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BACKGROUND: The aging society has resulted in enormous demand for long-term care services. However, ageism is a common phenomenon in long-term care facilities, which not only hinders the quality of care for the recipients but also negatively influences caregivers' well-being. In this paper, we first applied the Fraboni Scale of Ageism (FSA) to evaluate its reliability and construct validity among Chinese long-term caregivers in nursing homes. This study could contribute to assessing the prevalence of ageism in Chinese long-term caregivers, prompting facilities and the government to recognize the issue of ageism and explore necessary interventions to reduce ageism in long-term caregivers. METHODS: This is a cross-sectional study. We recruited 392 long-term caregivers using a convenience sampling strategy in nursing homes from two cities in Chinese central and northern regions. Parameters included the demographic characteristics, Cronbach's alpha coefficients, and intraclass correlation coefficient. The construct validity was conducted by exploratory factor analysis and confirmatory factor analysis. RESULTS: The Cronbach's alpha of FSA (Chinese version) was 0.856 and ICC was 0.871. The factor analysis identified 3 principal factors, explaining 43.95% of the total variance. The 3-factor model was confirmed to fit by confirmatory factor analysis. CONCLUSIONS: The findings confirm that the FSA is easy to use and has good psychometric properties. This study will contribute to improving the condition of ageism, thereby improving the quality of care for the elderly and retention of professional talents in the LTC system.
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Etarismo , Cuidadores , Casas de Saúde , Psicometria , Humanos , Casas de Saúde/normas , Etarismo/psicologia , Masculino , Feminino , Estudos Transversais , Psicometria/métodos , Cuidadores/psicologia , Pessoa de Meia-Idade , Idoso , Adulto , Assistência de Longa Duração/métodos , Idoso de 80 Anos ou mais , Reprodutibilidade dos Testes , Instituição de Longa Permanência para Idosos/normasRESUMO
BACKGROUND: There are a variety of determinants that are key to functional disability of older adults. However, little is known regarding the relationship between cognitive frailty and disability among older people. The aims of this study were to examine the associations between cognitive frailty and its six components with instrumental activities of daily living (IADL) functioning in community-dwelling older adults. METHODS: A total of 313 community-dwelling older adults (aged ≥ 65 years) were recruited from eight community centers in central China. Cognitive frailty was operationalized using the Mini-Mental State Examination for the evaluation of cognitive status and the Fried criteria for the evaluation of physical frailty. The outcome was functional disability assessed by the IADL scale. The association between cognitive frailty, as well as its components, and IADL limitations was identified by conducting binary logistic regression analysis. RESULTS: The prevalence of cognitive frailty was 8.9% in this study. The results showed that cognitive frailty (OR = 22.86) and frailty without cognitive impairment (OR = 8.15) were associated with IADL limitations. Subdimensions of cognitive frailty, exhaustion, weakness, low physical activity and cognitive impairment components were independently associated with IADL limitations. CONCLUSION: Cognitive frailty was associated with a higher prevalence of disability. Interventions for improving cognitive frailty should be developed to prevent IADL disability among community-dwelling older adults in China.
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Fragilidade , Idoso , Humanos , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Idoso Fragilizado/psicologia , Vida Independente/psicologia , Estudos Transversais , Atividades Cotidianas , China/epidemiologia , Cognição , Avaliação Geriátrica/métodosRESUMO
BACKGROUND X-PROLYL AMINOPEPTIDASE 3: (XPNPEP3) mutations are known to cause nephronophthisis-like nephropathy-1 (NPHPL1), a rare autosomal-recessive kidney disease characterized by progressive kidney failure and cystic kidney disease in childhood. The full phenotypic spectrum associated with mutations in XPNPEP3 is not fully elucidated. CASE PRESENTATION: A 13-year-old Chinese female patient with intellectual disability presented with a 2-year history of convulsions and fatigue, with a recent episode of swelling, breathlessness, and nocturnal dyspnea lasting 10 days. The patient was diagnosed with heart failure and kidney failure. Whole exome sequencing revealed a homozygous c.970-2 A > G mutation in XPNPEP3 associated with severe cardiac dysfunction and neurological symptoms, including epilepsy and intellectual disability. Notably, kidney ultrasound did not reveal the typical changes of NPHPL1, and kidney failure was hypothesized to be secondary to cardiac dysfunction rather than primary kidney pathology. CONCLUSIONS: This case suggests the possible association of additional phenotypic features associated with XPNPEP3 mutations, emphasizing the need for further investigation into the heterogeneous clinical presentations associated with XPNPEP3 mutations. The findings highlight the importance of considering alternative phenotypes in patients with genetic mutations traditionally associated with specific diseases. Segregation and functional analyses are necessary to determine causality between the c.970-2 A > G XPNPEP3 mutation and disease.
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Insuficiência Cardíaca , Mutação , Adolescente , Feminino , Humanos , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/etiologia , Deficiência Intelectual/genética , Fenótipo , Prolil OligopeptidasesRESUMO
BACKGROUND: The population aging trend and the shortage of elderly care workers require the long-term care profession to become more attractive. However, the professional attractiveness among long-term care workers has yet to be extensively studied. This study aims to identify the factors that influence the attractiveness of the long-term care profession for nursing home (NH) care workers.. METHODS: A cross-sectional study was conducted in more than 50 NHs. Perception of professional attractiveness among long-term care workers and potential associated factors were measured using the Attractive Work Questionnaire (AWQ) and structural instruments including the Fraboni Scale of Ageism (FSA) and the Maslach Burnout Inventory (MBI). A multiple linear regression method was employed to explore the influence of potential independent variables on professional attractiveness. RESULTS: The overall response rate was 99%. The results showed the score of professional attractiveness (185.37 ± 20.034), as well as the scores of each component (99.26 ± 11.258 for work condition, 30.13 ± 3.583 for work content, and 55.99 ± 7.074 for job satisfaction). Findings of multiple linear regression analysis indicated that age(ß = 0.129, p<.05), years of work(ß = 0.156, p<.05), 12-hour shifts(ß = 0.185, p<.05), and training times per year(ß = 0.148, p<.05) positively associated with long-term care workers perceived professional attractiveness. Whereas only ageism(ß=-0.267, p<.05) significantly and negatively influenced professional attractiveness. CONCLUSIONS: The perceived professional attractiveness of long-term care workers in NHs was acceptable. Age, years of work, shifts, training opportunities, and ageism contributed to the professional attractiveness of nursing home care workers in China. Target intervention measures should be taken to enhance the attractiveness of long-term care careers so as to avoid the shortage of long-term care workers.
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Assistência de Longa Duração , Casas de Saúde , Humanos , Estudos Transversais , China , Masculino , Feminino , Assistência de Longa Duração/psicologia , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Satisfação no Emprego , Etarismo/psicologia , Esgotamento Profissional/psicologiaRESUMO
AIMS: To identify correlations among job burnout, structural empowerment, and patient safety culture (PSC), and to explore the potential moderating effect of structural empowerment on the associations between burnout and PSC. DESIGN: The study used a cross-sectional survey design. METHODS: Convenient sampling was employed. We conducted an anonymous online survey in January 2024 among nurses employed at hospitals in three regions of China. Job burnout, structural empowerment, and perceptions of PSC were assessed. A total of 1026 useable surveys were included in the analyses. Descriptive statistics were performed using SPSS software. A latent structural equation modeling approach using Mplus software was used to analyze the moderating effect. RESULTS: The proposed hypothetical model was supported. Job burnout had a strong direct negative effect on structural empowerment and PSC. Structural empowerment had a significant moderating effect on the relationship between job burnout and PSC. CONCLUSION: The empirically validated moderation model and study results suggest that managers of healthcare organisations can improve patient safety and care quality by fostering empowerment and providing sufficient support to clinical nurses. IMPLICATION: The findings of this study suggest that providing more support, resources, and information is likely to be effective in weakening the detrimental impact of job burnout on PSC. This study provides insights into the possible approaches that may improve patient safety. To control the impact of nurses' burnout on care quality, nurse managers should increase empowerment as well as staff nurse engagement. REPORTING METHOD: We have adhered to relevant EQUATOR guidelines and conducted an observational study, following the STROBE checklist. PUBLIC CONTRIBUTION: During the data collection phase of this study, clinical caregivers participated in completing the online survey.
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We aimed to analyse the clinical characteristics of children with different types of anomalous aortic origin of the coronary artery (AAOCA) at different ages, and to discuss the factors related to myocardial ischaemia. In this retrospective study, we included 69 children diagnosed with AAOCA using CT coronary angiography; we classified the participants based on the type of AAOCA, age, and high-risk anatomy. The clinical characteristics of the different AAOCA types and age groups were compared, and the correlation between manifestations and high-risk anatomy was analysed. Anomalous origin of the left coronary artery from the right coronary artery sinus, anomalous origin of the right coronary artery from the left coronary artery sinus, and a coronary artery origin without coronary sinuses was found in 10 (14.5%), 57 (82.6%), 2 (2.9%) patients, respectively. There were no significant differences in sex, clinical manifestations, percentage of positive myocardial injury markers, electrocardiogram, transthoracic echocardiography, or proportion of high-risk anatomy among the groups with different AAOCA types. According to age group, the proportion of asymptomatic infants and pre-schoolers was the highest (p < 0.001). Forty-three patients (62.3%) had high-risk anatomy and were more likely to present with severe symptoms and cardiac syncope (p < 0.05). Conclusion: There were no significant differences in the proportions of high-risk anatomy and clinical characteristics among children with different AAOCA types. We found a relation between the severity of AAOCA clinical symptoms and anatomical risk. What is Known: ⢠Clinical symptoms in children with AAOCA are varied and the results of routine cardiological examinations lack specificity. ⢠High-risk anatomical features, exercise, cardiac symptoms, and ALCA are risk factors for the occurrence of SCD in patients with AAOCA. What is New: ⢠Compared the clinical characteristics of different types of AAOCA and ages. ⢠Analysed the correlation between symptoms and high-risk anatomical features.
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Blends with different proportions of protein or starch show different rheological behaviors, which may be related to the fibrous structure formation of extruded textured plant proteins. The consistency factor K and the viscosity exponent n of soybean-protein-isolate (SPI)/wheat-gluten (WG)/corn-starch (CS) blends were investigated through capillary rheometry. All blends exhibited shear-thinning behavior at 80 °C and 50% moisture. The CS content in SPI/CS blends or WG content in SPI/WG blends showed a positive relation to the viscosity exponent n and a negative relation to the consistency factor K. However, there was no correlation between the CS content in WG/CS blends and n or K. The coefficient of determination of the linear relationship between K and mass fraction in SPI/CS, SPI/WG/CS, SPI/WG and WG/CS decreased from 0.872 to 0.073. SPI was more likely to form a non-interactive structure, while wheat-gluten was more likely to form a highly interactive structure. It turned out that the materials with globular morphology, such as soybean-protein-isolate and corn-starch, are likely to form a non-interactive structure.
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Amido , Triticum , Glutens/química , Proteínas de Soja/química , Glycine max/metabolismo , Amido/química , Triticum/química , Viscosidade , Zea mays/químicaRESUMO
PURPOSE: We aim to compare the long-term oncologic outcomes, including overall survival (OS), cancer-specific survival (CSS), and bladder cancer recurrence (BCR) among patients with ureter carcinoma who received nephroureterectomy (RNU) or partial ureterectomy (PU). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results database between 2004 and 2015 of patients with ureter carcinoma who underwent RNU or PU. Propensity score matching (PSM) was applied to balance the baseline data. The Kaplan-Meier method with subgroup analysis was conducted to verify the effect of the two surgery types. Fine-Gray competing risk regression estimated the cumulative incidence of BCR. RESULTS: A total of 2509 patients were involved; 665 (26.5%) patients underwent PU, and 1844 (73.5%) patients underwent RNU. Patients who underwent PU experienced a similar OS and CSS compared with those who underwent RNU in both PSM cohorts (HR [hazard ratio], 1.07 (0.93-1.23); P = 0.37; HR, 1.10 (0.91-1.31); P = 0.32, respectively), adjust model (HR, 0.99 (0.88-1.11); P = 0.87; HR, 1.05 (0.90-1.20); P = 0.55, respectively), and the subgroup analysis. For BCR, the patients who underwent PU were associated with a similar risk of developing BCR compared with those that received RNU, according to the univariate competing risk model (P = 0.47), adjust model (HR, 1.00 (0.73-1.37); P = 1), and subgroup analysis. CONCLUSION: RNU did not confer a distinct survival advantage compared with PU, which supports the role of PU in treating patients with ureter carcinomas.
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Carcinoma de Células de Transição , Ureter , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Ureter/cirurgia , Nefroureterectomia , Estudos Retrospectivos , Nefrectomia/métodos , Carcinoma de Células de Transição/cirurgia , Neoplasias Ureterais/cirurgia , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Left-sided accessory pathways (APs) can be accessed with either a transaortic (TA) or transseptal approach (TS). For children with Marfan syndrome (MFS) who have aortic disease, the use of TA can aggravate the disease, making TS the best choice for these patients. CASE SUMMARY: A 10-year-old girl was hospitalized because of intermittent heart palpitations and chest tightness. She was diagnosed with MFS, supraventricular tachycardia, Wolff-Parkinson-White syndrome, and left-sided AP was detected by cardiac electrophysiological. Catheter ablation was successfully performed via TS under the guidance of the Ensite system. During the follow-up, no recurrence or complications occurred. CONCLUSION: The TS for catheter ablation of left-sided APs can be considered in children with MFS. Adequate evaluation and selection of the appropriate puncture site are particularly important.
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Tumor-draining lymph nodes (TDLNs) are the first sites where tumor components reach and dendritic cells (DCs) present tumor-associated antigens to T cells. DCs rely on autophagy to process tumor antigens into epitope peptides to form epitope-MHC complexes. Selective delivery of autophagy-stimulating drugs to TDLNs may be a precise strategy to boost chemotherapy-induced antitumor immunity. Here, a multistage stimulating strategy is proposed to activate the antitumor immunity cascade by inducing immunogenic death of tumor cells and elevating antigen presentation of DCs in TDLNs. A tumor-microenvironment-responsive "albumin-hitchhiking" micelle is established by self-assembling tumor-targeting oxaliplatin prodrug and lipophilized trehalose prodrug. This demonstrates that lipophilic modification of trehalose with a DSPE tail and the precise exposure in the tumor site enhances its binding to endogenous albumin and realizes TDLNs-selective reflux, where it upregulates antigen processing and presentation of DCs. This study introduces an approach for targeted delivery to TDLNs and provides insights into mechanisms of autophagy in tumor-specific immunity.
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Neoplasias , Pró-Fármacos , Humanos , Células Dendríticas , Pró-Fármacos/farmacologia , Pró-Fármacos/metabolismo , Trealose/metabolismo , Albuminas/metabolismo , Autofagia , Epitopos , Linfonodos , Microambiente TumoralRESUMO
The upregulated autophagy fuels the activation of hepatic stellate cells (HSCs) to promote hepatic fibrosis. However, the lack of specific inhibitors targeting autophagy and high requirements for cell targeting impede the application of antifibrotic therapy that targets autophagy. RNA interference (RNAi)-based short interfering RNA (siRNA) provides an approach to specifically inhibit autophagy. The therapeutic potential of siRNA, however, is far from being exploited due to the lack of safe and effective delivery vehicles. The cytoplasmic delivery of siRNA is essential for RNAi, and the intracellular trafficking pathway of vehicles determines the fate of siRNA. Unfortunately, the lysosomal degradation pathway, the intracellular fate of most gene vehicles, impedes RNAi efficiency. Inspired by the trafficking pathway of some viruses infecting cells, KDEL-grafted chondroitin sulfate (CK) was designed to alter the intracellular delivery fate of siRNA. The well-designed CD44-Golgi-ER trafficking pathway of CK was realized by triple cascade targeting including (1) CD44 targeting mediated by chondroitin sulfate, (2) Golgi apparatus targeting mediated by the caveolin-mediated endocytic pathway, and (3) endoplasmic reticulum (ER) targeting mediated by coat protein I (COP I) vesicles. CK was adsorbed on the complex of cationic liposomes (Lip) encapsulating siRNA targeting autophagy-related gene 7 (siATG7) to afford Lip/siATG7/CK. Lip/siATG7/CK functions as a drifting boat that follows the CD44-Golgi-ER flow and travels downstream to its destination (ER), bypassing the lysosomal degradation pathway and endowing HSCs with excellent RNAi efficiency. The efficient downregulation of ATG7 leads to an excellent antifibrotic effect both in vitro and in vivo.
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Sulfatos de Condroitina , Terapêutica com RNAi , Humanos , Interferência de RNA , Sulfatos de Condroitina/metabolismo , RNA Interferente Pequeno/genética , Cirrose Hepática/terapia , Cirrose Hepática/metabolismo , Autofagia , Complexo de Golgi/metabolismo , Retículo Endoplasmático/metabolismo , Receptores de Hialuronatos/metabolismoRESUMO
Background: Catheter ablation is recommended to eradicate supraventricular tachycardia caused by left-sided accessory pathways (APs) in children. This study aims to compare the safety and efficacy of the transseptal approach (TS) and aortic approach (TA) for catheter ablation of left-sided APs in a pediatric cohort. Methods: Patients < 18 years of age with left-sided APs who had undergone ablation at Beijing Children's Hospital between 13 January 2018 and 7 January 2020 were included and randomly categorized into either TS or TA group (follow-up for 22 months). In all, 60 patients in TS group and 41 patients in TA group were included in this study. Principal endpoints were success rate, recurrence rate, complications, procedure time, and radiation dose. Results: For TS group versus TA group, success rate was observed in 100 versus 97.56% (p = 0.402). The procedure time was 27.0 (32.0-23.0) versus 29.0 (38.0-24.5) min (p = 0.092). The rate of success or the procedure time was similar, but for the patients with Aps located in left posterior septum (LPS) or left posterior lateral (LPL), the TS group had a shorter procedure time compared with TA group (p < 0.01). The radiation dose was 28.0 (20.0-41.75) versus 0 mGy (p < 0.001). After successful ablation, no recurrence and complication were observed in either group. Conclusion: Both TS and TA for catheter ablation of left-sided Aps were shown to be safe and effective in children. Zero radiation and ease of mastery make TA the preferred choice. TS is recommended to be used by properly trained medical professionals, especially for patient with AP localized in the LPL or LPS. However, TS is a good alternative where patients have aortic lesions or when TA fails.
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Cancer-associated fibroblasts (CAFs)-mediated metabolic support plays a vital role in tumorigenesis. The metabolic network between cancer cells and CAFs may serve as promising targets for cancer therapy. Here, aiming at targeted blockade of the metabolic support of CAFs to cancer cells, a biomimetic nanocarrier is designed by coating solid lipid nanoparticles containing chemotherapeutic paclitaxel (PTX) and glycolysis inhibitor PFK15 with hybrid membranes of cancer cells and activated fibroblasts. The nanoparticles possess outstanding dual-targeting ability which can simultaneously target cancer cells and CAFs. The encapsulated glycolysis inhibitor PFK15 can prevent the glycolysis of cancer cells and CAFs at the same time, thus increasing the chemosensitivity of cancer cells and blocking the metabolic support of CAFs to cancer cells. The results showed that the combination of PTX and PFK15 exhibited synergistic effects and inhibited tumor growth effectively. Moreover, the biomimetic nanoparticles obviously reduced the lactate production in the tumor microenvironment, leading to activated immune responses and enhanced tumor suppression. This work presents a facile strategy to destroy the metabolic network between cancer cells and CAFs, and proves the potential to elevate chemo-immunotherapy by glycolysis inhibition. STATEMENT OF SIGNIFICANCE: In many solid tumors, most cancer cells produce energy and carry out biosynthesis through glycolysis, even in aerobic conditions. As the main tumor stromal cells, cancer-associated fibroblasts (CAFs) usually turn oxidative phosphorylation into aerobic glycolysis with metabolic reprogramming and provide high-energy glycolytic metabolites for cancer cells. The metabolic network between cancer cells and CAFs is regarded as the vulnerability among cancer cells. Moreover, lactate produced by cancer cells and CAFs through glycolysis often leads to the immunosuppressive tumor microenvironment. The present study provides an effective approach to destroy the metabolic network between cancer cells and CAFs and greatly improves the antitumor immune response by reducing lactate production, which serves as a promising strategy for combined chemo-immunotherapy mediated by glycolysis.
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Biomimética , Nanopartículas , Linhagem Celular Tumoral , Imunoterapia , Ácido Láctico/metabolismo , Lipossomos , Microambiente TumoralRESUMO
Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer affecting many people worldwide. Although the 5-year survival rate is 65% in localized disease, after metastasis, the survival rate is <10%. Emerging evidence has shown that microRNAs (miRNAs) play a crucial regulatory role in the progression of ccRCC. Here, we show that miR-335, an anti-onco-miRNA, is downregulation in tumor tissue and inhibited ccRCC cell proliferation, invasion, and migration. Our studies further identify the H3K9me1/2 histone demethylase KDM3A as a new miR-335-regulated gene. We show that KDM3A is overexpressed in ccRCC, and its upregulation contributes to the carcinogenesis and metastasis of ccRCC. Moreover, with the overexpression of KDM3A, YAP1 was increased and identified as a direct downstream target of KDM3A. Enrichment of KDM3A demethylase on YAP1 promoter was confirmed by CHIP-qPCR and YAP1 was also found involved in the cell growth and metastasis inhibitory of miR-335. Together, our study establishes a new miR-335/KDM3A/YAP1 regulation axis, which provided new insight and potential targeting of the metastasized ccRCC.
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Carcinoma de Células Renais , Histona Desmetilases com o Domínio Jumonji , Neoplasias Renais , MicroRNAs , Proteínas de Sinalização YAP , Carcinogênese/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias Renais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Sinalização YAP/genética , Proteínas de Sinalização YAP/metabolismoRESUMO
Hypoxia at the tumor site limits the therapeutic effects of photodynamic therapy (PDT) in oral squamous cell carcinoma (OSCC), which is an oxygen-consumption process. Inhibiting cellular oxygen consumption and reducing cellular ATP production are expected to enhance PDT. In this study, we designed and constructed dandelion-like size-shrinkable nanoparticles for tumor-targeted delivery of hypoxia regulator resveratrol (RES) and photodynamic agent chlorine e6 (CE6). Both drugs were co-encapsulated in small-sized micelles modified with EGFR targeting ligand GE11, which was further conjugated on hyaluronic nanogel (NG) to afford RC-GMN. After targeted accumulation in tumors mediated by GE11 and enhanced penetration and retention (EPR) effects, RC-GMN was degraded by hyaluronidase (HAase) and resulted in small-sized micelles, allowing for deep penetration and dual-receptor-mediated cellular internalization. Resveratrol inhibited cellular oxygen consumption and provided sufficient oxygen for PDT, which consequently activated PDT to produce reactive oxygen species (ROS). Notably, we found that autophagy was overactivated in PDT, which was further strengthened by the hypoxia regulator resveratrol, elevating autophagic cell death. The synergistic effects of resveratrol and CE6 promoted autophagic cell death and apoptosis in the enhanced PDT, resulting in stronger antitumor effects in the orthotopic OSCC model. Therefore, the facilitated delivery of hypoxia regulator enhanced PDT efficacy by elevating oxygen content in tumor cells and inducing autophagic cell death and apoptosis, which offers an alternative strategy for enhancing the PDT effects against OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Nanopartículas , Fotoquimioterapia , Trifosfato de Adenosina/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Hipóxia Celular , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Hialuronoglucosaminidase/metabolismo , Hipóxia/tratamento farmacológico , Ligantes , Micelas , Neoplasias Bucais/tratamento farmacológico , Nanogéis , Oxigênio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
Recent studies have shown that high miR-155 expression was associated with poor prognosis in patients with acute myelogeneous leukemia (AML). Furthermore, targeting miR-155 results in monocytic differentiation and apoptosis. However, the exact role and mechanisms of miR-155 in human AML remains speculative. HL-60 cells were treated with anti-miR-155 for 72 h. Cell growth and apoptosis in vitro were detected by MTT, BrdU proliferation, colony formation and flow cytometry assay. The effect of anti-miR-155 on growth of HL-60 cells was also evaluated in a leukemia mouse model. Slug cDNA and PUMA siRNA trannsfection was used to assess the signal pathway. Different protein expression was detected by western blot assay and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. The results shown that targeting miR-155 resulted in a 24-fold decrease of miR-155 expression compared to negative control in the HL-60 cells. Targeting miR-155 significantly downregulated Slug and upregulated PUMA expression, and decreased HL-60 cell growth by 70% , impaired colony formation by approximately 60%, and increased HL-60 cell apoptosis by 45%. Targeting PUMA reversed miR-155 sliencing-induced proliferation and apoptosis of HL-60 cells. Restoration of Slug decreased PUMA expression. In murine engraftment models of HL-60 cells, we showed that targeting miR-155 was able to reduce tumor growth. This was accompanied with decreased Slug expression and increased PUMA expression in these tumors. Collectively, our findings strongly suggest targeting miR-155 exhibited in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of Slug expression and increase of PUMA expression.