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1.
Exp Neurol ; 378: 114822, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38823676

RESUMEN

Post-stroke depression (PSD) is a complication of cerebrovascular disease, which can increase mortality after stroke. CRH is one of the main signaling peptides released after activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. It affects synaptic plasticity by regulating inflammation, oxidative stress and autophagy in the central nervous system. And the loss of spines exacerbates depression-like behavior. Therefore, synaptic deficits induced by CRH may be related to post-stroke depression. However, the underlying mechanism remains unclear. The Keap1-Nrf2 complex is one of the core components of the antioxidant response. As an autophagy associated protein, p62 participates in the Keap1-NrF2 pathway through its Keap1 interaction domain. Oxidative stress is involved in the feedback regulation between Keap1-Nrf2 pathway and p62.However, whether the relationship between CRH and the Keap1-Nrf2-p62 pathway is involved in PSD remains unknown. This study found that serum levels of CRH in 22 patients with PSD were higher than those in healthy subjects. We used MCAO combined with CUMS single-cage SD rats to establish an animal model of PSD. Animal experiments showed that CRHR1 antagonist prevented synaptic loss in the hippocampus of PSD rats and alleviated depression-like behavior. CRH induced p62 accumulation in the prefrontal cortex of PSD rats through CRHR1. CRHR1 antagonist inhibited Keap1-Nrf2-p62 pathway by attenuating oxidative stress. In addition, we found that abnormal accumulation of p62 induces PSD. It alleviates depression-like behavior by inhibiting the expression of p62 and promoting the clearance of p62 in PSD rats. These findings can help explore the pathogenesis of PSD and design targeted treatments for PSD.

2.
Heliyon ; 10(10): e31108, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38826749

RESUMEN

The fabrication of highly efficient yet stable noble-metal-free bifunctional electrocatalysts that can simultaneously catalyse both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) remains challenging. Herein, we employ the heterostructure coupling strategy, showcasing an aerosol-assisted chemical vapour deposition (AACVD) aided synthetic approach for the in-situ growth of cobalt molybdenum sulphide nanocomposites on carbon paper (CoMoS@CP) as a bifunctional electrocatalyst. The AACVD allows the rational incorporation of Co in the Mo-S binary structure, which modulates the morphology of CoMoS@CP, resulting in enhanced HER activity (ŋ10 = 171 mV in acidic and ŋ10 = 177 mV in alkaline conditions). Furthermore, the CoS2 species in the CoMoS@CP ternary structure extends the OER capability, yielding an ŋ100 of 455 mV in 1 M KOH. Lastly, we found that the synergistic effect of the Co-Mo-S interface elevates the bifunctional performance beyond binary counterparts, achieving a low cell voltage (1.70 V at 10 mA cm-2) in overall water splitting test and outstanding catalytic stability (∼90 % performance retention after 50-/30-h continuous operation at 10 and 100 mA cm-2, respectively). This work has opened up a new methodology for the controllable synthesis of self-supported transition metal-based electrocatalysts for applications in overall water splitting.

3.
Nat Prod Res ; : 1-7, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832674

RESUMEN

Five new sesquiterpenoids, (4S, 5S, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (1), (4S, 5 R, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (2), 6-O-propionyl-britannilactone (3), 1ß-hydroxy-3α-acetoxyeudesma-11(13)-en-12,8ß-olide (4) and 1ß,5ß-dihydroxyeudesma-11(13)-en-12,8ß-olide (5), along with twelve known ones were isolated from the flowers of Pentanema britannicum (L.) D.Gut.Larr. Among them, compounds 1 and 2 were stereoisomers which belong to 1,10-seco-eudesmane sesquiterpenoid with rare double bond between C-10 and C-14. The structures of the isolated compounds were elucidated by various spectroscopic methods, including 1D and 2D NMR experiments.

4.
Health Commun ; : 1-10, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693691

RESUMEN

Pornography is spreading more and more widely due to websites, applications, and social media. It has attracted the attention of a large number of researchers who are sometimes divided on the impact of pornography. However, the relationship between pornography and sexual violence myths has received little scholarly attention in China. Based on the 3AM model and previous research, the study examined hostile sexism (HS) as a mediator and perceived realism as a moderator in the links between pornography use frequency and sexual violence myths in a sample of Chinese men (N = 376). The results showed that although pornography use and sexual violence myths did not directly correlate with one another, there was an indirect correlation through HS. Further, perceived realism moderated the relationship between pornography use frequency and HS. When participants' perceived realism was high (i.e. +1 SD), the indirect effect of HS was strong; when participants' perceived realism was low (i.e. -1 SD), the indirect effect of HS was not significant. Taken together, the findings reveal the cross-cultural consistency of the 3AM theory in China, and the findings provide new insight into the potential impact of pornography on sexism. At the same time, the results suggest an increase in appropriate education and interventions to reduce the incidence of sexual violence.

5.
Heliyon ; 10(9): e29883, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38699036

RESUMEN

Background: Labor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns. Methods: In this prospective cohort study, parturients aged 25-35 years with a gestational age of 37-42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models. Results: We showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and ß-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (ß = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (ß = -449.36, adjusted P = 0.015), P. aeruginosa (ß = -192.55, adjusted P = 0.008), or S. maltophilia (ß = -142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (ß = -2702.77, adjusted P = 0.003) in neonates. Conclusion: LEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.

6.
Front Nutr ; 11: 1342113, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721026

RESUMEN

Background: Sarcopenia, a condition characterized by diminished skeletal muscle mass, strength, and function, accompanied by inflammation and oxidative stress, remains an area of limited exploration concerning its correlation with the Oxidative Balance Score (OBS). Methods: Leveraging data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES), we meticulously examined 16 dietary and four lifestyle factors to derive the OBS. Adjusting appendicular skeletal muscle mass (ASM) by body mass index (BMI) served as the designated marker for sarcopenia. To scrutinize the association between OBS and sarcopenia, we conducted weighted logistic regression and engaged in sensitivity analysis. Furthermore, we implemented subgroup analysis and interaction tests to gain comprehensive insights into the relationship across diverse populations. Results: In a sample comprising 6,677 individuals aged 20-59, logistic regression illuminated a negative association between OBS and sarcopenia [OR = 0.942 (0.920, 0.964), p < 0.001]. Robust associations were also discerned between diseases and both dietary and lifestyle OBS. Subgroup analysis unveiled a more pronounced negative association in older, married/living with partner or more educated individuals. Moreover, this association persisted in populations grappling with comorbidities such as hypertension, diabetes, cancer, and arthritis. Conclusion: Our study posits a perceptible link between OBS and the prevalence of sarcopenia among American adults.

7.
J Nanobiotechnology ; 22(1): 227, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711078

RESUMEN

BACKGROUND: Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes. RESULTS: In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia. CONCLUSIONS: CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy.


Asunto(s)
Chlorella , Portadores de Fármacos , Fotosíntesis , Animales , Ratones , Línea Celular Tumoral , Portadores de Fármacos/química , Humanos , Terapia Combinada , Fotoquimioterapia/métodos , Neoplasias/terapia , Antineoplásicos/farmacología , Ratones Endogámicos BALB C , Sistemas de Liberación de Medicamentos/métodos , Verde de Indocianina/farmacocinética , Verde de Indocianina/química , Femenino
8.
iScience ; 27(5): 109766, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38711448

RESUMEN

Swift and accurate diagnosis for earlier-stage monkeypox (mpox) patients is crucial to avoiding its spread. However, the similarities between common skin disorders and mpox and the need for professional diagnosis unavoidably impaired the diagnosis of earlier-stage mpox patients and contributed to mpox outbreak. To address the challenge, we proposed "Super Monitoring", a real-time visualization technique employing artificial intelligence (AI) and Internet technology to diagnose earlier-stage mpox cheaply, conveniently, and quickly. Concretely, AI-mediated "Super Monitoring" (mpox-AISM) integrates deep learning models, data augmentation, self-supervised learning, and cloud services. According to publicly accessible datasets, mpox-AISM's Precision, Recall, Specificity, and F1-score in diagnosing mpox reach 99.3%, 94.1%, 99.9%, and 96.6%, respectively, and it achieves 94.51% accuracy in diagnosing mpox, six like-mpox skin disorders, and normal skin. With the Internet and communication terminal, mpox-AISM has the potential to perform real-time and accurate diagnosis for earlier-stage mpox in real-world scenarios, thereby preventing mpox outbreak.

9.
Burns Trauma ; 12: tkae015, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38752203

RESUMEN

Background: Chronic skin wounds are a leading cause of hospital admissions and reduced life expectancy among older people and individuals with diabetes. Delayed wound healing is often attributed to a series of cellular abnormalities. Matrine, a well-studied component found in Sophora flavescens, is recognized for its anti-inflammatory effects. However, its impact on wound healing still remains uncertain. This study aims to explore the potential of matrine in promoting wound healing. Methods: In this study, we utilized gradient extrusion to produce fibroblast-derived exosome-mimetic vesicles as carriers for matrine (MHEM). MHEM were characterized using transmission electron microscopy and dynamic light scattering analysis. The therapeutic effect of MHEM in wound healing was explored in vitro and in vivo. Results: Both matrine and MHEM enhanced the cellular activity as well as the migration of fibroblasts and keratinocytes. The potent anti-inflammatory effect of matrine diluted the inflammatory response in the vicinity of wounds. Furthermore, MHEM worked together to promote angiogenesis and the expression of transforming growth factor ß and collagen I. MHEM contained growth factors of fibroblasts that regulated the functions of fibroblasts, keratinocytes and monocytes, which synergistically promoted wound healing with the anti-inflammatory effect of matrine. Conclusions: MHEM showed enhanced therapeutic efficacy in the inflammatory microenvironment, for new tissue formation and angiogenesis of wound healing.

10.
Technol Health Care ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38759051

RESUMEN

BACKGROUND: In recent years, hyperuricemia and acute gouty arthritis have become increasingly common, posing a serious threat to public health. Current treatments primarily involve Western medicines with associated toxic side effects. OBJECTIVE: This study aims to investigate the therapeutic effects of total flavones from Prunus tomentosa (PTTF) on a rat model of gout and explore the mechanism of PTTF's anti-gout action through the TLR4/NF-κB signaling pathway. METHODS: We measured serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) levels using an enzyme-linked immunosorbent assay (ELISA). Histopathological changes were observed using HE staining, and the expression levels of relevant proteins were detected through Western blotting. RESULTS: After PTTF treatment, all indicators improved significantly. PTTF reduced blood levels of UA, Cr, BUN, IL-1ß, IL-6, and TNF-α, and decreased ankle swelling. CONCLUSIONS: PTTF may have a therapeutic effect on animal models of hyperuricemia and acute gouty arthritis by reducing serum UA levels, improving ankle swelling, and inhibiting inflammation. The primary mechanism involves the regulation of the TLR4/NF-κB signaling pathway to alleviate inflammation. Further research is needed to explore deeper mechanisms.

11.
Acta Pharmacol Sin ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760544

RESUMEN

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

13.
Nat Commun ; 15(1): 4127, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750080

RESUMEN

Stress granules (SGs) are induced by various environmental stressors, resulting in their compositional and functional heterogeneity. SGs play a crucial role in the antiviral process, owing to their potent translational repressive effects and ability to trigger signal transduction; however, it is poorly understood how these antiviral SGs differ from SGs induced by other environmental stressors. Here we identify that TRIM25, a known driver of the ubiquitination-dependent antiviral innate immune response, is a potent and critical marker of the antiviral SGs. TRIM25 undergoes liquid-liquid phase separation (LLPS) and co-condenses with the SG core protein G3BP1 in a dsRNA-dependent manner. The co-condensation of TRIM25 and G3BP1 results in a significant enhancement of TRIM25's ubiquitination activity towards multiple antiviral proteins, which are mainly located in SGs. This co-condensation is critical in activating the RIG-I signaling pathway, thus restraining RNA virus infection. Our studies provide a conceptual framework for better understanding the heterogeneity of stress granule components and their response to distinct environmental stressors.


Asunto(s)
ADN Helicasas , Proteínas de Unión a Poli-ADP-Ribosa , ARN Helicasas , Proteínas con Motivos de Reconocimiento de ARN , Transducción de Señal , Gránulos de Estrés , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Ubiquitinación , Humanos , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Gránulos de Estrés/metabolismo , ARN Helicasas/metabolismo , ADN Helicasas/metabolismo , Proteína 58 DEAD Box/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Inmunidad Innata , ARN Bicatenario/metabolismo , Células HEK293 , Células HeLa , Gránulos Citoplasmáticos/metabolismo , Infecciones por Virus ARN/virología , Infecciones por Virus ARN/metabolismo , Infecciones por Virus ARN/inmunología , Receptores Inmunológicos/metabolismo
14.
Behav Brain Res ; : 115064, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38777261

RESUMEN

Post-stroke depression (PSD) is one of the most common mental sequelae after a stroke and can damage the brain. Although PSD has garnered increasing attention in recent years, the precise mechanism remains unclear. Studies have indicated that the expression of DAPK1 is elevated in various neurodegenerative conditions, including depression, ischemic stroke, and Alzheimer's disease. However, the specific molecular mechanism of DAPK1-mediated cognitive dysfunction and neuronal apoptosis in PSD rats is unclear. In this study, we established a rat model of PSD, and then assessed depression-like behaviors and cognitive dysfunction in rats using behavioral tests. In addition, we detected neuronal apoptosis and analyzed the expression of DAPK1 protein and proteins related to the ERK/CREB/BDNF signaling pathway. The findings revealed that MCAO combined with CUMS can induce more severe depression-like behaviors and cognitive dysfunction in rats, while overexpression of DAPK1 may hinder the downstream ERK/CREB/BDNF signaling pathways, resulting in neuronal loss and exacerbation of brain tissue damage. In this study, we will focus on DAPK1 and explore its role in PSD.

15.
JMIR Aging ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38771907

RESUMEN

BACKGROUND: Duration of sleep has a crucial role in the development of physiological functions that impact health. Little is known about the associations between sleep duration and functional disability among the older adults in China. OBJECTIVE: This study aims to explore the associations between sleep duration and functional disabilities in the older population aged 65 years and above in China. METHODS: The data for this cross-sectional study were gathered from respondents aged 65 years and above who participated in the 2018 survey of China Health and Retirement Longitudinal Study, an ongoing nationwide longitudinal investigation of Chinese adults. The duration of sleep per night was obtained through face-to-face interviews. Functional disability was assessed using activities of daily living (ADL) and instrumental activities of daily living (IADL). The association between sleep duration and functional disability was assessed by multivariable generalized linear model. Restricted cubic spline model was used to explore the dose-response relationship between sleep duration and functional disability. RESULTS: In total, 5 519 participants [Male: 2 471 (44.77%)] were included in this study with a mean age of 73.67 years old, containing 2 800 (50.73%) functional disabled, 1 978 (35.83%) ADL disabled, and 2 299 (41.66%) IADL disabled older adults. After adjusted for potential confounders, individuals reported shorter sleep durations (≤ 4, 5, 6 hours) or longer sleep durations (8, 9, ≥ 10 hours) per night exhibited a notably increased risk of functional disability compared to those who with 7 hours (P < 0.05), which revealed a U-shape association between sleep duration and dysfunction. When sleep duration fell below 7 h, increased sleep duration was associated with a significantly lower risk of functional disability (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.79-0.91; P < 0.001). When sleep duration exceeded 7 h, the risk of functional disability (OR, 1.16; 95% CI, 1.05-1.29; P < 0.001) would increase facing prolonged sleep duration. CONCLUSIONS: Shorter and longer sleep duration was associated with a higher risk of functional disability among the aged 65 and above Chinese adults. Future studies are needed to explore intervention strategies about sleep duration especially focus on functional disability.

16.
Psychol Health Med ; : 1-23, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38785256

RESUMEN

Numerous psychological interventions are available for suicidal and death ideation (SDI) and suicidal behavior among cancer patients. To identify the optimal psychological interventions for reducing SDI and suicidal behavior in cancer patients. However, it remains unclear which psychological intervention is the most effective. We performed a pairwise and network meta-analysis by searching seven databases from the date of inception until 8 April 2022. An important focus of this network meta-analysis was the comparison of the effects of various psychological interventions on the reduction of SDI and suicidal behavior among cancer patients. For determining efficacy, we used standardized mean differences (SMDs) and 95% confidence intervals (CIs). Besides, a pairwise meta-analysis, inconsistency test, network meta-analysis, the surface under the cumulative rankings curve (SUCRA), comparison-adjusted funnel plot, subgroup analysis, and sensitivity analysis were also carried out. A total of 8 studies involving 1,350 patients were searched in this study. It showed that empathy therapy (SUCRA = 95.3%) has the best effect among the six interventions. Comprehensive psychological intervention (SUCRA = 77.6%) was ranked in the top two positions, followed by meaning-centered therapy (SUCRA = 40.7%). Comparison-adjusted funnel plots revealed no significant publication bias. In addition, our conclusions have not changed significantly after the sensitivity analysis. In this network meta-analysis, empathy therapy was identified as the optimal choice for reducing SDI and suicidal behaviors in cancer patients. Further multi-center and high-quality RCT studies should be conducted to make our conclusion more rigorous.

18.
J Clin Nurs ; 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38764176

RESUMEN

AIMS AND OBJECTIVES: To describe a grading system that can be used to evaluate core competency of clinical nurse specialists (CNSs) at different levels. BACKGROUND: Evaluate core competence of CNSs at different levels reflects the quality of nursing and the development of the nursing profession. DESIGN: This research employed the Delphi method. METHODS: The STROBE checklist for observational cross-sectional studies was followed to report this research study. This study consisted of two main phases: a literature review and semistructured interviews. Individual semistructured interviews were conducted with 11 healthcare experts and two patients. Two rounds of questionnaire surveys were administered to 21 nursing experts using the Delphi method. The CNSs were classified as primary, intermediate or advanced based on their years of work, professional titles and educational qualifications. RESULTS: The graded competency evaluation system consisted of five first-level indicators (clinical practice, consulting guidance and teaching, scientific research innovation, management and discipline development, and ethical decision-making), 15 second level indicators, and 40 third-level indicators. The authority coefficients (Cr) of the experts were .865 and .901. The Kendall's concordance coefficients of the three-level indicators were .417, .289 and .316 for primary CNSs; .384, .294 and .337 for intermediate CNSs; and .489, .289 and .239 for advanced CNSs. CONCLUSION: The graded use evaluation system in clinical practice initially involves a comprehensive evaluation of the core abilities of CNSs. This is a tool for cultivating and grading the abilities of specialised nurses that can promote a practical upwards spiral. RELEVANCE TO CLINICAL PRACTICE: The evaluation system can promote the scientific management and continuous improvement of CNSs in clinical nursing and can serve as a practical and objective reference for the effective management and development of CNSs. PATIENT OR PUBLIC CONTRIBUTION: Patients participated in the data collection process, during which they shared their health-seeking experience with our research team.

19.
Analyst ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767669

RESUMEN

A novel nanocomposite, [Eu(BTD)3(DPBT)]-BSA@MnO2, is reported to serve as an effective nanoprobe for bimodal time-gated luminescence (TGL) and magnetic resonance (MR) imaging of H2O2in vitro and in vivo. The nanoprobe was fabricated by immobilizing visible-light-excitable Eu3+ complexes in bovine serum albumin (BSA)-coated lamellar MnO2 nanosheets. The TGL of the Eu3+ complex was effectively quenched by the MnO2 nanosheets. Upon exposure to H2O2, the MnO2 nanosheets underwent reduction to Mn2+, which simultaneously triggered rapid, selective and sensitive "turn-on" responses toward H2O2 in both TGL and MR detection modes. The presence of a protective "corona" formed by BSA enables the nanoprobe to withstand high concentrations of glutathione (GSH), a strong reducing agent of MnO2 nanosheets. This capability allows the nanoprobe to be utilized for detecting H2O2 in living biosamples. The combined utilization of TGL and MR detection modes enables the nanoprobe to image H2O2 across a wide range of resolutions, from the subcellular level to the whole body, without any depth limitations. The results obtained from these modes can be cross-validated, enhancing the accuracy of the detection. The capability of the nanoprobe was validated by TGL imaging of endogenous and exogenous H2O2 in live HeLa cells, as well as bimodal TGL-MR imaging of H2O2 in tumor-bearing mice. The research achievements suggest that the integration of luminescent lanthanide complexes with protein-coated MnO2 nanosheets offers a promising bimodal TGL-MR sensing platform for H2O2in vitro and in vivo.

20.
Front Med ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806989

RESUMEN

Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction (MI) can lead to heart failure. RNA N6-methyladenosine (m6A) methylation has been shown to play a pivotal role in the occurrence and development of many illnesses. In investigating the biological function of the m6A reader YTHDF1 in cardiac fibrosis, adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts, and MI surgery in vivo and transforming growth factor-ß (TGF-ß)-activated cardiac fibroblasts in vitro were performed to establish fibrosis models. Our results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis, whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic development. Mechanistically, zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene promoter. YTHDF1 augmented AXL translation and activated the TGF-ß-Smad2/3 signaling pathway, thereby aggravating the occurrence and development of cardiac dysfunction and myocardial fibrosis. Consistently, our data indicated that YTHDF1 was involved in activation, proliferation, and migration to participate in cardiac fibrosis in vitro. Our results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.

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