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1.
Mol Pharm ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32058727

RESUMO

Chemotherapy still accounts for a large proportion in the treatments of tumors, but the drug resistance and side effects caused by long-term chemotherapy should not be underestimated. In this work, the drug combination strategy has been widely developed to overcome the side effects brought by the use of single drugs and improve the therapeutic effect. However, in clinical applications, co-delivery of drugs is very difficult, and different in vivo kinetics due to different drug properties will lead to a decrease in efficacy. Thus, the design of novel anti-tumor therapeutic agents, including new platinum agents represent an area in need of urgent attention. Our investigation implies a promising strategy for the design of a platinum prodrug to enhance the treatment of breast cancer. Dual-drug delivery nanoparticle was developed for enhanced treatment of breast cancer based on two-into-one co-delivery strategy. Through the synergistic effect of released cisplatin hydrate and tolfenamic acid (COX-2 inhibitor) from the coordination prodrug, tumor growth is significantly suppressed, and survival time is greatly extended in breast tumor-bearing mice.

2.
Eur J Pharmacol ; : 172961, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044322

RESUMO

The tyrosine kinase inhibitor (TKI) gefitinib exerts good therapeutic effect on NSCLC patients with sensitive EGFR-activating mutations. However, most patients ultimately relapse due to the development of drug resistance after 6-12 months of treatment. Here, we showed that a HIF-1α inhibitor, YC-1, potentiated the antitumor efficacy of gefitinib by promoting EGFR degradation in a panel of human NSCLC cells with wild-type or mutant EGFRs. YC-1 alone had little effect on NSCLC cell survival but significantly enhanced the antigrowth and proapoptotic effects of gefitinib. In insensitive NSCLC cell lines, gefitinib efficiently inhibited the phosphorylation of EGFR but not the downstream signaling of ERK, AKT and STAT3; however, when combined with YC-1 treatment, these signaling pathways were strongly impaired. Gefitinib treatment induced EGFR arrest in the early endosome, and YC-1 treatment promoted delayed EGFR transport into the late endosome as well as receptor degradation. Moreover, the YC-1-induced reduction of HIF-1α protein was associated with the enhancement of EGFR degradation. HIF-1α knockdown promoted EGFR degradation, showing synergistic antigrowth and proapoptotic effects similar to those of the gefitinib and YC-1 combination treatment in NSCLC cells. Our findings provide a novel combination treatment strategy with gefitinib and YC-1 to extend the usage of gefitinib and overcome gefitinib resistance in NSCLC patients.

3.
Environ Int ; 137: 105570, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32078873

RESUMO

Electron-donating moieties (EDM) have recently been used to characterize the redox properties and treatability of dissolved organic matter during water and wastewater treatment. In this study, size exclusion chromatography followed by a derivatization-spectrometric method was developed to determine the molecular weight (MW) distribution of EDM in dissolved organic matter. The relationships between EDM concentration and chromophore content (indicated by UVA254), fluorophore content (indicated by fluorescence), and dissolved organic carbon (DOC) concentration were analyzed for different MW fractions. In general, natural organic matter (NOM) showed higher total EDM concentration and higher EDM average MW than effluent organic matter (EfOM). For NOM, fractions with MW between 1.8 k and 6.9 k Da accounted for most of the EDM (45.4%-48.6%), followed by the fractions with MW < 1.8 k Da (25.6%-42.4%). By contrast, the EDM in EfOM occurred predominantly in fractions with MW < 1 k Da (51.8%-58.6%), with lower concentrations in fractions with MW > 1.8 k Da (<20.2%). The heterogeneous MW distribution of EDM was strongly correlated to the presence of chromophores, but not DOC or fluorophores. The EDM difference between MW fractions suggested that the fraction with MW 1.8-6.9 k Da (40.7%-47.1%) and the fractions with MW < 1 k Da (50.2%-58.8%) should be the dominant oxidant consumers in NOM and EfOM, respectively. When the EDM was normalized by the DOC for each MW fraction (EDMMW/DOCMW), the EDMMW/DOCMW of relatively high-MW fractions (>1.8 k Da) is 1.2-1.9 times of relatively low-MW (<1 k Da) fractions for both NOM and EfOM, which indicates that higher-MW fractions are more susceptible to chemical oxidations. The relationship between EDM change and UVA254 change varied for different MW fractions during advanced ozonation treatment, because of the different oxidation mechanisms in operation for MW fractions. The ozonation of EfOM fractions with higher MW (>1.8 k Da) and lower MW (<1 k Da) preferentially resulted in benzoquinone formation and ring-cleavage, respectively.

4.
Bioorg Chem ; 97: 103659, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32078940

RESUMO

Seven flavonoid dimers, biflavocochins A-G, together with six known compounds were isolated from the red resins of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were elucidated based on extensive spectroscopic analysis. The absolute configurations of 1-7 was assigned by experimental and quantum chemical calculated ECD spectra, and that of 4 was further established by X-ray diffraction analysis using Cu Kα radiation. Compounds 1-3 are novel dimers of homoisoflavonoid and dihydrochalcone with a unique dibenzopyran ring. Compounds 2, 6, 7 exhibited moderate PTP1B inhibitory activities in an enzyme assay. Compound 1 showed neuroprotective effect on serum deficiency-induced cellular damage in PC12 cells.

5.
Medicine (Baltimore) ; 99(5): e18455, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000358

RESUMO

INTRODUCTION: Whole brain radiotherapy (WBRT) has been the mainstay treatment of brain metastases (BM) in non-small cell lung cancer (NSCLC) patients for years. Temozolomide (TMZ) could penetrate the blood-brain barrier and some studies showed that TMZ plus MBRT may improve clinical effectiveness. This meta-analysis is aim to evaluate the clinical effectiveness and safety of TMZ plus MBRT in the NSCLC patients with BM. METHODS AND ANALYSIS: We systematically searched databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database) without language restrictions from inception until July 26, 2019. Randomized controlled trials (RCTs) which compared TMZ plus WBRT with single WBRT in the advanced NSCLC patients with BM were included. The outcomes analysis reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), quality of life (QOL), and adverse effects. Two reviewers will independently extract data from the selected studies and assess the quality of studies. Statistical analyses will be performed using Review manager 5.3 software. Random-effects or fixed models were used to estimate pooled hazard ratio and relative risk. RESULTS: This systemic review and meta-analysis will evaluate the effects of TMZ plus MBRT in the NSCLC patients with BM in RCTs. CONCLUSION: Our study will provide evidence to judge if TMZ plus MBRT are effective treatment for NSCLC patients with BM.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Temozolomida/uso terapêutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Humanos , Neoplasias Pulmonares/patologia , Metanálise como Assunto , Revisão Sistemática como Assunto
6.
Eur J Med Chem ; 188: 112017, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926470

RESUMO

A series of xanthine compounds derived from the previous hit 20i with modification on the terminal side chain was discovered through ring formation strategy. Systematic optimization of the compounds with rigid heterocycles in the hydrophobic side chain led to the new lead compound HBK001 (21h) with the improved DPP-IV inhibition and moderate GPR119 agonism activity in vitro. As a continuing work to further study the PK and PD profiles, 21h and its hydrochloride (22) were synthesized on grams scale and evaluated on the ADME/T and oral glucose tolerance test (OGTT) in ICR mice. Compound 22 showed the improved bioavailability and blood glucose-lowering effect in vivo compared to its free base 21h probably attributed to its improved solubility and permeability. The preliminary toxicity studies on compound 22 exhibited that the result of mini-Ames was negative and the preliminary acute toxicity LD50 in mice was above 1.5 g/kg, while it showed moderate inhibition on hERG channel with IC50 4.9 µM maybe due to its high lipophilicity. These findings will be useful for the future drug design for more potent and safer dual ligand targeting DPP-IV and GPR119 for the treatment of diabetes.

7.
Phys Chem Chem Phys ; 22(5): 3058-3065, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31960886

RESUMO

Understanding the thermal transport mechanisms in amorphous organic materials is of great importance to solve hot-spot issues in organic-electronics nanodevices. Here we studied thermal transport in two popular molecular electronic materials, N,N-dicarbazolyl-3,5-benzene (mCP) and N,N'-diphenyl-N,N'-di(3-methylphenyl)-(1,1'-biphenyl)-4,4'diamine (TPD), in the amorphous state by molecular dynamics simulations. We found that due to the softness of organic materials, the low thermal conductivity of both systems can be greatly enhanced under pressure. Notably, in such systems, the convective term of heat flux provides an important contribution to thermal transport as it cross-correlates with the Virial term in the Green-Kubo formula. Mode diffusivity calculations reveal that low-frequency modes can contribute significantly to thermal transport in both mCP and TPD. By increasing the pressure, the sound velocity and relaxation time of such low-frequency modes can be enhanced, and a part of these modes converts from diffusons to propagons. The cooperation of these three effects is responsible for the strong pressure dependence of thermal transport in amorphous organic systems. Molecular pair heat flux calculations demonstrate that heat transfer mainly happens between pairs of molecules with distances below 1.4 nm. This work paves the way for the optimization of thermal transport in amorphous organic materials widely used in opto-electronics, e.g. as OLED and OPV.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31970615

RESUMO

Cancer metastasis is the main cause of death in various types of cancer. However, in the field of pharmacometrics, cancer disease progression models focus on the growth of primary tumors with tumor volume or weight as target values, while the metastasis process is less mentioned. We propose a series of mathematical models to quantitatively describe and predict the disease progression of 4T1 breast cancer in the aspect of primary breast tumor, lung metastasis and white blood cell. The 4T1 cells were injected into breast fat pad of female BALB/c mice to establish an animal model of breast cancer metastasis. The number and volume of lung metastases at different times were measured. Based on the above data, a disease progression model of breast cancer lung metastasis was established and parameter values were estimated. The white blood cell growth and the primary tumor growth of 4T1 mouse are also modeled. The established models can describe the lung metastasis of 4T1 breast cancer in three aspects: (1) the increase in metastasis number; (2) the growth of metastasis volume; (3) metastasis number-size distribution at different time points. Compared with the prior metastasis models based on von Forester equation, our models distinguished the growth rate of primary tumor and metastasis and got parameter values for 4T1 mouse model. And the current models optimized the metastasis number-size distribution model by utilizing logistic function instead of the prior power function. This study provides a comprehensive description of lung metastasis progression for 4T1 breast cancer model, as well as an alternative disease progression model structure for further pharmacodynamics modeling.

9.
Int J Pharm ; 573: 118736, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31756442

RESUMO

Oxaliplatin is a chemotherapeutic agent widely used in cancer treatment whereas its immunosuppressive effect hinders the progress of immunotherapy. Here we have synthesized a new compound NLGplatin constructed by combining oxaliplatin (OXA) and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919. The NLGplatin acquires chemotherapeutic properties of OXA and can activate the immune system, and also retains the ability to inhibit IDO enzyme activity without affecting the proliferation of immune cells. This difunctional drug has a great potential to achieve effective cancer chemoimmunotherapy.

10.
Cancer Med ; 9(1): 278-289, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701672

RESUMO

Breast cancer (BC) leads to the highest mortality in women worldwide, characterized by inevitable proliferation and metastasis of BC cells. Mounting evidence confirm that lncRNAs play a significant role in the tumorigenesis and development of BC. lncRNA CERS6-AS1 is a novel discovery, and its role and molecular mechanism in BC has not been studied. In this study, it was discovered that CERS6-AS1 was overexpressed in BC tissues and cells. CERS6-AS1 accelerated cell proliferation and suppressed cell apoptosis in BC. Moreover, molecular mechanism exploration uncovered that there was a positive association between CERS6 and CERS6-AS1 (or IGF2BP3) expression in BC. Furthermore, IGF2BP3 serves as a RNA-binding protein for CERS6-AS1 and CERS6-AS1 promoted CERS6 mRNA stability by binding to IGF2BP3. In the end, rescue experiments verified that overexpression of CERS6 rescues the inhibition of CERS6-AS1 deficiency on BC progression in vitro and vivo. Taken together, these evidences suggested that CERS6-AS1 promoted the progression of BC by binding to IGF2BP3 and thus enhancing the stability of CERS6 mRNA, providing a new underlying therapeutic target for BC to improve prognosis.

11.
Cell Microbiol ; 22(1): e13114, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31487436

RESUMO

Nuclear import of proteins relies on nuclear import receptors called importins/karyopherins (Kaps), whose functions were reported in yeasts, fungi, plants, and animal cells, including cell cycle control, morphogenesis, stress sensing/response, and also fungal pathogenecity. However, limited is known about the physiological function and regulatory mechanism of protein import in the rice-blast fungus Magnaporthe oryzae. Here, we identified an ortholog of ß-importin in M. oryzae encoded by an ortholog of KAP119 gene. Functional characterisation of this gene via reverse genetics revealed that it is required for vegetative growth, conidiation, melanin pigmentation, and pathogenicity of M. oryzae. The mokap119Δ mutant was also defective in formation of appressorium-like structure from hyphal tips. By affinity assay and liquid chromatography-tandem mass spectrometry, we identified potential MoKap119-interacting proteins and further verified that MoKap119 interacts with the cyclin-dependent kinase subunit MoCks1 and mediates its nuclear import. Transcriptional profiling indicated that MoKap119 may regulate transcription of infection-related genes via MoCks1 regulation of MoSom1. Overall, our findings provide a novel insight into the regulatory mechanism of M. oryzae pathogenesis likely by MoKap119-mediated nuclear import of the cyclin-dependent kinase subunit MoCks1.

12.
J Enzyme Inhib Med Chem ; 35(1): 404-413, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31880473

RESUMO

A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16 ± 0.05 and 3.86 ± 0.10 µM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (koff=1.60 × 10-3 s-1) from the catalytic domain.


Assuntos
Helicobacter pylori/efeitos dos fármacos , Ureia/farmacologia , Urease/antagonistas & inibidores , Antibacterianos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos , Helicobacter pylori/citologia , Helicobacter pylori/enzimologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/química , Urease/metabolismo
13.
Sci Total Environ ; 701: 134660, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31704401

RESUMO

The biogeochemical cycles of plant nitrogen (N) and phosphorus (P) are interlinked by ecological processes, and the N and P cycles become uncoupled in response to global change experiments. However, the complex natural hydrothermal conditions in arid, semiarid and humid grassland ecosystems may have different effects on the availability of soil nutrients and moisture and may induce different balances between the N and P cycles. Here, we evaluated how the aridity index (AI) affects the balance between N and P of alpine grassland by the collected 115 sites along water and heat availability gradients on the Tibetan Plateau. We found that AI was negatively related to the variation in the coefficients of soil total dissolved N (TDN) and soil availability of P (SAP), and positive effects of AI, TDN and SAP on the coupling of plant N and P were detected. Thus, AI was positively correlated with soil nutrients and moisture, which may favor the co-uptake of soil nutrients by plants, resulting in a small variation in plant N and P in humid environments. Conversely, in arid environments with temporally variable soil nutrients, the plants tend to be more flexible in their N:P stoichiometry. Generally, our findings suggest that plant N and P could be more strongly coupled in humid conditions than in arid environments across alpine grasslands, with potential decoupling of the N biogeochemical cycle from P in an arid environment with an asynchronous dynamic of temperature and precipitation.


Assuntos
Monitoramento Ambiental , Pradaria , Nitrogênio/análise , Fósforo/análise , Microbiologia do Solo , Ecossistema , Temperatura Ambiente , Água
14.
Phytother Res ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31833107

RESUMO

Berberine (BBR), a small alkaloid, is used as a hypoglycemic agent in China. Stachyose (Sta), a Rehmannia glutinosa oligosaccharide, acts as a prebiotic. This study aimed to evaluate whether BBR combined with Sta produced better glycometabolism than BBR alone, and explored the effects on gut microbiota and metabolomics. Type-2 diabetic db/db mice were administered BBR (100 mg/kg), Sta (200 mg/kg), or both by gavage once daily. Glucose metabolism, the balance of α- and ß-cells, and mucin-2 expression were ameliorated by combined treatment of BBR and Sta, with stronger effects than upon treatment with BBR alone. The microbial diversity and richness were altered after combined treatment and after treatment with BBR alone. The abundance of Akkermansia muciniphila was increased by combined treatment compared to treatment with BBR alone, while the levels of the metabolite all-trans-heptaprenyl diphosphate were decreased and the levels of fumaric acid were increased, which both showed a strong correlation with A. muciniphila. In summary, BBR combined with Sta produced better glycometabolism than BBR alone through modulating gut microbiota and fecal metabolomics, and may aid in the development of a novel pharmaceutical strategy for treating Type 2 diabetes mellitus.

15.
J Hazard Mater ; : 121898, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31879104

RESUMO

Elimination of commercial Kathon biocide (methyl-isothiazolinone (MIT) and chloro-methyl-isothiazolinone (CMIT) mixture) by ozonation was investigated in real RO influent and concentrate. MIT and CMIT had different reactivities (second-order-rate-constants) with molecular ozone and OH. Ozonation of biocides followed an instantaneous phase (16.6 %-36.9 % contributions) and then a gradual phase (33.6 %-78.8 % contributions). Newly developed kinetics including both phases demonstrated that O3 oxidation contributed 25.6 %-39.8 % and <10 % of MIT and CMIT eliminations, respectively, and OH oxidation contributed 60.2 %-74.4 % and >90 % of MIT and CMIT eliminations, respectively. OH oxidation at the instantaneous phase accounted 15.7 %-37.9 % of total OH oxidation. Mass ratios of O3/DOC of 0.24 and 0.32 were needed for ∼80 % eliminations of MIT and CMIT in RO concentrate, respectively. The kinetics including both phases allowed a para-chlorobenzoic acid indicator model to predict MIT and CMIT elimination better than that including gradual ozonation only, with 58.9 %-96.0 % lower relative error. The attenuations of electron-donating-moiety indicated that O3 may preferentially react with chromophores through aromatic cleavage and electrophilic extraction, while •OH may non-selectively react with chromophores through predominant electrophilic addition. A surrogate model for biocide elimination by UVA254 loss was proposed to be nonlinear rather than linear, which reduced 31.8 %-71.3 % surrogating error.

16.
Int J Biol Macromol ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31712138

RESUMO

The aim of the study was to investigate the antioxidant effect of seleno-amino-oligosaccharide (Se-AOS) on intestinal porcine epithelial cells (IPEC-1). MTT assay showed that Se-AOS had no effect on the viability of IPEC-1 cells up to a concentration of 9200 µg/L and Se-AOS significantly increased the viability of IPEC-1 cells compared to cells exposed to H2O2 alone. Se-AOS significantly increased the level of superoxide Dismutase (SOD) and decreased the levels of malonic dialdehyde (MDA) and lactate dehydrogenase (LDH) in IPEC-1 cells. The gene expression levels of different antioxidant enzymes dramatically increased by the pretreatment of Se-AOS compared to H2O2 treatment. In addition, the results indicated that Se-AOS up-regulated the intracellular Nrf2 and down-regulated the level of Keap1 by western blot. Taken together, these findings suggested that Se-AOS can protect IPEC-1 cells from oxidative damage through activating the Keap1/Nrf2 signaling pathway.

17.
Int J Mol Sci ; 20(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731602

RESUMO

Low molecular seleno-aminopolysaccharide (LSA) was synthesized with sodium selenite and low molecular aminopolysaccharide (LA), which is an organic selenium compound. This study is aimed to investigate the protective effect of LSA on the intestinal mucosal barrier in weaning stress rats by detecting the intestinal tissue morphology and function, mucosal thickness and permeability, the structure of MUC2, antioxidant index, the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2), and its related factors. The results showed that LSA significantly increased the height of intestinal villi (p < 0.05) and increased the thickness of intestinal mucosa and the number of goblet cells, which indicated that LSA has a protective effect on the intestinal mucosal barrier that is damaged by weaning. Moreover, LSA significantly reduced the level of DAO, D-LA, and LPS compared with the weaning group (p < 0.05), which indicated that LSA reduced the intestinal damage and permeability of weaning rats. In addition, LSA could increase the number and length of glycans chains and the abundance of acid glycans structures in the MUC2 structure, which indicated that LSA alleviated the changes of intestinal mucus protein structure. LSA significantly increased the levels of GSH-Px, SOD, LDH, and CAT, while it decreased the level of MDA in serum and intestinal tissue, which suggested that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress of weaning rats. RT-PCR results showed that LSA significantly increased the expression level of antioxidant genes (GSH-Px, SOD, Nrf2, HO-1), glycosyltransferase genes (GalNT1, GalNT3, GalNT7) and mucin gene (MUC2) in intestinal mucosa (p < 0.05). The results of western blot showed that the LSA activated the Nrf2 signaling pathway by down-regulating the expression of Keap1and up-regulating the expression of Nrf2, and protected the intestinal mucosa from oxidative stress. Overall, LSA could play a protective role in intestinal mucosal barrier of weaning rats by activating the Nrf2 pathway and alleviating the alnormal change of mucin MUC2.

18.
Biofactors ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778242

RESUMO

Breast cancer is a common cancer and becomes a severe healthy problem among females. Ras-ERK pathway and H2B phosphorylation at serine 14 (H2BS14ph) was involved in some cancers. Our research probed the feasible relationship between Ras-ERK1/2 and H2BS14ph in breast cancer cells and the underlying mechanism. MCF7 cells were transfected with RasG12V/T35S plasmid, and H2BS14ph, ERK1/2, Mst1, and MDM2 expression were evaluated through executing western blot. MTT, soft-agar colony formation, flow cytometry, and Transwell assays were applied for delving the functions of H2BS14 in MCF7 cells behavior. ERK1/2 pathway downstream factors and Mst1 expression was appraised via RT-PCR. The ChIP assay was utilized for detecting the relation between Ras and ERK1/2-downstream factors. We found that, RasG12V/T35S inhibited H2BS14ph expression while upregulated phospher-ERK1/2. In addition, RasG12V/T35S promoted MCF7 cell viability, colony numbers and migration, while H2BS14ph presented the opposite results. Transfection with RasG12V/T35S and cotransfection with RasG12V/T35S and H2BS14ph altered the expression of ERK1/2 downstream factors in an opposite direction. Additionally, RasG12V/T35S -ERK1/2 triggered H2BS14ph repression was concerned with MDM2-adjusted Mst1 degradation. Conclusions, RasG12V/T35S -ERK1/2 accelerated the development of breast cancer via mediating H2BS14ph by MDM2-modulated Mst1 degradation.

19.
BMC Genet ; 20(1): 80, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646976

RESUMO

BACKGROUND: Bleeker's yellow tail (Xenocypris davidi Bleeker, YT) and topmouth culter (Culter alburnus Basilewsky, TC) are both famous and important economic freshwater fish in China. YT, a kind of omnivorous fish, has strong resistance. TC, a kind of carnivorous fish, has high-quality meat but poor resistance. Distant hybridization can integrate the advantages of both parents. There has been no previous report regarding hybrid fish derived from female YT × male TC. It is expected that hybridization of these two kinds of fish will result in F1 hybrids with improved characteristics, such as faster growth rate, stronger resistance, and high-quality meat, which are of great significance in fish genetic breeding. RESULTS: In this study, we investigated the main biological characteristics of diploid hybrid fish derived from female YT × male TC. The hybrids had an intermediate number of upper lateral line scales between those for YT and TC. The hybrids were diploids with 48 chromosomes and had the same karyotype formula as their parents. The hybrids generated variations in 5S rDNA (designated class IV: 212 bp) and lost specific 5S rDNA derived from the maternal parent (designated class II: 221 bp), which might be related to hybridization. In terms of reproductive traits, all the tested female hybrids exhibited normal gonadal development, and the two-year-old F1 females produced mature eggs. However, all the tested testes of the male hybrids could not produce mature sperm. It is possible that the hybrid lineage will be established by back-crossing the fertile female hybrids and their parents. CONCLUSIONS: Obtaining a fertile female hybrid fish made the creation of a new type of fish possible, which was significant in fish genetic breeding.

20.
J Fish Biol ; 95(6): 1523-1529, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31631336

RESUMO

activin ßA and ßB from diploid and allotriploid crucian carp were cloned.The differential expression of activin ßA and ßB genes in female allotriploid and diploid red crucian carp Carassius auratus red var. were studied and found to be expressed in all the tested tissues; particularly, the expression of activin ßA and ßB was elevated in the ovaries of allotriploids and differential expression in pituitaries during the non-breeding season and the breeding season period. The immunohistochemistry indicated that the abnormal triploid ovaries were dominated by small oogonium-like cells with dense signals and that the elevated expression of activin ßA and ßB in the ovaries of allotriploids may be related to allotriploid sterility.

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