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1.
Anal Chem ; 96(11): 4544-4552, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38362708

RESUMO

Emerging contaminants have recently evolved into a severe worldwide environmental issue. Organophosphate flame retardants (OPFRs) with neurotoxicity, genotoxicity, and reproductive and developmental toxicity are a class of notorious emerging contaminants that cause great concern. The development of high-efficiency and portable sensors for rapid online monitoring of OPFRs has become the primary demand for the exploration of the environmental migration and transformation of OPFRs. In this work, interestingly, the cataluminescence (CTL) phenomenon of OPFRs is first observed, and an ingenious multidimensional ratiometric CTL sensing strategy is developed for the recognition of multiple OPFRs. Three characteristic ratios are extracted from the multipeak CTL spectral curves based on energy transfer of single Tb/Eu-modified MgO sensing material, and thus a novel three-dimensional (3D) code recognition could be mapped out. This obtained 3D coordinate is found to be a unique characteristic for a given OPFR, just like an exclusive person's ID number, which can successfully discriminate and detect 10 kinds of OPFR vapors, including homologous series and isomers. More importantly, CTL mechanism investigations for OPFRs demonstrate that OPFRs undergo a series of chemical reaction processes, e.g., oxidative pyrolysis and hydroxylation, and different high-energy excited intermediates are generated, which trigger discrepant energy-transfer efficiency toward rare earth ions, leading to multipeak spectral profiles. Briefly, this proposed CTL analytical platform for OPFRs recognition initiates a new sensing principle for the efficient identification of emerging contaminants and shows significant prospects on rapid on-site detection.

2.
J Cardiovasc Pharmacol ; 81(1): 45-54, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36166514

RESUMO

ABSTRACT: Long noncoding RNAs and microRNAs (miRNAs) are emerging biomarkers involved in human diseases, and we focused on the roles of long noncoding RNA taurine upregulated gene 1 (TUG1) and miR-30b-3p in the related mechanisms of atherosclerosis-induced myocardial injury. ApoE-deficient mice were fed with high-fat diet to establish atherosclerotic models and then were subjected to either TUG1 downregulation or miR-30b-3p upregulation treatment. The serum myocardial enzymes, inflammatory biomarkers, pathological changes, intramyocardial macrophage infiltration, and apoptosis of cardiomyocytes in atherosclerotic mice were determined. The expression of TUG1, miR-30b-3p, and bromodomain protein 4 (Brd4) in atherosclerotic models was evaluated. Moreover, the correlations of TUG1, miR-30b-3p, and Brd4 were verified. TUG1 and Brd4 were increased while miR-30b-3p was decreased in atherosclerotic mice. The silenced TUG1 or elevated miR-30b-3p attenuated atherosclerosis-induced myocardial injury mainly by reducing serum myocardial enzyme content and inflammatory response, improving pathological changes, and preventing macrophage infiltration and cardiomyocyte apoptosis in atherosclerotic mice. Mechanistically, TUG1 could competitively bind with miR-30b-3p to prevent the degradation of its target gene Brd4. This study reveals that the silencing of TUG1 ameliorates atherosclerosis-induced myocardial injury by upregulating miR-30b-3p and downregulating Brd4, which may provide novel targets for atherosclerosis treatment.


Assuntos
Aterosclerose , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Apoptose/genética , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/patologia , Proteínas de Ciclo Celular/genética , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética
3.
Environ Res ; 231(Pt 2): 116218, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37224952

RESUMO

The accumulation of antibiotics in aquatic environments poses a serious threat to human health. Photocatalytic degradation is a promising method for removing antibiotics from water, but its practical implementation requires improvements in photocatalyst activity and recovery. Here, a novel graphite felt-supported MnS/Polypyrrole composite (MnS/PPy/GF) was constructed to achieve effective adsorption of antibiotics, stable loading of photocatalyst, and rapid separation of spatial charge. Systematic characterization of composition, structure and photoelectric properties indicated the efficient light absorption, charge separation and migration of the MnS/PPy/GF, which achieved 86.2% removal of antibiotic ciprofloxacin (CFX), higher than that of MnS/GF (73.7%) and PPy/GF (34.8%). The charge transfer-generated 1O2, energy transfer-generated 1O2, and photogenerated h+ were identified as the dominant reactive species, which mainly attacked the piperazine ring in the photodegradation of CFX by MnS/PPy/GF. The •OH was confirmed to participate in the defluorination of CFX via hydroxylation substitution. The MnS/PPy/GF-based photocatalytic process could ultimately achieve the mineralization of CFX. The facile recyclability, robust stability, and excellent adaptability to actual aquatic environments further confirmed MnS/PPy/GF is a promising eco-friendly photocatalyst for antibiotic pollution control.


Assuntos
Ciprofloxacina , Grafite , Humanos , Ciprofloxacina/química , Grafite/química , Polímeros/química , Pirróis/química , Antibacterianos/química
4.
Teach Learn Med ; : 1-14, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37409881

RESUMO

Phenomenon: Problem-based learning (PBL) has been widely adopted in medical schools across the globe. However, the dynamics of discourse moves in time sequences during such learning remain underexplored. This study investigated discourse moves used by PBL tutors and tutees to facilitate collaborative knowledge construction, and adopted sequential analysis to unpack the temporal dynamics of such moves during PBL knowledge construction in an Asian context. Approach: This study's sample comprised 22 first-year medical students and two PBL tutors at an Asian medical school. Two 2-h PBL tutorials were video-recorded and transcribed, and notes were made about the participants' non-verbal behaviors, including but not limited to body language and technology use. Descriptive statistics and visual representations were used to discern participation patterns as they evolved over time, and discourse analysis was applied to identify specific types of teacher and student discourse moves within knowledge construction. Lastly, lag-sequential analysis (LSA) was adopted to understand the sequential patterns of those discourse moves. Findings: The PBL tutors mainly used probing questions, explanation and clarification, compliments, encouragement, affirmation, and requests when facilitating PBL discussions. LSA revealed that discourse moves had the following four major paths. Teachers' content-related questions elicited both lower- and higher-level thinking from students; teachers' statements mediated between students' thinking levels and teachers' questions; there were relationships among teachers' social-facilitation discourse, students' thinking modes, and teachers' statements; and there was a sequential relationship among teachers' statements, students' facilitation, teachers' process-related discourse, and students' silences. Insights: This study revealed the importance of using probing questions to facilitate students' knowledge construction as they proceeded from lower- to higher-level thinking. This study also fills a gap in the current literature by adopting the innovative LSA methodology to explore teachers' and students' discourse move sequences in PBL. The results have important practical implications for PBL tutors regarding when and how to facilitate their students' collaborative knowledge construction.

5.
Med Teach ; 45(12): 1387-1394, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37270764

RESUMO

PURPOSE: With undergraduate medical education shifting to an integrated, student-centered approach, self-regulated learning (SRL) skills are critical for student success. Educational research holds that learning strategy effectiveness is context dependent. Our study aims to explore what strategies medical students use to support SRL when engaged in the specific context of an integrated, student-centered curriculum. APPROACH: This study took place in two medical schools with integrated, student-centered curricula. Semi-structured interviews were conducted with first-year medical students from both schools, asking them to reflect on the learning strategies they used throughout their first year of medical school. Interview data was analyzed first deductively using the SRL framework and then inductively to understand the specific strategies being used. FINDINGS: Students engaged in strategies to support SRL in ways that were unique to the integrated, student-centered context. We found that medical students developed strategies to plan for integration and building connections across material during all three phases of self-regulated learning. INSIGHTS: By identifying specific tasks and behaviors students utilized during their first year of medical school, this study provides a roadmap that students and educators can use to help students become self-regulated learners.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Aprendizagem , Currículo , Faculdades de Medicina
6.
BMC Med Educ ; 23(1): 457, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340427

RESUMO

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.


Assuntos
Educação Interprofissional , Estudantes de Ciências da Saúde , Humanos , Aprendizagem , Resolução de Problemas , Universidades , Relações Interprofissionais , Atitude do Pessoal de Saúde
7.
J Environ Manage ; 340: 117999, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37119633

RESUMO

Electrolytic Manganese Residue (EMR) is a solid waste containing soluble sulfate, discharged by electrolytic manganese industries. The accumulation of EMR in ponds poses a significant hazard to both safety and the environment. This study utilized innovative geotechnical test techniques to conduct a series of tests, investigating the effect of soluble salts on the geotechnical characteristics of EMR. The results revealed that soluble sulfates had a significant impact on the geotechnical characteristics of the EMR. In particular, the infiltration of water leached away the soluble salts, causing a non-uniform particle size distribution and decreasing the shear strength, stiffness, and liquefaction resistance of the EMR. Nevertheless, an increase in the stacking density of EMR could improve its mechanical characteristics and inhibited the dissolution of soluble salts. Therefore, increasing the density of stacked EMR, ensuring the effectiveness and non-obstruction of the water interception facilities, and reducing rainwater infiltration could be effective measures to enhance the safety and reduce the environmental hazard of EMR ponds.


Assuntos
Manganês , Sais , Manganês/química , Eletrólitos/química , Resíduos Sólidos/análise , Água
8.
BMC Surg ; 22(1): 155, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501784

RESUMO

BACKGROUND: To investigate the effectiveness and feasibility of a novel vertebral osteotomy technique, transpedicular opening-wedge osteotomy (TOWO) was used to correct rigid thoracolumbar kyphotic deformities in patients with ankylosing spondylitis (AS). METHODS: Eighteen AS patients underwent TOWO to correct rigid thoracolumbar kyphosis. Radiographic parameters were compared before surgery, 1 week after surgery and at the last follow-up. The SRS-22 questionnaire was given before surgery and at the last follow-up to evaluate clinical improvement. The operating time, estimated blood loss and complications were analyzed. RESULTS: The mean operating time and estimated blood loss were 236 min and 595 ml, respectively. The mean preoperative sagittal vertical axis (SVA), thoracic kyphosis (TK), pelvic tilt (PT) and thoracolumbar kyphosis (TLK) were 158.97 mm, 51.24 mm, 43.63 mm and 41.74 mm, respectively, and decreased to 66.72 mm, 35.96 mm, 27.21 mm and 8.67 mm at the last follow-up. The mean preoperative lumbar lordosis (LL) and sacral slope (SS) were 8.30 ± 24.43 mm and 19.67 ± 9.40 mm, respectively, which increased to 38.23 mm and 28.13 mm at the last follow-up. The mean height of the anterior column of osteotomized vertebrae increased significantly from 25.17 mm preoperatively to 37.59 mm at the last follow, but the height of the middle column did not change significantly. SRS-22 scores were improved significantly at the last follow-up compared with preoperatively. Solid bone union was achieved in all patients after 12 months of follow-up, and no screw loosening, screw removal or rod breakage was noticed at the last follow-up. CONCLUSIONS: TOWO could achieve satisfactory kyphosis correction by opening the anterior column instead of vertebral body decancellation and posterior column closing, thus simplifying the osteotomy procedure and improving surgical efficacy.


Assuntos
Cifose , Espondilite Anquilosante , Humanos , Cifose/etiologia , Cifose/cirurgia , Vértebras Lombares/cirurgia , Osteotomia/métodos , Estudos Retrospectivos , Espondilite Anquilosante/complicações , Espondilite Anquilosante/cirurgia
9.
BMC Med Educ ; 22(1): 577, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35897094

RESUMO

BACKGROUND: Twitter has gained increasing popularity and attention as a professional learning environment to share knowledge, exchange information, make connections, and build networks. To evaluate the effectiveness of Twitter-facilitated online discussions, a community of inquiry framework could be used with the three key elements of online environments: cognitive presence, social presence, and teaching presence. This study aims to explore how medical educators participate in synchronous online discussions on Twitter using #MedEdChat, and how participants' perceptions toward the three presences, sense of connectedness and interactions influenced their online satisfaction. METHODS: A survey invitation was emailed using the medical education email list DR-ED and was posted during the weekly Twitter conversations in December 2020, to solicit participants who have been involved in any kind of #MedEdChat activities (i.e., read transcripts or directly participate in discussions). RESULTS: A total of 68 people responded. Through descriptive analysis and path analysis, we found that almost half of the survey respondents were lurkers on #MedEdChat who read others' tweets or transcripts. In addition, participants mainly used Twitter for resource sharing, collaborating with others, and networking. Participants rated teaching (i.e., moderator) presence the highest, followed by overall satisfaction, cognitive presence, sense of connectedness, social presence, and interactions. Among them, sense of connectedness and cognitive presence were significantly associated with participants' overall satisfaction. CONCLUSIONS: This study provided significant implications for using Twitter as a professional learning community to conduct online discussion activities. Facilitators could think of ways to improve participation by providing tutorials on how to participate on Twitter discussions, introduce or ask new participants to introduce themselves, facilitate discussion with intriguing questions, and invite medical educators of different roles as well as medical students and residents to join to bring in diverse perspectives.


Assuntos
Educação Profissionalizante , Mídias Sociais , Estudantes de Medicina , Humanos , Conhecimento , Satisfação Pessoal
10.
Neurochem Res ; 46(9): 2297-2306, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34086144

RESUMO

As a serious trauma of the neurological system, spinal cord injury (SCI) results in permanent disability, gives rise to immediate vascular damage and a wide range of matters that induce the breakage of blood spinal cord barrier (BSCB). SCI activates the expression of MMP-2/9, which are considered to accelerate the disruption of BSCB. Recent research shows that Dl-3-n-butylphthalide (NBP) exerted protective effects on blood spinal cord barrier in animals after SCI, but the underlying molecular mechanism of NBP on the BSCB undergoing SCI is unknown. Here, our research show that NBP inhibited the expression of MMP-2/9, then improved the permeability of BSCB following SCI. After the T9 level of spinal cord performed with a moderate injury, NBP was managed by intragastric administration and further performed once a day. NBP remarkably improved the permeability of BSCB and junction proteins degration, then promoted locomotion recovery. The protective effect of NBP on BSCB destruction is related to the regulation of MMP-2/9 induced by SCI. Moreover, NBP obviously inhibited the MMP-2/9 expression and junction proteins degradation in microvascular endothelial cells. In conclusion, our results indicate that MMP-2/9 are relevant to the breakdown of BSCB, NBP impairs BSCB destruction through inhibiting MMP-2/9 and promotes functional recovery subjected to SCI. NBP is likely to become a new nominee as a therapeutic to treat SCI via a transigent BSCB.


Assuntos
Benzofuranos/uso terapêutico , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Animais , Hipóxia Celular/efeitos dos fármacos , Claudina-5/metabolismo , Feminino , Glucose/deficiência , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Ocludina/metabolismo , Oxigênio/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/enzimologia
11.
J Appl Clin Med Phys ; 22(10): 239-248, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34480832

RESUMO

OBJECTIVES: This study was aimed to systematically review the existing literature and explore more the diagnostic value of T1 and T2 mapping in acute myocarditis. METHODS: Studies were searched from five electronic databases. Sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curves (SROC) were calculated to present diagnostic performance. A meta-regression and subgroup analysis was performed based on validation (endomyocardial biopsy [EMB] vs. clinical criteria). RESULTS: A total of 10 studies were included, with 400 myocarditis patients and 266 controls. Native T1, T2, and extracellular volume (ECV) values were significantly increased in the myocarditis group. Pooled sensitivities for T1, T2 mapping, and ECV were 0.84 (0.78-0.88), 0.77 (0.69-0.83), and 0.69 (0.50-0.83), respectively. Pooled specificities were 0.86 (0.69-0.95), 0.83 (0.73-0.89), and 0.77 (0.63-0.87), respectively. The DORs were 32 (12-87), 16 (8-30), and 7 (4-14), respectively. The areas under the curve (AUC) of SROC were 0.87 (0.84-0.90), 0.86 (0.82-0.89), and 0.80 (0.76-0.83), respectively. In the meta-regression and subgroup analysis, significantly lower specificities of T1 and T2 mapping were observed in EMB studies (p < 0.01). CONCLUSION: The currently available evidence shows that T1 and T2 mapping including ECV alone offer comparably good diagnostic performance for the detection of acute myocarditis. The reason for the observed mismatch with EMB findings should be further investigated.


Assuntos
Miocardite , Doença Aguda , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocardite/diagnóstico por imagem , Miocárdio , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
12.
Nanotechnology ; 31(29): 295101, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32203949

RESUMO

Despite the promising target of immunosuppressive enzyme indoleamine-2,3-dioxygenase (IDO) for cancer immunotherapy, IDO blockade monotherapy does not show significant benefit to cancer patients in the clinic. Recent research has focused on the combinatorial therapy of the IDO inhibitor and the immune checkpoint blockade or chemotherapy. Here, we synthesize a drug conjugate methyltryptophan-paclitaxel (MP) by linking the IDO inhibitor, D-1-methyltryptophan (D-1MT), to the chemotherapeutic agent, paclitaxel (PTX), through an ester bond. MP exhibits a similar tubulin-stabilizing effect to PTX. Like PTX, MP binds to human serum albumin to form albumin-bound MP nanoparticles (MP NPs) with a particle size of ∼115 nm in diameter. MP NPs significantly improve the tumor concentration of D-1MT due to the hydrolysis of MP in tumors. The codelivery of PTX and D-1MT offered by MP NPs in tumors significantly enhances the anti-tumor effect compared with the albumin-bound PTX NPs. Immune cell phenotyping reveals that MP NPs ameliorate the immune environment through increasing the number of the effector CD8+ T cells, and decreasing the population of regulatory T cells and granulocyte-like myeloid-derived suppressor cells. These results prove that the design of the twin drug from the IDO inhibitor and PTX synergizes the anti-tumor effect and shows promise in clinical translation.


Assuntos
Albuminas/farmacologia , Antineoplásicos/farmacologia , Melanoma Experimental/tratamento farmacológico , Paclitaxel/farmacologia , Triptofano/análogos & derivados , Albuminas/química , Animais , Antineoplásicos/química , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Composição de Medicamentos , Sinergismo Farmacológico , Feminino , Imunoterapia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Melanoma Experimental/imunologia , Camundongos , Nanopartículas , Paclitaxel/química , Tamanho da Partícula , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Resultado do Tratamento , Triptofano/química , Triptofano/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
BMC Med Educ ; 20(1): 100, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32234040

RESUMO

BACKGROUND: The flipped-classroom model is increasingly being adopted in competency-based medical education. However, it poses a major challenge to students who have not mastered self-regulated learning strategies. This study explores which self-regulated learning skills affect student learning performance in the first 2 years of medical school at a university in the midwestern United States. METHODS: Survey data were used to assess how 146 first- and second-year medical students' use of self-regulated learning strategies affected their performance on standardized tests. RESULTS: Based on the results of regression analysis and content analysis, it was found that the use of peer learning and help-seeking positively affected the performance of first- and second-year students, respectively; whereas the use of rehearsal had a negative effect on student learning outcomes. CONCLUSIONS: The study findings imply that during the transition period from traditional lecture-intensive learning to flipped-classroom learning, promoting peer learning and help-seeking could significantly improve students' academic achievement.


Assuntos
Educação de Graduação em Medicina/métodos , Autocontrole , Autoaprendizagem como Assunto , Estudantes de Medicina/psicologia , Currículo , Escolaridade , Comportamento de Busca de Ajuda , Humanos , Meio-Oeste dos Estados Unidos , Modelos Educacionais , Grupo Associado , Inquéritos e Questionários
14.
Neurochem Res ; 44(4): 763-775, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30603983

RESUMO

Traumatic spinal cord injury (SCI) is a devastating condition with few efficacious drugs. Sinomenine, a bioactive alkaloid extracted from medicinal herb, has been used as a treatment of rheumatoid diseases. This present study explored the therapeutic effects of sinomenine on locomotor dysfunction and neuropathology in SCI. Our findings revealed that sinomenine mitigated neurological deficits and enhanced neuronal preservation, paralleled with a reduction of apoptosis. Also, sinomenine significantly reduced inflammatory cytokines and oxidative stress factors. We further examined erythroid-2-related factor 2 (Nrf2) nuclear translocation, which mainly controls the coordinated expression of important antioxidant and detoxification genes. An increase in Nrf2 translocation from cytoplasm to nucleus and Nrf2-mediated transactivation was observed after sinomenine administration. Knocking down Nrf2 by siRNA could counteract sinomenine-mediated anti-oxidant stress and anti-inflammation following H2O2-stimulated and LPS-stimulated PC12 cells. Together, our findings indicated that sinomenine has the potential to be an effective therapeutic agent for SCI by inhibiting inflammation and oxidative stress via Nrf2 activation.


Assuntos
Morfinanos/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Animais , Feminino , Peróxido de Hidrogênio/toxicidade , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Morfinanos/farmacologia , Fator 2 Relacionado a NF-E2/agonistas , Estresse Oxidativo/fisiologia , Células PC12 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Vértebras Torácicas
15.
J Cell Mol Med ; 20(6): 1062-75, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26769343

RESUMO

After spinal cord injury (SCI), disruption of blood-spinal cord barrier (BSCB) elicits blood cell infiltration such as neutrophils and macrophages, contributing to permanent neurological disability. Previous studies show that epidermal growth factor (EGF) produces potent neuroprotective effects in SCI models. However, little is known that whether EGF contributes to the integrity of BSCB. The present study is performed to explore the mechanism of BSCB permeability changes which are induced by EGF treatment after SCI in rats. In this study, we demonstrate that EGF administration inhibits the disruption of BSCB permeability and improves the locomotor activity in SCI model rats. Inhibition of the PI3K/Akt pathways by a specific inhibitor, LY294002, suppresses EGF-induced Rac1 activation as well as tight junction (TJ) and adherens junction (AJ) expression. Furthermore, the protective effect of EGF on BSCB is related to the activation of Rac1 both in vivo and in vitro. Blockade of Rac1 activation with Rac1 siRNA downregulates EGF-induced TJ and AJ proteins expression in endothelial cells. Taken together, our results indicate that EGF treatment preserves BSCB integrity and improves functional recovery after SCI via PI3K-Akt-Rac1 signalling pathway.


Assuntos
Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/uso terapêutico , Transdução de Sinais , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/patologia , Junções Aderentes/efeitos dos fármacos , Junções Aderentes/metabolismo , Animais , Cromonas/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Fator de Crescimento Epidérmico/administração & dosagem , Feminino , Glucose/deficiência , Humanos , Morfolinas/farmacologia , Fármacos Neuroprotetores/farmacologia , Oxigênio , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo
16.
Neurochem Res ; 41(4): 813-25, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26582233

RESUMO

Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB), which leads to infiltration of blood cells, inflammatory responses and neuronal cell death, with subsequent development of spinal cord secondary damage. Recent reports pointed to an important role of retinoic acid (RA), the active metabolite of the vitamin A, in the induction of the blood-brain barrier (BBB) during human and mouse development, however, it is unknown whether RA plays a role in maintaining BSCB integrity under the pathological conditions such as SCI. In this study, we investigated the BSCB protective role of RA both in vivo and in vitro and demonstrated that autophagy are involved in the BSCB protective effect of RA. Our data show that RA attenuated BSCB permeability and also attenuated the loss of tight junction molecules such as P120, ß-catenin, Occludin and Claudin5 after injury in vivo as well as in brain microvascular endothelial cells. In addition, RA administration improved functional recovery of the rat model of trauma. We also found that RA could significantly increase the expression of LC3-II and decrease the expression of p62 both in vivo and in vitro. Furthermore, combining RA with the autophagy inhibitor chloroquine (CQ) partially abolished its protective effect on the BSCB and exacerbated the loss of tight junctions. Together, our studies indicate that RA improved functional recovery in part by the prevention of BSCB disruption via the activation of autophagic flux after SCI.


Assuntos
Autofagia , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/irrigação sanguínea , Tretinoína/farmacologia , Animais , Encéfalo/irrigação sanguínea , Cateninas/metabolismo , Células Cultivadas , Claudinas/metabolismo , Feminino , Humanos , Microvasos/metabolismo , Atividade Motora/efeitos dos fármacos , Ocludina/metabolismo , Permeabilidade , Ratos Sprague-Dawley , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , beta Catenina/metabolismo , delta Catenina
18.
Opt Express ; 22(13): 15924-31, 2014 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-24977847

RESUMO

For the first time, we studied the effect of structural relaxation on the NIR spectroscopic properties of bismuth-activated germanium glasses below glass transition temperature. Interestingly, distinct change behavior of NIR luminescence is observed at two different heat-treatment temperature ranges corresponding to two different relaxation behavior of glass structure. Besides, when structural modified by partly substituting B(2)O(3) for GeO(2), a narrower and more thermal sensitive luminescence is observed, which is inexplicable by "inhomogeneous broadening" and we tentatively attribute it to a defect-involved reason. Fundamentally the results here not only provide us a deeper insight into the optical property of bismuth-activated materials but also increase our understanding of the glassy state, and practically it delivers some valuable guidance in designing bismuth-activated glasses with superior NIR optical properties.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38240635

RESUMO

Physical activity (PA) is crucial for preschool-aged children's health and development. However, limited evidence exists regarding the feasibility of implementing home-based interventions and how program components influence parent cognitions and practices and child PA. This study evaluated the feasibility and potential efficacy of a family-based PA intervention on objectively measured PA, fundamental movement skills (FMS), parental efficacy, support, goal setting and parent-child co-activity. Guided by social cognitive theory, an 8-week cluster randomised controlled trial was conducted in Hong Kong. The trial included parental workshops, FMS training, PA homework, social media activity sharing and exercise equipment provision. Data were collected at baseline (Time 1; April 2019) and at the end of the intervention period (Time 2; approximately 2 months later) from 108 parent-child pairs in five preschools. The intervention led to increased moderate-to-vigorous PA and FMS in children, along with improved parental self-efficacy, goal setting, supportiveness and co-participation. However, parental PA did not show significant changes. Parents expressed high satisfaction, supporting the need for tailoring interventions to address the unique needs and preferences of young children and their parents. Reinforcing the parental role and providing informative materials and training can promote healthy lifestyles in early childhood.

20.
J Control Release ; 366: 596-610, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184232

RESUMO

Insufficient delivery of therapeutic agents into solid tumors by systemic administration remains a major challenge in cancer treatment. Secreted protein acidic and rich in cysteine (SPARC) has high binding affinity to albumin and has been shown to enhance the penetration and uptake of albumin-based drug carriers in tumors. Here, we developed a strategy to alter the tumor microenvironment (TME) by upregulating SPARC to enhance the delivery efficiency of albumin-based drug carriers into tumors. We prepared albumin nanoparticles encapsulating an NF-κB controllable CRISPR activation system (SP-NPs). SP-NPs achieved tumor-selective SPARC upregulation by responding to the highly activated NF-κB in tumor cells. Whereas a single dose of SP-NPs only modestly upregulated SPARC expression, serial administration of SP-NPs created a positive feedback loop that induced progressive increases in SPARC expression as well as tumor cell uptake and tumor penetration of the nanoparticles in vitro, in organoids, and in subcutaneous tumors in vivo. Additionally, pre-treatment with SP-NPs significantly enhanced the anti-tumor efficacy of Abraxane, a commercialized albumin-bound paclitaxel nanoformulation. Our data provide evidence that modulating SPARC in the TME can enhance the efficiency of albumin-based drug delivery to solid tumors, which may result in new strategies to increase the efficacy of nanoparticle-based cancer drugs.


Assuntos
NF-kappa B , Neoplasias , Humanos , Osteonectina , Albuminas , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Portadores de Fármacos , Paclitaxel Ligado a Albumina , Microambiente Tumoral
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