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1.
Comput Methods Programs Biomed ; 211: 106442, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34624633

RESUMO

BACKGROUND AND OBJECTIVE: Sleep apnea (SA) is a common sleep disorder in daily life and is also an aggravating factor for various diseases. Having the potential to replace traditional but complicated diagnostic equipment, portable medical devices are receiving increasing attention, and thus, the demand for supporting algorithms is growing. This study aims to identify SA with wearable devices. METHODS: Static information-based similarity (sIBS) and dynamic information-based similarity (dIBS) were proposed to analyze short-term fluctuations in heart rate (HR) with wearable devices. This study included overnight photoplethysmography (PPG) signals from 92 subjects obtained from wearable bracelets. RESULTS: The results showed that sIBS achieved the highest correlation coefficient with the apnea-hypopnea index (R=-0.653, p=0). dIBS showed a good balance in sensitivity and specificity (75.0% and 72.1%, respectively). Combining sIBS and dIBS with other classical time-frequency domain indices could simultaneously achieve good accuracy and balance (84.7% accuracy, 76.7% sensitivity and 89.6% specificity). CONCLUSIONS: This research showed that both classic time-frequency domain indices and IBS indices changed significantly only in the severe SA group. This novel method could serve as an effective way to assess SA and provide new insight into its pathophysiology.

2.
Bioengineered ; 12(1): 6855-6868, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34519612

RESUMO

Glioma is a common intracranial tumor originated from neuroglia cell. Chrysophanol is an anthraquinone derivative proved to exert anticancer effects in various cancers. This paper investigated the effect and mechanism of chrysophanol in glioma. Glioma cell lines U251 and SHG-44 were adopted in the experiments. The cells were treated with chrysophanol at different concentrations (0, 10, 20 50, 100 and 200 µM) for 48 h in the study, and then processed with MitoTempo. Mitochondria and cytosol were isolated to investigate the role of mitochondria during chrysophanol functioning on glioma cells. Cell viability was detected through 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl Tetrazolium Bromide (MTT) assay, and cell apoptosis, cell cycle as well as relative reactive oxygen species (ROS) were assessed by flow cytometry. Expressions of Cytosol Cyt C, cleaved caspase-3, cleaved caspase-9, Cyclin D1 and Cyclin E were evaluated by western blot. In U251 and SHG-44 cells, with chrysophanol concentration rising, cell viability, expressions of Cyclin D1 and Cyclin E were decreased while cell apoptosis, levels of cleaved caspase-3, cleaved caspase-9 and Cytosol Cyt C as well as ROS accumulation were increased with cell cycle arrested in G1 phase. Besides, chrysophanol promoted ROS accumulation, cell apoptosis and transfer of Cyt C from mitochondria to cytosol in cells while MitoTempo partly reversed the effect of chrysophanol. Chrysophanol promoted cell apoptosis via activating mitochondrial apoptosis pathway in glioma.

3.
Comput Biol Med ; 135: 104632, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34265554

RESUMO

Obstructive sleep apnea (OSA) is a serious sleep disorder, which leads to changes in autonomic nerve function and increases the risk of cardiovascular disease. Heart rate variability (HRV) has been widely used as a non-invasive method for assessing the autonomic nervous system (ANS). We proposed the two-dimensional sample entropy of the coarse-grained Gramian angular summation field image (CgSampEn2D) index. It is a new index for HRV analysis based on the temporal dependency complexity. In this study, we used 60 electrocardiogram (ECG) records from the Apnea-ECG database of PhysioNet (20 healthy records and 40 OSA records). These records were divided into 5-min segments. Compared with the classical indices low-to-high frequency power ratio (LF/HF) and sample entropy (SampEn), CgSampEn2D utilizes the correlation information between different time intervals in the RR sequences and preserves the temporal dependency of the RR sequences, which improves the OSA detection performance significantly. The OSA screening accuracy of CgSampEn2D (93.3%) is higher than that of LF/HF (80.0%) and SampEn (73.3%). Additionally, CgSampEn2D has a significant association with the apnea-hypopnea index (AHI) (R = -0.740, p = 0). CgSampEn2D reflects the complexity of the OSA autonomic nerve more comprehensively and provides a novel idea for the screening of OSA disease.


Assuntos
Apneia Obstrutiva do Sono , Sistema Nervoso Autônomo , Frequência Cardíaca , Humanos , Polissonografia , Análise de Sistemas
4.
Cell Death Dis ; 12(8): 733, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301924

RESUMO

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor for which new therapeutic approaches are urgently required. Unfolded protein response (UPR) plays an important role in the progression of GBM and is a promising target for developing novel therapeutic interventions. We identified ubiquitin-activating enzyme 1 (UBA1) inhibitor TAK-243 that can strongly induce UPR in GBM cells. In this study, we evaluated the functional activity and mechanism of TAK-243 in preclinical models of GBM. TAK-243 significantly inhibited the survival, proliferation, and colony formation of GBM cell lines and primary GBM cells. It also revealed a significant anti-tumor effect on a GBM PDX animal model and prolonged the survival time of tumor-bearing mice. Notably, TAK-243 more effectively inhibited the survival and self-renewal ability of glioblastoma stem cells (GSCs) than GBM cells. Importantly, we found that the expression level of GRP78 is a key factor in determining the sensitivity of differentiated GBM cells or GSCs to TAK-243. Mechanistically, UBA1 inhibition disrupts global protein ubiquitination in GBM cells, thereby inducing ER stress and UPR. UPR activates the PERK/ATF4 and IRE1α/XBP signaling axes. These findings indicate that UBA1 inhibition could be an attractive strategy that may be potentially used in the treatment of patients with GBM, and GRP78 can be used as a molecular marker for personalized treatment by targeting UBA1.

5.
J Cell Mol Med ; 25(15): 7395-7406, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216174

RESUMO

Glioblastoma multiforme (GBM), a fatal brain tumour with no available targeted therapies, has a poor prognosis. At present, radiotherapy is one of the main methods to treat glioma, but it leads to an obvious increase in inflammatory factors in the tumour microenvironment, especially IL-6 and CXCL1, which plays a role in tumour to resistance radiotherapy and tumorigenesis. Casein kinase 1 alpha 1 (CK1α) (encoded on chromosome 5q by Csnk1a1) is considered an attractive target for Tp53 wild-type acute myeloid leukaemia (AML) treatment. In this study, we evaluated the anti-tumour effect of Csnk1a1 suppression in GBM cells in vitro and in vivo. We found that down-regulation of Csnk1a1 or inhibition by D4476, a Csnk1a1 inhibitor, reduced GBM cell proliferation efficiently in both Tp53 wild-type and Tp53-mutant GBM cells. On the contrary, overexpression of Csnk1a1 promoted cell proliferation and colony formation. Csnk1a1 inhibition improved the sensitivity to radiotherapy. Furthermore, down-regulation of Csnk1a1 reduced the production and secretion of pro-inflammatory factors. In the preclinical GBM model, treatment with D4476 significantly inhibited the increase in pro-inflammatory factors caused by radiotherapy and improved radiotherapy sensitivity, thus inhibiting tumour growth and prolonging animal survival time. These results suggest targeting Csnk1a1 exert an anti-tumour role as an inhibitor of inflammatory factors, providing a new strategy for the treatment of glioma.

6.
Entropy (Basel) ; 23(3)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668394

RESUMO

Obstructive sleep apnea (OSA) is associated with reduced heart rate variability (HRV) and autonomic nervous system dysfunction. Sample entropy (SampEn) is commonly used for regularity analysis. However, it has limitations in processing short-term segments of HRV signals due to the extreme dependence of its functional parameters. We used the nonparametric sample entropy (NPSampEn) as a novel index for short-term HRV analysis in the case of OSA. The manuscript included 60 6-h electrocardiogram recordings (20 healthy, 14 mild-moderate OSA, and 26 severe OSA) from the PhysioNet database. The NPSampEn value was compared with the SampEn value and frequency domain indices. The empirical results showed that NPSampEn could better differentiate the three groups (p < 0.01) than the ratio of low frequency power to high frequency power (LF/HF) and SampEn. Moreover, NPSampEn (83.3%) approached a higher OSA screening accuracy than the LF/HF (73.3%) and SampEn (68.3%). Compared with SampEn (|r| = 0.602, p < 0.05), NPSampEn (|r| = 0.756, p < 0.05) had a significantly stronger association with the apnea-hypopnea index (AHI). Hence, NPSampEn can fully overcome the influence of individual differences that are prevalent in biomedical signal processing, and might be useful in processing short-term segments of HRV signal.

7.
World Neurosurg ; 149: e931-e934, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33508492

RESUMO

OBJECTIVE: Post-traumatic hydrocephalus (PTH) is a common complication of craniocerebral injury. If not diagnosed in time, PTH can lead to clinical deterioration and a poor prognosis. The early diagnosis of PTH can lead to success with early treatment. However, PTH can be easily ignored during rehabilitation. The main purpose of the present study was to investigate whether plasma S100B protein levels can be used as a biochemical predictive index of PTH. We also explored the correlation among S100B protein levels, intracranial pressure, and PTH severity. METHODS: The data from 235 patients with traumatic brain injury treated from June 2014 to June 2019 in our hospital were retrospectively analyzed. Statistical analysis was performed on 3 serum S100B samples from each patient. The first sample was taken 1-3 days after the injury and surgery. The second sample was harvested during the stable period after treatment, and the third sample was taken when PTH had been confirmed by computed tomography. We analyzed the change in S100B protein levels, and intracranial pressure was measured by lumbar puncture. RESULTS: A total of 235 patients (Glasgow coma scale score <12) with traumatic brain injury were investigated. Of these 235 patients, 46 (19%) had developed PTH. The first and second S100B samples showed no significant differences between the patients with and without PTH. In the third sample, the S100B level of the patients with PTH was significantly greater than that of the patients without PTH, with a statistically significant difference. Statistical analysis found no correlation between the S100B level and the severity of PTH. CONCLUSIONS: Measurements of serum S100B can be used to predict for PTH. We found a positive correlation between S100B levels and intracranial pressure but no correlation with the severity of PTH. Thus, serum S100B could have important clinical significance for the early detection and evaluation of PTH.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Hidrocefalia/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/etiologia , Hidrocefalia/fisiopatologia , Pressão Intracraniana , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Adulto Jovem
8.
J Craniofac Surg ; 32(1): e46-e49, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33235158

RESUMO

ABSTRACT: To explore a new surgical treatment for infection and obstruction of ventriculoperitoneal shunt in hydrocephalus. Two cases of post-operative infection of ventriculoperitoneal shunt were analyzed retrospectively. One case was cryptococcal infection, the other case was Acinetobacter lwoffii. The number of cerebrospinal fluid cells was high, the infection of ventriculoperitoneal shunt was generally complicated with abdominal obstruction, and the hydrocephalus was aggravated again, The authors try to pull out the drainage tube at the end of abdominal cavity for external drainage, combined with intravenous antibiotics, completely control of infection, and then use the original shunt device for intraventricular jugular shunt. The authors explore that this method is simple, safe and effective, and it is an effective and feasible method for the treatment of infection after ventriculoperitoneal shunt.


Assuntos
Derivação Ventriculoperitoneal/efeitos adversos , Acinetobacter , Humanos , Hidrocefalia/cirurgia , Estudos Retrospectivos
9.
Entropy (Basel) ; 22(9)2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-33286684

RESUMO

Obstructive sleep apnea (OSA) is a fatal respiratory disease occurring in sleep. OSA can induce declined heart rate variability (HRV) and was reported to have autonomic nerve system (ANS) dysfunction. Variance delay fuzzy approximate entropy (VD_fApEn) was proposed as a nonlinear index to study the fluctuation change of ANS in OSA patients. Sixty electrocardiogram (ECG) recordings of the PhysioNet database (20 normal, 14 mild-moderate OSA, and 26 severe OSA) were intercepted for 6 h and divided into 5-min segments. HRV analysis were adopted in traditional frequency domain, and nonlinear HRV indices were also calculated. Among these indices, VD_fApEn could significantly differentiate among the three groups (p < 0.05) compared with the ratio of low frequency power and high frequency power (LF/HF ratio) and fuzzy approximate entropy (fApEn). Moreover, the VD_fApEn (90%) reached a higher OSA screening accuracy compared with LF/HF ratio (80%) and fApEn (78.3%). Therefore, VD_fApEn provides a potential clinical method for ANS fluctuation analysis in OSA patients and OSA severity analysis.

10.
J Cell Mol Med ; 24(13): 7550-7562, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32452133

RESUMO

Glioblastoma multiforme (GBM) is the most common malignant tumour in the adult brain and hard to treat. Nuclear factor κB (NF-κB) signalling has a crucial role in the tumorigenesis of GBM. EGFR signalling is an important driver of NF-κB activation in GBM; however, the correlation between EGFR and the NF-κB pathway remains unclear. In this study, we investigated the role of mucosa-associated lymphoma antigen 1 (MALT1) in glioma progression and evaluated the anti-tumour activity and effectiveness of MI-2, a MALT1 inhibitor in a pre-clinical GBM model. We identified a paracaspase MALT1 that is involved in EGFR-induced NF-kB activation in GBM. MALT1 deficiency or inhibition significantly affected the proliferation, survival, migration and invasion of GBM cells both in vitro and in vivo. Moreover, MALT1 inhibition caused G1 cell cycle arrest by regulating multiple cell cycle-associated proteins. Mechanistically, MALTI inhibition blocks the degradation of IκBα and prevents the nuclear accumulation of the NF-κB p65 subunit in GBM cells. This study found that MALT1, a key signal transduction cascade, can mediate EGFR-induced NF-kB activation in GBM and may be potentially used as a novel therapeutic target for GBM.


Assuntos
Receptores ErbB/metabolismo , Glioblastoma/metabolismo , Terapia de Alvo Molecular , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , NF-kappa B/metabolismo , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Fator de Crescimento Epidérmico/farmacologia , Glioblastoma/patologia , Humanos , Camundongos Knockout , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/antagonistas & inibidores , Invasividade Neoplásica , Ensaio Tumoral de Célula-Tronco
11.
Cancer Cell Int ; 20: 97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256206

RESUMO

Background: Activation of nuclear factor-kappa B (NF-κΒ) through DNA damage is one of the causes of tumor cell resistance to radiotherapy. Chromosome region 1 (CRM1) regulates tumor cell proliferation, drug resistance, and radiation resistance by regulating the nuclear-cytoplasmic translocation of important tumor suppressor proteins or proto-oncoproteins. A large number of studies have reported that inhibition of CRM1 suppresses the activation of NF-κΒ. Thus, we hypothesize that the reversible CRM1 inhibitor S109 may induce radiosensitivity in glioblastoma (GBM) by regulating the NF-κΒ signaling pathway. Methods: This study utilized the cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assay to evaluate the effect of S109 combined with radiotherapy on the proliferation and survival of GBM cells. The therapeutic efficacy of S109 combined with radiotherapy was evaluated in vivo to explore the therapeutic mechanism of S109-induced GBM radiosensitization. Results: We found that S109 combined with radiotherapy significantly inhibited GBM cell proliferation and colony formation. By regulating the levels of multiple cell cycle- and apoptosis-related proteins, the combination therapy induced G1 cell cycle arrest in GBM cells. In vivo studies showed that S109 combined with radiotherapy significantly inhibited the growth of intracranial GBM and prolonged survival. Importantly, we found that S109 combined with radiotherapy promoted the nuclear accumulation of IκΒα, and inhibited phosphorylation of p65 and the transcriptional activation of NF-κΒ. Conclusion: Our findings provide a new therapeutic regimen for improving GBM radiosensitivity as well as a scientific basis for further clinical trials to evaluate this combination therapy.

12.
Cancer Cell Int ; 19: 305, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31832018

RESUMO

Background: Switch-associated protein 70 (SWAP-70) is a guanine nucleotide exchange factor that is involved in cytoskeletal rearrangement and regulation of migration and invasion of malignant tumors. However, the mechanism by which SWAP-70 regulates the migration and invasion of glioblastoma (GB) cells has not been fully elucidated. Methods: This study used an online database to analyze the relationship between SWAP-70 expression and prognosis in GB patients. The in vitro wound healing assay and transwell invasion assay were used to determine the role of SWAP-70 in GB cell migration and invasion as well as the underlying mechanism. Results: We found that patients with high SWAP-70 expression in the GB had a poor prognosis. Downregulation of SWAP-70 inhibited GB cell migration and invasion, whereas SWAP-70 overexpression had an opposite effect. Interestingly, SWAP-70 expression was positively correlated with the expression of the standard form of CD44 (CD44s) in GB tissues. Downregulation of SWAP-70 also reduced CD44s protein expression, whereas SWAP-70 overexpression enhanced CD44s protein expression. However, downregulation of SWAP-70 expression did not affect the mRNA expression of CD44s. Reversal experiments showed that overexpressing CD44s in cell lines with downregulated SWAP-70 partially abolished the inhibitory effects of downregulated SWAP-70 on GB cell migration and invasion. Conclusions: These results suggest that SWAP-70 may promote GB cell migration and invasion by regulating the expression of CD44s. SWAP-70 may serve as a new biomarker and a potential therapeutic target for GB.

13.
IEEE J Biomed Health Inform ; 23(1): 175-183, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29993964

RESUMO

Obstructive sleep apnea (OSA) is a common sleep disorder that is often associated with reduced heart rate variability (HRV), thus reflecting modulation of the autonomic system. Sliding trend fuzzy approximate entropy (SlTr-fApEn), which is based on the empirical mode decomposition (EMD) method, has been proposed as a novel index for analyzing HRV with OSA. This study included 60 electrocardiogram recordings from the PhysioNet database (40 OSA recordings and 20 healthy recordings) with apnea or no apnea in 5-minute segments. HRV indices obtained by sliding trend analysis were compared to those obtained by time-frequency domain analysis. Among all indices, the ratio of low-frequency power and high-frequency power (LF/HF) and sliding trend indices could significantly differentiate OSA recordings from normal recordings (p < 0.05). The OSA screening accuracy of SlTr-fApEn (85%) was higher than that of LF/HF (80%). Disease state analysis showed significant differences in SlTr-fApEn among the control group, normal OSA group, and apnea OSA group (p < 0.05). Therefore, SlTr-fApEn can reflect the complexity of autonomic changes during a short time period.


Assuntos
Frequência Cardíaca/fisiologia , Processamento de Sinais Assistido por Computador , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Eletrocardiografia/métodos , Entropia , Feminino , Humanos , Masculino , Polissonografia/métodos , Apneia Obstrutiva do Sono/fisiopatologia , Adulto Jovem
14.
Entropy (Basel) ; 20(10)2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33265883

RESUMO

Congestive heart failure (CHF) is a cardiovascular disease associated with autonomic dysfunction, where sympathovagal imbalance was reported in many studies using heart rate variability (HRV). To learn more about the dynamic interaction in the autonomic nervous system (ANS), we explored the directed interaction between the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS) with the help of transfer entropy (TE). This article included 24-h RR interval signals of 54 healthy subjects (31 males and 23 females, 61.38 ± 11.63 years old) and 44 CHF subjects (8 males and 2 females, 19 subjects' gender were unknown, 55.51 ± 11.44 years old, 4 in class I, 8 in class II and 32 in class III~IV, according to the New York Heart Association Function Classification), obtained from the PhysioNet database and then segmented into 5-min non-overlapping epochs using cubic spline interpolation. For each segment in the normal group and CHF group, frequency-domain features included low-frequency (LF) power, high-frequency (HF) power and LF/HF ratio were extracted as classical estimators of autonomic activity. In the nonlinear domain, TE between LF and HF were calculated to quantify the information exchanging between SNS and PNS. Compared with the normal group, an extreme decrease in LF/HF ratio (p = 0.000) and extreme increases in both TE(LF→HF) (p = 0.000) and TE(HF→LF) (p = 0.000) in the CHF group were observed. Moreover, both in normal and CHF groups, TE(LF→HF) was a lot greater than TE(HF→LF) (p = 0.000), revealing that TE was able to distinguish the difference in the amount of directed information transfer among ANS. Extracted features were further applied in discriminating CHF using IBM SPSS Statistics discriminant analysis. The combination of the LF/HF ratio, TE(LF→HF) and TE(HF→LF) reached the highest screening accuracy (83.7%). Our results suggested that TE could serve as a complement to traditional index LF/HF in CHF screening.

15.
Australas Phys Eng Sci Med ; 40(3): 595-602, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28831682

RESUMO

Grip force control is a crucial function for human to guarantee the quality of life. To examine the effects of age on grip force control, 10 young adults and 11 late middle-aged adults participated in visually guided tracking tasks using different target force levels (25, 50, and 75% of the subject's maximal grip force). Multiple measures were used to evaluate the tracking performance during force rising phase and force maintenance phase. The measurements include the rise time, fuzzy entropy, mean force percentage, coefficient of variation, and target deviation ratio. The results show that the maximal grip force was significantly lower in the late middle-aged adults than in the young adults. The time of rising phase was systematically longer among late middle-aged adults. The fuzzy entropy is a useful indicator for quantitating the force variability of the grip force signal at higher force levels. These results suggest that the late middle-aged adults applied a compensatory strategy that allow allows for sufficient time to reach the required grip force and reduce the impact of the early and subtle degenerative changes in hand motor function.


Assuntos
Força da Mão/fisiologia , Fenômenos Biomecânicos , Entropia , Feminino , Lógica Fuzzy , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Neuro Oncol ; 19(12): 1628-1639, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-28575494

RESUMO

Background: Golgi phosphoprotein 3 (GOLPH3) is associated with worse prognosis of gliomas, but its role and mechanism in glioma progression remain largely unknown. This study aimed to explore the role and mechanism of GOLPH3 in glioma progression. Methods: The expression of GOLPH3 in glioma tissues was detected by quantitative PCR, immunoblotting, and immunohistochemistry. GOLPH3's effect on glioma progression was examined using cell growth assays and an intracranial glioma model. The effect of GOLPH3 on epidermal growth factor receptor (EGFR) stability, endocytosis, and degradation was examined by immunoblotting and immunofluorescence. The activity of Rab5 was checked by glutathione S-transferase pulldown assay. Results: GOLPH3 was upregulated in gliomas, and its downregulation inhibited glioma cell proliferation both in vitro and in vivo. Furthermore, GOLPH3 depletion dampened EGFR signaling by enhancing EGFR endocytosis, driving EGFR into late endosome and promoting lysosome-mediated degradation. Interestingly, GOLPH3 bound to Rab5 and GOLPH3 downregulation promoted the activation of Rab5. In addition, Rab5 depletion abolished the effect of GOLPH3 on EGFR endocytosis and degradation. Conclusion: Our results imply that GOLPH3 promotes glioma cell proliferation via inhibiting Rab5-mediated endocytosis and degradation of EGFR, thereby activating the phosphatidylinositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway. We find a new mechanism by which GOLPH3 promotes tumor progression through regulating cell surface receptor trafficking. Extensive and intensive understanding of the role of GOLPH3 in glioma progression may provide an opportunity to develop a novel molecular therapeutic target for gliomas.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Endocitose/fisiologia , Receptores ErbB/metabolismo , Glioma/patologia , Proteínas de Membrana/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo , Animais , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Progressão da Doença , Receptores ErbB/genética , Glioma/genética , Glioma/metabolismo , Humanos , Proteínas de Membrana/genética , Camundongos Nus , Prognóstico , Transdução de Sinais , Proteínas rab5 de Ligação ao GTP/genética
17.
PLoS One ; 11(11): e0165304, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27835634

RESUMO

Risk assessment of congestive heart failure (CHF) is essential for detection, especially helping patients make informed decisions about medications, devices, transplantation, and end-of-life care. The majority of studies have focused on disease detection between CHF patients and normal subjects using short-/long-term heart rate variability (HRV) measures but not much on quantification. We downloaded 116 nominal 24-hour RR interval records from the MIT/BIH database, including 72 normal people and 44 CHF patients. These records were analyzed under a 4-level risk assessment model: no risk (normal people, N), mild risk (patients with New York Heart Association (NYHA) class I-II, P1), moderate risk (patients with NYHA III, P2), and severe risk (patients with NYHA III-IV, P3). A novel multistage classification approach is proposed for risk assessment and rating CHF using the non-equilibrium decision-tree-based support vector machine classifier. We propose dynamic indices of HRV to capture the dynamics of 5-minute short term HRV measurements for quantifying autonomic activity changes of CHF. We extracted 54 classical measures and 126 dynamic indices and selected from these using backward elimination to detect and quantify CHF patients. Experimental results show that the multistage risk assessment model can realize CHF detection and quantification analysis with total accuracy of 96.61%. The multistage model provides a powerful predictor between predicted and actual ratings, and it could serve as a clinically meaningful outcome providing an early assessment and a prognostic marker for CHF patients.


Assuntos
Insuficiência Cardíaca/diagnóstico , Frequência Cardíaca , Modelos Estatísticos , Máquina de Vetores de Suporte , Estudos de Casos e Controles , Bases de Dados Factuais , Árvores de Decisões , Insuficiência Cardíaca/fisiopatologia , Humanos , Prognóstico , Medição de Risco , Índice de Gravidade de Doença
18.
J Healthc Eng ; 5(3): 313-27, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25193370

RESUMO

Electrode configuration is an important issue in the continuous measurement of respiration using impedance pneumography (IP). The robust configuration is usually confirmed by comparing the amplitude of the IP signals acquired with different electrode configurations, while the relative change in waveform and the effects of body posture and respiratory pattern are ignored. In this study, the IP signals and respiratory volume are simultaneously acquired from 8 healthy subjects in supine, left lying, right lying and prone postures, and the subjects are asked to perform four respiratory patterns including free breathing, thoracic breathing, abdominal breathing and apnea. The IP signals are acquired with four different chest electrode configurations, and the volume are measured using pneumotachograph (PNT). Differences in correlation and absolute deviation between the IP-derived and PNT-derived respiratory volume are assessed. The influences of noise, respiratory pattern and body posture on the IP signals of different configurations have significant difference (p < 0.05). The robust electrode configuration is found on the axillary midline, which is suitable for long term respiration monitoring.


Assuntos
Monitorização Fisiológica/instrumentação , Testes de Função Respiratória/instrumentação , Mecânica Respiratória/fisiologia , Processamento de Sinais Assistido por Computador , Adulto , Eletrodos , Desenho de Equipamento , Humanos , Masculino , Monitorização Fisiológica/métodos , Postura/fisiologia , Testes de Função Respiratória/métodos , Volume de Ventilação Pulmonar/fisiologia , Adulto Jovem
19.
Australas Phys Eng Sci Med ; 37(3): 567-74, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24913617

RESUMO

To analyze motion artifact's affect on HRV measures, the age/gender related autonomic changes were investigated by using different HRV measures from wearable medical devices under ambulatory home-monitoring condition. Twelve healthy undergraduates and 20 healthy elderly subjects participated in the research. The electrocardiogram data was collected by using waist-worn device developed by us. Ten HRV measures were used to analyze the age-related automatic change including linear and nonlinear HRV indexes. Many linear HRV indexes were seriously contaminated by motion artefact, and did not reflect the age-related autonomic change. The approximate entropy (p < 0.001) was the best indicator among 10 HRV indexes. However, the approximate entropy was also contaminated by motion artefact and did not reflect the gender-related autonomic change. The study verified the hypothesis that the HRV measures could be contaminated under ambulatory monitoring condition. It is importance for ambulatory home-monitoring to study the robustness of HRV measures.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Voluntários Saudáveis , Frequência Cardíaca/fisiologia , Caracteres Sexuais , Fatores Etários , Idoso , Entropia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
20.
PLoS One ; 9(4): e93399, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24747432

RESUMO

Heart rate variability (HRV) analysis has quantified the functioning of the autonomic regulation of the heart and heart's ability to respond. However, majority of studies on HRV report several differences between patients with congestive heart failure (CHF) and healthy subjects, such as time-domain, frequency domain and nonlinear HRV measures. In the paper, we mainly presented a new approach to detect congestive heart failure (CHF) based on combination support vector machine (SVM) and three nonstandard heart rate variability (HRV) measures (e.g. SUM_TD, SUM_FD and SUM_IE). The CHF classification model was presented by using SVM classifier with the combination SUM_TD and SUM_FD. In the analysis performed, we found that the CHF classification algorithm could obtain the best performance with the CHF classification accuracy, sensitivity and specificity of 100%, 100%, 100%, respectively.


Assuntos
Algoritmos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Informática Médica/métodos , Adulto , Idoso , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Máquina de Vetores de Suporte , Fatores de Tempo
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