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Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.
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MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Masculino , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Genes Supressores de Tumor , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , MicroRNAs/genética , Movimento Celular/genética , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica , Receptores Depuradores Classe A/genética , Receptores Depuradores Classe A/metabolismoRESUMO
BACKGROUND: Atherosclerosis is the most frequent pathological process that causes cardiovascular diseases. OBJECTIVE: The present study aimed to confirm miRNAs associated with atherosclerosis and explore the molecular mechanism of miR-34c and its target high mobility group box protein 1 (HMGB1) in the control of growth of smooth muscle cells in the development of atherosclerosis. METHODS: Real-time PCR was firstly performed to confirm miRNA correlation with atherosclerosis, and computational analysis and luciferase assay were performed to explore the target of miR-34c, Western blot, and real-time PCR were also utilized to reveal the effect of whether high glucose (HG) and miR-34c affect miR-34c, HMGB1 levels, NF-κB p65 and TNF-α levels, and the role of miR-34c on vascular smooth muscle cells (VSMCs) viability induced by HG. Students' unpaired t test was performed to compare data between two groups. RESULTS: MiR-34c level was associated with atherosclerosis with different expression between VSMCs treated with high glucose or normal VSMCs. Then, HMGB1 is a virtual target of miR-34c with predicted binding site resided in HMGB1 3'UTR and further verified by that miR-34c remarkably reduced luciferase activity of wild HMGB1 3'UTR under a concentration-dependent fashion, and miR-34c cannot influence luciferase activity of mutant HMGB1 3'UTR. CONCLUSIONS: The results suggested miR-34c might be a novel therapeutic strategy in the management of atherosclerosis by suppressing the expression of HGMB1 and its downstream effectors.
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Proteína HMGB1/genética , MicroRNAs/genética , Músculo Liso Vascular/citologia , Regiões 3' não Traduzidas , Proliferação de Células/genética , Sobrevivência Celular , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glucose/farmacologia , Proteína HMGB1/metabolismo , Humanos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , NF-kappa B/genética , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To investigate the clinical features, diagnosis, treatment and prognosis of testicular mixed germ cell tumors (TMGCT). METHODS: This retrospective study included 27 cases (2 children and 25 adults) of TMGCT confirmed surgically and pathologically in our hospital from December 2007 to December 2012. The patients' ranged in the age of onset from 7 months to 63 years, averaging at 29.5 years. We analyzed the clinical data and reviewed the related literature. RESULTS: At pathological examination, the TMGCTs displayed a variety of subtypes, including 13 cases of yolk sac tumor (48.1%), 13 cases of seminoma (48.1%), 18 cases of embryonal carcinoma (66.7%), 4 cases of choriocarcinoma (14.8%) and 17 cases of teratoma (63.0%). Of the total number of cases, 15 (55.6%) contained two different germ cell histological elements, 11 (40.7%) contained three, and 1 (3.7%) contained four; 18 cases (66.7%) were in stage â , 6 (22.2%) in stage â ¡, and 3 (11.1%) in stage â ¢. All the patients underwent radical orchiectomy and, in addition, retroperitoneal lymph node dissection (RPLND) + BEP chemotherapy was administered for 3 cases of stage â ¡ and 1 case of stage â ¢. Three cases of stage â ¡ and 2 cases of stage â ¢ refused RPLND and 1 case of stage â ¢ refused chemotherapy. A 27ï¼49-month (mean 30 months) follow-up was completed for 21 of the patients, during which retroperitoneal metastasis was found in 3 cases of stage â and 2 cases of stage â ¡, who again received RPLND+BEP and experienced no more recurrence. One case of stage â ¢ refused both RPLND and chemotherapy and died at 12 months. CONCLUSIONS: TMGCT is a rare carcinoma with atypical clinical features, mostly comprising two or three different germ cell histological elements. Comprehensive treatment of RPLND combined with BEP chemotherapy may achieve a high survival rate and reduce recurrence for most of the patients with TMGCT of stage â ¡ or above.
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Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Adulto , Criança , Humanos , Excisão de Linfonodo , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Orquiectomia , Espaço Retroperitoneal , Estudos Retrospectivos , Seminoma/diagnóstico , Seminoma/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapiaRESUMO
BACKGROUND: Vascular hyporeactivity in severe hemorrhagic shock could induce refractory hypotension and is an important cause of death. The global acute inflammatory response induced in shock triggers the over-expression of reactive oxygen species, NO, ET1 and TNF-α, which play essential roles in the pathology of vascular hyporeactivity. This leads to a hypothesis that inhibition of the complement system, the mediator of the inflammatory cascade, might be a promising therapeutic exploration for vascular hyporeactivity. METHODS: We use cobra venom factor (CVF) and the soluble form of CR1 (sCR1) which deplete or inhibit complement C3 respectively to examine its role in vascular hyporeactivity in a conscious hemorrhagic shock rat model. RESULTS: We first confirmed the over-activation of C3 during shock and the down-regulation effects of CVF and sCR1 on C3. Then, both CVF and sCR1 could significantly mitigate the over-expression of serum NO, ET-1, TNF-α and reactive oxygen species. Finally, the vascular reactivity of superior mesenteric arteries (SMA) was examined in vitro, which confirmed the massive reduction of vascular reactivity in shock, which was significantly rescued by both CVF and sCR1. CONCLUSIONS: Inhibition of C3 might improve the reactivity of SMA to norepinephrine during hemorrhagic shock possibly through the downregulation of NO, ET1, TNF-α and reactive oxygen radicals.
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Ativação do Complemento/efeitos dos fármacos , Complemento C3/antagonistas & inibidores , Inativadores do Complemento/administração & dosagem , Venenos Elapídicos/administração & dosagem , Artéria Mesentérica Superior/efeitos dos fármacos , Receptores de Complemento 3b/administração & dosagem , Choque Hemorrágico/tratamento farmacológico , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/administração & dosagem , Vasoconstritores/metabolismo , Animais , Complemento C3/metabolismo , Inativadores do Complemento/metabolismo , Modelos Animais de Doenças , Endotelina-1/sangue , Artéria Mesentérica Superior/fisiopatologia , Óxido Nítrico/sangue , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/sangue , Receptores de Complemento 3b/metabolismo , Choque Hemorrágico/etiologia , Choque Hemorrágico/fisiopatologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND The objective of this study was to investigate the molecular mechanism by which miR-637 interferes with the expression of CDK6, which contributes to the development of pulmonary hypertension (PH) with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS We used an online miRNA database to identify CDK6 as a virtual target of miR-637, and validated the hypothesis using luciferase assay. Furthermore, we transfected SMCs with miR-637 mimics and inhibitor, and expression of CDK6 was determined using Western blot and real-time PCR. RESULTS In this study, we identified CDK6 as a target of miR-637 in smooth muscle cells (SMCs), and determined the expression of miR-637 in SMCs from PH patients with COPD and normal controls. We also identified the exact miR-637 binding site in the 3'UTR of CDK6 by using a luciferase reporter system. The mRNA and protein expression levels of CDK6 in SMCs from PH patients with COPD were clearly upregulated compared with the normal controls. Cells exposed to hypoxia also showed notably increased CKD6 mRNA and protein expression levels, and when treated with miR-637 or CDK6 siRNA, this increase in CKD6 expression was clearly attenuated. Additionally, cell viability and cell cycle analysis showed that hypoxia markedly increased viability of SMCs by causing an accumulation in S phase, which was relieved by the introduction of miR-637 or CDK6 siRNA. CONCLUSIONS Our study proved that the CDK6 gene is a target of miR-637, and demonstrated the regulatory association between miR-637 and CDK6, suggesting a possible therapeutic target for PH, especially in patients with COPD.
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Quinase 6 Dependente de Ciclina/biossíntese , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Estudos de Casos e Controles , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Quinase 6 Dependente de Ciclina/genética , Regulação para Baixo , Humanos , Hipertensão Pulmonar/enzimologia , Hipóxia/enzimologia , Hipóxia/genética , Hipóxia/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Cultura Primária de Células , RNA Mensageiro/metabolismo , RNA Interferente PequenoRESUMO
BACKGROUND: The brown planthopper (Nilaparvata lugens) is one of the most destructive rice plant pests in Asia. N. lugens causes extensive damage to rice by sucking rice phloem sap, which results in hopper burn (complete death of the rice plants). Despite its importance, little is known about the digestion, development and defense mechanisms of this hemimetabolous insect pest. In this study, we aim to identify the serine protease (SP) and serine protease homolog (SPH) genes, which form a large family in eukaryotes, due to the potential for multiple physiological roles. Having a fully sequenced genome for N. lugens allows us to perform in-depth analysis of the gene structures, reveal the evolutionary relationships and predict the physiological functions of SP genes. RESULTS: The genome- and transcriptome-wide analysis identified 90 putative SP (65) and SPH (25) genes in N. lugens. Detailed gene information regarding the exon-intron organization, size, distribution and transcription orientation in the genome revealed that many SP/SPH loci are closely situated on the same scaffold, indicating the frequent occurrence of gene duplications in this large gene family. The gene expression profiles revealed new findings with regard to how SPs/SPHs respond to bacterial infections as well as their tissue-, development- and sex-specific expressions. CONCLUSIONS: Our findings provide comprehensive gene sequence resources and expression profiles of the N. lugens SP and SPH genes, which give insights into clarifying the potentially functional roles of these genes in the biological processes including development, digestion, reproduction and immunity.
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Hemípteros/genética , Família Multigênica , Serina Proteases/genética , Transcriptoma , Sequência de Aminoácidos , Animais , Expressão Gênica , Perfilação da Expressão Gênica , Ordem dos Genes , Genes de Insetos , Loci Gênicos , Genômica , Hemípteros/imunologia , Imunidade/genética , Dados de Sequência Molecular , Especificidade de Órgãos/genética , Filogenia , Alinhamento de Sequência , Serina Proteases/química , Tripsina/química , Tripsina/genéticaRESUMO
Phthalate acid esters (PAEs) are one of the most widely used plasticizers globally, extensively employed in various decoration materials. However, studies on the impact of these materials on indoor environmental PAE pollution and their effects on human health are limited. In this study, forty dust samples were collected from four types of stores specializing in decoration materials (flooring, furniture boards, wall coverings, and household articles). The levels, sources, exposure doses, and potential health risks of PAEs in dust from decoration material stores were assessed. The total concentrations of Σ9PAE (the sum of nine PAEs) in dust from all decoration-material stores ranged from 46,100 ng/g to 695,000 ng/g, with a median concentration of 146,000 ng/g. DMP, DEP, DBP, and DEHP were identified as the predominant components. Among all stores, furniture board stores exhibited the highest Σ9PAE (159,000 ng/g, median value), while flooring stores exhibited the lowest (95,300 ng/g). Principal component analysis (PCA) showed that decoration materials are important sources of PAEs in the indoor environment. The estimated daily intakes of PAEs through non-dietary dust ingestion and dermal-absorption pathways among staff in various decoration-material stores were 60.0 and 0.470 ng/kg-bw/day (flooring stores), 113 and 0.780 ng/kg-bw/day (furniture board stores), 102 and 0.510 ng/kg-bw/day (wall covering stores), and 114 and 0.710 ng/kg-bw/day (household article stores). Particularly, staff in wall-covering and furniture-board stores exhibited relatively higher exposure doses of DEHP. Risk assessment indicated that although certain PAEs posed potential health risks, the exposure levels for staff in decoration material stores were within acceptable limits. However, staff in wall covering stores exhibited relatively higher risks, necessitating targeted risk-management strategies. This study provides new insights into understanding the risk associated with PAEs in indoor environments.
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BACKGROUND: The brown planthopper (Nilaparvata lugens) is one of the most serious rice plant pests in Asia. N. lugens causes extensive rice damage by sucking rice phloem sap, which results in stunted plant growth and the transmission of plant viruses. Despite the importance of this insect pest, little is known about the immunological mechanisms occurring in this hemimetabolous insect species. RESULTS: In this study, we performed a genome- and transcriptome-wide analysis aiming at the immune-related genes. The transcriptome datasets include the N. lugens intestine, the developmental stage, wing formation, and sex-specific expression information that provided useful gene expression sequence data for the genome-wide analysis. As a result, we identified a large number of genes encoding N. lugens pattern recognition proteins, modulation proteins in the prophenoloxidase (proPO) activating cascade, immune effectors, and the signal transduction molecules involved in the immune pathways, including the Toll, Immune deficiency (Imd) and Janus kinase signal transducers and activators of transcription (JAK-STAT) pathways. The genome scale analysis revealed detailed information of the gene structure, distribution and transcription orientations in scaffolds. A comparison of the genome-available hemimetabolous and metabolous insect species indicate the differences in the immune-related gene constitution. We investigated the gene expression profiles with regards to how they responded to bacterial infections and tissue, as well as development and sex expression specificity. CONCLUSIONS: The genome- and transcriptome-wide analysis of immune-related genes including pattern recognition and modulation molecules, immune effectors, and the signal transduction molecules involved in the immune pathways is an important step in determining the overall architecture and functional network of the immune components in N. lugens. Our findings provide the comprehensive gene sequence resource and expression profiles of the immune-related genes of N. lugens, which could facilitate the understanding of the innate immune mechanisms in the hemimetabolous insect species. These data give insight into clarifying the potential functional roles of the immune-related genes involved in the biological processes of development, reproduction, and virus transmission in N. lugens.
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Genoma de Inseto , Hemípteros/genética , Imunidade Inata/genética , Transcriptoma , Sequência de Aminoácidos , Animais , Proteínas de Transporte/química , Proteínas de Transporte/classificação , Proteínas de Transporte/genética , Hemípteros/crescimento & desenvolvimento , Hemípteros/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/classificação , Proteínas de Insetos/genética , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismoRESUMO
Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.
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Inspired by a recently experiment by M. Lettner et al. [Phys. Rev. Lett. 106, 210503 (2011)], we propose a robust scheme to prepare three-dimensional entanglement state between a single atom and a Bose-Einstein condensate (BEC) via stimulated Raman adiabatic passage (STIRAP) technique. The atomic spontaneous radiation, the cavity decay, and the fiber loss are efficiently suppressed by the engineering adiabatic passage. Our strictly numerical simulation shows our proposal is good enough to demonstrate the generation of three-dimensional entanglement with high fidelity and within the current experimental technology.
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Luz , Modelos Teóricos , Espalhamento de Radiação , Análise Espectral Raman/métodosRESUMO
OBJECTIVE: To compare the accuracy of whole body diffusion weighted magnetic resonance imaging (WB-DWI) with that of somatostatin receptor scintigraphy (SRS) in the detection and localization of the lesions in patients with oncogenic osteomalacia (OOM). METHODS: Totally 6 patients with clinically suspected oncogenic osteomalacia were enrolled. All of them underwent WB-DWI and SRS within 2 weeks to evaluate the possible presence of tumors that lead to osteomalacia. Surgical and pathological findings were considered as the gold standard. The sensitivity, specificity, and accuracy were calculated. RESULTS: Pathology confirmed the diagnosis of two soft tissue tumors (including 1 angiolipoma and 1 mesenchymal tumor) and one bone tumor of malignant neurofibroma. The sensitivity, specificity, and accuracy in the identification of lesions in patients with oncogenic osteomalacia were 33.33%, 100%, 66.67% for WB-DWI and 33.33%, 66.67%, 50% for SRS (P>0.05). CONCLUSION: For adult patients with osteomalacia, WB-DWI and SRS can provide mutually supportive data and be used for identifying potential oncogenic osteomalacia.
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Neoplasias Ósseas/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias de Tecido Conjuntivo/diagnóstico , Imagem Corporal Total/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteomalacia , Síndromes Paraneoplásicas , Receptores de Somatostatina , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Epigenetics exerts a vital role in the onset and development of renal cell carcinoma (RCC). Mounting evidence has shed light on the significance of human immune system in response to tumor infiltrating T cells. Hereby, we sought to unmask the immunomodulatory role of histone deacetylase 3 (HDAC3) and its potential upstream molecule, programmed cell death 5 (PDCD5) in RCC. METHODS: RCC and adjacent non-cancerous tissues were clinically resected from 58 patients, in which the expression profile of microRNA-195-5p (miR-195-5p), PDCD5, HDAC3, and serum glucocorticoid-inducible kinase 1 (SGK1) was determined by RT-qPCR and Western blot analysis. Their relations were investigated by a series of luciferase assays in combination with ChIP and co-IP. RCC cells (A498) were intervened using gain- and loss-of-function approaches, followed by cell proliferation evaluation. After co-culture with CD3+ T cells, flow cytometry and interferon-γ (IFN-γ) determination were performed. A xenograft tumor mouse model was developed for in vivo validation. RESULTS: PDCD5 was downregulated in RCC tissues and A498 cells. Upregulation of HDAC3, as well as of SGK1, resulted in suppression of A498 cell proliferation and promotion of T cell activation as evidenced by higher IFN-γ expression. Re-expression of PDCD5 downregulated HDAC3, causing a subsequent upregulation of miR-195-5p, while miR-195-5p could inversely modulate its target gene, SGK1. The regulatory mechanism appeared to be functional in vivo. CONCLUSION: Our results highlight the possible manipulation by PDCD5 on RCC cell proliferation and T cell activation, which provides new clues to better understand the immune balance in RCC progression.
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Proteínas Reguladoras de Apoptose , Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Proteínas de Neoplasias , Animais , Humanos , Camundongos , Proteínas Reguladoras de Apoptose/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Metilação de DNA , Interferon gama/genética , Neoplasias Renais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/genética , Linfócitos T/metabolismoRESUMO
LncRNAs can be transported to tumor cells where they exert regulatory effects by bone marrow mesenchymal stem cells (BMSC)-derived exosomes. Here, we aimed to investigate the functional mechanism of BMSC-derived exosomal lncRNA PTENP1 in the progression of bladder cancer (BC). Methods of BMSC were identified by detecting surface markers through flow cytometry. Exosomes from BMSC were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blot analysis of exosome markers. Cellular internalization of BMSC-derived exosomes (BMSC-Exo) into BC cells was detected by confocal microscopy. CCK-8, colony formation, flow cytometry, wound healing, and transwell assays were adopted to estimate cell proliferation, apoptosis, migration, and invasion abilities, respectively. Interplay between miR-17 and lncRNA PTENP1 or SCARA5 was verified by dual-luciferase reporter, RNA pull down, and/or RNA immunoprecipitation (RIP) assays. Tumor xenograft assay was conducted in nude mice to study the role of exosomal lncRNA PTENP1 in BC progression in vivo. We showed exosomal lncRNA PTENP1 can be delivered into and suppress the malignant phenotypes of BC cells. LncRNA PTENP1 was identified as a sponge of miR-17, and SCARA5 was identified as a target gene of miR-17. The exosomes derived from PTENP1-overexpressing BMSC (BMSCOE-PTENP1-Exo) abolished the promotive effects of miR-17 overexpression or SCARA5 knockdown on the malignant phenotypes of BC cells. Moreover, exosomal lncRNA PTENP1 was demonstrated to inhibit BC tumor growth in nude mice by miR-17/SCARA5 axis. In conclusion, BMSC-derived exosomal PTENP1 suppressed the BC progression by upregulating the expression of SCARA5 via sponging miR-17, offering a potential novel therapeutic target for BC therapy.
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Animais , Proliferação de Células/genética , Exossomos/genética , Exossomos/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Fenótipo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Receptores Depuradores Classe A/genética , Receptores Depuradores Classe A/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
To investigate the regulatory role of microRNA-223 (miR-223) on c-myc and its role in hepatocarcinogenesis. miR-223 and c-myc mRNA expressions in normal tissue, paraneoplastic tissue, liver cancer tissue and liver cancer cells were tested with microRNA microarray and quantitative real-time PCR (qRT-PCR). C-myc protein expression was detected by Western blot. MiR-223 mimic was transfected into HepG2 cells and the expression changes of c-myc mRNA and protein were tested with qRT-PCR and Western blot respectively. MiR-223 was down-regulated by 61.53% and 30.77% respectively in hepatocellular carcinoma and adjacent tissues as compared to normal liver tissues and the expression of miR-223 was also decreased in HepG2 cell as compared to fetal liver cells L02, whereas the expressions of c-myc mRNA and protein increased in paraneoplastic and HCC tissues compared with normal liver tissues. It prompts that the expressions of miR-223 and c-myc are negatively correlated. No obvious difference found among c-myc mRNA expressions after miR-223 mimics transfection. The c-myc abnormal high-expression may play a dynamic role in hepatocarcinogenesis due to the miR-223 down-regulation.
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Cancer associated fibroblasts (CAFs) play crucial roles in cancer development, however, the specific mechanisms of CAFs associated renal cancer progression remain poorly understood. Our study observed enriched CAFs in high degree malignant tumor tissues from renal cancer patients. These CAFs isolated from tumor tissues are prone to facilitate drugs resistance and promote tumor progression in vitro and in vivo. Mechanistically, CAFs up-regulated tryptophan 2, 3-dioxygenase (TDO) expression, resulting in enhanced secretion of kynurenine (Kyn). Kyn produced from CAFs could up-regulated the expression of aromatic hydrocarbon receptor (AhR), eventually resulting in the AKT and STAT3 signaling pathways activation. Inhibition of AKT signal prevented cancer cells proliferation, while inhibition of the STAT3 signal reverted drugs resistance and cancer migration induced by kynurenine. Application of AhR inhibitor DMF could efficiently suppress distant metastasis of renal cancer cells, and improve anticancer effects of sorafenib (Sor)/sunitinib (Sun), which described a promising therapeutic strategy for clinical renal cancer.
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OBJECTIVE: To study the effect of smoking on resting energy expenditure (REE) and the relationships among REE, smoking, inflammation and oxidative stress in patients with diabetic kidney disease. METHODS: A case control study of 31 smokers and 40 non-smokers with early stage of diabetic kidney disease (stage III) were performed to evaluate the chronic effect of smoking on REE. REE/fat free mass (FFM), biomarkers of oxidative stress malondialdehyde (MDA), superoxide dismutase (SOD) and inflammation high-sensitivity C-reactive protein (hs-CRP), adiponectin, TNFα were also measured in these subjects. Data were analyzed by Pearson correlation analysis. RESULTS: Compared with non-smokers, REE/FFM in smokers group was significantly increased by 15.96% (P = 0.001). Pearson analysis showed that smoking was significantly correlated with REE/FFM (t = 0.395, P = 0.001). There were significantly different between smokers and non-smokers in MDA, SOD and hs-CRP (P < 0.05). But no difference between two groups in adiponectin and TNFα (P > 0.05). No significant relationships between REE/FFM and MDA, SOD, hs-CRP, adiponectin, TNFα was found (P > 0.05). CONCLUSION: Chronic smoking can lead to increased REE, arouse oxidative stress and inflammatory in patients with early stage of diabetic kidney disease. However, there is no relationship between increased REE due to smoking and oxidative stress and inflammatory.
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Metabolismo Basal/efeitos dos fármacos , Nefropatias Diabéticas/metabolismo , Fumar/efeitos adversos , Adulto , Idoso , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Estresse OxidativoRESUMO
OBJECTIVE: To investigate the expression of integrin beta 1 in hepatic cirrhosis (HC) and hepatocellular carcinoma (HCC). METHODS: The expression of integrin beta 1 in HCC, HC and normal liver tissues was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and laser scanning confocal microscopy (LSCM). The association between the integrin beta 1 expression and clinical pathological features were analyzed. RESULTS: (1) The levels of integrin beta 1 mRNA and protein in the HCC (1.30+/-0.24, 90.50+/-33.50) and HC (1.58+/-0.31, 123.10+/-38.90) were much higher than that in the normal hepatic tissue (0.37+/-0.08, 11.90+/-6.00) (P less than 0.05). (2) The expression of integrin beta 1 was associated with HC (r = 0.692), Edmondson pathologic grade (F = 13.618), encapsulation (F = 17.857) and metastasis (F = 38.857) (P less than 0.01). CONCLUSIONS: Integrin beta 1 may play an important role in the development of hepatic fibrosis, hepatic cirrhosis and hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/metabolismo , Integrina beta1/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/patologia , Humanos , Integrina beta1/genética , Fígado/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , RNA Mensageiro/genéticaRESUMO
To realize the effect of space flight factors on chemical component of alfalfa seeds and its possible mechanism, seeds were loaded onto satellite "Jianbing No. 1" in 2006 for 14 days' space flight and then analyzed by Raman spectroscopy. Results showed that the intensity of two peaks (358 and 553 cm(-1)) of space flight seeds had been increased and the intensity of four peaks (814, 1 122, 1 531 and 1 743 cm(-1)) of space flight seeds had been decreased compared with its ground control. Based on the classification of Raman spectra, the increased peaks of 358 and 553 cm(-1) are related to DNA and Ca2+ respectively, which mean that the content of DNA and Ca2+ of alfalfa seeds had increased after space flight. The decreased peaks of 814, 1 122 and 1 743 cm(-1) are related to saccharide and fatty acid respectively, which mean that the content of reserve energy of alfalfa seeds had decreased after space flight. These findings can be explained as follows: (1) The increase in the content of DNA may be explained by the DNA damage induced by space flight factors and DNA syntheses and duplication before the cell division. (2) The increase in the content of Ca2+ may be stimulated by the complexity of gravity during the space flight, especially the hypergravity. Recent researches in Abrabidopsis thaliana have provided additional proof. (3) The decrease of the energy materials such as saccharide and fatty acid may be explained by the consumption both during the repair process of DNA damage induced by cosmic radiation and during the germination of seeds because the dormancy of alfalfa seeds had been broken up by space flight factors (cosmic radiation, microgravity, vibration or others) which subsequently resulted in that nutritious materials of alfalfa seeds were used earlier than its ground control.
Assuntos
Medicago sativa , Sementes , Voo Espacial , Análise Espectral Raman , Cálcio/análise , Radiação Cósmica , DNA de Plantas/análise , Mutação , Ausência de PesoRESUMO
A new approach to the fabrication of magnetic thermosensitive microcontainers of Fe(3)O(4) nanoparticles with poly(N-isopropylacrylamide) walls is presented. The microcontainers undergo a temperature-induced volume phase transition and present an impressive magnetic response. The microcontainers have a well-defined structure with a narrow size distribution. The wall thicknesses of the microcontainers can be controlled according to requirements. Compared to other preparation methods, the process is simple and reproducible. The magnetic saturation of these microcontainers is high enough to meet most requirements of bioapplications. To further investigate the potential application of these microcontainers, they are tested as drug carriers, with the drug loading and releasing processes carefully studied. The drug encapsulation efficiency and drug content in the carriers are pH-dependent, and the carriers have a maximal drug loading of about 50 wt% under alkaline conditions. The release of the drug from the microcontainers can be controlled by the environmental pH, temperature, and magnetic force.