Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 881
Filtrar
1.
J Sleep Res ; : e14330, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238202

RESUMO

People who use substances commonly experience sleep disruptions, affecting the regulation of physical and mental health, and presenting a significant barrier to treatment success. Sleep impairments are noted in all phases of substance use; however, differences between subjective versus objective methods used to measure sleep quality have been reported. While polysomnography is the gold-standard for sleep measurement, recent advances in actigraphy may help address the discordance between subjective and objective sleep reports. This systematic review examined emerging evidence (2016-present) for sleep impairment in people who use substances, with the twofold goal of: (1) identifying whether sleep outcomes vary across substance type (alcohol, nicotine, cannabis, cocaine, methamphetamine and opioids); and (2) contrasting results from subjective and objective measures. While some differences between subjective and objective sleep were noted, there was overwhelming evidence of clinically relevant sleep impairment in people who use alcohol, nicotine, cocaine, methamphetamine and opioids, with less consistent results for cannabis. Gaps in the literature are identified and future recommendations are presented, including utilization of common methodological frameworks, identification of mechanisms, and closer examination of sleep across stages of substance use and the interconnection between sleep and return to use.

2.
Bioorg Med Chem Lett ; 113: 129948, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39236793

RESUMO

KAT6, a histone acetyltransferase from the MYST family, has emerged as an attractive oncology target due to its role in regulating genes that control cell cycle progression and cellular senescence. Amplification of the KAT6A gene has been seen among patients with worse clinical outcome in ER+ breast cancers. Although multiple inhibitors have been reported, no KAT6 inhibitors have been approved to date. Here, we report the fragment-based discovery of a series of N-(1-phenyl-1H-1,2,3-triazol-4-yl)benzenesulfonamide KAT6 inhibitors and early hit-to-lead efforts to improve the KAT6 potency.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39207396

RESUMO

Cocaine use disorder (CUD) is a major public health issue, and greater cocaine use severity has been associated with worse treatment retention and outcomes. Therefore, greater understanding of processes that influence cocaine use is needed. Both anhedonia (i.e., undervaluation of nondrug rewards) and cocaine demand (i.e., cocaine valuation) are related to cocaine use severity and thematically related to each other at face value, but no studies have directly compared these outcomes to our knowledge. The present study represents a secondary analysis from a two-phase sequential, multiple assignment, randomized trial aimed at developing adaptive interventions for CUD. We examined the relationship between anhedonia and cocaine demand and how these measures were related to cocaine use severity. Participants (N = 116) were treatment-seeking adults with CUD. All measures were taken at baseline before treatment initiation. Analyses revealed (a) moderate and very strong evidence of relationships between cocaine demand factors (i.e., persistence, amplitude) and anhedonia (PP values ≥ 77.8%); (b) positive association between cocaine demand (both persistence and amplitude) and measures of cocaine use severity, with the exception of one relationship, which was in the opposite direction; and (c) demand amplitude continued to be positively related to cocaine use severity, even when considering anhedonia. Overall, findings from this study indicate cocaine demand relates to cocaine use severity more strongly than anhedonia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

4.
BMJ Open ; 14(8): e089118, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39122403

RESUMO

INTRODUCTION: Children who are deaf or hard-of-hearing (DHH) are at risk for speech and language delay. Language outcomes are worse in DHH children from lower socioeconomic backgrounds, due in part to disparities in access to specialised speech-language therapy. Teletherapy may help improve access to this specialised care and close this language gap. Inclusion of diverse DHH children in prospective randomised clinical trials has been challenging but is necessary to address disparities and pursue hearing health equity. Stakeholder input regarding decisions on study design elements, including comparator groups, masking, assessments and compensation, is necessary to design inclusive studies. We have designed an inclusive, equitable comparativeness effectiveness trial to address disparities in paediatric hearing health. The specific aims of the study are to determine the effect of access to and utilisation of speech-language teletherapy in addressing language disparities in low-income children who are DHH. METHODS AND ANALYSIS: After stakeholder input and pilot data collection, we designed a randomised clinical trial and concurrent longitudinal cohort trial to be conducted at four tertiary children's hospitals in the USA. Participants will include 210 DHH children aged 0-27 months. 140 of these children will be from lower income households, who will be randomised 1:1 to receive usual care versus usual care plus access to supplemental speech-language teletherapy. 70 children from higher income households will be simultaneously recruited as a comparison cohort. Primary outcome measure will be the Preschool Language Scales Auditory Comprehension subscale standard score, with additional speech, language, hearing and quality of life validated measures as secondary outcomes. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards of the participating sites: the University of California, San Francisco (19-28356), Rady Children's Hospital (804651) and Seattle Children's Hospital (STUDY00003750). Parents of enrolled children will provide written informed consent for their child's participation. Professional and parent stakeholder groups that have been involved throughout the study design will facilitate dissemination and implementation of study findings via publication and through national and regional organisations. TRIAL REGISTRATION NUMBER: NCT04928209.


Assuntos
Surdez , Humanos , Pré-Escolar , Lactente , Pessoas com Deficiência Auditiva , Recém-Nascido , Transtornos do Desenvolvimento da Linguagem/terapia , Disparidades em Assistência à Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Fonoterapia/métodos , Estudos Multicêntricos como Assunto , Terapia da Linguagem/métodos , Masculino , Estudos Prospectivos , Projetos de Pesquisa , Acessibilidade aos Serviços de Saúde , Qualidade de Vida
5.
Cureus ; 16(7): e63949, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39104972

RESUMO

Introduction Myocardial infarction (MI) in young South Indians presents a shifting epidemiological landscape, challenging traditional perceptions of cardiovascular diseases. This study investigates the clinical and angiographic profiles of MI in this subgroup of the population in detail, emphasizing the interaction between lifestyle, environmental, and genetic factors that contribute to the incidence of MI in younger people. Methodology Utilizing a descriptive observational design, the study analyzed data from 70 young adults (aged 18-45 years) admitted to Frontier Lifeline Hospital, Chennai, with acute MI over six months. Patient demographics, clinical characteristics, and angiographic findings were collected and analyzed using standardized protocols. Statistical analysis employed chi-square tests and subgroup analyses to assess associations and differences between diabetic and non-diabetic patients. Results The study revealed a predominance of males (84.29%) among MI cases, with ST-elevation myocardial infarction (STEMI) being the most common presentation (52.86%). Anterior wall involvement was prevalent (50%), and left ventricular systolic dysfunction (LVSD) was observed in the majority (67%) of patients. Chest pain (87%) was the predominant symptom, and diabetes (47%) and hypertension (47%) were the risk variables that were most common. Angiographically, the left anterior descending artery (LAD) was often affected (51%), with single-vessel disease predominating (41.43%). Conclusion The findings underscore the significance of early detection and intervention strategies for MI in young South Indians. Gender-specific risk assessment, prompt diagnosis, and tailored treatment approaches are imperative. The high prevalence of LVSD highlights the burden of cardiac morbidity, particularly in diabetic individuals. Lifestyle modifications and weight management interventions are crucial for MI prevention. This study provides insights into the frequency and features of MI in young South Indians, emphasizing the importance of collaborative efforts for early identification and control of modifiable risk factors to mitigate the burden of coronary artery disease (CAD) in this population subset.

6.
Animals (Basel) ; 14(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39123736

RESUMO

The hypothesis that pigs fed a low crude protein (CP) diet with 6% spray-dried plasma (SDP) in phase 1 will have improved growth and intestinal health if the phase-2 diet contains 2.5% SDP was tested. Three hundred weaned pigs were used. Growth performance, feces, blood, and intestinal tissue were evaluated. Pigs fed 6% SDP in phase 1 had improved average daily gain (ADG) and final body weight (BW), but had reduced villus-height-to-crypt-depth ratio in phase 2 if 2.5% SDP was included in the normal-CP diet (p < 0.05), but not in the low-CP diet. Diarrhea incidence was less (p < 0.05) with 2.5% SDP in the phase 2 diet and for the low-CP diet. Ileal mucosa interleukin-1α (IL-1α) and IL-1ß decreased (p < 0.05) for pigs fed the phase-1 diet with 6% SDP compared with pigs fed the diet without SDP. Addition of 2.5% SDP in phase 2 reduced (p < 0.05) IL-1ß compared with the diet without SDP. Although the combination of SDP and low CP did not affect intestinal health in phase 2, diarrhea incidence and pro-inflammatory cytokines were reduced in pigs fed SDP in phase 1 or phase 2 or if a low-CP diet was fed.

7.
Dis Model Mech ; 17(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38967226

RESUMO

Robinow syndrome is a rare disease caused by variants of seven WNT pathway genes. Craniofacial features include widening of the nasal bridge and jaw hypoplasia. We used the chicken embryo to test whether two missense human FZD2 variants (1301G>T, p.Gly434Val; 425C>T, p.Pro142Lys) were sufficient to change frontonasal mass development. In vivo, the overexpression of retroviruses with wild-type or variant human FZD2 inhibited upper beak ossification. In primary cultures, wild-type and variant human FZD2 significantly inhibited chondrogenesis, with the 425C>T variant significantly decreasing activity of a SOX9 luciferase reporter compared to that for the wild type or 1301G>T. Both variants also increased nuclear shuttling of ß-catenin (CTNNB1) and increased the expression of TWIST1, which are inhibitory to chondrogenesis. In canonical WNT luciferase assays using frontonasal mass cells, the variants had dominant-negative effects on wild-type FZD2. In non-canonical assays, the 425C>T variant failed to activate the reporter above control levels and was unresponsive to exogenous WNT5A. This is the first single amino acid change to selectively alter ligand binding in a FZD receptor. Therefore, FZD2 missense variants are pathogenic and could lead to the altered craniofacial morphogenesis seen in Robinow syndrome.


Assuntos
Condrogênese , Anormalidades Craniofaciais , Receptores Frizzled , Animais , Embrião de Galinha , Humanos , Bico , beta Catenina/metabolismo , Núcleo Celular/metabolismo , Condrogênese/genética , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Nanismo , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Deformidades Congênitas dos Membros , Crânio/patologia , Crânio/embriologia , Proteína 1 Relacionada a Twist/metabolismo , Proteína 1 Relacionada a Twist/genética , Anormalidades Urogenitais , Via de Sinalização Wnt
8.
Front Mol Biosci ; 11: 1366278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011141

RESUMO

The examination of drug accumulation within complex biological systems offers valuable insights into the molecular aspects of drug metabolism and toxicity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is an innovative methodology that enables the spatial visualization and quantification of biomolecules as well as drug and its metabolites in complex biological system. Hence, this method provides valuable insights into the metabolic profile and any molecular changes that may occur as a result of drug treatment. The renal system is particularly vulnerable to adverse effects of drug-induced harm and toxicity. In this study, MALDI MSI was utilized to examine the spatial distribution of drug and renal metabolites within kidney tissues subsequent to a single oral dosage of the anticancer compound rotenone. The integration of ion mobility spectrometry with MALDI MSI enhanced the data acquisition and analysis, resulting to improved mass resolution. Subsequently, the MS/MS fragment ions of rotenone reference drug were detected and characterized using MALDI HDMS/MS imaging. Notably, drug accumulation was observed in the cortical region of the representative kidney tissue sections treated with rotenone. The histological examination of treated kidney tissues did not reveal any observable changes. Differential ion intensity of renal endogenous metabolites was observed between untreated and rotenone-treated tissues. In the context of treated kidney tissues, the ion intensity level of sphingomyelin (D18:1/16:0), a sphingolipid indicator of glomerular cell injury and renal damage, was found to be elevated significantly compared to untreated kidney tissues. Conversely, the ion intensities of choline, glycero-3-phosphocholine (GPC), inosine, and a lysophosphatidylcholine LysoPC(18:0) exhibited a significant decrease. The results of this study demonstrate the potential of MALDI MSI as a novel technique for investigating the in situ spatial distribution of drugs and renal endogenous molecules while preserving the anatomical integrity of the kidney tissue. This technique can be used to study drug-induced metabolism and toxicity in a dynamic manner.

9.
medRxiv ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38947003

RESUMO

There is a growing focus on better understanding the complexity of dietary patterns and how they relate to health and other factors. Approaches that have not traditionally been applied to characterize dietary patterns, such as machine learning algorithms and latent class analysis methods, may offer opportunities to measure and characterize dietary patterns in greater depth than previously considered. However, there has not been a formal examination of how this wide range of approaches has been applied to characterize dietary patterns. This scoping review synthesized literature from 2005-2022 applying methods not traditionally used to characterize dietary patterns, referred to as novel methods. MEDLINE, CINAHL, and Scopus were searched using keywords including machine learning, latent class analysis, and least absolute shrinkage and selection operator (LASSO). Of 5274 records identified, 24 met the inclusion criteria. Twelve of 24 articles were published since 2020. Studies were conducted across 17 countries. Nine studies used approaches that have applications in machine learning to identify dietary patterns. Fourteen studies assessed associations between dietary patterns that were characterized using novel methods and health outcomes, including cancer, cardiovascular disease, and asthma. There was wide variation in the methods applied to characterize dietary patterns and in how these methods were described. The extension of reporting guidelines and quality appraisal tools relevant to nutrition research to consider specific features of novel methods may facilitate complete and consistent reporting and enable evidence synthesis to inform policies and programs aimed at supporting healthy dietary patterns.

10.
Viruses ; 16(7)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39066262

RESUMO

Few studies have addressed viral diversity in lemurs despite their unique evolutionary history on the island of Madagascar and high risk of extinction. Further, while a large number of studies on animal viromes focus on fecal samples, understanding viral diversity across multiple sample types and seasons can reveal complex viral community structures within and across species. Groups of captive lemurs at the Duke Lemur Center (Durham, NC, USA), a conservation and research center, provide an opportunity to build foundational knowledge on lemur-associated viromes. We sampled individuals from seven lemur species, i.e., collared lemur (Eulemur collaris), crowned lemur (Eulemur coronatus), blue-eyed black lemur (Eulemur flavifrons), ring-tailed lemur (Lemur catta), Coquerel's sifaka (Propithecus coquereli), black-and-white ruffed lemur (Varecia variegata variegata), and red ruffed lemur (Varecia rubra), across two lemur families (Lemuridae, Indriidae). Fecal, blood, and saliva samples were collected from Coquerel's sifaka and black-and-white ruffed lemur individuals across two sampling seasons to diversify virome biogeography and temporal sampling. Using viral metagenomic workflows, the complete genomes of anelloviruses (n = 4), cressdnaviruses (n = 47), caudoviruses (n = 15), inoviruses (n = 34), and microviruses (n = 537) were determined from lemur blood, feces, and saliva. Many virus genomes, especially bacteriophages, identified in this study were present across multiple lemur species. Overall, the work presented here uses a viral metagenomics approach to investigate viral communities inhabiting the blood, oral cavity, and feces of healthy captive lemurs.


Assuntos
Fezes , Genoma Viral , Lemur , Animais , Fezes/virologia , Lemur/virologia , Filogenia , Viroma , DNA Viral/genética , Boca/virologia , Madagáscar , Sangue/virologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-38954848

RESUMO

Food literacy is a growing area of interest given its potential to support healthy and sustainable diets. Most existing food literacy measures focus on nutrition and food skills but fail to address food systems and socio-environmental aspects of food literacy. Further, measures developed and tested in the Canadian context are lacking. The objective of this project was to develop and test the validity and reliability of a brief self-administered measure, in French and English, designed to assess multiple dimensions of food literacy among adults living in Canada. The 23-item Canadian Food Literacy Measure was developed through an iterative process that included assessment of face and content validity through expert review (n=20) and cognitive interviews (n=20), and construct validity and reliability, i.e., internal consistency through an online survey (n=154). The results indicate that the measure is well understood by both English- and French-speaking adults. The measure's construct validity is demonstrated by the observed differences in total scores in hypothesized directions by gender (p=0.003), age (p=0.007), education level (p=0.002), health literacy (p<0.001) and smoking status (p=0.001) and the significant positive correlation (r = 0.29; p=0.002) between total scores and fruit and vegetable intake. The measure also has high internal consistency with a Cronbach's coefficient alpha of 0.80. This measure can be used in surveillance studies to provide insight into the food literacy of adults living in Canada and in epidemiologic research that aims to explore how food literacy is associated with a variety of health outcomes.

12.
Arch Sex Behav ; 53(9): 3687-3698, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39020242

RESUMO

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting injectable PrEP among sexually active adult PWUD. The data were collected from adult participants (n = 270) residing in Harris County, TX, who self-reported problematic substance use and who reported oral, anal, or vaginal sex in the six months prior to completing the survey. The survey was distributed and completed online via Qualtrics Panels in March of 2022 and included measures of PrEP and HIV knowledge, PrEP stigma, sexual health self-efficacy, experiences of discrimination, health literacy, and medical mistrust. The majority of participants reported circumstances or behaviors that increased their susceptibility to HIV. Findings indicated that PrEP user stereotypes and PrEP anticipated disapproval by others were associated with interest in using daily oral PrEP and willingness to use long acting injectable PrEP. These results provide insight into reasons for low PrEP uptake among PWUD who live in a high HIV prevalence jurisdiction. Implications for HIV prevention intervention are discussed.


Assuntos
Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , Profilaxia Pré-Exposição , Humanos , Masculino , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Profilaxia Pré-Exposição/estatística & dados numéricos , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Estigma Social , Prevalência , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Adulto Jovem , Fármacos Anti-HIV/uso terapêutico , Inquéritos e Questionários
13.
Dev Biol ; 516: 71-81, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39059678

RESUMO

The dentition is critical to animal survival and teeth are present in modern vertebrates including teleost fish, sharks, amphibians, mammals and reptiles. The developmental processes that give rise to teeth are not just preserved through evolution but also share high level of similarity with the embryogenesis of other ectodermal organs. In this review we go beyond the embryonic phase of tooth development to life-long tooth replacement. We will address the origins of successional teeth, the location of putative tissue-resident stem cells, how de novo tooth formation continues throughout life and how teeth are shed in a spatially and temporally controlled manner. We review the evidence that the dental epithelium, which is the earliest recognizable dental structure in the reptilian dentition, serves as a putative niche for tissue-resident epithelial stem cells and recent molecular findings from transcriptomics carried out in reptilian dentitions. We discuss how odontoclasts resorb the primary tooth allowing eruption of the successional tooth. The reptiles, particularly lizards, are emerging as some of the most accessible animals to study tooth replacement which has relevance to evolution of the dentition and human dental disorders.


Assuntos
Dentição , Odontogênese , Répteis , Dente , Animais , Répteis/embriologia , Répteis/fisiologia , Dente/embriologia , Odontogênese/fisiologia , Evolução Biológica , Humanos , Células-Tronco/fisiologia
14.
ACS Chem Neurosci ; 15(15): 2897-2915, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39012782

RESUMO

Rexinoids are compounds that bind to the rexinoid X receptor (RXR) to modulate gene expression and have been proposed as a new class of therapeutics to treat Alzheimer's disease. Different rexinoids will initiate downstream effects that can be quite marked even though such compounds can be structurally similar and have comparable RXR binding affinities. RXR can both homo- and heterodimerize, and these protein-protein interactions and subsequent transactivating potential lead to differential gene expression, depending on the RXR dimeric partner, additional cofactors recruited, and downstream transcription factors that are up- or downregulated. Expression analysis was performed in the U87 human glioblastoma cell line treated with a panel of rexinoids, and our analysis demonstrated that rexinoids with similar RXR EC50 values can have pronounced differences in differential gene expression. Rexinoid binding likely leads to distinctive RXR conformations that cause major downstream gene expression alterations via modulation of RXR interacting proteins. Yeast two-hybrid analysis of RXR bait with two RXR interacting partners demonstrates that rexinoids drive differential binding of RXR to distinctive protein partners. Physiochemical analysis of the rexinoids reveals that the molecules cluster similarly to their gene expression patterns. Thus, rexinoids with similar RXR binding affinities drive differential gene expression by stimulating additional binding patterns in RXR and its homo- and heteropartners, driven by the physicochemical characteristics of these molecules.


Assuntos
Glioblastoma , Receptores X de Retinoides , Técnicas do Sistema de Duplo-Híbrido , Humanos , Glioblastoma/metabolismo , Glioblastoma/genética , Linhagem Celular Tumoral , Receptores X de Retinoides/metabolismo , Receptores X de Retinoides/genética , Ligação Proteica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
15.
Microbiol Resour Announc ; 13(8): e0033124, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-38975773

RESUMO

House mice, Mus musculus, are highly adapted to anthropogenic spaces. Fecal samples were collected from house mice entering primate enclosure areas at the Duke Lemur Center (Durham, NC, USA). We identified 14 cressdnavirus and 59 microvirus genomes in these mouse feces.

16.
Cancer Res Commun ; 4(8): 1991-2007, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38994678

RESUMO

Aggressive breast cancers harbor TP53 missense mutations. Tumor cells with TP53 missense mutations exhibit enhanced growth and survival through transcriptional rewiring. To delineate how TP53 mutations in breast cancer contribute to tumorigenesis and progression in vivo, we created a somatic mouse model driven by mammary epithelial cell-specific expression of Trp53 mutations. Mice developed primary mammary tumors reflecting the human molecular subtypes of luminal A, luminal B, HER2-enriched, and triple-negative breast cancer with metastases. Transcriptomic analyses comparing MaPR172H/- or MaPR245W/- mammary tumors to MaP-/- tumors revealed (1) differences in cancer-associated pathways activated in both p53 mutants and (2) Nr5a2 as a novel transcriptional mediator of distinct pathways in p53 mutants. Meta-analyses of human breast tumors corroborated these results. In vitro assays demonstrate mutant p53 upregulates specific target genes that are enriched for Nr5a2 response elements in their promoters. Co-immunoprecipitation studies revealed p53R172H and p53R245W interact with Nr5a2. These findings implicate NR5A2 as a novel mediator of mutant p53 transcriptional activity in breast cancer. SIGNIFICANCE: Our findings implicate NR5A2 as a novel mediator of mutant p53 transcriptional activity in breast cancer. NR5A2 may be an important therapeutic target in hard-to-treat breast cancers such as endocrine-resistant tumors and metastatic triple-negative breast cancers harboring TP53 missense mutations.


Assuntos
Neoplasias Mamárias Experimentais , Transcriptoma , Proteína Supressora de Tumor p53 , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/metabolismo , Mutação , Mutação de Sentido Incorreto , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
17.
Poult Sci ; 103(9): 104028, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39043026

RESUMO

Enteropathies are a serious concern in racing pigeons as they significantly impair performance in races and their training, and viruses are suspected to be one of the main factors. Astroviruses are well-known to be responsible for causing enteric disease in humans and various other animals including birds, although their prevalence and pathogenicity in pigeons is poorly understood. In this study, we investigated 2 groups of young racing pigeons (sick-study group and healthy-control group) to assess the correlation between the number of astrovirus genome copies in cloacal swabs and the occurrence of enteropathy. To determine this, we developed a novel TaqMan quantitative PCR (qPCR) and digital droplet PCR (ddPCR) methods for astrovirus detection and absolute quantitative analysis. We also performed high-throughput sequencing to obtain the complete genome sequences and establish the genetic similarity of the obtained strains to known astroviruses of poultry and other avian species. Two new complete genome sequences of pigeon astroviruses in the Avastrovirus genus were identified, representing 2 new species. These were found most closely related to astroviruses identified in Columbidae species and chickens. They share an average of 75.8% genome-wide pairwise identity and 57.6% and 64.6% capsid protein sequence identity with other unclassified columbid avastrovirus sequences in GenBank. Although the difference in prevalence of astrovirus in the study and control group was found statistically insignificant, there was a significant difference between the number of genome copies in positive samples from both groups. These unambiguous results leave the role of astroviruses as enteropathogenic factors in pigeons still undetermined.


Assuntos
Infecções por Astroviridae , Avastrovirus , Doenças das Aves , Columbidae , Genoma Viral , Filogenia , Animais , Columbidae/virologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Infecções por Astroviridae/epidemiologia , Doenças das Aves/virologia , Doenças das Aves/epidemiologia , Avastrovirus/genética , Avastrovirus/isolamento & purificação , Avastrovirus/classificação
19.
Toxicol Pathol ; 52(2-3): 114-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38828567

RESUMO

Gliosis, including microgliosis and astrocytosis, can be challenging to interpret in nonclinical studies. Incidences of glial foci in brains and spinal cords of control rats and nonhuman primates (NHPs) were reviewed in the historical control databases from two contract research organizations, including one specializing in neuropathology. In the brain, minimal to mild (grades 1-2) microgliosis was the most common diagnosis, especially in NHPs, although occasional moderate or marked microgliosis (grades 3 and 4) was encountered in both species. Microgliosis was more common in the cerebral cortex, cerebellum, and medulla oblongata in both species and was frequent in the white matter (brain), thalamus, and basal nuclei of NHPs. Gliosis ("not otherwise specified") of minimal severity was diagnosed in similar brain sub-sites for both species and was more common in NHPs compared with rats. Astrocytosis was most prominent in the cerebellum (molecular layer) of NHPs but was otherwise uncommon. In the spinal cord, microgliosis was most common in the lateral white matter tracts in rats and NHPs, and in the dorsal white matter tracts in NHPs. These data indicate that low-grade spontaneous glial responses occur with some frequency in control animals of two common nonclinical species.


Assuntos
Gliose , Medula Espinal , Animais , Gliose/patologia , Ratos , Medula Espinal/patologia , Masculino , Encéfalo/patologia , Feminino , Sistema Nervoso Central/patologia , Macaca fascicularis
20.
Sci Rep ; 14(1): 14223, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902271

RESUMO

Absorption methods using polyurethane foams (PUFs) have recently gained popularity in treating oil spills. However, conventional petroleum-based PUFs lack selectivity and are commonly surface-modified using complicated processes that require toxic and harmful solvents to enhance their hydrophobicity and oil sorption capacities. In this paper, a novel naturally superoleophilic foam with inherent hydrophobic properties has been developed through the conventional one-shot foaming method with the integration of coconut oil-based polyol. This bio-based polyol was explicitly handpicked as it is chiefly saturated, highly abundant, and inexpensive. The foam is characterized by an oil sorption capacity range of 14.89-24.65 g g-1 for different types of oil, equivalent to 578-871 times its weight. Its hydrophobic behavior is expressed through a water contact angle of ~ 139°. The foam also showcased excellent chemical stability and high recyclability without a significant loss in absorption capacity after 20 cycles. The incorporation of the coconut oil-based polyol is also shown to improve the morphological, mechanical, and thermal behavior of the foam. It can be inferred from these findings that this novel material holds great potential for revolutionizing sorbents, pioneering a more sustainable and eco-friendly functional material produced via a facile method.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA