH neurons that are prime candidate vectors for TRH action on food intake. These include the caudal raphe nuclei projecting to the dorsal motor nucleus of the vagus, and possibly TRH neurons from the tuberal lateral hypothalamus projecting to the tuberomammillary nuclei. For other TRH neurons, the anatomical or physiological context and impact of TRH in each synaptic domain are still poorly understood. The manipulation of TRH expression in well-defined neuron types will facilitate the discovery of its role in food intake control in each anatomical scene.

RESUMO

Cancer stem cells (CSCs) are a group of tumor cells with high tumorigenic ability and self-renewal potential similar to those of normal stem cells. CSCs are the key "seeds" for tumor development, metastasis, and recurrence. A better insight into the key mechanisms underlying CSC survival improves the efficiency of cancer therapy via specific targeting of CSCs. Insulin-like growth factor (IGF)/IGF-1 receptor (IGF-1R) signaling plays an important role in the maintenance of cancer stemness. However, the effect of IGF/IGF-1R signaling on stemness and CSCs and the underlying mechanisms are still controversial. Based on the similarity between CSCs and normal stem cells, this review discusses emerging data on the functions of IGF/IGF-1R signaling in normal stem cells and CSCs and dissects the underlying mechanisms by which IGF/IGF-1R signaling is involved in CSCs. On the other hand, this review highlighted the role of IGF/IGF-1R signaling blockade in multiple CSCs as a potential strategy to improve CSC-based therapy.

RESUMO

Propolis is a resinous bee product with a very complex composition, which is dependent upon the plant sources that bees visit. Due to the promising antimicrobial activities of red Brazilian propolis, it is paramount to identify the compounds responsible for it, which, in most of the cases, are not commercially available. The aim of this study was to develop a quick and clean preparative-scale methodology for preparing fractions of red propolis directly from a complex crude ethanol extract by combining the extractive capacity of counter-current chromatography (CCC) with preparative HPLC. The CCC method development included step gradient elution for the removal of waxes (which can bind to and block HPLC columns), sample injection in a single solvent to improve stationary phase stability, and a change in the mobile phase flow pattern, resulting in the loading of 2.5 g of the Brazilian red propolis crude extract on a 912.5 mL Midi CCC column. Three compounds were subsequently isolated from the concentrated fractions by preparative HPLC and identified by NMR and high-resolution MS: red pigment, retusapurpurin A; the isoflavan 3(R)-7-O-methylvestitol; and the prenylated benzophenone isomers xanthochymol/isoxanthochymol. These compounds are markers of red propolis that contribute to its therapeutic properties, and the amount isolated allows for further biological activities testing and for their use as chromatographic standards.

Assuntos

Distribuição Contracorrente , Própole , Própole/química , Distribuição Contracorrente/métodos , Cromatografia Líquida de Alta Pressão , Brasil , Animais , Fracionamento Químico/métodos , Abelhas/química

RESUMO

Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT1R blockade has anti-inflammatory effects. The use of an AT1 receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT1 receptor gene silencing on the modulation of cytokines (e.g., IL-1ß, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. MATERIALS AND METHODS: We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT1R, NF-κB, and cytokines (IL-1ß, TNF-α, and IL-10) were measured by RT-qPCR. RESULTS: We observed that silencing of the AT1 receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1ß and TNF-α), NF-κB, and PPAR-γ. CONCLUSIONS: We conclude that AT1R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1ß via NF-κB in macrophages and having high blood pressure decrease.

RESUMO

Among cattle, Bos taurus breeds and their crosses are more sensitive to tick infestations than Bos indicus breeds that are more resistant to infestation and more adaptable to tropical climates. The presence of susceptible individuals in herds and inadequate tick control lead to direct and indirect losses in the meat production chain, in addition to increased mortality due to cattle tick fever. The objective of this study was to describe, compare and rank the sensitivity of different breeds of stabled cattle to the tick Rhipicephalus microplus and to present, as an innovative result, a scale called the Tick Ruler. Secondary data on the number of retrieved engorged females, engorged female ticks' weight, egg mass weight and number of larvae were extracted from research reports of experiments conducted over 18 years with eight breeds to describe and report the sensitivity of the breeds to artificial infestation by R. microplus larvae. For analyses, the recovery rate of engorged female ticks and the percentile of dispersion of individuals in their respective races were calculated, and comparison of these percentiles between races was performed. The ranking of the percentiles resulted in the organization of the breeds by their susceptibility to R. microplus; we call this scale the "Tick Ruler." The ruler is a simple, easy-to-understand tool that can be used by technicians and producers to evaluate the tick sensitivity of a breed of interest and can assist producers in decision-making to find a balance between increased production gains and the risk of economic losses depending on the breed composition in a cattle herd.

Assuntos

Doenças dos Bovinos , Larva , Rhipicephalus , Infestações por Carrapato , Animais , Rhipicephalus/fisiologia , Rhipicephalus/genética , Bovinos , Infestações por Carrapato/veterinária , Infestações por Carrapato/parasitologia , Feminino , Doenças dos Bovinos/parasitologia , Larva/crescimento & desenvolvimento , Larva/fisiologia , Cruzamento

RESUMO

The MC1R protein is a receptor found in melanocytes that plays a role in melanin synthesis. Mutations in this protein can impact hair color, skin tone, tanning ability, and increase the risk of skin cancer. The MC1R protein is activated by the alpha-melanocyte-stimulating hormone (α-MSH). Previous studies have shown that mutations affect the interaction between MC1R and α-MSH; however, the mechanism behind this process is poorly understood. Our study aims to shed light on this mechanism using molecular dynamics (MD) simulations to analyze the Asp84Glu and Asp294His variants. We simulated both the wild-type (WT) protein and the mutants with and without ligand. Our results reveal that mutations induce unique conformations during state transitions, hindering the switch between active and inactive states and decreasing cellular levels of cAMP. Interestingly, Asp294His showed increased ligand affinity but decreased protein activity, highlighting that tighter binding does not always lead to increased activation. Our study provides insights into the molecular mechanisms underlying the impact of MC1R mutations on protein activity.

Assuntos

AMP Cíclico , Mutação , Receptor Tipo 1 de Melanocortina , alfa-MSH , Humanos , alfa-MSH/química , alfa-MSH/metabolismo , alfa-MSH/genética , Sítios de Ligação , AMP Cíclico/metabolismo , AMP Cíclico/química , Ligantes , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica , Receptor Tipo 1 de Melanocortina/genética , Receptor Tipo 1 de Melanocortina/química , Receptor Tipo 1 de Melanocortina/metabolismo

RESUMO

Leukodystrophies represent a large and complex group of inherited disorders affecting the white matter of the central nervous system. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare leukodystrophy which still needs the proper identification of diagnostic, prognostic, and monitoring biomarkers. The aim of this study was to determine the diagnostic and prognostic value of chitinases and neurofilament light chain as biomarkers for ALSP. A cross-sectional study was performed to analyze cerebrospinal fluid levels of chitinases (chitotriosidase and chitinase 3-like 2) and neurofilament light chain in five different groups: (i) normal health individuals; (ii) patients with definitive diagnosis of ALSP and genetic confirmation; (iii) asymptomatic patients with CSF1R variants; (iv) patients with other adult-onset leukodystrophies; and (v) patients with amyotrophic lateral sclerosis (external control group). Chitinase levels showed a statistical correlation with clinical assessment parameters in ALSP patients. Chitinase levels were also distinct between ALSP and the other leukodystrophies. Significant differences were noted in the levels of chitinases and neurofilament light chain comparing symptomatic (ALSP) and asymptomatic individuals with CSF1R variants. This study is the first to establish chitinases as a potential biomarker for ALSP and confirms neurofilament light chain as a good biomarker for primary microgliopathies.

RESUMO

BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. RESULTS: miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. CONCLUSIONS: These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.

Assuntos

Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , MicroRNAs , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Glioma/genética , Glioma/metabolismo , Animais , Camundongos , Xenoenxertos , Transplante de Neoplasias , Neoplasias Encefálicas/genética , MicroRNAs/metabolismo

RESUMO

To use scanning electron microscopy and energy dispersive X-ray spectroscopy to evaluate the metallurgical-chemical changes of WaveOne Gold (WOG) and R-Motion (RM), after multiple uses. The instruments were divided into groups (n = 8): WOG and RM-control groups, new instruments; WOG1 and RM1; WOG2 and RM2; WOG3 and RM3 after instrumentation of 1, 2 or 3 molars, respectively. Burrs occurred mainly in the control group and after the first use. The RM files were found to have a higher nickel content, which increased during reuse, and a decrease in oxygen content with increasing reuse, in addition to calcium impregnation, which occurred in greater amounts in the corrosion areas in the WOG files. The presence of topographic and chemical changes was demonstrated, indicating that caution should be taken when reusing endodontic instruments to avoid fractures.

RESUMO

This prospective study examined the primary, secondary and complex conceptual models of religious/spiritual struggles with 18 indicators of whole person functioning across five domains: psychological well-being, psychological distress, social well-being, physical well-being and character. We used three waves of longitudinal data (Wave 1: August/September 2021, Wave 2: October/November 2021, Wave 3: February 2022) from Colombian university students (N = 2878, Mage = 20.88 ± 4.05 years). Adjusting for covariates assessed in Wave 1, our primary analysis applied the analytic templates for outcome-wide and lagged exposure-wide designs to estimate two sets of lagged linear regression models. Religious/spiritual struggles in Wave 2 were associated with a small-to-medium-sized decline in subsequent functioning on 17/18 indicators in Wave 3, and worse functioning on 16/18 indicators in Wave 2 was associated with very small-to-medium-sized increases in subsequent religious/spiritual struggles in Wave 3. The results provided evidence in favour of the complex conceptual model for 16/18 indicators of whole person functioning. Our findings extend existing evidence on the reciprocal association between religious/spiritual struggles and individual functioning to a wide range of indicators, reinforcing the need for practitioners to consider the dynamic interplay between religious/spiritual struggles and individual functioning as they work with younger populations.