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1.
Artigo em Inglês | MEDLINE | ID: mdl-32071245

RESUMO

Recurrence and metastasis remain the major obstacles to successful treatment of hepatocellular carcinoma (HCC). Chromatin remodeling factor ARID2 is commonly mutated in HCC, indicating its important role in cancer development. However, its role in HCC metastasis is largely elusive. In this study, we find that ARID2 expression is significantly decreased in metastatic HCC tissues, showing negative correlation with pathological grade, organ metastasis and positive association with survival of HCC patients. ARID2 inhibits migration and invasion of HCC cells in vitro and metastasis in vivo. Moreover, ARID2 knockout promotes pulmonary metastasis in different HCC mouse models. Mechanistic study reveals that ARID2 represses epithelial-mesenchymal transition (EMT) of HCC cells by recruiting DNMT1 to Snail promoter, which increases promoter methylation and inhibits Snail transcription. In addition, we discover that ARID2 mutants with disrupted C2H2 domain lose the metastasis suppressor function, exhibiting a positive association with HCC metastasis and poor prognosis. In conclusion, our study reveals the metastasis suppressor role as well as the underlying mechanism of ARID2 in HCC and provides a potential therapeutic target for ARID2-deficient HCC.

2.
Bioengineered ; 11(1): 229-240, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32050844

RESUMO

This paper identified the dominant protozoan species in the four layers of rhizosphere soil during the six growth stages of Beta vulgaris L. and analyzed the correlations of the abundance and diversity of the dominant protozoan species with soil properties at different growth stages and soil depth. A total of 15 species of protozoa were identified; among them, Colpoda sp., Bodo sp., two kinds of Oxytricha sp., and Tachysoma sp. were the most dominant species of Beta vulgaris L. rhizosphere soil. The Colpoda sp. was eurytopic species in the Beta vulgaris L. rhizosphere soil and Tachysoma sp., Vorticella sp., Colpoda sp., Oxytricha sp.1, and Oxytricha sp. 2 were noted closely related to the acceleration function of circulation of N and P elements in soils. These dominant protozoan species were proposed to play a significant role of fertilization on N supply in rhizosphere soil during the initial growth of Beta vulgaris L.

3.
J Chromatogr A ; : 460917, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32037073

RESUMO

A method for sample pretreatment using liquid-liquid chromatography combined with a conventional liquid chromatography was developed for quantitative determination of trace chemical component in traditional Chinese medicine. The main effective component, wilforlide A, in the traditional Chinese medicinal herb Tripterygium wilfordii as well as in its Chinese patent medicine glycosides tablets was successfully determined after sample pretreatment by liquid-liquid chromatography. A biphasic solvent system n-hexane-ethyl acetate-ethanol-water (6:4:6:4, v/v) was screened for crude sample treatment by liquid-liquid chromatography. The collection time of eluted fractions containing target component could be well predicted using a continuous-stirred tank reactors model after determination of its retention time. Then, quantitative analysis of wilforlide A in Tripterygium wilfordii as well as in its tablets could be successfully determined by conventional reversed-phase high performance liquid chromatography with UV detector. Under the optimized conditions, the method showed good linearity (R2 = 0.9999) for wilforlide A in the range of 0.01 mg mL-1 -0.10 mg mL-1. The limit of detection and limit of quantity were 1.35 ng mL-1 and 4.50 ng mL-1, respectively. The average recovery rate, intra-day and inter-day precisions of wilforlide A were 96.43%, 0.67% and 1.14%, respectively. Compared with previous studies, the present method showed advantages of complete recovery of target component in the sample pretreatment and good repeatability.

4.
J Orthop Surg Res ; 15(1): 37, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005205

RESUMO

BACKGROUND: It is difficult for the surgeon to measure pelvic displacement in the closed reduction operation for unstable pelvic fracture. We therefore developed a pelvic deformity measurement software program based on standardized radiographs. The objectives of the present study were to evaluate the inter-observer reliability of the program for measuring specific fracture types on preoperative pelvic films and to assess the validity of the measurement software program by comparing it with a gold standard. METHODS: Twenty-five patients diagnosed with AO/OTA type B or C pelvic fractures with the unilateral pelvis fractured and dislocated were included in this study. Four separate observers repeatedly determined the translational and rotational patterns and outcomes using the software program and hand measurement, and calculated the displacement using computed tomography (CT) coupled with a three-dimensional (3D) CT model. The validity of the measurement software was calculated by assessing the consistency between the software measurements and the gold standard. Additionally, inter-observer reliability was assessed for the software. The software was also applied in preliminary clinical practice for closed reduction procedures. RESULTS: The overall inter-observer reliabilities of the software program, CT coupled with 3D reconstruction, and hand measurements were high, with kappa values of 0.956, 0.958, and 0.853, respectively. The software showed validity similar to that of CT coupled with 3D reconstruction (0.939 vs. 0.969), and better than that of hand measurement (0.939 vs. 0.858). A preliminary clinical application demonstrated that the software is effective for guiding closed reduction of pelvic fractures. CONCLUSIONS: Our newly established pelvic deformity measurement program is a reliable and accurate tool for analyzing pelvic displacement patterns and can be used for guidance of closed reduction and planning of the reduction pathway. LEVEL OF EVIDENCE: III.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32035228

RESUMO

To better understand the potential function of carotenoids in the chemoprevention of cancers, mechanistic understanding of carotenoid action on genetic and epigenetic signaling pathways is critically needed for human studies. The use of appropriate animal models is the most justifiable approach to resolve mechanistic issues regarding protective effects of carotenoids at specific organs and tissue sites. While the initial impetus for studying the benefits of carotenoids in cancer prevention was their antioxidant capacity and pro-vitamin A activity, significant advances have been made in the understanding of the action of carotenoids with regards to other mechanisms. This review will focus on two common carotenoids, provitamin A carotenoid ß-cryptoxanthin and non-provitamin A carotenoid lycopene, as promising chemopreventive agents or chemotherapeutic compounds against cancer development and progression. We reviewed animal studies demonstrating that ß-cryptoxanthin and lycopene effectively prevent the development or progression of various cancers and the potential mechanisms involved. We highlight recent research that the biological functions of ß-cryptoxanthin and lycopene are mediated, partially via their oxidative metabolites, through their effects on key molecular targeting events, such as NF-κB signaling pathway, RAR/PPARs signaling, SIRT1 signaling pathway, and p53 tumor suppressor pathways. The molecular targets by ß-cryptoxanthin and lycopene, offer new opportunities to further our understanding of common and distinct mechanisms that involve carotenoids in cancer prevention. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

6.
Pharmacol Res ; : 104695, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061839

RESUMO

The primary cause of cancer-related death from solid tumors is metastasis. While unraveling the mechanisms of this complicated process continues, our ability to effectively target and treat it to decrease patient morbidity and mortality remains disappointing. Early detection of metastatic lesions and approaches to treat metastases (both pharmacological and genetic) are of prime importance to obstruct this process clinically. Metastasis is complex involving both genetic and epigenetic changes in the constantly evolving tumor cell. Moreover, many discrete steps have been identified in metastatic spread, including invasion, intravasation, angiogenesis, attachment at a distant site (secondary seeding), extravasation and micrometastasis and tumor dormancy development. Here, we provide an overview of the metastatic process and highlight a unique pro-metastatic gene, melanoma differentiation associated gene-9/Syntenin (MDA-9/Syntenin) also called syndecan binding protein (SDCBP), which is a major contributor to the majority of independent metastatic events. MDA-9 expression is elevated in a wide range of carcinomas and other cancers, including melanoma, glioblastoma multiforme and neuroblastoma, suggesting that it may provide an appropriate target to intervene in metastasis. Pre-clinical studies confirm that inhibiting MDA-9 either genetically or pharmacologically profoundly suppresses metastasis. An additional benefit to blocking MDA-9 in metastatic cells is sensitization of these cells to a second therapeutic agent, which converts anti-invasion effects to tumor cytocidal effects. Continued mechanistic and therapeutic insights hold promise to advance development of truly effective therapies for metastasis in the future.

7.
Mol Med Rep ; 21(3): 1590-1596, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016461

RESUMO

Increasing research has demonstrated that expression of brain and muscle ARNT­like 1 (BMAL1) and other circadian clock genes can be regulated by drugs and toxicants. We previously demonstrated that icariin, extracted from Herba Epimedii, sromotes osteogenic differentiation. However, the mechanism underlying the association between icariin and BMAL1 in osteogenic differentiation of bone marrow­derived mesenchymal stem cells (BMSCs) remains unclear. The present study was designed with an aim to clarify the association between icariin and BMAL1 in osteogenic differentiation of BMSCs. The Cell Counting Kit­8 assay was used to evaluate cell proliferation. The expression of bone morphogenetic protein 2 (BMP2), RUNX family transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OC) and BMAL1 in BMSCs was evaluated by reverse transcription­quantitative PCR and western blotting. ALP and Alizarin red S (ARS) staining were also performed. Icariin promoted BMSC proliferation, and upregulated expression of osteogenic genes and BMAL1. In addition, expression of the osteogenic genes BMP2, RUNX2, ALP and OC were upregulated by BMAL1 overexpression. Furthermore, we confirmed that BMAL1 deficiency suppressed osteogenic differentiation in BMSCs. Finally, ARS staining of BMAL1­/­ BMSCs revealed that BMAL1 was an essential intermediary in matrix mineralization during osteogenic differentiation. In conclusion, these results demonstrated that icariin promoted osteogenic differentiation through BMAL1­BMP2 signaling in BMSCs. The present study thus described a novel target of icariin that has potential applications in the treatment of osteogenic disorders.

8.
Mol Med Rep ; 21(3): 1517-1526, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016472

RESUMO

Non­small cell lung cancer (NSCLC) is prevalent worldwide. Lung squamous cell carcinoma (LUSC) is one of the main subtypes of NSCLC yet, currently, few biomarkers are available for the diagnosis of LUSC. The present study aimed to investigate the expression and role of adenosine deaminase RNA specific B1 (ADARB1) in lung squamous cell carcinoma (LUSC). Integrative bioinformatics analysis was used to identify the effects of ADARB1 expression on the occurrence and prognosis of LUSC. The expression of ADARB1 was further examined by immunohistochemistry (IHC). Bioinformatics analysis suggested that ADARB1 was downregulated in LUSC, serving as a potential tumor suppressor, and these results were verified by IHC performed on a lung cancer tissue array. Clinical studies suggested that ADARB1 expression and methylation levels were significantly associated with patient characteristics in LUSC. Moreover, ADARB1 global methylation levels were upregulated in LUSC tissues compared with normal lung tissues. Higher methylation levels of cg24063645 were associated with shorter overall survival time of patients with LUSC. A negative correlation was identified between ADARB1 and epidermal growth factor receptor (EGFR) expression in LUSC. Using the Gene Expression Omnibus database, it was suggested that the expression of ADARB1 in LUSC was significantly different compared with that in lung adenocarcinoma. Furthermore, protein­protein interactions were studied and a biological process annotation analysis was conducted. The present study suggested that ADARB1 was downregulated in LUSC; therefore, ADARB1 may serve as a specific biomarker and a potential therapeutic target for LUSC.

9.
Bull Math Biol ; 82(2): 29, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32025912

RESUMO

There is a substantial interest in detailed models of viral infection and antiviral drug kinetics in order to optimize the treatment against viruses such as HIV. In this paper, we study within-viral dynamics under general intracellular distributed delays and periodic combination antiviral therapy. The basic reproduction number [Formula: see text] is established as a global threshold determining extinction versus persistence, and spectral methods are utilized for analytical and numerical computations of [Formula: see text]. We derive the critical maturation delay for virus and optimal phase difference between sinusoidally varying drug efficacies under various intracellular delays. Furthermore, numerical simulations are conducted utilizing realistic pharmacokinetics and gamma-distributed viral production delays for HIV. Our results demonstrate that the relative timing of the key viral replication cycle steps and periodic antiviral treatment schedule involving distinct drugs all can interact to critically affect the overall viral dynamics.

10.
Acta Otolaryngol ; : 1-4, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068453

RESUMO

Background: It has been demonstrated that miRNAs play critical roles in the tumorigenesis and progression of various tumors.Objective: The purpose of this research was to determine the serum miR-632 levels in patients with laryngeal squamous cell carcinoma (LSCC) and to investigate its diagnostic and prognostic value.Materials and methods: We detected serum miR-632 levels in 162 LSCC patients and 42 healthy volunteers. The ROC curve was carried out to determine diagnostic accuracy.Results: We observed that serum miR-632 levels were upregulated in LSCC patients compared with healthy volunteers (p < .01). Subsequent results from ROC indicated that high sensitivity and specificity of serum miR-632 for diagnosing LSCC (area under the curve 0.8828). In addition, it was found that high expressions of serum miR-632 were significantly associated with advanced N stage (p = .020), histological grade (p = .001), and TNM stage (p = .014). Furthermore, patients with higher serum miR-632 expression had a shorter OS and DFS time than those with lower serum miR-632 levels.Conclusion: Our data revealed that serum miR-632 may be a potential noninvasive biomarker which may become a potential diagnostic and prognostic biomarker for LSCC patients.

11.
Medicine (Baltimore) ; 99(3): e18767, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011466

RESUMO

RATIONALE: About one-third of the lung tumors are staged as locally advanced at the time of initial diagnosis; however, the optimal induction treatment before curative resection has not been elucidated. To date, the evidence regarding the preoperative apatinib plus S-1 for locally advanced pulmonary adenocarcinoma is scarce. PATIENT CONCERNS: A 29-year-old female was admitted because of persistent cough, sputum, and chest distress for 2 months. DIAGNOSES: Primary pulmonary adenocarcinoma (cT3N2M0, IIIB) with unknown driver gene mutation status. INTERVENTIONS: The patient had received 4 months of neoadjuvant therapy using oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval), followed by anatomical lobectomy with curative intent. Adjuvant apatinib (425 mg daily for a month, and 250 mg daily for another month) plus S-1 at the same dosage were administered for 2 months. Thereafter, maintenance of low-dose S-1 monotherapy (40 mg, twice daily for 4 weeks with a 2-week drug-free interval) was continued for 6 months. OUTCOMES: The adverse events were tolerable and well-controlled. A postoperative recurrence-free survival for 2 years and a half up to now was indicated. LESSONS: Preoperative apatinib plus S-1 showed efficacy in locally advanced pulmonary adenocarcinoma. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Ácido Oxônico/administração & dosagem , Piridinas/administração & dosagem , Tegafur/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Feminino , Humanos , Terapia Neoadjuvante , Pneumonectomia
12.
Nat Commun ; 11(1): 739, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029730

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with features that vary by ethnicity. A systematic characterization of the genomic landscape of Chinese ccRCC is lacking, and features of ccRCC associated with tumor thrombus (ccRCC-TT) remain poorly understood. Here, we applied whole-exome sequencing on 110 normal-tumor pairs and 42 normal-tumor-thrombus triples, and transcriptome sequencing on 61 tumor-normal pairs and 30 primary-thrombus pairs from 152 Chinese patients with ccRCC. Our analysis reveals that a mutational signature associated with aristolochic acid (AA) exposure is widespread in Chinese ccRCC. Tumors from patients with ccRCC-TT show a higher mutational burden and genomic instability; in addition, mutations in BAP1 and SETD2 are highly enriched in patients with ccRCC-TT. Moreover, patients with/without TT show distinct molecular characteristics. We reported the integrative genomic sequencing of Chinese ccRCC and identified the features associated with tumor thrombus, which may facilitate ccRCC diagnosis, prognosis and treatment.

13.
J Chem Inf Model ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050066

RESUMO

Farnesoid X receptor (FXR) agonists can reverse dysregulated bile acid metabolism thus are potential therapeutics to prevent and treat non-alcoholic fatty liver disease. The low success rate of FXR agonists R&D and the side effects of the clinical candidates such as obeticholic acid make it urgent to discover new chemotypes. Unfortunately, structure-based virtual screening (SBVS) that can speed up drug discovery had rarely been reported with success for FXR, which was likely hindered by the failure in addressing protein flexibility. To address this issue, we devised human FXR- (hFXR-) specific ensemble learning models based on pose filters from 24 agonist-bound hFXR crystal structures and coupled them to traditional SBVS approaches of FRED docking plus Chemgauss4 scoring function. It turned out that hFXR-specific pose filters ensemble (PFE) was able to improve ligand enrichment significantly, which rendered 3RUT-based SBVS with its PFE as the ideal approach for FXR agonists discovery. By screening of the Specs chemical library and in vitro FXR transactivation bioassay, we identified a new class of FXR agonists with compound XJ034 as the representative, which would have been missed if the PFE was not coupled to. Following that, we performed in-depth biological studies which demonstrated that XJ034 resulted in a downtrend of intracellular triglyceride in vitro, significantly decreased the serum/liver TG in high fat diet-induced C57BL/6J obese mice, and more importantly, showed metabolic stabilities in both plasma and liver microsomes. To provide insight into further structure-based lead optimization, we solved the crystal structure of hFXR complexed with compound XJ034 that uncovers a unique hydrogen bond between compound XJ034 and residue Y375. The current work highlights the power of our pose filter-based ensemble learning approach in term of scaffold hopping and provides a promising lead compound for further development.

14.
Inorg Chem ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077694

RESUMO

The MnII(HCO3-)-H2O2 (MnII-BAP) system shows high reactivity toward oxidation of electron-rich organic substrates; however, the predominant oxidizing species and its formation pathways involved in the MnII-BAP system are still under debate. In this study, we used the MnII-BAP system to oxidize As(III) in that As(III), Mn2+, and HCO3- are common components in As(III)-contaminated groundwater. Kinetic results show that MnII(HCO3-)n [including MnII(HCO3)+ and MnII(HCO3)2] is a key factor in the MnII-BAP system to oxidize As(III). Quenching experiments rule out contributions of OH• and 1O2 to As(III) oxidation and reveal that O2•- and the oxidizing species generated from O2•- play predominant roles in the oxidation of As(III). We further reveal that the MnO2+(HCO3-)n intermediate generated in the reaction between MnII(HCO3-)n and O2•-, instead of O2•-, is the predominant oxidizing species. Although CO3•- also contributes to As(III) oxidation, the high reaction rate constant between CO3•- and O2•- indicates that CO3•- is not the predominant oxidizing species in the As(III)-MnII-BAP system. In addition, the presence of Mn(III) further indicates the important Mn(II)-Mn(III) cycling in the MnII-BAP system. We therefore suggest two important roles of MnII(HCO3-)n in the MnII-BAP system: (i) MnII(HCO3-)n reacts with H2O2 to form the MnIII(HCO3)3 intermediate, followed by a subsequent reaction between MnIII(HCO3)3 and H2O2 to produce O2•-; (ii) MnII(HCO3-)n can also stabilize O2•- with the formation of MnO2+(HCO3-)n. MnO2+(HCO3-)n is an electrophilic reagent and plays the predominant role in the oxidation of As(III) to As(V).

15.
J Org Chem ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32013428

RESUMO

A silver-assisted method for [3 + 2] annulation of nitrones with isocyanides has been developed. The developed protocol allows access to a variety of 2,3,4-trisubstituted 1,2,4-oxadiazolidin-5-one derivatives as single diastereomers in good to excellent yields using silver oxide as the catalyst and molecular oxygen as the terminal oxidant. A plausible mechanism involving a nucleophilic addition/cyclization/protodeargentation/oxidation pathway is proposed on the basis of experimental results.

16.
J Cell Physiol ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037547

RESUMO

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.

17.
Chemosphere ; 248: 126018, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32035384

RESUMO

In recent years, prometryn was utilized as watergrass remover in the aquaculture industry, resulting in the accumulated residual in the aquatic products. The present study focuses on the ozone degradation of prometryn in the Ruditapes philippinarum. The ozone concentration in water increased along with the injection time (60min). The contents of hydroxyl (·OH) and superoxide (O2·-) radicals increased along with the ozone injection time. The effects of temperature, pH, prometryn initial concentration and ozone concentration on the removal efficiency of prometryn were evaluated. The maximum removal efficiency of 86.12% was obtained under the conditions of pH 7, prometryn initial concentration 0.05 mg/kg and the ozone concentration 4.2 mg/L at 28 °C for 30 min. Ion chromatography (IC) and Fourier transform infrared (FT-IR) spectroscopy results show that the S and N atoms in the outer layer of the triazine ring during the prometryn degradation process were oxidized and removed. A total of 30 intermediate compounds were identified using the gas chromatography-mass spectrometry (GC-MS) method. Combined with the IC and FT-IR results, three possible degradation pathways of prometryn were proposed. The prometryn was finally degraded into some small molecules with reduced toxicity by 63.16% for 120 min ozonization treatment. Overall, our work provides a novel approach for prometryn degradation in Ruditapes philippinarum, which can be extended for removing the residues of agricultural and veterinary drugs in other aquatic products.

18.
Chemosphere ; 249: 126157, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32062217

RESUMO

Waterborne metals may be hazardous to aquatic organisms and trigger stress responses. The present study aimed to assess the effect of exposure to 100 µg/L cadmium (Cd) or copper (Cu) for 48 h on juvenile Marsupenaeus japonicus, in terms of bioaccumulation and the whole body transcriptome. The results demonstrated that Cu accumulation in M. japonicas was much higher than that of Cd. Meanwhile, transcriptome analysis identified 1802 and 2670 differentially expressed genes (DEGs) after 48 h exposure to 100 µg/L Cd and Cu, respectively. Among them, 851 DEGs responded to both metals. Cd and Cu stress shared genes were related to the cytoskeleton, immunity, antioxidation, and detoxification. Metallothionein 1 (MT1) was specifically induced in the Cd-stress response, while glycometabolism, heat shock protein 90 (HSP90), metallothionein 2 (MT2), apoptosis, and iron transport-related genes were changed specifically in response to Cu stress. In addition, real-time PCR was used to verify the expression patterns of 28 randomly selected DEGs. The sequencing and real-time PCR results were consistent. Moreover, based on the number of significantly modulated genes and their expression levels, we deduced that Cu acts as a stronger stress inducer than Cd in M. japonicus. The identified Cd and Cu stress related genes and pathways will provide new insights into the common and different molecular mechanisms underlying Cd and Cu toxicity effects in M. japonicus.

19.
Int J Biol Sci ; 16(5): 827-837, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32071552

RESUMO

We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.

20.
Sci Rep ; 10(1): 3211, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081942

RESUMO

In an attempt to improve the oral bioavailability of taxanes, a series of new analogues were synthesized and tested in a panel of human tumor cell lines and cellular permeability assays. Compounds T-13 and T-26 showed potent cytotoxicity and exhibited the highest permeability, so they were selected for pharmacokinetic studies. Here, pharmacokinetics of T-13 and T-26 were studied after intravenous injection (5 mg/kg) and oral administration (60 mg/kg) in male Sprague-Dawley (S.D.) rats, respectively. Plasma concentrations were characterized using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The oral bioavailability of T-13 and T-26 was determined to be 10.71% and 65.79%, respectively. Compounds T-13 and T-26 were both poor substrates of P-glycoprotein (P-gp), and they had a much higher bioavailability than paclitaxel, especially T-26. T-26 with good oral bioavailability represented a potential candidate for potent antitumor activity given oral administration.

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