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PURPOSE: Colorectal cancer (CRC) is one most cancer type of high incidence and high mortality rate. Metastasis play an important role in survival rate and life quality of colorectal cancer patients. Nerve growth factor (NGF) has been shown to be involved in the metastasis and deterioration in many cancers, but the detail mechanisms in promoting the metastasis of colorectal cancer remain unknown. In this study, we aimed to explore the mechanism of NGF promoting colorectal cancer metastasis to provide new insights for developing NGF anti-colorectal cancer drugs. METHODS: We examined the expression of NGF in human colorectal cancer by immunohistochemical staining, and Western blot to evaluate the relationship between NGF and colorectal cancer metastasis. Using biochemical experiments including wound healing assay, transwell migration and invasion assay, RT-PCR, Western blot and ELISA to explore the relative mechanism of NGF promoting colorectal cancer cells metastasis in vivo. RESULTS: Our results found that the high expression of NGF was related with high incidence of metastasis. The binding of NGF to TrkA phosphorylated TrkA, which activated MAPK/Erk signaling pathway increasing the expression NGAL to enhance the activity of MMP2 and MMP9, promoted colorectal cancer metastasis. CONCLUSION: Our finding demonstrated that NGF increased NGAL expression to enhance MMPs activity to promoted colorectal cancer cell metastasis by TrkA-MAPK/Erk axis.
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Neoplasias Colorrectales/patología , Lipocalina 2/fisiología , Metaloproteinasas de la Matriz/fisiología , Factor de Crecimiento Nervioso/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
PURPOSE: Current gastric cancer staging systems overlook the anatomic extent of metastatic lymph nodes (AEMLNs). This study aimed to analyze the prognostic impact of AEMLNs on gastric cancer (GC). METHODS: GC patients with metastatic lymph nodes (MLNs) undergoing curative surgery were retrospectively reviewed and assigned to perigastric (MLNs in station 1-6, PG) and extraperigastric group (7-12, with or without MLNs in PG area, EPG). Overall survival (OS), disease-free survival (DFS) and recurrence patterns were compared before and after 1:1 propensity score matching (PSM). RESULTS: 662 patients were enrolled, 341 (51.5%) and 321 (48.5%) of whom were in the PG and EPG, respectively. After PSM (n = 195), EPG showed poorer 5-year OS (43.4% vs 54.5%, p = 0.014) and DFS (65.0% vs 73.4%, p = 0.068) than PG. EPG had higher incidence of peritoneal recurrence (PR) than PG (19.4% vs 7.4%, p = 0.002). Multivariate analysis identified AEMLNs as prognostic factor for OS [HR = 1.409, 95% confidence interval (CI) 1.062-1.868), DFS (HR = 1.600, 95% CI 1.059-2.416) and PR (HR = 3.708, 95% CI 1.685-8.160). CONCLUSIONS: The anatomic extent of metastatic lymph nodes has an independent prognostic role for GC. Including this element may improve the accuracy of current staging systems.
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Ganglios Linfáticos/patología , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Varianza , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Peritoneales/secundario , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Gástricas/cirugíaRESUMEN
PURPOSE: To assess the performance of computed tomography (CT) reconstruction in evaluating the response in metastatic lymph nodes after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Patients undergoing pre-NAC and post-NAC CT were identified from the Peking University Cancer Hospital database. Axillary Lymph nodes (ALNs) that shrunk to < 5 mm in short-axis diameter after NAC on CT reconstruction images were classified as clinical complete response. Evaluations of CT reconstruction on ALNs were correlated with residual nodal disease in the final pathology. Overall, 53 invasive breast cancer patients between October 2016 and March 2018 were eligible for our study. The median age was 48 (range 35-70) years. Most women presented with T2 tumors (35/53, 66.0%). RESULTS: After NAC, 20 (37.7%) patients without residual nodal disease were defined as pCR. Of 53 patients, 18 (33.9%) showed negative conversion of ALNs on CT reconstruction evaluation; axillary pCR was present in 16/18 (88.9%) patients. Among 35 patients with abnormal nodes on post-NAC CT reconstruction, 31 (88.6%) had axillary metastasis on the final pathology. The sensitivity and specificity of CT reconstruction in predicting node-negative status were 80.0% and 93.9%, respectively. The positive predictive value was 84.9% for lymph node pCR. The area under the receiver operating characteristic curve of each imaging modality was 0.870 (95% confidence interval 0.755-0.984). CONCLUSIONS: CT reconstruction was useful for evaluating ALNs response following NAC and may be used to predict axillary nodes' pCR with adequate accuracy.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Ganglios Linfáticos/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Terapia Neoadyuvante/métodos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Área Bajo la Curva , Axila , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama , Quimioterapia Adyuvante/métodos , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Humanos , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/tratamiento farmacológico , Persona de Mediana Edad , Neoplasia Residual , Paclitaxel/uso terapéutico , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Numerous inherent and acquired genetic alterations have been demonstrated with resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC) patients. Although the common oncogenic driver mutations identified include KRAS, NRAS, BRAF, and PI3K, recent studies report a vital role played by human epithelial growth factor receptor-2 (HER2) amplification in acquired resistance to anti-EGFR therapy. HER2 amplification has been associated with poor prognosis in many malignancies including breast and gastric cancer and is also a negative predictor of anti-EGFR therapy. Given the relevance of HER2 amplification in conferring an anti-EGFR resistance, this paper reviews the prevalence of HER2 amplification in mCRC while exploring the prognostic and predictive values of this biomarker. Further, we also discuss the results of the studies that explored the utilization of anti-HER2-targeted therapies in mCRC. HER2-directed therapies have the ability to change the treatment algorithm in clinically relevant small subset of patients with HER2-amplified mCRC.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptor ErbB-2/genética , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Receptores ErbB/uso terapéutico , Humanos , Mutación , Prevalencia , PronósticoRESUMEN
BACKGROUND: Angiogenesis is a critical biological process essential for solid cancer growth and metastasis. It has been shown that microRNAs (miRNAs) play a vital role in a variety of biological processes in cancers. However, whether miR-130b is involved in prostate cancer angiogenesis remains ill-defined. METHODS: We performed the miRNA microarray to analyze miRNA expression in human prostate cancer specimens. In vitro gain-of-function assays and loss-of-function assays were conducted to explore the potential functions of miR-130b in human prostate cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether tumor necrosis factor-α (TNF-α) was a direct target of miR-130b. The Matrigel plug and tumor vascular imaging assays were performed to confirm the anti-angiogenic activity of miR-130b in nude mice. RESULTS: We found that miR-130b was one of the miRNAs being most significantly downregulated. Subsequently, we found that miR-130b expression was markedly downregulated in human prostate cancer cell lines. Down-regulation of miR-130b in prostate cancer cells significantly promoted the proliferation, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs), while ectopic expression of miR-130b blocked prostate cancer angiogenesis in vitro and in vivo. Mechanistic analyses indicated that tumor necrosis factor-α (TNF-α) was regulated by miR-130b directly. MiR-130b attenuated nuclear factor-κB (NF-κB) signaling and its downstream gene vascular endothelial growth factor-A (VEGFA) by directly inhibiting TNF-α expression. Additionally, subsequent investigations identified that the ectopic level of VEGFA markedly abrogated the anti-angiogenic effect induced by miR-130b. Interestingly, VEGFA could in turn decrease the expression of miR-130b, thus forming a negative feedback loop that drives the angiogenesis of prostate cancer. CONCLUSION: These findings show that miR-130b/TNF-α/NF-κB/VEGFA feedback loop is significantly correlated with angiogenesis in prostate cancer and miR-130b could be regarded as potential therapeutic target for prostate cancer anti-angiogenesis treatment.
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Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , FN-kappa B/metabolismo , Neovascularización Patológica/patología , Neoplasias de la Próstata/irrigación sanguínea , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FN-kappa B/genética , Neovascularización Patológica/metabolismo , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Transducción de Señal , Tasa de Supervivencia , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/genética , Factor A de Crecimiento Endotelial Vascular/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: We consider a network topology according to the cortico-cortical connection network of the human brain, where each cortical area is composed of a random network of adaptive exponential integrate-and-fire neurons. APPROACH: Depending on the parameters, this neuron model can exhibit spike or burst patterns. As a diagnostic tool to identify spike and burst patterns we utilise the coefficient of variation of the neuronal inter-spike interval. MAIN RESULTS: In our neuronal network, we verify the existence of spike and burst synchronisation in different cortical areas. SIGNIFICANCE: Our simulations show that the network arrangement, i.e. its rich-club organisation, plays an important role in the transition of the areas from desynchronous to synchronous behaviours.
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Modelos Neurológicos , Red Nerviosa/fisiología , Humanos , Potenciales de la Membrana , Red Nerviosa/citología , Neuronas/citologíaRESUMEN
Circular RNAs (CircRNAs) are a type of non-coding RNAs (NcRNAs) with a closed annular structure. Until next-generation sequencing (NGS) is developed, the misunderstanding of circRNAs 'splicing error' has changed, and the mysterious veil of circRNAs has been revealed. NGS provides an approach to investigate circRNAs. Many scholars point out that circRNAs may play an important role in many diseases, especially cancer. At the same time, exosomes, as a kind of extracellular vesicles loaded with many contents, are a hotspot in recent years. They can act as 'messengers' between cells, especially in cancer. Lately, it is interesting circRNAs are enriched and stable in exosomes, also called exo-circRNAs, and there have been several articles on circRNAs associated with exosomes. In this review, we summarize the characteristics of circRNAs, especially its main functions. Then, we briefly introduce exosomes and their function in cancer. Finally, the known relation between circRNAs and exosomes is discussed. With further researches, exo-circRNAs may be a novel pathway for cancer diagnosis and targeted therapy.
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Exosomas/fisiología , Neoplasias/genética , ARN/fisiología , Humanos , Sistema Inmunológico/fisiología , MicroARNs/fisiología , Metástasis de la Neoplasia , ARN CircularRESUMEN
PURPOSE: Anoctamin 1 (ANO1), a recently identified calcium-activated chloride channel, has been found to have a critical role in tumorigenesis and tumor progression in several types of cancer. However, its role in non-small cell lung cancer (NSCLC) remains to be elucidated. In this study, we evaluated the utility of ANO1 as a prognostic marker. PATIENTS AND METHODS: ANO1 expression was detected in tumor tissues and paraneoplastic tissues of I-IV stage NSCLC patients who received surgical treatment by using immunohistochemical and quantitative RT-PCR analyses. Epidermal growth factor receptor (EGFR) was investigated using immunohistochemistry. Then the TNM stage of the tumor samples was assessed and patients were followed up for developing recurrence. RESULTS: ANO1 expression was significantly increased in NSCLC tumor tissues compared to the paraneoplastic tissues at both RNA and protein level. In addition, ANO1 overexpression was correlated with the high expression of EGFR and led to an advanced tumor stage. And also high ANO1 expression was significantly correlated with high recurrence rate at 1-year follow-up. CONCLUSIONS: ANO1 overexpression associated with the high expression of EGFR can be a predictive marker of recurrence after surgery in NSCLC patients.
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Anoctamina-1/biosíntesis , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/biosíntesis , Adulto , Anciano , Anoctamina-1/análisis , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Receptores ErbB/análisis , Receptores ErbB/biosíntesis , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Recurrencia Local de Neoplasia/patología , Neumonectomía , PronósticoRESUMEN
Helicobacter pylori employs unique methods to colonize the stomach, which induces chronic inflammation. It is also able to avoid eradication by macrophages and other immune cells. Leukocyte cell-derived chemotaxin 2 (LECT2), a multi-functional cytokine involved in many pathological conditions, has recently been shown to activate macrophages via the CD209a receptor. Therefore, we aimed to investigate the effects of LECT2 on H. pylori-infected macrophages. Macrophages were treated with recombinant LECT2, and both their ability to kill H. pylori and produce nitric oxide were analyzed. Western blot was performed to determine nuclear translocation and protein phosphorylation of p65, a subunit of nuclear factor (NF)-κB. Transfection experiments were performed to analyze the signaling pathway of LECT2 in macrophages. We found that treatment with LECT2 enhanced H. pylori killing and nitric oxide production in macrophages. In addition, DNA-binding activity and nuclear translocation of p65 were up-regulated by LECT2 treatment. Furthermore, we found that NF-κB activation by LECT2 was mediated by Raf-1 in macrophages, and Raf-1 phosphorylation was specifically altered in response to LECT2. Moreover, LECT2 induced Ser28 phosphorylation in the intracellular domain of CD209a. CD209a Ser28 phosphorylation was required for LECT2-induced Raf-1 and NF-κB activation in RAW264.7 macrophages. Our study showed that the effects of LECT2 on H. pylori killing and nitric oxide production were dependent on CD209a phosphorylation, Raf-1, and NF-κB activation. Together, these results demonstrate for the first time that exposure to LECT2 can modulate specific intracellular mechanisms downstream of CD209a to enhance H. pylori killing and nitric oxide production in macrophages.
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Infecciones por Helicobacter/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Proteínas Recombinantes/genética , Factor de Transcripción ReIA/biosíntesis , Animales , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/inmunología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Humanos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Macrófagos/inmunología , Ratones , Óxido Nítrico/biosíntesis , Óxido Nítrico/genética , Fosforilación , Células RAW 264.7 , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Proteínas Recombinantes/farmacología , Transducción de Señal/genética , Estómago/inmunología , Estómago/microbiología , Factor de Transcripción ReIA/genética , Activación Transcripcional/genética , TransfecciónRESUMEN
There is high incidence of periodontal disease in high-altitude environments; hypoxia may influence the proliferation and clone-forming ability of periodontal ligament stem cells (PDLSCs). The MAPK signaling pathway is closely correlated with cell proliferation, differentiation, and apoptosis. Thus, we isolated and cultured PDLSCs under hypoxic conditions to clarify the impact of hypoxia on PDLSC proliferation and the underlying mechanism. PDLSCs were separated and purified by the limiting dilution method and identified by flow cytometry. PDLSCs were cultured under hypoxic or normoxic conditions to observe their cloning efficiency. PDLSC proliferation at different oxygen concentrations was evaluated by MTT assay. Expression of p38/MAPK and MAPK/ERK signaling pathway members was detected by western blotting. Inhibitors for p38/MAPK or ERK were applied to PDLSCs to observe their impacts on clone formation and proliferation. Isolated PDLSCs exhibited typical stem cell morphological characteristics, strong abilities of globular clone formation and proliferation, and upregulated expression of mesenchymal stem cell markers. Stem cell marker expression was not statistically different between PDLSCs cultured under hypoxia and normoxia (P > 0.05). The clone number in the hypoxia group was significantly higher than that in the control (P < 0.05). PDLSC proliferation under hypoxia was higher than that of the control (P < 0.001). p38 and ERK1/2 phosphorylation in hypoxic PDLSCs was markedly enhanced compared to that in the control (P < 0.05). Either P38/MAPK inhibitor or ERK inhibitor treatment reduced clone formation and proliferation. Therefore, hypoxia enhanced PDLSC clone formation and proliferation by activating the p38/MAPK and ERK/MAPK signaling pathways.
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Sistema de Señalización de MAP Quinasas , Ligamento Periodontal/citología , Células Madre/citología , Adolescente , Adulto , Apoptosis , Diferenciación Celular , Hipoxia de la Célula , Proliferación Celular , Células Cultivadas , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Members of the archaeal phylum Bathyarchaeota are widespread and abundant in the energy-deficient marine subsurface sediments. However, their life strategies have remained largely elusive. Here, we provide genetic evidence that some lineages of Bathyarchaeota are acetogens, being capable of homoacetogenesis, a metabolism so far restricted to the domain Bacteria. Metabolic reconstruction based on genomic bins assembled from the metagenome of deep-sea subsurface sediments shows that the metabolism of some lineages of Bathyarchaeota is similar to that of bona fide bacterial homoacetogens, by having pathways for acetogenesis and for the fermentative utilization of a variety of organic substrates. Heterologous expression and activity assay of the acetate kinase gene ack from Bathyarchaeota, demonstrate further the capability of these Bathyarchaeota to grow as acetogens. The presence and expression of bathyarchaeotal genes indicative of active acetogenesis was also confirmed in Peru Margin subsurface sediments where Bathyarchaeota are abundant. The analyses reveal that this ubiquitous and abundant subsurface archaeal group has adopted a versatile life strategy to make a living under energy-limiting conditions. These findings further expand the metabolic potential of Archaea and argue for a revision of the role of Archaea in the carbon cycle of marine sediments.
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Acetatos/metabolismo , Archaea/enzimología , Archaea/genética , Sedimentos Geológicos/microbiología , Metagenoma , Agua de Mar/microbiología , Acetato Quinasa/genética , Archaea/clasificación , Archaea/metabolismo , Ciclo del Carbono , ADN de Archaea , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Oxidación-Reducción , Perú , Filogenia , ARN Ribosómico 16S , Sulfatos/metabolismoRESUMEN
The aim of this study was to establish recheck rules of urinalysis in children by investigating the concordance rate of the results obtained using the LabUMat urine dry chemistry analyzer (referred to as dry chemistry) and the UriSed tangible composition analyzer with that of the microscopic examination. First, 1040 urine samples from children (mean age 6.5 years) were analyzed using LabUMat and UriSed analyzers, and subsequently subjected to microscopic examination. The missed detection rate was evaluated and recheck rules were established to avoid missed diagnoses of abnormal renal function. Finally, clinical validations of the recheck rules were performed on 200 additional specimens. Among the samples used to investigate the recheck rules, the samples with positive microscopic examination results accounted for 58.65% of the total, while the samples with negative results accounted for 41.35%. Of the positive samples, a major portion (>50%) were RBC positive. The samples that were WBC positive and CAST positive accounted for 23.08 and 7.69%, respectively. The concordance rate was 87.5% and the missed detection rate was 2.9%. For the validation of the recheck rules in 200 urine samples, the concordance rate was 87.5% and the missed detection rate was 2.4%. When the detection of occult blood, WBC, and protein by dry chemistry, and the detection of RBC, WBC, and CAST by the UriSed analyzer are inconsistent, or the differences between them greater than 2 levels, recheck by microscopic examination is suggested.
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Recuento de Células , Enfermedades Renales/orina , Microscopía , Urinálisis/métodos , Adolescente , Niño , Preescolar , Eritrocitos/patología , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades Renales/patología , Leucocitos/patología , Masculino , Sangre OcultaRESUMEN
The protective effect of procyanidine and its oligomers against high glucose-mediated oxidative stress injury in endothelial progenitor cells (EPCs), and effect of procyanidin on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and downstream signal pathway were analyzed in vitro. Rat bone marrow mononuclear cells were isolated, cultured under normal and high glucose (HG) conditions, and the changes in cell morphology observed. The EPCs were identified, and the oxidative stress products produced by EPCs (under normal and HG conditions) were quantified. Subsequently, an appropriate number of EPCs were cultured with and without procyanidin (OPC), and the MDA concentration and relative expression of VEGFR-2, AKT, IκB-α, and nuclear factor (NF)-κB were detected 1, 3, 5, and 7 days post-culture. We observed minor (round, translucent, gradually adhering) and significant (fusiform morphology/pebble distribution) cell morphological changes 3 and 7 days post-culture, respectively. Apoptosis and oxidative stress product release in EPCs cultured with HG increased significantly compared to the control group (P < 0.05). The oxidative stress product generation and relative expression of VEGFR-2, AKT, IkB-α, and NF-κB were not significantly affected by OPC addition in normal glucose conditions (P > 0.05); alternately, products generated as a result of oxidative stress were significantly reduced, the relative expression of VEGFR-2, AKT, and NF-κB protein was upregulated, and that of IκB-α was downregulated (P < 0.05) in HG + OPC EPCs. Therefore, procyanidin may promote cell proliferation by alleviating oxidative damage to EPCs under HG conditions, and upregulating VEGFR-2 expression and its downstream signal pathway.
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Biflavonoides/farmacología , Catequina/farmacología , Células Progenitoras Endoteliales/efectos de los fármacos , Células Progenitoras Endoteliales/metabolismo , Glucosa/farmacología , Proantocianidinas/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Células Cultivadas , Estrés Oxidativo/efectos de los fármacos , Ratas , Transducción de Señal/efectos de los fármacosRESUMEN
The treatment of obese patients is a topic investigated by an increasing number of researchers. This study aimed to elucidate the possible inhibitory effect of tangeritin on the development and function of fat cells. 3T3-L1 fat cells were grown to confluence and subjected to different concentrations of tangeritin. The most effective tangeritin inhibition concentration was determined by the MTT assay. The treated cells were subjected to real-time reverse transcriptase PCR and western blot analysis, to detect changes in the CCAAT/enhancer binding protein (C/EBP)α, C/EBPß, and peroxisome proliferator activated receptor (PPAR)γ expression levels. The MTT assay revealed that the fat cell growth was inhibited at a 20 ng/mL concentration of tangeritin. The results of real-time PCR revealed a significant decrease in the expression of C/EBPα, C/EBPß, and PPARγ mRNA, following the treatment with tangeritin. Western blot analysis also presented similar results at a protein level. Therefore, we concluded that tangeritin inhibits adipogenesis via the down-regulation of C/EBPα, C/EBPß, and PPARγ mRNA and protein expression in 3T3-L1 cells.
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Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína beta Potenciadora de Unión a CCAAT/genética , Flavonas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , PPAR gamma/genética , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Ratones , ARN Mensajero/genéticaRESUMEN
Machine learning techniques are of great importance in the analysis of microarray expression data, and provide a systematic and promising way to predict core cancer genes. In this study, a hybrid strategy was introduced based on machine learning techniques to select a small set of informative genes, which will lead to improving classification accuracy. First feature filtering algorithms were applied to select a set of top-ranked genes, and then hierarchical clustering and collapsing dense clusters were used to select core cancer genes. Through empirical study, our approach is capable of selecting relatively few core cancer genes while making high-accuracy predictions. The biological significance of these genes was evaluated using systems biology analysis. Extensive functional pathway and network analyses have confirmed findings in previous studies and can bring new insights into common cancer mechanisms.
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Pruebas Genéticas/métodos , Aprendizaje Automático , Análisis por Micromatrices/métodos , Modelos Genéticos , Neoplasias/genética , Algoritmos , Bases de Datos Genéticas , Humanos , Valor Predictivo de las Pruebas , Estadística como Asunto/métodosRESUMEN
The pink pineapple mealybug (PPM), Dysmicoccus brevipes (Cockerell) (Hemiptera: Pseudococcidae), is a widespread plant-sucking insect of considerable concern because it transmits the pineapple mealybug wilt-associated virus. Its distribution is closely linked with its host, the pineapple [Ananas comosus (L.) Merrill] because of its wingless and parthenogenetic characteristics. To investigate the history of D. brevipes introduction and the cultivation of pineapple in China, samples of D. brevipes were collected from the main pineapple production region in China, and from Thailand, and the mitochondrial cytochrome c oxidase subunit I (COI) gene was analyzed. Homologous sequences of D. brevipes COI from Brazil, Thailand, and Philippines that are deposited in GenBank were compared. Phylogenetic analyses suggest there are close genetic relationships between PPM populations from Hawaii, Brazil, the Philippines, and from Thailand and China, which probably originate from South America. It is suggested that most PPMs in China were introduced from South America by way of Southeast Asia, being accompanied by the pineapple seedling. Conversely, some PPMs represented by Haplotype-WN from Wanning of China, and Lampang of Thailand were found to differ greatly from populations in Hawaii, Brazil, the Philippines, Thailand, and China. It is possible that another route was used for the introduction and distribution of pineapple, or that pineapple might have originated in Southeast Asia.
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Ananas/parasitología , Hemípteros/clasificación , Hemípteros/genética , Filogeografía , Animales , Análisis por Conglomerados , Evolución Molecular , Genotipo , Geografía , Haplotipos , FilogeniaRESUMEN
Cytochrome P4502E1 (CYP2E1) is a key enzyme in the metabolic activation of many carcinogens, but the roles of CYP2E1 polymorphisms in cervical neoplasia (CN) are inconclusive. Published case-control cohort studies from the Pubmed, Embase, and China National Knowledge Infrastructure databases were retrieved. Data were extracted and pooled odds ratios with 95% confidence intervals were calculated. Seven studies examining 1097 cases and 1117 controls were included in this meta-analysis. The pooled effect size showed no association between CYP2E1 RsaI and DraI polymorphisms and CN risk in a codominant model. However, using a recessive model, an association between the PstI polymorphism and CN risk was observed (odds ratio: 2.10, 95% confidence interval: 0.96-4.62, P = 0.06), indicating that individuals with the homozygous rare genotype have a higher risk of developing CN compared to those with homozygous wild-type and heterozygous genotypes. When stratified by ethnicity, the PstI polymorphism was significantly correlated with CN susceptibility in non-Asians (odds ratio: 3.74, 95% confidence interval: 1.13-12.43, P = 0.03). This meta-analysis suggests that the CYP2E1 PstI polymorphism increases the risk of CN in non-Asians.
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Citocromo P-450 CYP2E1/genética , Predisposición Genética a la Enfermedad , Neoplasias/genética , Neoplasias del Cuello Uterino/genética , Pueblo Asiatico/genética , China , Femenino , Genotipo , Humanos , Neoplasias/patología , Factores de Riesgo , Neoplasias del Cuello Uterino/patologíaRESUMEN
In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (Et) according to their expression profiles. The results showed that the Et values of G protein-coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.
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Regeneración Hepática/genética , Transducción de Señal/genética , Fosfolipasas de Tipo C/genética , Animales , Proliferación Celular/genética , Hepatocitos/metabolismo , Hígado/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Factores de Transcripción/genética , Fosfolipasas de Tipo C/aislamiento & purificación , Fosfolipasas de Tipo C/metabolismoRESUMEN
Cytidine monophosphate (CMP) N-acetylneuraminic acid (NeuNAc) synthetase, which is encoded by the neuA gene, can catalyze the activation of sialic acid with CMP, and plays an important role in Streptococcus agalactiae infection pathogenesis. To study the structure and function of the S. agalactiae neuA gene, we isolated it from diseased tilapia, amplified it using polymerase chain reaction (PCR) with specific primers, and cloned it into a pMD19-T vector. The recombinant plasmid was confirmed by PCR and restriction enzyme digestion, and identified by sequencing. Molecular characterization analyses of the neuA nucleotide amino acid sequence were performed using bioinformatic tools and an online server. The results showed that the neuA nucleotide sequence contained a complete coding region, which comprised 1242 bp, encoding 413 amino acids (aa). The aa sequence was highly conserved and contained a Glyco_tranf_GTA_type superfamily and an SGNH_hydrolase superfamily conserved domain, which are related to sialic acid activation catalysis. The NeuA protein possessed many important sites related to post-translational modification, including 28 potential phosphorylation sites and 2 potential N-glycosylation sites, had no signal peptides or transmembrane regions, and was predicted to reside in the cytoplasm. Moreover, the protein had some B-cell epitopes, which suggests its potential in development of a vaccine against S. agalactiae infection. The codon usage frequency of neuA differed greatly in Escherichia coli and Homo sapiens genes, and neuA may be more efficiently expressed in eukaryotes (yeast). S. agalactiae neuA from tilapia maintains high structural homology and sequence identity with CMP-NeuNAc synthetases from other bacteria.
Asunto(s)
Acetiltransferasas/genética , Secuencia de Aminoácidos , Biología Computacional , Streptococcus agalactiae/enzimología , Animales , Clonación Molecular , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Humanos , Sistemas de Lectura Abierta , Homología de Secuencia de Aminoácido , Streptococcus agalactiae/genética , Tilapia/microbiologíaRESUMEN
The aim of the present study was to investigate the anti-ovarian cancer effect of the inhibitor of signal transducer and activator of transcription 3 (STAT3), WP1066. Western blot was used to detect the phosphorylation of STAT3 in ovarian cancer cell line SKOV3 and cisplatin-resistant ovarian cancer cell line SKOV3/DDP. MTT and colony-forming assays were performed to evaluate the viability and growth of ovarian cancer cells. The apoptosis of ovarian cancer cells was determined by flow cytometry. The wound healing assay and Transwell assay were performed to examine the migration and invasion of ovarian cancer cells. WP1066 significantly inhibited the phosphorylation of STAT3 in SKOV3 and SKOV3/DDP cells. WP1066 treatment inhibited the proliferation and clonogenicity of both SKOV3 and SKOV3/DDP cells. After WP1066 treatment for 24 h, the apoptosis rates of SKOV3 and SKOV3/DDP cells were significantly increased compared with the control cells. After treatment with WP1066, the reduction of the wound gaps was significantly less in both SKOV3 and SKOV3/DDP cells. WP1066 also significantly inhibited the invasion capacity of SKOV3 and SKOV3/DDP cells compared with the control group. Treatment with WP1066 combined with cisplatin significantly increased proliferation inhibition and apoptosis in SKOV3 and SKOV3/ DDP cells compared with treatment with cisplatin alone. A synergistic action between WP1066 and cisplatin on the proliferation and apoptosis of ovarian cancer cells was determined. In conclusion, inhibition of STAT3 may suppress the proliferation, migration and invasion, induce apoptosis and enhance the chemosensitivity of ovarian cancer cells, indicating that STAT3 is a new therapeutic target of ovarian cancer.