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BACKGROUND: Myocardial cell death is the hallmark of myocardial infarction. In the process of myocardial injury, platelets contribute to the pathogenesis by triggering intense inflammatory responses. Yet, it is still unclear if platelets regulate cardiomyocyte death directly, thereby exacerbating myocardial injury in myocardial infarction. METHODS: We describe a mechanism underlying the correlative association between platelets accumulation and myocardial cell death by using myocardial infarction mouse model and patient specimens. RESULTS: Myocardial infarction induces platelets internalization, resulting in the release of miR-223-3p, a platelet-enriched miRNA. By targeting the ACSL3, miR-223-3p delivered by internalized platelets cause the reduction of stearic acid-phosphatidylcholine in cardiomyocytes. The presence of stearic acid-phosphatidylcholine protects cardiomyocytes against ferroptosis. CONCLUSIONS: Our work reveals a novel mechanism of platelet-mediated myocardial injury, highlighting antiplatelet therapies could potentially represent a multimechanism treatment of myocardial infarction, and implying ferroptosis being considered as novel target for therapeutics.
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Ferroptose , MicroRNAs , Infarto do Miocárdio , Camundongos , Animais , Plaquetas/metabolismo , Infarto do Miocárdio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Morte Celular , Miócitos Cardíacos/metabolismoRESUMO
Shoot multiplication induced by exogenous cytokinins (CKs) has been commonly used in Phalaenopsis micropropagation for commercial production. Despite this, mechanisms of CKs action on shoot multiplication remain unclear in Phalaenopsis. In this study, we first identified key CKs metabolic genes, including six isopentenyltransferase (PaIPTs), six cytokinin riboside 5' monophosphate phosphoribohydrolase (PaLOGs), and six cytokinin dehydrogenase (PaCKXs), from the Phalaenopsis genome. Then, we investigated expression profiles of these CKs metabolic genes and endogenous CKs dynamics in shoot proliferation by thidiazuron (TDZ) treatments (an artificial plant growth regulator with strong cytokinin-like activity). Our data showed that these CKs metabolic genes have organ-specific expression patterns. The shoot proliferation in vitro was effectively promoted with increased TDZ concentrations. Following TDZ treatments, the highly expressed CKs metabolic genes in micropropagated shoots were PaIPT1, PaLOG2, and PaCKX4. By 30 days of culture, TDZ treatments significantly induced CK-ribosides levels in micropropagated shoots, such as tZR and iPR (2000-fold and 200-fold, respectively) as compared to the controls, whereas cZR showed only a 10-fold increase. Overexpression of PaIPT1 and PaLOG2 by agroinfiltration assays resulted in increased CK-ribosides levels in tobacco leaves, while overexpression of PaCKX4 resulted in decreased CK-ribosides levels. These findings suggest de novo biosynthesis of CKs induced by TDZ, primarily in elevation of tZR and iPR levels. Our results provide a better understanding of CKs metabolism in Phalaenopsis micropropagation.
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Citocininas , Orchidaceae , Citocininas/metabolismo , Citocininas/farmacologia , Orchidaceae/metabolismo , Reguladores de Crescimento de Plantas/metabolismoRESUMO
Gastric cancer (GC) is one of the most common malignant tumors in China and the third leading cause of cancer-related death. Parkin has been shown to be a tumor suppressor in a variety of malignancies, including GC. However, the mechanism of Parkin in GC remains unclear. In this study, the low expression of Parkin in GC cells and patient tumor tissues was observed, and Parkin inhibited proliferation and migration of GC cells. Additionally, doxorubicin (DOX) upregulated the expression of Parkin and promoted its anticancer effect. Forkhead box O3 (FOXO3a) is a crucial transcription factor that involves in the regulation of cancer cell proliferation, apoptosis, and metabolism. Here, we found that FOXO3a inhibits cell proliferation, migration, and promotes apoptosis in GC by regulating Parkin expression at the transcriptional level. In addition, Parkin inhibited cell proliferation, migration, and promoted apoptosis by inhibiting ATP-binding box protein E1 (ABCE1) expression. In summary, our results demonstrated a new regulatory axis of FOXO3a-Parkin-ABCE1 that modulated GC cell proliferation, migration, and apoptosis, and it can serve as a potential therapeutic target in GC.
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Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteína Forkhead Box O3/metabolismo , Neoplasias Gástricas/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Antibióticos Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Doxorrubicina/farmacologia , Proteína Forkhead Box O3/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Transdução de Sinais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/genéticaRESUMO
Cucumber green mottle mosaic virus (CGMMV), as a typical seed-borne virus, causes costly and devastating diseases in the vegetable trade worldwide. Genetic sources for resistance to CGMMV in cucurbits are limited, and environmentally safe approaches for curbing the accumulation and spread of seed-transmitted viruses and cultivating completely resistant plants are needed. Here, we describe the design and application of RNA interference-based technologies, containing artificial microRNA (amiRNA) and synthetic trans-acting small interfering RNA (syn-tasiRNA), against conserved regions of different strains of the CGMMV genome. We used a rapid transient sensor system to identify effective anti-CGMMV amiRNAs. A virus seed transmission assay was developed, showing that the externally added polycistronic amiRNA and syn-tasiRNA can successfully block the accumulation of CGMMV in cucumber, but different virulent strains exhibited distinct influences on the expression of amiRNA due to the activity of the RNA-silencing suppressor. We also established stable transgenic cucumber plants expressing polycistronic amiRNA, which conferred disease resistance against CGMMV, and no sequence mutation was observed in CGMMV. This study demonstrates that RNA interference-based technologies can effectively prevent the occurrence and accumulation of CGMMV. The results provide a basis to establish and fine-tune approaches to prevent and treat seed-based transmission viral infections.
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Cucumis sativus , Resistência à Doença/genética , MicroRNAs , Doenças das Plantas , Plantas Geneticamente Modificadas , RNA de Plantas , Tobamovirus , Cucumis sativus/genética , Cucumis sativus/metabolismo , Cucumis sativus/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/prevenção & controle , Doenças das Plantas/virologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/virologia , RNA de Plantas/genética , RNA de Plantas/metabolismo , Tobamovirus/genética , Tobamovirus/metabolismoRESUMO
Salvia miltiorrhiza Bunge contains various active constituents, some of which have been developed as commercially available medicine. Moreover, some other ingredients in Salvia miltiorrhiza play roles in anti-platelet activity. The aim of the present study was to investigate the effects and the underlying mechanism of miltirone, a lipophilic compound of Salvia miltiorrhiza Bunge. The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments. Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer. Clot retraction and spreading were imaged by digital camera and fluorescence microscope. Ferric chloride-induced carotid injury model and pulmonary thromboembolism model were used to check miltirone antithrombotic effect in vivo. To elucidate the mechanisms of anti-platelet activity of miltirone, flow cytometry and western blotting were performed. Miltirone (2, 4, 8 µM) was shown to suppress platelet aggregation, dense granule, and α granule secretion in a dose-dependent manner. Meanwhile, miltirone inhibited the clot retraction and spreading of washed platelets. It reduced the phosphorylation of PLCγ2, PKC, Akt, GSK3ß and ERK1/2 in the downstream signal pathway of collagen receptor. It also reduced the phosphorylation of Src and FAK in the integrin αIIbß3-mediated "outside-in" signaling, while it did not suppress the phosphorylation of ß3. In addition, miltirone prolonged the occlusion time and reduced collagen/epinephrine-induced pulmonary thrombi. Miltirone suppresses platelet "inside-out" and "outside-in" signaling by affecting PLCγ2/PKC/ERK1/2, PI3K/Akt, and Src/FAK signaling. Therefore, miltirone might represent a potential anti-platelet candidate for the prevention of thrombotic disorders.
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Plaquetas/efeitos dos fármacos , Fenantrenos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Animais , Plaquetas/fisiologia , Fibrinolíticos/farmacologia , Masculino , Camundongos , Fosforilação , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Transdução de SinaisRESUMO
BACKGROUND: Erythropoietin (EPO) is a hypoxia-inducible stimulator of erythropoiesis. Besides its traditional application in anemia therapy, it offers an effective treatment in the cancer patients, especially those who receive chemotherapy. Several reports indicated that it could promote the tumor cell proliferation through its specific receptor (EPOR). Unfortunately, the role of EPO/EPOR in hepatocellular carcinoma (HCC) progressing is still uncertain. METHODS: Protein in tumor tissue from HCC patients or H22 tumor-bearing mice was detected with immunohistochemistry. Cells were cultured under 1% oxygen to establish hypoxia. RT-PCR and western blotting were used to measure mRNA and protein of EPO/EPOR, respectively. MTT, flow cytometry and PCNA staining were used to detect cell proliferation. Immunofluorescence staining was applied to study the expression and location of cellular EPOR. The EPOR binding studies were performed with 125I-EPO radiolabeling assay. RESULTS: EPO and EPOR protein were up-regulated in HCC tissue of patients and H22-bearing mice. These were positively correlated with hypoxia-inducible factor -1 α and ki-67. Hypoxia up-regulated the expression of EPO and EPOR in HepG2 cells. It also induced the proliferation and increased the percentage of divided cells after 24, 48 and 72 h treatment. These were inhibited in cells pre-treated with 0.5 µg/mL soluble-EPOR. Immunofluorescence staining presented that EPOR was obviously translocated from nucleus to cytoplasm and membrane under hypoxia. EPOR binding activity was also increased after exposure to hypoxia. Recombinant human erythropoietin obviously elevated cell proliferation rate and the percentage of divided under hypoxia but not normoxia, which were also inhibited by soluble-EPOR. CONCLUSIONS: Our result indicated for the first time that EPO promoted the proliferation of HCC cells through hypoxia induced translocation of it specific receptor. Trial registration TJC20141113, retrospectively registered.
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Platelets, anucleate blood cells derive from megakaryocytes, are involved in cardiovascular diseases and tumors. FcγRIIA, the only FcγR expressed on human platelets, is known for its role in immune-related diseases. A growing body of evidence reveals that platelet FcγRIIA is a potential target for the prevention and control of cardiovascular disease and cancer, and is an advantageous biomarker. In this review, we describe the structure and physiological function of platelet FcγRIIA, its regulatory role in cardiovascular disease and cancer, and its potential clinical application.
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Plaquetas , Doenças Cardiovasculares , Neoplasias , Receptores de IgG , Humanos , Receptores de IgG/metabolismo , Plaquetas/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Neoplasias/sangue , Biomarcadores/sangue , AnimaisRESUMO
Iron overload is common in cardiovascular disease, it is also the factor that drives ferroptosis. Noncoding RNAs play an important role in heart disease; however, their regulatory role in iron overload-mediated ferroptosis remains much unknown. In our study, the iron overload model in mice was constructed through a high-iron diet, and ammonium iron citrate treatment was used to mimic iron overload in vitro. We found iron overload induced ferroptosis in cardiomyocytes, which was dependent on the high expression of transferrin receptor (TFRC). MiR-31-5p was downregulated during iron overload; it inhibited cardiomyocyte ferroptosis by targeting TFRC. CircPIK3C2A, a highly expressed circRNA in the heart, was upregulated when iron was overloaded. CircPIK3C2A enhanced the expression of TFRC by sponging miR-31-5p and promoted ferroptosis during iron overload. Our results reveal a novel mechanistic insight into noncoding RNA-based ferroptosis and identify the circPIK3C2A/miR-31-5p/TFRC axis as a promising therapeutic target for myocardial damage.
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Circular RNAs (circRNAs) are a class of single-stranded non-coding RNAs that form circular structures through irregular splicing or post-splicing events. CircRNAs are abnormally expressed in many cancers and regulate the occurrence and development of tumors. Circulating circRNAs are cell-free circRNAs present in peripheral blood, they are considered promising biomarkers due to their high stability. In recent years, more and more studies have revealed that circulating circRNAs participate in various cellular communication and regulate the occurrence and development of tumors, which involve many pathological processes such as tumorigenesis, tumor-related immunity, tumor angiogenesis, and tumor metastasis. Understanding the role of cell communication mediated by circulating circRNAs in tumor will further reveal the value and significance behind their use as biomarkers and potential therapeutic targets. In this review, we summarize the recent findings and provide an overview of the cell-cell communication mediated by circulating circRNAs, aiming to explore the role and application value of circulating circRNAs in tumors.
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Functional near-infrared spectroscopy (fNIRS) as an emerging optical neuroimaging technique has attracted the interest and attention of many investigators. With the growth of fNIRS data volume, effective data compression methods are urgent. Compressive sensing (CS) has been demonstrated a promising tool to deal with biomedical data. However, whether the compressibility of fNIRS data can discriminate different brain states is unclear. In this study, the fNIRS signals from fifteen attention-deficit/hyperactivity disorder (ADHD) children and fifteen typically developing (TD) children were recorded during an N-back task and a Go/NoGo task respectively. A block sparse Bayesian learning-based CS method was used to reconstruct the compressed fNIRS data. To assess the performance of the CS method, we adopted two metrics, structural similarity index (SSIM) and mean squared error (MSE), both of them effective in evaluating the compressibility of fNIRS data. Then, the two metrics were analyzed to discriminate the brain states of ADHD children and TD children during the two tasks using the multivariate pattern analysis (MVPA) method. As indicated by the results, the CS method could reconstruct the compressed fNIRS data with a high reconstruction quality at different compression ratio ([Formula: see text] and [Formula: see text]). Furthermore, the MVPA method could distinguish different brain states with high accuracy, and identify that the prefrontal cortex is a key brain region for distinguishing ADHD vs. TD or N-back vs. Go/NoGo. These findings indicated that CS is very promising for the storage and transmission of massive fNIRS data, and the compressibility of fNIRS data is a potential biomarker for the diagnosis of ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Teorema de Bayes , Encéfalo , Córtex Pré-FrontalRESUMO
In view of the increasing number of malignant tumors worldwide and their high mortality, efforts are being made to find effective biomarkers for early detection and effective treatment measures of cancer. In recent years, the roles of platelets in tumors have attracted considerable attention. Although platelets do not have nuclei, they are rich in miRNAs, which are important molecules in platelet regulation of tumors. Platelet miRNA expression in tumor patients is abnormal and tumor-specific. Platelet miRNAs have higher accuracy and specificity than conventional tumor detection markers and circulating miRNAs in tumor diagnosis. Platelets enriched miRNAs are involved in the regulation of tumor proliferation, metastasis, tumor-related immunity, tumor-related thrombosis, and antitumor therapy. To understand the role of platelet miRNAs in tumors, this article reviews the biological functions of miRNAs in platelets and summarizes the regulatory roles of platelet miRNAs in tumors and the potential roles of platelet miRNAs in tumor diagnosis and treatment.
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Plaquetas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/diagnóstico , Neoplasias/terapia , Animais , Humanos , Neoplasias/sangue , Neoplasias/genéticaRESUMO
Post-translational modification of proteins is an important biochemical process that occurs at the protein level. Succinylation is a newly discovered post-translational modification with the hallmark of a significant chemical and structural change. Succinylation has many similarities with other modifications, but succinylation may lead to more functional changes. Although the physiological significance of succinylation has not been well characterized, the lysine succinylation modification shows great potentials during disease processes. The discovery of SIRT5 has made great progress in exploring the role of succinylation in energy metabolism, heart disease and tumorigenesis. In this review, we focus on the discovery of succinylation in organisms and mechanism of succinylation. We are also concerned with the metabolic reactions and heart diseases associated with succinylation.
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Cardiopatias/metabolismo , Ácido Succínico/metabolismo , Animais , Humanos , Lisina/metabolismo , Processamento de Proteína Pós-Traducional/fisiologiaRESUMO
The mechanisms and biological functions of migrating platelets in cancer remain largely unknown. Here, we analyzed platelet infiltration in hepatocellular carcinoma. We detected platelet extravasation in both mouse and human HCC tissues. CX3CL1 directly induced platelet migration, and hypoxia enhanced platelet migration by upregulating CX3CL1 expression. Knocking down CX3CL1 in HCC cells reduced platelet migration in vitro, as well as infiltration of HCC tissue in an orthotopic HCC mouse model. Components of the CX3CR1/Syk/PI3K pathway were essential for CX3CL1-induced platelet migration. Migrating platelets induced HCC cell apoptosis in vitro, as indicated by a reduced mitochondrial membrane potential and an increased percentage of apoptotic cells. In the orthotopic tumor implantation model, decreased platelet infiltration was associated with accelerated tumor growth. Taken together, our findings indicate that HCC cell-derived CX3CL1 contributes to tumor infiltration by platelets, which in turn promotes apoptosis of HCC cells.
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Apoptose , Plaquetas/patologia , Receptor 1 de Quimiocina CX3C/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Quimiocina CX3CL1/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Movimento Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Quinase Syk/metabolismo , Regulação para CimaRESUMO
Tumor-associated thrombosis is the second leading risk factor for cancer patient death, and platelets activity is abnormal in cancer patients. Discovering the mechanism of platelet activation and providing effective targets for therapy are urgently needed. Cancer cell- derived IgG has been reported to regulate development of tumors. However, studies on the functions of cancer cell-derived IgG are quite limited. Here we investigated the potential role of cancer cell-derived IgG in platelet activation. We detected the expression of CD62P on platelets by flow cytometry and analyzed platelet function by platelets aggregation and ATP release. The content of IgG in cancer cell supernatants was detected by enzyme-linked immune sorbent assay. The distribution of cancer-derived IgG in cancer cells was analyzed by immunofluorescence assay. Western blot was performed to quantify the relative expression of FcγRIIa, syk, PLCγ2. The interaction between cancer cell-derived IgG and platelet FcγRIIa was analyzed by co-immunoprecipitation. The results showed that higher levels of CD62P were observed in cancer patients' platelets compared with that of healthy volunteers. Cancer cell culture supernatants increased platelet CD62P and PAC-1 expression, sensitive platelet aggregation and ATP release in response to agonists, while blocking FcγRIIa or knocking down IgG reduced the activation of platelets. Coimmunoprecipitation results showed that cancer cell-derived IgG interacted directly with platelet FcγRIIa. In addition, platelet FcγRIIa was highly expressed in liver cancer patients. In summary, cancer cell-derived IgG interacted directly with FcγRIIa and activated platelets; targeting this interaction may be an approach to prevent and treat tumor-associated thrombosis.
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Plaquetas/metabolismo , Imunoglobulina G/sangue , Neoplasias/sangue , Receptores de IgG/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Humanos , Neoplasias/imunologia , Ativação Plaquetária , Transdução de SinaisRESUMO
We have previously demonstrated that miR-1236-3p has the robust ability to up-regulate p21 expression by targeting the p21 promoter, thus inhibiting bladder cancer progression. Microarray experiments displayed that miR-1236-3p significantly increased the expression of the oncogenic F-box protein S-phase kinase-associate protein 2 (Skp2) while activating p21 expression in bladder cancer cells. Here, we confirmed that Skp2 was over-expressed following transfection with miR-1236-3p. Further, we demonstrated that miR-1236-3p and its sequence homology dsRNA, dsRNA-245 (which is completely complementary to the p21 promoter), both are able to potently induce p21 expression. We found that dsRNA-245 did not induce changes in Skp2 expression, while miR-1236-3p could increase Skp2 expression; this influence was independent of p21 activation. Moreover, transfection of miR-1236-3p or dsRNA-245 into bladder cancer cells significantly inhibited cell proliferation and clonegenesis and induced cell cycle arrest mainly by regulating p21 expression. However, the growth inhibition caused by dsRNA-245 was more effective than that caused by miR-1236-3p. This difference in effect size is mainly related to the miR-1236-3p-induced expression of Skp2. In summary, our results provided evidence that both endogenous and exogenous small RNAs might function to induce p21 expression by interacting with the same promoter region, therefore impeding bladder cancer cell growth. Additionally, our results indicated that microRNA activation can activate the expression of some tumor suppressor genes as well as some oncogenes. This indicated the need for the further study of clinical applications of RNA activation.
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OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting children and adults. Previous studies found that functional near-infrared spectroscopy (fNIRS) can reveal significant group differences in several brain regions between ADHD children and healthy controls during working memory tasks. This study aimed to use fNIRS activation patterns to identify ADHD children from healthy controls. APPROACH: FNIRS signals from 25 ADHD children and 25 healthy controls performing the n-back task were recorded; then, multivariate pattern analysis was used to discriminate ADHD individuals from healthy controls, and classification performance was evaluated for significance by the permutation test. MAIN RESULTS: The results showed that 86.0% ([Formula: see text]) of participants can be correctly classified in leave-one-out cross-validation. The most discriminative brain regions included the bilateral dorsolateral prefrontal cortex, inferior medial prefrontal cortex, right posterior prefrontal cortex, and right temporal cortex. SIGNIFICANCE: This study demonstrated that, in a small sample, multivariate pattern analysis can effectively identify ADHD children from healthy controls based on fNIRS signals, which argues for the potential utility of fNIRS in future assessments.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Córtex Cerebral/metabolismo , Hemodinâmica/fisiologia , Memória de Curto Prazo/fisiologia , Desempenho Psicomotor/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Córtex Cerebral/fisiopatologia , Criança , Feminino , Humanos , Masculino , Distribuição Aleatória , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
Current studies indicate that microRNAs (miRNAs) are widely decreased in various tumors and function as tumor suppressors by inhibiting cancer cell proliferation, survival, invasion, and migration. The potential application of using miRNAs to predict therapeutic responses to multiple types of cancer treatment holds high promise. In current study, we demonstrate that miR-3619-5p is downregulated in bladder cancer (BCa) tissues and cells. Exogenous overexpression of miR-3619-5p in BCa cells inhibits proliferation, migration, and invasion. Moreover, a nude mouse xenograft model shows that miR-3619-5p inhibits BCa cell growth. We also demonstrate that miR-3619-5p leads to the activation of p21 by targeting its promoter in BCa cells. Enforced miR-3619-5p expression consistently leads to the downregulation of ß-catenin and cyclin-dependent kinase 2 (CDK2) through predicted binding sites within the ß-catenin and CDK2 3'-untranslated regions (UTRs), respectively. Moreover, ß-catenin and CDK2 knockdown is able to mimic BCa cells growth and metastasis effects induced by overexpressing miR-3619-5p. We further confirm that miR-3619-5p inhibits Wnt-ß-catenin signal pathway and EMT progression in BCa cells. We also found that miR-3619-5p-induced growth arrest and metastasis inhibition are p21-dependent in BCa cells. Taken together, these results confirm that miR-3619-5p plays a tumor suppressive role in BCa by interfering with cell growth and metastasis and may serve as a potential therapeutic target in BCa treatment.
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Quinase 2 Dependente de Ciclina/metabolismo , MicroRNAs/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , beta Catenina/metabolismo , Proliferação de Células/genética , Proliferação de Células/fisiologia , Quinase 2 Dependente de Ciclina/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias da Bexiga Urinária/genética , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia , beta Catenina/genéticaRESUMO
Previous studies showed that miR-373 had the capacity to induce tumor suppressor gene E-cadherin expression in prostate cancer cells. However, whether miR-373 can activate the expression of E-cadherin in human bladder cancer (BCa) cells and inhibit cells remains to be elucidated. Here, we found that both miR-373 and E-cadherin were low expressed in BCa tissues and cell lines, and significantly correlated with tumor stage, grade, and lymph node metastasis. In addition, decreased E-cadherin expression or low expression of both miR-373 and E-cadherin is associated with poor overall survival in patients with BCa. Transfection of miR-373 into BCa cells readily activated E-cadherin expression by targeting promoter. Moreover, miR-373 exhibited robust capacity to inhibit cells proliferation, suppress migration and invasion by enhancing E-cadherin expression, and significantly suppress the growth of xenografts and metastasis in nude mice. Altogether, our findings indicate that miR-373 may as a tumor suppressor in BCa by activating E-cadherin expression.
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Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders in children and affects 3 to 5% of school-aged children. This study is to demonstrate whether functional near-infrared spectroscopy (fNIRS) can detect the changes in the concentration of oxygenated hemoglobin (oxy-HB) in children with ADHD and typically developing children (TD children). Method: In this study, 14 children with ADHD and 15 TD children were studied. Metabolic signals of functional blood oxygen were recorded by using fNIRS during go/no-go task. A statistic method is used to compare the fNIRS between the ADHD children and controls. Results: A significant oxy-HB increase in the left frontopolar cortex (FPC) in control subjects but not in children with ADHD during inhibitory tasks. Moreover, ADHD children showed reduced activation in left FPC relative to TD children. Conclusion: Functional brain imaging using fNIRS showed reduced activation in the left prefrontal cortex (PFC) of children with ADHD during the inhibition task. The fNIRS could be a promising tool for differentiating children with ADHD and TD children.
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Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children. Neuroimaging studies have revealed abnormalities of neural activities in some brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Recently, some investigators have demonstrated that nonlinear complexity analysis of neural activity may provide a new index to indicate ADHD. In the present study, we used the permutation entropy (PE) to measure the complexity of functional near-infrared spectroscopy (fNIRS) signals in children with and without ADHD during a working memory task, it was aimed to investigate the relationship between the PE values and the cortical activations, and the different PE values between the children with and without ADHD. We found that PE values exhibited significantly negative correlation with the cortical activations (r = -0.515, p = 0.003), and the PE values of right dorsolateral prefrontal cortex in ADHD children were significantly larger than those in normal controls (p = 0.027). In addition, the PE values of right dorsolateral prefrontal cortex were positively correlated to the ADHD index (r = 0.448, p = 0.012). These results suggest that complexity analysis of fNIRS signals could be a promising tool in diagnosing children with ADHD.