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1.
Cardiovasc Res ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900927

RESUMEN

AIMS: MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear. METHODS AND RESULTS: Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the PI3 K/AKT pathway, enhancing platelet activation through activating the integrin αIIbß3-mediated outside-in signaling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease of platelet activity. CONCLUSIONS: Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.

2.
Childs Nerv Syst ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850295

RESUMEN

OBJECTIVE: The objective of this study was to explore the effect of intraoperative neurophysiological monitoring (IONM) on tethered spinal cord release in children. METHODS: The clinical data of 454 children with tethered cord syndrome who underwent surgery for tethered cord release were retrospectively analyzed. The children were divided into two groups: the non-IONM group and the IONM group. SPSS 26.0 software was used for statistical analysis. The evaluation indices included the effective rate and incidence of new neurological dysfunction. RESULTS: The short-term results showed that the effective rate of the non-IONM group was 14.8%, while that of the IONM group was 15.2%. Additionally, the incidence of new neurological dysfunction was 7.8% in the non-IONM group and 5.6% in the IONM group. However, there was no significant difference between the two groups (P > 0.05). The medium- to long-term follow-up had significant difference (P < 0.05), the response rate was 32.1% in the IONM group and 23.7% in the non-IONM group, and deterioration rates regarding neurological dysfunction were 3.3% in the IONM group and 8.5% in the non-IONM group. CONCLUSION: This study revealed that the use of IONM does not significantly improve the short-term treatment effect of patients undergoing surgery for tethered cord release or reduce the short-term incidence of postoperative new neurological dysfunction. However, the medium- to long-term prognoses of patients in the IONM group were better than those of patients in the non-IONM group.

3.
J Multidiscip Healthc ; 17: 2227-2237, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38751667

RESUMEN

Background: Home-based medical care services (HMCS) play a crucial role in China's response to an aging population. Given the scarcity of quantitative research on motivating medical staff in relevant institutions, this study aimed to explore the impact of institutional support on motivating the provision of HMCS. Methods: The medical staff involved in this study originated from seven community health service centers in Beijing. We utilized a self-designed questionnaire to conduct the survey, gathering socioeconomic information, institutional support for service delivery, as well as the frequency and types of services the respondents provided. Statistical analysis involved the one-way tests and multivariate regressions, and structural equation modeling (SEM) was employed to enhance the results obtained from the regression analysis. Results: A total of 673 valid questionnaires were considered, with 66.12% of respondents indicating their involvement in offering HMCS services and 51.86% reporting the provision of home-based treatment and care services. Upon adjusting for all covariates, multiple regression results highlighted that the establishment of a clear service pathway significantly influenced the motivation to provide services. Furthermore, the results obtained from SEM validated the findings derived from the regression analysis. Conclusion: Standardized institutional support is an essential means of bolstering the motivation of medical staff to provide HMCS and deserves heightened attention from health administrators.

4.
PLoS One ; 19(5): e0299097, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38809857

RESUMEN

As a new business model, E-commerce brings new changes to the global economy and society. So, can E-commerce development policies promote high-quality agricultural development? This article regards the pilot construction of national e-commerce demonstration cities as a quasi-natural experiment for the development of e-commerce. Based on the E-commerce pilot and economic and social development data of national prefecture-level cities from 2004 to 2018, the agricultural total factor productivity calculated by the Fare-Primont index method is used as the characterization of the quality of urban agricultural development, and an empirical model is constructed under the progressive Differences-in-Differences framework. This paper empirically tests the overall impact of E-commerce development on the high-quality development of agriculture and its sources, analyzes the heterogeneity and dynamics of the impact, and investigates the possible impact mechanism. The result shows that from the overall impact and its sources, the development of E-commerce in cities has a positive impact on the high-quality development of agriculture, and the impact is mainly due to its role in promoting technological innovation and economies of scale. From the perspective of heterogeneity, the larger the population size of a city, the more significant the level of e-conomic development or Internet development. From the perspective of the dynamic impact, the positive impact of e-commerce development becomes more significant over time. With the passage of time, the impact of E-commerce on high-quality agricultural development policies shows a trend of first increasing and then decreasing. Overall, this study provides empirical evidence for the rationality and effectiveness of policies and measures related to E-commerce to promote the high-quality development of agriculture.


Asunto(s)
Agricultura , Ciudades , Agricultura/métodos , China , Comercio , Humanos , Desarrollo Económico
5.
Neural Netw ; 178: 106403, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38815470

RESUMEN

The goal of multi-modal neural machine translation (MNMT) is to incorporate language-agnostic visual information into text to enhance the performance of machine translation. However, due to the inherent differences between image and text, these two modalities inevitably suffer from semantic mismatch problems. To tackle this issue, this paper adopts a multi-grained visual pivot-guided multi-modal fusion strategy with cross-modal contrastive disentangling to eliminate the linguistic gaps between different languages. By using the disentangled multi-grained visual information as a cross-lingual pivot, we can enhance the alignment between different languages and improve the performance of MNMT. We first introduce text-guided stacked cross-modal disentangling modules to progressively disentangle image into two types of visual information: MT-related visual and background information. Then we effectively integrate these two kinds of multi-grained visual elements to assist target sentence generation. Extensive experiments on four benchmark MNMT datasets are conducted, and the results demonstrate that our proposed approach achieves significant improvement over the other state-of-the-art (SOTA) approaches on all test sets. The in-depth analysis highlights the benefits of text-guided cross-modal disentangling and visual pivot-based multi-modal fusion strategies in MNMT. We release the code at https://github.com/nlp-mnmt/ConVisPiv-MNMT.

6.
Patient Educ Couns ; 124: 108282, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38593483

RESUMEN

OBJECTIVE: To quantify medical staff preferences for providing health education service in hospitals. METHODS: This study took medical staff in the department of internal medicine of hospitals in Beijing, China as the research subjects, and designed a discrete choice experiment (DCE) to investigate the health education service provision preferences of them. Through various methods, 8 attributes and corresponding levels were determined. An online survey was conducted among the medical staff of the sample hospitals from May to June 2023. Participants' preferences were analyzed using conditional logit and mixed logit models. RESULTS: Finally, 831 respondents completed the questionnaire, among which 600 cases passed the consistency test. All the attributes included in this study had an impact on medical staff' health education service preferences (P < 0.001). The most important one with the greatest impact on the health education service delivery behavior of the respondents was "department working atmosphere-encouraging health education" (ß = 4.062, P < 0.001). CONCLUSION: In this study, the departmental work atmosphere and performance bonuses emerged as crucial factors influencing the engagement of medical staff in health education work. PRACTICAL IMPLICATIONS: Hospitals should prioritize measures to improve the health education working atmosphere in departments to increase the enthusiasm of medical staff to provide services.


Asunto(s)
Conducta de Elección , Educación en Salud , Humanos , Masculino , Femenino , Encuestas y Cuestionarios , Adulto , China , Actitud del Personal de Salud , Beijing , Persona de Mediana Edad , Cuerpo Médico/psicología , Cuerpo Médico/educación
7.
BMC Public Health ; 24(1): 499, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365639

RESUMEN

BACKGROUND: Chronic kidney disease (CKD), often coexisting with various systemic disorders, may increase the risk of falls. Our study aimed to assess the prevalence and risk of falls among patients with CKD in China. METHODS: We included patients with/without CKD from China Health and Retirement Longitudinal Study (CHARLS). Our primary outcome was the occurrence of fall accidents within the past 2 years. To enhance the robustness of our findings, we employed a multivariable logistic regression model, conducted propensity score analysis, and applied an inverse probability-weighting model. RESULTS: A total of 12,658 participants were included, the prevalence of fall accident rates were 17.1% (2,028/11,837) among participants without CKD and 24.7% (203/821) among those with CKD. In the inverse probability-weighting model, participants with CKD exhibited higher fall accident rates (OR = 1.28, 95% CI: 1.08-1.53, p = 0.005 ). Sensitivity and subgroup analysis showed the results still stable. CONCLUSIONS: The population in China afflicted with CKD has a significantly heightened risk of experiencing falls, underscoring the crucial importance of intensifying efforts in assessing and preventing fall risks.


Asunto(s)
Insuficiencia Renal Crónica , Jubilación , Humanos , Estudios Longitudinales , Accidentes por Caídas , Insuficiencia Renal Crónica/epidemiología , China/epidemiología
8.
Math Biosci Eng ; 21(1): 1305-1320, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38303466

RESUMEN

Multimodal aspect term extraction (MATE) and multimodal aspect-oriented sentiment classification (MASC) are two crucial subtasks in multimodal sentiment analysis. The use of pretrained generative models has attracted increasing attention in aspect-based sentiment analysis (ABSA). However, the inherent semantic gap between textual and visual modalities poses a challenge in transferring text-based generative pretraining models to image-text multimodal sentiment analysis tasks. To tackle this issue, this paper proposes a self-adaptive cross-modal attention fusion architecture for joint multimodal aspect-based sentiment analysis (JMABSA), which is a generative model based on an image-text selective fusion mechanism that aims to bridge the semantic gap between text and image representations and adaptively transfer a textual-based pretraining model to the multimodal JMASA task. We conducted extensive experiments on two benchmark datasets, and the experimental results show that our model significantly outperforms other state of the art approaches by a significant margin.

9.
Inorg Chem ; 63(1): 416-430, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38101319

RESUMEN

Bismuth-based coordination complexes are advantageous over other metal complexes, as bismuth is the heaviest nontoxic element with high spin-orbit coupling and potential optoelectronics applications. Herein, four bismuth halide-based coordination complexes [Bi2Cl6(phen-thio)2] (1), [Bi2Br6(phen-thio)2] (2), [Bi2I6(phen-thio)2] (3), and [Bi2I6(phen-Me)2] (4) were synthesized, characterized, and subjected to detailed photophysical studies. The complexes were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and NMR studies. Spectroscopic analyses of 1-4 in solutions of different polarities were performed to understand the role of the organic and inorganic components in determining the ground- and excited-state properties of the complexes. The photophysical properties of the complexes were characterized by ground-state absorption, steady-state photoluminescence, microsecond time-resolved photoluminescence, and absorption spectroscopy. Periodic density functional theory (DFT) calculations were performed on the solid-state structures to understand the role of the organic and inorganic parts of the complexes. The studies showed that changing the ancillary ligand from chlorine (Cl) and bromine (Br) to iodine (I) bathochromically shifts the absorption band along with enhancing the absorption coefficient. Also, changing the halides (Cl, Br to I) affects the photoluminescent quantum yields of the ligand-centered (LC) emissive state without markedly affecting the lifetimes. The combined results confirmed that ground-state properties are strongly influenced by the inorganic part, and the lower-energy excited state is LC. This study paves the way to design novel bismuth coordination complexes for optoelectronic applications by rigorously choosing the ligands and bismuth salt.

10.
Small ; : e2308579, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38048537

RESUMEN

Chemical bath deposited (CBD) SnO2 is one of the most prevailing electron transport layers for realizing high-efficiency perovskite solar cells (PSCs) so far. However, the state-of-the-art CBD SnO2 process is time-consuming, contradictory to its prospect in industrialization. Herein, a simplified yet efficient method is developed for the fast deposition of SnO2 electrodes by incorporating a concentrated Sn source stabilized by the ethanol ligand with antimony (Sb) doping. The higher concentration of Sn source promotes the deposition rate, and Sb doping improves the hole-blocking capability of the CBD SnO2 layer so that its target thickness can be reduced to further save the deposition time. As a result, the deposition time can be appreciably reduced from 3-4 h to only 5 min while maintaining 95% of the maximum efficiency, indicating the power of the method toward high-throughput production of efficient PSCs. Additionally, the CBD SnO2 substrates are recyclable after removing the upper layers of complete PSCs, and the refurbished PSCs can maintain ≈98% of their initial efficiency after three recycling-and-fabrication processes.

11.
Front Pharmacol ; 14: 1243734, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37900164

RESUMEN

Background and aims: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality worldwide. Apoptosis of trophoblast cells induced by oxidative stress is a principal reason of placental injury in PE. 6-Gingerol, an antioxidant from ginger, plays an important role in many disease models, but its effect on obstetric diseases has not been elucidated. In this study, we investigated the protective effect of 6-gingerol against placental injury. Methods: In vitro hypoxia/reoxygenation (H/R) model of HTR8/Svneo cells and preeclamptic mice model were established to simulate PE. The effects of 6-Gingerol on PE were evaluated by morphological detection, biochemical analysis, and Western blot. Results: We found that H/R treatment induced cell apoptosis, increased the production of reactive oxygen species, malondialdehyde and lactate dehydrogenase, and decreased superoxide dismutase in trophoblast. In addition, the polarization of mitochondrial membrane potential and the cellular calcium flux were also destroyed under H/R condition, which also activated BCL2-interacting protein 3 (BNIP3) and provoked excessive mitophagy. Importantly, 6-Gingerol reversed these corrosive effects. Furthermore, the placenta damage in PE-like mouse caused by the cell apoptosis, oxidative stress and mitophagy was mitigated by 6-Gingerol. Conclusion: These findings suggest that 6-Gingerol exerts a protective effect against placental injury in PE by reducing oxidative stress and inhibiting excessive mitophagy caused by mitochondrial dysfunction.

12.
Commun Chem ; 6(1): 223, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37845500

RESUMEN

Polycyclic aromatic hydrocarbons are the main precursors to soot particles in combustion systems. A lack of direct experimental evidence has led to controversial theoretical explanations for the transition from gas-phase species to organic soot clusters. This work focuses on sampling infant soot particles from well-defined flames followed by analysis using state-of-the-art mass spectrometry. We found that PAH molecules present in soot particles are all stabilomers. Kinetic Monte Carlo simulations and thermodynamic stability calculations further identify the detected PAHs as peri-condensed and without aliphatic chains. Van der Waals forces can easily link PAHs of such size and shape to form PAH dimers and larger clusters under the specified flame conditions. Our results provide direct experimental evidence that soot inception is initiated by a physical process under typical flame conditions. This work improves our understanding of aerosol particulates, which has implications for their environmental and climate change impacts.

13.
Eur J Pediatr ; 182(11): 5095-5108, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37672063

RESUMEN

Obesity represents a risk factor for multiple coexisting conditions and complications. Liraglutide is mainly reserved for populations who fail to achieve weight loss goals with lifestyle changes alone. This study aims to systematically evaluate the safety and effectiveness of liraglutide in weight management in children and youth. A systematic search was performed of PubMed, Embase, Cochrane Library, and Web of Science from inception to February 23rd, 2023. Randomized controlled trials (RCTs) evaluating the effects of liraglutide in children and youth were included. All data analyses were performed using Review Manager 5.3 version. Seven eligible articles were finally included, covering a population of 547 participants. Liraglutide use was associated with reduced body weight (WMD: -2.13 kg; 95%CI: -4.23, -0.03), BMI (WMD: -1.56 kg/m2; 95% CI: -2.41, -0.7), and BMI SDS (WMD: -0.17; 95% CI: -0.26, -0.08). Similar associations were found in HbA1c (WMD: -0.29%; 95% CI: -0.52, -0.06) and fasting plasma glucose (SMD: -0.39; 95% CI: -0.64, -0.14). Subgroup analysis shows an improvement in HbA1c control only among children with type 2 diabetes (WMD: -1.06%; 95% CI: -1.44, -0.67). No differences were found in fasting serum insulin, SBP, DBP, HDL, LDL, and TG between liraglutide and placebo. In addition, no difference was found in the frequencies of adverse events, serious adverse events, and adverse events resulting in discontinuation of therapy between liraglutide and placebo treatment groups. CONCLUSION: Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents. WHAT IS KNOWN: • A few first-line treatment of these children and adolescents with overweight and obesity is a multi-component lifestyle intervention. • Lifestyle modifications are not suitable for all individuals, therefore, new treatment strategies urgent need to be established. WHAT IS NEW: • This is the first meta-analysis conducted to assess the efficacy and safety of liraglutide for weight management in children and adolescents. • Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents.


Asunto(s)
Hipoglucemiantes , Liraglutida , Adolescente , Niño , Humanos , Liraglutida/efectos adversos , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada , Ensayos Clínicos Controlados Aleatorios como Asunto , Obesidad
14.
Elife ; 122023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37737576

RESUMEN

Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in vivo and in vitro. We confirmed that PM2.5 induced adverse gestational outcomes such as increased fetal mortality rates, decreased fetal numbers and weight, damaged placental structure, and increased apoptosis of trophoblasts. Additionally, PM2.5 induced dysfunction of the trophoblast cell line HTR8/SVneo, including in its proliferation, apoptosis, invasion, migration and angiogenesis. Moreover, we comprehensively analyzed the transcriptional landscape of HTR8/SVneo cells exposed to PM2.5 through RNA-Seq and observed that PM2.5 triggered overexpression of pathways involved in oxidative stress and mitochondrial apoptosis to damage HTR8/SVneo cell biological functions through CYP1A1. Mechanistically, PM2.5 stimulated KLF9, a transcription factor identified as binding to CYP1A1 promoter region, which further modulated the CYP1A1-driven downstream phenotypes. Together, this study demonstrated that the KLF9/CYP1A1 axis played a crucial role in the toxic progression of PM2.5 induced adverse pregnancy outcomes, suggesting adverse effects of environmental pollution on pregnant females and putative targeted therapeutic strategies.


Asunto(s)
Placenta , Trofoblastos , Embarazo , Femenino , Humanos , Trofoblastos/metabolismo , Placenta/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/farmacología , Resultado del Embarazo , Estrés Oxidativo , Apoptosis , Movimiento Celular , Proliferación Celular , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo
15.
Nano Lett ; 23(19): 9143-9150, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37747809

RESUMEN

This study demonstrates an acetate ligand (AcO-)-assisted strategy for the controllable and tunable synthesis of colloidal methylammonium lead iodide (MAPbI3) perovskite nanocrystals (PNCs) for efficient photovoltaic and photodetector devices. The size of colloidal MAPbI3 PNCs can be tuned from 9 to 20 nm by changing the AcO-/MA ratio in the reaction precursor. In situ observations and detailed characterization results show that the incorporation of the AcO- ligand alters the formation of PbI6 octahedral cages, which controls PNC growth. A well-optimized AcO-/MA ratio affords MAPbI3 PNCs with a low defect density, a long carrier lifetime, and unique solid-state isotropic properties, which can be used to fabricate solution-processed dual-mode photovoltaic and photodetector devices with a conversion efficiency of 13.34% and a detectivity of 2 × 1011 Jones, respectively. This study provides an avenue to further the precisely controllable synthesis of hybrid PNCs for multifunctional optoelectronic applications.

16.
Neural Netw ; 166: 225-235, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37515902

RESUMEN

End-to-End aspect-based sentiment analysis (E2E-ABSA) aims to jointly extract aspect terms and identify their sentiment polarities. Although previous research has demonstrated that syntax knowledge can be beneficial for E2E-ABSA, standard syntax dependency parsing struggles to capture the block-level relation between aspect and opinion terms, which hinders the role of syntax in E2E-ABSA. To address this issue, this paper proposes a block-level dependency syntax parsing (BDEP) based model to enhance the performance of E2E-ABSA. BDEP is constructed by incorporating routine dependency syntax parsing and part-of-speech tagging, which enables the capture of block-level relations. Subsequently. the BDEP-guided interactive attention module (BDEP-IAM) is used to obtain the aspect-aware representation of each word. Finally the adaptive fusion module is leveraged to combine the semantic-syntactic representation to simultaneously extract the aspect term and identify aspect-orient sentiment polarity. The model is evaluated on five benchmark datasets, including Laptop14, Rest _ALL, Restaurant14, Restaurant15, and TWITTER, with F1 scores of 62.67%, 76.53%, 75.42%, 62.21%, and 58.03%, respectively. The results show that our model outperforms the other compared state-of-the-art (SOTA) methods on all datasets. Additionally, ablation experiments confirm the efficacy of BDEP and IAM in improving aspect-level sentiment analysis.


Asunto(s)
Semántica , Análisis de Sentimientos , Humanos , Habla
17.
Adv Mater ; 35(38): e2302839, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37391877

RESUMEN

Dual-interface modulation including buried interface as well as the top surface has recently been proven to be crucial for obtaining high photovoltaic performance in lead halide perovskite solar cells (PSCs). Herein, for the first time, the strategy of using functional covalent organic frameworks (COFs), namely HS-COFs for dual-interface modulation, is reported to further understand its intrinsic mechanisms in optimizing the bottom and top surfaces. Specifically, the buried HS-COFs layer can enhance the resistance against ultraviolet radiation, and more importantly, release the tensile strain, which is beneficial for enhancing device stability and improving the order of perovskite crystal growth. Furthermore, the detailed characterization results reveal that the HS-COFs on the top surface can effectively passivate the surface defects and suppress non-radiation recombination, as well as optimize the crystallization and growth of the perovskite film. Benefiting from the synergistic effects, the dual-interface modified devices deliver champion efficiencies of 24.26% and 21.30% for 0.0725 cm2 and 1 cm2 -sized devices, respectively. Moreover, they retain 88% and 84% of their initial efficiencies after aging for 2000 h under the ambient conditions (25 °C, relative humidity: 35-45%) and a nitrogen atmosphere with heating at 65 °C, respectively.

19.
Front Immunol ; 14: 1114620, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37122710

RESUMEN

Introduction: Gestational diabetes mellitus (GDM), a common complication of pregnancy, is risky for both mother and fetus. Previous studies about TP53-induced glycolysis and apoptosis regulator (TIGAR) focused on the occurrence and development of cancer, cardiovascular disease, and neurological disease, however, it is still unclear whether TIGAR plays a regulatory role in gestational diabetes mellitus (GDM). Methods: Utilizing HG exposure, we explored the role of TIGAR in oxidative stress limitation, excessive inflammatory toxicity defense, and pyroptosis prevention. Results: TIGAR was up-regulated in vivo and in vitro under HG condition, and loss of TIGAR increased ROS in trophoblast cells which drove a phenotypic switch and hindered the capacity of migration, invasion, and tube formation. This switch depended on the increased activation of NLRP3-ASC-caspase-1 signaling, which caused a distinctive characteristic of pyroptosis, and these findings could finally be reverted by antioxidant treatment (NAC) and receptor block (MCC950). Collectively, trophoblast pyroptosis is an upstream event of TIGAR deficiency-induced inflammation, which is promoted by ROS accumulation through NLRP3-ASC inflammasome. Conclusion: Taken together, our results uncovered that, as the upstream event of TIGAR deficiency-induced inflammation, pyroptosis is stimulated by ROS accumulation through NLRP3-ASC inflammasome.


Asunto(s)
Diabetes Gestacional , Inflamasomas , Humanos , Femenino , Embarazo , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Trofoblastos , Caspasa 1 , Especies Reactivas de Oxígeno , Proteínas Reguladoras de la Apoptosis/genética , Caspasas , Inflamación
20.
J Assist Reprod Genet ; 40(7): 1573-1587, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37227568

RESUMEN

PURPOSE: PE is a pregnancy-specific syndrome and one of the main causes of maternal, fetal, and neonatal mortality. PRDX1 is an antioxidant that regulates cell proliferation, differentiation, and apoptosis. The aim of this study is to investigate the effect of PRDX1 on the regulation of trophoblast function by affecting autophagy and oxidative stress in preeclampsia. METHODS: Western blotting, RT-qPCR, and immunofluorescence were used to examine the expression of PRDX1 in placentas. PRDX1-siRNA was transfected to knockdown PRDX1 in HTR-8/SVneo cells. The biological function of HTR-8/SVneo cells was detected by wound healing, invasion, tube formation, CCK-8, EdU, flow cytometry, and TUNEL assays. Western blotting was used to detect the protein expression of cleaved-Caspase3, Bax, LC3II, Beclin1, PTEN, and p-AKT. DCFH-DA staining was used to detect ROS levels by flow cytometry. RESULTS: PRDX1 was significantly decreased in placental trophoblasts in PE patients. Following the exposure of HTR-8/SVneo cells to H2O2, PRDX1 expression was significantly decreased, LC3II and Beclin1 expression was notably increased, and ROS level was also markedly increased. PRDX1 knockdown impaired migration, invasion, and tube-formation abilities and promoted apoptosis, which was accompanied by an increased expression of cleaved-Caspase3 and Bax. PRDX1 knockdown induced a significant decrease in LC3II and Beclin1 expression, along with an elevated p-AKT expression and a decreased PTEN expression. PRDX1 knockdown increased intracellular ROS levels, and NAC attenuated PRDX1 knockdown-induced apoptosis. CONCLUSION: PRDX1 regulated trophoblast function through the PTEN/AKT signaling pathway to affect cell autophagy and ROS level, which provided a potential target for the treatment of PE.


Asunto(s)
Preeclampsia , Trofoblastos , Recién Nacido , Humanos , Embarazo , Femenino , Trofoblastos/metabolismo , Placenta/metabolismo , Línea Celular , Proteínas Proto-Oncogénicas c-akt/genética , Proteína X Asociada a bcl-2 , Preeclampsia/genética , Preeclampsia/metabolismo , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Peroxirredoxinas/farmacología , Beclina-1/metabolismo , Beclina-1/farmacología , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular , Estrés Oxidativo/genética , Autofagia/genética , Apoptosis
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