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1.
Front Cardiovasc Med ; 11: 1388164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826816

RESUMO

Background: This study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization. Methods: This cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire. Results: This study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0-26) and 43.68 ± 6.01 (range: 21-50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000-5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2-3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2-3 months (OR = 3.342, P = 0.033) were independently associated with attitude. Conclusion: CAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

2.
Front Pharmacol ; 15: 1337883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828452

RESUMO

Background: The interaction between environmental endocrine-disrupting chemicals, such as Bisphenol A (BPA), and their influence on cancer progression, particularly regarding the GOLPH3 gene in colorectal cancer, remains unclear. Methods: We performed an integrated analysis of transcriptional profiling, clinical data, and bioinformatics analyses utilizing data from the Comparative Toxicogenomics Database and The Cancer Genome Atlas. The study employed ClueGO, Gene Set Enrichment Analysis, and Gene Set Variation Analysis for functional enrichment analysis, alongside experimental assays to examine the effects of BPA exposure on colorectal cancer cell lines, focusing on GOLPH3 expression and its implications for cancer progression. Results: Our findings demonstrated that BPA exposure significantly promoted the progression of colorectal cancer by upregulating GOLPH3, which in turn enhanced the malignant phenotype of colorectal cancer cells. Comparative analysis revealed elevated GOLPH3 protein levels in cancerous tissues versus normal tissues, with single-cell analysis indicating widespread GOLPH3 presence across various cell types in the cancer microenvironment. GOLPH3 was also associated with multiple carcinogenic pathways, including the G2M checkpoint. Furthermore, our investigation into the colorectal cancer microenvironment and genomic mutation signature underscored the oncogenic potential of GOLPH3, exacerbated by BPA exposure. Conclusion: This study provides novel insights into the complex interactions between BPA exposure and GOLPH3 in the context of colorectal cancer, emphasizing the need for heightened awareness and measures to mitigate BPA exposure risks. Our findings advocate for further research to validate these observations in clinical and epidemiological settings and explore potential therapeutic targets within these pathways.

3.
Cell Biol Int ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825780

RESUMO

Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis-related genes in CRC. The overexpression of GOLPH3 in Erastin-induced Caco-2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT-29 CRC cells. GOLPH3 induced the expression of prohibitin-1 (PHB1) and prohibitin-2 (PHB2), which also inhibited ferroptosis in Erastin-treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2) in Caco-2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2.

4.
Food Res Int ; 188: 114505, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823848

RESUMO

Consumers care about the texture of fresh fish flesh, but a rapid quantitative analytical method for this has not been properly established. In this study, texture-associated biomarkers were selected by DIA-based proteomics for possible future application. Results indicated a significant decline in texture and moisture characteristics with extended storage under chilled and iced conditions, and flesh quality was categorized into three intervals. A total of 8 texture-associated biomarkers were identified in the chilled storage group, and 3 distinct ones in the iced storage group. Biomarkers were further refined based on their expression levels. Isobutyryl-CoA dehydrogenase, mitochondrial and [Phosphatase 2A protein]-leucine-carboxy methyltransferase were identified as effective texture-associated biomarkers for chilled fish, and Staphylococcal nuclease domain-containing protein 1 for iced fish. This study provided suitable proteins as indicators of fresh fish flesh texture, which could help establish a rapid and convenient texture testing method in future studies.


Assuntos
Biomarcadores , Carpas , Proteínas de Peixes , Proteômica , Alimentos Marinhos , Animais , Carpas/metabolismo , Proteômica/métodos , Biomarcadores/análise , Proteínas de Peixes/metabolismo , Alimentos Marinhos/análise , Armazenamento de Alimentos/métodos
5.
J Colloid Interface Sci ; 672: 600-609, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38857568

RESUMO

Solar-light driven oxidation of benzylic alcohols over photocatalysts endows significant prospects in value-added organics evolution owing to its facile, inexpensive and sustainable process. However, the unsatisfactory performance of actual photocatalysts due to the inefficient charge separation, low photoredox potential and sluggish surface reaction impedes the practical application of this process. Herein, we developed an innovative Z-Scheme Cs3BiBr9 nanoparticles@porous C3N4 tubes (CBB-NP@P-tube-CN) heterojunction photocatalyst for highly selective benzyl alcohol oxidation. Such composite combining increased photo-oxidation potential, Z-Scheme charge migration route as well as the structural advantages of porous tubular C3N4 ensures the accelerated mass and ions diffusion kinetics, the fast photoinduced carriers dissociation and sufficient photoredox potentials. The CBB-NP@P-tube-CN photocatalyst demonstrates an exceptional performance for selective photo-oxidation of benzylic alcohol into benzaldehyde with 19, 14 and 3 times higher benzylic alcohols conversion rate than those of C3N4 nanotubes, Cs3Bi2Br9 and Cs3Bi2Br9@bulk C3N4 photocatalysts, respectively. This work offers a sustainable photocatalytic system based on lead-free halide perovskite toward large scale solar-light driven value-added chemicals production.

6.
BMC Plant Biol ; 24(1): 511, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844870

RESUMO

The invasion of Mikania micrantha by climbing and covering trees has rapidly caused the death of many shrubs and trees, seriously endangering forest biodiversity. In this study, M. micrantha seedlings were planted together with local tree species (Cryptocarya concinna) to simulate the process of M. micrantha climbing under the forest. We found that the upper part of the M. micrantha stem lost its support after climbing to the top of the tree, grew in a turning and creeping manner, and then grew branches rapidly to cover the tree canopy. Then, we simulated the branching process through turning treatment. We found that a large number of branches had been formed near the turning part of the M. micrantha stem (TP). Compared with the upper part of the main stem (UP), the contents of plant hormones (auxin, cytokinin, gibberellin), soluble sugars (sucrose, glucose, fructose) and trehalose-6-phosphate (T6P) were significantly accumulated at TP. Further combining the transcriptome data of different parts of the main stem under erect or turning treatment, a hypothetical regulation model to illustrate how M. micrantha can quickly cover trees was proposed based on the regulation of sugars and hormones on plant branching; that is, the lack of support after ascending the top of the tree led to turning growth of the main stem, and the enhancement of sugars and T6P levels in the TP may first drive the release of nearby dormant buds. Plant hormone accumulation may regulate the entrance of buds into sustained growth and maintain the elongation of branches together with sugars to successfully covering trees.


Assuntos
Espécies Introduzidas , Mikania , Árvores , Mikania/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/metabolismo
7.
SLAS Technol ; : 100149, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38796035

RESUMO

OBJECTIVE: This study aims to diagnose Rotator Cuff Tears (RCT) and classify the severity of RCT in patients with Osteoporosis (OP) through the analysis of shoulder joint anteroposterior (AP) X-ray-based localized proximal humeral bone mineral density (BMD) measurements and clinical information based on machine learning (ML) models. METHODS: A retrospective cohort of 89 patients was analyzed, including 63 with both OP and RCT (OPRCT) and 26 with OP only. The study analyzed a series of shoulder radiographs from April 2021 to April 2023. Grayscale values were measured after plotting ROIs based on AP X-rays of shoulder joint. Five kinds of ML models were developed and compared based on their performance in predicting the occurrence and severity of RCT from ROIs' greyscale values and clinical information (age, gender, advantage side, lumbar BMD, and acromion morphology (AM)). Further analysis using SHAP values illustrated the significant impact of selected features on model predictions. RESULTS: R1-6 had a positive correlation with BMD respectively. The nine variables, including greyscale R1-6, age, BMD, and AM, were used in the prediction models. The RF model was determined to be superior in effectively diagnosing RCT in OP patients, with high AUC scores of 0.998, 0.889, and 0.95 in the training, validation, and testing sets, respectively. SHAP values revealed that the most influential factors on the diagnostic outcomes were the grayscale values of all cancellous bones in ROIs. A column-line graph prediction model based on nine variables was constructed, and DCA curves indicated that RCT prediction in OP patients was favored based on this model. Furthermore, the RF model was also the most superior in predicting the types of RCT within the OPRCT group, with an accuracy of 86.364% and 73.684% in the training and test sets, respectively. SHAP values indicated that the most significant factor affecting the predictive outcomes was the AM, followed by the grayscale values of the greater tubercle, among others. CONCLUSIONS: ML models, particularly the RF algorithm, show significant promise in diagnosing RCT occurrence and severity in OP patients using conventional shoulder X-rays based on the nine variables. This method presents a cost-effective, accessible, and non-invasive diagnostic strategy that has the potential to substantially enhance the early detection and management of RCT in OP patient population.

8.
Nanoscale ; 16(21): 10448-10457, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38752569

RESUMO

With continuous advances in medical technology, non-invasive embolization has emerged as a minimally invasive treatment, offering new possibilities in cancer therapy. Fluorescent labeling can achieve visualization of therapeutic agents in vivo, providing technical support for precise treatment. This paper introduces a novel in situ non-invasive embolization composite material, Au NPs@(mPEG-PLGTs), created through the electrostatic combination of L-cysteine-modified gold nanoparticles (Au NPs) and methoxy polyethylene glycol amine-poly[(L-glutamic acid)-(L-tyrosine)] (mPEG-PLGTs). Experiments were undertaken to confirm the biocompatibility, degradability, stability and performance of this tumor therapy. The research results demonstrated a reduction in tumor size as early as the fifth day after the initial injection, with a significant 90% shrinkage in tumor volume observed after a 20-day treatment cycle, successfully inhibiting tumor growth and exhibiting excellent anti-tumor effects. Utilizing near-infrared in vivo imaging, Au NPs@(mPEG-PLGTs) displayed effective fluorescence tracking within the bodies of nude BALB-c mice. This study provides a novel direction for the further development and innovation of in situ non-invasive embolization in the field, highlighting its potential for rapid, significant therapeutic effects with minimal invasiveness and enhanced safety.


Assuntos
Ouro , Nanopartículas Metálicas , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis , Ouro/química , Animais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Embolização Terapêutica , Ácido Poliglutâmico/química , Ácido Poliglutâmico/análogos & derivados
9.
Mol Cancer ; 23(1): 111, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778348

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. METHODS: This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. RESULTS: Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). CONCLUSIONS: Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Animais , Camundongos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Prognóstico , Histona-Lisina N-Metiltransferase
10.
Langmuir ; 40(21): 11239-11250, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38751154

RESUMO

Water is the lifeblood of everything on earth, nourishing and nurturing all forms of life, while also contributing to the development of civilization. However, with the rapid development of economic construction, especially the accelerated process of modern industrialization, the pollution of oily sewage is becoming increasingly serious, affecting the ecological balance and human health. The efficient elimination of pollutants in sewage is, therefore, particularly urgent. In this paper, a core-shell microbial reactor (MPFA@CNF-SA-AM) was fabricated by using nanocellulose and sodium alginate (SA) particles embedded with microorganisms as the core and lipophilic and hydrophobic fly ash as the outer shell layer. Compared with that of free microorganisms and cellulose and SA aerogel pellets loading with microorganisms (CNF-SA-AM), which has a degradation efficiency of 60.69 and 82.89%, respectively, the MPFA@CNF-SA-AM possesses a highest degradation efficiency of 90.60% within 240 h. So that this self-floating microbial reactor has selective adsorption properties to achieve oil-water separation in oily wastewater and high effective degradation of organic pollutants with low cost. The adsorption curves of MPFA@CNF-SA-AM for diesel and n-hexadecane were studied. The results showed that the adsorption follows the Freundlich model and is a multimolecular layer of physical adsorption. In addition, the degradation mechanism of diesel oil was studied by gas chromatography-mass spectrometry. The results showed that diesel oil was selectively adsorbed to the interior of MPFA@CNF-SA-AM, and it was degraded by enzymes in microorganisms into n-hexadecanol, n-hexadecaldehyde, and n-hexadecanoic acid in turn, and finally converted to water and carbon dioxide. Compared with existing oily wastewater treatment methods, this green and pollution-free dual-functional core-shell microbial reactor has the characteristics of easy preparation, high efficiency, flexibility, and large-scale degradation. It provides a new, effective green choice for oily wastewater purification and on-site oil spill accidents.


Assuntos
Águas Residuárias , Adsorção , Águas Residuárias/química , Poluentes Químicos da Água/química , Alginatos/química , Celulose/química , Óleos/química , Biodegradação Ambiental , Polímeros/química
11.
Nat Plants ; 10(5): 815-827, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38745100

RESUMO

A comprehensive understanding of inflorescence development is crucial for crop genetic improvement, as inflorescence meristems give rise to reproductive organs and determine grain yield. However, dissecting inflorescence development at the cellular level has been challenging owing to a lack of specific marker genes to distinguish among cell types, particularly in different types of meristems that are vital for organ formation. In this study, we used spatial enhanced resolution omics-sequencing (Stereo-seq) to construct a precise spatial transcriptome map of the developing maize ear primordium, identifying 12 cell types, including 4 newly defined cell types found mainly in the inflorescence meristem. By extracting the meristem components for detailed clustering, we identified three subtypes of meristem and validated two MADS-box genes that were specifically expressed at the apex of determinate meristems and involved in stem cell determinacy. Furthermore, by integrating single-cell RNA transcriptomes, we identified a series of spatially specific networks and hub genes that may provide new insights into the formation of different tissues. In summary, this study provides a valuable resource for research on cereal inflorescence development, offering new clues for yield improvement.


Assuntos
Inflorescência , Meristema , Transcriptoma , Zea mays , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Inflorescência/genética , Inflorescência/crescimento & desenvolvimento , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/metabolismo , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica
12.
Front Cardiovasc Med ; 11: 1297218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694566

RESUMO

Introduction: To investigate the prognostic value of the consistency between the residual quantitative flow ratio (QFR) and postpercutaneous coronary intervention (PCI) QFR in patients undergoing revascularization. Methods: This was a single-center, retrospective, observational study. All enrolled patients were divided into five groups according to the ΔQFR (defined as the value of the post-PCI QFR minus the residual QFR): (1) Overanticipated group; (2) Slightly overanticipated group; (3) Consistent group; (4) Slightly underanticipated group; and (5) Underanticipated group. The primary outcome was the 5-year target vessel failure (TVF). Results: A total of 1373 patients were included in the final analysis. The pre-PCI QFR and post-PCI QFR were significantly different among the five groups. TVF within 5 years occurred in 189 patients in all the groups. The incidence of TVF was significantly greater in the underanticipated group than in the consistent group (P = 0.008), whereas no significant differences were found when comparing the underanticipated group with the other three groups. Restricted cubic spline regression analysis showed that the risk of TVF was nonlinearly related to the ΔQFR. A multivariate Cox regression model revealed that a ΔQFR≤ -0.1 was an independent risk factor for TVF. Conclusions: The consistency between the residual QFR and post-PCI QFR may be associated with the long-term prognosis of patients. Patients whose post-PCI QFR is significantly lower than the residual QFR may be at greater risk of TVF. An aggressive PCI strategy for lesions is anticipated to have less functional benefit and may not result in a better clinical outcome.

13.
Medicine (Baltimore) ; 103(19): e38042, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728482

RESUMO

Postmenopausal osteoporosis (PMOP) is a common metabolic inflammatory disease. In conditions of estrogen deficiency, chronic activation of the immune system leads to a hypo-inflammatory phenotype and alterations in its cytokine and immune cell profile, although immune cells play an important role in the pathology of osteoporosis, studies on this have been rare. Therefore, it is important to investigate the role of immune cell-related genes in PMOP. PMOP-related datasets were downloaded from the Gene Expression Omnibus database. Immune cells scores between high bone mineral density (BMD) and low BMD samples were assessed based on the single sample gene set enrichment analysis method. Subsequently, weighted gene co-expression network analysis was performed to identify modules highly associated with immune cells and obtain module genes. Differential analysis between high BMD and low BMD was also performed to obtain differentially expressed genes. Module genes are intersected with differentially expressed genes to obtain candidate genes, and functional enrichment analysis was performed. Machine learning methods were used to filter out the signature genes. The receiver operating characteristic (ROC) curves of the signature genes and the nomogram were plotted to determine whether the signature genes can be used as a molecular marker. Gene set enrichment analysis was also performed to explore the potential mechanism of the signature genes. Finally, RNA expression of signature genes was validated in blood samples from PMOP patients and normal control by real-time quantitative polymerase chain reaction. Our study of PMOP patients identified differences in immune cells (activated dendritic cell, CD56 bright natural killer cell, Central memory CD4 T cell, Effector memory CD4 T cell, Mast cell, Natural killer T cell, T follicular helper cell, Type 1 T-helper cell, and Type 17 T-helper cell) between high and low BMD patients. We obtained a total of 73 candidate genes based on modular genes and differential genes, and obtained 5 signature genes by least absolute shrinkage and selection operator and random forest model screening. ROC, principal component analysis, and t-distributed stochastic neighbor embedding down scaling analysis revealed that the 5 signature genes had good discriminatory ability between high and low BMD samples. A logistic regression model was constructed based on 5 signature genes, and both ROC and column line plots indicated that the model accuracy and applicability were good. Five signature genes were found to be associated with proteasome, mitochondria, and lysosome by gene set enrichment analysis. The real-time quantitative polymerase chain reaction results showed that the expression of the signature genes was significantly different between the 2 groups. HIST1H2AG, PYGM, NCKAP1, POMP, and LYPLA1 might play key roles in PMOP and be served as the biomarkers of PMOP.


Assuntos
Biomarcadores , Densidade Óssea , Osteoporose Pós-Menopausa , Humanos , Feminino , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/imunologia , Densidade Óssea/genética , Biomarcadores/sangue , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos , Curva ROC , Idoso , Aprendizado de Máquina
14.
Cell Mol Life Sci ; 81(1): 182, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38615283

RESUMO

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.


Assuntos
Células-Tronco Embrionárias , Células-Tronco Neurais , Animais , Camundongos , Estudos Prospectivos , Diferenciação Celular/genética , Carcinogênese/genética , Transformação Celular Neoplásica , Apoptose/genética , Proliferação de Células/genética
15.
Int J Biol Macromol ; 268(Pt 2): 131911, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679263

RESUMO

Starch is a common ingredient to improve gel property of freshwater fish surimi, but the function of natural starch to mask fishy odor compounds in surimi products has not been investigated systematacially. Therefore, this study aimed to determine which natural starch could effectively mask fishy odor compounds and clarify their interaction by GC-MS, FT-IR spectroscopy, raman spectroscopy, X-ray diffraction, scanning electron microscopy and 13C nuclear magnetic resonance. The results showed that when the concentration, crystal type, amylose content, and dispersion degree of starch was 1 %, type C, 48 % (w/v), and 200 mesh with 0.88 span, the starch had the strongest masking effect on typical fishy odor compounds, namely hexanal, 1-Octen-3-ol, (E,E)-2,4-Heptadienal and (E)-2-Octenal. It indicated that complexation and hydrogen bonding both occurred between the fishy odor compounds and starch.


Assuntos
Odorantes , Amido , Odorantes/análise , Amido/química , Animais , Peixes , Amilose/química , Amilose/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Aldeídos/química
16.
Am J Physiol Cell Physiol ; 326(6): C1697-C1709, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38586875

RESUMO

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study used APP/PS1 mice as an animal model of AD and amyloid-ß (Aß)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aß deposition in mice and apoptosis, respectively. Protein expression was assessed by Western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of Sirt4. Subsequently, the binding of transcription factors to Sirt4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aß-treated HT-22 cells compared with their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aß deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD.NEW & NOTEWORTHY The study reveals that in Alzheimer's disease models, SIRT4 expression increases, contributing to neuronal apoptosis and amyloid-ß deposition. Reducing SIRT4 lessens apoptosis and amyloid-ß accumulation, improving memory in mice. This process involves the mTOR pathway, regulated by STAT2 transcription factor. These findings suggest targeting the STAT2-SIRT4-mTOR axis as a potential Alzheimer's treatment strategy.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Apoptose , Modelos Animais de Doenças , Camundongos Transgênicos , Neurônios , Fator de Transcrição STAT2 , Transdução de Sinais , Sirtuínas , Serina-Treonina Quinases TOR , Animais , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Sirtuínas/metabolismo , Sirtuínas/genética , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Neurônios/metabolismo , Neurônios/patologia , Fator de Transcrição STAT2/metabolismo , Fator de Transcrição STAT2/genética , Peptídeos beta-Amiloides/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Linhagem Celular , Proteínas Mitocondriais
17.
Cancer Cell Int ; 24(1): 144, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654350

RESUMO

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Toxoplasma gondii (T. gondii) has shown anticancer activity in breast cancer mouse models, and exerted beneficial effect on the survival of breast cancer patients, but the mechanism was unclear. METHODS: The effect of tachyzoites of T. gondii (RH and ME49 strains) on human breast cancer cells (MCF-7 and MDA-MB-231 cells) proliferation and migration was assessed using cell growth curve and wound healing assays. Dual RNA-seq was performed for T. gondii-infected and non-infected cells to determine the differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction Networks analysis (PPI) were performed to explore the related signaling pathway and hub genes. Hub genes were validated using the Kaplan-Meier plotter database, and Pathogen Host Interaction (PHI-base) database. The results were verified by qRT-PCR. RESULTS: The tachyzoites of T. gondii decreased the expression of Ki67 and increased the expression of E-cadherin, resulting in suppressing the proliferation and migration of infected human breast cancer cells. The inhibitory effect of T. gondii on breast cancer cells showed a significant dose-response relationship. Compared with the control group, 2321 genes were transcriptionally regulated in MCF-7 cells infected with T. gondii, while 169 genes were transcriptionally regulated in infected MDA-MB-231 cells. Among these genes, 698 genes in infected MCF-7 cells and 67 genes in infected MDA-MB-231 cells were validated by the publicly available database. GO and KEGG analyses suggested that several pathways were involved in anticancer function of T. gondii, such as ribosome, interleukin-17 signaling, coronavirus disease pathway, and breast cancer pathway. BRCA1, MYC and IL-6 were identified as the top three hub genes in infected-breast cancer cells based on the connectivity of PPI analysis. In addition, after interacting with breast cancer cells, the expression of ROP16 and ROP18 in T. gondii increased, while the expression of crt, TgIST, GRA15, GRA24 and MIC13 decreased. CONCLUSIONS: T. gondii transcriptionally regulates several signaling pathways by altering the hub genes such as BRCA1, MYC and IL-6, which can inhibit the breast tumor growth and migration, hinting at a potential therapeutic strategy.

18.
Signal Transduct Target Ther ; 9(1): 104, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654010

RESUMO

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Fator 7 de Crescimento de Fibroblastos , Ilhotas Pancreáticas , Organoides , Animais , Humanos , Masculino , Camundongos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/genética , COVID-19/metabolismo , COVID-19/virologia , COVID-19/patologia , Fator 7 de Crescimento de Fibroblastos/genética , Fator 7 de Crescimento de Fibroblastos/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Secreção de Insulina/genética , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/virologia , Ilhotas Pancreáticas/patologia , Organoides/virologia , Organoides/metabolismo , Organoides/patologia , SARS-CoV-2/genética
19.
Colloids Surf B Biointerfaces ; 238: 113888, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599077

RESUMO

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.


Assuntos
Gálio , Gálio/química , Humanos , Neoplasias/tratamento farmacológico , Terapia Fototérmica/métodos , Animais
20.
Int J Mol Sci ; 25(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38674036

RESUMO

CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases.


Assuntos
Quimiocina CX3CL1 , Viroses , Quimiocina CX3CL1/metabolismo , Humanos , Viroses/metabolismo , Viroses/imunologia , Viroses/virologia , Animais , COVID-19/virologia , COVID-19/metabolismo , COVID-19/imunologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Microglia/metabolismo , Microglia/virologia , Receptor 1 de Quimiocina CX3C/metabolismo , Receptor 1 de Quimiocina CX3C/genética
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