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1.
Photodiagnosis Photodyn Ther ; 47: 104198, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729232

RESUMO

BACKGROUD: To investigate the safety of repetitive low-level red-light therapy (RLRLT) in children with myopia. METHODS: Children with myopia were assigned to the RLRL and control groups. Axial length (AL) and spherical equivalent refraction (SER) were followed up at 3-, 6-, and 12-month. To evaluate the safety of RLRLT, at 6 and 12 months in the RLRL group, multifocal electroretinography (mfERG) and contrast sensitivity were recorded. Furthermore, optical coherence tomography was used to measure the relative reflectance of the ellipsoid zone (rEZR), photoreceptor outer segment (rPOSR), and retinal pigment epithelium (rRPER). RESULTS: A total of 108 children completed the trial (55 in the RLRL group and 53 in the control group). After 3, 6, and 12 months, AL was shorter and SER less myopic in the RLRL group than in the control group. Regarding the safety of the RLRLT, the response density and amplitude of the P1 wave of the first ring of the mfERG increased significantly at 6 months (P = 0.001 and P = 0.017, respectively). At 6 and 12 months, contrast sensitivity at the high spatial frequency increased. Moreover, the rEZR increased significantly at 6 months (P = 0.029), the rPOSR increased significantly at 6 and 12 months (both P < 0.001), and the increase in rPOSR was greater with greater AL regression. CONCLUSIONS: Based on retinal function and structure follow-up, RLRLT was safe within 12 months. However, rEZR and rPOSR increased, the effects of this phenomenon requires further observation.


Assuntos
Miopia , Tomografia de Coerência Óptica , Humanos , Miopia/fisiopatologia , Miopia/terapia , Criança , Masculino , Feminino , Terapia com Luz de Baixa Intensidade/métodos , Eletrorretinografia , Sensibilidades de Contraste/fisiologia
2.
iScience ; 27(2): 109018, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38357665

RESUMO

Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of bona fide NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating in vitro and in vivo transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages. We show that TGF-ß inhibition enhances the yield and homogeneity of notochordal lineage commitment in vitro. Furthermore, this study characterizes regulators of cell-fate decision and matrisome enriched in the notochordal niche. Importantly, we identify specific cell-surface markers opening avenues for differentiation refinement, NC purification, and functional studies. Altogether, this study provides a human notochord transcriptomic reference that will serve as a resource for notochord identification in human systems, diseased-tissues modeling, and facilitating future biomedical research.

3.
BMC Cancer ; 23(1): 1081, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946141

RESUMO

PURPOSE: The pathological diagnosis and prognosis prediction of hepatocellular carcinoma (HCC) is challenging due to the lack of specific biomarkers. This study aimed to validate the diagnostic and prognostic efficiency of Kidney-type glutaminase (GLS1) for HCC in prospective cohorts with a large sample size. METHODS: A total of 1140 HCC patients were enrolled in our prospective clinical trials. Control cases included 114 nontumour tissues. The registered clinical trial (ChiCTR-DDT-14,005,102, chictr.org.cn) was referred to for the exact protocol. GLS1 immunohistochemistry was performed on the whole tumour section. The diagnostic and prognostic performances of GLS1 was evaluated by the receiver operating characteristic curve and Cox regression model. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under the curve of GLS1 for the diagnosis of HCC were 0.746, 0.842, 0.979, 0.249, 0.588, and 0.814, respectively, which could be increased to 0.846, 0.886, 0.987,0.366, 0.732, and 0.921 when combined with glypican 3 (GPC3) and alpha-fetoprotein (AFP), indicating better diagnostic performance. Further, we developed a nomogram with GPC3 and GLS1 for identifying HCC which showed good discrimination and calibration. GLS1 expression was also related with age, T stage, TNM stage, Edmondson-Steiner grade, microvascular invasion, Ki67, VEGFR2, GPC3, and AFP expression in HCC. GLS1 expression was negatively correlated with disease-free survival (P < 0.001) probability of patients with HCC. CONCLUSIONS: It was validated that GLS1 was a sensitive and specific biomarker for pathological diagnosis of HCC and had prognostic value, thus having practical value for clinical application.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Estudos Prospectivos , Neoplasias Hepáticas/patologia , Glutaminase , Biomarcadores Tumorais , Prognóstico , Rim/patologia , Glipicanas
4.
Oncol Lett ; 25(6): 234, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37153040

RESUMO

Primary pulmonary intravascular large B-cell lymphoma (IVLBCL) is a rare, malignant extranodal lymphoma. It is difficult to diagnose clinically as it requires a combination of clinical and computed tomography (CT) evaluations, as well as laboratory and pathological examinations. In the present study, 4 cases of primary pulmonary IVLBCL were reviewed. The patients' ages ranged from 60 to 69 years old. Of the 4 patients, 3 developed progressive dyspnea on exertion and intermittent fever. Other symptoms included coughing, chest tightness and weight loss. Laboratory data indicated that all patients had anemia, thrombocytopenia, hypoxemia, a markedly high serum lactate dehydrogenase level, elevated erythrocyte sedimentation rate and increased C-reactive protein. CT demonstrated increased attenuation in bilateral lung parenchyma, especially in the upper lobes, with multiple ground-glass opacities associated with small nodules in these patients. Initially, all 4 patients were misdiagnosed with pneumonia. However, none of them responded to anti-inflammatory treatments. The pathologies of all patients were confirmed using lung biopsy. Only 1 patient received regular combination chemotherapy. Based on the observations of the present study, a standard regimen for lymphoma treatment may result in a notable clinical response.

5.
Int Ophthalmol ; 43(9): 3297-3307, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37160587

RESUMO

PURPOSE: To investigate the effect of endothelin-1 (ET-1) in excessive accumulation of extracellular matrix (ECM) of the trabecular meshwork (TM) and its role in intraocular pressure (IOP) regulation. METHODS: Cultured human TM cells (HTMCs) were treated with ET-1, ET-1 + ETA receptor (ETAR) antagonist BQ123, ET-1 + ETB receptor (ETBR) antagonist BQ788. The expressions of fibronectin (FN) and collagen type IV (Col IV) were evaluated by western blotting and immunofluorescence. A time course effect of ET-1 on the transcription level of connective tissue growth factor (CTGF) was investigated by qRT-PCR. Next, the transcription level of CTGF was downregulated by using antisense oligodeoxynucleotide sequence. Then HTMCs were treated with ET-1, and the expression levels of FN and Col IV were evaluated by western blotting. In addition, by using an ex-vivo model of cultured anterior eye segment, we explored the effect of ET-1 on IOP changes and the expressions of FN and Col IV. RESULTS: In cultured HTMCs, the expressions of FN and Col IV were significantly increased after ET-1 treatment, which were blocked by the pretreatment of ETAR antagonist BQ123, rather than ETBR antagonist BQ788. Besides, the CTGF mRNA level increased significantly and reached a peak after 48 h of ET-1 treatment. However, the effect of ET-1 on increasing the expressions of FN and Col IV in HTMCs could be inhibited by the downregulation of CTGF. In an ex-vivo model, IOP increased significantly after ET-1 administration, which could be blocked by BQ123 but not by BQ788. Furthermore, elevated expressions of FN and Col IV in TM were observed after ET-1 perfusion, and could be inhibited by BQ123 pretreatment. CONCLUSION: Excessive ET-1 in aqueous humor could lead to the abnormal accumulation of FN and Col IV in TM via the ETA-CTGF pathway, thereby increasing IOP.


Assuntos
Glaucoma de Ângulo Aberto , Malha Trabecular , Humanos , Malha Trabecular/metabolismo , Pressão Intraocular , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Fator de Crescimento do Tecido Conjuntivo/farmacologia , Matriz Extracelular/metabolismo , Glaucoma de Ângulo Aberto/metabolismo
6.
Front Med (Lausanne) ; 9: 900486, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669923

RESUMO

Purpose: To compare macular retinal microcirculation in myopia, emmetropia, and hyperopia groups and investigate the relationship between macular retinal microcirculation and axial length (AL) in children. Methods: Forty myopic, 29 emmetropic, and 34 hyperopic eyes were included. All the recruited eyes underwent optical coherence tomography angiography (OCTA) examinations. After adjusting the image size by the Littmann method and Bennett formula, the vessel density (VD) of the deep capillary plexus (DCP) and superficial vascular plexus (SVP) were assessed. Results: The VD of the DCP was significantly lower in the myopia group than in the hyperopia group, whereas no significant differences in the VD of the SVP were observed among the myopia, emmetropia, and hyperopia groups. The VD of the DCP was significantly associated with AL, spherical equivalent (SE), and foveal retinal thickness (FRT), whereas the VD of the SVP was only significantly associated with FRT but not with AL or SE. Conclusions: The myopic VD of the DCP was significantly lower than the hyperopic one, and the VD of the DCP was significantly associated with AL, indicating that myopia has a lower VD of the DCP, and AL could have a negative effect on the VD of the DCP. Thus, early myopic axial stretching might decrease retinal blood perfusion of the DCP in children.

7.
Front Physiol ; 13: 854240, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370764

RESUMO

Purpose: To investigate choroidal vascularity (CV) and choriocapillaris blood perfusion before and after accommodation in myopia, emmetropia, and hyperopia groups among children. Methods: This study included 39 myopic eyes from 22 subjects, 17 emmetropic eyes from 11 subjects, and 18 hyperopic eyes from 10 subjects. All subjects were children. Choroidal thickness (CT) and CV, including total choroidal area (TCA), luminal area (LA), and stromal area (SA) were measured using swept-source optical coherence tomography (SS-OCT). Choriocapillaris luminal area (CLA) was measured using SS-OCT-angiography before and after accommodation (near reading with an additional -3 diopter lens). Results: For baseline results, except horizontal CV (showing no significant differences between myopia and emmetropia groups), both horizontal and vertical CT and CV were significantly smaller in the myopia group than in the emmetropia or hyperopia groups. In terms of CLA, no significant differences were observed among the myopia, emmetropia, and hyperopia groups. In addition, only myopic eyes showed significant decreases in CT and CV, whereas most CT and CV of emmetropic and hyperopic eyes showed non-significant decreases after accommodation. Furthermore, accommodation induced no significant changes in CLA in the myopia, emmetropia, or hyperopia groups. Conclusion: Myopia had thinner baseline choroid and lower baseline choroidal blood perfusion. Furthermore, myopic eyes were more prone to choroidal thinning and blood perfusion decreases after accommodation.

8.
Exp Lung Res ; 47(4): 161-172, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33590796

RESUMO

Background Asthma is a chronic inflammatory heterogeneous respiratory disease. Previous studies showed that the lncRNA NEAT1 (nuclear paraspeckle assembly transcript 1) might play an important role in the pathogenesis of asthma, but its potential mechanism in airway smooth muscle cell (ASMC) inflammation remains largely unknown and needs further investigation.Methods We performed cellular immunofluorescence to identify the features of ASMCs and detected the expression levels of lncRNA NEAT1, miR-139, TNF-α, IL-6, IL-8 and IL-1ß by quantitative real-time PCR (Q-PCR) and ELISA. Western blotting (WB) was used to measure the protein expression of the related genes, and bioinformatics as well as dual luciferase assays were used to validate the interaction between lncRNA NEAT1 and miR-139 and the interaction between miR-139 and the 3'-UTR of JAK3.Results The expression of lncRNA NEAT1 was increased in the ASMCs of asthma patients, but miR-139 was decreased. Overexpression of lncRNA NEAT1 promoted the expression of the inflammatory cytokines such as TNF-α, IL-6, IL-8 and IL-1ß in ASMCs. LncRNA NEAT1 was able to target miR-139 to activate the JAK3/STAT5 signaling pathway and induced the expression of these inflammatory cytokines in ASMCs. Overexpression of miR-139 or suppression of the JAK3/STAT5 signaling pathway reversed the inflammatory effect of lncRNA NEAT1.Conclusion LncRNA NEAT1 played a pivotal role in ASMC inflammation and exerted its function through the miR-139/JAK3/STAT5 signaling network.


Assuntos
MicroRNAs , Miócitos de Músculo Liso/patologia , RNA Longo não Codificante , Humanos , Inflamação/genética , Janus Quinase 3 , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT5
9.
Carbohydr Polym ; 231: 115728, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888838

RESUMO

A water-soluble acidic polysaccharide, XB-PS3, was isolated from the twigs of Juniperus pingii var. Wilsonii with a molecular weight of 86.04 kDa. By means of monosaccharide composition analysis, methylation, 2D NMR spectroscopy and UPLC-MS analysis, we concluded that XB-PS3 had a backbone composed of →2,4)-α-Manp-(1→ and →4)-α-GalpA-(1→ (60 % esterified), with an araban branch attached to O-2 of →2,4)-α-Manp-(1→. The possible repeating units were further validated by oligosaccharide analysis and partial acid hydrolysis. XB-PS3 exhibited potent anticomplement activity with CH50 value of 117.23 ± 18.74 µg/mL and interacted with C3, C4, C5 and C9 in the complement activation cascade. However, the anticomplement activity was significantly weakened when the galacturonic acids were reduced (CH50: 268.55 ± 16.82 µg/mL) or the branches were removed by partial hydrolysis (CH50: 197.76 ± 21.81 µg/mL), indicating the important role of uronic acids and branch structure in the polysaccharide's anticomplement activity.


Assuntos
Proteínas Inativadoras do Complemento/química , Juniperus/química , Polissacarídeos/química , Ácidos/química , Cromatografia Líquida , Complemento C3/antagonistas & inibidores , Complemento C3/química , Proteínas Inativadoras do Complemento/isolamento & purificação , Proteínas Inativadoras do Complemento/farmacologia , Carboidratos da Dieta/farmacologia , Humanos , Hidrólise , Peso Molecular , Monossacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Espectrometria de Massas em Tandem , Ácidos Urônicos/química , Água/química
10.
Biomed Res Int ; 2019: 6502793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828114

RESUMO

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.


Assuntos
Antineoplásicos/farmacologia , Mesilato de Imatinib/farmacologia , Células K562 , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células K562/efeitos dos fármacos , Células K562/metabolismo , Fator 2 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Tiorredoxina Dissulfeto Redutase/análise , Tiorredoxina Dissulfeto Redutase/metabolismo
11.
Hum Cell ; 32(4): 487-494, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31338708

RESUMO

Paraoxonase-2 (PON2) belongs to the paraoxonase (PON) protein family. Unlike paraoxonase-1 (PON1), the expression and significance of PON2 remained largely unknown in gastric cancer (GC). Thus, the purpose of our study was to investigate the role of PON2 in GC. First, we found PON2 expression was obviously increased in GC samples compared with paired normal tissue samples at The Cancer Genome Atlas (TCGA) database. Then the high expression status of PON2 mRNA and protein in GC tissues was confirmed by RT-qPCR and immunohistochemistry. Furthermore, we performed the immunohistochemical analysis to study the correlation between PON2 expression and clinicopathological parameters of GC patients, and found high PON2 expression had significantly positive association with diffuse type, clinical stage, tumor invasion, lymph node metastasis and distant metastasis in GC patients. Moreover, survival analysis suggested GC patients with high PON2 expression resulted in a remarkably shorter overall survival compared with GC patients with low PON2 expression, and high expression of PON2 acted as an unfavorable predictor for overall survival. The in vitro studies indicated that silencing of PON2 expression inhibited GC cell proliferation, migration and invasion. In conclusion, our findings give first evidence that PON2 serves as oncogene in GC.


Assuntos
Arildialquilfosfatase/genética , Arildialquilfosfatase/metabolismo , Oncogenes , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
12.
Int J Biol Macromol ; 129: 246-253, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30708019

RESUMO

Juniperus pingii var. wilsonii has been traditionally used in Tibetan medicine for the treatment of inflammatory diseases. In the present study, J. pingii var. wilsonii polysaccharides (JPWP), with high content of d­galacturonic acid, showed potent anti-complementary activity in vitro and significantly attenuated acute lung injury (ALI) induced by H1N1 influenza virus in vivo through reducing the inflammatory responses, alleviating oxidative stress and inhibiting the activation of complement. Thus, anti-complementary activity-guided fractionation of JPWP led to the isolation of an acidic homogeneous polysaccharide, JPWP-PS, whose structure was further elucidated by acid hydrolysis, PMP derivation, methylation and NMR analysis. JPWP-PS had potent anti-complementary activity with the CH50 value of 0.073 ±â€¯0.009 mg/mL, and was characterized by the residues of T-Araf-(1→, →3)-Araf-(1→, →3,5)-Araf-(1→, →3)-Galp-(1→ and →4)-GalpA-(1→.


Assuntos
Lesão Pulmonar Aguda/etiologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Juniperus/química , Infecções por Orthomyxoviridae/complicações , Infecções por Orthomyxoviridae/virologia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Biomarcadores , Proteínas do Sistema Complemento , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Polissacarídeos/química , Análise Espectral
13.
CNS Neurol Disord Drug Targets ; 18(2): 103-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30394219

RESUMO

BACKGROUND & OBJECTIVE: Alzheimer's disease (AD) and Parkinson's disease (PD) affect an increasing number of the elderly population worldwide. The existing treatments mainly improve the core symptoms of AD and PD in a temporary manner and cause alarming side effects. Naturally occurring flavonoids are well-documented for neuroprotective and neurorestorative effects against various neurodegenerative diseases. Thus, we analyzed the pharmacokinetics of eight potent natural products flavonoids for the druggability and discussed the neuroprotective and neurorestorative effects and the underlying mechanisms. CONCLUSION: This review provides valuable clues for the development of novel therapeutics against neurodegenerative diseases.


Assuntos
Flavonoides/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Humanos , Doença de Parkinson/tratamento farmacológico
14.
Zhonghua Xue Ye Xue Za Zhi ; 34(6): 527-31, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23827113

RESUMO

OBJECTIVE: To explore the effect of nuclear factor erythroid-2 related factor 2 (Nrf2) and thioredoxin reductase (TrxR) gene on proliferation of chronic myeloid leukemia (CML) line cells and its mechanism. METHODS: Four interfering sequences of Nrf2 and one negative control sequence were designed and synthesised based on the principle of target sequence of siRNA, then constructed lentivirus vectors, which were transfected into K562 cell lines. The transfection effect was observed by laser scanning confocal microscope (LSCM) and flow cytometer (FCM); The depressing effect of siRNA was analyzed by real-time PCR. The cell proliferation inhibiting rate was measured with CCK-8 assay, the apoptotic rate by Annexin V-PE/PI with FCM and the apoptotic morphology of cells by LSCM. RESULTS: The transfection efficiency of lentivirus was 65%. One cell line K562-C3 which significantly inhibited Nrf2 mRNA was obtained by real-time PCR, Nrf2 relative quantitation (RQ) expressions were 1.003±0.093 and 0.344±0.032 in the control group and K562-C3 respectively; TrxR expression also decreased with RQ as 1.090±0.549 and 0.395±0.029 respectively. The cellular proliferation inhibition rates of K562-C3 were (4.74±0.39)%, (6.13±1.78)% and (25.36±3.77)%, respectively at 24, 48 and 72 h. The apoptotic rate induced by K562-C3 (29.9%) at 72 hours was obviously higher than in the control group (7.9%). The Annexin V-PE positive K562-C3 cells presented the following apoptotic characteristics, such as karyopyknosis, nuclear fragmentation and apoptotic bodies observed by LSCM. CONCLUSION: Nrf2 specific siRNA could repress its expression at the cellular level and down-regulate the expression of its downstream antioxidant enzyme, such as TrxR, which lead to increased apoptotic rate and decreased cell proliferation.


Assuntos
Proliferação de Células , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo , Apoptose , Regulação para Baixo , Vetores Genéticos , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética
15.
Int J Comput Biol Drug Des ; 3(3): 226-36, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21228457

RESUMO

An evolutionary tree represents the relationship among a group of species or sequences. The quality of tree topology relies heavily on an efficient Multiple Sequence Alignment (MSA). Efficient and parallel algorithms are designed to utilise the computing power and memory in a supercomputer. A divide and conquer based parallel algorithm is implemented to perform optimal three sequence alignment with much reduced memory cost. All internal nodes generated from a parallel Maximum Likelihood tree software are labelled using our level order based parallel approach. Such node labelling process is also parallelised to lead to a two-level nested parallel computing strategy.


Assuntos
Filogenia , Alinhamento de Sequência , Funções Verossimilhança , Software
16.
Int J Comput Biol Drug Des ; 2(3): 278-87, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20090165

RESUMO

Time-lagging in expression occurs when a gene's expression triggers a delayed expression in its co-regulated or anti-co-regulated peers. Arbitrary time-lagging also might appear due to experiment or measurement error. Traditional methods will either under-estimate or completely miss such correlation, which is not unusual and plays important roles. Since the traditional similarity measurement cannot capture the true relationship, a simple time-lagging captured algorithm integrated with some existing time-lagging and similarity measurement techniques is proposed with parallel implementation. Improvements such as isolation of experimental conditions and weighted averages are used to achieve better accuracy and give user flexibility to differentiate different experiments.


Assuntos
Biologia Computacional/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Algoritmos , Humanos
17.
BMC Genomics ; 9 Suppl 2: S18, 2008 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-18831783

RESUMO

BACKGROUND: Microarray technology is often used to identify the genes that are differentially expressed between two biological conditions. On the other hand, since microarray datasets contain a small number of samples and a large number of genes, it is usually desirable to identify small gene subsets with distinct pattern between sample classes. Such gene subsets are highly discriminative in phenotype classification because of their tightly coupling features. Unfortunately, such identified classifiers usually tend to have poor generalization properties on the test samples due to overfitting problem. RESULTS: We propose a novel approach combining both supervised learning with unsupervised learning techniques to generate increasingly discriminative gene clusters in an iterative manner. Our experiments on both simulated and real datasets show that our method can produce a series of robust gene clusters with good classification performance compared with existing approaches. CONCLUSION: This backward approach for refining a series of highly discriminative gene clusters for classification purpose proves to be very consistent and stable when applied to various types of training samples.


Assuntos
Algoritmos , Inteligência Artificial , Perfilação da Expressão Gênica/métodos , Reconhecimento Automatizado de Padrão/métodos , Análise por Conglomerados , Biologia Computacional/métodos , Simulação por Computador , Análise Discriminante , Humanos , Leucemia Mieloide Aguda/genética , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
18.
BMC Genomics ; 9 Suppl 2: S5, 2008 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-18831796

RESUMO

BACKGROUND: Using genomic DNA as common reference in microarray experiments has recently been tested by different laboratories. Conflicting results have been reported with regard to the reliability of microarray results using this method. To explain it, we hypothesize that data processing is a critical element that impacts the data quality. RESULTS: Microarray experiments were performed in a gamma-proteobacterium Shewanella oneidensis. Pair-wise comparison of three experimental conditions was obtained either with two labeled cDNA samples co-hybridized to the same array, or by employing Shewanella genomic DNA as a standard reference. Various data processing techniques were exploited to reduce the amount of inconsistency between both methods and the results were assessed. We discovered that data quality was significantly improved by imposing the constraint of minimal number of replicates, logarithmic transformation and random error analyses. CONCLUSION: These findings demonstrate that data processing significantly influences data quality, which provides an explanation for the conflicting evaluation in the literature. This work could serve as a guideline for microarray data analysis using genomic DNA as a standard reference.


Assuntos
Biologia Computacional/métodos , Processamento Eletrônico de Dados/normas , Genômica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Variância , DNA Bacteriano/genética , Perfilação da Expressão Gênica , Genoma Bacteriano , Padrões de Referência , Projetos de Pesquisa , Shewanella/genética
19.
BMC Genomics ; 9 Suppl 2: S6, 2008 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-18831797

RESUMO

BACKGROUND: Sudden death syndrome (SDS) of soybean (Glycine max L. Merr.) is an economically important disease, caused by the semi-biotrophic fungus Fusarium solani f. sp. glycines, recently renamed Fusarium virguliforme (Fv). Due to the complexity and length of the soybean-Fusarium interaction, the molecular mechanisms underlying plant resistance and susceptibility to the pathogen are not fully understood. F. virguliforme has a very wide host range for the ability to cause root rot and a very narrow host range for the ability to cause a leaf scorch. Arabidopsis thaliana is a host for many types of phytopathogens including bacteria, fungi, viruses and nematodes. Deciphering the variations among transcript abundances (TAs) of functional orthologous genes of soybean and A. thaliana involved in the interaction will provide insights into plant resistance to F. viguliforme. RESULTS: In this study, we reported the analyses of microarrays measuring TA in whole plants after A. thaliana cv 'Columbia' was challenged with fungal pathogen F. virguliforme. Infection caused significant variations in TAs. The total number of increased transcripts was nearly four times more than that of decreased transcripts in abundance. A putative resistance pathway involved in responding to the pathogen infection in A. thaliana was identified and compared to that reported in soybean. CONCLUSION: Microarray experiments allow the interrogation of tens of thousands of transcripts simultaneously and thus, the identification of plant pathways is likely to be involved in plant resistance to Fusarial pathogens. Dissection of the set functional orthologous genes between soybean and A. thaliana enabled a broad view of the functional relationships and molecular interactions among plant genes involved in F. virguliforme resistance.


Assuntos
Arabidopsis/genética , Fusarium/patogenicidade , Regulação da Expressão Gênica de Plantas , Glycine max/genética , Arabidopsis/microbiologia , Biologia Computacional , Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica , Genes de Plantas , Genoma de Planta , Análise de Sequência com Séries de Oligonucleotídeos , Filogenia , Raízes de Plantas/genética , Raízes de Plantas/microbiologia , RNA de Plantas/genética , Alinhamento de Sequência , Software , Glycine max/microbiologia
20.
BMC Genomics ; 9 Suppl 1: I1, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18366597

RESUMO

Bioinformatics and Genomics are closely related disciplines that hold great promises for the advancement of research and development in complex biomedical systems, as well as public health, drug design, comparative genomics, personalized medicine and so on. Research and development in these two important areas are impacting the science and technology.High throughput sequencing and molecular imaging technologies marked the beginning of a new era for modern translational medicine and personalized healthcare. The impact of having the human sequence and personalized digital images in hand has also created tremendous demands of developing powerful supercomputing, statistical learning and artificial intelligence approaches to handle the massive bioinformatics and personalized healthcare data, which will obviously have a profound effect on how biomedical research will be conducted toward the improvement of human health and prolonging of human life in the future. The International Society of Intelligent Biological Medicine (http://www.isibm.org) and its official journals, the International Journal of Functional Informatics and Personalized Medicine (http://www.inderscience.com/ijfipm) and the International Journal of Computational Biology and Drug Design (http://www.inderscience.com/ijcbdd) in collaboration with International Conference on Bioinformatics and Computational Biology (Biocomp), touch tomorrow's bioinformatics and personalized medicine throughout today's efforts in promoting the research, education and awareness of the upcoming integrated inter/multidisciplinary field. The 2007 international conference on Bioinformatics and Computational Biology (BIOCOMP07) was held in Las Vegas, the United States of American on June 25-28, 2007. The conference attracted over 400 papers, covering broad research areas in the genomics, biomedicine and bioinformatics. The Biocomp 2007 provides a common platform for the cross fertilization of ideas, and to help shape knowledge and scientific achievements by bridging these two very important disciplines into an interactive and attractive forum. Keeping this objective in mind, Biocomp 2007 aims to promote interdisciplinary and multidisciplinary education and research. 25 high quality peer-reviewed papers were selected from 400+ submissions for this supplementary issue of BMC Genomics. Those papers contributed to a wide-range of important research fields including gene expression data analysis and applications, high-throughput genome mapping, sequence analysis, gene regulation, protein structure prediction, disease prediction by machine learning techniques, systems biology, database and biological software development. We always encourage participants submitting proposals for genomics sessions, special interest research sessions, workshops and tutorials to Professor Hamid R. Arabnia (hra@cs.uga.edu) in order to ensure that Biocomp continuously plays the leadership role in promoting inter/multidisciplinary research and education in the fields. Biocomp received top conference ranking with a high score of 0.95/1.00. Biocomp is academically co-sponsored by the International Society of Intelligent Biological Medicine and the Research Laboratories and Centers of Harvard University--Massachusetts Institute of Technology, Indiana University--Purdue University, Georgia Tech--Emory University, UIUC, UCLA, Columbia University, University of Texas at Austin and University of Iowa etc. Biocomp--Worldcomp brings leading scientists together across the nation and all over the world and aims to promote synergistic components such as keynote lectures, special interest sessions, workshops and tutorials in response to the advances of cutting-edge research.


Assuntos
Biologia Computacional/educação , Biologia Computacional/métodos , Genômica/educação , Genômica/métodos , Pesquisa , Redes Reguladoras de Genes/genética , Análise em Microsséries/métodos , Conformação Proteica , Análise de Sequência de DNA/métodos
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