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1.
Genes Dev ; 35(7-8): 542-555, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33664057

RESUMEN

p53 is critical for tumor suppression but also elicits detrimental effects when aberrantly overexpressed. Thus, multiple regulators, including RNA-binding protein RBM38, are found to tightly control p53 expression. Interestingly, RBM38 is unique in that it can either suppress or enhance p53 mRNA translation via altered interaction with eIF4E potentially mediated by serine-195 (S195) in RBM38. Thus, multiple RBM38/eIF4E knock-in (KI) cell lines were generated to investigate the significance of eIF4E-RBM38 interaction in controlling p53 activity. We showed that KI of RBM38-S195D or -Y192C enhances, whereas KI of RBM38-S195K/R/L weakens, the binding of eIF4E to p53 mRNA and subsequently p53 expression. We also showed that KI of eIF4E-D202K weakens the interaction of eIF4E with RBM38 and thereby enhances p53 expression, suggesting that D202 in eIF4E interacts with S195 in RBM38. Moreover, we generated an Rbm38 S193D KI mouse model in which human-equivalent serine-193 is substituted with aspartic acid. We showed that S193D KI enhances p53-dependent cellular senescence and that S193D KI mice have a shortened life span and are prone to spontaneous tumors, chronic inflammation, and liver steatosis. Together, we provide in vivo evidence that the RBM38-eIF4E loop can be explored to fine-tune p53 expression for therapeutic development.


Asunto(s)
Factor 4E Eucariótico de Iniciación/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de Unión al ARN/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Carcinogénesis/genética , Línea Celular , Senescencia Celular/genética , Factor 4E Eucariótico de Iniciación/genética , Hígado Graso/genética , Técnicas de Sustitución del Gen , Inflamación/genética , Longevidad/genética , Ratones , Unión Proteica/genética , Proteínas de Unión al ARN/genética , Proteína p53 Supresora de Tumor/genética
2.
Proc Natl Acad Sci U S A ; 121(39): e2403222121, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39302967

RESUMEN

Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated traits (e.g., rapid wound healing) are poorly understood. Here, we report the genome of Halimeda opuntia, a giant multinucleate unicellular chlorophyte characterized by interutricular calcification. We achieve a high-quality genome assembly that shows segregation into four subgenomes, with evidence for polyploidization concomitant with historical sea level and climate changes. We further find myosin VIII missing in H. opuntia and three other unicellular multinucleate chlorophytes, suggesting a potential mechanism that may underpin multinucleation. Genome analysis provides clues about how the unicellular alga could survive fragmentation and regenerate, as well as potential signatures for extracellular calcification and the coupling of calcification with photosynthesis. In addition, proteomic alkalinity shifts were found to potentially confer plasticity of H. opuntia to ocean acidification (OA). Our study provides crucial genetic information necessary for understanding multinucleation, cell regeneration, plasticity to OA, and different modes of calcification in algae and other organisms, which has important implications in reef conservation and bioengineering.


Asunto(s)
Calcificación Fisiológica , Calcificación Fisiológica/genética , Chlorophyta/genética , Chlorophyta/metabolismo , Filogenia , Genoma de Planta , Fotosíntesis/genética
3.
PLoS Pathog ; 20(8): e1012291, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39102426

RESUMEN

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.


Asunto(s)
COVID-19 , Senescencia Celular , Células Gigantes , Insuficiencia Cardíaca , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/virología , Animales , Células Gigantes/virología , Células Gigantes/metabolismo , Células Gigantes/patología , COVID-19/metabolismo , COVID-19/complicaciones , COVID-19/virología , COVID-19/patología , Humanos , Glicoproteína de la Espiga del Coronavirus/metabolismo , Ratones , Vesículas Extracelulares/metabolismo
4.
Genes Dev ; 31(12): 1243-1256, 2017 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-28747430

RESUMEN

Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to iron overload in developing embryos. Interestingly, mice heterozygous in Fdxr had a short life span and were prone to spontaneous tumors and liver abnormalities, including steatosis, hepatitis, and hepatocellular carcinoma. We also found that FDXR was necessary for mitochondrial iron homeostasis and proper expression of several master regulators of iron metabolism, including iron regulatory protein 2 (IRP2). Surprisingly, we found that p53 mRNA translation was suppressed by FDXR deficiency via IRP2. Moreover, we found that the signal from FDXR to iron homeostasis and the p53 pathway was transduced by ferredoxin 2, a substrate of FDXR. Finally, we found that p53 played a role in iron homeostasis and was required for FDXR-mediated iron metabolism. Together, we conclude that FDXR and p53 are mutually regulated and that the FDXR-p53 loop is critical for tumor suppression via iron homeostasis.


Asunto(s)
Ferredoxina-NADP Reductasa/metabolismo , Homeostasis/genética , Proteína 2 Reguladora de Hierro/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Modelos Animales de Enfermedad , Desarrollo Embrionario/genética , Ferredoxina-NADP Reductasa/genética , Regulación de la Expresión Génica/genética , Células HCT116 , Células Hep G2 , Humanos , Hierro/metabolismo , Proteína 2 Reguladora de Hierro/genética , Hepatopatías/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neoplasias/genética , Biosíntesis de Proteínas , Proteína p53 Supresora de Tumor/genética
5.
J Biol Chem ; 299(10): 105226, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37673339

RESUMEN

Successful muscle regeneration following injury is essential for functional homeostasis of skeletal muscles. Krüppel-like factor 15 (KLF15) is a metabolic transcriptional regulator in the muscles. However, little is known regarding its function in muscle regeneration. Here, we examined microarray datasets from the Gene Expression Omnibus database, which indicated downregulated KLF15 in muscles from patients with various muscle diseases. Additionally, we found that Klf15 knockout (Klf15KO) impaired muscle regeneration following injury in mice. Furthermore, KLF15 expression was robustly induced during myoblast differentiation. Myoblasts with KLF15 deficiency showed a marked reduction in their fusion capacity. Unbiased transcriptome analysis of muscles on day 7 postinjury revealed downregulated genes involved in cell differentiation and metabolic processes in Klf15KO muscles. The FK506-binding protein 51 (FKBP5), a positive regulator of myoblast differentiation, was ranked as one of the most strongly downregulated genes in the Klf15KO group. A mechanistic search revealed that KLF15 binds directly to the promoter region of FKBP5 and activates FKBP5 expression. Local delivery of FKBP5 rescued the impaired muscle regeneration in Klf15KO mice. Our findings reveal a positive regulatory role of KLF15 in myoblast differentiation and muscle regeneration by activating FKBP5 expression. KLF15 signaling may be a novel therapeutic target for muscle disorders associated with injuries or diseases.


Asunto(s)
Mioblastos , Proteínas de Unión a Tacrolimus , Animales , Humanos , Ratones , Diferenciación Celular/genética , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones Noqueados , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Regeneración/genética , Proteínas de Unión a Tacrolimus/metabolismo , Masculino , Ratones Endogámicos C57BL
6.
Antimicrob Agents Chemother ; 68(4): e0153923, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38470195

RESUMEN

Murepavadin is a peptidomimetic that specifically targets the lipopolysaccharide transport protein LptD of Pseudomonas aeruginosa. Here, we found that murepavadin enhances the bactericidal efficacies of tobramycin and amikacin. We further demonstrated that murepavadin enhances bacterial respiration activity and subsequent membrane potential, which promotes intracellular uptake of aminoglycoside antibiotics. In addition, the murepavadin-amikacin combination displayed a synergistic bactericidal effect in a murine pneumonia model.


Asunto(s)
Amicacina , Péptidos Cíclicos , Infecciones por Pseudomonas , Animales , Ratones , Amicacina/farmacología , Pseudomonas aeruginosa , Potenciales de la Membrana , Antibacterianos/farmacología , Aminoglicósidos/farmacología , Tobramicina/farmacología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pruebas de Sensibilidad Microbiana
7.
Brief Bioinform ; 23(6)2022 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-36124777

RESUMEN

A transcriptional regulatory network (TRN) is a collection of transcription regulators with their associated downstream genes, which is highly condition-specific. Understanding how cell states can be programmed through small molecules/drugs or conditions by modulating the whole gene expression system granted us the potential to amend abnormal cells and cure diseases. Condition Orientated Regulatory Networks (CORN, https://qinlab.sysu.edu.cn/home) is a library of condition (small molecule/drug treatments and gene knockdowns)-based transcriptional regulatory sub-networks (TRSNs) that come with an online TRSN matching tool. It allows users to browse condition-associated TRSNs or match those TRSNs by inputting transcriptomic changes of interest. CORN utilizes transcriptomic changes data after specific conditional treatment in cells, and in vivo transcription factor (TF) binding data in cells, by combining TF binding information and calculations of significant expression alterations of TFs and genes after the conditional treatments, TRNs under the effect of different conditions were constructed. In short, CORN associated 1805 different types of specific conditions (small molecule/drug treatments and gene knockdowns) to 9553 TRSNs in 25 human cell lines, involving 204TFs. By linking and curating specific conditions to responsive TRNs, the scientific community can now perceive how TRNs are altered and controlled by conditions alone in an organized manner for the first time. This study demonstrated with examples that CORN can aid the understanding of molecular pathology, pharmacology and drug repositioning, and screened drugs with high potential for cancer and coronavirus disease 2019 (COVID-19) treatments.


Asunto(s)
COVID-19 , Redes Reguladoras de Genes , Humanos , COVID-19/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcriptoma
8.
Mol Cell Biochem ; 479(7): 1553-1570, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38856795

RESUMEN

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.


Asunto(s)
Adenosina , Neoplasias Gastrointestinales , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Epigénesis Genética , Metilación
9.
Br J Nutr ; 131(8): 1377-1383, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38073288

RESUMEN

It is now generally believed that elderly may have slightly higher dietary protein requirements than those of the young-middle-aged adults. We have previously conducted related studies by the indicator amino acid oxidation (IAAO) technique, but more research data are needed to revise the protein requirements of the elderly. The main objective was to reevaluate the dietary protein requirements of healthy Chinese adults (65-80 years) without sarcopenia by using the IAAO technique. Nine healthy adult men and seven healthy adult women participated in the study, with protein intakes ranging from 0·1 to 1·8 g/(kg·d). Diets that delivered energy at a 1·5 resting energy expenditure were isocaloric. The amounts of phenylalanine and tyrosine needed to remain constant for each protein dosage. By applying a nonlinear mixed-effects model analysis on the F13CO2 data, which revealed a breakpoint in F13CO2 in response to graded protein intakes, the mean protein requirement was calculated. The mean estimated average requirement (EAR) for healthy elderly Chinese adults without sarcopenia was determined to be 0·94 g/(kg·d). The protein recommended nutrient intake (RNI) determined using various derivation approaches ranged from 1·13 to 1·36 g/(kg·d). The EAR for Chinese adults without sarcopenia aged 65-80 years in this study is 6·8 % higher than the current recommended EAR (0·88 g/(kg·d)). The RNI derived using various derivation approaches are all greater than the current RNI (0·98 g/(kg·d)). This trial was registered with the Chinese clinical trial registry as ChiCTR2200061382.


Asunto(s)
Aminoácidos , Sarcopenia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aminoácidos/metabolismo , Dióxido de Carbono , Isótopos de Carbono , China , Proteínas en la Dieta , Necesidades Nutricionales , Oxidación-Reducción
10.
Bioorg Med Chem Lett ; 113: 129961, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39278366

RESUMEN

The EGFR-TK pathway is pivotal in non-small-cell lung cancer (NSCLC) treatment, drugs targeting both EGFR wild-type and mutant tumor cells are still urgently needed. The focus of our study is on ATP-competitive inhibitors crucial for NSCLC therapy, specifically targeting the epidermal growth factor receptor (EGFR). A series of derivatives of Erlotinib and Icotinib were developed by incorporating a macrocyclic polyamine into a quinazoline scaffold to enhance their inhibitory activity against drug-resistant cells. The compounds exhibit modest activity against EGFR triple mutants (EGFRdel19/T790M/C797S). Compound b demonstrated slightly improved inhibition activity against PC-9del19/T790M/C797S (IC50 = 496.3 nM). This could provide some insights for optimizing EGFR inhibitors, particularly in the context of EGFR triple mutants.

11.
Fish Shellfish Immunol ; 148: 109441, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38354965

RESUMEN

The battle between host and viral is ubiquitous across all ecosystems. Despite this, research is scarce on the antiviral characteristics of fish, particularly in those that primarily rely on innate immune responses. This study, comprehensively explored the genetic and antiviral features of ISG15 in spotted seabass, focusing on its response to largemouth bass ulcerative syndrome virus (LBUSV). Through whole-genome BLAST and PCR cloning, two ISG15 homologs, namely LmISG15a and LmISG15b, were identified in spotted seabass, both encoding highly conserved proteins. However, a distinctive contrast emerged in their expression patterns, with LmISG15a exhibiting high expression in immune organs while LmISG15b remained largely silent across various organs. Regulatory elements analysis indicated an asymmetric evolution of the two ISG15s, with the minimal expression of LmISG15b may attribute to the loss of a necessary ISRE and an additional instability "ATTTA" motif. Association analysis demonstrated a significant correlation between LmISG15a expression and LBUSV infection. Subsequent antiviral activity detection revealed that LmISG15a interacted with LBUSV, inhibiting its replication by activating ISGylation and downstream pro-inflammatory mediators. In summary, this study unveils a distinct evolutionary strategy of fish antiviral gene ISG15 and delineates its kinetic characteristics in response to LBUSV infection.


Asunto(s)
Lubina , Enfermedades de los Peces , Virosis , Animales , Ecosistema , Proteínas de Peces , Inmunidad Innata/genética , Antivirales
12.
J Chem Inf Model ; 64(9): 3689-3705, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38676916

RESUMEN

Combination therapy is a promising strategy for the successful treatment of cancer. The large number of possible combinations, however, mean that it is laborious and expensive to screen for synergistic drug combinations in vitro. Nevertheless, because of the availability of high-throughput screening data and advances in computational techniques, deep learning (DL) can be a useful tool for the prediction of synergistic drug combinations. In this study, we proposed a multimodal DL framework, MMSyn, for the prediction of synergistic drug combinations. First, features embedded in the drug molecules were extracted: structure, fingerprint, and string encoding. Then, gene expression data, DNA copy number, and pathway activity were used to describe cancer cell lines. Finally, these processed features were integrated using an attention mechanism and an interaction module and then input into a multilayer perceptron to predict drug synergy. Experimental results showed that our method outperformed five state-of-the-art DL methods and three traditional machine learning models for drug combination prediction. We verified that MMSyn achieved superior performance in stratified cross-validation settings using both the drug combination and cell line data. Moreover, we performed a set of ablation experiments to illustrate the effectiveness of each component and the efficacy of our model. In addition, our visual representation and case studies further confirmed the effectiveness of our model. All results showed that MMSyn can be used as a powerful tool for the prediction of synergistic drug combinations.


Asunto(s)
Aprendizaje Profundo , Sinergismo Farmacológico , Humanos , Línea Celular Tumoral , Combinación de Medicamentos , Antineoplásicos/farmacología , Antineoplásicos/química
13.
J Chem Inf Model ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888465

RESUMEN

Small molecule antioxidants can inhibit or retard oxidation reactions and protect against free radical damage to cells, thus playing a key role in food, cosmetics, pharmaceuticals, the environment, as well as materials. Experimentally driven antioxidant discovery is a major paradigm, and computationally assisted antioxidants are rarely reported. In this study, a functional-group-based alternating multitask self-supervised molecular representation learning method is proposed to simultaneously predict the antioxidant activities of small molecules for eight commonly used in vitro antioxidant assays. Extensive evaluation results reveal that compared with the baseline models, the multitask FG-BERT model achieves the best overall predictive performance, with the highest average F1, BA, ROC-AUC, and PRC-AUC values of 0.860, 0.880, 0.954, and 0.937 for the test sets, respectively. The Y-scrambling testing results further demonstrate that such a deep learning model was not constructed by accident and that it has reliable predictive capabilities. Additionally, the excellent interpretability of the multitask FG-BERT model makes it easy to identify key structural fragments/groups that contribute significantly to the antioxidant effect of a given molecule. Finally, an online antioxidant activity prediction platform called AOP (freely available at https://aop.idruglab.cn/) and its local version were developed based on the high-quality multitask FG-BERT model for experts and nonexperts in the field. We anticipate that it will contribute to the discovery of novel small-molecule antioxidants.

14.
Int J Colorectal Dis ; 39(1): 46, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38565736

RESUMEN

PURPOSE: Lymph node metastasis (LNM) is a crucial factor that determines the prognosis of T1 colorectal cancer (CRC) patients. We aimed to develop a practical prediction model for LNM in T1 CRC. METHODS: We conducted a retrospective analysis of data from 825 patients with T1 CRC who underwent radical resection at a single center in China. All enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3 using R software. Risk factors for LNM were identified through multivariate logistic regression analyses. Subsequently, a prediction model was developed using the selected variables. RESULTS: The lymph node metastasis (LNM) rate was 10.1% in the training cohort and 9.3% in the validation cohort. In the training set, risk factors for LNM in T1 CRC were identified, including depressed endoscopic gross appearance, sex, submucosal invasion combined with tumor grade (DSI-TG), lymphovascular invasion (LVI), and tumor budding. LVI emerged as the most potent predictor for LNM. The prediction model based on these factors exhibited good discrimination ability in the validation sets (AUC: 79.3%). Compared to current guidelines, the model could potentially reduce over-surgery by 48.9%. Interestingly, we observed that sex had a differential impact on LNM between early-onset and late-onset CRC patients. CONCLUSIONS: We developed a clinical prediction model for LNM in T1 CRC using five factors that are easily accessible in clinical practice. The model has better predictive performance and practicality than the current guidelines and can assist clinicians in making treatment decisions for T1 CRC patients.


Asunto(s)
Neoplasias Colorrectales , Modelos Estadísticos , Humanos , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Distribución Aleatoria , China
15.
BMC Cardiovasc Disord ; 24(1): 417, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127656

RESUMEN

Mutations in fibrillin 1 (FBN1) is the main cause of Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA) as the main complication. Activation of the complement system plays a key role in the formation of thoracic and abdominal aortic aneurysms. However, the role of the complement system in MFS-associated aortic aneurysms remains unclear. In this study, we observed increased levels of complement C3a and C5a in the plasma of MFS patients and mouse, and the increased deposition of the activated complement system product C3b/iC3b was also observed in the elastic fiber rupture zone of 3-month-old MFS mice. The expression of C3a receptor (C3aR) was increased in MFS aortas, and recombinant C3a promoted the expression of cytokines in macrophages. The administration of a C3aR antagonist (C3aRA) attenuated the development of thoracic aortic aneurysms in MFS mice. The increased inflammation response and matrix metalloproteinases activities were also attenuated by C3aRA treatment in MFS mice. Therefore, these findings indicate that the complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.


Asunto(s)
Adipoquinas , Aneurisma de la Aorta Torácica , Complemento C3a , Fibrilina-1 , Síndrome de Marfan , Receptores de Complemento , Animales , Femenino , Humanos , Masculino , Ratones , Adipoquinas/genética , Aorta Torácica/patología , Aneurisma de la Aorta Torácica/prevención & control , Aneurisma de la Aorta Torácica/etiología , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/patología , Complemento C3a/antagonistas & inhibidores , Complemento C3a/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fibrilina-1/genética , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Síndrome de Marfan/complicaciones , Síndrome de Marfan/genética , Síndrome de Marfan/tratamiento farmacológico , Ratones Endogámicos C57BL , Receptores de Complemento/antagonistas & inhibidores , Receptores Acoplados a Proteínas G , Transducción de Señal
16.
Surg Endosc ; 38(7): 3783-3798, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38806955

RESUMEN

BACKGROUND: Many studies reported the presence of adenomas with high-grade dysplasia (HGD) at index colonoscopy increased the incidence of advanced neoplasia (AN) and colorectal cancer (CRC) following. However, the conclusion remains obscure due to lack of studies on the specific population of adenomas with HGD. This study aimed to assess the long-term risk of AN and CRC after removal of adenomas with HGD. METHODS: A total of 814 patients who underwent adenomas with HGD removal between 2010 and 2019 were retrospectively analyzed. The outcomes were the incidences of AN and CRC during surveillance colonoscopy. Cox proportional hazards models were utilized to identify risk factors associated with AN and CRC. RESULTS: During more than 2000 person-years of follow-up, we found that AN and CRC incidence densities were 44.3 and 4.4 per 1000 person-years, respectively. The 10-year cumulative incidence of AN and CRC were 39.1% and 5.5%, respectively. In the multivariate model, synchronous low-risk polyps (HR 1.80, 95% CI 1.10-2.93) and synchronous high-risk polyps (HR 3.99, 95% CI 2.37-6.72) were risk factors for AN, whereas participation in surveillance colonoscopy visits (HR 0.56, 95% CI 0.36-0.88 for 1 visit; HR 0.10, 95% CI 0.06-0.19 for ≥ 2 visits) were associated with decreased AN incidence. Additionally, elevated baseline carcinoembryonic antigen (CEA) level (HR 10.19, 95% CI 1.77-58.59) was a risk factor for CRC, while participation in ≥ 2 surveillance colonoscopy visits (HR 0.11, 95% CI 0.02-0.56) were associated with decreased CRC incidence. Interestingly, for 11 patients who developed CRC after removal of adenomas with HGD, immunohistochemistry revealed that 8 cases (73%) were deficient mismatch repair CRCs. CONCLUSIONS: Patients who have undergone adenoma with HGD removal are at higher risk of developing AN and CRC, while surveillance colonoscopy can reduce the risk. Patients with synchronous polyps, or with elevated baseline CEA level are considered high-risk populations and require more frequent surveillance.


Asunto(s)
Adenoma , Colonoscopía , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adenoma/patología , Adenoma/cirugía , Adenoma/epidemiología , Incidencia , Factores de Riesgo , Anciano , Pólipos del Colon/cirugía , Pólipos del Colon/patología , Adulto
17.
Cardiovasc Ultrasound ; 22(1): 9, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075466

RESUMEN

BACKGROUND: Currently, no normal ultrasound data of the fetuses during the 20-40 gestation have been obtained for references of fetal growth and development. If such ultrasound data existed for prenatal diagnosis of possible diseases and abnormalities, neonates would be able to get timely treatment immediately after birth. This study was thus performed to obtain ultrasound parameters of normal fetuses during the 20-40 week gestation and the distribution of ultrasound parameters with the gestational age for references of detecting potential fetal diseases and abnormalities. METHODS: Normal fetuses without any abnormalities were enrolled, and the ultrasound parameters of the general biology, arteries, and aorta were measured and analyzed. RESULTS: 417 normal fetuses were enrolled. A significant (P < 0.05) negative correlation with the gestational age was detected in the peak systolic velocity/peak diastolic velocity (S/D), pulsatility index (PI) and resistance index (RI) of the umbilical artery (UA). A relatively stable relationship with the gestational age was detected in the fetal weight%, S/D, PI and RI of the middle cerebral artery (MCA), peak systolic velocity (PSV) and velocity time integral (VTI) of the intra-abdominal UA, fetal heart to chest ratio, mitral valve (MV)- and tricuspid valve (TV)-E/A peak flow velocity, aortic isthmic Z-score and displacement, distance between the brachiocephalic artery-left common carotid artery (BA-LCCA) and LCCA-left subclavian artery (LSA), Z-score of aorta, ascending aorta (AAO), pulmonary artery (PA), main pulmonary artery (MPA), and descending aorta (DAO). A significant (P < 0.05) positive correlation with the gestational age was detected in the fetal biological data, MCA PSV and VTI, free-UA PSV and VTI and cardio-thoracic ratio, cardiac parameters, ductus arteriosus (DA) and isthmus diameter, aortic parameters, PA and MPA diameter, MPA PSV and VTI, isthmus flow volume and velocity and PA flow volume, DA and BA parameters, and LCCA and LSA parameters (flow volume, PSV, and VTI). CONCLUSION: A certain correlation and distribution trend is detected in the ultrasound parameters of normal fetuses, and the ratios among different parameters remain relative stable. These findings can be used for determination of abnormal growth of the fetuses in prenatal ultrasound scan.


Asunto(s)
Corazón Fetal , Edad Gestacional , Ultrasonografía Prenatal , Humanos , Ultrasonografía Prenatal/métodos , Femenino , Corazón Fetal/diagnóstico por imagen , Corazón Fetal/fisiopatología , Embarazo , Velocidad del Flujo Sanguíneo/fisiología , Valores de Referencia , Adulto , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/embriología , Reproducibilidad de los Resultados
18.
BMC Public Health ; 24(1): 508, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38368327

RESUMEN

BACKGROUND: Social media has become an indispensable part of contemporary young people's lives, and the influence of social media on college students' eating and other health-related behaviors has become increasingly prominent. However, there is no assessment tool to determine the effects of social media on Chinese college students' eating behavior. This study aims to translate the Scale of Effects of Social Media on Eating Behaviour (SESMEB) into Chinese. Its applicability to Chinese college students was examined through reliability and validity indexes, and the influencing factors of SESMEB were explored. METHODS: The questionnaire survey included 2374 Chinese college students. The Brislin translation model was used to translate the original scale into Chinese. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to test the construct validity of the scale, and the content validity of the scale was assessed through the content validity index. The internal consistency of the scale was assessed by calculating Cronbach's alpha coefficient, McDonald's Omega coefficient, split-half reliability, and test-retest reliability. Multiple stepwise linear regression analysis was performed to identify potential influences on the effects of social media on eating behavior. RESULTS: EFA supported the one-factor structure, and the factor loadings of each item on this dimension were higher than 0.40. CFA showed good model fitness indexes. The content validity index of the scale was 0.94. The Cronbach's alpha coefficient and McDonald's Omega coefficient for the scale were 0.964, the split-half reliability coefficient was 0.953, and the test-retest reliability was 0.849. Gender, education, major, frequency of social media use, online sexual objectification experiences, fear of negative evaluations, and physical appearance perfectionism explained 73.8% of the variance in the effects of social media on eating behavior. CONCLUSIONS: The Chinese version of the SESMEB has good psychometric properties and is a valid measurement tool for assessing the effects of social media on college students' eating behavior. Subjects who were female, highly educated, non-medical, had frequent social media use, online sexual objectification experiences, fear of negative evaluations, and physical appearance perfectionism used social media to have a higher impact on eating behavior.


Asunto(s)
Conducta Alimentaria , Medios de Comunicación Sociales , Adolescente , Femenino , Humanos , Masculino , China , Psicometría/métodos , Reproducibilidad de los Resultados , Estudiantes , Encuestas y Cuestionarios , Pueblos del Este de Asia
19.
BMC Health Serv Res ; 24(1): 425, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570847

RESUMEN

BACKGROUND: This study aimed to investigate the turnover intention among nurses in eastern China and explore the association between turnover intention and personal characteristics, family factors, and work-related factors. METHODS: A total of 2504 nurses participated in a cross-sectional survey administered in 26 hospitals in Eastern China from October to November 2017. In December 2021, a survey was conducted on nurses who resigned between December 2017 and November 2021. RESULTS: The turnover intention score of in-service nurses was 15 (12-17), and 43% of nurses had a high turnover intention, which was mainly due to the following reasons: age < 40 years, raising two or more children, monthly income of USD786.10-1572.20 or < USD786.10, occupation was assigned or selected according to parental wishes, ≤ 1 or ≥ 2-night shifts per week, contractual or third-party personnel agents, full-time nurses with part-time jobs, and high job stress. Among 102 retired nurses, 80.4% reported family reasons for leaving, 39.2% for work reasons, and 21.6% for other personal reasons. CONCLUSION: Nurses' intention to leave their occupation is high in Eastern China. Age < 40 years old, > 1 child, low income, involuntary career selection, frequent night shifts, informal employment, part-time, and high job stress are significant factors associated with nurses' willingness to leave. Government and hospital administrators should consider ways to address these factors to retain nurses in hospitals in eastern China and improve the quality of nursing services.


Asunto(s)
Enfermeras y Enfermeros , Personal de Enfermería en Hospital , Estrés Laboral , Niño , Humanos , Adulto , Estudios Transversales , Intención , Satisfacción en el Trabajo , China , Encuestas y Cuestionarios , Reorganización del Personal
20.
Int J Qual Health Care ; 36(2)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38619120

RESUMEN

BACKGROUND: Falls were among the most common adverse nursing events. The incidence of falls in patients with neuropsychiatric disorders was high, and the occurrence of falls not only caused physical and psychological harm to patients but also led to medical disputes. Therefore, interventions for falls prevention were essential, but evaluations of the intervention process were lacking. METHODS: In this study, a process management program to prevent falls based on the "structure-process-outcome" quality evaluation model was designed and applied to the clinical practice of falls prevention in hospitalized patients with neuropsychiatric disorders. The process quality evaluation checklist to prevent falls was used to supervise the implementation effect of intervention measures to prevent falls, identify the problems in the intervention measures, and make continuous improvements, to reduce the incidence of falls in such hospitalized patients as the final index. RESULTS: The incidence of inpatient falls decreased from 0.199‰ (0.199 per 1000 patient-days) to 0.101‰ (0.101 per 1000 patient-days) before and after the implementation of the process management program for 12 months, 24 months, and 36 months, respectively, and the difference was statistically significant (P < .05). The probability of falls was reduced by 49% after 36 months of monitoring. Furthermore, the proportion of patients at high risk of falls exhibited a downward trend. CONCLUSION: This quality improvement program was feasible and effective at reducing falls in hospitalized patients with neuropsychiatric disorders. Therefore, attention should be given to monitoring process quality in the management of falls.


Asunto(s)
Accidentes por Caídas , Trastornos Mentales , Mejoramiento de la Calidad , Humanos , Accidentes por Caídas/prevención & control , Mejoramiento de la Calidad/organización & administración , Trastornos Mentales/terapia , Femenino , Hospitalización , Masculino , Incidencia , Pacientes Internos , Anciano , Persona de Mediana Edad , Lista de Verificación
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