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1.
Proc Natl Acad Sci U S A ; 118(17)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33883283

RESUMO

Vimentin is a cytoskeletal intermediate filament protein that plays pivotal roles in tumor initiation, progression, and metastasis, and its overexpression in aggressive cancers predicted poor prognosis. Herein described is a highly effective antitumor and antimetastatic metal complex [PtII(C^N^N)(NHC2Bu)]PF6 (Pt1a; HC^N^N = 6-phenyl-2,2'-bipyridine; NHC= N-heterocyclic carbene) that engages vimentin via noncovalent binding interactions with a distinct orthogonal structural scaffold. Pt1a displays vimentin-binding affinity with a dissociation constant of 1.06 µM from surface plasmon resonance measurements and fits into a pocket between the coiled coils of the rod domain of vimentin with multiple hydrophobic interactions. It engages vimentin in cellulo, disrupts vimentin cytoskeleton, reduces vimentin expression in tumors, suppresses xenograft growth and metastasis in different mouse models, and is well tolerated, attributable to biotransformation to less toxic and renal-clearable platinum(II) species. Our studies uncovered the practical therapeutic potential of platinum(II)‒NHC complexes as effective targeted chemotherapy for combating metastatic and cisplatin-resistant cancers.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Vimentina/efeitos dos fármacos , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Feminino , Células HCT116 , Humanos , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Simulação de Dinâmica Molecular , Compostos Organoplatínicos/metabolismo , Compostos Organoplatínicos/farmacologia , Ratos , Vimentina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
J Adv Nurs ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38586889

RESUMO

AIM: To examine the main effects and interaction effects of outcome expectations (e.g., anticipated satisfactory salary and benefits), nurse identity (a sense of membership in the nursing profession), and information-access efficiency of the electronic medical record system (how the system enables nurses to quickly retrieve the needed information) on nurses' retention. DESIGN: This study uses a cross-sectional survey and adopts proportionate random sampling to recruit a representative sample of nurses of a medical centre in Taiwan. METHODS: This study successfully obtained completed questionnaires from 430 nurses during December 2021 to January 2022. Data are analysed by using hierarchical regressions. RESULTS: Positive outcome expectations and identification as a member in the nursing profession are associated with retention. Information-access efficiency strengthens the link between outcome expectations and retention, while nurse identity weakens this link. CONCLUSION: Outcome expectations can help retain nurses, particularly those who perceive high levels of information-access efficiency and possess weak nurse identity. That is, outcome expectations have a complementary role with nurse identity in retaining nurses. IMPLICATIONS FOR THE PROFESSION: Nurse managers should devise means to build positive outcome expectations for nurses. In addition, either strengthening nurses' identification with the nursing profession or improving the information-access efficiency of the electronic medical system may also help retain nurses. IMPACT: This study examined how to transform outcome expectation to nurse retention, offering nurse managers to devise new means to retain nurses. REPORTING METHOD: STROBE statement was chosen as EQUATOR checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

3.
J Cell Mol Med ; 27(18): 2792-2803, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37610061

RESUMO

Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , MicroRNAs/genética , Carioferinas
4.
J Cell Sci ; 134(16)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34338780

RESUMO

One of the greatest unmet needs hindering the successful treatment of nasopharyngeal carcinomas (NPCs) is for representative physiological and cost-effective models. Although Epstein-Barr virus (EBV) infection is consistently present in NPCs, most studies have focused on EBV-negative NPCs. For the first time, we established and analyzed three-dimensional (3D) spheroid models of EBV-positive and EBV-negative NPC cells and compared these to classical two-dimensional (2D) cultures in various aspects of tumor phenotype and drug responses. Compared to 2D monolayers, the 3D spheroids showed significant increases in migration capacity, stemness characteristics, hypoxia and drug resistance. Co-culture with endothelial cells, which mimics essential interactions in the tumor microenvironment, effectively enhanced spheroid dissemination. Furthermore, RNA sequencing revealed significant changes at the transcriptional level in 3D spheroids compared to expression in 2D monolayers. In particular, we identified known (VEGF, AKT and mTOR) and novel (Wnt-ß-catenin and Eph-ephrin) cell signaling pathways that are activated in NPC spheroids. Targeting these pathways in 3D spheroids using FDA-approved drugs was effective in monoculture and co-culture. These findings provide the first demonstration of the establishment of EBV-positive and EBV-negative NPC 3D spheroids with features that resemble advanced and metastatic NPCs. Furthermore, we show that NPC spheroids have potential use in identifying new drug targets.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Efrinas , Herpesvirus Humano 4/metabolismo , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Transdução de Sinais , Microambiente Tumoral , beta Catenina/genética , beta Catenina/metabolismo
5.
Exp Cell Res ; 416(1): 113150, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35405118

RESUMO

Among all gynecological malignancies, ovarian cancer (OC) accounts for the highest mortality rate due to high therapeutic resistance, prolonged latency and a lack of effective treatments. This calls for preclinical models that could recapitulate the histological, molecular and pathophysiological features of distinct OC subtypes. Various mouse models including tumor xenografts, genetically modified models, and novel 3D tumor models including organoids and organotypic co-culture models have been developed, and they serve as valuable assets to fulfill this demand. These models, particularly those patient-derived, can address the heterogeneity of OC and simulate OC progression in patients, hence bringing important insights for personalized treatments. In this review, we will discuss the merits and challenges of these models, and summarize their current preclinical applications in patient stratification and therapeutic research. Though limitations are inevitable, further optimization will render these models more clinically translatable in OC research.


Assuntos
Neoplasias Ovarianas , Animais , Carcinoma Epitelial do Ovário/patologia , Modelos Animais de Doenças , Feminino , Xenoenxertos , Humanos , Camundongos , Organoides , Neoplasias Ovarianas/patologia
6.
Emerg Infect Dis ; 28(6): 1128-1136, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35470794

RESUMO

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Adulto , Canadá/epidemiologia , Clostridioides difficile/genética , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Atenção à Saúde , Humanos , Testes de Sensibilidade Microbiana , Ribotipagem
7.
J Nurs Manag ; 30(8): 3863-3873, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35862237

RESUMO

AIMS: To examine the relationships among effort ensuring robots' smooth operation (EERSO), time pressure, missed care, and nurses' turnover intention, and how robot performance moderates such relations. BACKGROUND: Robots may reduce nurses' workload but typically still require some effort of nurses for robots' smooth operation. However, the negative impact of EERSO on nurses' workplace outcomes is unknown. METHODS: This study used a two-wave follow-up design. Data were collected in a medical center in Taiwan, with first wave collected in 2019 and second wave collected between 2019 and 2020. A total of 331 participants were followed through the two waves. RESULTS: EERSO is positively linked to missed care and time pressure. Time pressure is also positively linked to missed care and turnover intention. Positive robot performance weakens the positive link between EERSO and time pressure. CONCLUSION: Using robots may help reduce nurses' workload, but it also requires nurses' efforts to maintain robots' continuous operation, that is, EERSO. It may adversely impact nursing professional workplaces. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should reduce nurses' time pressure whilst suggest hospital managers to seek robots that require minimal EERSO.


Assuntos
Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Robótica , Humanos , Estudos Transversais , Atitude do Pessoal de Saúde , Satisfação no Emprego , Inquéritos e Questionários , Intenção , Local de Trabalho , Reorganização de Recursos Humanos
8.
J Neurosci ; 39(38): 7576-7590, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31405928

RESUMO

The hippocampus has been highly implicated in depression symptoms. Recent findings suggest that the expression and susceptibility of depression symptoms are related to the enhanced functioning of the hippocampus. We reasoned that hippocampal engrams, which represent ensembles of neurons with increased activity after memory formation, could underlie some contributions of the hippocampus to depression symptoms. Using the chronic social defeat stress model, we examined social defeat-related hippocampal engrams in mice that are either susceptible or resilient to the stressor. TetTag mice were used to label social defeat-related hippocampal ensembles by LacZ. Engram cells correspond to ensembles that were reactivated by the same stressor. Compared with resilient and nonstressed control mice, susceptible mice exhibited a higher reactivation of social defeat-related LacZ-labeled cells (i.e., engram cells) in both the dorsal and ventral hippocampal CA1 regions. The density of CA1 engram cells correlated with the level of social avoidance. Using DREADD and optogenetic approaches to activate and inactivate social defeat-related CA1 engram cells enhanced and suppressed social avoidance, respectively. Increased engram cells in susceptible mice could not be found in the dentate gyrus. Susceptible mice exhibited more negative stimuli-related, but not neutral stimuli-related, CA1 engram cells than resilient mice in the dorsal hippocampus. Finally, chronic, but not a short and subthreshold, social defeat protocol was necessary to increase CA1 engram cell density. The susceptibility to chronic social defeat stress is regulated by hippocampal CA1 engrams for negative memory. Hippocampal negative memory engrams may underlie the vulnerability and expression of cognitive symptoms in depression.SIGNIFICANCE STATEMENT We provided evidence that negative memory hippocampal engrams contribute to the susceptibility to developing depression-related behavior after chronic social defeat stress. The activation of positive memory engrams has been shown to alleviate depression-related behaviors, while our findings reveal the pathological roles of negative memory engrams that could lead to those behaviors. Increased negative memory engrams could be a downstream effect of the reported high hippocampal activity in animal models and patients with depression. Unlike affective symptoms, we know much less about the cellular mechanisms of the cognitive symptoms of depression. Given the crucial roles of hippocampal engrams in memory formation, enhanced reactivation of negative memory engrams could be an important cellular mechanism that underlies the cognitive symptoms of depression.


Assuntos
Região CA1 Hipocampal/fisiologia , Memória/fisiologia , Neurônios/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Depressão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
9.
J Am Chem Soc ; 142(24): 10769-10779, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32441923

RESUMO

Molecules that are capable of disrupting cellular ion homeostasis offer unique opportunities to treat cancer. However, previously reported synthetic ion transporters showed limited value, as promiscuous ionic disruption caused toxicity to both healthy cells and cancer cells indiscriminately. Here we report a simple yet efficient synthetic K+ transporter that takes advantage of the endogenous subcellular pH gradient and membrane potential to site-selectively mediate K+/H+ transport on the mitochondrial and lysosomal membranes in living cells. Consequent mitochondrial and lysosomal damages enhanced cytotoxicity to chemo-resistant ovarian cancer stem cells (CSCs) via apoptosis induction and autophagy suppression with remarkable selectivity (up to 47-fold). The eradication of CSCs blunted tumor formation in mice. We believe this strategy can be exploited in the structural design and applications of next-generation synthetic cation transporters for the treatment of cancer and other diseases related to dysfunctional K+ channels.


Assuntos
Células-Tronco Neoplásicas/metabolismo , Organelas/metabolismo , Potássio/metabolismo , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Transporte de Íons , Estrutura Molecular , Células-Tronco Neoplásicas/química , Organelas/química , Potássio/química
10.
Emerg Infect Dis ; 26(9): 2247-2250, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32818423

RESUMO

Rates of vancomycin-resistant enterococci bloodstream infections have remained relatively low in Canada. We recently observed an increase of 113% in these infections rates, which coincided with emergence of Enterococcus faecium pstS-null sequence type 1478. The proportion of this sequence type increased from 2.7% to 38.7% for all tested isolates from 2013-2018.


Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Antibacterianos/farmacologia , Canadá/epidemiologia , Células Clonais , Enterococcus faecium/genética , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Vancomicina/farmacologia , Enterococos Resistentes à Vancomicina/genética
11.
Mod Pathol ; 33(1): 138-152, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383965

RESUMO

Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm2. Thirty-seven patients (67%) had operable tumors. After a median follow-up of 15 months, only nine patients (16%) were alive. Eight of the nine survivors did not have lymph node metastasis. Using 5% as the threshold, PD-L1 expression was observed in 55%, 50%, and 33% of vulvar, vaginal, and cervical tumors, respectively, when the Roche SP263 antibody was used and 20%, 53%, and 0%, respectively, when the Dako 28-8 antibody was used. The median CD8 tumor-infiltrating lymphocyte density was significantly higher in vulvar/vaginal than cervical melanomas and correlated with PD-L1 expression. No cases exhibited loss of mismatch repair proteins. Five cases harbored KIT mutations, three of which were hotspots. BRAF V600E mutation was not detected. Univariable analysis showed that tumor size greater than or equal to 33 mm, mitotic figures of greater than or equal to 10 per mm2, lymph node metastasis, and low CD8+ tumor-infiltrating lymphocyte density were adverse prognostic factors. Thus, patients with genital melanomas have a poor prognosis, and evaluation of multiple biomarkers is necessary to identify patients who may benefit from immunotherapy or targeted therapy.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias dos Genitais Femininos/patologia , Melanoma/patologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/imunologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Melanoma/genética , Melanoma/imunologia , Pessoa de Meia-Idade
12.
J Med Internet Res ; 22(10): e22324, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33104004

RESUMO

BACKGROUND: Chronic low back pain is a common problem and is associated with high costs, including those related to health care and indirect costs due to absence at work or reduced productivity. Previous studies have demonstrated that acupuncture or electroacupuncture can relieve low back pain. Electronic acupuncture shoes (EAS) are a novel device designed in this study. This device combines the properties of acupuncture and transcutaneous electrical nerve stimulation for clinical use. OBJECTIVE: The aim of this study was to evaluate the efficacy of EAS in patients with chronic low back pain. METHODS: In this prospective double-blinded randomized controlled study, the data of 83 patients who experienced chronic low back pain were analyzed. Patients came to our clinic for 20 visits and underwent assessment and treatment. Patients were randomly allocated to receive either EAS plus placebo nonsteroidal anti-inflammatory drugs (NSAIDs) (EAS group, n=42) or sham EAS plus NSAIDs (NSAID group, n=41). The visual analog scale (VAS) score and range of motion were assessed at baseline, before and after each EAS treatment, and 2 weeks after the last treatment. The time for achieving pain remission was recorded. Quality of life was assessed at the 2nd, 14th, and 20th visits. RESULTS: After 6 weeks of treatment, the treatment success rate in each visit in the EAS group was higher than that in the NSAID group, as revealed by the intention-to-treat (ITT) and per-protocol (PP) analyses, but significant differences were observed only during the 16th visit in the ITT analysis (EAS group: 31/37, 84% and NSAID group: 21/34, 62%; P=.04). The change in the VAS score from baseline in each visit in the EAS group was greater than that in the NSAID group, as revealed by the ITT and PP analyses, and significant differences were observed in the 5th visit and 9th visit in the ITT analysis (P=.048 and P=.048, respectively). Significant differences were observed in the left rotation in the 2nd visit and 4th visit (P=.049 and P=.03, respectively). No significant differences were observed in the VAS score before and after treatment in each visit and in the quality of life in both groups. CONCLUSIONS: EAS might serve as a reliable alternative therapeutic tool for patients with chronic low back pain who are contraindicated for oral NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02468297 https://clinicaltrials.gov/ct2/show/NCT02468297.


Assuntos
Terapia por Acupuntura/métodos , Dor Crônica/terapia , Dor Lombar/terapia , Qualidade de Vida/psicologia , Sapatos/normas , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
13.
Sensors (Basel) ; 20(9)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365543

RESUMO

The fifth generation (5G) mobile network delivers high peak data rates with ultra-low latency and massive network capacity. Wireless sensor network (WSN) in Internet of Thing (IoT) architecture is of prominent use in 5G-enabled applications. The electronic healthcare (e-health) system has gained a lot of research attention since it allows e-health users to store and share data in a convenient way. By the support of 5G technology, healthcare data produced by sensor nodes are transited in the e-health system with high efficiency and reliability. It helps in reducing the treatment cost, providing efficient services, better analysis reports, and faster access to treatment. However, security and privacy issues become big concerns when the number of sensors and mobile devices is increasing. Moreover, existing single-server architecture requires to store a massive number of identities and passwords, which causes a significant database cost. In this paper, we propose a three-factor fast authentication scheme with time bound and user anonymity for multi-server e-health systems in 5G-based wireless sensor networks. In our work, the three-factor authentication scheme integrating biometrics, password, and smart card ensures a high-security sensor-enabled environment for communicating parties. User anonymity is preserved during communication process. Besides, time bound authentication can be applied to various healthcare scenarios to enhance security. The proposed protocol includes fast authentication, which can provide a fast communication for participating parties. Our protocol is also designed with multi-server architecture to simplify network load and significantly save database cost. Furthermore, security proof and performance analysis results show that our proposed protocol can resist various attacks and bear a rational communication cost.

14.
Pediatr Phys Ther ; 32(1): 35-43, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31815924

RESUMO

INTRODUCTION: The purposes of this study were to develop an instructional leaflet on home video recording for the General Movement Assessment (GMA) and to examine the concurrent and predictive validity of the GMA completed by physical therapists (PTs) and completed by parents. METHODS: The GMA and the Alberta Infant Motor Scale (AIMS) were completed by PTs in the clinic. Parents completed the GMA following the instructional leaflet. RESULTS: The content validity of the leaflet was 0.83. The consistency of the GMA results between sources was κ = 0.869. The concurrent validity of the GMA at a corrected age of 3 months was κ = 0.266 (PT) versus 0.525 (parent) using the 10th-percentile cutoffs of the AIMS. The positive likelihood ratio was 26 (PT) versus 25 (parents) at a corrected age of 12 months based on 5th-percentile cutoffs of the AIMS. CONCLUSIONS: Home GMA videos are valid for clinical assessment following the instructional leaflet.


Assuntos
Movimento/fisiologia , Pais/educação , Gravação em Vídeo/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Reprodutibilidade dos Testes
15.
J Cell Mol Med ; 23(7): 4569-4581, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31037837

RESUMO

Although invasive epithelial ovarian cancer (IOC) and low malignant potential ovarian tumour (LMP) are similar, they are associated with different outcomes and treatment strategies. The current accuracy in distinguishing these diseases is unsatisfactory, leading to delays or unnecessary treatments. We compared the molecular signature of IOC and LMP cases by analysing their transcriptomic data and re-clustered them according to these data rather than the pathological dissection. We identified that FAM83D was highly expressed in IOC. To verify the role of FAM83D in the progression and metastasis, we used the isogenic ovarian cancer metastatic models, highly metastatic cells (HM) and non-metastatic cells (NM). Overexpression of FAM83D significantly promoted cell proliferation, migration and spheroid formation. This was consistent with previous data showing that high FAM83D expression is associated with poor prognosis in cancer patients. Moreover, similar to the HM cells, the FAM83D-overexpressing NM cells demonstrated stronger phosphorylation of the epidermal growth factor receptor (EGFR) and c-Raf. This indicates that the action of FAM83D is mediated by the activation of the EGFR pathway. Taken together, this report suggested that FAM83D might be an excellent molecular marker to discriminate between IOC and LMP.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Progressão da Doença , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Animais , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos SCID , Proteínas Associadas aos Microtúbulos/genética , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Curva ROC , Transdução de Sinais , Análise de Sobrevida , Transcriptoma/genética , Regulação para Cima/genética
16.
CMAJ ; 191(36): E981-E988, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501180

RESUMO

BACKGROUND: Health care-associated infections are a common cause of patient morbidity and mortality. We sought to describe the trends in these infections in acute care hospitals, using data from 3 national point-prevalence surveys. METHODS: The Canadian Nosocomial Infection Surveillance Program (CNISP) conducted descriptive point-prevalence surveys to assess the burden of health care-associated infections on a single day in February of 2002, 2009 and 2017. Surveyed infections included urinary tract infection, pneumonia, Clostridioides difficile infection, infection at surgical sites and bloodstream infections. We compared the prevalence of infection across the survey years and considered the contribution of antimicrobial-resistant organisms as a cause of these infections. RESULTS: We surveyed 28 of 33 (response rate 84.8%) CNISP hospitals (6747 patients) in 2002, 39 of 55 (response rate 71.0%) hospitals (8902 patients) in 2009 and 47 of 66 (response rate 71.2%) hospitals (9929 patients) in 2017. The prevalence of patients with at least 1 health care-associated infection increased from 9.9% in 2002 (95% confidence interval [CI] 8.4%-11.5%) to 11.3% in 2009 (95% CI 9.4%-13.5%), and then declined to 7.9% in 2017 (95% CI 6.8%-9.0%). In 2017, device-associated infections accounted for 35.6% of all health care-associated infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 3.9% of all organisms identified from 2002 to 2017; other antibiotic-resistant organisms were uncommon causes of infection for all survey years. INTERPRETATION: In CNISP hospitals, there was a decline in the prevalence of health care-associated infection in 2017 compared with previous surveys. However, strategies to prevent infections associated with medical devices should be developed. Apart from MRSA, few infections were caused by antibiotic-resistant organisms.


Assuntos
Anti-Infecciosos/uso terapêutico , Infecção Hospitalar/epidemiologia , Controle de Infecções , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/epidemiologia , Adolescente , Adulto , Canadá/epidemiologia , Criança , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Resistência Microbiana a Medicamentos , Feminino , Inquéritos Epidemiológicos , Hospitais/estatística & dados numéricos , Humanos , Lactente , Controle de Infecções/tendências , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/prevenção & controle
17.
Environ Sci Technol ; 53(7): 3917-3928, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30844260

RESUMO

Hypoxia is a pressing environmental problem in both marine and freshwater ecosystems globally, and this problem will be further exacerbated by global warming in the coming decades. Recently, we reported that hypoxia can cause transgenerational impairment of sperm quality and quantity in fish (in F0, F1, and F2 generations) through DNA methylome modifications. Here, we provide evidence that female fish ( Oryzias melastigma) exposed to hypoxia exhibit reproductive impairments (follicle atresia and retarded oocyte development), leading to a drastic reduction in hatching success in the F2 generation of the transgenerational group, although they have never been exposed to hypoxia. Further analyses show that the observed transgenerational impairments in ovarian functions are related to changes in the DNA methylation and expression pattern of two gene clusters that are closely associated with stress-induced cell cycle arrest and cell apoptosis. The observed epigenetic and transgenerational alterations suggest that hypoxia may pose a significant threat to the sustainability of natural fish populations.


Assuntos
Ecossistema , Oryzias , Animais , Metilação de DNA , Feminino , Hipóxia , Masculino , Reprodução
18.
Mol Ther ; 26(1): 70-83, 2018 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-29241971

RESUMO

Metastasis is the cause of most (>90%) cancer deaths and currently lacks effective treatments. Approaches to understanding the biological process, unraveling the most effective molecular target(s), and implementing nanotechnology to increase the therapeutic index are expected to facilitate cancer therapy against metastasis. Here, we demonstrate the potential advantages of bringing these three approaches together through the rational design of a small interfering RNA (siRNA) that targets p70S6K in cancer stem cells (CSCs) in combination with dendrimer nanotechnology-based siRNA delivery. Our results demonstrated that the generation 6 (G6) poly(amidoamine) dendrimer can be used as a nanovector to effectively deliver p70S6K siRNA by forming uniform dendriplex nanoparticles that protect the siRNA from degradation. These nanoparticles were able to significantly knock down p70S6K in ovarian CSCs, leading to a marked reduction in CSC proliferation and expansion without obvious toxicity toward normal ovarian surface epithelial cells. Furthermore, treatment with the p70S6K siRNA/G6 dendriplexes substantially decreased mesothelial interaction, migration and invasion of CSCs in vitro, as well as tumor growth and metastasis in vivo. Collectively, these results suggest that p70S6K constitutes a promising therapeutic target, and the use of siRNA in combination with nanotechnology-based delivery may constitute a new approach for molecularly targeted cancer therapy to treat metastasis.


Assuntos
Dendrímeros , Técnicas de Transferência de Genes , Células-Tronco Neoplásicas/metabolismo , Neoplasias Ovarianas/genética , RNA Interferente Pequeno/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Animais , Adesão Celular , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Interferência de RNA , Estabilidade de RNA , RNA Interferente Pequeno/administração & dosagem , Recidiva , Nanomedicina Teranóstica
19.
J Adv Nurs ; 75(12): 3577-3587, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31486112

RESUMO

AIMS: Our study investigates the influence of career facilitators and barriers on nurses' improvement of their professional capabilities and their professional turnover intention. BACKGROUND: Reducing nurses' professional turnover intention could help alleviate the global nursing shortage. Nevertheless, little research has addressed how career facilitators and barriers, nurses' improvement of their professional capabilities and professional turnover intention are related, indicating a gap. DESIGN: This study used a cross-sectional design. METHODS: We surveyed 502 out of 2,660 full-time nurses who worked for a medical centre in Taiwan between January-March 2018. Our items were adapted from Cunningham et al. and Teng et al. and had adequate reliability and validity. Structural equation modelling was used to test the study hypotheses. RESULTS: Human capital, social capital, and discrimination were positively related to intention to improve professional capabilities. Moreover, intention to improve professional capabilities was positively related to action to improve professional capabilities, which was negatively related to professional turnover intention. CONCLUSION: Most of the career facilitators and even barriers, boost the improvement of professional capabilities and are useful for retaining nurses in the nursing profession. IMPACT: Findings of this study should have an impact on nursing managers by offering them means to retain nurses, for example, enhancing human capital and social capital among nurses to reduce their turnover intention.


Assuntos
Atitude do Pessoal de Saúde , Mobilidade Ocupacional , Recursos Humanos de Enfermagem/psicologia , Recursos Humanos de Enfermagem/estatística & dados numéricos , Reorganização de Recursos Humanos/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Intenção , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Capital Social , Discriminação Social , Inquéritos e Questionários , Taiwan , Adulto Jovem
20.
Molecules ; 24(13)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277214

RESUMO

Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus Panax in the family Araliaceae that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.


Assuntos
Panax/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Saponinas/química , Saponinas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Carboidratos/química , Sistema Nervoso Central/efeitos dos fármacos , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade
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