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1.
Sci Rep ; 14(1): 15568, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971818

RESUMEN

The issue of academic procrastination is highly prevalent among university students. It not only has a deterimental effect on students' academic performance but also poses a risk to their physical and mental well-being. Anxiety, as a negative emotion, has attracted researchers' attention in relation to academic procrastination. Research indicates a correlation between state anxiety and academic procrastination, but the underlying mechanisms that drive this association remain unclear. When individuals experience ego-depletion, it can lead to psychological exhaustion, subsequently leading to procrastination. Gender role conceptions, shaped by sociocultural and psychological mechanisms, have profound implications on individuals' cognition, emotions, and behaviors. This study primarily aims to explore the relationship between state anxiety and academic procrastination among university students, with a particularly focus on the mediating role of ego-depletion and the moderating role of gender. A survey using the State Anxiety Scale, Ego-Depletion Scale, and Irrational Procrastination Scale was administered to 3370 undergraduates. State anxiety shows positive correlations with ego depletion and academic procrastination (r = 0.665, p < 0.01; r = 0.491, p < 0.01), while ego depletion is also positively linked to academic procrastination (r = 0.500, p < 0.01). State anxiety serves as a positive predictor of academic procrastination, with a confidence interval of 95% [0.626, 0.696]; additionally, ego depletion partially mediates the relationship between state anxiety and academic procrastination, with a confidence interval of 95% [0.168, 0.251]. Gender acts as a moderator in directly predicting the impact of state anxiety on academic procrastination and in the latter stage of mediating the effect of ego depletion. State anxiety can significantly and positively predict academic procrastination among university students. Ego-depletion partially mediates the relationship between state anxiety and academic procrastination. The direct predictive effect of state anxiety on academic procrastination, as well as the mediating role of ego-depletion, is moderated by gender. This provides educators and university students themselves with reference for addressing the issue of academic procrastination.


Asunto(s)
Ansiedad , Ego , Procrastinación , Estudiantes , Humanos , Femenino , Masculino , Estudiantes/psicología , Ansiedad/psicología , Universidades , Adulto Joven , Adulto , Encuestas y Cuestionarios , Adolescente
2.
Free Radic Res ; 58(5): 311-322, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38946540

RESUMEN

It is well known that the adaptations of muscular antioxidant system to aerobic exercise depend on the frequency, intensity, duration, type of the exercise. Nonetheless, the timing of aerobic exercise, related to circadian rhythms or biological clock, may also affect the antioxidant defense system, but its impact remains uncertain. Bain and muscle ARNT-like 1 (BMAL1) is the core orchestrator of molecular clock, which can maintain cellular redox homeostasis by directly controlling the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2). So, our research objective was to evaluate the impacts of aerobic exercise training at various time points of the day on BMAL1 and NRF2-mediated antioxidant system in skeletal muscle. C57BL/6J mice were assigned to the control group, the group exercising at Zeitgeber Time 12 (ZT12), and the group exercising at ZT24. Control mice were not intervened, while ZT12 and ZT24 mice were trained for four weeks at the early and late time point of their active phase, respectively. We observed that the skeletal muscle of ZT12 mice exhibited higher total antioxidant capacity and lower reactive oxygen species compared to ZT24 mice. Furthermore, ZT12 mice improved the colocalization of BMAL1 with nucleus, the protein expression of BMAL1, NRF2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, glutamate-cysteine ligase modifier subunit and glutathione reductase in comparison to those of ZT24 mice. In conclusion, the 4-week aerobic training performed at ZT12 is more effective for enhancing NRF2-mediated antioxidant responses of skeletal muscle, which may be attributed to the specific activation of BMAL1.


Asunto(s)
Factores de Transcripción ARNTL , Antioxidantes , Ratones Endogámicos C57BL , Músculo Esquelético , Condicionamiento Físico Animal , Animales , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Músculo Esquelético/metabolismo , Ratones , Antioxidantes/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Especies Reactivas de Oxígeno/metabolismo
3.
Artículo en Inglés | MEDLINE | ID: mdl-38969601

RESUMEN

The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and for assessing the efficacy of immunotherapy in unresectable HCC. This review examines how gut microbiota dysbiosis, with varied functional profiles, contributes to HCCs of different etiologies. We discuss therapeutic strategies to modulate the gut microbiome including diets, antibiotics, probiotics, fecal microbiota transplantation, and nano-delivery systems, and underscore their potential as an adjunctive treatment modality for HCC.

4.
Front Public Health ; 12: 1382217, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846615

RESUMEN

Introduction: The mental health of unverisity students is influenced by diverse factorsis multifaceted, requiring further investigation to evaluate its current status and determinants. The present study aims to address this gap by targeting Chinese university students and employing the Psychological Resilience Dynamic System model. Through a questionnaire survey, this research endeavors to explore the mental health status and influencing factors. Ultimately, the findings of this study aim to provide a theoretical basis and tailored practical guidance for the development of mental health intervention strategies for university students. Methods: Based on the Psychological Resilience Dynamic System Model, the mental health status of 3,390 Chinese university students from 15 universities was empirically investigated with the principle of stratified sampling and the geographical distribution and disciplinary diversity of universities. The questionnaires used included Kessler psychological distress scale, psychological resilience scale,positive psychological capital scale, family hardiness index and social support scale. Among the participants, 47.85% were male and 52.15% were female. Regarding the origin, 42.89% of the students were from rural areas, while 57.11% were from urban areas. Results: Key findings unveil: (1) A prevalence of 24.54% in students has suboptimal mental health, with 18.70 and 5.84%, respectively, representing those with poor and relatively poor mental health conditions; (2) A noteworthy negative correlation (p < 0.01) between mental health scores of university students and nine pivotal factors, including psychological resilience, self-efficacy, optimism, hope, resilience, family resilience, objective support, subjective support, and support utilization; (3) Eight factors, including grade, family economic status, psychological resilience, self-efficacy, optimism, family resilience, objective support, and support utilization, emerge as significant predictors of university students' mental health (p <0.001), collectively elucidating 57.9% of the total variance in mental health. Discussion: The aforementioned research results, indicate that the influencing factors on the mental health of university students encompass four main aspects. These include individual demographic factors such as grade and family economic status, positive psychological capital factors such as psychological resilience, self-efficacy, optimism, hope, and resilience, family resilience factors including responsibility, control, and challenge, and societal support factors including objective support, subjective support, and support utilization. Based on this, this paper focuses on four recommendations: giving full play to the leading role of universities in mental health education and stress intervention, strengthening the educational power of positive family ideals and role modeling, building a support system for positive social atmosphere and psychological counseling, and improving the self-shaping ability of university students' psychological resilience and positive psychological capital. These recommendations aspire to better promote the mental health of university students and provide a strength reserve for psychological problem intervention.


Asunto(s)
Salud Mental , Resiliencia Psicológica , Estudiantes , Humanos , Femenino , Estudiantes/psicología , Masculino , Universidades , China , Encuestas y Cuestionarios , Adulto Joven , Apoyo Social , Adulto , Modelos Psicológicos , Adolescente
5.
Helicobacter ; 29(3): e13100, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873839

RESUMEN

BACKGROUND: The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms. METHODS: scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (n = 6) and liver transplant donor gallbladder mucosal samples (n = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation. RESULTS: Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified Helicobacter pylori as a key bacterium associated with gallbladder chronic inflammation and stone formation. CONCLUSIONS: Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified H. pylori as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.


Asunto(s)
Antígenos Bacterianos , Proteínas Bacterianas , Células Epiteliales , Vesícula Biliar , Cálculos Biliares , Helicobacter pylori , Animales , Cálculos Biliares/microbiología , Cálculos Biliares/patología , Células Epiteliales/microbiología , Ratones , Humanos , Vesícula Biliar/microbiología , Vesícula Biliar/patología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Antígenos Bacterianos/genética , Antígenos Bacterianos/metabolismo , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Helicobacter pylori/fisiología , ARN Ribosómico 16S/genética , Modelos Animales de Enfermedad , Permeabilidad , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Femenino , Masculino , Ratones Endogámicos C57BL
6.
J Opt Soc Am A Opt Image Sci Vis ; 41(5): 844-851, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856571

RESUMEN

Fluorescence molecular tomography (FMT) is a non-invasive, radiation-free, and highly sensitive optical molecular imaging technique for early tumor detection. However, inadequate measurement information along with significant scattering of near-infrared light within the tissue leads to high ill-posedness in the inverse problem of FMT. To improve the quality and efficiency of FMT reconstruction, we build a reconstruction model based on log-sum regularization and introduce an online maximum a posteriori estimation (OPE) algorithm to solve the non-convex optimization problem. The OPE algorithm approximates a stationary point by evaluating the gradient of the objective function at each iteration, and its notable strength lies in the remarkable speed of convergence. The results of simulations and experiments demonstrate that the OPE algorithm ensures good reconstruction quality and exhibits outstanding performance in terms of reconstruction efficiency.

7.
J Ethnopharmacol ; 333: 118488, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38925319

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated. AIM OF THE STUDY: This study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism. METHODS: The buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting. RESULTS: The buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion.


Asunto(s)
Modelos Animales de Enfermedad , Flavonoides , Hiperuricemia , Transportadores de Anión Orgánico , Ácido Úrico , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/inducido químicamente , Ácido Úrico/sangre , Masculino , Flavonoides/farmacología , Flavonoides/análisis , Ratones , Transportadores de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico/genética , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Flores/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Transportadores de Anión Orgánico Sodio-Independiente/genética , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Alopurinol/farmacología , Ratones Endogámicos ICR
8.
Food Chem ; 457: 140124, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38908239

RESUMEN

Phenolics in bound form extensively exist in cereal dietary fiber, especially insoluble fiber, while their release profile in gastrointestinal tract and contribution to the potential positive effects of dietary fiber in modulating gut microbiota still needs to be disclosed. In this work, the composition of bound phenolics (BPs) in triticale insoluble dietary fiber (TIDF) was studied, and in vitro gastrointestinal digestion as well as colonic fermentation were performed to investigate BPs liberation and their role in regulating intestinal flora of TIDF. It turned out that most BPs were unaccessible in digestion but partly released continuously during fermentation. 16 s rRNA sequencing demonstrated that TIDF possessed prebiotic effects by promoting anti-inflammatory while inhibiting proinflammatory bacteria alongside boosting SCFAs production and antioxidative BPs contributed a lot to these effects. Results indicated that TIDF held capabilities to regulate intestinal flora and BPs were important functional components to the health benefits of cereal dietary fiber.

9.
Med Oncol ; 41(6): 153, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743323

RESUMEN

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.


Asunto(s)
Antraquinonas , Ciclo Celular , Proliferación Celular , ADN (Citosina-5-)-Metiltransferasas , ADN Metiltransferasa 3B , Neoplasias Esofágicas , Humanos , Antraquinonas/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Biología Computacional , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Rheum/química
10.
J Surg Res ; 299: 343-352, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38795557

RESUMEN

INTRODUCTION: Ovarian metastases from gastrointestinal cancers such as colorectal cancer, also known as Krukenberg tumors (KTs), present unique challenges in management due to diagnostic uncertainty, decreased responsiveness to systemic therapies compared to other sites of metastasis, and associated debilitating symptomatology. Thus, we sought to characterize our institutional outcomes in metastatic colorectal cancer (mCRC) patients with KTs. METHODS: A retrospective single-institution study was performed identifying adult, female patients from 2012 to 2021 with a diagnosis of mCRC. Patient demographics and clinicopathologic characteristics were collected and analyzed. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival analyses were performed. RESULTS: Of 235 mCRC patients, 45 (19.1%) had KTs, 41 (91.1%) of whom had KTs in conjunction with other metastatic sites. Other initial sites of metastasis included the liver (n = 93, 39.6%), lung (n = 28, 11.9%), and peritoneum (n = 18, 7.7%). In the KT cohort, the median age was 48 y, 53.3% were non-Hispanic White, 100% had microsatellite stable tumors, 33.3% had Kristen Rat Sarcoma Virus (KRAS) mutations, and 6.7% had V-raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations. Fifty five point six percent of KT patients underwent cytoreductive surgery (CRS), 24.4% underwent palliative debulking, and 20% underwent no surgical intervention. Reasons for not undergoing CRS were disease-related (n = 14, 70%), due to poor performance status (n = 1, 5%), or both (n = 5, 25%). Five-year overall survival was 48.2% in KT patients who underwent CRS. Poor tumor grade was an independent predictor of mortality (hazard ratio 10.69, 95% confidence interval 1.20-95.47, P = 0.03). CONCLUSIONS: Almost 90% of our patient cohort with KTs from mCRC experience additional sites of metastasis. Around half of KT patients who underwent CRS were alive at 5 y.


Asunto(s)
Neoplasias Colorrectales , Tumor de Krukenberg , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Tumor de Krukenberg/terapia , Tumor de Krukenberg/mortalidad , Tumor de Krukenberg/diagnóstico , Tumor de Krukenberg/secundario , Adulto , Anciano , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/diagnóstico , Estimación de Kaplan-Meier , Resultado del Tratamiento , Procedimientos Quirúrgicos de Citorreducción , Proteínas Proto-Oncogénicas B-raf/genética
11.
Am J Transl Res ; 16(4): 1322-1336, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715831

RESUMEN

OBJECTIVES: Triple-negative breast cancer (TNBC) is characterized by significant heterogeneity, presenting a formidable challenge with a poor prognosis and a deficiency of efficacious treatment options. METHODS: In this comprehensive study, we investigated the multifaceted role of Microfibril-associated glycoprotein 2 (MFAP2) in TNBC using a combination of bioinformatics analysis involving Gene Expression Omnibus (GEO), OncoDB, UALCAN, Human Protein Atlas (HPA), TIMER, STRING, DAVID, and GSCA databases and in vitro experiments, such as cell culture, MFAP2 gene knockdown, RT-qPCR, western Blot, colony formation, Cell counting kit-8, and wound healing assays. RESULTS: Our findings demonstrated a significant up-regulation of MFAP2 mRNA in TNBC cell lines, emphasizing its potential as a diagnostic biomarker. Validation across multiple datasets further affirmed the elevated expression of MFAP2 in TNBC tissues, underscoring its prognostic relevance. Notably, our study revealed a correlation between MFAP2 expression and immune cell infiltration, suggesting its role in shaping the tumor microenvironment. STRING analysis unveiled interactions with proteins involved in elastic fibers and extracellular matrix constituents. Furthermore, KEGG pathway analysis highlighted enrichment in the TGF-beta signaling pathway, implicating MFAP2 in key cancer-related processes. Drug sensitivity analysis identified potential therapeutic targets, supporting MFAP2's utility in personalized treatment strategies. In vitro experiments corroborated the oncogenic impact of MFAP2, demonstrating its influence on TNBC cell proliferation and migration. CONCLUSION: These comprehensive findings position MFAP2 as a promising biomarker and therapeutic target in TNBC, offering valuable insight for future research and clinical application.

12.
Clin Ther ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38734524

RESUMEN

PURPOSE: This analysis aimed to provide mechanistic understanding and clinical relevance of pharmacokinetic drug-drug interactions (DDIs) associated with drugs approved by the Food and Drug Administration in 2022. METHODS: Drug metabolism, transport, and DDI data available in New Drug Applications (NDAs) of small molecular drugs approved (n = 22) was analyzed. The mechanism and clinical magnitude of these interactions were characterized based on in vitro, in silico, and clinical data. FINDINGS: As victims, 10 drugs were identified as clinical substrates. Of these, 7 drugs were substrates of CYP3A, including the sensitive substrates daridorexant and mitapivat. As perpetrators, 3 drugs (adagrasib, lenacapavir, and vonoprazan) were clinical inhibitors of CYP enzymes, and 2 drugs (mavacamten and mitapivat) showed induction. Regarding transporter data, abrocitinib and deucravacitinib were found to be substrates of OAT3 and P-gp/BCRP, respectively, and 4 drugs (abrocitinib, adagrasib, lenacapavir, and oteseconazole) were found to inhibit P-gp and/or BCRP. As expected, all clinical DDIs with AUC changes ≥ 2-fold triggered label recommendations. Over half of DDIs with an AUC change < 2 also had label recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Overall, CYP3A played a major role in the drug disposition of the drugs approved in 2022, mediating all strong drug interactions. IMPLICATIONS: The mechanistic information obtained from studying these new therapeutics with marker compounds can be extrapolated to common concomitant medications sharing the same pharmacokinetic properties, enhancing the safe and effective administration of these products in situations of polytherapy.

13.
Phys Med Biol ; 69(11)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38636505

RESUMEN

Objective.Pharmacokinetic parametric images obtained through dynamic fluorescence molecular tomography (DFMT) has ability of capturing dynamic changes in fluorescence concentration, thereby providing three-dimensional metabolic information for applications in biological research and drug development. However, data processing of DFMT is time-consuming, involves a vast amount of data, and the problem itself is ill-posed, which significantly limits the application of pharmacokinetic parametric images reconstruction. In this study, group sparse-based Taylor expansion method is proposed to address these problems.Approach.Firstly, Taylor expansion framework is introduced to reduce time and computational cost. Secondly, group sparsity based on structural prior is introduced to improve reconstruction accuracy. Thirdly, alternating iterative solution based on accelerated gradient descent algorithm is introduced to solve the problem.Main results.Numerical simulation andin vivoexperimental results demonstrate that, in comparison to existing methods, the proposed approach significantly enhances reconstruction speed without a degradation of quality, particularly when confronted with background fluorescence interference from other organs.Significance.Our research greatly reduces time and computational cost, providing strong support for real-time monitoring of liver metabolism.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Hígado , Hígado/diagnóstico por imagen , Hígado/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Animales , Tomografía/métodos , Ratones , Imagen Óptica/métodos , Algoritmos , Fluorescencia
15.
Ecotoxicol Environ Saf ; 274: 116231, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38503102

RESUMEN

Deposition of potentially toxic elements (PTEs) in soils due to different types of mining activities has been an increasingly important concern worldwide. Quantitative differences of soil PTEs contamination and related health risk among typical mines remain unclear. Herein, data from 110 coal mines and 168 metal mines across China were analyzed based on 265 published literatures to evaluate pollution characteristics, spatial distribution, and probabilistic health risks of soil PTEs. The results showed that PTE levels in soil from both mine types significantly exceeded background values. The geoaccumulation index (Igeo) revealed metal-mine soil pollution levels exceeded those of coal mines, with average Igeo values for Cd, Hg, As, Pb, Cu, and Zn being 3.02-15.60 times higher. Spearman correlation and redundancy analysis identified natural and anthropogenic factors affecting soil PTE contamination in both mine types. Mining activities posed a significant carcinogenic risk, with metal-mine soils showing a total carcinogenic risk an order of magnitude higher than in coal-mine soils. This study provides policymakers a quantitative foundation for developing differentiated strategies for sustainable remediation and risk-based management of PTEs in typical mining soils.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Metales Pesados/análisis , Carbón Mineral/análisis , Monitoreo del Ambiente/métodos , Contaminación Ambiental/análisis , Suelo , Medición de Riesgo/métodos , China , Contaminantes del Suelo/análisis , Cadmio/análisis
16.
Opt Lett ; 49(5): 1161-1164, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426963

RESUMEN

Optical molecular tomography (OMT) can monitor glioblastomas in small animals non-invasively. Although deep learning (DL) methods have made remarkable achievements in this field, improving its generalization against diverse reconstruction systems remains a formidable challenge. In this Letter, a free space matching network (FSMN-Net) was presented to overcome the parameter mismatch problem in different reconstruction systems. Specifically, a novel, to the best of our knowledge, manifold convolution operator was designed by considering the mathematical model of OMT as a space matching process. Based on the dynamic domain expansion concept, an end-to-end fully convolutional codec further integrates this operator to realize robust reconstruction with voxel-level accuracy. The results of numerical simulations and in vivo experiments demonstrate that the FSMN-Net can stably generate high-resolution reconstruction volumetric images under different reconstruction systems.

17.
BMC Med Educ ; 24(1): 232, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38438890

RESUMEN

BACKGROUND: Early childhood caries (ECC) causes severe, widespread oral health issues in children. Dental undergraduates and residents are expected to have a solid understanding of ECC for children's oral health promotion. This study aimed to evaluate the knowledge, attitude, and clinical practice on ECC among dental undergraduates and residents in China. METHODS: A 23-item electronic questionnaire was distributed to 598 dental undergraduates (4th- and 5th-year undergraduates) and residents (1st-, 2nd-, and 3rd-year residents) at the School of Stomatology, Wuhan University, China (in April-May 2023). SPSS Statistics was used to analyze the data using the Chi-square test at a significance level of 0.05. RESULTS: A total of 422 questionnaires were completed by participants (recovery rate: 70.6%) from various academic levels. Around 77.3% of participants had heard of ECC (mainly from textbooks), and only 27.5% considered themselves familiar with it. Residents (79.8%) had higher risk awareness of ECC on children's overall health than undergraduates (58.3%) (p < 0.05), but only 54.0% of participants correctly defined ECC. Most participants had a positive understanding of ECC's pathogenic factors and preventive measures, including feeding patterns (71.6%), fluoride application (93.4%), and teeth cleaning (93.1%). Furthermore, only 50.2% of participants encountered ECC cases in clinic. CONCLUSIONS: Despite having a suboptimal level of ECC-related knowledge and practice, dental undergraduates and residents in China demonstrated a more positive attitude towards its etiology-based prevention. Strengthening ECC education, guidance, and practice may enable them to gain a better understanding of ECC learning, which would benefit children's oral health.


Asunto(s)
Susceptibilidad a Caries Dentarias , Caries Dental , Preescolar , Niño , Humanos , Conocimientos, Actitudes y Práctica en Salud , Estudiantes , Caries Dental/epidemiología , Caries Dental/prevención & control , China/epidemiología
18.
Acta Pharmacol Sin ; 45(6): 1201-1213, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38491160

RESUMEN

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.


Asunto(s)
Vía de Señalización Hippo , Interleucina-6 , Regeneración Hepática , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas , Receptor de Angiotensina Tipo 2 , Transducción de Señal , Animales , Masculino , Ratones , Acetaminofén , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Interleucina-6/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Regeneración Hepática/efectos de los fármacos , Regeneración Hepática/fisiología , Ratones Noqueados , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Proteínas Señalizadoras YAP/metabolismo
19.
Int Endod J ; 57(6): 682-699, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38403990

RESUMEN

AIM: This study aimed to determine the effects of iRoot BP Plus on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and inflammation-mediated bone resorption in vivo and investigated the underlying molecular mechanisms. METHODOLOGY: CCK-8 was performed to test cell viability in RANKL-induced RAW 264.7 cells and BMDMs in response to iRoot BP Plus. The effect of iRoot BP Plus on osteoclastogenesis was determined using TRAP staining and phalloidin staining, respectively. Pit formation assay was conducted to measure osteoclast resorptive capacity. Western blot and qPCR were performed to examine osteoclast-related proteins and gene expression, respectively. Western blot was also used to investigate the signalling pathways involved. For in vivo experiments, an LPS-induced mouse calvarial bone resorption model was established to analyse the effect of iRoot BP Plus on bone resorption (n = 6 per group). At 7 days, mouse calvaria were collected and prepared for histological analysis. RESULTS: We identified that iRoot BP Plus extracts significantly attenuated RANKL-induced osteoclastogenesis, reduced sealing zone formation, restrained osteolytic capacity and decreased osteoclast-specific gene expression (p < .01). Mechanistically, iRoot BP Plus extracts reduced TRAF6 via proteasomal degradation, then suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), blocked the nuclear translocation of c-Fos and diminished nuclear factor-κB (NF-κB) p65 and NFATc1 accumulation. Consistent with the in vitro results, iRoot BP Plus extracts attenuated osteoclast activity thus protecting against inflammatory bone resorption in vivo (p < .05), which was accompanied by a suppression of TRAF6, c-Fos, NFATc1 and cathepsin K expression. CONCLUSION: These findings provide valuable insights into the signalling mechanisms underlying nanoparticulate bioceramic putty-mediated bone homeostasis.


Asunto(s)
Resorción Ósea , Osteoclastos , Osteogénesis , Ligando RANK , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Animales , Ratones , Factor 6 Asociado a Receptor de TNF/metabolismo , Transducción de Señal/efectos de los fármacos , Resorción Ósea/metabolismo , Células RAW 264.7 , Osteogénesis/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Ligando RANK/metabolismo , Nanopartículas , Cerámica/farmacología , Inflamación/metabolismo , Supervivencia Celular/efectos de los fármacos
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