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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124312, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38688210

RESUMO

The ubiquity of diverse material entities in environmental matrices renders the deployment of unifunctional fluorescent indicators inadequate. Consequently, this study introduces a ratiometric dual-emission fluorescent sensor (Probe CP), synthesized by conjugating phenothiazine coumarin to hydroxycoumarin through a piperazine linker for concurrent detection of HClO and H2S. Upon interaction with HClO, the phenothiazine unit's sulfur atom undergoes oxidation to sulfoxide, facilitating a shift from red to green fluorescence in a ratiometric manner. Concurrently, at the opposite terminus of Probe CP, 2,4-dinitroanisole serves as the reactive moiety for H2S recognition; it restores the blue emission characteristic of 7-hydroxycoumarin while maintaining the red fluorescence emanating from phenothiazine coumarin as an internal standard for ratio-based assessment. Exhibiting elevated specificity and sensitivity coupled with minimal detection thresholds (0.0506 µM for HClO and 1.7292 µM for H2S) alongside rapid equilibration periods (3 min for HClO and half an hour for H2S), this sensor was efficaciously employed in cellular environments and within zebrafish models as well as imaging applications pertaining to alcohol-induced hepatic injury in murine subjects.


Assuntos
Cumarínicos , Corantes Fluorescentes , Sulfeto de Hidrogênio , Fenotiazinas , Peixe-Zebra , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Fenotiazinas/química , Fenotiazinas/síntese química , Cumarínicos/química , Cumarínicos/síntese química , Sulfeto de Hidrogênio/análise , Camundongos , Espectrometria de Fluorescência/métodos , Humanos
2.
Mol Brain ; 16(1): 24, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782228

RESUMO

The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene is inactivated in neural progenitor cells in the developing cerebellum. We report that conditional knockout (cKO) of Ggps1 leads to severe ataxia and deficient locomotion. To identify the underlying mechanisms, we completed a series of cellular and molecular experiments. First, our morphological analysis revealed significantly decreased population of granule cell progenitors (GCPs) and impaired proliferation of GCPs in the developing cerebellum of Ggps1 cKO mice. Second, our molecular analysis showed increased expression of p21, an important cell cycle regulator in Ggps1 cKO mice. Together, this study highlights a critical role of Ggpps-dependent protein prenylation in the proliferation of cerebellar GCPs during cerebellar development.


Assuntos
Células-Tronco Neurais , Prenilação de Proteína , Camundongos , Animais , Cerebelo , Ataxia , Proliferação de Células , Camundongos Knockout
3.
Adv Biol (Weinh) ; 7(9): e2200150, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36599632

RESUMO

There are no known approved pharmacotherapies for non-alcoholic fatty liver disease (NAFLD) in the clinical setting. Although studies have provided substantial evidence that geranylgeranyl diphosphate synthase (GGPPS) is a potential therapeutic target for the treatment of NAFLD corresponding drug screening is rare. A GGPPS-targeted inhibitor is identified using a structure-based virtual small molecule screening method. The interaction of 4-AZ and GGPPS is detected by microscale thermophoresis. 4-AZ degradation of GGPPS by the ubiquitin-proteasome pathway is detected by western blotting. The anti-steatotic effect of 4-AZ in vivo is detected by CT. Lipid-related gene detection is detected by real-time PCR both in primary hepatocytes and mice. The compound inhibits the accumulation of lipids in primary hepatocytes and decreases lipogenic gene expression through GGPPS. Pharmacological studies show that 4-AZ can attenuate hepatic steatosis and improve liver injury in high-fat diet-induced mice. This data provides a novel application of 4-AZ NAFLD therapy, proving that the inhibition of GGPPS is a novel strategy for the treatment of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Farnesiltranstransferase/genética , Farnesiltranstransferase/metabolismo , Complexo de Endopeptidases do Proteassoma , Ubiquitinas
4.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36674733

RESUMO

Skuld (skd) is a subunit of the Mediator complex subunit complex. In the heart, skd controls systemic obesity, is involved in systemic energy metabolism, and is closely linked to cardiac function and aging. However, it is unclear whether the effect of cardiac skd on cardiac energy metabolism affects cardiac function. We found that cardiac-specific knockdown of skd showed impaired cardiac function, metabolic impairment, and premature aging. Drosophila was subjected to an exercise and high-fat diet (HFD) intervention to explore the effects of exercise on cardiac skd expression and cardiac function in HFD Drosophila. We found that Hand-Gal4>skd RNAi (KC) Drosophila had impaired cardiac function, metabolic impairment, and premature aging. Regular exercise significantly improved cardiac function and metabolism and delayed aging in HFD KC Drosophila. Thus, our study found that the effect of skd on cardiac energy metabolism in the heart affected cardiac function. Exercise may counteract age-related cardiac dysfunction and metabolic disturbances caused by HFD and heart-specific knockdown of skd. Skd may be a potential therapeutic target for heart disease.


Assuntos
Senilidade Prematura , Proteínas de Drosophila , Cardiopatias , Animais , Camundongos , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Coração , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Proteínas do Olho/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-36554435

RESUMO

Although studies have shown that myomesin 2 (MYOM2) mutations can lead to hypertrophic cardiomyopathy (HCM), a common cardiovascular disease that has a serious impact on human life, the effect of MYOM2 on cardiac function and lifespan in humans is unknown. In this study, dMnM (MYOM2 homologs) knockdown in cardiomyocytes resulted in diastolic cardiac defects (diastolic dysfunction and arrhythmias) and increased cardiac oxidative stress. Furthermore, the knockdown of dMnM in indirect flight muscle (IFM) reduced climbing ability and shortened lifespan. However, regular exercise significantly ameliorated diastolic cardiac dysfunction, arrhythmias, and oxidative stress triggered by dMnM knockdown in cardiac myocytes and also reversed the reduction in climbing ability and shortening of lifespan caused by dMnM knockdown in Drosophila IFM. In conclusion, these results suggest that Drosophila cardiomyocyte dMnM knockdown leads to cardiac functional defects, while dMnM knockdown in IFM affects climbing ability and lifespan. Furthermore, regular exercise effectively upregulates cardiomyocyte dMnM expression levels and ameliorates cardiac functional defects caused by Drosophila cardiomyocyte dMnM knockdown by increasing cardiac antioxidant capacity. Importantly, regular exercise ameliorates the shortened lifespan caused by dMnM knockdown in IFM.


Assuntos
Proteínas de Drosophila , Cardiopatias Congênitas , Animais , Humanos , Drosophila/fisiologia , Longevidade , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação para Baixo , Exercício Físico
6.
Front Psychol ; 13: 918427, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783791

RESUMO

Using data from the China Family Panel Studies (CFPS), this paper investigates the effects of Internet use on residents' risk attitudes. Both Generalized Ordered Logit Model and Logit model are used to identify the effects of Internet use. The results reveal an association between Internet use and increases in both subjective and objective risk preferences that remains even after we adjust for possible endogeneity. The heterogeneity analysis also reveals that these impacts are different among groups with different reasons for Internet use and different personal characteristics. Our study expands the research on the effects of Internet on people's concepts from the micro perspective and suggests that while promoting the application of information technology we should also pay attention to the individual characteristics of residents so that we can better share the "digital dividend" brought by the popularization of information technology in the whole society.

8.
Plants (Basel) ; 11(15)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35893641

RESUMO

Cnidoscolus aconitifolius (Mill.) I.M. Johnst is a multipurpose woody plant. In this study, an in vitro efficient propagation system of stem segment explants derived from field-grown C. aconitifolius plants was established for the first time. The sterilization effect, axillary bud initiation, and proliferation efficiency of stem segments were evaluated. The results showed that the sterilization time of 0.1% mercuric chloride, the concentration of Plant Preservative Mixture (PPM), the pretreatment method, and the sampling season had significant effects on the sterilization of stem segments (p < 0.05). The type of medium and plant growth regulators (PGRs) affected the initiation of axillary buds, and the proliferation efficiency was significantly affected by PGRs. The results showed that the best sterilization method for stem segment explants was as follows: a pretreatment by rinsing with running water for 120 min, soaking in 75% ethanol for 50 s, soaking in 0.1% mercuric chloride for 10 min, and medium supplemented with 3 mL/L PPM. When inoculated on the medium in spring, the contamination rate was as low as 25.56%. The optimal initiation medium for axillary buds in stem segments was half-strength Murashige and Skoog (1/2 MS) medium supplemented with 0.5 mg/L 6-benzyladenine (6-BA). The induction rate was as high as 93.33%, and the mean length of axillary buds was 2.47 cm. The optimal proliferation medium was 1/2 MS medium supplemented with 4.0 mg/L 6-BA and 0.2 mg/L indole-3-butyric acid (IBA). The induction rate was up to 80.00%, the total proliferation coefficient was 4.56, and the net proliferation coefficient was 5.69. The 1/2 MS medium supplemented with 0.1 mg/L 6-BA and 1.5 mg/L indole-3-acetic acid (IAA) was most conducive to the elongation of the adventitious shoot, and the adventitious shoot of approximately 1 cm reached 1.93 cm after culturing for 14 days. The best medium for adventitious shoot rooting was 1/2 MS medium supplemented with 0.1 mg/L α-naphthalene acetic acid (NAA), the highest rooting rate was 82.00%, and the survival rate of transplanting was over 90%.

9.
Front Endocrinol (Lausanne) ; 13: 790414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418948

RESUMO

The major reason of human morbidity and mortality is obesity and related diseases. Brown adipose tissue (BAT) is associated with low total adipose tissue content and a lower risk of type 2 diabetes mellitus. Studies have shown that exercise and cold expose may induce browning. In this study, we verified (1) whether exercise and/or cold exposure can improve the expression level of ucp4c, serca, ampkα, camkII, sirt1, octß3r, and hamlet; (2) if these interventions can save cardiac dysfunction induced by a high-fat diet (HFD) in Drosophila. w1118 (wild-type) virgin female flies collected within 8 h after eclosion were divided into eight groups: the normal feed control group (NFD-C), the normal feed exercise group (NFD-E), the normal feed cold exposure group (NFD-CA), the normal feed exercise/cold exposure group (NFD-EC), the HFD control group (HFD-C), the HFD exercise group (HFD-E), the HFD cold exposure group (HFD-CA), and the HFD exercise/cold exposure group (HFD-EC). After exercise and/or cold exposure for 7 days, the mRNA expression levels of ucp4c, serca, ampkα, camk II, sirt1, octß3r, and hamlet were tested by qRT-PCR, and m-mode was used to assess cardiac function. In addition, we assessed the triacylglycerol (TAG) levels, motor ability, fat mass (by Oil Red O [ORO] staining), and morphological features. The results of TAG, ORO staining, and morphological features all indicate that after interventions, body size of Drosophila was smaller compared with the control group, irrespective of the feeding patterns. The mRNA expression levels of ucp4c, serca, octß3r, hamlet, ampkα, camkII, and sirt1 were changed to varying degrees under different intervention states (exercise and/or cold exposure). Cold exposure and exercise/cold exposure partly improved cardiac function and the normal fruit flies' cardiac function and exercise ability. However, after exercise intervention, exercise ability and heart function were improved in both HFD and normal-fat diet (NFD) fruit flies. In conclusion, different intervention states (exercise and/or cold exposure) can change the mRNA expression levels of ucp4c, serca, octß3r, hamlet, ampkα, camkII, and sirt1. Exercise is the most effective way to restore HFD-induced cardiac dysfunction.


Assuntos
Diabetes Mellitus Tipo 2 , Proteínas de Drosophila , Cardiopatias , Tecido Adiposo Marrom/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Corpo Adiposo/metabolismo , Feminino , Proteínas de Membrana Transportadoras/metabolismo , RNA Mensageiro , Sirtuína 1/genética , Sirtuína 1/metabolismo , Transcriptoma
10.
ACS Omega ; 6(25): 16488-16497, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34235320

RESUMO

Aluminum hydroxide is an effective defluoridation adsorbent; however, the poor defluoridation performance limits its wide application. In this work, amorphous and crystalline AlOOH adsorbents are synthesized through hydrolysis of Al salts, and their defluoridation performances are evaluated in terms of adsorption capacity and rate, sensitivity to pH value, and water quality after defluoridation. The defluoridation performance of AlOOH is closely related to the hydrolysis pH value, but hardly to the type of Al salts. The adsorbent can remove >95% fluoride in the first 2 min and reach adsorption equilibrium within 2 h, and the maximum defluoridation capacity is 41.9 mg/g. Furthermore, the adsorbent exhibits an excellent defluoridation efficiency at a wide pH range of 4.5-10.5. After fluoride removal, the adsorbents prepared at pH values of 6 and 7 exhibit low residual Al concentration. The Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) results confirm that the fluoride removal mechanism is the ligand exchange between fluoride and hydroxyl groups. The excellent defluoridation capacity and low residual Al demonstrate that AlOOH is a potential adsorbent for fluoride separation from water.

11.
J Antibiot (Tokyo) ; 73(12): 863-867, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32655142

RESUMO

A marine-sediment-derived bacterium Bacillus velezensis SH-B74 can produce cyclic lipopeptides (CLPs). This study presented the isolation, characterization, and activity evaluation of a new CLP from the bacterial cultures of the strain SH-B74. Multiple chromatographic methods (solid-phase extraction and reversed-phase high-performance liquid chromatography) were applied to the purifying procedure of CLP, and the structural characterization of the new CLP was conducted by various spectroscopy (1D and 2D nuclear magnetic resonance together with Fourier transform infrared spectroscopy) and spectrometry (liquid chromatography-mass spectrometry, high-resolution mass spectrometry and tandem mass spectrometry) techniques as well as Marfey's method. The results displayed that the new CLP (anteiso-C15 Ile2,7 surfactin, 1) consists of a peptidic backbone of L-Glu1, L-Ile2, D-Leu3, L-Val4, L-Asp5, D-Leu6, L-Ile7, and an anteiso-C15 type saturated fatty acid chain. Further activity assay showed that the new CLP displays activity on the inhibition of the appressoria formation of rice blast causal pathogen Magnaporthe oryzae. To sum up, the results presented the perspective of potential application of the new CLP as a green agrichemical to control M. oryzae.


Assuntos
Antifúngicos/isolamento & purificação , Bacillus/química , Lipopeptídeos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Antifúngicos/química , Antifúngicos/farmacologia , Organismos Aquáticos/química , Ascomicetos/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Lipopeptídeos/química , Lipopeptídeos/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Oryza/microbiologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Doenças das Plantas/prevenção & controle , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Massas em Tandem
12.
Med Sci Monit ; 25: 2835-2844, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30995213

RESUMO

BACKGROUND This study aims to demonstrate the underlying correlation between the resolution of liver fibrosis induced by Gexia-Zhuyu decoction (GZD) treatment and myeloid cell-mediated angiogenesis. MATERIAL AND METHODS A liver fibrosis mouse model induced by carbon tetrachloride (CCl4) intervention was employed in this study. Dynamics of blood liver function parameters were followed. The liver pathology was detected by Sirius Red and Masson staining. Matrix metalloproteinase (MMP) 2/9, tissue inhibitors of metalloproteinase (TIMP)-1/2, and vascular endothelial growth factor (VEGF)-A expression levels were measured. Bone marrow chimera mice were generated by transfer of bone morrow cells from green fluorescent protein (GFP)-knockin mice into irradiated wild-type mice, and were used it to visualize the role of myeloid cells on the fibrosis resolution induced by GZD treatment. RESULTS The result of Sirius Red and Masson staining and the dynamics of blood liver function parameters showed that 5 weeks of GZD treatment attenuated the severity of liver fibrosis with continual CCl4 administration. GZD treatment promoted the expression of MMP2/9 and repressed the heightened level of TIMP-1/2 in the recovery phase. More notably, the increased VEGF-A and augmented endothelial progenitor cells were observed in the liver and blood in mice that received GZD, and contributed to the remodeling of hepatic vascular though the CXCL12/CXCR4 axis. Then, chimera mice with GFP-positive bone marrow cells were used to show angiogenesis driven by GZD-induced myeloid cell motivation. We found that GZD facilitated myeloid cells binding to the vascular CXCR4 and induced the resolution of fibrosis. CONCLUSIONS This study shows that activation of myeloid cells induced by GZD administration accelerates the functional angiogenesis, which benefits the resolution of CCl4-induced liver fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/tratamento farmacológico , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Indutores da Angiogênese/farmacologia , Animais , Células da Medula Óssea/citologia , Tetracloreto de Carbono/farmacologia , Modelos Animais de Doenças , Feminino , Fígado/química , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional Chinesa/métodos , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/efeitos dos fármacos , Neovascularização Patológica/metabolismo , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Sci Rep ; 9(1): 583, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679533

RESUMO

With rapid spread of the urbanization, many environmental factors, such as climate, soil pH and nutrients have been changed. However, the plant pollination affected by urbanization was seldom conducted. Here, we studied the flower visitation rates, seed production, pollen limitation and flower morphological characters of Gentiana dahurica at 3 populations along an urban-peri-urban gradient around Xi'ning over 4 consecutive years, aiming to test the effects of urbanization on plant pollination service. Our results showed that the pollinator visit frequencies, interannual stability of pollinator assemblages and visit frequencies declined with the intensification of urbanization. As urbanization intensified, plant borne more flowers and the flower morphological sizes became "longer" (the length of flowers, filaments and styles were increased, but the width of flowers kept stable at the 3 populations); the flower duration, especially the female phase duration prolonged. The seed-set ratio of G. dahurica in natural condition decreased and more severe pollen limitation occurred in more urbanized populations. Also, an interannual variation of seed-set ratio and index of pollen limitation (IPL), which related with the variation of pollinator visit frequencies, were found in this study. These results suggest that the pollination service can be threatened by urbanization over a long-time interval for G. dahurica. This finding highlights the importance of pollinator affections acting on plant pollination system. Additionally, as pollinator assemblages and visit frequencies interannually changed, a long-time scale observation is needed to understand the plant-pollinator relationships.


Assuntos
Gentiana/crescimento & desenvolvimento , Polinização , Reprodução , Urbanização , Exposição Ambiental , Flores/anatomia & histologia , Flores/crescimento & desenvolvimento , Gentiana/anatomia & histologia , Sementes/anatomia & histologia , Sementes/crescimento & desenvolvimento
14.
Zhongguo Gu Shang ; 31(7): 604-607, 2018 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-30103581

RESUMO

OBJECTIVE: To investigate clinical effects of calcaneal fracture with closed reduction and minimally invasive plate fixation assisted with bidirectional distractor distraction. METHODS: From September 2015 to October 2016, 11 male patients(13 feet) with calcaneal fractures treated with bidirectional distractor distraction assisted with minimally invasive plate fixation were retrospectively studied. They were aged from 24 to 57 years old with an average of 36.4 years old;8 feet were type IIand 5 feet were type III according to Sanders classification. Postoperative incision, fracture healing, Böhler angle, Gissane angle were observed and Maryland scoring system was used to evaluate clinical effects. RESULTS: All fractures healed well without incision inflammation and incision disunion. All patients were followed up from 12 to 15 months with an average of 13.5 months. Böhler angle were improved from (9.6±7.3)° before operation to (20.2±4.6) ° at 1 year after operation, and had statistical meaning; Gissane angle increased from (92.7 ±8.5)° before operation to (121.7 ±7.6) ° at 1 year after operation. Maryland score at 1 year after operation was 88.79±8.25, and 11 feet got excellent results and 2 feet moderate. CONCLUSIONS: Bidirectional distractor distraction assisted with minimally invasive plate fixation could effectively fix calcaneal fractures, reduce postoperative complications, and get satisfied results of postoperative images and functional recovery. It is one of effective methods for treating Sanders II and III calcaneal fractures.


Assuntos
Calcâneo , Fraturas Ósseas , Adulto , Placas Ósseas , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Biochem Biophys Res Commun ; 501(4): 1060-1067, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29777702

RESUMO

Over-expression of the bromodomain and extraterminal (BET) family protein BRD4 is associated with hepatocellular carcinoma (HCC) progression. In the present study, we indentified a novel putative anti-BRD4 microRNA: microRNA-608 ("miR-608"). In HepG2 cells and primary human HCC cells, over-expression of miR-608, using a lentiviral construct, induced BRD4 downregulation and proliferation inhibition. Conversely, transfection of the miR-608 inhibitor increased BRD4 expression to promote HepG2 cell proliferation. Our results suggest that BRD4 is the primary target gene of miR-608 in HepG2 cells. shRNA-mediated knockdown or CRSIPR/Cas9-mediated knockout of BRD4 mimicked and overtook miR-608's actions in HepG2 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant BRD4 (UTR-A1718G) blocked miR-608-induced c-Myc downregulation and proliferation inhibition in HepG2 cells. In vivo, HepG2 xenograft tumor growth was significantly inhibited after expressing miR-608 or BRD4 CRSIPR/Cas9-KO construct. Importantly, BRD4 mRNA was upregulated in human HCC tissues, which was correlated with downregulation of miR-608. Together, we conclude that miR-608 inhibits HCC cell proliferation possibly via targeting BET family protein BRD4.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Animais , Sequência de Bases , Proteínas de Ciclo Celular , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Camundongos SCID , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Biochem Biophys Res Commun ; 499(3): 531-537, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29596834

RESUMO

The development of novel anti-papillary thyroid carcinoma agents is urgent. AZD5153 is a novel and specific Bromodomain-containing protein 4 (BRD4) inhibitor. Here, we show that AZD5153 dose-dependently inhibited survival, proliferation and cell cycle progression in TPC-1 cells and primary human thyroid carcinoma cells. Yet, it was non-cytotoxic to the primary thyroid epithelial cells. AZD5153 induced caspase-3/-9 and apoptosis activation in TPC-1 cells and primary cancer cells. Its cytotoxicity in TPC-1 cells was significantly attenuated with co-treatment of the caspase inhibitors. BRD4 expression was elevated in TPC-1 and primary human thyroid carcinoma cells, but was low in the thyroid epithelial cells. BRD4-regulated proteins, including c-Myc, Bcl-2 and cyclin D1, were significantly downregulated following AZD5153 treatment in TPC-1 and primary cancer cells. In vivo, oral administration of AZD5153 at well-tolerated doses significantly inhibited TPC-1 xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-dependent proteins, Myc, Bcl-2 and cyclin D1, were also downregulated in AZD5153-treated tumor tissues. Collectively, the results suggest that targeting BRD4 by AZD5153 inhibits human thyroid carcinoma cell growth in vitro and in vivo.


Assuntos
Compostos Heterocíclicos com 2 Anéis/uso terapêutico , Proteínas Nucleares/antagonistas & inibidores , Piperazinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Fatores de Transcrição/antagonistas & inibidores , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Compostos Heterocíclicos com 2 Anéis/administração & dosagem , Compostos Heterocíclicos com 2 Anéis/farmacologia , Humanos , Masculino , Camundongos SCID , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Piperazinas/administração & dosagem , Piperazinas/farmacologia , Pirazóis , Piridazinas , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Oncotarget ; 8(39): 65329-65338, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029434

RESUMO

Developing novel strategies against human colorectal cancer (CRC) cells is needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit CRC cells. Protein kinase C ζ (PKCζ) is an AMPK negative regulator. Here we found that PKCζ expression was significantly elevated in human colon cancer tissues and CRC cells. PKCζ upregulation was correlated with AMPK in-activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCζ shRNA knockdown activated AMPK signaling and inhibited HT-29 cell proliferation. Significantly, downregulation of microRNA-25-5p (miR-25-5p), a PKCζ-targeting miRNA, could be the cause of PKCζ upregulation. Exogenous expression of miR-25-5p silenced PKCζ to activate AMPK signaling, which inhibited HT-29 cell proliferation. In vivo studies showed that HT-29 xenograft growth in mice was inhibited after expressing PKCζ shRNA or miR-25-5p. Collectively, PKCζ could be a novel oncogenic protein of human CRC. PKCζ silence, by targeted-shRNA or miR-25-5p expression, activates AMPK and inhibits HT-29 cell proliferation.

18.
PLoS One ; 12(1): e0169585, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28081222

RESUMO

AKT is often hyper-activated in human colorectal cancers (CRC). This current study evaluated the potential anti-CRC activity by AT7867, a novel AKT and p70S6K1 (S6K1) dual inhibitor. We showed that AT7867 inhibited survival and proliferation of established (HT-29, HCT116 and DLD-1 lines) and primary human CRC cells. Meanwhile, it provoked caspase-dependent apoptosis in the CRC cells. Molecularly, AT7867 blocked AKT-S6K1 activation in CRC cells. Restoring AKT-S6K1 activation, via expression of a constitutively-active AKT1 ("ca-AKT1"), only partially attenuated AT7867-induced HT-29 cell death. Further studies demonstrated that AT7867 inhibited sphingosine kinase 1 (SphK1) activity to promote pro-apoptotic ceramide production in HT-29 cells. Such effects by AT7867 were independent of AKT inhibition. AT7867-indued ceramide production and subsequent HT-29 cell apoptosis were attenuated by co-treatment of sphingosine-1-phosphate (S1P), but were potentiated with the glucosylceramide synthase (GCS) inhibitor PDMP. In vivo, intraperitoneal injection of AT7867 inhibited HT-29 xenograft tumor growth in nude mice. AKT activation was also inhibited in AT7867-treated HT-29 tumors. Together, the preclinical results suggest that AT7867 inhibits CRC cells via AKT-dependent and -independent mechanisms.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Piperidinas/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Pirazóis/farmacologia , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Soft Matter ; 12(43): 8819-8824, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27722463

RESUMO

This communication describes an innovative photocurable leaky dielectric for electrohydrodynamic patterning (EHDP). Based on the well-designed molecular structure, the material in its liquid state exhibits low viscosity, high homogeneity, and more importantly a leaky dielectric characteristic; meanwhile, UV light irradiation transforms it from a liquid leaky dielectric into a solid perfect dielectric instantaneously via an interfacial reaction. Two typical EHDP processes have confirmed that the beneficial properties of this material help to rapidly fulfill a higher aspect ratio and/or smaller feature size patterning compared to its perfect dielectric counterpart. Therefore, this material provides the potential in accessing high-performance EHDP towards fabricating electrically insulating micro-/nanostructures.

20.
Zhong Yao Cai ; 38(2): 254-8, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26415398

RESUMO

OBJECTIVE: To study the medicinal plant resources and their diversity in Kangle County, Gansu Province, and to provide scientific basis on utilization and protection of the medicinal plant resources of the county. METHODS: By field survey, sample collection, taxonomic identification and data verification methods. RESULTS: There were 258 species, 65 families in existing medicinal plants, of which 43 species, 39 genera and 24 families were national protection medicinal plants. Dominant families were mainly Asteraceae and Rosaceae. In this area,the plants used whole herbs and roots ( or rhizomes) as medicinal materials represented 40.31% and 25.19% respectively, and antipyretic and rheumatism medicine accounted for 28.68% and 12.79% respectively. 12 medicinal plants were cultivated and the cultivated area was 3,000 hectares. CONCLUSION: However, the reserves of most medicinal plants are less enough and the resources are diminishing increasingly in recent years. So we should accelerate the research progress as well as developing and utilizing rationally on the premise of protection.


Assuntos
Biodiversidade , Plantas Medicinais/classificação , Asteraceae , China , Raízes de Plantas , Rizoma , Rosaceae
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