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1.
Oxid Med Cell Longev ; 2020: 5138539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273945

RESUMO

Our previous work revealed that Nrf1α exerts a tumor-repressing effect because its genomic loss (to yield Nrf1α-/- ) results in oncogenic activation of Nrf2 and target genes. Interestingly, ß-catenin is concurrently activated by loss of Nrf1α in a way similar to ß-catenin-driven liver tumor. However, a presumable relationship between Nrf1 and ß-catenin is not yet established. Here, we demonstrate that Nrf1 enhanced ubiquitination of ß-catenin for targeting proteasomal degradation. Conversely, knockdown of Nrf1 by its short hairpin RNA (shNrf1) caused accumulation of ß-catenin so as to translocate the nucleus, allowing activation of a subset of Wnt/ß-catenin signaling responsive genes, which leads to the epithelial-mesenchymal transition (EMT) and related cellular processes. Such silencing of Nrf1 resulted in malgrowth of human hepatocellular carcinoma, along with malignant invasion and metastasis to the lung and liver in xenograft model mice. Further transcriptomic sequencing unraveled significant differences in the expression of both Wnt/ß-catenin-dependent and Wnt/ß-catenin-independent responsive genes implicated in the cell process, shape, and behavior of the shNrf1-expressing tumor. Notably, we identified that ß-catenin is not a target gene of Nrf1, but this CNC-bZIP factor contributes to differential or opposing expression of other critical genes, such as CDH1, Wnt5A, Wnt11A, FZD10, LEF1, TCF4, SMAD4, MMP9, PTEN, PI3K, JUN, and p53, each of which depends on the positioning of distinct cis-regulatory sequences (e.g., ARE and/or AP-1 binding sites) in the gene promoter contexts. In addition, altered expression profiles of some Wnt/ß-catenin signaling proteins were context dependent, as accompanied by decreased abundances of Nrf1 in the clinic human hepatomas with distinct differentiation. Together, these results corroborate the rationale that Nrf1 acts as a bona fide dominant tumor repressor, by its intrinsic inhibition of Wnt/ß-catenin signaling and relevant independent networks in cancer development and malignant progression.

2.
Water Res ; 175: 115690, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172056

RESUMO

Mainstream anammox still faces the challenges of non-ideal NO2-/NH4+ ratios and excess nitrate resulted from the instability of partial nitrification (PN) in municipal wastewater. To address these problems, in this study, we developed a novel two-sludge process that combined PN with synchronous anammox and endogenous partial denitrification (SAEPD); the process was tested with pre-treated domestic sewage at ambient temperatures for 205 d. High nitrogen removal efficiency of 91.2% was achieved with an influent C/N ratio of 1.7 at 15.4 °C; the success was attributed to the fact that EPD replenished the deficient nitrite by reducing nitrate and the excess nitrite was further reduced to nitrogen gas. With a non-ideal NO2-/NH4+ ratio of 0.89, the contribution of the SAEPD-sequencing batch reactor (SBR) during the anoxic stage reached 98.2% and the proportional contributions of the anammox and denitrification pathways were 77.2% and 22.8%, respectively. Although the low nitrite accumulation (66.1%) caused 10.8 mg N/L of nitrate to be transported into the SAEPD-SBR and the anammox reaction also converted 20% of nitrite to nitrate, only 1.1 mg N/L of nitrate remained in the effluent. High-throughput sequencing analysis revealed that although NH2OH was added, some genera of nitrite-oxidizing bacteria (0.73%) remained in the PN-SBR and potentially resulted in the oxidation of nitrite to nitrate. In the SAEPD-SBR, anammox and endogenous denitrifying bacteria co-existed and synergistically achieved the removal of ammonium, nitrite, and nitrate. Overall, the PN-SAEPD process has great potential for achieving cost-effective and energy-efficient municipal wastewater treatment.


Assuntos
Desnitrificação , Águas Residuárias , Reatores Biológicos , Nitrificação , Nitrogênio , Oxirredução , Esgotos , Temperatura
3.
Chem Biodivers ; 17(2): e1900473, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31961474

RESUMO

Veratrum plant contains a family of compounds called steroidal alkaloids which have been previously reported to cause DNA damage and blood pressure decrease in vivo. In this study, the antihypertensive effects and DNA damage in brain cells of 12 steroidal alkaloids separated from Veratrum plant were all evaluated to develop a relationship among chemical structure, antihypertensive activity and neurotoxicity by utilization of chemical principal component analysis (PCA) and hierarchical cluster analysis (HCA). Twelve steroidal alkaloids markedly reduced high blood pressure of hypertensive mice and also similarly induced varying degrees of DNA single-strand breaks in mouse cerebellum and cerebral cortex after oral administration. On the basis of the PCA and HCA results, it was suggested that the 3-carboxylic esters and benzene group play a core role in the DNA damage of brain cells, while more hydroxy groups in the A-ring and B-ring structure of jervine-type alkaloid led to stronger antihypertensive activity. The primary structure, activity and neurotoxicity relationship were discussed briefly.


Assuntos
Anti-Hipertensivos/química , Alcaloides de Veratrum/química , Veratrum/química , Administração Oral , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Análise por Conglomerados , Dano ao DNA/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Análise de Componente Principal , Relação Estrutura-Atividade , Veratrum/metabolismo , Alcaloides de Veratrum/farmacologia
4.
J Cell Biochem ; 120(11): 19098-19106, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31265170

RESUMO

Thymosin ß-4 (Tß4) is a ubiquitous protein, which has been suggested to regulate multiple cell signal pathways and a variety of cellular functions. However, the role Tß4 plays in the cardiac microvascular endothelial cells (CMECs) under myocardial ischemia/reperfusion injury is currently unknown. Here we investigated the effects of Tß4 on hypoxia/reoxygenation (H/R) induced CMECs injury and its potential molecular mechanism. Cultured CMECs were positively identified by flow cytometry using antibody against CD31 and VWF/Factor VIII, which are constitutively expressed on the surface of CMECs. Then the reduced level of Tß4 was detected in H/R-CMECs by a real-time quantitative polymerase chain reaction. To determine the effects of Tß4 on H/R-CMECs, we transfected the overexpression or silence vector of Tß4 into CMECs under H/R condition. Our results indicated that H/R treatment could reduce proliferation, increased apoptosis, adhesion, and reactive oxygen species (ROS) production in CMECs, which were attenuated by Tß4 overexpression or aggravated by Tß4 silencing, implying Tß4 is able to promote CMECs against H/R-induced cell injury. Furthermore, the microRNA-200a (miR-200a) level was also increased by Tß4 in H/R-CMECs or reduced by Tß4 small interfering RNA. To investigated the mechanism of protective effects of Tß4 on CMECs injury, the miR-200a inhibitor was transfected into H/R-CMECs. The results indicated that inhibition of miR-200a inversed the protection of Tß4 on H/R-CMECs, specifically including cell proliferation, cell adhesion, cell apoptosis, and ROS production, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation. In conclusion, our results determined that Tß4 attenuated H/R-induced CMECs injury by miR-200a-Nrf2 signaling.

5.
J Cell Biochem ; 120(4): 6605-6613, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30484891

RESUMO

Myocarditis is an inflammatory disease of the myocardium. MicroRNA-203 (miR-203) is involved in various physiological and pathological processes. In this work, we aimed to explore the roles and potential mechanisms of miR-203 in myocarditis in vitro. Cardiomyocyte H9c2 was subjected to 10 µg/mL lipopolysaccharide (LPS) for 24 hours. Real-time polymerase chain reaction analysis revealed that LPS upregulated miR-203 expression in H9c2 cells. Cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays demonstrated that inhibition of miR-203 reduced cell injury induced by LPS. The cell apoptosis rate, caspase 3 activity, caspase 3/7 activities, and the expression of cleaved-caspase 3 (c-caspase 3) were declined upon miR-203 depletion. In addition, miR-203 silencing attenuated the expression and production of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-8). On the contrary, overexpression of miR-203 showed the opposite trend in cell apoptosis and inflammation. Luciferase reporter assay confirmed that miR-203 could bind with the nuclear factor interleukin-3 (NFIL3) 3'-untranslated regions (3'-UTR), and miR-203 regulated the expression of NFIL3 negatively. Moreover, NFIL3 silencing partly abolished the myocardial protective functions of miR-203 inhibitor. Herein, we suggest that miR-203 promoted cell apoptosis and inflammation induced by LPS via targeting NFIL3.

6.
Psychol Rep ; : 33294118805007, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30428267

RESUMO

This study investigated the inhibitory process of collaborative inhibition. An emotional Stroop task was manipulated three times after a group-recall task across three experiments. The results showed that, when participants performed an emotional Stroop task immediately after a group-recall task (Experiment 1) or between two subsequent individual-recall tasks after a group-recall task (Experiment 3), they were able to discriminate color information relating to studied but nonrecalled emotional stimuli more rapidly in the collaborative-recall condition than in the nominal-recall condition. This indicated that participants experienced a stronger inhibition effect in the former condition. However, when the emotional Stroop task was performed after the final individual-recall task (Experiment 2), there were no differences in discrimination between the conditions. These results suggest that the inhibition effect occurs immediately after the group-recall phase and lasts until the final individual-recall task is completed (4 minutes or longer in Experiment 3). It is therefore possible to discuss retrieval inhibition as an underlying mechanism of collaborative inhibition.

7.
ACS Chem Neurosci ; 9(7): 1616-1624, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29708326

RESUMO

Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as "Lilu" and is reported to contain a family of compounds called stilbenes that can have positive biological activity. In this study, nine stilbenes were isolated from the aerial parts of V. maackii Regel, and their structures were identified as cis-mulberroside A (1), resveratrol-4,3'- O-ß-d-diglucopyranoside (2), mulberroside A (3), gentifolin K (4), resveratrol-3,5- O-ß-d-diglucopyranoside (5), oxyresveratrol- 4'- O-ß-d-glucopyranoside (6), oxyresveratrol-3- O-ß-d-glucopyranoside (7), oxyresveratrol (8), and resveratrol (9) using ESI-MS and NMR techniques. The total concentration of extracted compounds 2-9 was 2.04 mg/g, suggesting that V. maackii Regel is a novel viable source of these compounds. In an in vivo comet assay, compounds 1-9 were observed to decrease DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration. Histological observation also revealed decreased brain injury in mice administered with compounds 1-9 after acute ethanol administration. The protective effects of compound 6 were associated with increasing T-SOD and GSH-PX activities and a decrease in NO and MDA concentrations. These findings suggest that these compounds are potent inhibitors of ethanol-induced brain injury possibly via the inhibition of oxidative stress and may be valuable leads for future therapeutic development.


Assuntos
Depressores do Sistema Nervoso Central/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Etanol/efeitos adversos , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Veratrum , Transtornos Relacionados ao Uso de Álcool/tratamento farmacológico , Transtornos Relacionados ao Uso de Álcool/metabolismo , Transtornos Relacionados ao Uso de Álcool/patologia , Animais , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Cerebelo/patologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Masculino , Camundongos , Estrutura Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fototerapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Distribuição Aleatória , Estilbenos/química , Estilbenos/isolamento & purificação
8.
Plant Physiol Biochem ; 125: 178-184, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29459286

RESUMO

Crop growth and productivity are often impacted by the increased ethylene content induced by adverse environmental conditions such drought. Inoculations with bacteria producing ACC deaminase is considered as a potential biological approach to improve the growth and tolerance of stressed plants by lowering endogenous ethylene level. In this study, germinated wheat seeds were inoculated using three species of the rhizobacteria, which were isolated from the rhizosphere of wheat growing in dryland, and sown in pots. After three weeks, wheat seedlings were exposed to non-limiting water condition, medium drought and severe drought, respectively, for six weeks. The results showed that, irrespective of rhizobacterial inoculations, decreased soil water contents stimulated wheat ethylene metabolism, which was reflected by the significantly increased activity of ACC synthetase and ACC oxidase, besides an increased content of ACC both in the roots and leaves, and an enhanced capacity of leaves to release ethylene, concomitant with a significant decline in shoot and roots biomass. The inoculations of all three rhizobacterial species under each water condition reduced ACC content in wheat leaves, but effects of the inoculations on ACC synthase and ACC oxidase activity in the leaves and roots, ACC content in the roots, the capacity of leaves to release ethylene, and wheat growth varied with water conditions and bacterial species. Hence, both soil water conditions and rhizobacterial inoculations acted on all the processes of ethylene metabolism, with the former being dominant. The inoculations under non-limiting water condition and medium drought promoted shoot and root growth of wheat plants.


Assuntos
Proteínas de Bactérias/metabolismo , Carbono-Carbono Liases/metabolismo , Enterobacter/enzimologia , Etilenos/metabolismo , Microbiologia do Solo , Solo , Triticum , Água , Triticum/crescimento & desenvolvimento , Triticum/microbiologia
9.
Front Psychol ; 8: 1895, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163277

RESUMO

Remembering to perform an action when a specific event occurs is referred to as Event-Based Prospective Memory (EBPM). This study investigated how EBPM performance is affected by task duration by having university students (n = 223) perform an EBPM task that was embedded within an ongoing computer-based color-matching task. For this experiment, we separated the overall task's duration into the filler task duration and the ongoing task duration. The filler task duration is the length of time between the intention and the beginning of the ongoing task, and the ongoing task duration is the length of time between the beginning of the ongoing task and the appearance of the first Prospective Memory (PM) cue. The filler task duration and ongoing task duration were further divided into three levels: 3, 6, and 9 min. Two factors were then orthogonally manipulated between-subjects using a multinomial processing tree model to separate the effects of different task durations on the two EBPM components. A mediation model was then created to verify whether task duration influences EBPM via self-reminding or discrimination. The results reveal three points. (1) Lengthening the duration of ongoing tasks had a negative effect on EBPM performance while lengthening the duration of the filler task had no significant effect on it. (2) As the filler task was lengthened, both the prospective and retrospective components show a decreasing and then increasing trend. Also, when the ongoing task duration was lengthened, the prospective component decreased while the retrospective component significantly increased. (3) The mediating effect of discrimination between the task duration and EBPM performance was significant. We concluded that different task durations influence EBPM performance through different components with discrimination being the mediator between task duration and EBPM performance.

10.
J Cell Biochem ; 2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28857257

RESUMO

Thymosin beta-4 (Tß4) is a ubiquitous protein, which has been suggested to regulate multiple cell signal pathways and a variety of cellular functions. However, the role Tß4 plays in the cardiac microvascular endothelial cells (CMECs) under myocardial ischemia/reperfusion injury (MIRI) is currently unknown. Here we investigated the effects of Tß4 on hypoxia/reoxygenation (H/R) induced CMECs injury and its potential molecular mechanism. Cultured CMECs were positively identified by flow cytometry using antibody against CD31 and VWF/Factor VIII, which are constitutively expressed on the surface of CMECs. Then the reduced level of Tß4 was detected in H/R-CMECs by RT-qPCR. In order to determine the effects of Tß4 on H/R-CMECs, we transfected the overexpression or silence vector of Tß4 into CMECs under H/R condition. Our results indicated that H/R treatment could reduce proliferation, increased apoptosis, adhesion and ROS production in CMECs, which were attenuated by Tß4 overexpression or aggravated by Tß4 silence, implying Tß4 is able to promote CMECs against H/R-induced cell injury. Furthermore, the microRNA 200a (miR-200a) level was also increased by Tß4 in H/R-CMECs or reduced by Tß4 siRNA. To investigated the mechanism of protective effects of Tß4 on CMECs injury, the miR-200a inhibitor was transfected into H/R-CMECs. The results indicated that inhibition of miR-200a inversed the protection of Tß4 on H/R-CMECs, specifically including cell proliferation, cell adhesion, cell apoptosis and ROS production, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation. In conclusion, our results determined that Tß4 attenuated H/R induced CMECs injury by miR-200a-Nrf2 signaling. This article is protected by copyright. All rights reserved.

11.
FEBS Lett ; 591(21): 3670-3681, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28948615

RESUMO

NDRG2, a newly identified tumor suppressor, is also responsive to various stresses, such as hypoxia and DNA damage. Here, we reported that in human hepatoma SK-Hep-1 and HepG2 cells, NDRG2 mRNA and protein levels were upregulated by different endoplasmic reticulum stress inducers including Tg, Tm, and DTT. Further, using NDRG2-overexpressing hepatoma cell lines and Ndrg2KO mice liver tissues, we found that, among the three branches of unfolded protein response signaling, NDRG2 facilitates protein kinase RNA-like ER kinase (PERK) pathway via interaction with PERK, enhancing its downstream ATF4 and CHOP. Functionally, NDRG2 promotes ERS-induced apoptosis partially through ATF4 or CHOP. Thus, NDRG2 is a novel ERS-responsive protein and acts as PERK co-factor to facilitate PERK branch, thereby contributing to ERS-induced apoptosis.


Assuntos
Apoptose/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Proteínas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Células Hep G2 , Humanos , Fígado/metabolismo , Camundongos , Camundongos Knockout , Proteínas/genética , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Proteínas Supressoras de Tumor/genética , eIF-2 Quinase/genética
12.
Front Plant Sci ; 8: 156, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28261230

RESUMO

RAR1 is a eukaryotic zinc-binding protein first identified as required for race-specific resistance to powdery mildew in barley. To study the function of TaRAR1 involvement in wheat (Triticum aestivum L.) defense against the infection of stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst), we identified and cloned three wheat homeologous genes highly similar to the barley HvRar1, designated as TaRar1-2A, TaRar1-2B, and TaRar1-2D. The three TaRAR1 proteins all contain two conserved cysteine-and histidine-rich domains (CHORD-I and -II) shared by known RAR1-like proteins. Characterization of TaRar1 expression revealed that the expression was tissue-specific and up-regulated in wheat during stripe rust infection. Moreover, the transcription of TaRar1 was induced by methyl jasmonate, ethylene, and abscisic acid hormones. The same results were observed with drought and wound treatments. After TaRar1 was silenced in wheat cultivar Suwon11 containing the stripe rust resistance gene YrSu, the endogenous salicylic acid (SA) level, the hydrogen peroxide (H2O2) accumulation and the degree of hypersensitive response (HR) were significantly decreased, and the resistance to the avirulent pathotype of stripe rust was compromised. Meanwhile, the expression of catalase, an enzyme required for H2O2-scavenging, was up-regulated. Taken together, we concluded that TaRar1 is involved in wheat defense against stripe rust mediated by YrSu, and the defense was through SA to influence reactive oxygen species accumulation and HR.

13.
Biochem Biophys Res Commun ; 484(1): 118-124, 2017 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-28104397

RESUMO

PTEN inducible kinase-1 (PINK1) mutant induces mitochondrial dysfunction of cells, resulting in an inherited form of Parkinson's disease. However its exact role in the cardiomyocytes is unclear. The present study examined the function of PINK1 in hypoxia-reoxygenation (H/R) induced H9c2 cell damage and its potential mechanism. The H/R model in H9c2 cells was established by 6 h of hypoxia and 12 h of reoxygenation. The CCK8 and LDH assay indicated that the cell viability was obviously reduced after H/R. The expression of PINK1 was decreased in H/R-induced H9c2 cells compared with control group. The vector overexpressing PINK1 was constructed to transfect into H/R-induced H9c2 cells. Our results showed that cell viability was increased, cell apoptosis and caspase 3, cytochrome C (Cyto C) levels were decreased after LV-PINK1 transfection. Furthermore, PINK1 overexpression stabilized electron transport chain (ETC) activity, increased ATP production, mPTP opening and mitochondrial membrane potential (MMP), inhibited ROS-generating mitochondria, implying PINK1 alleviates H/R induced mitochondrial dysfunction in cardiomyocytes. In addition, the TRAP-1 siRNA was transfected into PINK1 treated H9c2 cells after H/R to detected the molecular mechanism of PINK1 protecting cardiomyocytes. The results indicated that silence of TRAP-1 reversed the effects of PINK1 in H/R-induced H9c2 cells. In conclusion, these results suggest that PINK1 overexpression alleviates H/R-induced cell damage of H9c2 cells by phosphorylation of TRAP-1, and that is a valid approach for protection from myocardial I/R injury.


Assuntos
Mitocôndrias Cardíacas/fisiologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Oxigênio/metabolismo , Proteínas Quinases/fisiologia , Animais , Linhagem Celular , Sobrevivência Celular/fisiologia , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Fosforilação , Proteínas Quinases/metabolismo , Ratos
14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(12): 1647-1651, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29382425

RESUMO

Objective To study the effect of the knock-down of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) on the cell cycle of the multidrug-resistant (MDR) Bel7402/5-Fu hepatocellular carcinoma cells and its MDR mechanism. Methods After cationic liposome-mediated siDNA-PKcs oligonucleotide transfection, the drug sensitivity of Bel7402/5-Fu cells to 5-fluorouracil (5-Fu) and adriamycin (ADM) was determined by MTT assay; the cell cycle were detected by flow cytometry; meanwhile, the protein expressions of cell cycle-related proteins P21, cell cycle protein B1 (cyclin B1), cell cycle division protein 2 (CDC2) were tested by Western blotting; the expressions of ataxia telangiectasia mutated (ATM) and p53 at both mRNA and protein levels were detected by real-time PCR and Western blot analysis. Results The MTT results showed siDNA-PKcs increased the chemotherapeutic sensitivity of Bel7402/5-Fu cells to 5-Fu and ADM. The flow cytometric analysis showed siDNA-PKcs decreased the percentage of S-phase cells but increased the percentage of G2/M phase cells. Western blotting showed siDNA-PKcs increased the protein expression of P21 but decreased cyclinB1 and CDC2 proteins. In addition, siDNA-PKcs also increased the expressions of ATM and p53. Conclusion DNA-PKcs silencing increases P21 while decreases cyclin B1 and CDC2 expressions, and finally induces G2/M phase arrest in Bel7402/5-Fu cells, which may be related to ATM-p53 signaling pathway.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Proteína Quinase Ativada por DNA/genética , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Nucleares/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína Quinase CDC2/análise , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclina B1/análise , Inibidor de Quinase Dependente de Ciclina p21/análise , Resistencia a Medicamentos Antineoplásicos , Inativação Gênica , Humanos , Neoplasias Hepáticas/patologia , Proteína Supressora de Tumor p53/genética
15.
Am J Transl Res ; 8(7): 2937-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27508014

RESUMO

OBJECTIVE: The study aimed to simulate the microenvironment of gastric cancer to promote the malignant transformation of bone marrow mesenchymal stem cells (BMSCs) and further evaluate the effect of Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions on BMSCs. METHODS: Transwell co-culture was performed on the human gastric cancer cell strains BGC-823 and BMSCs to simulate the microenvironment of gastric cancer. The drug-containing serum prepared by Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions was used, and its influence on BMSCs with malignant transformation was observed. RESULTS: BMSCs were harvested successfully from the rat bone marrow, and flow cytometer identification indicated that CD44+/CD34- cells accounted for 70.64%. The co-culture of BGC-823 cells can induce malignant transformation of BMSCs. And the drug-containing serum can induce G2 phase arrest, inhibit cell proliferation, simultaneously inhibit TERT and c-myc expression, lower the cellular ability of chemotactic migration, inhibit the tumor-forming ability of BGC-823 in nude rats and promote the tumor apoptosis. CONCLUSION: The effective components of Pinelliae Decoction for Purging Stomach-Fire in gastric cancer treatment are pinelliae and dried ginger, and the main acting mechanism is to inhibit tumor cell proliferation and chemotactic migration and promote apoptosis.

16.
Sci Rep ; 6: 28352, 2016 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-27329306

RESUMO

Chronic myeloid leukemia (CML) is characterized by constitutively active fusion protein tyrosine kinase BCR-ABL. Although the tyrosine kinase inhibitor (TKI) against BCR-ABL, imatinib, is the first-line therapy for CML, acquired resistance almost inevitably emerges. The underlying mechanism are point mutations within the BCR-ABL gene, among which T315I is notorious because it resists to almost all currently available inhibitors. Here we took use of a previously generated chimeric ubiquitin ligase, SH2-U-box, in which SH2 from the adaptor protein Grb2 acts as a binding domain for activated BCR-ABL, while U-box from CHIP functions as an E3 ubiquitin ligase domain, so as to target the ubiquitination and degradation of both native and T315I-mutant BCR-ABL. As such, SH2-U-box significantly inhibited proliferation and induced apoptosis in CML cells harboring either the wild-type or T315I-mutant BCR-ABL (K562 or K562R), with BCR-ABL-dependent signaling pathways being repressed. Moreover, SH2-U-box worked in concert with imatinib in K562 cells. Importantly, SH2-U-box-carrying lentivirus could markedly suppress the growth of K562-xenografts in nude mice or K562R-xenografts in SCID mice, as well as that of primary CML cells. Collectively, by degrading the native and T315I-mutant BCR-ABL, the chimeric ubiquitin ligase SH2-U-box may serve as a potential therapy for both imatinib-sensitive and resistant CML.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Fusão bcr-abl/genética , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Proteínas Recombinantes de Fusão/genética , Animais , Proliferação de Células/efeitos dos fármacos , Proteína Adaptadora GRB2/química , Vetores Genéticos/administração & dosagem , Vetores Genéticos/farmacologia , Humanos , Células K562 , Lentivirus/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Camundongos , Mutação Puntual , Transdução de Sinais/efeitos dos fármacos , Ubiquitina-Proteína Ligases/química , Ensaios Antitumorais Modelo de Xenoenxerto , Domínios de Homologia de src
17.
Neurosci Lett ; 628: 132-5, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27291459

RESUMO

Consciousness is thought to scale with brain complexity, and it may be diminished in anesthesia. Lempel-Ziv complexity (LZC) of field potentials has been shown to be a promising measure of the level of consciousness in anesthetized human subjects, neurological patients, and across the sleep-wake states in rats. Whether this relationship holds for intrinsic networks obtained by functional brain imaging has not been tested. To fill this gap of knowledge, we estimated LZC from large-scale dynamic analysis of functional magnetic resonance images (fMRI) in conscious sedated and unconscious anesthetized rats. Blood oxygen dependent (BOLD) signals were obtained from 30-min whole-brain resting-state scans while the anesthetic propofol was infused intravenously at constant infusion rates of 20mg/kg/h (conscious sedated) and 40mg/kg/h (unconscious). Dynamic brain networks were defined at voxel level by sliding window analysis of regional homogeneity (ReHo) of the BOLD signal. From scans performed at low to high propofol dose, the LZC was significantly reduced by 110%. The results suggest that the difference in LZC between conscious sedated and anesthetized unconscious subjects is conserved in rats and this effect is detectable in large-scale brain network obtained from fMRI.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Estado de Consciência/efeitos dos fármacos , Estado de Consciência/fisiologia , Propofol/administração & dosagem , Animais , Mapeamento Encefálico , Imagem por Ressonância Magnética , Masculino , Ratos , Ratos Sprague-Dawley
18.
Plant Biotechnol J ; 14(10): 1998-2009, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26929151

RESUMO

Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion-limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM-IBP fusion polypeptides composed of a carbohydrate-binding module family 11 (CBM11) and an iron-binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM-IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM-IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. CBM-IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization.


Assuntos
Arabidopsis/metabolismo , Biomassa , Parede Celular/metabolismo , Ferro/metabolismo , Oryza/metabolismo , Sementes/metabolismo , Arabidopsis/genética , Biocombustíveis , Parede Celular/genética , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(10): 1224-1228, 2016 10.
Artigo em Chinês | MEDLINE | ID: mdl-30641011

RESUMO

Objective To observe the effects of Banxia Xiexin Decoction (BXD) containing ser- um on proliferation, invasion and metastasis of in vitro human gastric cancer peritoneum cell strain GC9811-P (which has high metastatic potential). Methods BXD containing serum was prepared. GC9811-P cells were inoculated in the E-Plate 96 and CIM Plate 16, and then 0, 25, 50, 100 µL/mL BXD containing serums were added respectively. Meanwhile, GC9811-P cells were stained by Diff-Quik stai- ning method. Inhibition of BXD containing serum on cell index (CI) for proliferation of GC9811-P cells, invasion and metastasis were observed by real time cellular analysis (RTCA) and Diff-Quik staining method. Results BXD containing serum could obviously inhibit the proliferation of GC9811-P cells. The Cl approximated to 0 after 70 h. Most stained Diff-Quik cells died. Cell migration curve showed that 25, 50, 100 µL/mL BXD containing serums could obviously inhibit the capacities for cell migration of GC9811-P cells in concentration dependent manner. The number of migration cells was reduced more obviously, as com- pared with 0 µL/mL BXD containing serum (P <0. 05). Conclusion BXD containing serums could inhibit the proliferation, invasion and metastasis of GC9811-P cells, which might be associated with blocking peritoneal metastasis of gastric cancer.


Assuntos
Medicamentos de Ervas Chinesas , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Peritoneais , Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Peritônio , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
20.
FEBS Lett ; 589(18): 2347-58, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26231763

RESUMO

O-Linked N-acetylglucosamine transferase (OGT) was identified as an Nrf1-interacting protein. Herein, we show that Nrf1 enables interaction with OGT and their co-immunoprecipitates are O-GlcNAcylated by the enzyme. The putative O-GlcNAcylation negatively regulates Nrf1/TCF11 to reduce both its protein stability and transactivation activity of target gene expression. The turnover of Nrf1 is enhanced upon overexpression of OGT, which promotes ubiquitination of the CNC-bZIP protein. Furthermore, the serine/theorine-rich sequence of PEST2 degron within Nrf1 is identified to be involved in the protein O-GlcNAcylation by OGT. Overall, Nrf1 is negatively regulated by its O-GlcNAcylation status that depends on the glucose concentrations.


Assuntos
Acetilglucosamina/metabolismo , Fator 1 Relacionado a NF-E2/metabolismo , Sequência de Aminoácidos , Animais , Antioxidantes/metabolismo , Técnicas de Silenciamento de Genes , Glicosilação , Células HEK293 , Humanos , Camundongos , Dados de Sequência Molecular , N-Acetilglucosaminiltransferases/deficiência , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Fator 1 Relacionado a NF-E2/química , Estabilidade Proteica , Proteínas Repressoras/metabolismo , Elementos de Resposta/genética , Ativação Transcricional
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