Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 237
Filter
1.
PLoS One ; 19(6): e0304084, 2024.
Article in English | MEDLINE | ID: mdl-38900751

ABSTRACT

BACKGROUND: Depression is a common psychological problem in adolescents worldwide. Although the World Health Organization recommends that members of this population engage in physical activity to reduce depressive symptoms, compliance with this recommendation is often low. Furthermore, although behavioral activation (BA) is recommended as a treatment for adolescents with depression, the reported effect size is small. Compared with traditional exercises, gamified physical activity (GPA) can be particularly appealing to adolescents because it is perceived as an enjoyable experience. In this study, we integrated BA and GPA to create behavioral activation play therapy (BAPT). We designed a clinical trial to investigate the feasibility, acceptability, and effectiveness of this treatment in adolescents with depression. METHODS: This study is a randomized controlled trial (RCT) with a three-arm, assessor-blinded design, conducted to validate the effectiveness and applicability of BAPT for treating adolescent with depression. We will recruit 258 participants and randomly assign them to a BAPT group, BA group, or GPA group using a ratio of 1:1:1. Based on conventional strategies for treatment and care, the three groups will receive nine BAPT sessions, nine BA sessions, or nine GPA sessions, respectively. We will compare the outcomes of the BAPT with those of the BA and GPA interventions. DISCUSSION: This is the first RCT to explore the effectiveness and applicability of BAPT in adolescents with depression. This study will provide evidence that may help to decrease depressive symptoms in adolescents, and will demonstrate the treatment effectiveness in terms of increasing levels of physical activity, reducing the rate of non-suicidal self-injury behaviors, and improving sleep quality. We will also assess the presence of side effects and the treatment adherence of patients receiving BAPT. TRIAL REGISTRATION: Trial registration: Chinese Clinical Trial Registry, ChiCTR2300072671. Registered on 20 June 2023.


Subject(s)
Depression , Exercise , Humans , Adolescent , Depression/therapy , Depression/psychology , Male , Female , Exercise/psychology , Behavior Therapy/methods , Play Therapy/methods , Treatment Outcome , Randomized Controlled Trials as Topic
2.
Neurosci Bull ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874677

ABSTRACT

Preeclampsia is a serious obstetric complication. Currently, there is a lack of effective preventive approaches for this disease. Recent studies have identified transcutaneous auricular vagus nerve stimulation (taVNS) as a potential novel non-pharmaceutical therapeutic modality for preeclampsia. In this study, we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt. Our results showed that taVNS promoted the release of acetylcholine (ACh). ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS (mtROS), presumably through M3AChR. This reduced the release of pro-apoptotic proteins (cleaved caspase-3, NF-κB-p65, and cytochrome C) and helped preserve the morphological and functional integrity of mitochondria, thus reducing the apoptosis of placental trophoblasts, improving placental function, and relieving preeclampsia. Our study unravels the potential pathophysiological mechanism of preeclampsia. In-depth characterization of the UPRmt is essential for developing more effective therapeutic strategies for preeclampsia targeting mitochondrial function.

3.
Heliyon ; 10(11): e31804, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38845898

ABSTRACT

Background: Senecio cannabifolius Less. is a perennial herb belonging to the Compositae family that has been used in traditional medicine as an antitussive and expectorant for treating chronic bronchitis and acute respiratory infections. Traditionally, Feining Granules are prepared from water extracts of the raw plant material. However, the chemical composition and pharmacological mechanisms of Feining Granules have not been thoroughly investigated. Methods: A systematic strategy for the rapid detection and identification of the constituents of Feining Granules was developed using ultrahigh-performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry (MS) with parallel reaction monitoring. Results: Overall, 162 compounds, including flavonoids, alkaloids, organic acids, and others, were identified unambiguously and tentatively by comparing the retention times and MS fragmentation with reference standards and literature data. Ninety-nine of these were reported for the first time to the best of our knowledge. Network pharmacology suggests that Feining Granules can be used to treat chronic bronchitis as they contain active components associated with the ALB, VEGFA, and SRC target genes influenced by HIF-1, VEGF, and other signaling pathways. Conclusion: These results provide information that can help understand the effective substances of S. cannabifolius Less. and improve quality control.

4.
ChemSusChem ; : e202400832, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845094

ABSTRACT

The performance of zinc-air battery is constrained by the sluggish rate of oxygen electrode reaction, particularly under high current discharge conditions where the kinetic process of the oxygen reduction reaction (ORR) decelerates significantly. To address this challenge, we present a novel phase transition strategy that facilitates the creation of a heteroatom-doped heterointerface (CoN/CoS2). The meticulously engineered CoN/CoS2/NC electrocatalyst displays a superior ORR half-wave potential of 0.87 V and an OER overpotential of 320 mV at 10 mA cm-2. Experimental and computational analysis confirm that the CoN/CoS2 heterostructure optimizes local charge distribution, accelerates electron transfer, and tunes active sites for enhanced catalysis. Notably, this heterojunction improves stability by resisting corrosion and degradation under harsh alkaline conditions, thus demonstrating superior performance and longevity in a custom-made liquid zinc-air battery. This research provides valuable practical and theoretical foundations for designing efficient heterointerfaces in electrocatalysis applications.

5.
ACS Appl Mater Interfaces ; 16(22): 29439-29452, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38775098

ABSTRACT

Neural electrodes have recently been developed with surface modifications of conductive polymers, in particular poly(3,4-ethylenedioxythiophene) (PEDOT), and extensively studied for their roles in recording and stimulation, aiming to improve their biocompatibility. In this work, the implications for the design of practical neural sensors are clarified, and systematic procedures for their preparation are reported. In particular, this study introduces the use of in vitro double electrode experiments to mimic the responses of neural electrodes with a focus on signal-recording electrodes modified with PEDOT. Specifically, potential steps on one unmodified electrode in an array are used to identify the responses for PEDOT doped with different anions and compared with that of a bare platinum (Pt) electrode. The response is shown to be related to the rearrangement of ions in solution near the detector electrode resulting from the potential step, with a current transient seen at the detector electrode. A rapid response for PEDOT doped with chloride (ca. 0.04 s) ions was observed and attributed to the fast movement of chloride ions in and out of the polymer film. In contrast, PEDOT doped with poly(styrenesulfonate) (PSS) responds much slower (ca. 2.2 s), and the essential immobility of polyanion constrains the direction of current flow.

6.
Sci Total Environ ; 935: 173431, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38782283

ABSTRACT

Deep treatment and bioenergy recovery of swine wastewater (SW) are beneficial for constructing a low-carbon footprint and resource-recycling society. In this study, Fe (III) addition from 0 to 600 mg/L significantly increased the methane (CH4) content of the recovered biogas from 61.4 ± 2.0 to 89.3 ± 2.0 % during SW treatment in an anaerobic membrane digestion system. The specific methane yields (SMY) also increased significantly from 0.20 ± 0.05 to 0.29 ± 0.02 L/g COD. Fe (III) and its bio-transformed products which participated in establishing direct interspecific electron transfer (DIET), upregulated the abundance of e-pili and Nicotinamide adenine dinucleotide (NADH), enriched electroactive bacteria. The increase in cellular adenosine triphosphate (cATP) from 6583 to 14,518 ng/gVSS and electron transport system (ETS) from 1468 to 1968 mg/(g·h) promoted the intensity of energy flow and electron flow during anaerobic digestion of SW. Moreover, Fe (III) promoted the hydrolysis and acidification of organic matters, and strengthened the acetoacetic methanogenesis pathway. This study established an approach for harvesting high quality bioenergy from SW and revealed the effects and mechanisms from the view of carbon flow, energy metabolic intensity and metagenomics.


Subject(s)
Methane , Waste Disposal, Fluid , Wastewater , Waste Disposal, Fluid/methods , Animals , Swine , Methane/metabolism , Anaerobiosis , Energy Metabolism , Bioreactors , Carbon/metabolism , Biofuels , Iron/metabolism , Ferric Compounds
7.
Psych J ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38725387

ABSTRACT

Available evidence demonstrates that individuals with body-image disturbance (BID) are prone to suffer from depression. This systematic review provides, to our knowledge, the first synthesis of the psychological mechanism of the association between BID and depression. We conducted a thorough search of online databases, including PubMed, Web of Science, and PsycINFO, for articles published up until February 2024. The final analysis comprised a total of 23 studies that focused on the mediating or moderating effects of psychological factors between depression and BID. This review identifies self-esteem and social support as both mediators and moderators of the relationship between BID and depression, while perceived stress acted only as a mediator. High self-esteem and strong social support as well as low levels of perceived stress may help individuals experience lower levels of BID, thereby contributing to a decreased likelihood of depression. Interventions aimed at increasing self-esteem, developing strong support, and decreasing perceived stress may hold promise to reduce the risk of depression in those with BID.

8.
Comput Biol Chem ; 110: 108092, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38754259

ABSTRACT

The number of mitotic cells is an important indicator of grading invasive breast cancer. It is very challenging for pathologists to identify and count mitotic cells in pathological sections with naked eyes under the microscope. Therefore, many computational models for the automatic identification of mitotic cells based on machine learning, especially deep learning, have been proposed. However, converging to the local optimal solution is one of the main problems in model training. In this paper, we proposed a novel multilevel iterative training strategy to address the problem. To evaluate the proposed training strategy, we constructed the mitotic cell classification model with ResNet50 and trained the model with different training strategies. The results showed that the models trained with the proposed training strategy performed better than those trained with the conventional strategy in the independent test set, illustrating the effectiveness of the new training strategy. Furthermore, after training with our proposed strategy, the ResNet50 model with Adam optimizer has achieved 89.26% F1 score on the public MITOSI14 dataset, which is higher than that of the state-of-the-art methods reported in the literature.


Subject(s)
Mitosis , Humans , Breast Neoplasms/pathology , Deep Learning , Machine Learning
9.
Sci Rep ; 14(1): 11384, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762679

ABSTRACT

Land is the spatial background and basic carrier of human survival and development. The study of land function evaluation at different scales can promote the harmonious coexistence of humans and nature. Taking Fuping County, Hebei Province, China, as an example, this study establishes the theoretical framework of county-level land scale division using a digital elevation model (DEM)-based watershed analysis method and establishes the theory and methodological system of land function evaluation from the perspective of the characteristic scale. The multifunctionality of the land was evaluated using the Carnegie-Ames-Stanford approach (CASA), the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model and comprehensive index evaluation. By using the methods of DEM-based watershed analysis, dominant factor differentiation and layer superposition, a three-level scale system of 'subwatershed scale-land chain scale-land segment scale' and a multifunctional multiscale evaluation index system containing 18 evaluation indices were established. The single-function and multifunction evaluation results of land at different scales were obtained by the comprehensive index method and Getis-Ord Gi* index method. The accuracy of land function evaluation results mainly depends on the selection of the measurement scale. The land measurement scale determined by DEM-based watershed analysis is close to the intrinsic scale of land function evaluation. The scale effect of land function in different temporal and spatial ranges is also evident and shows obvious spatial heterogeneity and difference. At larger scales, individual functions show synergistic effects.

10.
Curr Res Food Sci ; 8: 100753, 2024.
Article in English | MEDLINE | ID: mdl-38725963

ABSTRACT

Camellia oleifera oil is a pure and natural high-grade oil prevalent in South China. Camellia oleifera oil is known for its richness in unsaturated fatty acids and high nutritional value. There is increasing evidence indicating that a diet rich in unsaturated fatty acids is beneficial to health. Despite the widespread production of Camellia oleifera oil and its bioactive components, reports on its nutritional components are scarce, especially regarding systematic reviews of extraction methods and biological functions. This review systematically summarized the latest research on the bioactive components and biological functions of Camellia oleifera oil reported over the past decade. In addition to unsaturated fatty acids, Camellia oleifera oil contains six main functional components contributing to its antioxidant, antibacterial, anti-inflammatory, antidiabetic, anticancer, neuroprotective, and cardiovascular protective properties. These functional components are vitamin E, saponins, polyphenols, sterols, squalene, and flavonoids. This paper reviewed the biological activity of Camellia oleifera oil and its extraction methods, laying a foundation for further development of its bioactive components.

11.
Angew Chem Int Ed Engl ; : e202408292, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38818627

ABSTRACT

Redox-active azo compounds are emerging as promising cathode materials due to their multi-electron redox capacity and fast redox response. However, their practical application is often limited by low output voltage and poor thermal stability. Herein, we use a heteroatomic substitution strategy to develop 4,4'-azopyridine. This modification results in a 350 mV increase in reduction potential compared to traditional azobenzene, increasing the energy density at the material level from 187 to 291 Wh kg-1. The introduced heteroatoms not only raise the melting point of azo compounds from 68 °C to 112 °C by forming an intermolecular hydrogen-bond network but also improves electrode kinetics by reducing energy band gaps. Moreover, 4,4'-azopyridine forms metal-ligand complexes with Zn2+ ions, which further self-assemble into a robust superstructure, acting as a molecular conductor to facilitate charge transfer. Consequently, the batteries display a good rate performance (192 mAh g-1 at 20 C) and an ultra-long lifespan of 60,000 cycles. Notably, we disclose that the depleted batteries spontaneously self-charge when exposed to air, marking a significant advancement in the development of self-powered aqueous systems.

12.
Clin Med Insights Oncol ; 18: 11795549241234637, 2024.
Article in English | MEDLINE | ID: mdl-38558880

ABSTRACT

Helicobacter pylori (H pylori), a gastric bacterium, has been extensively studied for its association with gastritis, peptic ulcers, and gastric cancer. However, recent evidence suggests its potential implications beyond the stomach, linking it to other gastrointestinal malignancies, such as esophageal cancer, liver cancer, pancreatic cancer, gallbladder cancer, and colorectal cancer. In light of the expanding research landscape and the increasing interest in exploring H pylori broader role in gastrointestinal tumorigenesis, this comprehensive review aims to elucidate the relationship between H pylori and gastrointestinal tumors. This review encompasses recent epidemiological studies, research progress, and emerging perspectives, providing a comprehensive assessment of the relationship between H pylori and gastrointestinal tumors. The findings highlight the captivating world of H pylori and its intricate involvement in gastrointestinal malignancies.

13.
BMC Med Genomics ; 17(1): 111, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678264

ABSTRACT

BACKGROUND: Statistical epistasis, or "gene-gene interaction" in genetic association studies, means the nonadditive effects between the polymorphic sites on two different genes affecting the same phenotype. In the genetic association analysis of complex traits, nevertheless, the researchers haven't found enough clues of statistical epistasis so far. METHODS: We developed a statistical model where the statistical epistasis was presented as an extra linkage disequilibrium between the polymorphic sites of different risk genes. The power of statistical test for identifying the gene-gene interaction was calculated and then compared in different hypothesis scenarios. RESULTS: Our results show the statistical power increases with the increasing of interaction coefficient, relative risk, and linkage disequilibrium with genetic markers. However, the power of interaction discovery is much lower than that of regular single-site association test. When rigorous criteria were employed in statistical tests, the identification of gene-gene interaction became a very difficult task. Since the criterion of significance was given to be p-value ≤ 5.0 × 10-8, the same as that of many genome-wide association studies, there is little chance to identify the gene-gene interaction in all kind of circumstances. CONCLUSIONS: The lack of epistasis tends to be an inevitable result caused by the statistical principles of methods in the genetic association studies and therefore is the inherent characteristic of the research itself.


Subject(s)
Epistasis, Genetic , Genome-Wide Association Study , Linkage Disequilibrium , Humans , Models, Genetic , Polymorphism, Single Nucleotide , Models, Statistical
14.
BMC Psychiatry ; 24(1): 331, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689265

ABSTRACT

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.


Subject(s)
Depressive Disorder, Major , Psychometrics , Humans , Adolescent , Male , Female , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Reproducibility of Results , Child , China , Factor Analysis, Statistical , Patient Health Questionnaire , Surveys and Questionnaires/standards , Psychiatric Status Rating Scales/standards , Sensitivity and Specificity , Asian People/psychology , East Asian People
15.
J Anim Sci Biotechnol ; 15(1): 42, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468340

ABSTRACT

BACKGROUND: The reproductive performance of chickens mainly depends on the development of follicles. Abnormal follicle development can lead to decreased reproductive performance and even ovarian disease among chickens. Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer. In recent years, the involvement of circRNAs in follicle development and atresia regulation has been confirmed. RESULTS: In the present study, we used healthy and atretic chicken follicles for circRNA RNC-seq. The results showed differential expression of circRALGPS2. It was then confirmed that circRALGPS2 can translate into a protein, named circRALGPS2-212aa, which has IRES activity. Next, we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1. CONCLUSIONS: Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.

17.
Adv Sci (Weinh) ; 11(20): e2307319, 2024 May.
Article in English | MEDLINE | ID: mdl-38502885

ABSTRACT

The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti-aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2-mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE-/- mice on a high-fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.


Subject(s)
Aortic Valve Stenosis , Calcinosis , Cellular Senescence , Flavonoids , Signal Transduction , Animals , Humans , Male , Mice , Aortic Valve/metabolism , Aortic Valve/pathology , Aortic Valve Stenosis/metabolism , Aortic Valve Stenosis/genetics , Aortic Valve Stenosis/pathology , Calcinosis/metabolism , Calcinosis/genetics , Cellular Senescence/drug effects , Cyclin D1/metabolism , Cyclin D1/genetics , Disease Models, Animal , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Osteogenesis/drug effects , Signal Transduction/drug effects , Transcription Factors/metabolism , Transcription Factors/genetics , Flavonoids/administration & dosage
18.
Langmuir ; 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38326982

ABSTRACT

In this work, the interaction performance of zwitterionic surfactant [dodecyl dimethyl sulfopropyl betaine (DSB-12) and hexadecyl dimethyl sulfopropyl betaine (DSB-16)] at the n-octadecane oil surface is investigated from experimental and simulation insights. For a macroscopic experiment, interfacial interferometry technology was developed for real-time monitor interaction performances and to obtain the quantitative interfacial thickness and mass results. The Langmuir model was characterized by thermodynamic analysis, deducing the aggregation spontaneity of DSB-16 > DSB-12 with ΔGagg(DSB-16) = -5.94 kJ mol-1 < ΔGagg(DSB-12) = 24.08 kJ mol-1. A three-step dynamic model (adsorption, arrangement, and aggregation) was characterized by kinetic analysis, indicating arrangement process as slow-limiting step with k2(arr) < k1(ads), k3(agg). For microscopic simulation, and molecular dynamic (MD) method was utilized to theoretically investigate interaction performances and obtain the interfacial configuration and energy results. The interaction stability and interaction strength were indicated to be DSB-16 > DSB-12 with differences of final energy ΔEfin = 48-88 kcal mol-1. The interaction mechanism was explained by proposing the model of "response enhancement" and "deposition activity" for DSB-16 interactions, and "response decrease" and "elution activity" for DSB-12 interactions. The different performances can be attributed to the different interaction forms and forces of surfactants. This work provided a platform for performance and mechanism investigation between the surfactant molecule and oil surface, which is of great significance in reservoir exploitation and enhanced oil recovery (EOR).

19.
Contemp Clin Trials Commun ; 38: 101263, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38304570

ABSTRACT

Introduction: Delirium is a common acute brain dysfunction syndrome in patients admitted to intensive care units (ICUs). Family engagement strategies, based on the theory of multi-sensory stimulation to ameliorate sensory deprivation in patients, may be an effective and scalable method to reduce the burden of delirium. Methods: /design: This is a assessor-blinded, randomised controlled trial of the feasibility of multi-sensory stimulation (MS) in patients with delirium. A total of 72 mechanically ventilated patients (n = 24 in each group) admitted to the ICU will be randomised to routine non-pharmacological delirium care (control), family multi-sensory stimulation and nurse multi-sensory stimulation groups. All participants except the control group will receive multi-sensory stimulation, including visual, auditory, tactile and kinesthetic stimulation, for 5 days. Our primary aim is to determine the feasibility of the study procedure (recruitment, eligibility, retention and attrition rates, appropriateness of clinical outcome measures), feasibility, acceptability and safety of the intervention (adverse events, satisfaction and other). Our secondary objective is to assess the preliminary efficacy of the MS protocol in reducing the incidence, duration and severity of delirium. Sedation levels and delirium severity will be assessed twice daily. Enrolled participants will be followed in hospital until death, discharge or up to 28 days after treatment. Ethics and dissemination: The current study was approved by the Ethics Review Board of Huazhong University of Science and Technology Union Shenzhen Hospital, China (KY-2023-031-01). The results of this study will be presented at scientific conferences and submitted for publication in peer-reviewed journals. Trial registration number: ChiCTR2300071457.

20.
Cancer Lett ; 585: 216693, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38301909

ABSTRACT

Necroptosis is a regulated necrotic cell death mechanism and plays a crucial role in the progression of cancers. However, the potential role and mechanism of necroptosis in colorectal cancer (CRC) has not been fully elucidated. In this study, we found that nuclear receptor subfamily 4 group A member 1 (NR4A1) was highly expressed in CRC cells treated with TNF-α, Smac mimetic, and z-VAD-FMK (TSZ). The depletion of NR4A1 significantly enhanced the sensitivity of CRC cells to TSZ-induced necroptosis, while NR4A1 overexpression suppressed these effects, as evidenced by the LDH assay, flow cytometry analysis of cell death, PI staining, and expression analysis of necrosome complexes (RIPK1, RIPK3, and MLKL). Moreover, NR4A1 deficiency made HT29 xenograft tumors sensitive to necroptotic cell death in vivo. Mechanistically, NR4A1 depletion promoted necroptosis activation in CRC through the RIG-I-like receptor pathway by interacting with DDX3. Importantly, the RIG-I pathway agonist poly(I:C) or inhibitor cFP abolished the effects of NR4A1 overexpression or suppression on necroptosis in CRC cells. Moreover, we observed that NR4A1 was highly expressed in CRC tissues and was associated with a poor prognosis. In conclusion, our results suggest that NR4A1 plays a critical role in modulating necroptosis in CRC cells and provide a new therapeutic target for CRC.


Subject(s)
Colorectal Neoplasms , Protein Kinases , Humans , Protein Kinases/metabolism , Necroptosis/physiology , Cell Death , Necrosis , Colorectal Neoplasms/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Apoptosis , Nuclear Receptor Subfamily 4, Group A, Member 1/genetics , Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...