Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 323
Filtrar
1.
Sci Total Environ ; 946: 174435, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38964402

RESUMO

The retreat of Himalayan glaciers and the expansion of glacial lakes due to global warming have increased the occurrence of glacial lake outburst debris flow (GLODF), posing a serious threat to downstream communities. However, there are gaps in understanding the changes in GLODF occurrence driven by climate change, which challenges disaster management and cross-border cooperation in the Himalayas. To consider this issue, our study presents a novel framework integrating environmental evolution, a process-driven indicator system, and a hybrid machine learning model to predict Himalayan GLODF occurrence in the 21st century. Our findings indicate ongoing temperature (0.27-0.60 °C/10a) and precipitation (1.30-5.00 %/10a) increases under both SSP245 and SSP585 scenarios. Meanwhile, Himalayan glaciers are projected to lose between 70 % and 86 % of their mass by 2100 compared to 2020. Additionally, 2722 ± 207 new glacial lakes are expected to emerge by 2100. GLODF occurrence probability index is anticipated to rise to 1.27-1.30 times the current levels, with the Western Himalayas and Indus basin as high-incidence areas. Currently and in the future, the China-Nepal border remains a hotspot for cross-border GLODF. Our framework offers valuable long-term insights into Himalayan GLODF occurrence trends in response to climate change.

2.
Stem Cell Res Ther ; 15(1): 167, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872206

RESUMO

BACKGROUND: Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases. METHODS: Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR. RESULTS: The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process. CONCLUSION: This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.


Assuntos
Benzilaminas , Colite , Ciclamos , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Tacrolimo , Animais , Colite/induzido quimicamente , Colite/terapia , Colite/tratamento farmacológico , Colite/patologia , Camundongos , Masculino , Ciclamos/farmacologia , Ciclamos/uso terapêutico , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Modelos Animais de Doenças , Terapia de Imunossupressão , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Microesferas , Espécies Reativas de Oxigênio/metabolismo
3.
Adv Drug Deliv Rev ; 211: 115355, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38849004

RESUMO

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.


Assuntos
Técnicas de Transferência de Genes , Mitocôndrias , Nanoestruturas , Humanos , Mitocôndrias/metabolismo , Nanoestruturas/química , Animais , Transporte Biológico , DNA Mitocondrial/genética , Edição de Genes/métodos
4.
BMJ Open ; 14(5): e076727, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754883

RESUMO

INTRODUCTION: Dementia is a growing public health concern, and providing long-term care for individuals affected by this condition is challenging for their family caregivers. While researchers have explored various intervention options to provide psychological support for dementia caregivers, mentalising imagery therapy (MIT) has gained significant recognition as an effective programme. Despite its significance and effectiveness, there is a lack of comprehensive scoping reviews of MIT in dementia caregiving. Thus, conducting such a review can provide valuable insights into the status and outcomes of MIT, identify gaps in existing research and provide recommendations for a more effective clinical practice. METHODS AND ANALYSIS: This study proposes a scoping review conducted according to the Joanna Briggs Institute, Arksey and O'Malley's methodological framework, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension. PubMed, Web of Science, Embase, Scopus, CINAHL and PsycINFO databases will be searched while grey literature will be retrieved via Google Scholar. Covidence will be used to manage the literature selection process and remove duplicate publications. Two researchers will independently screen the literature according to the inclusion criteria, with any discrepancies resolved through discussions with a third researcher. Data will be presented in a structured tabular format, with a narrative synthesis providing an overview of the findings on the identified research gaps and the effectiveness of MIT in the field of dementia caregiving. ETHICS AND DISSEMINATION: In a scoping review, no ethical approval is necessary. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The scoping review protocol has been registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/FHRG8).


Assuntos
Cuidadores , Demência , Imagens, Psicoterapia , Projetos de Pesquisa , Humanos , Cuidadores/psicologia , Demência/terapia , Imagens, Psicoterapia/métodos , Literatura de Revisão como Assunto , Revisões Sistemáticas como Assunto
5.
Opt Express ; 32(6): 9486-9494, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571182

RESUMO

Substrate integrated waveguides (SIWs) components play a crucial role in microwave devices fabricated by printed circuit board (PCB) technology. Bound states in the continuum (BICs) have high-quality factors that approach infinity. So far, there is little research on BICs in SIWs. Therefore, we studied a symmetry-protected BIC generated by the coupling between SIW and SIW resonators to fill this gap. Using the revised coupled mode theory (CMT), we explored the mechanism of resonance generation in this system. In addition, the effect of the geometrical parameters on the resonance is also investigated and higher Q3dB factors are obtained. The findings offer new insights into the design of BIC devices by traditional PCB technology, thus contributing to future applications in the integrated circuits field.

6.
Adv Sci (Weinh) ; 11(19): e2401254, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38483920

RESUMO

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.


Assuntos
Matriz Extracelular , Fibrose , Nanopartículas , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Matriz Extracelular/metabolismo , Animais , Fibrose/metabolismo , Resveratrol/farmacologia , Humanos , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatopatias/metabolismo , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Vitamina A/metabolismo , Camundongos , Ratos , Sistemas de Liberação de Medicamentos/métodos
7.
Food Chem ; 447: 138997, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38513493

RESUMO

Herein we developed a multicolor lateral flow immunoassay (LFIA) test strip for rapid and simultaneous quantitative detection of aflatoxin B1 (AFB1) and zearalenone (ZEN). Three differently colored aggregation-induced emission nanoparticles (AIENPs) were designed as LFIA signal tags, with red and green AIENPs for targeting AFB1 and ZEN at the test line, and yellow AIENPs for indicating the validity of the test strip at the control (C) line. After surface functionalization with antibodies, the developed AIENP-based multicolor LFIA allows simultaneous and accurate quantification of AFB1 and ZEN using an independent C-line assisted ratiometric signal output strategy. The detection limits of AFB1 and ZEN were 6.12 and 26 pg/mL, respectively. The potential of this method for real-world applications was well demonstrated in corn and wheat. Overall, this multicolor LFIA shows great potential for field screening of multiple mycotoxins and can be extended to rapid and simultaneous monitoring of other small molecule targets.


Assuntos
Nanopartículas Metálicas , Micotoxinas , Zearalenona , Zearalenona/análise , Aflatoxina B1/análise , Anticorpos Monoclonais , Micotoxinas/análise , Imunoensaio/métodos , Limite de Detecção , Contaminação de Alimentos/análise
8.
Nat Commun ; 15(1): 2759, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553451

RESUMO

Non-small cell lung cancer (NSCLC) shows high drug resistance and leads to low survival due to the high level of mutated Tumor Protein p53 (TP53). Cisplatin is a first-line treatment option for NSCLC, and the p53 mutation is a major factor in chemoresistance. We demonstrate that cisplatin chemotherapy increases the risk of TP53 mutations, further contributing to cisplatin resistance. Encouragingly, we find that the combination of cisplatin and fluvastatin can alleviate this problem. Therefore, we synthesize Fluplatin, a prodrug consisting of cisplatin and fluvastatin. Then, Fluplatin self-assembles and is further encapsulated with poly-(ethylene glycol)-phosphoethanolamine (PEG-PE), we obtain Fluplatin@PEG-PE nanoparticles (FP NPs). FP NPs can degrade mutant p53 (mutp53) and efficiently trigger endoplasmic reticulum stress (ERS). In this study, we show that FP NPs relieve the inhibition of cisplatin chemotherapy caused by mutp53, exhibiting highly effective tumor suppression and improving the poor NSCLC prognosis.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Fosfatidiletanolaminas , Polietilenoglicóis , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Fluvastatina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Mutação
9.
BMJ Open ; 14(2): e079812, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38355172

RESUMO

OBJECTIVES: To examine whether patients who had a stroke with high recurrence risk perception would have healthier behaviour and to explore whether perceived social support would function as a mediator. DESIGN: A cross-sectional study. SETTING: The study was conducted in a public tertiary hospital in China. PARTICIPANTS: A total of 254 patients with stroke were invited to participate, and 250 patients with stroke completed questionnaires validly. PRIMARY AND SECONDARY OUTCOME MEASURES: Questionnaires were administered offline to collect data, consisting of four parts: general demographics and scales related to recurrence risk perception, perceived social support, and health behaviour. A path analysis and correlation analysis were used to analyse the data. RESULTS: Out of 250 patients with stroke, 78.4% had moderately low health behaviour. The majority (70.8%) of these patients were elderly. High recurrence risk perception and high perceived social support were significantly associated with better health behaviour (all p<0.001). Perceived social support mediated the relationship between recurrence risk perception and health behaviour after controlling for age, gender, education and monthly income in the regression model (95% CI 0.263 to 0.460) and the effect value was 0.360. It was also confirmed that perceived social support had the highest mediation effect with a proportion of mediation up to 59.31%. CONCLUSIONS: Recurrence risk perception and perceived social support were influential factors in promoting health behaviour. Moreover, the impact of recurrence risk perception on health behaviour was partially mediated by perceived social support. Therefore, to enhance the sustainability of health behaviour, it is crucial to inform patients with stroke about the risk of recurrence. Patients with more perception of recurrence risk can improve their recovery confidence and thus perceive more social support.


Assuntos
Comportamentos Relacionados com a Saúde , Acidente Vascular Cerebral , Humanos , Idoso , Estudos Transversais , Apoio Social , Percepção , China , Inquéritos e Questionários
10.
Anticancer Res ; 44(2): 797-803, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307578

RESUMO

BACKGROUND/AIM: This study examined the clinical significance of very high preoperative carbohydrate antigen 19-9 (CA19-9) levels in patients with early-stage colorectal cancer (CRC). PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent curative resection for primary CRC (c-Stage I-III) between 2004 and 2022 in our facility. The patients were classified into three groups according to the preoperative CA19-9 level: normal (≤37.0 U/ml), high (>37.0 to ≤100.0 U/ml), and very high (>100.0 U/ml). RESULTS: Of 971 patients, 885 (91.1%), 67 (6.9%), and 19 (2.0%) had normal, high, and very high CA19-9 levels, respectively. Overall survival (very high vs. normal: p<0.0001, very high vs. high: p=0.01) and recurrence-free survival (very high vs. normal: p<0.0001, very high vs. high: p=0.18) were significantly worse in the very high group. On multivariate analysis including TNM stage, very high preoperative CA19-9 levels were independently associated with worse overall (odds ratio=4.54; 95% confidence interval=2.03-10.16; p=0.0002) and recurrence-free survival (odds ratio=3.49; 95% confidence interval=1.82-6.69; p=0.0002). CONCLUSION: High preoperative CA19-9 levels were associated with poor survival in early-stage CRC. Careful intraoperative observation and close follow-up might be necessary.


Assuntos
Antígeno CA-19-9 , Neoplasias Colorretais , Humanos , Biomarcadores Tumorais , Estudos Retrospectivos , Antígeno Carcinoembrionário , Prognóstico , Estadiamento de Neoplasias , Neoplasias Colorretais/patologia
11.
Int J Biol Macromol ; 263(Pt 2): 130356, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395283

RESUMO

Mesenchymal stem cell (MSC)-based therapies show great potential in treating various diseases. However, control of the fate of injected cells needs to be improved. In this work, we developed an efficient methodology for modulating chondrogenic differentiation of MSCs. We fabricated heterospheroids with two sustained-release depots, a quaternized chitosan microsphere (QCS-MP) and a poly (lactic-co-glycolic acid) microsphere (PLGA-MP). The results show that heterospheroids composed of 1 × 104 to 5 × 104 MSCs formed rapidly during incubation in methylcellulose medium and maintained high cell viability in long-term culture. The MPs were uniformly distributed in the heterospheroids, as shown by confocal laser scanning microscopy. Incorporation of transforming growth factor beta 3 into QCS-MPs and of dexamethasone into PLGA-MPs significantly promoted the expression of chondrogenic genes and high accumulation of glycosaminoglycan in heterospheroids. Changes in crucial metabolites in the dual drug depot-engineered heterospheroids were also evaluated using 1H NMR-based metabolomics analysis to verify their successful chondrogenic differentiation. Our heterospheroid fabrication platform could be used in tissue engineering to study the effects of various therapeutic agents on stem cell fate.


Assuntos
Quitosana , Células-Tronco Mesenquimais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Microesferas , Quitosana/farmacologia , Ácido Poliglicólico/farmacologia , Ácido Láctico/farmacologia , Glicóis , Preparações de Ação Retardada/farmacologia , Células Cultivadas , Diferenciação Celular , Condrogênese
12.
J Control Release ; 366: 732-745, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38242209

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality. The Food and Drug Administration-approved drugs, nintedanib and pirfenidone, could delay progressive fibrosis by inhibiting the overactivation of fibroblast, however, there was no significant improvement in patient survival due to low levels of drug accumulation and remodeling of honeycomb cyst and interstitium surrounding the alveoli. Herein, we constructed a dual drug (verteporfin and pirfenidone)-loaded nanoparticle (Lip@VP) with the function of inhibiting airway epithelium fluidization and fibroblast overactivation to prevent honeycomb cyst and interstitium remodeling. Specifically, Lip@VP extensively accumulated in lung tissues via atomized inhalation. Released verteporfin inhibited the fluidization of airway epithelium and the formation of honeycomb cyst, and pirfenidone inhibited fibroblast overactivation and reduced cytokine secretion that promoted the fluidization of airway epithelium. Our results indicated that Lip@VP successfully rescued lung function through inhibiting honeycomb cyst and interstitium remodeling. This study provided a promising strategy to improve the therapeutic efficacy for IPF.


Assuntos
Cistos , Fibrose Pulmonar Idiopática , Nanopartículas , Humanos , Verteporfina , Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão
13.
Adv Mater ; 36(16): e2311474, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38194906

RESUMO

During liver fibrogenesis, the reciprocal crosstalk among capillarized liver sinusoidal endothelial cells (LSECs), activated hepatic stellate cells (HSCs), and dysfunctional hepatocytes constructs a self-amplifying vicious cycle, greatly exacerbating the disease condition and weakening therapeutic effect. Limited by the malignant cellular interactions, the previous single-cell centric treatment approaches show unsatisfactory efficacy and fail to meet clinical demand. Herein, a vicious cycle-breaking strategy is proposed to target and repair pathological cells separately to terminate the malignant progression of liver fibrosis. Chondroitin sulfate-modified and vismodegib-loaded nanoparticles (CS-NPs/VDG) are designed to efficiently normalize the fenestrae phenotype of LSECs and restore HSCs to quiescent state by inhibiting Hedgehog signaling pathway. In addition, glycyrrhetinic acid-modified and silybin-loaded nanoparticles (GA-NPs/SIB) are prepared to restore hepatocytes function by relieving oxidative stress. The results show successful interruption of vicious cycle as well as distinct fibrosis resolution in two animal models through multiregulation of the pathological cells. This work not only highlights the significance of modulating cellular crosstalk but also provides a promising avenue for developing antifibrotic regimens.


Assuntos
Células Endoteliais , Lipossomos , Nanopartículas , Animais , Células Endoteliais/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Cirrose Hepática , Fígado/metabolismo
15.
Adv Sci (Weinh) ; 11(7): e2306899, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38064164

RESUMO

In advanced liver fibrosis (LF), macrophages maintain the inflammatory environment in the liver and accelerate LF deterioration by secreting proinflammatory cytokines. However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug-loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG-E8) (named MUA/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier. MFG-E8 is released in response to the high reactive oxygen species (ROS) environment in LF, transforming macrophages from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype and inducing macrophages to phagocytose collagen. Collagen ablation increases AC73 and siUSP1 accumulation in hepatic stellate cells (HSCs) and inhibits HSCs overactivation. Interestingly, complete resolution of liver inflammation, significant collagen degradation, and HSCs deactivation are observed in methionine choline deficiency (MCD) and CCl4 models after tail vein injection of MUA/Y. Overall, this work reveals a macrophage-focused regulatory treatment strategy to eliminate LF progression at the source, providing a new perspective for the clinical treatment of advanced LF.


Assuntos
Cirrose Hepática , Macrófagos , Humanos , Cirrose Hepática/terapia , Macrófagos/metabolismo , Colágeno , Fenótipo
16.
Biomaterials ; 305: 122447, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38154441

RESUMO

Ferroptosis is a promising therapeutic approach for combating malignant cancers, but its effectiveness is limited in clinical due to the adaptability and self-repair abilities of cancer cells. Mitochondria, as the pivotal player in ferroptosis, exhibit tremendous therapeutic potential by targeting the intramitochondrial anti-ferroptotic pathway mediated by dihydroorotate dehydrogenase (DHODH). In this study, an albumin-based nanomedicine was developed to induce augmented ferroptosis in triple-negative breast cancer (TNBC) by depleting glutathione (GSH) and inhibiting DHODH activity. The nanomedicine (ATO/SRF@BSA) was developed by loading sorafenib (SRF) and atovaquone (ATO) into bovine serum albumin (BSA). SRF is an FDA-approved ferroptosis inducer and ATO is the only drug used in clinical that targets mitochondria. By combining the effects of SRF and ATO, ATO/SRF@BSA promoted the accumulation of lipid peroxides within mitochondria by inhibiting the glutathione peroxidase 4 (GPX4)-GSH pathway and downregulating the DHODH-coenzyme Q (CoQH2) defense mechanism, triggers a burst of lipid peroxides. Simultaneously, ATO/SRF@BSA suppressed cancer cell self-repair and enhanced cell death by inhibiting the synthesis of adenosine triphosphate (ATP) and pyrimidine nucleotides. Furthermore, the anti-cancer results showed that ATO/SRF@BSA exhibited tumor-specific killing efficacy, significantly improved the tumor hypoxic microenvironment, and lessened the toxic side effects of SRF. This work presents an efficient and easily achievable strategy for TNBC treatment, which may hold promise for clinical applications.


Assuntos
Ferroptose , Neoplasias de Mama Triplo Negativas , Humanos , Di-Hidro-Orotato Desidrogenase , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Peróxidos Lipídicos , Soroalbumina Bovina , Atovaquona , Glutationa , Linhagem Celular Tumoral , Microambiente Tumoral
17.
J Control Release ; 365: 981-1003, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38123072

RESUMO

Stem cells have garnered significant attention in regenerative medicine owing to their abilities of multi-directional differentiation and self-renewal. Despite these encouraging results, the market for stem cell products yields limited, which is largely due to the challenges faced to the safety and viability of stem cells in vivo. Besides, the fate of cells re-infusion into the body unknown is also a major obstacle to stem cell therapy. Actually, both the functional protection and the fate tracking of stem cells are essential in tissue homeostasis, repair, and regeneration. Recent studies have utilized cell engineering techniques to modify stem cells for enhancing their treatment efficiency or imparting them with novel biological capabilities, in which advances demonstrate the immense potential of engineered cell therapy. In this review, we proposed that the "engineered stem cells" are expected to represent the next generation of stem cell therapies and reviewed recent progress in this area. We also discussed potential applications of engineered stem cells and highlighted the most common challenges that must be addressed. Overall, this review has important guiding significance for the future design of new paradigms of stem cell products to improve their therapeutic efficacy.


Assuntos
Engenharia Celular , Medicina Regenerativa , Medicina Regenerativa/métodos , Transplante de Células-Tronco , Diferenciação Celular
18.
BMC Public Health ; 23(1): 2323, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-37996796

RESUMO

BACKGROUND: Compassion is closely linked to psychological well-being, and several assessment tools have been developed and studied to assess the level of compassion in different populations and for more precise measurement. There is currently a scarcity of comprehensive knowledge about compassion-related assessment tools, and our research provides an overview of these tools. AIMS: To identify scales used to measure compassion from different flows, and to assess their measurement properties and quality. METHODS: Focusing on compassion assessment tools, the authors conducted a thorough search of 10 Chinese and English databases from their establishment until August 14, 2022. Data extracted included the author, year, country, objectives, target population, as well as the primary evaluation content. Using the COSMIN checklist, the methodological quality and measurement properties of the included studies were appraised. This scoping review was registered with the Open Science Framework and followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. RESULTS: There were 15,965 papers searched, and 36 compassion-related measurement tools were identified in this study. None of the 36 studies provided possessed all nine psychometric properties, as outlined by the COSMIN criteria. On the basis of a systematic evaluation of quality, measurement qualities were ranked. The results for internal consistency and content validity were relatively favorable, whereas the results for structural validity were variable and the results for the remaining attributes were either uncertain or negative. A Venn diagram was used to illustrate the overlapping groups of compassion measurement tools based on the three-way flow of compassion. An overview of the reference instrument and theoretical basis for the included studies was provided, and half of them did not contain any theoretical or scale-based evidence. CONCLUSION: In this study, 36 compassion-related measuring instruments were identified, and the methodological quality and measurement properties of the included studies were acceptable. The included measurements were consistent with flows of compassion. A further focus of further research should be on developing theories in the compassion domain and developing instruments for measuring compassion that are multidimensional, multi-populations, and culturally relevant.


Assuntos
Lista de Checagem , Empatia , Humanos , Autorrelato , Lista de Checagem/métodos , Psicometria/métodos , Bem-Estar Psicológico , Reprodutibilidade dos Testes
19.
BMJ Open ; 13(11): e078051, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37918934

RESUMO

OBJECTIVE: To identify profiles of nurses' perceived professional benefits as well as their predictors. DESIGN: Cross-sectional study. SETTING: The study was carried out online in China. METHODS: From 6 July to 27 July 2022, a total of 1309 registered nurses participated in the survey by convenient sampling. We collected the Nurses' Perceived Professional Benefits Questionnaire and demographic data. Using latent profile analysis (LPA), subgroups of nurses' perceived professional benefits were identified. Moreover, univariate and multinomial logistic regression analyses were conducted to find the factors that were linked with the profiles. RESULTS: The survey was validly completed by 1309 nurses, with a 92.9% effective return rate. The findings of the LPA demonstrated three unique profiles: low-perceived professional benefits (11.8%), moderate-perceived professional benefits (57.1%) and high-perceived professional benefits (31.1%). There was a correlation between marital status, the number of night shifts per month and leadership role. CONCLUSIONS: According to our research, registered nurses have three unique professional benefit profiles. In order to sustain the nursing workforce, despite the fact that nurses get a high level of professional benefits, interventions are necessary to increase nurses' perception of their professional value.


Assuntos
Esgotamento Profissional , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Recursos Humanos de Enfermagem , Humanos , Estudos Transversais , China , Inquéritos e Questionários , Satisfação no Emprego
20.
Adv Sci (Weinh) ; 10(34): e2304287, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37867235

RESUMO

Circulating tumor cells (CTCs) and tumor-derived exosomes (TDEs) play an irreplaceable role in the metastatic cascade and preventing them from reaching distant organs via blood circulation helps to reduce the probability of cancer recurrence and metastasis. However, technologies that can simultaneously prevent CTCs and TDEs from reaching distant organs have not been thoroughly developed until now. Here, inspired by hemoperfusion, a pro-metastatic derivative eliminator (PMDE) is developed for the removal of both CTCs and TDEs from the peripheral blood, which also inhibits their biodistribution in distant organs. This device is designed with a dual antibody-modified immunosorbent filled into a capture column that draws peripheral blood out of the body to flow through the column to specifically capture CTCs and TDEs, followed by retransfusing the purified blood into the body. The PMDE can efficiently remove CTCs and TDEs from the peripheral blood and has excellent biocompatibility. Interestingly, the PMDE device can significantly inhibit the biodistribution of CTCs and TDEs in the lung and liver by scavenging them. This work provides a new perspective on anti-metastatic therapy and has broad prospects in clinical applications to prevent metastasis and recurrence.


Assuntos
Exossomos , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Distribuição Tecidual , Exossomos/metabolismo , Recidiva Local de Neoplasia/metabolismo , Pulmão/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...