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1.
J Hazard Mater ; 392: 122230, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32066016

RESUMO

It is difficult to stabilize gaseous elemental mercury (Hg°) on a sorbent from SO2-containing industrial flue gas. Enhancing Hg° oxidation and activating surface-active sulfur (S*) can benefit the chemical mercury adsorption process. A Mn-SnS2 composite was prepared using the Mn modification of SnS2 nanosheets to expose more Mn oxidation and sulfur adsorption sites. The results indicate that Mn-Sn2 exhibits better Hg° removal performances at a wide temperature range of 100-250 °C. A sufficient amount of surface Mn with a valance state of Mn4+ is favorable for Hg° oxidation, while the electron transfer properties of Sn can accelerate this oxidation process. Oxidized mercury primary exists as HgS with surface S*. A larger surface area, stable crystal structure, and active valance state of each element are favorable for Hg° oxidation and adsorption. The Mn-SnS2 exhibits an excellent SO2 resistance when the SO2 concentration is lower than 1500 ppm. The effects of H2O and O2 were also evaluated. The results show that O2 has no influence, while H2O and SO2 coexisting in the flue gas have a toxic effect on the Hg° removal performance. The Mn-SnS2 has a great potential for the Hg° removal from SO2-containing flue gas such as non-ferrous smelting gas.

2.
Fitoterapia ; 140: 104431, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759031

RESUMO

Two novel heptanornemoralisin-type diterpenoids nornemoralisins A (1) and B (2), together with two known compounds nemoralisin (3) and nemoralisin A (4), were isolated from the stem bark and leaves of Aphanamixis polystachya (Wall.) R. Parker. Their structures were established through comprehensive analyses of NMR spectroscopic data and high resolution mass spectrometric (HR-ESI-MS) data. The absolute configurations of carbon stereocenters were elucidated by circular dichroism (CD) analyses. The four compounds were tested for their potential cytotoxic effects against ACHN, HeLa, SMMC-7721, and MCF-7 cell lines. Nornemoralisins A (1) and B (2) exhibited significant cytotoxicity on ACHN with an IC50 value of 13.9 ± 0.8 and 10.3 ± 0.4 µM, respectively, and other compounds failed to reveal obvious cytotoxicity on the tested cell lines, compared to positive control vinblastine (IC50, 28.0 ± 0.9 µM).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Meliaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , China , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Folhas de Planta/química
4.
J Hazard Mater ; : 121824, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31843400

RESUMO

Metal nanoparticles (NPs) have high reaction rate and atom utilization with respect to pollutants in aqueous environments. However, the aggregation and instability in acidic solution limit their practical applications. Mercury removed from acidic solution are still a big problem. In this study, we used a tunable porous covalent organic framework (COF) material as a support for in situ growth of Ag NPs via a one-step solution infiltration method, to enhance the spatial dispersion of NPs and their stability in acidic solution, and for the first time studying the mercury adsorption performance. More importantly, the Ag NPs@COF composite exhibited high removal rate (99 %), ultrahigh Ag atom utilization (150 %), high selectivity and stability, and reusability for Hg(II) removal from acidic aqueous solutions. Meantime, through common characterizations and density functional theory calculations verifying the microscopic adsorption process, we found COF material played an important role in the entire purification process because it provided some electrons to Hg(II) ions via Ag NPs, finally generating an amalgam. Therefore, the present work not only provides a COF-supported Ag NPs material for Hg(II) ions removal from acidic waste water but also opens a new field of design of functionalized COFs material for applications in environmental pollutions control.

5.
Am J Transl Res ; 11(8): 4967-4975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497213

RESUMO

Distal tibiofibular syndesmosis injury (DTS) occurs frequently with ankle sprains. Current treatments pose several limitations including causing soft tissue irritation, bringing damage to fixation secondary to weight-bearing, and requiring follow-up surgeries. Here, we investigated the clinical effects of a new technique, titanium cable isotonic annular fixation, for the treatment of DTS injury. From January 2015 to June 2017, 36 patients with ankle fractures and DTS injuries had their fractures repaired with the titanium cable isotonic annular fixation system. Recovery was scored by the AOFAS ankle function score system. We also assessed the differences in ankle motion between healthy and operative joints, and recorded the complications. All patients recovered from surgery without any serious complications. We followed all the cases for 18-25 months with an average follow-up of 21.26±3.23 months. 12 months after the operation, X-ray images showed that the titanium cables were fixed in the correct position without any fracture or loosening. Additionally, no degeneration or traumatic arthritis was observed in the ankle joint. There were no incision or bone mineral density changes between the titanium fix and tibiofibular bones. Nearly all patients recovered well except for three who developed inflammation and infection. However, these three patients recovered following 1 week of intravenous antibiotics and local radiofrequency physiotherapy. According to the AOFAS scoring system, all patients achieved satisfactory recovery 12 months post operation. Our titanium cable isotonic annular fixation system has both the advantages of elastic and rigid fixations. It can restore isotonic strength of the distal tibiofibular joint, and its biomechanical performance approaches normal physiological function. After the operation, patients tolerated weight-bearing exercise and recovered joint mobility. Finally, there is no need to remove the distal tibiofibular implant after 12 weeks. Overall, it is a highly effective surgical method to treat DTS injury.

6.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480267

RESUMO

Phalaenopsis cultivar 'Panda' is a beautiful and valuable ornamental for its big flower and unique big spots on the petals and sepals. Although anthocyanins are known as the main pigments responsible for flower colors in Phalaenopsis, and the anthocyanins biosynthetic pathway in Phalaenopsis is generally well known, the detailed knowledge of anthocynins regulation within the spot and non-spot parts in 'Panda' flower is limited. In this study, transcriptome and small RNA libraries analysis from spot and non-spot sepal tissues of 'Panda' were performed, and we found PeMYB7, PeMYB11, and miR156g, miR858 is associated with the purple spot patterning in its sepals. Transcriptome analyses showed a total 674 differentially expressed genes (DEGs), with 424 downregulated and 250 upregulated (Non-spot-VS-Spot), and 10 candidate DEGs involved in anthocyanin biosynthetic pathway. The qPCR analysis confirmed that seven candidate structure genes (PeANS, PeF3'H, PeC4H, PeF3H, PeF3H1, Pe4CL2, and PeCHI) have significantly higher expressing levels in spot tissues than non-spot tissues. A total 1552 differentially expressed miRNAs (DEMs) were detected with 676 downregulated and 876 upregulated. However, microRNA data showed no DEMs targeting on anthocyanin biosynthesis structure gene, while a total 40 DEMs target transcription factor (TF) genes, which expressed significantly different level in spot via non-spot sepal, including 2 key MYB regulator genes. These results indicated that the lack of anthocyanidins in non-spot sepal may not directly be caused by microRNA suppressing anthocyanidin synthesis genes rather than the MYB genes. Our findings will help in understanding the role of miRNA molecular mechanisms in the spot formation pattern of Phalaenopsis, and would be useful to provide a reference to similar research in other species.


Assuntos
Flores/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Orchidaceae/genética , Antocianinas/biossíntese , Antocianinas/metabolismo , Mapeamento Cromossômico , Flores/anatomia & histologia , Biblioteca Gênica , Genoma de Planta , MicroRNAs/metabolismo , Modelos Biológicos , Anotação de Sequência Molecular , Orchidaceae/anatomia & histologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
Front Med ; 13(6): 639-645, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31468282

RESUMO

Esophageal cancer-related gene-4 (Ecrg4) is cloned from the normal epithelium of the esophagus. It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis, and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells, validating that Ecrg4 is a real tumor suppressor gene. Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins, Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells, specialized epithelial cells, and human leukocytes, where it can be processed tissue dependently into several small peptides upon cell activation. Ecrg4 is expressed in a wide variety of other cells/tissues, including cardiomyocytes and conduction system of the heart, the glomus cells of the carotid body, adrenal glands, choroid plexus, and leukocytes among others, where it exerts distinct functions, such as promoting/suppressing inflammation, inducing neuron senescence, stimulating the hypothalamus-pituitary-adrenal axis, maintaining the stemness of stem cells, participating in the rhythm and rate control of the heart, and possibly gauging the responsiveness of the cardiovascular system (CVS) to hypoxia, in addition to tumor suppression. Here, we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.

8.
J Cell Mol Med ; 23(9): 6085-6097, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270949

RESUMO

The surged systemic vascular inflammation after acute myocardial infarction (AMI) aggravates the atherosclerotic endothelial injury. To explore roles of miR-499 released from cardiomyocytes during AMI in endothelial injury. Using qPCR and ELISA, we discovered that patients with AMI had significantly increased plasma miR-499, which was directly correlated with serum thrombomodulin, a marker for endothelial injury. Plasma of AMI patients, when incubated with human umbilical vein endothelial cells (HUVECs), significantly increased the expression of endothelial injury markers, which could be abrogated by antagomiR-499. In vitro, neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation (HX/R) released miR-499 that could be internalized into rat pulmonary microvascular endothelial cells (RPMECs), worsening the high glucose-induced injury. In silico analysis demonstrated that CHRNA7 encoding α7-nAchR is a target of miR-499, which was validated in cell lines expressing endogenous α7-nAchR. In high glucose-induced RPMECs injury model, miR-499 aggravated, whereas forced CHRNA7 expression ameliorated the injury. Moreover, the perfusate from Langendorff perfused rat heart subjected to HX/R contained higher level of miR-499 that significantly impaired the Bradykinin-mediated endothelium-dependent relaxation in both conduit and resistance arteries, which could be partially abrogated by antagomiR-499. Finally, the correlation between plasma miR-499 and endothelial injury was further confirmed in another cohort of AMI patients. We conclude that miR-499 released from injured cardiomyocytes contributes to the endothelial injury by targeting α7-nAchR. This study implies that miR-499 may serve as a potential target for the treatment of the surged vascular inflammation post-AMI.

9.
Cell Signal ; 62: 109327, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31152845

RESUMO

Esophageal cancer related gene-4 (ECRG4) inhibits the malignant phenotype of oral squamous cell carcinoma. However, the molecular mechanisms remain to be explored. Using the tongue carcinoma cell line, TCA8113 as a cell model, we showed that forced expression of ECRG4 down-regulated the expression of the BC200 long non-coding RNA (lncRNA) and matrix metalloproteinases (MMP-9 and MMP-13). Restoration of BC200 lncRNA rescued ECRG4-mediated down-regulation of MMP-9 and -13. Furthermore, over-expression of Ecrg4 inhibited cell proliferation and migration, which was abolished by forced expression of BC200 lncRNA in TCA8113 cells. Our results indicate that ECRG4 inhibits the malignant phenotype of TCA8113 cells most likely through suppression of BC200 lncRNA/MMPs signaling pathway, rationalizing that BC200 lncRNA may be a potential target for oral squamous cell carcinoma (OSCC) therapy.

10.
J Cell Biochem ; 120(9): 16153-16159, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31081956

RESUMO

Our previous findings show that insulin-produced cells are found in human pancreatic ducts. However, the underlying molecular mechanism of transdifferentiation in pancreatic ductal cells is not yet totally uncovered. High-fat diet (HFD) and high-glucose diet (HGD) fed mice were subjected to the biochemical tests in sera. And the pancreatic samples were used for immunostaining and immunoblotting assays, respectively. These serological findings showed that fasting blood glucose, insulin, blood lipids (triglyceride, total cholesterol), liver functional enzymes (glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase) were increased in HFD fed mice. Immunostaining observations showed that insulin protein was positively expressed in pancreatic islets and ducts, characterized with elevated immunoreactive cells of insulin, neurogenin-3, poly (ADP-ribose) polymerase (PARP), and reduced F-box/WD repeat-containing protein 7-positive cells in pancreatic islets and ducts of HFD and HGD fed mice. Interestingly, immunoblotting assays suggested that intrapancreatic expressions of insulin, Krüppel-like Factor 2, PARP, p42/44MAPK proteins were upregulated in HFD and HGD exposed mice, while Fbxw7 protein content in pancreas samples were reduced. Taken together, the current findings reveal that there may be potential transdifferentiation of insulin-producing cells in pancreatic ducts through inducing a pathway of intracellular Fbxw7 ubiquitination.

11.
Nat Prod Res ; : 1-5, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30990080

RESUMO

A new isopimarane-type diterpenoid, crolaevinoid A, along with four known analogues was isolated from the twigs and leaves of Croton laevigatus. The structures of the isolated compounds were established on the basis of NMR and MS spectroscopic analyses. The isolated compounds were examined the antibacterial activities. Unfortunately, the compounds showed no antibacterial activity against Micrococcus luteus, Methicillin-resistant Staphylococcus aureus, Aeromonas hydrophila, Klebsiella pneumoniae ssp pneumoniae, Acinetobacter Baumanii, and Escherichia coli.

12.
FASEB J ; 33(6): 7667-7683, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30893559

RESUMO

Current pharmacological intervention for the treatment of osteolytic bone diseases such as osteoporosis focuses on the prevention of excessive osteoclastic bone resorption but does not enhance osteoblast-mediated bone formation. In our study, we have shown that 4-iodo-6-phenylpyrimidine (4-IPP), an irreversible inhibitor of macrophage migration inhibitory factor (MIF), can inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and potentiate osteoblast-mediated mineralization and bone nodule formation in vitro. Mechanistically, 4-IPP inhibited RANKL-induced p65 phosphorylation and nuclear translocation by preventing the interaction of MIF with thioredoxin-interacting protein-p65 complexes. This led to the suppression of late osteoclast marker genes such as nuclear factor of activated T cells cytoplasmic 1, resulting in impaired osteoclast formation. In contrast, 4-IPP potentiated osteoblast differentiation and mineralization also through the inhibition of the p65/NF-κB signaling cascade. In the murine model of pathologic osteolysis induced by titanium particles, 4-IPP protected against calvarial bone destruction. Similarly, in the murine model of ovariectomy-induced osteoporosis, 4-IPP treatment ameliorated the bone loss associated with estrogen deficiency by reducing osteoclastic activities and enhancing osteoblastic bone formation. Collectively, these findings provide evidence for the pharmacological targeting of MIF for the treatment of osteolytic bone disorders.-Zheng, L., Gao, J., Jin, K., Chen, Z., Yu, W., Zhu, K., Huang, W., Liu, F., Mei, L., Lou, C., He, D. Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF-κB signaling pathway.

13.
Medicine (Baltimore) ; 97(36): e12183, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30200123

RESUMO

RATIONALE: In 1891, Dr. Hermann Kümmell, a German surgeon, described a clinical entity characterized by the development of progressive painful kyphosis following an asymptomatic period of months or years after a minor spinal trauma, leading to a gradual collapse of the vertebra and dynamic instability, ultimately progressing to kyphosis with prolonged back pain and/or paraparesis. To date, the main pathologic eliciting event remains unclear, and no standard treatment or single effective treatment are available for Kümmell disease. PATIENT CONCERNS: A 74-year-old woman presented with severe back pain and numbness of both legs for approximately 2 months. DIAGNOSES: According to the clinical symptoms and imaging examinations, the patient was diagnosed with stage III Kümmell disease. INTERVENTIONS: The patient underwent titanium mesh bone grafting combined with pedicle screw internal fixation. OUTCOMES: Postoperative kyphosis was corrected, and the vertebra was reconstructed. LESSONS: Kümmell disease is not a rare complication of osteoporotic vertebral compression fractures, and treatment of each patient must be individualized. The application of titanium mesh bone grafting combined with pedicle screw internal fixation is an effective treatment option for stage III Kümmell disease.


Assuntos
Dor nas Costas/cirurgia , Transplante Ósseo , Fixação Interna de Fraturas/métodos , Cifose/cirurgia , Compressão da Medula Espinal/cirurgia , Idoso , Dor nas Costas/diagnóstico por imagem , Dor nas Costas/etiologia , Feminino , Humanos , Hipestesia/diagnóstico por imagem , Hipestesia/etiologia , Hipestesia/cirurgia , Cifose/complicações , Cifose/diagnóstico por imagem , Parafusos Pediculares , Compressão da Medula Espinal/complicações , Compressão da Medula Espinal/diagnóstico por imagem , Telas Cirúrgicas , Titânio
14.
Cancer Gene Ther ; 25(9-10): 248-259, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29983418

RESUMO

Esophageal cancer related gene-4 (Ecrg4) has been shown to be a tumor suppressor in many organs. Exosomes are naturally secreted nanosized particles that carry signal molecules including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) among others. Upon internalization, exosomes unload their cargos that in turn modulate the biology of the recipient cells. Mounting evidence has shown that exosomal miRNAs are functional. However, reports that exosomes carry functional mRNAs remain scarce. We found that serum exosomes contain ECRG4 open reading frame. To simulate serum exosomal ECRG4, stable cell line expressing ECRG4 was created, from which exosomes were isolated and characterized, and the internalization and the resulting biological effects of exosomal ECRG4 were evaluated. Results showed that serum exosomes contain higher levels of ECRG4 mRNA in healthy individuals than their cancer counterparts. Exosomal ECRG4 can be internalized and unload the encapsulated ECRG4 into recipient cells, which subsequently suppressed cell proliferation in vitro, and inhibited tumor growth in a xenograft mouse model. Mechanistically, ECRG4-containing exosomes, when internalized, suppressed the expression of genes commonly implicated in inflammation, cell proliferation, and angiogenesis. Given that exosome is an ideal vehicle for therapeutics delivery and that ECRG4 is a tumor suppressor gene, the exosomal ECRG4 can be exploited as a formulation for cancer gene therapy.


Assuntos
Proliferação de Células , Exossomos/metabolismo , Genes Supressores de Tumor , Proteínas de Neoplasias/sangue , Neoplasias , Neovascularização Patológica/sangue , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Células A549 , Animais , Exossomos/patologia , Feminino , Células HEK293 , Humanos , Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/sangue , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Neovascularização Patológica/patologia , Proteínas Supressoras de Tumor
15.
J Cell Physiol ; 233(12): 9724-9738, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30059597

RESUMO

Osteoporosis (OP) is a serious metabolic disease that, due to the increased number or function of osteoclasts, results in increased bone brittleness and, therefore, fragile fracture. Some recent studies report the importance of the transforming growth factor ß (TGFß) pathway in bone homeostasis. RepSox is a small molecule inhibitor of TGFßRI that has a wide range of potential application in clinical medicine, except OP. The aim of our study is to evaluate the effects of RepSox on the differentiation and bone resorption of osteoclasts in vitro and in vivo in an ovariectomy (OVX)-induced OP model. An initial analysis showed TGFßRI messenger RNA expression in both bone samples and bone cells. In the in vitro study, RepSox inhibited the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation and bone resorption activity. Real-time polymerase chain reaction (PCR) analysis showed that RepSox suppressed osteoclastic marker gene expression in both dose-dependent and time-dependent manners. In addition, RepSox did not affect osteoblast differentiation, migration or osteoblastic-specific gene expression in vitro. Furthermore, western blot analysis indicated the underlying mechanisms of the RepSox suppression of osteoclastogenesis via the Smad3 and c-Jun N-terminal kinase/activator protein-1 (JNK/AP-1) signaling pathways. Finally, our animal experiments revealed that RepSox prevented OVX-induced bone loss in vivo. Together, our data suggest that RepSox regulates osteoclast differentiation, bone resorption, and OVX-induced OP via the suppression of the Smad3 and JNK/AP-1 pathways.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Osteoporose/tratamento farmacológico , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Proteína Smad3/genética , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Camundongos , Osteoclastos/efeitos dos fármacos , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/patologia , Ovariectomia/efeitos adversos , Ligante RANK/genética , Bibliotecas de Moléculas Pequenas/administração & dosagem , Fator de Transcrição AP-1/genética , Fator de Crescimento Transformador beta/genética
16.
Org Lett ; 20(4): 1158-1161, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29420039

RESUMO

A bifunctional squaramide-catalyzed reaction of pyrazolin-5-ones with o-quinone methides in situ generated from 2-(1-tosylalkyl)phenols has been successfully developed, providing a facile access to chiral pyrazolones with high enantioselectivities. In addition, the chiral spiropyrazolones with adjacent tertiary and quaternary stereogenic centers can also be obtained through cascade chlorination/cyclization of the chiral pyrazolones.

18.
Gene ; 642: 26-31, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29126922

RESUMO

Epidemiogical evidence has shown that the incidence of atrial fibrillation in tumor patients is higher than non-tumor patients and general population. The potential risk factors predisposing tumor patients to atrial fibrillation include advanced age, comorbidities, direct anatomic local occupying effect of tumors in the heart or adjacent organs, paraneoplastic manifestations of some tumors, tumor-induced dys-regulation of metabolism, radio-, bio- and chemo-therapeutics, disturbance of autonomous nerve system because of physical pain and psychological sufferings, chronic inflammation typical of most tumors, and surgical interventions among others. However, whether tumor suppressor genes commonly mutated or dys-regulated in tumor play any roles in the pathogenesis of atrial fibrillation remain largely unexplored. Tumor suppressor genes or genes possessing tumor suppressing function have been reported to be constitutively expressed in quiescent heart, and mutations, small nucleotide polymorphisms, or disturbed expression of tumor suppressor genes has been implicated in the pathogenesis of atrial fibrillation. Here, we provide a state-of-the-art overview of the unrecognized roles of tumor suppressor genes in the pathogenesis of atrial fibrillation, focusing mainly on the two well-characterized tumor suppressor genes, zinc finger homeobox protein-3 and esophageal cancer related gene-4.


Assuntos
Fibrilação Atrial/genética , Proteínas de Homeodomínio/genética , Proteínas de Neoplasias/genética , Neoplasias/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Mutação , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Polimorfismo Genético , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
19.
Oncotarget ; 8(59): 100045-100055, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29245959

RESUMO

A low dose of formononetin accelerates the proliferation of nasopharyngeal carcinoma cells in vitro; however, the underlying mechanism remains unknown. Here, we investigated the molecular mechanism of formononetin in CNE2 cell proliferation. CNE2 cells were treated with 0 to 1 µM formononetin. To inhibit mitogen activated protein kinase / extracellular regulate kinase (MAPK/ERK) kinase (MEK) and microRNA (miR)-375, cells were pretreated with either PD98059 or a miR-375 inhibitor, respectively, followed by co-treatment with formononetin (0.3 µM) plus an inhibitor. Female rats were ovariectomized (OVX), and some OVX rats received formononetin or estrogen (E2) injections. Sham operated animals were used as controls. Compared to control, 0.3 µM formononetin accelerated proliferation and decreased late apoptosis of CNE2 cells. However, formononetin-induced pro-growth and anti-apoptosis activity was abolished by PD98059 and the miR-375 inhibitor. In addition, 0.1 and 0.3 µM formononetin significantly increased estrogen receptor-α (ERα) and bcl-2, but decreased protein-phosphatase and tensin homologue (PTEN) protein expression, all of which was reversed by the miR-375 inhibitor. Additionally, formononetin treatment resulted in a transient upregulation of phosphorylated (p)-ERK1/2. In vivo studies indicated that formononetin significantly increased endometrium thickness and down-regulated ERα expression in OVX rats. Taken together, our study demonstrates that a low concentration of formononetin can promote growth of CNE2 cells and uterine tissues, possibly through regulating the ERα-miR-375-PTEN-ERK1/2-bcl-2 signaling pathway.

20.
Front Plant Sci ; 8: 1274, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769969

RESUMO

Epimedium species have been widely used both as traditional Chinese medicinal plants and ornamental perennials. Both flavonols, acting as the major bioactive components (BCs) and anthocyanins, predominantly contributing to the color diversity of Epimedium flowers belong to different classes of flavonoids. It is well-acknowledged that flavonoid biosynthetic pathway is predominantly regulated by R2R3-MYB transcription factor (TF) as well as bHLH TF and WD40 protein at the transcriptional level. MYB TFs specifically regulating anthocyanin or flavonol biosynthetic pathway have been already isolated and functionally characterized from Epimedium sagittatum, but a R2R3-MYB TF involved in regulating both these two pathways has not been functionally characterized to date in Epimedium plants. In this study, we report the functional characterization of EsMYB9, a R2R3-MYB TF previously isolated from E. sagittatum. The previous study indicated that EsMYB9 belongs to a small subfamily of R2R3-MYB TFs containing grape VvMYB5a and VvMYB5b TFs, which regulate flavonoid biosynthetic pathway. The present studies show that overexpression of EsMYB9 in tobacco leads to increased transcript levels of flavonoid pathway genes and increased contents of anthocyanins and flavonols. Yeast two-hybrid assay indicates that the C-terminal region of EsMYB9 contributes to the autoactivation activity, and EsMYB9 interacts with EsTT8 or AtTT8 bHLH regulator. Transient reporter assay shows that EsMYB9 slightly activates the expression of EsCHS (chalcone synthase) promoter in transiently transformed leaves of Nicotiana benthamiana, but the addition of AtTT8 or EsTT8 bHLH regulator strongly enhances the transcriptional activation of EsMYB9 against five promoters of the flavonoid pathway genes except EsFLS (flavonol synthase). In addition, co-transformation of EsMYB9 and EsTT8 in transiently transfected tobacco leaves strongly induces the expressions of flavonoid biosynthetic genes. The potential role of EsMYB9 in modulating the biosynthesis and accumulation of sucrose-induced anthocyanin and flavonol-derived BCs is also discussed. These findings suggest that EsMYB9 is a novel R2R3-MYB TF, which regulates the flavonoid biosynthetic pathway in Epimedium, but distinctly different with the anthocyanin or flavonol-specific MYB regulators identified previously in Epimedium plants.

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