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1.
J Cell Physiol ; 238(3): 533-548, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36649308

RESUMO

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Current treatment modalities are not completely effective and can lead to severe neurological and cognitive adverse effects. In addition to urgently needing better treatment approaches, new diagnostic and prognostic biomarkers are required to improve the therapy outcomes of MB patients. The RNA-binding proteins, LIN28A and LIN28B, are known to regulate invasive phenotypes in many different cancer types. However, the expression and function of these proteins in MB had not been studied to date. This study identified the expression of LIN28A and LIN28B in MB patient samples and cell lines and assessed the effect of LIN28 inhibition on MB cell growth, metabolism and stemness. LIN28B expression was significantly upregulated in MB tissues compared to normal brain tissues. This upregulation, which was not observed in other brain tumors, was specific for the aggressive MB subgroups and correlated with patient survival and metastasis rates. Functionally, pharmacological inhibition of LIN28 activity concentration-dependently reduced LIN28B expression, as well as the growth of D283 MB cells. While LIN28 inhibition did not affect the levels of intracellular ATP, it reduced the expression of the stemness marker CD133 in D283 cells and the sphere formation of CHLA-01R cells. LIN28B, which is highly expressed in the human cerebellum during the first few months after birth, subsequently decreased with age. The results of this study highlight the potential of LIN28B as a diagnostic and prognostic marker for MB and open the possibility to utilize LIN28 as a pharmacological target to suppress MB cell growth and stemness.


Assuntos
Neoplasias Cerebelares , Regulação Neoplásica da Expressão Gênica , Meduloblastoma , Criança , Humanos , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Cerebelo/crescimento & desenvolvimento , Cerebelo/metabolismo , Meduloblastoma/diagnóstico , Meduloblastoma/genética , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Linhagem Celular Tumoral , Trifosfato de Adenosina/metabolismo , Recém-Nascido , Lactente , Pré-Escolar , Envelhecimento/metabolismo , Prognóstico
2.
J Med Internet Res ; 24(1): e27487, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040799

RESUMO

BACKGROUND: Photoplethysmography is a noninvasive and low-cost method to remotely and continuously track vital signs. The Oura Ring is a compact photoplethysmography-based smart ring, which has recently drawn attention to remote health monitoring and wellness applications. The ring is used to acquire nocturnal heart rate (HR) and HR variability (HRV) parameters ubiquitously. However, these parameters are highly susceptible to motion artifacts and environmental noise. Therefore, a validity assessment of the parameters is required in everyday settings. OBJECTIVE: This study aims to evaluate the accuracy of HR and time domain and frequency domain HRV parameters collected by the Oura Ring against a medical grade chest electrocardiogram monitor. METHODS: We conducted overnight home-based monitoring using an Oura Ring and a Shimmer3 electrocardiogram device. The nocturnal HR and HRV parameters of 35 healthy individuals were collected and assessed. We evaluated the parameters within 2 tests, that is, values collected from 5-minute recordings (ie, short-term HRV analysis) and the average values per night sleep. A linear regression method, the Pearson correlation coefficient, and the Bland-Altman plot were used to compare the measurements of the 2 devices. RESULTS: Our findings showed low mean biases of the HR and HRV parameters collected by the Oura Ring in both the 5-minute and average-per-night tests. In the 5-minute test, the error variances of the parameters were different. The parameters provided by the Oura Ring dashboard (ie, HR and root mean square of successive differences [RMSSD]) showed relatively low error variance compared with the HRV parameters extracted from the normal interbeat interval signals. The Pearson correlation coefficient tests (P<.001) indicated that HR, RMSSD, average of normal heart beat intervals (AVNN), and percentage of successive normal beat-to-beat intervals that differ by more than 50 ms (pNN50) had high positive correlations with the baseline values; SD of normal beat-to-beat intervals (SDNN) and high frequency (HF) had moderate positive correlations, and low frequency (LF) and LF:HF ratio had low positive correlations. The HR, RMSSD, AVNN, and pNN50 had narrow 95% CIs; however, SDNN, LF, HF, and LF:HF ratio had relatively wider 95% CIs. In contrast, the average-per-night test showed that the HR, RMSSD, SDNN, AVNN, pNN50, LF, and HF had high positive relationships (P<.001), and the LF:HF ratio had a moderate positive relationship (P<.001). The average-per-night test also indicated considerably lower error variances than the 5-minute test for the parameters. CONCLUSIONS: The Oura Ring could accurately measure nocturnal HR and RMSSD in both the 5-minute and average-per-night tests. It provided acceptable nocturnal AVNN, pNN50, HF, and SDNN accuracy in the average-per-night test but not in the 5-minute test. In contrast, the LF and LF:HF ratio of the ring had high error rates in both tests.


Assuntos
Eletrocardiografia , Fotopletismografia , Frequência Cardíaca , Humanos , Modelos Lineares , Sono
3.
Sensors (Basel) ; 22(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36015816

RESUMO

Accurate peak determination from noise-corrupted photoplethysmogram (PPG) signal is the basis for further analysis of physiological quantities such as heart rate. Conventional methods are designed for noise-free PPG signals and are insufficient for PPG signals with low signal-to-noise ratio (SNR). This paper focuses on enhancing PPG noise-resiliency and proposes a robust peak detection algorithm for PPG signals distorted due to noise and motion artifact. Our algorithm is based on convolutional neural networks (CNNs) with dilated convolutions. We train and evaluate the proposed method using a dataset collected via smartwatches under free-living conditions in a home-based health monitoring application. A data generator is also developed to produce noisy PPG data used for model training and evaluation. The method performance is compared against other state-of-the-art methods and is tested with SNRs ranging from 0 to 45 dB. Our method outperforms the existing adaptive threshold, transform-based, and machine learning methods. The proposed method shows overall precision, recall, and F1-score of 82%, 80%, and 81% in all the SNR ranges. In contrast, the best results obtained by the existing methods are 78%, 80%, and 79%. The proposed method proves to be accurate for detecting PPG peaks even in the presence of noise.


Assuntos
Fotopletismografia , Processamento de Sinais Assistido por Computador , Algoritmos , Artefatos , Frequência Cardíaca/fisiologia , Movimento (Física) , Redes Neurais de Computação , Fotopletismografia/métodos
4.
Comput Inform Nurs ; 40(12): 856-862, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35234703

RESUMO

Smart rings, such as the Oura ring, might have potential in health monitoring. To be able to identify optimal devices for healthcare settings, validity studies are needed. The aim of this study was to compare the Oura smart ring estimates of steps and sedentary time with data from the ActiGraph accelerometer in a free-living context. A cross-sectional observational study design was used. A convenience sample of healthy adults (n = 42) participated in the study and wore an Oura smart ring and an ActiGraph accelerometer on the non-dominant hand continuously for 1 week. The participants completed a background questionnaire and filled out a daily log about their sleeping times and times when they did not wear the devices. The median age of the participants (n = 42) was 32 years (range, 18-46 years). In total, 191 (61% of the potential) days were compared. The Oura ring overestimated the step counts compared with the ActiGraph. The mean difference was 1416 steps (95% confidence interval, 739-2093 steps). Daily sedentary time was also overestimated by the ring; the mean difference was 17 minutes (95% confidence interval, -2 to 37 minutes). The use of the ring in nursing interventions needs to be considered.


Assuntos
Actigrafia , Comportamento Sedentário , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Estudos Transversais , Monitorização Ambulatorial , Exercício Físico
5.
Cell Mol Life Sci ; 77(14): 2701-2722, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32008085

RESUMO

Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological phenomena. EMT is involved in embryonic development, organogenesis and tissue repair, as well as in fibrosis, cancer metastasis and drug resistance. In recent years, the ability to edit the genome using the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system has greatly contributed to identify or validate critical genes in pathway signaling. This review delineates the complex EMT networks and discusses recent studies that have used CRISPR/Cas technology to further advance our understanding of the EMT process.


Assuntos
Sistemas CRISPR-Cas/genética , Transição Epitelial-Mesenquimal/genética , Edição de Genes/métodos , Desenvolvimento Embrionário/genética , Humanos , Organogênese/genética , Transdução de Sinais/genética
6.
Sensors (Basel) ; 21(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805217

RESUMO

Pregnancy is a unique time when many mothers gain awareness of their lifestyle and its impacts on the fetus. High-quality care during pregnancy is needed to identify possible complications early and ensure the mother's and her unborn baby's health and well-being. Different studies have thus far proposed maternal health monitoring systems. However, they are designed for a specific health problem or are limited to questionnaires and short-term data collection methods. Moreover, the requirements and challenges have not been evaluated in long-term studies. Maternal health necessitates a comprehensive framework enabling continuous monitoring of pregnant women. In this paper, we present an Internet-of-Things (IoT)-based system to provide ubiquitous maternal health monitoring during pregnancy and postpartum. The system consists of various data collectors to track the mother's condition, including stress, sleep, and physical activity. We carried out the full system implementation and conducted a real human subject study on pregnant women in Southwestern Finland. We then evaluated the system's feasibility, energy efficiency, and data reliability. Our results show that the implemented system is feasible in terms of system usage during nine months. We also indicate the smartwatch, used in our study, has acceptable energy efficiency in long-term monitoring and is able to collect reliable photoplethysmography data. Finally, we discuss the integration of the presented system with the current healthcare system.


Assuntos
Exercício Físico , Estilo de Vida , Feminino , Finlândia , Humanos , Lactente , Monitorização Fisiológica , Gravidez , Reprodutibilidade dos Testes
7.
Lab Invest ; 100(2): 224-233, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31243341

RESUMO

The Ca2+ signal is essential in both hypoxia- and epidermal growth factor (EGF)-mediated epithelial to mesenchymal transition (EMT) in MDA-MB-468 breast cancer cells. This finding suggests that Ca2+-permeable ion channels participate in the induction of expression of some mesenchymal markers such as vimentin. However, the ion channels involved in vimentin expression induction have not been fully characterized. This work sought to define how differential modulation of the calcium signal effects the induction of vimentin and the Ca2+ influx pathways involved. We identified that the intracellular Ca2+ chelator EGTA-AM, cytochalasin D (a modulator of cytoskeletal dynamics and cell morphology), and the sarco/endoplasmic reticulum ATPase inhibitor thapsigargin are all inducers of vimentin in MDA-MB-468 breast cancer cells. EGTA-AM- and thapsigargin-mediated induction of vimentin expression in MDA-MB-468 cells involves store-operated Ca2+ entry, as evidenced by sensitivity to silencing of the molecular components of this pathway, STIM1 and ORAI1. In stark contrast, cytochalasin D-mediated vimentin induction was insensitive to silencing of ORAI1, despite sensitivity to silencing of its canonical activator the endoplasmic reticulum Ca2+ sensor STIM1. Cytochalasin D-mediated vimentin induction was, however, sensitive to silencing of another reported STIM1 target, TRPC1. Subsequent studies identified that EGTA-AM-induced vimentin expression also partially involved a TRPC1-dependent pathway. These studies define a complex interplay between vimentin expression in this model and the specific Ca2+-permeable ion channels involved. The complexity in the engagement of different Ca2+ influx pathways that regulate vimentin induction are opportunities but also potential challenges in targeting Ca2+ signaling to block EMT in cancer cells. Our findings further highlight the need to identify potential indispensable ion channels that can regulate induction of specific mesenchymal markers via different stimuli.


Assuntos
Sinalização do Cálcio/fisiologia , Proteína ORAI1/metabolismo , Canais de Cátion TRPC/metabolismo , Vimentina/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Linhagem Celular Tumoral , Citocalasina D/farmacologia , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Proteínas de Neoplasias/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Tapsigargina/farmacologia
8.
Int J Mol Sci ; 21(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33322037

RESUMO

Epithelial to mesenchymal transition (EMT) in cancer is important in therapeutic resistance and invasiveness. Calcium signaling is key to the induction of EMT in breast cancer cells. Although inhibition of specific calcium-permeable ion channels regulates the induction of a sub-set of EMT markers in breast cancer cells, it is still unclear if activation of a specific calcium channel can be a driver for the induction of EMT events. In this study, we exploited the availability of a selective pharmacological activator of the calcium-permeable ion channel TRPV4 to assess the direct role of calcium influx in EMT marker induction. Gene association studies revealed a link between TRPV4 and gene-ontologies associated with EMT and poorer relapse-free survival in lymph node-positive basal breast cancers. TRPV4 was an important component of the calcium influx phase induced in MDA-MB-468 breast cancer cells by the EMT inducer epidermal growth factor (EGF). Pharmacological activation of TRPV4 then drove the induction of a variety of EMT markers in breast cancer cells. These studies demonstrate that calcium influx through specific pathways appears to be sufficient to trigger EMT events.


Assuntos
Neoplasias da Mama/genética , Transição Epitelial-Mesenquimal , Canais de Cátion TRPV/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Leucina/análogos & derivados , Leucina/farmacologia , Sulfonamidas/farmacologia , Análise de Sobrevida , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/genética
9.
J Cell Sci ; 130(14): 2292-2305, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28559303

RESUMO

Hypoxia is a feature of the tumour microenvironment that promotes invasiveness, resistance to chemotherapeutics and cell survival. Our studies identify the transient receptor potential canonical-1 (TRPC1) ion channel as a key component of responses to hypoxia in breast cancer cells. This regulation includes control of specific epithelial to mesenchymal transition (EMT) events and hypoxia-mediated activation of signalling pathways such as activation of the EGFR, STAT3 and the autophagy marker LC3B, through hypoxia-inducible factor-1α (HIF1α)-dependent and -independent mechanisms. TRPC1 regulated HIF1α levels in PTEN-deficient MDA-MB-468 and HCC1569 breast cancer cell lines. This regulation arises from effects on the constitutive translation of HIF1α under normoxic conditions via an Akt-dependent pathway. In further support of the role of TRPC1 in EMT, its expression is closely associated with EMT- and metastasis-related genes in breast tumours, and is enhanced in basal B breast cancer cell lines. TRPC1 expression is also significantly prognostic for basal breast cancers, particularly those classified as lymph node positive. The defined roles of TRPC1 identified here could be therapeutically exploited for the control of oncogenic pathways in breast cancer cells.


Assuntos
Neoplasias da Mama/metabolismo , Hipóxia Celular/fisiologia , PTEN Fosfo-Hidrolase/deficiência , Proteínas Proto-Oncogênicas c-akt/metabolismo , Canais de Cátion TRPC/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Claudina-4/metabolismo , Transição Epitelial-Mesenquimal , Receptores ErbB/metabolismo , Feminino , Inativação Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Canais de Cátion TRPC/biossíntese , Canais de Cátion TRPC/genética
10.
BMC Pregnancy Childbirth ; 19(1): 34, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654747

RESUMO

BACKGROUND: Smart wristbands enable the continuous monitoring of health parameters, for example, in maternity care. Understanding the feasibility and acceptability of these devices in an authentic context is essential. The aim of this study was to evaluate the feasibility of using a smart wristband to collect continuous activity, sleep and heart rate data from the beginning of the second trimester until one month postpartum. METHODS: The feasibility of a smart wristband was tested prospectively through pregnancy in nulliparous women (n = 20). The outcomes measured were the wear time of the device and the participants' experiences with the smart wristband. The data were collected from the wristbands, phone interviews, questionnaires, and electronic patient records. The quantitative data were analyzed with hierarchical linear mixed models for repeated measures, and qualitative data were analyzed using content analysis. RESULTS: Participants (n = 20) were recruited at a median of 12.9 weeks of gestation. They used the smart wristbands for an average of 182 days during the seven-month study period. The daily use of the devices was similar during the second (17.9 h, 95% CI 15.2 to 20.7) and third trimesters (16.7 h, 95% CI 13.8 to 19.5) but decreased during the postpartum period (14.4 h, 95% CI 11.4 to 17.4, p = 0.0079). Participants who could not wear smart wristbands at work used the device 300 min less per day than did those with no use limitations. Eight of the participants did not wear the devices or wore them only occasionally after giving birth. Nineteen participants reported that the smart wristband did not have any permanent effects on their behavior. Problems with charging and synchronizing the devices, perceiving the devices as uncomfortable, or viewing the data as unreliable, and the fear of scratching their babies with the devices were the main reasons for not using the smart wristbands. CONCLUSIONS: A smart wristband is a feasible tool for continuous monitoring during pregnancy. However, the daily use decreased after birth. The results of this study may support the planning of future studies and help with overcoming barriers related to the use of smart wristbands on pregnant women.


Assuntos
Monitorização Ambulatorial/instrumentação , Cuidado Pós-Natal/métodos , Cuidado Pré-Natal/métodos , Dispositivos Eletrônicos Vestíveis/estatística & dados numéricos , Adulto , Estudos de Viabilidade , Feminino , Frequência Cardíaca , Humanos , Recém-Nascido , Monitorização Ambulatorial/psicologia , Cuidado Pós-Natal/psicologia , Período Pós-Parto/fisiologia , Gravidez , Segundo Trimestre da Gravidez/fisiologia , Terceiro Trimestre da Gravidez/fisiologia , Cuidado Pré-Natal/psicologia , Dispositivos Eletrônicos Vestíveis/psicologia , Punho
11.
Cell Mol Life Sci ; 75(24): 4525-4537, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30105615

RESUMO

Store-operated Ca2+ entry is a pathway that is remodelled in a variety of cancers, and altered expression of the components of store-operated Ca2+ entry is a feature of breast cancer cells of the basal molecular subtype. Studies of store-operated Ca2+ entry in breast cancer cells have used non-specific pharmacological inhibitors, complete depletion of intracellular Ca2+ stores and have mostly focused on MDA-MB-231 cells (a basal B breast cancer cell line). These studies compared the effects of the selective store-operated Ca2+ entry inhibitors Synta66 and YM58483 (also known as BTP2) on global cytosolic free Ca2+ ([Ca2+]CYT) changes induced by physiological stimuli in a different breast cancer basal cell line model, MDA-MB-468. The effects of these agents on proliferation as well as serum and epidermal growth factor (EGF) induced migration were also assessed. Activation with the purinergic receptor activator adenosine triphosphate, produced a sustained increase in [Ca2+]CYT that was entirely dependent on store-operated Ca2+ entry. The protease activated receptor 2 activator, trypsin, and EGF also produced Ca2+ influx that was sensitive to both Synta66 and YM58483. Serum-activated migration of MDA-MB-468 breast cancer cells was sensitive to both store-operated Ca2+ inhibitors. However, proliferation and EGF-activated migration was differentially affected by Synta66 and YM58483. These studies highlight the need to define the exact mechanisms of action of different store-operated calcium entry inhibitors and the impact of such differences in the control of tumour progression pathways.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico/metabolismo , Feminino , Humanos , Proteína ORAI1/metabolismo
12.
Bioorg Med Chem ; 26(12): 3406-3413, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-29776832

RESUMO

The proteins Orai1 and STIM1 control store-operated Ca2+ entry (SOCE) into cells. SOCE is important for migration, invasion and metastasis of MDA-MB-231 human triple negative breast cancer (TNBC) cells and has been proposed as a target for cancer drug discovery. Two hit compounds from a medium throughput screen, displayed encouraging inhibition of SOCE in MDA-MB-231 cells, as measured by a Fluorescence Imaging Plate Reader (FLIPR) Ca2+ assay. Following NMR spectroscopic analysis of these hits and reassignment of their structures as 5-hydroxy-5-trifluoromethylpyrazolines, a series of analogues was prepared via thermal condensation reactions between substituted acylhydrazones and trifluoromethyl 1,3-dicarbonyl arenes. Structure-activity relationship (SAR) studies showed that small lipophilic substituents at the 2- and 3-positions of the RHS and 2-, 3- and 4-postions of the LHS terminal benzene rings improved activity, resulting in a novel class of potent and selective inhibitors of SOCE.


Assuntos
Bloqueadores dos Canais de Cálcio/química , Proteína ORAI1/antagonistas & inibidores , Pirazóis/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Proteína ORAI1/metabolismo , Análise Serial de Proteínas , Pirazóis/metabolismo , Pirazóis/farmacologia , Espectrometria de Fluorescência , Relação Estrutura-Atividade
13.
Bioorg Med Chem ; 25(1): 440-449, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27856238

RESUMO

The Orai1 Ca2+ permeable ion channel is an important component of store operated Ca2+ entry (SOCE) in cells. It's over-expression in basal molecular subtype breast cancers has been linked with poor prognosis, making it a potential target for drug development. We pharmacologically characterised a number of reported inhibitors of SOCE in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader (FLIPR) assay, and show that the rank order of their potencies in this assay is the same as those reported in a wide range of published assays. The assay was also used in a screening project seeking novel inhibitors. Following a broad literature survey of classes of calcium channel inhibitors we used simplified ligand structures to query the ZINC on-line database, and following two iterations of refinement selected a novel Orai1-selective dichlorophenyltriazole hit compound. Analogues of this were synthesized and evaluated in the FLIPR assay to develop structure-activity relationships (SAR) for the three domains of the hit; triazole (head), dichlorophenyl (body) and substituted phenyl (tail). For this series, the results suggested the need for a lipophilic tail domain and an out-of-plane twist between the body and tail domains.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Proteína ORAI1/antagonistas & inibidores , Bloqueadores dos Canais de Cálcio/síntese química , Linhagem Celular Tumoral , Bases de Dados de Compostos Químicos , Estabilidade de Medicamentos , Fluorescência , Células HEK293 , Ensaios de Triagem em Larga Escala , Humanos , Estereoisomerismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/farmacologia
14.
Biochem Biophys Res Commun ; 458(3): 509-514, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25666946

RESUMO

Epithelial-mesenchymal transition (EMT), a process implicated in cancer metastasis, is associated with the transcriptional regulation of members of the ATP-binding cassette superfamily of efflux pumps, and drug resistance in breast cancer cells. Epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells is calcium signal dependent. In this study induction of EMT was shown to result in the transcriptional up-regulation of ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter superfamily, which has a recognized role in multidrug resistance. Buffering of cytosolic free calcium inhibited EGF-mediated ABCC3 increases, indicating a calcium-dependent mode of regulation. Silencing of TRPM7 (an ion channel involved in EMT associated vimentin induction) did not inhibit ABCC3 up-regulation. Silencing of the store operated calcium entry (SOCE) pathway components ORAI1 and STIM1 also did not alter ABCC3 induction by EGF. However, the calcium permeable ion channel transient receptor potential cation channel, subfamily C, member 1 (TRPC1) appears to contribute to the regulation of both basal and EGF-induced ABCC3 mRNA. Improved understanding of the relationship between calcium signaling, EMT and the regulation of genes important in therapeutic resistance may help identify novel therapeutic targets for breast cancer.


Assuntos
Neoplasias da Mama/genética , Mama/patologia , Cálcio/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mama/metabolismo , Neoplasias da Mama/patologia , Sinalização do Cálcio , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , RNA Mensageiro/genética , Canais de Cátion TRPC/metabolismo
15.
PLoS One ; 19(6): e0298949, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38900745

RESUMO

Loneliness is linked to wide ranging physical and mental health problems, including increased rates of mortality. Understanding how loneliness manifests is important for targeted public health treatment and intervention. With advances in mobile sending and wearable technologies, it is possible to collect data on human phenomena in a continuous and uninterrupted way. In doing so, such approaches can be used to monitor physiological and behavioral aspects relevant to an individual's loneliness. In this study, we proposed a method for continuous detection of loneliness using fully objective data from smart devices and passive mobile sensing. We also investigated whether physiological and behavioral features differed in their importance in predicting loneliness across individuals. Finally, we examined how informative data from each device is for loneliness detection tasks. We assessed subjective feelings of loneliness while monitoring behavioral and physiological patterns in 30 college students over a 2-month period. We used smartphones to monitor behavioral patterns (e.g., location changes, type of notifications, in-coming and out-going calls/text messages) and smart watches and rings to monitor physiology and sleep patterns (e.g., heart-rate, heart-rate variability, sleep duration). Participants reported their loneliness feeling multiple times a day through a questionnaire app on their phone. Using the data collected from their devices, we trained a random forest machine learning based model to detect loneliness levels. We found support for loneliness prediction using a multi-device and fully-objective approach. Furthermore, behavioral data collected by smartphones generally were the most important features across all participants. The study provides promising results for using objective data to monitor mental health indicators, which could provide a continuous and uninterrupted source of information in mental healthcare applications.


Assuntos
Solidão , Saúde Mental , Smartphone , Humanos , Solidão/psicologia , Masculino , Feminino , Adulto Jovem , Adulto , Dispositivos Eletrônicos Vestíveis , Inquéritos e Questionários , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Frequência Cardíaca/fisiologia , Aplicativos Móveis , Sono/fisiologia
16.
NPJ Digit Med ; 7(1): 82, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553625

RESUMO

Generative Artificial Intelligence is set to revolutionize healthcare delivery by transforming traditional patient care into a more personalized, efficient, and proactive process. Chatbots, serving as interactive conversational models, will probably drive this patient-centered transformation in healthcare. Through the provision of various services, including diagnosis, personalized lifestyle recommendations, dynamic scheduling of follow-ups, and mental health support, the objective is to substantially augment patient health outcomes, all the while mitigating the workload burden on healthcare providers. The life-critical nature of healthcare applications necessitates establishing a unified and comprehensive set of evaluation metrics for conversational models. Existing evaluation metrics proposed for various generic large language models (LLMs) demonstrate a lack of comprehension regarding medical and health concepts and their significance in promoting patients' well-being. Moreover, these metrics neglect pivotal user-centered aspects, including trust-building, ethics, personalization, empathy, user comprehension, and emotional support. The purpose of this paper is to explore state-of-the-art LLM-based evaluation metrics that are specifically applicable to the assessment of interactive conversational models in healthcare. Subsequently, we present a comprehensive set of evaluation metrics designed to thoroughly assess the performance of healthcare chatbots from an end-user perspective. These metrics encompass an evaluation of language processing abilities, impact on real-world clinical tasks, and effectiveness in user-interactive conversations. Finally, we engage in a discussion concerning the challenges associated with defining and implementing these metrics, with particular emphasis on confounding factors such as the target audience, evaluation methods, and prompt techniques involved in the evaluation process.

17.
BMC Cell Biol ; 14: 57, 2013 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-24359162

RESUMO

BACKGROUND: The entry of calcium ions into mammary gland epithelial cells is one of the least well-understood processes in the transport of calcium into milk during lactation. The store-operated calcium entry channel ORAI1, has been suggested as a potential mechanism for the entry of Ca(2+) into mammary gland epithelial cells from the maternal blood supply during lactation. The down regulation of the canonical ORAI1 activator STIM1 during lactation suggests that other known ORAI activators such as STIM2 and SPCA2 may be important during lactation. RESULTS: Differentiation of HC11 mammary gland epithelial cells was associated with enhanced basal Ca(2+) influx. Silencing of Orai1 abolished this enhancement of Ca(2+) influx. Stim2 had a modest effect on Ca(2+) influx in this in vitro model of lactation, whereas Stim1 and Spca2 silencing had no effect. Despite pronounced increases in Spca2 mRNA during lactation there was no change in the generation of the alternative splice product generated by Mist1, which increases during lactation. CONCLUSIONS: These studies support the hypothesis that lactation is associated with a remodelling of Ca(2+) influx and this is associated with enhancement of basal Ca(2+) influx. This enhanced Ca(2+) influx appears to occur through the calcium channel Orai1.


Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , Processamento Alternativo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Canais de Cálcio/genética , ATPases Transportadoras de Cálcio/genética , ATPases Transportadoras de Cálcio/metabolismo , Cátions Bivalentes , Diferenciação Celular , Células Cultivadas , Células Epiteliais/citologia , Feminino , Transporte de Íons , Lactação/fisiologia , Glândulas Mamárias Animais/citologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Proteína ORAI1 , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Molécula 1 de Interação Estromal , Molécula 2 de Interação Estromal
18.
Artigo em Inglês | MEDLINE | ID: mdl-38082791

RESUMO

Sleep is crucial for physical, mental, and emotional well-being. Physical activity and sleep are known to be interrelated; however, limited research has been performed to investigate their interactions in long-term. Conventional studies have presented sleep quality prediction, focusing on a single sleep quality aspect, such as sleep efficiency. In addition, the relationship between daily physical activity and sleep quality has yet to be explored, despite physical activities being utilized in previous studies for sleep quality prediction. In this paper, we develop an Extreme Gradient boosting method to predict sleep duration, sleep efficiency, and deep sleep based on users' daily activity information collected from wearable devices. Our model is trained and tested using data collected with an OURA ring from 34 pregnant mothers for six months under free-living conditions. Our finding shows an accuracy of 90.58%, 95.38%, and 91.45% for sleep duration, efficiency, and deep sleep, respectively. Moreover, we assess the contribution of each physical activity parameter to the prediction results using the Shapley Additive Explanations method. Our results indicate that sedentary time is the most influential parameter for sleep duration prediction, while the inactive time feature (e.g., resting or lying down) has a strong negative relationship with sleep efficiency, and the pregnancy week is the most critical parameter for deep sleep prediction.


Assuntos
Qualidade do Sono , Dispositivos Eletrônicos Vestíveis , Gravidez , Feminino , Humanos , Sono , Exercício Físico , Comportamento Sedentário
19.
Front Digit Health ; 5: 1253087, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781455

RESUMO

The proliferation of Internet-connected health devices and the widespread availability of mobile connectivity have resulted in a wealth of reliable digital health data and the potential for delivering just-in-time interventions. However, leveraging these opportunities for health research requires the development and deployment of mobile health (mHealth) applications, which present significant technical challenges for researchers. While existing mHealth solutions have made progress in addressing some of these challenges, they often fall short in terms of time-to-use, affordability, and flexibility for personalization and adaptation. ZotCare aims to address these limitations by offering ready-to-use and flexible services, providing researchers with an accessible, cost-effective, and adaptable solution for their mHealth studies. This article focuses on ZotCare's service orchestration and highlights its capabilities in creating a programmable environment for mHealth research. Additionally, we showcase several successful research use cases that have utilized ZotCare, both in the past and in ongoing projects. Furthermore, we provide resources and information for researchers who are considering ZotCare as their mHealth research solution.

20.
Life Sci ; 335: 122275, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37984514

RESUMO

Cancer and stem cells share many characteristics related to self-renewal and differentiation. Both cell types express the same critical proteins that govern cellular stemness, which provide cancer cells with the growth and survival benefits of stem cells. LIN28 is an example of one such protein. LIN28 includes two main isoforms, LIN28A and LIN28B, with diverse physiological functions from tissue development to control of pluripotency. In addition to their physiological roles, LIN28A and LIN28B affect the progression of several cancers by regulating multiple cancer hallmarks. Altered expression levels of LIN28A and LIN28B have been proposed as diagnostic and/or prognostic markers for various malignancies. This review discusses the structure and modes of action of the different LIN28 proteins and examines their roles in regulating cancer hallmarks with a focus on malignancies of the nervous system. This review also highlights some gaps in the field that require further exploration to assess the potential of targeting LIN28 proteins for controlling cancer.


Assuntos
MicroRNAs , Neoplasias , Neoplasias do Sistema Nervoso , Humanos , Neoplasias/metabolismo , Neoplasias do Sistema Nervoso/metabolismo , Células-Tronco/metabolismo , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/metabolismo
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