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1.
Rev Cardiovasc Med ; 25(8): 287, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39228499

RESUMO

Background: Recent studies have indicated a close relationship between the thickness of epicardial adipose tissue (EAT) and the occurrence as well as persistence of atrial fibrillation (AF). However, the pathogenesis of this association is still in the exploratory stage. The aim of this study is to explore the correlation EAT, as measured by echocardiography, and P-wave dispersion (Pd) in the context of atrial fibrillation. Additionally, the study seeks to analyze the utility of EAT at different anatomical sites in identifying individuals who are predisposed to atrial fibrillation. Methods: A total of 136 subjects were enrolled and categorized into groups based on the guidelines: paroxysmal atrial fibrillation group (PAF group), persistent atrial fibrillation group (AF group), and non-atrial fibrillation group. Comprehensive clinical data, including general information and medications that could impact the occurrence of atrial fibrillation, were gathered for all patients. Echocardiography was employed to measure the maximum EAT thickness near the apex of the heart on the anterior right ventricular wall and near the base of the right ventricle for each participant. Pd values were computed for each patient based on standard 12-lead synchronous electrocardiogram (ECG). The study involved comparing the disparity in EAT thickness between the two specified sites across the three groups. Additionally, correlation analyses were performed to assess the relationship between EAT thickness at the two sites and Pd. Regression analysis was applied to explore potential risk factors for atrial fibrillation. The diagnostic value of EAT at each site in predicting atrial fibrillation was evaluated using Receiver Operating Characteristic curve (ROC) analysis. Results: EAT thickness of the anterior wall near the apex of the heart and near the base of the right ventricle were significantly positively correlated with Pd (p < 0.05), EAT thickness near the base and left atrial diameter were independent risk factors for atrial fibrillation (OR = 13.673, 95% CI 2.819~66.316, p = 0.001; OR = 2.294, 95% CI 1.020~5.156, p = 0.045). ROC analysis showed that the area under the curve of EAT thickness near the heart base was 0.723, and the best threshold for predicting the occurrence of AF was 1.05 cm. Conclusions: The echocardiography-measured epicardial adipose tissue thickness, particularly in proximity to the heart base, exhibits a significant correlation with Pd. Notably, EAT thickness near the heart base demonstrates superior predictive capability for atrial fibrillation compared to thickness near the apex.

2.
Genes Dis ; 11(6): 101143, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39253579

RESUMO

Pancreatic cancer, a highly fatal malignancy, is predicted to rank as the second leading cause of cancer-related death in the next decade. This highlights the urgent need for new insights into personalized diagnosis and treatment. Although molecular subtypes of pancreatic cancer were well established in genomics and transcriptomics, few known molecular classifications are translated to guide clinical strategies and require a paradigm shift. Notably, chronically developing and continuously improving high-throughput technologies and systems serve as an important driving force to further portray the molecular landscape of pancreatic cancer in terms of epigenomics, proteomics, metabonomics, and metagenomics. Therefore, a more comprehensive understanding of molecular classifications at multiple levels using an integrated multi-omics approach holds great promise to exploit more potential therapeutic options. In this review, we recapitulated the molecular spectrum from different omics levels, discussed various subtypes on multi-omics means to move one step forward towards bench-to-beside translation of pancreatic cancer with clinical impact, and proposed some methodological and scientific challenges in store.

3.
Int J Biol Macromol ; 280(Pt 1): 135697, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39288861

RESUMO

The FecBB mutation, a single-point mutation (c.A746G; p.Q249R) in bone morphogenetic protein receptor type 1 B (BMPR1B), is associated with increased ovulation quotas and litter size in sheep. However, the regulatory mechanism of the FecBB mutation in increased fecundity remains to be elucidated. Therefore, creating an immortal cell model harboring the FecBB mutation would elucidate the regulatory mechanism of this mutation. Here, we report the creation of a human granulosa cell, COV434, model containing a homozygous FecBB mutation through homology-directed repair (HDR) induced by clustered, regularly-interspaced, short palindromic repeats-CRISPR-associated protein 9 along with a single-stranded oligodeoxynucleotide (ssODN) template. We found that the FecBB mutation enhanced the basal SMAD1/5 signaling activity in COV434 cells, leading to increased expression of FSHR, probably through increased formation of the SMAD1/5-SMAD4 complex to bind to the SBE element, which in turn promotes the binding of USF1 to the regulatory element E-box in the promoter of FSHR. Furthermore, the FecBB mutation substantially enhanced estradiol (E2) synthesis in granulosa cells under follicle stimulating hormone (FSH) stimulation, indicating an enhanced sensitivity to FSH, which may promote the growth of more small follicles into mature follicles, leading to increased fecundity. Our study provides novel insights into the possible regulatory mechanisms of FecBB mutations in increased fecundity.

4.
Front Psychol ; 15: 1413151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295752

RESUMO

Background: Psychological capital has become a prominent focus in positive psychology, highlighting the positive influence of higher psychological capital on individuals. Self-directed learning ability is a fundamental skill for students, vital for enhancing academic performance and professional development, and is integral to the continuous learning process of nursing students. Recognizing the relationship between psychological capital and self-directed learning ability is crucial for the progress and development of undergraduate nursing students. Objective: This study aims to investigate the correlation between psychological capital and self-directed learning ability in undergraduate nursing students, as well as to explore the factors that influence these variables. Methods: A cross-sectional survey was conducted with 667 full-time undergraduate nursing students from a nursing school in Taizhou, China. Psychological capital and self-directed learning ability were assessed using the Psychological Capital Questionnaire and Self-Directed Learning Scale, respectively. Correlation and stepwise multiple regression analyses were then carried out to evaluate the relationship between psychological capital and self-directed learning ability among the participants. Results: The study revealed that the psychological capital score averaged at 103.24 ± 15.51, while the self-directed learning scale score averaged at 230.67 ± 27.66. Variations in psychological capital scores were noted based on factors including grade level, being an only child, growth environment, monthly living expenses, parental education level, voluntary selection of nursing major, and club experience. Similarly, differences in self-directed learning scores were associated with factors such as grade level, gender, parental education level, and voluntary selection of nursing major. Moreover, a positive correlation was identified between the overall psychological capital scores and the total self-directed learning ability scores among nursing students. Notably, the multiple regression analysis highlighted that optimism and resilience played significant roles as predictors of self-directed learning ability. Conclusion: Psychological capital is positively correlated with the self-directed learning ability of nursing students, with optimism and resilience identified as crucial predictors. Nursing educators can utilize strategies rooted in positive psychology and perseverance to improve the self-directed learning ability of nursing students.

5.
Asian J Pharm Sci ; 19(4): 100892, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39246509

RESUMO

Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery. However, prodrug activation remains a rate-limiting step for exerting therapeutic actions, which requires to quickly reach the minimum valid concentrations of free drugs. Fortunately, we find that a natural compound (BL-193) selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin (PPT) at ineffective dose concentrations. Based on this, we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT. Specifically, a redox-sensitive prodrug (PSSF) of PPT is synthesized by coupling 9-fluorenyl-methanol (Fmoc-OH) with PPT linked via disulfide bond. Intriguingly, PSSF with a π-conjugated structure readily co-assembles with BL-193 into stable nanoassembly. Significantly, BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic window for PPT. Moreover, prodrug design and precise hybrid nanoassembly well manage off-target toxicity. As expected, such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses. This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.

6.
Talanta ; 281: 126877, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39277933

RESUMO

The ubiquity of plastic products has led to an increased exposure to micro and nano plastics across diverse environments, presenting a novel class of pollutants with substantial health implications. Emerging research indicates their capacity to infiltrate human organs, posing risks of tissue damage and carcinogenesis. Given the prevalent consumption of beverages as a primary vector for these plastics' entry into the human system, there is an imperative need for the advancement of precise detection methodologies in liquids. In this study, we introduce a substrate comprising a Nickel Oxide (NiO) nanosheet array decorated with Silver Nanoparticles (AgNPs) for the Surface-Enhanced Raman Spectroscopy (SERS) analysis of micro//nano plastics. This configuration, leveraging a unique nanowell architecture alongside silver plasmonic enhancement, demonstrates unparalleled sensitivity and repeatability in signal, facilitating the accurate quantification of these contaminants. Through the application of a portable Raman apparatus, this study successfully identifies prevalent micro/nano plastics including polystyrene (PS), polyethylene (PE), and polypropylene (PP), achieving detection sensitivities of 5 µg/mL, 25 µg/mL, and 25 µg/mL, respectively. Moreover, the substrate's efficacy extends to the detection of PS within commonly consumed beverages such as water, milk, and liquor with sensitivities of 25 µg/mL, 50 µg/mL, and 50 µg/mL, respectively. These findings highlight the substrate's potential as an expedient and effective sensor for the real-time monitoring of micro/nano plastic pollutants.

7.
Virulence ; 15(1): 2403566, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39285518

RESUMO

The filamentous fungus Magnaporthe oryzae is widely recognized as a notorious plant pathogen responsible for causing rice blasts. With rapid advancements in molecular biology technologies, numerous regulatory mechanisms have been thoroughly investigated. However, most recent studies have predominantly focused on infection-related pathways or host defence mechanisms, which may be insufficient for developing novel structure-based prevention strategies. A substantial body of literature has utilized cryo-electron microscopy and X-ray diffraction to explore the relationships between functional components, shedding light on the identification of potential drug targets. Owing to the complexity of protein extraction and stochastic nature of crystallization, obtaining high-quality structures remains a significant challenge for the scientific community. Emerging computational tools such as AlphaFold for structural prediction, docking for interaction analysis, and molecular dynamics simulations to replicate in vivo conditions provide novel avenues for overcoming these challenges. In this review, we aim to consolidate the structural biological advancements in M. oryzae, drawing upon mature experimental experiences from other species such as Saccharomyces cerevisiae and mammals. We aim to explore the potential of protein construction to address the invasion and proliferation of M. oryzae, with the goal of identifying new drug targets and designing small-molecule compounds to manage this disease.


Assuntos
Proteínas Fúngicas , Oryza , Doenças das Plantas , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ascomicetos/genética , Ascomicetos/patogenicidade , Ascomicetos/química , Microscopia Crioeletrônica
8.
Ann Hematol ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287653

RESUMO

Co-occurring mutations are frequently observed in acute myeloid leukemia (AML) with NPM1 mutation, and NPM1 measurable residual disease (MRD) is an effective prognostic biomarker. This retrospective study investigated the impact of gene co-mutations and NPM1 MRD on outcomes in these patients. Among 234 patients, 11.5% carried the rare type NPM1 mutation (NPM1RT). The median age was 49 years (IQR 36-58), with a median follow-up of 30.4 months (IQR 12.1-55.7). Nine genes were mutated in > 10%, with DNMT3A (53.8%) and FLT3-ITD (44.4%) being most prevalent. Univariable analysis in 137 patients showed FLT3-ITD, DNMT3A co-mutations, and MRD2 < 3 log reduction predicted poorer survival. FLT3-ITD and DNMT3A co-mutations correlated with the lowest event-free (EFS) and overall survival (OS) (3-year EFS 30.0%; 3-year OS 34.4%; both p < 0.001). FLT3-ITD alone did not worsen survival compared to patients without FLT3-ITD. Multivariable analysis identified DNMT3A co-mutation [EFS, HR = 1.9, p = 0.021; OS, HR = 2.2, p = 0.023] and MRD2 ≥ 3 log reduction (EFS, HR = 0.2; OS, HR = 0.1, both p < 0.001) as independent survival predictors. Patients with FLT3-ITD and DNMT3A co-mutations or a MRD2 < 3 log reduction were identified as high risk, but allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved survival significantly compared to chemotherapy only (3-year EFS, 57.9% vs. 30.0%, p = 0.012; 3-year OS, 72.9% vs. 34.4%, p = 0.001). In AML patients with NPM1 mutation, the detrimental impact of FLT3-ITD mutation was exacerbated by DNMT3A co-mutation. Poor-risk younger patients identified by FLT3-ITD and DNMT3A co-mutations or MRD2 < 3 log reduction benefit from allo-HSCT.

9.
Patterns (N Y) ; 5(8): 101028, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39233690

RESUMO

The digital twin (DT) is a concept widely used in industry to create digital replicas of physical objects or systems. The dynamic, bi-directional link between the physical entity and its digital counterpart enables a real-time update of the digital entity. It can predict perturbations related to the physical object's function. The obvious applications of DTs in healthcare and medicine are extremely attractive prospects that have the potential to revolutionize patient diagnosis and treatment. However, challenges including technical obstacles, biological heterogeneity, and ethical considerations make it difficult to achieve the desired goal. Advances in multi-modal deep learning methods, embodied AI agents, and the metaverse may mitigate some difficulties. Here, we discuss the basic concepts underlying DTs, the requirements for implementing DTs in medicine, and their current and potential healthcare uses. We also provide our perspective on five hallmarks for a healthcare DT system to advance research in this field.

10.
Aging Med (Milton) ; 7(4): 449-452, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39234204

RESUMO

This article presents a brief overview of the researches on ICOPE in China, the barriers influencing the implementation of ICOPE are identified, and the recommendations are proposed to advance the ICOPE practice in China.

11.
Nanomaterials (Basel) ; 14(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39120404

RESUMO

In this work, ß-NiS nanoparticles (NPs) were efficiently prepared by a straightforward hydrothermal process. The difference in morphology between these NiS NPs was produced by adding different amounts of thiourea, and the corresponding products were denoted as NiS-15 and NiS-5. Through electrochemical tests, the specific capacity (Cs) of NiS-15 was determined to be 638.34 C g-1 at 1 A g-1, compared to 558.17 C g-1 for NiS-5. To explore the practical application potential of such ß-NiS NPs in supercapacitors, a hybrid supercapacitor (HSC) device was assembled with activated carbon (AC) as an anode. Benefitting from the high capacity of the NiS cathode and the large voltage window of the device, the NiS-15//AC HSC showed a high energy density (Ed) of 43.57 W h kg-1 at 936.92 W kg-1, and the NiS-5//AC HSC provided an inferior Ed of 37.89 W h kg-1 at 954.79 W kg-1. Both HSCs showed excellent cycling performance over 6000 cycles at 10 A g-1. The experimental findings suggest that both NiS-15 and NiS-5 in this study can serve as potential cathodes for high-performance supercapacitors. This current synthesis method is simple and can be extended to the preparation of other transition metal sulfide (TMS)-based electrode materials with exceptional electrochemical properties.

12.
Geriatr Nurs ; 59: 351-356, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39127011

RESUMO

OBJECTIVE: To investigate the reliability and validity of the Chinese version of simplified nutritional appetite questionnaire (SNAQ). METHODS: The SNAQ was translated and back-translated for the study population. We surveyed 122 community-dwelling residents aged ≥60 years in Beijing's residential communities. Participants underwent face-to-face surveys including the SNAQ, mini-nutritional assessment short-form (MNA-SF), FRAIL scale, Sarcopenia-Five (SCAR-F), 15-item Geriatric Depression Scale (GDS-15), 7-item Generalized Anxiety Disorder (GAD-7), 8-item Oral Frailty Index (OFI-8), 10-item Eating Assessment Tool (EAT-10), and Mini-Mental State Examination (MMSE). Cronbach's alpha was used to measure the internal consistency and the relationship between individual items. The construct validity was verified using the KMO-Bartlett. Concurrent validity was established to validate measures of the same constructs. RESULTS: Cronbach's alpha measured the internal consistency of the questionnaire at 0.694. The split-half reliability stood at 0.725. The construct validity of the SNAQ was confirmed using a KMO-Bartlett value of 0.648 (P <0.001). The MNA-SF, as validation benchmark, has a correlation coefficient of 0.345 (P =0.001). CONCLUSION: The Chinese version of the SNAQ has good reliability and validity for older adults in community settings.

13.
Chem Sci ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39165726

RESUMO

High voltage/high temperature operation aggravates the risk of capacity attenuation and thermal runaway of layered oxide cathodes due to crystal degradation and interfacial instability. A combined strategy of bulk regulation and surface chemistry design is crucial to handle these issues. Here, we present a simultaneous Li2WO4-coated and gradient W-doped 0.98LiNi0.5Mn0.5O2·0.02Li2WO4 cathode through modulating the content of the exotic dopant and stoichiometric lithium salt during lithiation calcination. Benefiting from the slightly Li-enriched chemistry induced by the hetero-epitaxially grown Li2WO4 surface, the 0.98LiNi0.5Mn0.5O2·0.02Li2WO4 cathode demonstrates superior electrochemical performance to W-doped LiNi0.49Mn0.49W0.02O2 and WO3 coated 0.98LiNi0.5Mn0.5O2·0.02WO3 cathodes without a Li-enriched phase. Specifically, when cycled in the potential range of 2.7-4.5 V at 30 °C, the 0.98LiNi0.5Mn0.5O2·0.02Li2WO4 cathode possesses a high discharge capacity of 199.2 and 156.5 mA h g-1 at 0.1 and 5C and a capacity retention of 92.88% after 300 cycles at 1C. Even at a high cut-off voltage of 4.6 V, it still retains a capacity retention of 91.15% after 200 cycles at 1C and 30 °C. Compared with LiNi0.5Mn0.5O2, the enhanced performance of 0.98LiNi0.5Mn0.5O2·0.02Li2WO4 can be attributed to its robust bulk and stable interface, inhibited lattice oxygen release, and improved Li+ transport kinetics. Our work emphasizes the significance of the slightly Li-enriched chemistry and bulk modulation strategy in stabilizing cathodes and hence unlocks vast possibilities for future cathode design.

14.
Cureus ; 16(7): e65472, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39188441

RESUMO

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade malignant lymphoproliferative disease, representing a low percentage of newly diagnosed lymphoma cases. Although its exact cause is still unclear, it is commonly associated with infections or autoimmune diseases. The stomach is the most frequent site for MALT lymphoma, with primary hepatic MALT lymphoma being exceptionally rare. Cases of primary hepatic MALT lymphoma often coincide with viral hepatitis. In this report, we present a case of primary hepatic MALT lymphoma in a patient with no history of hepatitis but complicated by primary biliary cholangitis (PBC) and Hashimoto's thyroiditis.

15.
EClinicalMedicine ; 75: 102758, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39157811

RESUMO

Background: Ischemic stroke remains a major contributor to global mortality and morbidity. This study aims to provide an updated assessment of rates in ischemic stroke prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, specifically focusing on including prevalence investigation alongside other measures. The analysis is stratified by sex, age, and socio-demographic index (SDI) at global, regional, and national levels. Methods: Data for this study was obtained from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized rates of ischemic stroke prevalence (ASPR), incidence (ASIR), mortality (ASDR), and DALYs, estimated annual percentage changes (EAPCs) were computed over the study period. The analyses were disaggregated by gender, 20 age categories, 21 GBD regions, 204 nations/territories, and 5 SDI quintiles. R statistical package V 4.4.2 was performed for statistical analyses and plot illustrations. Findings: In 2021, the global burden of ischemic stroke remained substantial, with a total of 69,944,884.8 cases with an ASPR of 819.5 cases per 100,000 individuals (95% UI: 760.3-878.7). The ASIR was 92.4 per 100,000 people (95% UI: 79.8-105.8), while the ASDR was 44.2 per 100,000 persons (95% UI: 39.3-47.8). Additionally, the age-standardized DALY rate was 837.4 per 100,000 individuals (95% UI: 763.7-905). Regionally, areas with high-middle SDI exhibited the greatest ASPR, ASIR, ASDR, and age-standardized DALY rates, whereas high SDI regions had the lowest rates. Geospatially, Southern Sub-Saharan Africa had the highest ASPR, while Eastern Europe showed the highest ASIR. The greatest ASDR and age-standardized DALY rates were observed in Eastern Europe, Central Asia, as well as North Africa, and the Middle East. Among countries, Ghana had the highest ASPR, and North Macedonia had both the highest ASIR and ASDR. Furthermore, North Macedonia also exhibited the highest age-standardized DALY rate. Interpretation: Regions with high-middle and middle SDI continued to experience elevated ASPR, ASIR, ASDR and age-standardized DALY rates. The highest ischemic stroke burden was observed in Southern Sub-Saharan Africa, Central Asia, Eastern Europe, and the Middle East. Funding: None.

16.
Sci Total Environ ; 951: 175441, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39151616

RESUMO

Quantification mercury (Hg) pools in forests is crucial for understanding the Hg assimilation, flux and even biogeochemical cycle in forest ecosystems. While several investigations focused on Hg pools among broad-leaved, coniferous and mixed forests, there was still absent information on alpine forest. We sampled soil, moss and various tissues of the dominant Qinghai spruce (Picea crassifolia Kom.) to investigate Hg concentrations and pools, and assess Hg accumulation dynamics in the Qilian Mountains, northwestern China. The mean Hg concentration increased in the following order: trunk wood (1.8 ± 0.7 ng g-1) < branch (4.6 ± 0.8 ng g-1) < root (12.2 ± 2.9 ng g-1) < needle (19.3 ± 5.6 ng g-1) < bark (28.7 ± 9.0 ng g-1) < soil (34.1 ± 7.7 ng g-1) < litterfall (42.9 ± 2.9 ng g-1) < moss (62.5 ± 5.0 ng g-1). The soil contained Hg pools two orders of magnitude higher than vegetation and accounted for 92.2 % of the total Hg pool in the alpine forest ecosystem. Moss, despite representing only 2.7 % of total vegetation biomass, contained a disproportionate 16.7 % of the Hg pool. Although species-specific, aboveground spruce tissues exhibited higher Hg pools in alpine forests compared to other forests in China and America. The dynamic accumulation indicated that increasing atmospheric Hg concentration and enhancing tree productivity contributed to rising Hg assimilation in remote alpine forests, particularly after the 1960s. Our results highlight the relatively high levels of Hg pools in aboveground tree tissues of alpine forest and reveal a significant increase in Hg accumulation. We recommend that when assessing Hg dynamics in forest ecosystems, it is crucial to consider both the variability in atmospheric Hg exposure levels and the forest productivity.


Assuntos
Monitoramento Ambiental , Florestas , Mercúrio , Mercúrio/análise , Mercúrio/metabolismo , China , Picea/metabolismo , Árvores , Poluentes Atmosféricos/análise , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Solo/química
17.
Cell Rep Med ; 5(8): 101666, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39094578

RESUMO

Epithelial ovarian cancer (EOC) is the deadliest women's cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.3 million methylome-wide CpG sites and validated them in 1,800 independent cfDNA samples. We then utilize a pretrained AI transformer system called MethylBERT to develop an EOC diagnostic model which achieves 80% sensitivity and 95% specificity in early-stage EOC diagnosis. We next develop a simple digital droplet PCR (ddPCR) assay which archives good performance, facilitating early EOC detection.


Assuntos
Biomarcadores Tumorais , Ácidos Nucleicos Livres , Metilação de DNA , Detecção Precoce de Câncer , Neoplasias Ovarianas , Humanos , Feminino , Metilação de DNA/genética , Biomarcadores Tumorais/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/sangue , Detecção Precoce de Câncer/métodos , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Inteligência Artificial , Ilhas de CpG/genética , Pessoa de Meia-Idade , Biópsia Líquida/métodos
18.
Int J Biol Macromol ; 278(Pt 3): 134186, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39173790

RESUMO

Diabetic cognitive dysfunction (DCD) refers to cognitive impairment in individuals with diabetes, which is one of the most important comorbidities and complications. Preliminary evidence suggests that consuming sufficient dietary fiber could have benefits for both diabetes and cognitive function. However, the effect and underlying mechanism of dietary fiber on DCD remain unclear. We conducted a cross-sectional analysis using data from NHANES involving 2072 diabetics and indicated a significant positive dose-response relationship between the dietary fiber intake and cognitive performance in diabetics. Furthermore, we observed disrupted cognitive function and neuronal morphology in high-fat diet induced DCD mice, both of which were effectively restored by fucoidan supplementation through alleviating DNA epigenetic metabolic disorders. Moreover, fucoidan supplementation enhanced the levels of short-chain fatty acids (SCFAs) in the cecum of diabetic mice. These SCFAs enhanced TET2 protein stability by activating phosphorylated AMPK and improved TETs activity by reducing the ratio of (succinic acid + fumaric acid)/ α-ketoglutaric acid, subsequently enhancing TET2 function. The positive correlation between dietary fiber intake and cognitive function in diabetics was supported by human and animal studies alike. Importantly, fucoidan can prevent the occurrence of DCD by promoting TET2-mediated active DNA demethylation in the cerebral cortex of diabetic mice.


Assuntos
Disfunção Cognitiva , Desmetilação do DNA , Proteínas de Ligação a DNA , Diabetes Mellitus Experimental , Dieta Hiperlipídica , Dioxigenases , Polissacarídeos , Animais , Polissacarídeos/farmacologia , Camundongos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Dioxigenases/metabolismo , Masculino , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Humanos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Desmetilação do DNA/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Fibras na Dieta/farmacologia , Feminino
19.
RSC Adv ; 14(34): 24969, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39131500

RESUMO

[This corrects the article DOI: 10.1039/D4RA02811B.].

20.
Heliyon ; 10(15): e35551, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170241

RESUMO

Background: This research aimed to create a predictive model and an innovative risk classification system for patients with gallbladder cancer who undergo radical surgery. Methods: A cohort of 1387 patients diagnosed with gallbladder cancer was selected from the SEER database. The researchers devised a prognostic tool known as a nomogram, which was subjected to assessment and fine-tuning using various statistical measures such as the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve, decision curve analysis (DCA), and risk stratification were included in the catalog of comparisons. An external validation set comprising 93 patients from Nanchong Central Hospital was gathered for evaluation purposes. Results: The nomogram effectively incorporated seven variables and demonstrated satisfactory discriminatory ability, as evidenced by the C-index (training cohort: 0.737, validation cohort: 0.730) and time-dependent AUC (>0.7). Additionally, calibration plots confirmed the excellent alignment between the nomogram and actual observations. Our investigation unveiled NRI scores of 0.79, 0.81, and 0.81 in the training group, while the validation group exhibited NRI values of 0.82, 0.77, and 0.78. Additionally, when evaluating CSS at three-, six-, and nine-year intervals using DCA curves, our established nomograms demonstrated significantly improved performance compared to the old model (P < 0.05), showcasing enhanced discriminatory ability. The results of the external validation set proved the above results. Conclusions: The current investigation has devised a practical prognostic nomogram and risk stratification framework to aid healthcare practitioners in evaluating the postoperative outlook of individuals who have received extensive surgical treatment for gallbladder carcinoma.

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