RESUMEN
Pollution of surface water by heavy metal hexavalent chromium ions poses a serious threat to human health; herein, a two-dimensional (2D) cationic breathing Ni-MOF with free nitrate ions between the layers was designed and synthesized according to the characteristics of hexavalent chromium ions, {[Ni(L)2](NO3)2·5H2O}n (L = 1,3,5-tris[4-(imidazol-1-yl)phenyl]benzene). The flexible layer spacing of the 2D breathing Ni-MOF allows the exchange of NO3- by CrO42- without destroying the original structure. Electrostatic and hydrogen bonding interactions between CrO42- and Ni-MOF facilitate its exchange with NO3-. Moreover, CrO42- exhibits a higher binding energy with Ni-MOF compared to NO3-, and the hydrophobic channels of Ni-MOF favor CrO42- trapping due to its lower hydration energy. Consequently, Ni-MOF demonstrates both effective sorption and electrochemical sensing of Cr(VI), achieving a sensitivity of 2.091 µA µM-1 and a detection limit of 0.07 µM.
RESUMEN
AIMS: Clarify and define the concept of professional bereavement in nursing. DESIGN: Rodgers' evolutionary method was used to identify the attributes, antecedents, and consequences of professional bereavement in nursing. DATA SOURCES: Literature from inception to May 20, 2024, was searched from PubMed, Embase, Web of Science, CINAHL, PsycINFO, Scopus, Medline, EBSCO host, Proquest, Ovid, and Cochrane. REPORTING METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were adopted. RESULTS: The 32 articles included in the study provided data on the concept of professional bereavement in nursing. We propose the concept of professional bereavement in nursing as follows: Professional bereavement in nursing is the experience of a patient or colleague's death in the workplace, influenced by contextual, internal, and external factors. Nurses perceive personal and professional losses, exhibit a multidimensional liminal state, and experience personal impacts (life and worldview) and professional impacts (health-related productivity and professional ability). CONCLUSIONS: We developed a preliminary conceptual model of professional bereavement in nursing based on its attributes, antecedents, and consequences. This conceptual model promotes the development of theories related to professional bereavement. IMPACT: This is the first article to clarify and define professional bereavement in nursing. We have clarified the antecedents, attributes, and consequences of professional bereavement, which provides a conceptual framework for understanding professional bereavement. The conceptual framework guides the content of interventions and suggests future professional bereavement interventions from a dialectical perspective. PATIENT OR PUBLIC CONTRIBUTION: Not applicable.
RESUMEN
BACKGROUND: Vicarious trauma can significantly affect the physical and mental health of nurses, as well as their ability to provide quality of care. However, the concept of vicarious trauma has received limited attention and remains controversial in the nursing context. OBJECTIVE: The purpose of this study was to clarify and define the concept of vicarious trauma as it pertains to the nursing context. METHODS: The Schwartz and Kim's three-stage hybrid concept analysis method was used to define the concept. In the theoretical phase, PubMed, CINAHL, OVID, Medline, Embase, Web of Science, Scopus, ProQuest, PsycINFO, CNKI database, VIP database and Wanfang database were used using keywords "nurs*"and "vicarious trauma*", resulting in a total of 25 papers. In the fieldwork phase, we conducted participatory observations in three hospitals and semi-structured in-depth interviews with 18 clinical nurses from seven cities. In the analysis phase, the results of the previous two phases were integrated to develop a comprehensive concept of vicarious trauma in nursing. RESULTS: Based on the results of the theoretical and field phases, we propose the concept of vicarious trauma in nursing as follows: vicarious trauma is a psychological trauma impacting nurses' cognitive schema which they may experience in clinical settings or on social media, resulting from deeply empathize with the physical or emotional trauma of patients, family, or colleagues, such as patients' physical injuries or death, family's grieving feelings and colleagues' received threats and attacks. Positively, vicarious trauma can transform into vicarious post-trauma growth through repositioning and connection, nourishing nurses and promoting their personal and professional development. CONCLUSION: The concept of vicarious trauma in nursing is multidimensional and holistic. This study clarifies the concept of vicarious trauma in nursing using the hybrid concept analysis, providing a framework for future research and practice on vicarious trauma in the nursing field. PATIENT OR PUBLIC CONTRIBUTION: Nurses contributed to the conduct of the study by participating in the data collection via interviews.
Asunto(s)
Desgaste por Empatía , Humanos , Salud Mental , EmocionesRESUMEN
BACKGROUND: The shortage of nurses threatens the entire healthcare system, and nursing professionalism can improve nurse retention and enhance the quality of care. However, nursing professionalism is dynamic, and the factors influencing its development are not fully understood. METHODS: A qualitative descriptive study was conducted. Using maximum variation and purposive sampling, 14 southern and northern China participants were recruited. Semi-structured interviews were conducted from May 2022 to August 2023 in face-to-face conversations in offices in the workplace or via voice calls. The interviews were transcribed verbatim and analyzed via thematic analysis. RESULTS: Three main themes emerged: (1) nourishment factors: promoting early sprouting; (2) growth factors: the power of self-activation and overcoming challenges; and (3) rootedness factors: stability and upward momentum. Participants described the early acquisition of nursing professionalism as derived from personality traits, family upbringing, and school professional education, promoting the growth of nursing professionalism through self-activation and overcoming challenges, and maintaining the stable and upward development of nursing professionalism through an upward atmosphere and external motivation. CONCLUSION: We revealed the dynamic factors that influence the development of nursing professionalism, including "nourishment factors", "growth factors", and "rootedness factors". Our findings provide a foundation for future development of nursing professionalism cultivation strategies. Nursing administrators can guide the development of nurses' professionalism from many angles according to the stage they are in, and the development of professionalism deserves more attention. In the future, we can no longer consider the development of nursing professionalism solely as the responsibility of individual nurses; the power of families, organizations, and society is indispensable to jointly promoting nursing professionalism among nurses.
RESUMEN
Iron-based catalysts play an important role in the ammonia industry. As one of the most abundant iron minerals, Fe3O4 containing FeII and FeIII sites is widely distributed in the earth's crust and even on exoplanets, theoretically giving it both economic and catalytic potentials in ammonia synthesis. However, in the absence of specific active co-catalyst and harsh conditions, Fe3O4 is impossible to achieve ammonia synthesis alone. Here, we designed to activate the relatively inert FeII and FeIII sites in Fe3O4 with a third FeIII site inlayed in a coordination framework (MIL-101(Fe)) to achieve the unpresented multi-site collaborative catalysis. In-depth mechanism study confirmed the roles of three different Fe sites in N2 activation, H2 activation, and product transfer, respectively. Efficient N2-H2 activation to NH3 on the Fe3O4-based catalytic system has been achieved at extremely mild conditions. Our research provides a theoretical basis and a new strategy for designing efficient non-noble metal-based ammonia synthesis catalyst with minimized energy consumption.
RESUMEN
BACKGROUND: Nursing professionalism plays an important role in clinical nursing. However, a clear conceptual understanding of nursing professionalism is lacking. METHOD: Walker and Avant's strategy was used to analyse the concept of nursing professionalism. We searched electronic databases, including PubMed, Scopus, and CINAHL, for studies published from 1965 to 2021. Quantitative or qualitative studies published in English that focused on nursing professionalism were included in the study. RESULTS: The three attributes of nursing professionalism are multidimensional, dynamic, and culture oriented. Based on the analysis, nursing professionalism is defined as providing individuals care based on the principles of professionalism, caring, and altruism. CONCLUSIONS: This study offers a theoretical definition and conceptual model of nursing professionalism that may be applied to develop standardized assessment tools or nursing professionalism training programs.
RESUMEN
We summarize the evidence on non-pharmacological interventions for sleep disturbances in people living with dementia(PlwD). A literature search was performed using PubMed, Embase, Cochrane library, Web of Science, PsycINFO, CINAHL, and clinicaltrials.gov. Up to August 20, 2022. Six studies met our eligibility criteria. Light therapy, the therapeutic pet-type robotic seal(PRAO), and slow-stroke back massage(SSBM) are non-pharmacological interventions for sleep disturbances in PlwD.PARO increased night-time sleep duration (p < 0.05). The benefit of SSBM for sleep disturbances in PlwD is unclear (p > 0.05). Although there is a lack of evidence for the effect of light therapy on sleep disturbances in PlwD (p > 0.05), light therapy reduced sleep disturbance (SMD = -0.38; 95% CI:1.25, 0.48), increased sleep efficiency (MD = 3.77; 95% CI:-0.23, 7.78), and also reduced depression (MD = -2.49; 95% CI: -2.92, -2.06). More large-scale randomized controlled trials are needed and consider combining multiple non-pharmacological measures for sleep interventions in PlwD.
Asunto(s)
Demencia , Trastornos del Sueño-Vigilia , Humanos , Sueño , Trastornos del Sueño-Vigilia/terapia , Demencia/complicaciones , Demencia/terapiaRESUMEN
Some cellular enzymatic pathways are located within a single organelle, while most others involve enzymes that are located within multiple compartmentalized cellular organelles to realize the efficient multi-step enzymatic process. Herein, bioinspired by enzyme-mediated biosynthesis and biochemical defense, a compartmented nanoreactor (Burr-NCs@GlSOD ) was constructed through a self-confined catalysis strategy with burr defect-engineered molybdenum disulfide/Prussian blue analogues (MoS2 /PBA) and an interfacial diffusion-controlled hydrogel network. The specific catalytic mechanism of the laccase-like superactivity induced hydrogelation and cascade enzyme catalytic therapy were explored. The confined hydrogelation strategy introduces a versatile means for nanointerface functionalization and provides insight into biological construction of simulated enzymes with comparable activity and also the specificity to natural enzymes.
Asunto(s)
Hidrogeles , Nanotecnología , CatálisisRESUMEN
OBJECTIVE: We want to investigate the effect of aquaporin-4 (AQP4) on cerebral edema induced by ischemic stroke in rats and explore whether inhibiting the expression of AQP4 through acetazolamide (AZA) could attenuate brain edema and protect cerebral function. METHODS: The Sprague Dawley (SD) rats were randomly divided into four groups: sham + saline group, sham + AZA group, AZA intervention group, and nonintervention group. Each group was divided into five subgroups according to the time of cerebral ischemia (6 h, 1 day, 3 days, 5 days, and 7 days). The model of cerebral infarction in rats was adopted by means of the bilateral carotid arteries ligation (2-VO) method. The rats in intervention group were given intraperitoneal injection of AZA (35 mg/kg/day). Hematoxylin-eosin staining was performed for pathological analysis of the infarcted area. The brain water content was calculated to evaluate the degree of brain edema. The messenger RNA (mRNA) and protein expressions of AQP4 in the brain were measured by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Significant cerebral pathological damages were found in ischemic stroke rats. The brain water content, protein, and mRNA expression of AQP4 of the intervention and nonintervention groups were markedly higher than those of the sham groups. By contrast, AZA administration reduced the brain water content, whereas improved cerebral dysfunction was induced by ischemic stroke. Moreover, AZA obviously reduced the protein and mRNA expression of AQP4 after ischemic stroke in rats' brains. CONCLUSIONS: The expression of AQP4 was closely related to cerebral edema induced by ischemic stroke. Decreasing the expression of AQP4 mRNA by AZA administration can effectively relieve cerebral edema and decrease cerebral pathological damage.
Asunto(s)
Edema Encefálico , Accidente Cerebrovascular Isquémico , Acetazolamida/farmacología , Animales , Acuaporina 4/metabolismo , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Edema Encefálico/metabolismo , ARN Mensajero , Ratas , Ratas Sprague-DawleyRESUMEN
As bona fide p53 transcriptional targets, miR-34 microRNAs (miRNAs) exhibit frequent alterations in many human tumor types and elicit multiple p53 downstream effects upon overexpression. Unexpectedly, miR-34 deletion alone fails to impair multiple p53-mediated tumor suppressor effects in mice, possibly due to the considerable redundancy in the p53 pathway. Here, we demonstrate that miR-34a represses HDM4, a potent negative regulator of p53, creating a positive feedback loop acting on p53. In a Kras-induced mouse lung cancer model, miR-34a deficiency alone does not exhibit a strong oncogenic effect. However, miR-34a deficiency strongly promotes tumorigenesis when p53 is haploinsufficient, suggesting that the defective p53-miR-34 feedback loop can enhance oncogenesis in a specific context. The importance of the p53/miR-34/HDM4 feedback loop is further confirmed by an inverse correlation between miR-34 and full-length HDM4 in human lung adenocarcinomas. In addition, human lung adenocarcinomas generate an elevated level of a short HDM4 isoform through alternative polyadenylation. This short HDM4 isoform lacks miR-34-binding sites in the 3' untranslated region (UTR), thereby evading miR-34 regulation to disable the p53-miR-34 positive feedback. Taken together, our results elucidated the intricate cross-talk between p53 and miR-34 miRNAs and revealed an important tumor suppressor effect generated by this positive feedback loop.
Asunto(s)
Adenocarcinoma/fisiopatología , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/fisiopatología , MicroARNs/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adenocarcinoma del Pulmón , Animales , Línea Celular Tumoral , Eliminación de Gen , Haploinsuficiencia , Humanos , Ratones , MicroARNs/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
In this work, the frequency doubling effect of thermoacoustic speakers is studied, and a method is analyzed to suppress the frequency doubling effect. Three cases were analyzed by superimposing the DC bias on the AC excitation: (1) DC is less than AC; (2) DC is equal to AC; (3) DC is greater than AC. We found that the frequency doubling effect can be well suppressed by superimposing a larger DC excitation on the AC excitation. The laser scribing technology was used to prepare graphene film in only one step, and the screen printing technology was used to prepare conductive electrodes. The microphone and B&K system was used to record the sound pressure level and study the suppression of frequency doubling effect. Finally, the sound pressure levels with the three different kinds of excitations were measured. The measured results show that they have a good agreement with the theoretical results. The suppression effect will be better when DC amplitude is greater than AC amplitude. Therefore, this work has certain reference significance for the further study and application of thermoacoustic speakers.
Asunto(s)
Grafito , Sonido , Conductividad Eléctrica , Electrodos , Rayos LáserRESUMEN
The design of enzyme mimics from stable and nonprotein systems is especially attractive for applications in highly specific cancer diagnosis and treatment, and it has become an emerging field in recent years. Herein, metal crosslinked polymeric nanogels (MPGs) were prepared using FeII ion coordinated biocompatible acryloyl-lysine polymer brushes obtained from an enzyme-catalyzed atomic transfer radical polymerization (ATRPase) method. The monoatomic and highly dispersed Fe ions in the MPGs serve as efficient crosslinkers of the gel network, and also as active centers of multienzyme mimics of superoxide dismutase (SOD) and peroxidase (POD). The catalytic activities were compared to those of conventional Fe-based nanozymes. Studies on both cells and animals verify that efficient reactive oxygen species (ROS) responsive biofluorescence imaging can be successfully realized using the MPGs.
Asunto(s)
Complejos Multienzimáticos/química , Nanoestructuras/química , Polimerizacion , Animales , Catálisis , Línea Celular , Reactivos de Enlaces Cruzados , Compuestos Ferrosos/química , Geles , Humanos , Nanogeles , Imagen Óptica , Peroxidasas/química , Polietilenglicoles , Polietileneimina , Especies Reactivas de Oxígeno , Superóxido Dismutasa/químicaRESUMEN
Small ubiquitin-like modifier (SUMO) family proteins regulate target-protein functions by post-translational modification. However, a potent and selective inhibitor targeting the SUMO pathway has been lacking. Here we describe ML-792, a mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, thus decreasing cancer cell proliferation. Moreover, we found that induction of the MYC oncogene increased the ML-792-mediated viability effect in cancer cells, thus indicating a potential application of SAE inhibitors in treating MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic-subunit (UBA2) S95N M97T mutant rescued SUMOylation loss and the mitotic defect induced by ML-792, thus confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins, thereby facilitating novel insights into SUMO biology.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/antagonistas & inhibidores , Sumoilación , Proliferación Celular/efectos de los fármacos , Segregación Cromosómica/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes myc , Humanos , Mitosis/efectos de los fármacos , Neoplasias/genética , Neoplasias/patología , Procesamiento Proteico-Postraduccional , Células Tumorales CultivadasRESUMEN
Introduction: Adverse childhood experiences (ACEs) impact cognitive function, but the relationship remains unclear. We aim to identify cognitive function trajectories and scrutinize the correlation between ACEs and cognitive function. Methods: To identify cognitive trajectories, we employed a group-based trajectory model, and influential factors were determined using multinomial unordered logistic regression analysis. Results: Three cognitive decline subgroups emerged: low-start decline, high-start stability, and mid-start decline. There is no dose-response relationship between cumulative adverse childhood experiences and cognitive function. The high-start stability group had specific residence and education traits, while sibling death affected them. The mid-start decline group was vulnerable to parental death, physical abuse, and domestic violence. The low-start decline group should consider age structure and childhood friendships. Conclusions: No dose-response association between cumulative ACEs and cognitive decline. Still, specific ACE metrics are correlated with cognitive trajectories. We can incorporate patients' ACEs into cognitive function assessments for early risk factor identification and tailored interventions. Moreover, recognizing the influence of early-life experiences on cognitive function, we can advocate for nurturing positive family and societal environments to optimize cognitive function.
RESUMEN
Purpose: Rapid detection and diagnosis of diseases facilitate timely and effective treatment of cardiovascular diseases (CVD). The establishment of a one-step rapid detection method provides a new method for the initial screening and disease risk assessment of patients with cardiovascular diseases in primary medical units. Methods: Hollow gold nanoparticles (HGNPs) were synthesized using a cobalt template method followed by use as signal amplification probes for ultra-sensitive quantitative detection of serum C-reactive protein (CRP). To induce the localized surface plasmon resonance (LSPR) and improve protein labeling efficiency, we developed a sensitive detection mode by coating polyvinylpyrrolidone (PVP-K30) on the HGNPs, resulting in a significant improvement in detection performance. Results: Compared to traditional colloidal GNP-based LFTA, PVP-coated HGNPs exhibit a lower visual detection limit of 1 ng/mL, which a 25-fold decrement compare to using GNPs as the antibody-labeled probe, and the detection limit could be reduced to 0.14 ng/mL under the quantitative instrument. Conclusion: The one-step method based on HGNP immunochromatographic strips modified with PVP established in this study can be used for the detection of CRP and hs-CRP in biological samples. The performance of the immunochromatographic technique designed in this study was evaluated from the perspective of synthetic markers, and the application conditions of this strip were screened, verifying its high specificity, indicating that it has high sensitivity and strong detection limit compared to colloidal gold. The sensitivity of the hollow gold immunochromatographic test strip in this article has been increased by about 25 times, providing a new method for rapid detection of CVD in clinical diagnosis.
Asunto(s)
Enfermedades Cardiovasculares , Nanopartículas del Metal , Humanos , Proteína C-Reactiva , Oro , Nanopartículas del Metal/química , Enfermedades Cardiovasculares/diagnóstico , Anticuerpos , InmunoensayoRESUMEN
Ischemic stroke (IS) is a major cause of mortality and morbidity worldwide. Beyond thrombolysis, strategies targeting anti-oxidative apoptosis and angiogenesis are considered prospective therapeutic strategies. Nevertheless, existing natural and clinical remedies have limited efficacy in the management of IS. Moreover, despite their millennial legacy of IS remediation, natural remedies such as ginseng incur high production costs. The novel glycopeptide APMCG-1, extracted from mountain-cultivated ginseng dregs in our previous study, is a potent therapeutic candidate for IS. This study investigated APMCG-1's remedial mechanisms against IS injury using an H2O2-induced oxidative stress paradigm in human umbilical vein endothelial cells (HUVECs) emulating ischemic endothelial cells, in a ponatinib-induced zebrafish IS model, and in rat middle cerebral artery occlusion (MCAO) prototypes. Cellular assays confirmed the proficiency of APMCG-1 in preventing oxidative stress and cell death, fostering regeneration, and facilitating neovascularization within the H2O2-stressed HUVECs framework. Moreover, APMCG-1 augmented hemodynamic velocity, oxidative stress mitigation, apoptosis reduction, and motor enhancement in a zebrafish model of IS. In MCAO rats, APMCG-1 ameliorated neurological deficits and cerebral injury, as evidenced by increased neurological scores and diminished infarct dimensions. In cells and animal models, APMCG-1 activated the PI3K/AKT signaling pathway, modulating factors such as Nrf2, Bcl-2, Caspase 3, eNOS, and VEGFA, thereby ameliorating cellular oxidative distress and catalyzing angiogenesis. Collectively, these results demonstrate the potential protective effects of APMCG-1 in IS pharmacotherapy and its prospective utility as an herbal-derived IS treatment modality.
RESUMEN
OBJECTIVE: This study aimed to develop and validate a prediction model for premature circuit clotting of continuous renal replacement therapy (CRRT) in critically ill patients. DESIGN: A retrospective cohort study was conducted on ICU patients undergoing CRRT. The Medical Information Mart for Intensive Care-III Clinical Database CareVue subset and Medical Information Mart for Intensive Care-IV were utilized for model development, while the eICU Collaborative Research Database was employed for external validation. Predictive factors were selected through Least Absolute Shrinkage and Selection Operator Regression and univariate logistic regression. A prediction model was then developed using binary logistic regression. Internal and external validations assessed the model's discrimination, calibration, and clinical net benefit. RESULTS: This study encompassed 2531 patients overall, with a premature circuit clotting rate of 31.88 %. The prediction model comprises five variables: body temperature, anticoagulation, mean arterial pressure, maximum transmembrane pressure change within two hours, and vasopressor. The model demonstrated robust predictive performance, achieving an area under the receiver operating characteristic curve of 0.897 (95 % CI: 0.879-0.915) in the training set and 0.877 (95 % CI: 0.852-0.902) in the external validation set. Internal validation yielded a Brier score of 0.087, while external validation showed a Brier score of 0.120. Calibration curves indicated good model calibration for both validations. The decision curve analysis indicates that the model yields a clinical net benefit across a wide range of decision thresholds. CONCLUSION: The model demonstrates robust discrimination, calibration, and clinical net benefit, with readily available variables indicating substantial potential for valuable clinical applications. IMPLICATIONS FOR CLINICAL PRACTICE: Healthcare providers in the ICU can leverage the model to evaluate the risk of premature circuit clotting in critically ill patients undergoing continuous renal replacement therapy, facilitating timely intervention to mitigate its incidence.
Asunto(s)
Terapia de Reemplazo Renal Continuo , Enfermedad Crítica , Unidades de Cuidados Intensivos , Humanos , Masculino , Femenino , Terapia de Reemplazo Renal Continuo/métodos , Terapia de Reemplazo Renal Continuo/normas , Terapia de Reemplazo Renal Continuo/estadística & datos numéricos , Enfermedad Crítica/terapia , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Unidades de Cuidados Intensivos/organización & administración , Estudios de Cohortes , Adulto , Modelos Logísticos , Curva ROCRESUMEN
In the development of asthma, subepithelial fibrosis and vascular proliferation cause airway remodeling and narrowing, leading to disease deterioration and respiratory failure. In the clinic, the treatment of asthma was aimed at reducing the frequency of acute asthma attacks through inhaled corticosteroids (ICSs). However, ICSs cannot prevent the progression into refractory asthma due to the formation of airway remodeling mainly by subepithelial fibrosis and angiogenesis surrounding the tracheal lumen. Herein, we constructed surface-engineered mesenchymal stem cells (MSCs/PVLA) via the bioconjugation of MSCs and reactive oxygen species-responsive polymeric micelles loaded with vactosertib (VST) and linifanib (LFN) for treating refractory asthma through reversing airway remodeling. MSCs/PVLA migrated to the tracheal lumen due to the inflammation tropism of MSCs, and subsequently released VST and LFN could inhibit the formation of airway remodeling by preventing subepithelial fibrosis and angiogenesis. Meanwhile, MSCs reduced inflammatory cell infiltration and cytokine secretion to regulate the pathological microenvironment. Our results suggested that MSCs/PVLA could serve as a promising candidate to prevent disease exacerbations and treat refractory asthma.
RESUMEN
AIMS: To identify whether and how a younger systemic internal milieu alleviates acute kidney injury (AKI) in grafts after kidney transplantation. MATERIALS AND METHODS: We conducted an allogenic heterotopic rat kidney transplantation model with young and adult recipients receiving similar donor kidneys. We evaluated the renal function, histological damage, apoptosis, dedifferentiation, proliferation, hub regulating cytokines, and signaling pathways involved in young and adult recipients based on transcriptomics, proteomics, and experimental validation. We also validated the protective effect and mechanism of interleukin-13 (IL-13) on tubular epithelial cell injury induced by transplantation in vivo and by cisplatin in vitro. KEY FINDINGS: Compared with adult recipients, the young recipients had lower levels of renal histological damage and apoptosis, while had higher levels of dedifferentiation and proliferation. Serum IL-13 levels were higher in young recipients both before and after surgery. Pretreating with IL-13 decreased apoptosis and promoted regeneration in injured rat tubular epithelial cells induced by cisplatin, while this effect can be counteracted by a JAK2 and STAT3 specific inhibitor, AG490. Recipients pretreated with IL-13 also had lower levels of histological damage and improved renal function. SIGNIFICANCE: Higher levels of IL-13 in young recipients ameliorates tubular epithelial cell apoptosis and promotes regeneration via activating the JAK-STAT signaling pathway both in vivo and in vitro. Our results suggest that IL-13 is a promising therapeutic strategy for alleviating AKI. The therapeutic potential of IL-13 in injury repair and immune regulation deserves further evaluation and clinical consideration.
Asunto(s)
Lesión Renal Aguda , Trasplante de Riñón , Daño por Reperfusión , Ratas , Animales , Interleucina-13/metabolismo , Cisplatino/efectos adversos , Lesión Renal Aguda/metabolismo , Riñón/metabolismo , Apoptosis , Transducción de Señal , Daño por Reperfusión/metabolismoRESUMEN
A global decrease in microRNA (miRNA) levels is often observed in human cancers, indicating that small RNAs may have an intrinsic function in tumour suppression. To identify miRNA components of tumour suppressor pathways, we compared miRNA expression profiles of wild-type and p53-deficient cells. Here we describe a family of miRNAs, miR-34a-c, whose expression reflected p53 status. Genes encoding miRNAs in the miR-34 family are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo. Ectopic expression of miR-34 induces cell cycle arrest in both primary and tumour-derived cell lines, which is consistent with the observed ability of miR-34 to downregulate a programme of genes promoting cell cycle progression. The p53 network suppresses tumour formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation.