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1.
Huan Jing Ke Xue ; 41(6): 2679-2687, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608783

RESUMO

Picophytoplankton (<3 µm), comprising picocyanobacteria (PCY) and photosynthetic picoeukaryotes (PPEs), are considerably important in the material circulation and energy flow of aquatic ecosystems. To explore the temporal and spatial variation patterns of picophytoplankton and their correlations with environmental factors in lotic Yangtze-connected lakes, field in-situ investigations were performed on a monthly basis during the wet season (May to August) in 2019 in East Lake Dongting, a Yangtze-connected lake. The results indicated that both the Chla biomass and abundances of picophytoplankton exhibited significant spatial and temporal variability (P<0.05). The picophytoplankton Chla biomass showed an average concentration of 8.52 µg·L-1 and accounted for 41.6% to total phytoplankton on an average. From May to August, Chla biomass of picophytoplankton kept increasing with increasing temperature, especially in the north and south of the lake, and it was the lowest in the east of the lake. PCY dominated picophytoplankton abundance in East Lake Dongting and was 3.4 times the abundance of PPEs on an average. Similar spatial and temporal variation patterns were observed between PCY and PPEs. The abundances of PCY and PPEs both increased first and then decreased during the wet season. Spatially, picophytoplankton showed a trend to migrate from the northern lake to the southern lake from May to July, and the abundance significantly declined in August and peaked mainly in the north of the lake. The analysis results showed that picophytoplankton in East Lake Dongting exhibited significant spatial and temporal variability during the wet season; the water level and N:P ratio were determined to be the most important factors explaining the variation of the abundance proportion of PCY and PPEs.


Assuntos
Ecossistema , Lagos , China , Monitoramento Ambiental , Fotossíntese , Fitoplâncton , Estações do Ano
2.
Cell Death Dis ; 11(7): 571, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709922

RESUMO

Oxysterol-binding protein like protein 3 (OSBPL3) has been shown involving in the development of several human cancers. However, the relationship between OSBPL3 and colorectal cancer (CRC), particularly the role of OSBPL3 in the proliferation, invasion and metastasis of CRC remains unclear. In this study, we investigated the role of OSBPL3 in CRC and found that its expression was significantly higher in CRC tissues than that in normal tissues. In addition, high expression of OSBPL3 was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of OSBPL3 promoted the proliferation, invasion and metastasis of CRC in vitro and in vivo models. Moreover, we revealed that OSBPL3 promoted CRC progression through activation of RAS signaling pathway. Furthermore, we demonstrated that hypoxia induced factor 1 (HIF-1A) can regulate the expression of OSBPL3 via binding to the hypoxia response element (HRE) in the promoter of OSBPL3. In summary, Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. This novel mechanism provides a comprehensive understanding of both OSBPL3 and the RAS signaling pathway in the progression of CRC and indicates that the HIF1A-OSBPL3-RAS axis is a potential target for early therapeutic intervention in CRC progression.

3.
Stem Cell Res Ther ; 11(1): 41, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996252

RESUMO

Adipocytes arising from mesenchymal stem cells (MSCs) requires MSC adipocyte commitment and differentiation of preadipocytes to mature adipocytes. Several signaling and some cytokines affect the adipogenesis of MSCs. This review focuses on the roles of TGF-ß/SMAD signaling in adipocyte commitment of MSCs. BMP4 and BMP7 signaling are sufficient to induce adipocyte lineage determination of MSCs. The roles of BMP2, TGF-ß, and myostatin signaling in this process are unclear. Other TGF-ß/SMAD signaling such as BMP3 and BMP6 signaling have almost no effect on commitment because of limited research available, while GDF11 signaling inhibits adipocyte commitment in human MSCs. In this review, we summarize the available information on TGF-ß/SMAD signaling regulation of MSCs in adipocyte commitment. Deeper study of this commitment mechanism will offer new approaches in treating obesity, diabetes mellitus, and obesity-related metabolism syndrome.

4.
Front Neurosci ; 13: 584, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258460

RESUMO

Spinal cord edema, mainly including vasogenic and cytotoxic edema, influences neurological outcome after spinal cord contusion (SCC). Aquaporin 4 (AQP4) is the most ubiquitous water channel in the central nervous system (CNS), which is a rate-limiting factor in vasogenic edema expressing in brain injury, and it contributes to the formation of cytotoxic edema locating in astrocytes. However, little is known about the regulatory mechanism of AQP4 within vasogenic and cytotoxic edema in SCC, and whether the regulation mechanism of AQP4 is related to Cytochrome coxidase (COX5A) affecting energy metabolism. Therefore, the SCC model is established by Allen's method, and the degree of edema and neuronal area is measured. The motor function of rats is evaluated by the Basso, Beattie, and Bresnahan (BBB) scoring system. Meanwhile, AQP4 and COX5A are detected by real-time quantitative PCR (qRT-PCR) and western blot (WB). The localization of targeted protein is exhibited by immunohistochemical staining (IHC) and immunofluorescence (IF). Additionally, the methodology of AQP4 lentivirus-mediated RNA interference (AQP4-RNAi) is used to reveal the effect on edema of SCC and the regulating molecular mechanism. Firstly, we observe that the tissue water content increases after SCC and decreases after the peak value of tissue water content at 3 days (P < 0.05) with abundant expression of AQP4 protein locating around vascular endothelial cells (VECs), which suggests that the increasing AQP4 promotes water reabsorption and improves vasogenic edema in the early stage of SCC. However, the neuronal area is larger than in the sham group in the 7 days (P < 0.05) with the total water content of spinal cord decrease. Meanwhile, AQP4 migrates from VECs to neuronal cytomembrane, which indicates that AQP4 plays a crucial role in aggravating the formation and development of cytotoxic edema in the middle stages of SCC. Secondly, AQP4-RNAi is used to elucidate the mechanism of AQP4 to edema of SCC. The neuronal area shrinks and the area of cytotoxic edema reduces after AQP4 downregulation. The BBB scores are significantly higher than in the vector group after AQP4-RNAi at 5, 7, and 14 (P < 0.05). There is a relationship between AQP4 and COX5A shown by bioinformatics analysis. After AQP4 inhibition, the expression of COX5A is significantly upregulated in the swelling astrocytes. Therefore, the inhibition of AQP4 expression reduces cytotoxic edema in SCC and improves motor function, which may be associated with upregulation of COX5A via affecting energy metabolism. Moreover, it is not clear how the inhibition of AQP4 directly causes the upregulation of COX5A.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31234355

RESUMO

Before being administered as medicinal products, Chinese herbal medicines (CHMs) must be processed and decocted for human consumption. While the presence of pesticide residues in CHMs is a major concern, pesticide dissipation behavior during CHM processing has rarely been reported. In this study, the dissipation of three pesticide residues in the CHM Paeoniae Radix Alba (PRA) was investigated during each step of industrial processing. The boiling process was found to significantly reduce pesticide residues (61-89%), and the peeling process also contributed to pesticide degradation (29-68%). The high temperature (60 °C) during the drying process led to further pesticide degradation. The processing factors of all three pesticides after each processing step were less than one, and the processing factors for the overall process were lower than 0.027, indicating that industrial processing clearly reduced the amount of pesticide residues (97.3-99.4%). The findings provide guidance for the safe use of fungicides in CHMs and can help establish maximum residue limits for PRA to reduce human exposure to pesticides.


Assuntos
Medicamentos de Ervas Chinesas/química , Fungicidas Industriais/química , Paeonia/química , Indústria Química , Temperatura Alta , Humanos , Resíduos de Praguicidas/análise
6.
Lab Invest ; 99(8): 1143-1156, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30911150

RESUMO

Acute respiratory distress syndrome (ARDS) is a uniform progression of overwhelming inflammation in lung tissue with extensive infiltration of inflammatory cells. Neutrophil apoptosis is thought to be a significant process in the control of the resolution phase of inflammation. It has been proved that 5-Aza-2'-deoxycytidine (Aza) can inhibit cancer by activating death-associated protein kinase 1 (DAPK1) to promote apoptosis. However, the effect of DAPK1 on neutrophil apoptosis is unclear, and research on the role of Aza in inflammation is lacking. Here, we investigated whether Aza can regulate DAPK1 expression to influence the fate of neutrophils in ARDS. In vitro, we stimulated neutrophil-like HL-60 (dHL-60) cells with different concentrations of Aza for different durations and used RNA interference to up- or downregulate DAPK1 expression. We observed that culturing dHL-60 cells with Aza increased apoptosis by inhibiting NF-κB activation to modulate the expression of Bcl-2 family proteins, which was closely related to the levels of DAPK1. In vivo, ARDS was evoked by intratracheal instillation of lipopolysaccharide (LPS; 3 mg/kg). One hour after LPS administration, mice were treated with Aza (1 mg/kg, i.p.). To inhibit DAPK1 expression, mice were intraperitoneally injected with a DAPK1 inhibitor. Aza treatment accelerated inflammatory resolution in LPS-induced ARDS by suppressing pulmonary edema, alleviating lung injury and decreasing the infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF). Moreover, Aza reduced the production of proinflammatory cytokines. However, administration of the DAPK1 inhibitor attenuated the protective effects of Aza. Similarly, the proapoptotic function of Aza was prevented when DAPK1 was inhibited either in vivo or in vitro. In summary, Aza promotes neutrophil apoptosis by activating DAPK1 to accelerate inflammatory resolution in LPS-induced ARDS. This study provides the first evidence that Aza prevents LPS-induced neutrophil survival by modulating DAPK1 expression.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases Associadas com Morte Celular , Inflamação/metabolismo , Neutrófilos/efeitos dos fármacos , /metabolismo , Animais , Citocinas/metabolismo , Proteínas Quinases Associadas com Morte Celular/metabolismo , Proteínas Quinases Associadas com Morte Celular/farmacologia , Decitabina/metabolismo , Decitabina/farmacologia , Modelos Animais de Doenças , Células HL-60 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
7.
Int Immunopharmacol ; 69: 289-298, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30753968

RESUMO

The timely resolution of pulmonary inflammation coordinated by endogenous pro-resolving mediators helps limit lung tissue injury, but few endogenous pro-resolving mediators that are normally operative during acute inflammation. The protective effects of BML-111 (5(S)-6(R)-7-trihydroxyheptanoic acid methyl ester), a potent commercially available anti-inflammatory and pro-resolving mediator, on ventilation-induced lung injury (VILI) have been extensively studied, but its characteristics as a pro-resolving mediator have not. Here, anesthetized Sprague-Dawley rats were ventilated with a high tidal volume (20 mL/kg, HVT) for 1 h and randomly allocated to recover for 6, 12, 24, 48, 72, 96 or 168 h; BML-111 was administered at the peak of inflammation to evaluate its pro-resolving effect on VILI. The one-hour HVT induced a maximal pulmonary inflammatory response at 12 h that was largely resolved by 72 h. BML-111 largely resolved the maximal inflammatory response at 48 h; the resolution interval (Ri) was shortened by 26 h. Similarly, HVT elicited a time course of changes in histopathology and pulmonary edema, and BML-111 alleviates these changes. Mechanistically, neutrophil apoptosis was significantly increased in BML-111-treated rats subjected to HVT. The apoptosis inhibitor z-VAD-fmk partially reversed the proapoptotic actions of BML-111 on neutrophil and the resolving effects of BML-111 on VILI but had no effect alone. Importantly, the HVT treatment activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) and NF-κB signaling pathways in the lung tissue, and BML-111 further induced Nrf2 and HO-1 expression but inhibited the NF-κB pathway. Intriguingly, when we inhibited the Nrf2/HO-1 pathway with the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX), Nrf2 expression was further increased, but the inhibitory effects of BML-111 on the NF-κB pathway and on the subsequent inflammatory response, and the proapoptotic actions on neutrophil were reversed. The results suggest that BML-111 promotes the resolution of HVT-induced inflammation to mitigate VILI in rats, perhaps by modulating the Nrf2/HO-1 and NF-κB pathways and subsequently increasing neutrophil apoptosis.


Assuntos
Ácidos Heptanoicos/uso terapêutico , Inflamação/tratamento farmacológico , Pulmão/efeitos dos fármacos , Neutrófilos/patologia , Lesão Pulmonar Induzida por Ventilação Mecânica/tratamento farmacológico , Animais , Apoptose , Células Cultivadas , Modelos Animais de Doenças , Heme Oxigenase-1/metabolismo , Humanos , Pulmão/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Protoporfirinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
8.
J Pharm Biomed Anal ; 161: 20-27, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30142493

RESUMO

In Traditional Chinese Medicine (TCM), crude herbs are processed to obtain the medicinal parts of the plant, from which extracts are prepared for people to take as medicine. However, there is no report on the pesticide residual behavior in Chinese medicines during processing at present, and thus, a systematic study of the effects of different processing factors (PF) on pesticide removal in Chinese medicines and the associated risk of dietary exposure is urgently needed. This study main investigated the dissipation and metabolism of pesticides in Chinese medicine Paeoniae Radix Alba during processing, and the calculated pesticide PFs were also used to assess the risk of dietary exposure. For analyze samples, a simple and high-throughput multiresidue pesticide analysis method was developed and validated for pesticides and their metabolites in P. Radix. based on QuEChERS procedure combined with HPLC-MS/MS. Recoveries at three concentration levels were within 61.37%-117.82% with an associated precision RSD < 15% indicating satisfactory accuracy. TCM processing could be useful for the partial removal of several pesticide residues, with removal rate reaching 98%. The polarity is the dominant variable, which with a high contribution was the effectiveness of the treatment and the concentration factors for pesticides. The hazard quotients of all pesticides were much lower than the safety level, indicating low risk of dietary exposure. Results are of great theoretical and practical value for the scientific evaluation of the safety of Chinese medicines, improvement of the quality and safety level of Chinese medicine.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Paeonia/metabolismo , Praguicidas/farmacocinética , Cromatografia Líquida de Alta Pressão , Substâncias Perigosas/análise , Espectrometria de Massas em Tandem
9.
J Biotechnol ; 281: 144-149, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30016740

RESUMO

4-vinylguaiacol, a kind of volatile phenolic compound with tobacco flavor, is widely used as a component of edible flavor and intermediate of medicine. Ferulic acid is usually used as substrate for the biosynthesis of 4-vinylguaiacol. However, the price of ferulic acid is high, leading to high production cost. In this study, a feasible low-cost process for the production of 4-vinylguaiacol was developed. The ultrasonic assisted weak alkali was used to extract protein from rice bran, and waste liquid and residue were then mixed to extract crude ferulic acid by alkaline hydrolysis. Subsequently crude ferulic acid without further purification was directly converted into 4-vinylguaiacol via alginate-immo cells of the strain Bacillus licheniformis DLF-17056, which was newly isolated and highly active with ferulic acid conversion to 4-vinylguaiacol. 4-Vinylguaiacol could be produced up to 0.76 g/L from 1.0 g/L ferulic acid within 24 h biotransformation. Furthermore, the immobilized biocatalysts retained above 60% initial activity even after 8 times biotransformations. Thereby, it was assumed that our study would contribute to the industrial production of 4-vinylguaiacol from ferulic acid.


Assuntos
Bacillus licheniformis/metabolismo , Ácidos Cumáricos/metabolismo , Guaiacol/análogos & derivados , Alginatos , Bacillus licheniformis/genética , Biocatálise , Biotransformação , Células Imobilizadas/metabolismo , DNA Ribossômico/genética , Ácido Glucurônico , Guaiacol/metabolismo , Ácidos Hexurônicos , Oryza/química
10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(5): 602-610, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29125100

RESUMO

Objective To observe the effects of force signals and inflammatory cytokines on the expressions of functional proteins during the differentiation of periodontal ligament cells(PDLCs) into osteoclasts. Methods The caries-free premolars that needed to be removed for orthodontic treatment were collected,human periodontal ligament cells were cultured in vitro.Human PDLCs were exposed to inflammatory cytokines including interleukin(IL)-1ß,-6,-23,and tumor necrosis factor alpha(TNF-α). Cyclicmechanical tension with a maximum 5% elongation for different durations(0,2,4,8,12,and 24 hours) were applied. Then the expressions of signaling molecules related to osteoclastogenesis(OPG) and receptor activated nuclear factor κB ligand(RANKL) were determined at protein levels by Western blotting. Results Inflammatory cytokines improved the expressions of osteoclastgenesis regulators in hPDLCs,while cyclic-tension force reduced their expressions. However,the combined effect of inflammatory cytokines and cyclic-tension force resulted in high expressions of osteoclastgenesis regulators. Conclusion Inflammatory cytokines can promote the expressions of the osteoclastgenic factors,which can not be offset by cyclic-tension force.


Assuntos
Interleucinas/farmacologia , Osteoclastos/citologia , Osteogênese , Ligamento Periodontal/citologia , Estresse Mecânico , Fator de Necrose Tumoral alfa/farmacologia , Diferenciação Celular , Células Cultivadas , Humanos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo
11.
Int J Syst Evol Microbiol ; 67(10): 3739-3743, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28884674

RESUMO

The Gram-stain-negative, rod-shaped, strictly aerobic, motile bacterial strain, designated YM155T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain YM155T was related to the genus Thalassotalea and had highest 16S rRNA gene sequence similarities with the type strains of Thalassotalea piscium T202T (97.2 %) and Thalassotalea agariperforans M-M1T (97.2 %). The predominant cellular fatty acids were C17 : 1ω8c, summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1ω7c) and iso-C16 : 0. Ubiquinone 8 (Q-8) was the respiratory quinone. The polar lipid profile contained phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and one unidentified lipid. The genomic DNA G+C content of strain YM155T was 36.1 mol%. On the basis of the evidence presented in this study, strain YM155T represents a novel species of the genus Thalassotalea, for which we propose the name Thalassotalea profundi sp. nov. (type strain YM155T=KACC 18563T=CGMCC 1.15922T).


Assuntos
Gammaproteobacteria/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/genética , Gammaproteobacteria/isolamento & purificação , Oceano Pacífico , Fosfatidilgliceróis/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
12.
Int J Syst Evol Microbiol ; 67(6): 1996-2000, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28629507

RESUMO

A Gram-stain-negative, rod-shaped, strictly aerobic, motile bacterial strain, designated YM319T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain YM319T was related to the genus Oceanisphaera and had highest 16S rRNA gene sequence similarities with the type strains Oceanisphaera profunda SM1222T (97.4 %), Oceanisphaera sediminis TW92T (97.3 %) and Oceanisphaera ostreae T-w6T (97.1 %). The predominant cellular fatty acids were summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1 ω7c), C16 : 0 and C18 : 1ω7c. Strain YM319T had Q-8 as the predominant ubiquinone. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and four unidentified lipids. The genomic DNA G+C content of strain YM319T was 54.8 mol%. On the basis of the evidence presented in this study, strain YM319T represents a novel species of the genus Oceanisphaera, for which we propose the name Oceanisphaera marina sp. nov. (type strain YM319T=KACC 18564T=CGMCC 1.15923T).


Assuntos
Aeromonadaceae/classificação , Filogenia , Água do Mar/microbiologia , Aeromonadaceae/genética , Aeromonadaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Oceano Pacífico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
13.
Sci Rep ; 7: 46078, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28470188

RESUMO

Response gene to complement 32 (RGC32) is a transcription factor that regulates the expression of multiple genes involved in cell growth, viability and tissue-specific differentiation. However, the role of RGC32 in tumorigenesis and tumor progression in colorectal cancer (CRC) has not been fully elucidated. Here, we showed that the expression of RGC32 was significantly up-regulated in human CRC tissues versus adjacent normal tissues. RGC32 expression was significantly correlated with invasive and aggressive characteristics of tumor cells, as well as poor survival of CRC patients. We also demonstrated that RGC32 overexpression promoted proliferation, migration and tumorigenic growth of human CRC cells in vitro and in vivo. Functionally, RGC32 facilitated epithelial-mesenchymal transition (EMT) in CRC via the Smad/Sip1 signaling pathway, as shown by decreasing E-cadherin expression and increasing vimentin expression. In conclusion, our findings suggested that overexpression of RGC32 facilitates EMT of CRC cells by activating Smad/Sip1 signaling.


Assuntos
Proteínas de Ciclo Celular/genética , Neoplasias Colorretais/genética , Transição Epitelial-Mesenquimal , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Musculares/metabolismo , Invasividade Neoplásica , Fenótipo , Análise de Sobrevida , Regulação para Cima/genética
14.
Hepatology ; 65(4): 1206-1221, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27809333

RESUMO

Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. CONCLUSION: There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221).


Assuntos
Carcinoma Hepatocelular/genética , Fator 4 Nuclear de Hepatócito/genética , Neoplasias Hepáticas/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Biópsia por Agulha , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfoproteínas/genética , Distribuição Aleatória , Ratos , Ratos Wistar , Sensibilidade e Especificidade , Transdução de Sinais , Fatores de Transcrição/genética
15.
Oncotarget ; 7(47): 77306-77318, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27764793

RESUMO

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-ß3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-ß3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-ß3/SMAD-mediated EMT of CRC cells.


Assuntos
Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Camundongos , Transplante de Neoplasias , Prognóstico , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Regulação para Cima
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 38(1): 22-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26956851

RESUMO

OBJECTIVE: To investigate the expression and effect of Connexin43 (Cx43) on tensile tension-stimulated osteogenic transcription factors of human periodontal ligament fibroblasts (hPDLFs). METHODS: After hPDLFs were treated with 5% elongation tension for 1 h, 2 h, 4 h, 8 h, and 24 h, we examined the expressions of Cx43, Osterix, and RUNX2 at the mRNA level. After Cx43 expression was suppressed by siRNA or 18α-GA, the changes The mRNA in hPDLFs of Osterix and RUNX2 were observed. RESULTS: The expressions of Cx43, Osterix, and RUNX2 mRNA in hPDLFs increased in a time-dependent fashion following tensile strain (all P<0.05), with the highest level at 5% elongation for 24 h. After Cx43 expression was blocked by two different methods, the increasing expressions of Osterix and RUNX2 were inhibited. CONCLUSIONS: 5% cyclic tension upregulates Cx43 expression and promotes the expression of Osterix and RUNX2 in a time-dependent manner. Cx43 may be involved in the osteogenic response of hPDLFs to mechanical tension.


Assuntos
Fibroblastos , Ligamento Periodontal , Células Cultivadas , Conexina 43 , Ácido Glicirretínico/análogos & derivados , Humanos , Osteogênese , RNA Mensageiro , RNA Interferente Pequeno , Estresse Mecânico , Fatores de Transcrição , Regulação para Cima
17.
Oncotarget ; 7(10): 11733-43, 2016 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-26887056

RESUMO

Our earlier findings indicate that the long non-coding RNA MALAT1 promotes colorectal cancer (CRC) cell proliferation, invasion and metastasis in vitro and in vivo by increasing expression of AKAP-9. In the present study, we investigated the molecular mechanism by which MALAT1 enhances AKAP9 expression in CRC SW480 cells. We found that MALAT1 interacts with both SRPK1 and SRSF1. MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation. Following MALAT1 knockdown, overexpression of SRPK1 was sufficient to restore SRSF1 phosphorylation and AKAP-9 expression to a level that promoted cell proliferation, invasion and migration in vitro. Conversely, SRPK1 knockdown after overexpression of MALAT1 in SW480 cells diminished SRSF1 phosphorylation and AKAP-9 expression and suppressed cell proliferation, invasion and migration in vitro. These findings suggest MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in CRC cells. These results reveal a novel molecular mechanism by which MALAT1 regulates AKAP-9 expression in CRC cells.


Assuntos
Proteínas de Ancoragem à Quinase A/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Processamento de Serina-Arginina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Fosforilação , RNA Longo não Codificante/genética , Fatores de Processamento de Serina-Arginina/genética , Transfecção
18.
Gastroenterology ; 150(3): 659-671.e16, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26619963

RESUMO

BACKGROUND & AIMS: Activation of WNT signaling promotes the invasive activities of several types of cancer cells, but it is not clear if it regulates the same processes in colorectal cancer (CRC) cells, or what mechanisms are involved. We studied the expression and function of OVOL2, a member of the Ovo family of conserved zinc-finger transcription factors regulated by the WNT signaling pathway, in intestinal tumors of mice and human beings. METHODS: We analyzed the expression of OVOL2 protein and messenger RNA in CRC cell lines and tissue arrays, as well as CRC samples from patients who underwent surgery at Xiamen University in China from 2009 to 2012; clinical information also was collected. CRC cell lines (SW620) were infected with lentivirus expressing OVOL2, analyzed in migration and invasion assays, and injected into nude mice to assess tumor growth and metastasis. Tandem affinity purification was used to purify the OVOL2-containing complex from CRC cells; the complex was analyzed by liquid chromatography, tandem mass spectrometry, and immunoprecipitation experiments. Gene promoter activities were measured in luciferase reporter assays. We analyzed mice with an intestine-specific disruption of Ovol2 (Ovol2(flox/+) transgenic mice), as well as Apc(min/+) mice; these mice were crossed and analyzed. RESULTS: Analysis of data from patients indicated that the levels of OVOL2 messenger RNA were significantly lower in colon carcinomas than adenomas, and decreased significantly as carcinomas progressed from grades 2 to 4. Immunohistochemical analysis of a tissue array of 275 CRC samples showed a negative association between tumor stage and OVOL2 level. Overexpression of OVOL2 in SW620 cells decreased their migration and invasion, reduced markers of the epithelial-to-mesenchymal transition, and suppressed their metastasis as xenograft tumors in nude mice; knockdown of OVOL2 caused LS174T cells to transition from epithelial to mesenchymal phenotypes. OVOL2 bound T-cell factor (TCF)4 and ß-catenin, facilitating recruitment of histone deacetylase 1 to the TCF4-ß-catenin complex; this inhibited expression of epithelial-to-mesenchymal transition-related genes regulated by WNT, such as SLUG, in CRC cell lines. OVOL2 was a downstream target of WNT signaling in LS174T and SW480 cells. The OVOL2 promoter was hypermethylated in late-stage CRC specimens from patients and in SW620 cells; hypermethylation resulted in OVOL2 down-regulation and an inability to inhibit WNT signaling. Disruption of Ovol2 in Apc(min/+) mice increased WNT activity in intestinal tissues and the formation of invasive intestinal tumors. CONCLUSIONS: OVOL2 is a colorectal tumor suppressor that blocks WNT signaling by facilitating the recruitment of histone deacetylase 1 to the TCF4-ß-catenin complex. Strategies to increase levels of OVOL2 might be developed to reduce colorectal tumor progression and metastasis.


Assuntos
Movimento Celular , Neoplasias Colorretais/metabolismo , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Células CACO-2 , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Regulação para Baixo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Genótipo , Células HCT116 , Células HEK293 , Histona Desacetilase 1/metabolismo , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos Transgênicos , Invasividade Neoplásica , Metástase Neoplásica , Fenótipo , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fatores de Tempo , Fator de Transcrição 4 , Fatores de Transcrição/genética , Transfecção , Carga Tumoral , beta Catenina/metabolismo
19.
Lab Anim ; 48(2): 132-42, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24362593

RESUMO

Compared with single nodular liver cancer, the prominent biological characteristics of multinodular liver cancer include rapid progression and short survival. Here, we developed a multinodular liver cancer model in mice and assessed the biological characteristics of the resulting neoplasms. H22 hepatoma cells at a dose of 2 × 10(5)/mouse, suspended in 1.6 mL, 0.8 mL, or 200 µL saline were injected via the tail vein of BALB/c mice at a velocity of 200 µL per second. The mice were sacrificed at different time points after injection. And at the time of death the liver, lungs, spleen, kidneys and heart were removed for morphological study. The biological characteristics of the tumor nodules were evaluated by immunohistochemistry. In the mice treated with a large volume injection of H22 cells, by day 7, there was a 100% occurrence of multinodular tumors in the livers, determined by histology. At the time of death, there were 100%, 100%, 37.5% and 37.5% occurrences of tumors in the lungs, kidneys, spleen and heart, respectively. The neoplastic cells in the liver nodules showed pleomorphism, and exhibited high expression of proliferating cell nuclear antigen (PCNA), c-myc, vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2). In mice treated with a small or medium volume injection, no tumor cells were identified in the livers, spleen, kidneys or heart at any of the examined time points. By day 7 and at the time of death, there was a 100% occurrence of tumor in the lungs. A multinodular liver cancer model in mice was achieved using a large volume injection of H22 cells.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Metaloproteinase 2 da Matriz/genética , Proteínas Nucleares/genética , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/ultraestrutura , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Injeções Intravenosas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/ultraestrutura , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Proteínas Nucleares/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 36(6): 675-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25556745

RESUMO

With the improvement of living standards and oral health awareness in people and with the development of the techniques in orthodontic therapy,the number of adult patients in orthodontics is gradually increasing. Due to adults' social occupations,psychological factors,complicated intraoral status,these factors make adult patients differences from adolescents. In this paper,the problems related with adult orthodontic treatment were reviewed.


Assuntos
Ortodontia Corretiva , Adolescente , Adulto , Humanos , Má Oclusão/terapia
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