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1.
J Stomatol Oral Maxillofac Surg ; : 102098, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39357811

RESUMEN

OBJECTIVE: Malignant transformation of craniofacial fibrous dysplasia (FD) is not common and its clinicopathological as well as molecular characteristics remain largely unknown with limited literature reports. STUDY DESIGN: Patients diagnosed with FD including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD), accompanied by malignant transformation at our institution over the past 18 years (2005-2023) were retrospectively screened and analyzed to investigate the epidemiology and clinicopathological features of these tumors. RESULTS: Three hundred and five patients were diagnosed as FD in our hospital from 2005 to 2023, with 176 females (57.7 %) and 129 males (42.3 %). The average age at diagnosis was 28.35 years, ranging from 7 to 70 years. A total number of 15 (4. 9 %) cases of FD with malignant transformation were selected. Among these 15 patients, the age of the initial diagnosis of FD ranged from 6 to 54 years (mean age 28.87 ± 16.77), and the ages when malignant transformation occurred ranged from 18 to 57 years (mean age 38.53 ± 13.05). Among 15 patients, 12 patients were female (80 %) and 3 were male (20 %). Fifteen cases included MSA in 2 patients, PFD in 4 patients, and MFD in 9 patients. Of the anatomical sites in craniofacial bones, the most common site of the lesion was the maxilla, followed by the mandible. Malignant neoplasm arising in FD were osteosarcoma (12/15), chondrosarcoma (1/15) and high-grade sarcoma of uncertain differentiation (2/15). The 3- and 5-year overall survival rate was 33.3 % (5/15) and 20 % (3/15) respectively. In secondary osteosarcoma from FD, MDM2 and CDK4 positivity were 33.3 % and 41.7 % respectively, and only one case was MDM2-amplified and CDK4-amplified. CONCLUSION: Malignant transformation in fibrous dysplasia was an exceedingly rare event and with a female predominance. The overall survival rate was poor. Osteosarcoma was the most common malignant neoplasm arising in FD. MDM2 and CDK4 expression may aid in the diagnosis of secondary osteosarcoma in FD.

2.
Biomed Res ; 45(5): 187-195, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39370297

RESUMEN

Electromagnetic fields (EMFs) noninvasively promote fracture healing, prevent osteoporosis, promote diaphyseal growth, enhance differentiation, and stimulate cell division. However, no good model systems for analyzing bone regeneration have been reported. In this study, we examined the in vivo regeneration of scales having osteoblasts and osteoclasts using a new magnetic field generator for exposing aquatic animals to EMFs at a sine-wave frequency of 60 Hz. Goldfish scales were put into a fish-breeding space with the developed magnetic field generator and exposed to extremely low-frequency electromagnetic fields (ELF-EMFs) of 60 Hz at an intensity of 1, 3, and 5 mT for 10 days while being regenerated the scales. After exposure, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities in the goldfish scales were measured as markers of osteoblasts and osteoclasts, respectively. As a result, both ALP and TRAP activities in regenerating scales exposed to 3 mT ELF-EMFs were higher than those in regenerating scales exposed to 1 and 5 mT ELF-EMFs. Exposure of scales to 3 mT ELF-EMFs significantly enhanced the scale regeneration rate. Exposure of rat calvaria to 3 mT ELF-EMFs also increased both ALP and TRAP activities like in goldfish scales. Thus, we concluded that 3 mT ELF-EMFs contribute to the medical treatment of bone diseases.


Asunto(s)
Fosfatasa Alcalina , Escamas de Animales , Regeneración Ósea , Campos Electromagnéticos , Carpa Dorada , Osteoblastos , Osteoclastos , Fosfatasa Ácida Tartratorresistente , Animales , Osteoclastos/metabolismo , Fosfatasa Ácida Tartratorresistente/metabolismo , Fosfatasa Alcalina/metabolismo , Osteoblastos/metabolismo , Osteoblastos/citología , Ratas
3.
Nat Commun ; 15(1): 8296, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333117

RESUMEN

Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors.


Asunto(s)
Microscopía por Crioelectrón , Histamina , Receptores Histamínicos , Ligandos , Humanos , Histamina/metabolismo , Histamina/química , Receptores Histamínicos/metabolismo , Receptores Histamínicos/química , Células HEK293 , Unión Proteica , Sitios de Unión , Agonistas de los Receptores Histamínicos/química , Agonistas de los Receptores Histamínicos/metabolismo , Agonistas de los Receptores Histamínicos/farmacología , Modelos Moleculares
4.
Front Public Health ; 12: 1436304, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301513

RESUMEN

Introduction: This study investigates the experiences of leading Chinese companies in environmental conservation under varying extreme climate conditions, focusing on the role of artificial intelligence (AI) and governmental assistance. Methods: A survey was conducted involving 200 participants to assess recognition and endorsement of AI's role in environmental protection and to explore the adoption of AI technologies by firms for enhancing environmental management practices. Results: The survey revealed widespread recognition of Tencent's green initiatives and strong support for AI's role in environmental protection. Many firms are considering adopting AI technologies to optimize energy management, deploy intelligent HVAC systems, and improve the operations of data centers and smart lighting systems. Discussion: The findings highlight a strong belief in AI's potential to advance environmental protection efforts, with a call for increased governmental support to foster this development. The study underscores the importance of a partnership between businesses and governments to leverage AI for environmental sustainability, contributing significantly to conservation efforts.


Asunto(s)
Inteligencia Artificial , China , Humanos , Encuestas y Cuestionarios , Conservación de los Recursos Naturales , Contaminación Ambiental , Cambio Climático , Pueblos del Este de Asia
5.
Nurse Educ Pract ; 80: 104119, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39226852

RESUMEN

AIM: Compare the effects of Simulation with problem-based learning (SPBL) and Problem-based learning (PBL) in nursing ethics education on nursing students' moral sensitivity, empathy, critical thinking, test scores and teaching satisfaction. BACKGROUND: Promoting nursing students' individual and ethical and abilities through education is an essential way to improve their ethical performance and build trustful relationship with patients. Despite significant efforts in this area, few have evaluated the effectiveness of Simulation with problem-based learning and Problem-based learning as applied to nursing ethics education. DESIGN: A quasi-experimental design based on a non-equivalent control group pre-test/post-test. METHODS: A quasi-experimental design was used. Participants were 161 undergraduate nursing students from two levels of a university, 88 subjects in the experimental group were taught using Simulation with problem-based learning and 73 subjects in the control group were taught using Problem-based learning. A pre-test, post-test and questionnaire were used to assess the effectiveness of student nursing ethics education. χ2 test was used to examine group differences in students' characteristics and satisfaction with teaching post-intervention. Student's t-test was used to assess group differences in scale scores and test scores. RESULTS: Compared to the pre-test, empathy as well as critical thinking were significantly higher in the PBL group (P<0.05), but there was no significant change in moral sensitivity (P>0.05); moral sensitivity, empathy and critical thinking were significantly higher in the SPBL group (P<0.05). Moreover, this study also showed that improvement in moral sensitivity, empathy, critical thinking and grades was more significant in the SPBL group of nursing students compared to the PBL group (P<0.05) and no statistically significant difference was found between the two groups in terms of teaching satisfaction (P>0.05). CONCLUSION: The use of Simulation with problem-based learning in nursing ethics education has a positive impact on nursing students' competency development and knowledge acquisition. Nurse educators should consider this teaching method and promote change to increase the effectiveness of nursing ethics education.

6.
Int J Biol Macromol ; 279(Pt 4): 135523, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39260649

RESUMEN

The developmental changes in the granular surface structure and functional properties of starch during the entire grain filling period of rice (around 40 days) were investigated. The specific surface area of rice starch significantly decreased firstly then stabilized during growth due to increasing granular size. The pore volume decreased from 5.40 cm3/g at 6th day after anthesis (DAA-6) to 3.02 cm3/g (DAA-46). More starch granule-associated proteins (SGAPs) accumulated on the surface and in channels. Swelling power decreased by 46 %, whereas the flow behavior index (n) decreased by 32 % in upward curve during starch development from DAA-6 to DAA-30. Tan δ first dropped then remained steady at DAA 22-34 and lightly rebounded at the final stage, indicating that starch in the middle stage tended to have greater viscoelastic gel behavior at all sweeps. Mature starch showed lower in vitro hydrolysis rate and exhibited stronger enzymatic resistance. The results showed that granular surface features of rice starch may be an essential factor in determining rheological behavior and resistance to hydrolysis.


Asunto(s)
Grano Comestible , Oryza , Almidón , Oryza/química , Oryza/crecimiento & desarrollo , Almidón/química , Hidrólisis , Grano Comestible/química , Grano Comestible/crecimiento & desarrollo , Reología , Propiedades de Superficie , Proteínas de Plantas/química , Viscosidad
7.
Chem Biodivers ; : e202401641, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187940

RESUMEN

As a part of systematic research, an ongoing phytochemical investigation of the sesquiterpenoid-containing fraction led to the isolation of five new sesquiterpenoids from the peeled stems of Syringa pinnatifolia, including two pairs of enantiomeric humulane-type (±)-alashanoids A1 and B1 (1 and 2) and one eremophilane-type alashanoid C1 (3). These structures were elucidated by the analysis of extensive spectroscopic data, including ESI-MS and 1D and 2D NMR, and the absolute configuration was determined by comparing its experimental and calculated electronic circular dichroism and calculated NMR. These isolates exhibited moderate in vitro cardioprotective effects against oxidative injuries in H9c2 cells.

8.
Asian J Surg ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39214812

RESUMEN

OBJECTIVE: Breast cancer has become one of the main diseases threatening women's health and lives. Ultrasound (US) is the first diagnostic option for several patients because of its non-radiation, convenient, and low-cost features. Conventional US combined with contrast-enhanced US (CEUS) has improved diagnostic accuracy, while due to the presence of numerous parameters, no international consensus on diagnostic criteria could be attained. Therefore, it is necessary to develop a reliable diagnostic model with the involvement of a few parameters while increasing the diagnostic accuracy. METHODS: Data from 265 patients, including conventional US, CEUS, and postoperative pathological results, were collected. 21 parameters from the conventional US and both qualitative and quantitative aspects of CEUS were analyzed through univariate and multivariate logistic regression analyses. Specific parameters with independent influential factors were identified. A nomogram was subsequently developed to visually represent the contribution and linear weighting of each parameter. The effectiveness of the new model was assessed through calibration curves and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Six independent influential factors for breast malignant tumors were identified, including homogeneous echo, lesion vascularity, enhancement mode, enhancement shape, nourishing vessels, and slope. The area under the curve (AUC) values in the training and test datasets were 0.933 and 0.860, respectively. The modified model exhibited satisfactory diagnostic accuracy and operability. CONCLUSION: The modified model, despite incorporating fewer parameters, maintained diagnostic accuracy. It is exhibited as a convenient, effective, and easily deployable model for diagnosing malignant breast nodules.

9.
Bioorg Chem ; 152: 107732, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39178702

RESUMEN

Phytochemical analysis of the peeled stems of Syringa pinnatifolia Hemsl. led to the discovery of 13 undescribed lignans, namely helanols A and B (1 and 2) and alashanenols W-G1 (3-13), as well as four known analogues, of which helanols A and B were lignans with novel skeleton of α-ß' linkage. The structures were unambiguously established by extensive spectroscopic analyses, NMR calculations, ECD calculations, and single crystal X-ray crystallography. Five lignans (1, 2, 5, 11 and 13) exhibited a moderate protective effect against H2O2-induced oxidative injuries in H9c2 cells with the protective rates of 11.3-20.6 % at the concentration of 0.3-20 µM, while the positive control quercetin showed protective rates of 58.7 % at 10 µM. Further mechanism investigation suggested that 1 and 2 exerted the protective effect by regulating the expression of Nrf2/HO-1.


Asunto(s)
Peróxido de Hidrógeno , Lignanos , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Syringa , Lignanos/farmacología , Lignanos/química , Lignanos/aislamiento & purificación , Factor 2 Relacionado con NF-E2/metabolismo , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Syringa/química , Estructura Molecular , Ratas , Relación Estructura-Actividad , Animales , Relación Dosis-Respuesta a Droga , Hemo-Oxigenasa 1/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Línea Celular , Supervivencia Celular/efectos de los fármacos
10.
School Psych Rev ; 53(4): 365-381, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100141

RESUMEN

Supporting Indigenous students' social-emotional learning (SEL) is important given the systemic impact of colonialism that has contributed to their higher mental health and academic disparities compared to White students. One way to promote SEL is through professional development for educators, yet there has been little research on the development of SEL programs that are culturally responsive to Indigenous people and contexts. The purpose of this study is to highlight the process of culturally adapting a social-emotional program, Educators Navigating and Generating Approaches for Genuine Empowerment (ENGAGE), for educators at a school located in a tribal nation in the Rocky Mountain region. Driven by transformative SEL and tribal critical race theory, we co-adapted ENGAGE with community members through community-based participatory research. Through thematic analysis, we examined the unique values and culturally responsive considerations that arose during the research process. Five themes emerged from the data: (1) Understanding resilience in the face of trauma; (2) Fostering culture and traditions; (3) Building Relationships, respect, and reciprocity; (4) Highlighting the core role of educators in SEL; and (5) Educators supporting each other. Implications for school psychologists, including considerations for decolonizing research and practice, are discussed.

11.
Lipids Health Dis ; 23(1): 265, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39175030

RESUMEN

BACKGROUND: The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet. METHODS: 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017-2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram. RESULTS: In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11-2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04-3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745-0.819), which was assessed by DCA to be clinically important. CONCLUSION: In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.


Asunto(s)
HDL-Colesterol , Cálculos Biliares , Encuestas Nutricionales , Humanos , Femenino , Cálculos Biliares/sangre , Cálculos Biliares/epidemiología , Masculino , Persona de Mediana Edad , Adulto , HDL-Colesterol/sangre , Estudios Transversales , Factores de Riesgo , Modelos Logísticos , Estados Unidos/epidemiología , Colesterol/sangre , Biomarcadores/sangre
12.
Shanghai Kou Qiang Yi Xue ; 33(3): 324-327, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39104352

RESUMEN

PURPOSE: To investigate the clinical and pathological features of osteochondroma in maxillofacial region, and to summarize the clinicopathological features of rare osteochondroma malignant transformation in order to provide clinical guidance. METHODS: From January 2018 to September 2023, a total of 171 patients with osteochondroma were retrospectively collected in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Their preoperative CT and clinicopathological features were analyzed. RESULTS: Of the 171 patients with osteochondroma in maxillofacial bone, 66%(113/171) were females and 34% were male. Their age ranged from 11-76 with an average age was 44 years old. Of the 171 cases, 95.3%(163/171)in mandible condyle, 4%(7/171) in mandible processus coronoideus, and 0.5%(1/171) in zygomatic arch. The imaging findings showed that the thickness of cartilaginous cap was less than 1 cm in 98%(159/161) cases with condyle lesions. Only 2 cases(2/171, 1.1%) had malignant transformation. One was diagnosed with secondary chondrosarcoma, another developed low-grade osteosarcoma. CONCLUSIONS: Osteochondroma in maxillofacial region mostly occurs in females, and most commonly located in condylar process, with a malignant change rate of 1.1%, which is similar to that of other parts of the body. Imaging findings have important guiding significance for the diagnosis of osteochondroma malignant change.


Asunto(s)
Transformación Celular Neoplásica , Osteocondroma , Humanos , Osteocondroma/patología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Adolescente , Estudios Retrospectivos , Niño , Anciano , Tomografía Computarizada por Rayos X , Neoplasias Mandibulares/patología , Neoplasias Mandibulares/diagnóstico por imagen , Adulto Joven , Osteosarcoma/patología , Neoplasias Óseas/patología , Cóndilo Mandibular/patología , Condrosarcoma/patología , Cigoma/patología
13.
Shanghai Kou Qiang Yi Xue ; 33(3): 328-331, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39104353

RESUMEN

PURPOSE: To summarize the ultrasonographic features of head and neck Castleman disease (CD), and to clarify its diagnostic key points. METHODS: Seven patients with head and neck CD confirmed by histopathology were collected from Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The clinical features and ultrasound findings of the patients were evaluated. RESULTS: Of the 7 patients (1 male and 6 females), the mean age at diagnosis was 31.4 years (7-60 years). All the cases were hyaline vascular type. On ultrasound, 3 lesions (42.9%) were located in the parotid gland, 4 lesions(57.1%) in the neck. All the lesions presented as a solitary, well-defined and solid mass without calcification. The echogenicity was markedly hypoechoic in 1 case(14.3%) and hypoechoic in 6 cases (85.7%). Of the 7 CD cases, 4 cases (57.1%) were heterogeneous masses with linear echogenic septa. All lesions had mixed pattern in vascularity on color Doppler sonography. CONCLUSIONS: Most CDs in the head and neck represent as a markedly hypoechoic or hypoechoic lesion with mixed pattern in vascularity. The neoplasm may be characterized by the presence of linear echogenic septa within the mass.


Asunto(s)
Enfermedad de Castleman , Cuello , Ultrasonografía , Humanos , Enfermedad de Castleman/diagnóstico por imagen , Enfermedad de Castleman/patología , Masculino , Cuello/diagnóstico por imagen , Adulto , Femenino , Ultrasonografía/métodos , Persona de Mediana Edad , Cabeza/diagnóstico por imagen , Niño , Adolescente , Ultrasonografía Doppler en Color/métodos , Adulto Joven , Glándula Parótida/diagnóstico por imagen , Glándula Parótida/patología
14.
Shanghai Kou Qiang Yi Xue ; 33(2): 219-224, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-39005103

RESUMEN

PURPOSE: To summarize the ultrasound, CT and MRI manifestations of Warthin-like mucoepidermoid carcinoma (WT-MEC), and to explore its imaging characteristics, so as to provide reference for clinical and preoperative diagnosis. METHODS: The clinical information and imaging data of ultrasound, CT and MRI of 12 patients with WT-MEC diagnosed by pathology in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were collected, and their specific characteristics were retrospectively summarized. RESULTS: Among the 12 WT-MEC patients, there were 7 males and 5 females, with an average age of (42.7±16) years. Seven cases underwent ultrasound examination, 6 cases underwent CT examination, and 2 cases underwent MRI examination. Radiologically, all the lesions presented as a solitary mass. 11/12 lesions(91.7%) were identified as well-defined margins, and 10/12(83.3%) as solid-cystic masses. All solid-cystic lesions contained multiple cystic areas with variable sizes. On US images, most lesions showed mixed-echoic echogenicity(5/7, 71.4%), poor vascularization (6/7, 85.7%) and acoustic enhancement (6/7, 85.7%). CT revealed all the lesions (6/6, 100%) as a soft-tissue mass with heterogeneous enhancement (5/6, 83.3%). MRI imaging demonstrated the neoplasm with low or iso-signal intensity on plain T1WI and hyperintensity on T2WI. The heterogeneous enhancement was shown on contrast-enhanced T1WI. CONCLUSIONS: Most WT-MECs represent as a solitary, well-defined, solid-cystic mass in the parotid gland. The neoplasm may be characterized by the multiple and variable-sized cystic components within the tumor.


Asunto(s)
Carcinoma Mucoepidermoide , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , Carcinoma Mucoepidermoide/diagnóstico por imagen , Masculino , Femenino , Adulto , Ultrasonografía/métodos , Estudios Retrospectivos , Adenolinfoma/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico por imagen , Persona de Mediana Edad
15.
Acta Pharm Sin B ; 14(7): 2927-2941, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39027254

RESUMEN

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.

16.
Front Biosci (Landmark Ed) ; 29(7): 274, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39082350

RESUMEN

BACKGROUND: Diabetic cardiomyopathy (DCM) is an important cause of heart failure in diabetic patients. The aim of this study was to investigate the pathogenesis of DCM and to identify potential therapeutic targets. METHODS: A mouse model of type 1 DCM was constructed by continuous intraperitoneal injection of streptozotocin (STZ). Systolic and diastolic functions were measured by ultrasound. The expression of La-related protein 7 (LARP7), the stimulator of interferon genes (STING) pathway and light chain 3 (LC3) in myocardial tissue was detected by Western blot and immunofluorescence analyses. Neonatal mouse ventricular cardiomyocytes (NMVCMs) were isolated and cultured. An in vitro type 1 diabetes mellitus (T1DM) model was established by treatment with high glucose. Knockdown/overexpression of LARP7 and STING was achieved by adenovirus transduction, C-176 (a potent covalent inhibitor of STING), and plasmid transfection. The expression, activation, and localization of STING and LARP7 in cardiomyocytes was evaluated, as well as the interaction between the two. The effect of this interaction on the STING-dependent autophagy‒lysosomal pathway was also explored. In addition, the fibrosis and apoptosis of cardiomyocytes were evaluated. RESULTS: High glucose was found to increase the expression and activation of STING and LARP7 in mouse myocardial tissue. This was accompanied by myocardial fibrosis, impaired autophagy degradation function and impaired cardiac function. These findings were further confirmed by in vitro experiments. High glucose caused LARP7 to translocate from the nucleus to the cytoplasm, where it interacted with accumulated STING to inhibit its degradation. Inhibition of STING or LARP7 expression significantly improved myocardial injury induced by high glucose. CONCLUSIONS: Targeted inhibition of LARP7 or STING expression may be a potential therapeutic strategy for the treatment of DCM.


Asunto(s)
Apoptosis , Cardiomiopatías Diabéticas , Fibrosis , Glucosa , Proteínas de la Membrana , Miocitos Cardíacos , Ribonucleoproteínas , Animales , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Glucosa/metabolismo , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/etiología , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Ratones , Masculino , Antígeno SS-B , Ratones Endogámicos C57BL , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Autofagia , Miocardio/metabolismo , Miocardio/patología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo
17.
Cereb Cortex ; 34(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39042032

RESUMEN

Delay discounting refers to the tendency of individuals to devalue future rewards as the delay in their receipt increases over time. Previous studies have indicated that future self-continuity correlates with delay discounting rates. However, the neural basis underlying the relationship between future self-continuity and delay discounting is not clear. To address this question, we used voxel-based morphometry and resting-state functional connectivity analyses to investigate the neural basis underlying the association between future self-continuity and delay discounting. Behavioral result showed that future self-continuity was positively associated with delay discounting. Voxel-based morphometry analysis result indicated that gray matter volume in the right dorsal anterior insula was positively correlated with future self-continuity. Resting-state functional connectivity analysis found that functional connectivity between the right dorsal anterior insula and anterior cingulate cortex was positively associated with future self-continuity. Mediation analysis showed that the right dorsal anterior insula-right anterior cingulate cortex functional connectivity partially mediated the relationship between future self-continuity and delay discounting. These results suggested that right dorsal anterior insula-right anterior cingulate cortex functional connectivity could be the neural basis underlying the association between future self-continuity and delay discounting. In summary, the study provided novel insights into how future self-continuity affected delay discounting and offers new explanations from a neural perspective.


Asunto(s)
Descuento por Demora , Giro del Cíngulo , Corteza Insular , Imagen por Resonancia Magnética , Humanos , Masculino , Descuento por Demora/fisiología , Giro del Cíngulo/fisiología , Giro del Cíngulo/diagnóstico por imagen , Femenino , Adulto Joven , Corteza Insular/fisiología , Corteza Insular/diagnóstico por imagen , Adulto , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagen , Mapeo Encefálico , Recompensa
18.
bioRxiv ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39005467

RESUMEN

Transfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications - the tRNA epitranscriptome - very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a Pseudomonas aeruginosa transposon insertion mutant library comprising 5,746 strains. Analysis of >200,000 tRNA modification data points validated the annotations of predicted tRNA modification genes, uncovered novel tRNA-modifying enzymes, and revealed tRNA modification regulatory networks in P. aeruginosa. Platform adaptation for RNA-seq library preparation would complement epitranscriptome studies, while application to human cell and mouse tissue demonstrates its utility for biomarker and drug discovery and development.

19.
BMC Gastroenterol ; 24(1): 221, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987694

RESUMEN

BACKGROUND: Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US. METHODS: Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations. RESULTS: A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74-12.70], 2.84 [2.38-3.39], 3.02 [2.02-4.51], and 9.53 [7.79-11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42-1.53; P < 0.001). WC also demonstrated strong discriminatory ability for NAFLD in Receiver Operating Characteristic (ROC) analysis, achieving an Area Under the Curve (AUC) of 0.802. CONCLUSIONS: Different patterns of obesity are risk factors for NAFLD. An increase in WC significantly increased NAFLD risk. More attention should be paid to preventing different patterns of obesity among adults.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Obesidad , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Estudios Transversales , Obesidad/complicaciones , Obesidad/epidemiología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Femenino , Índice de Masa Corporal , Circunferencia de la Cintura , Estados Unidos/epidemiología , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Obesidad Abdominal/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología
20.
Int J Biol Macromol ; 275(Pt 2): 133493, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38960230

RESUMEN

Cotton has attracted considerable attention due to its functional characteristics. The focus of research on cotton has shifted in recent years towards designing multi-functional and modified media for cotton fibers, which can be firmly combined with textiles, giving them reusability and extending their service life. This study constructed a synergistic antibacterial layer of quaternary ammonium compounds (QACs) and N-halamine (Hals) using an in-situ free radical copolymerization method in water, named QACs/Hals@cotton-Cl. The route significantly increases the number of antibacterial active centers. FTIR, XPS, and SEM were used to systematically analyze the product's chemical structure, surface morphology, and other characteristics. The modified fabric's antibacterial efficiency, wound healing, renewability, and durability were also evaluated. The chlorinated modified cotton fabric could completely eradicate S. aureus and E. coli within 10 min. Compared with pure cotton, it notably promoted the healing rate of infected wounds in mice. The modification method imparted excellent hydrophobicity to the cotton fabric, with a contact angle exceeding 130°, making it easy to remove surface stains. After 30 days of regular storage and 24 h of UV irradiation, the active chlorine concentration (Cl+%) only decreased by 25 % and 39 %, respectively, and the reduced Cl+% was effectively recharged via simple re-chlorination. The hydrophobicity and antimicrobial properties of QACs/Hals@cotton-Cl remained stable even after 20 cycles of friction. This simple synthesis technique provides a convenient approach for the scalable fabrication of multifunctional and rechargeable antibacterial textiles, with potential applications in medical devices and personal hygiene protection.


Asunto(s)
Aminas , Antibacterianos , Fibra de Algodón , Escherichia coli , Staphylococcus aureus , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Ratones , Staphylococcus aureus/efectos de los fármacos , Aminas/química , Escherichia coli/efectos de los fármacos , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Textiles , Pruebas de Sensibilidad Microbiana
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