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OBJECTIVES: This study aimed to investigate whether accelerometer-measured light physical activity (LPA) is associated with cognitive function and whether engaging in ≥3 h/day of LPA can reduce the chance of cognitive impairment among a sample of older adults in Taiwan. DESIGN: Cross-sectional study. SETTING: An outpatient department in a medical center. PARTICIPANTS: Participants were community-dwelling older adults aged 65 years and older who were able to walk independently from September 2020 to March 2021. MEASUREMENTS: A tri-axial accelerometer was used to measure LPA for 7 consecutive days, and the Mini-Mental State Examination (MMSE) scale was used to assess the chance of cognitive impairment. Multiple linear regression model and binary logistic regression model were performed to examine the association between LPA and MMSE scores. RESULTS: 145 older Taiwanese adults (51.7% men; 81.2±6.8 years; 6.9% at chance of cognitive impairment) were included. After adjusting for moderate-to-vigorous physical activity (MVPA) and wear time, we found that there was a significant association between LPA and cognitive function (95% confidence interval [CI]: 0.64-1.65; P<0.001), and further found that those who engaged in LPA ≥3 h/day were at reduced chance of cognitive impairment compared with people who engaged in LPA <3 h/day (odds ratio [OR]: 0.16; 95% CI: 0.03-0.80; P=0.025). CONCLUSION: This study demonstrated that engaging in LPA ≥3 h/day could be viewed as a protective factor for maintaining cognitive function in older adults. We recommend further longitudinal research to elucidate the association between intensity-specific LPA and cognitive function.
Assuntos
Acelerometria , Exercício Físico , Idoso , Cognição , Estudos Transversais , Exercício Físico/psicologia , Feminino , Humanos , Vida Independente , MasculinoRESUMO
A systematic review of histopathology from experimental animal systems is an essential part of up-to-date biomedical research. Pathologists at university hospitals are especially and increasingly challenged by these specialized and time-consuming duties. This article presents and analyzes a new laboratory structure of comparative experimental pathology-jointly lead by veterinary and human pathologists-which might solve this problem. The focus is on the establishment and full integration of this laboratory structure into a local, regional, and nationwide biomedical research cluster. A detailed comparison with an established structure of routine histopathology laboratories discusses merits and benefits as well as disadvantages.
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Pesquisa Biomédica , Pesquisa Translacional Biomédica , Academias e Institutos , Animais , Hospitais Universitários , Humanos , LaboratóriosRESUMO
BACKGROUND: Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC). METHODS: Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft. RESULTS: We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis. CONCLUSIONS: Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.
Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Células HEK293 , Células HT29 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Receptor Tirosina Quinase AxlRESUMO
Rates of the most common gynecologic cancer, endometrioid adenocarcinoma (EAC), continue to rise, mirroring the global epidemic of obesity, a well-known EAC risk factor. Thus, identifying novel molecular targets to prevent and/or mitigate EAC is imperative. The prevalent Type 1 EAC commonly harbors loss of the tumor suppressor, Pten, leading to AKT activation. The major endoplasmic reticulum (ER) chaperone, GRP78, is a potent pro-survival protein to maintain ER homeostasis, and as a cell surface protein, is known to regulate the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. To determine whether targeting GRP78 could suppress EAC development, we created a conditional knockout mouse model using progesterone receptor-Cre-recombinase to achieve Pten and Grp78 (cPten(f/f)Grp78(f/f)) deletion in the endometrial epithelium. Mice with a single Pten (cPten(f/f)) deletion developed well-differentiated EAC by 4 weeks. In contrast, no cPten(f/f)Grp78(f/f) mice developed EAC, even after more than 8 months of observation. Histologic examination of uteri from cPten(f/f)Grp78(f/f) mice also revealed no complex atypical hyperplasia, a well-established EAC precursor. These histologic observations among the cPten(f/f)Grp78(f/f) murine uteri also corresponded to abrogation of AKT activation within the endometrium. We further observed that GRP78 co-localized with activated AKT on the surface of EAC, thus providing an opportunity for therapeutic targeting. Consistent with previous findings that cell surface GRP78 is an upstream regulator of PI3K/AKT signaling, we show here that in vivo short-term systemic treatment with a highly specific monoclonal antibody against GRP78 suppressed AKT activation and increased apoptosis in the cPten(f/f) tumors. Collectively, these findings present GRP78-targeting therapy as an efficacious therapeutic option for EAC.
Assuntos
Anticorpos Monoclonais/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/metabolismo , Proteínas de Choque Térmico/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinogênese/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Chaperonas Moleculares/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Four 2-(styryl)triphenylene derivatives (TSs) were synthesized for deep-blue dopant materials. By using a pyrene-containing compound, DMPPP, as the host, the TS-doped devices exhibited significant delayed fluorescence via triplet-triplet annihilation, providing the highest quantum efficiency of 10.2% and a current efficiency of 12.3 cd A(-1).
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Idiopathic dilated cardiomyopathy complicated with brain cardioembolism is rarely documented by both 2-dimensional echocardiography and cranial computed tomography in pediatric patients. A 2-year-old girl developed hemiparalysis 15 months after diagnosis of idiopathic dilated cardiomyopathy. The 2-dimensional echocardiograms of left ventricular thrombi, computed tomographic findings of brain embolism, clinical course, treatment and outcome are presented. Previous reports of idiopathic dilated cardiomyopathy in children are reviewed.