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1.
Cell Death Dis ; 11(5): 386, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439850

RESUMO

Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient or overexpressed PDAC cell lines were constructed, using shRNA or plasmids with HJURP insert. MTT, sphere formation assay, migration, and invasion assays were performed to evaluate the viability, proliferation, migration, and invasion of PDAC cells. We used xenograft mice models to assess the tumor growth and metastasis in vivo. RNA-seq was applicated in search of the potential downstream target of HJURP in PDAC and subsequent verification were fulfilled via multiple assays, including immunofluorescence. Additionally, chromatin immunoprecipitation and luciferase reporter assay were conducted to explore the potential regulation of MDM2 expression by HJURP through H3K4me2. In this current research, we found that the expression of HJURP in PDAC cells and tissue was significantly higher than those of adjacent normal tissue, and high HJURP expression predicted poor survival. HJURP significantly promoted the viability, sphere formation, migration, and invasion of PDAC cells in vitro, HJURP also facilitated tumor growth and metastasis in vivo. Mechanically, MDM2/p53 axis is critical for HJURP-mediated malignant behaviors in PDAC, and HJURP regulates MDM2 expression through H3K4me2. HJURP could serve as a promising biomarker, and target for PDAC prognosis and treatment.

2.
Pharmacol Res ; 157: 104784, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305492

RESUMO

The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitters (using UHPLC-MS/MS) of 26 children with ASD and 24 normal children. All 26 children with ASD participated in the intervention stage, and we measured the gut microbiota profiles, SCFAs and neurotransmitters before and after probiotics + FOS (n = 16) or placebo supplementation (n = 10). We found that gut microbiota was in a state of dysbiosis and significantly lower levels of Bifidobacteriales and Bifidobacterium longum were observed at the discovery stage in children with ASD. An increase in beneficial bacteria (Bifidobacteriales and B. longum) and suppression of suspected pathogenic bacteria (Clostridium) emerged after probiotics + FOS intervention, with significant reduction in the severity of autism and gastrointestinal symptoms. Compared to children in the control group, significantly lower levels of acetic acid, propionic acid and butyric acid were found, and a hyperserotonergic state (increased serotonin) and dopamine metabolism disorder (decreased homovanillic acid) were observed in children with ASD. Interestingly, the above SCFAs in children with autism significantly elevated after probiotics + FOS intervention and approached those in the control group. In addition, our data demonstrated that decreased serotonin and increased homovanillic acid emerged after probiotics + FOS intervention. However, the above-mentioned changes did not appear in the placebo group for ASD children. Probiotics + FOS intervention can modulate gut microbiota, SCFAs and serotonin in association with improved ASD symptoms, including a hyper-serotonergic state and dopamine metabolism disorder.

3.
Biosci Biotechnol Biochem ; 84(7): 1362-1372, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32154766

RESUMO

We recently reported that Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L) activated Rho GTPases as guanine nucleotide exchange factor to stimulate liver tumorigenesis. The present study continued to explore the effect of ARHGEF10L on the tumorigenic process of gastric cancer. This study detected increased expression of ARHGEF10L in GC tissues compared to peritumoral tissue samples. SGC7901 cells with ARHGEF10L overexpression showed increased cell proliferation, cell migration, and tube-like structure formation abilities, as well as increased expression of GTP-RhoA, ROCK1, and phospho-Ezrin/Radixin/Moesin. ARHGEF10L overexpression downregulated the expression of E-cadherin and upregulated the expression of N-cadherin and Slug, indicating an activation of EMT in the transfected cells. RNA-sequencing assay detected an increased expression of Heat shock 70 kDa protein 6 in the SGC7901 cells overexpressing ARHGEF10L. The above results suggest that ARHGEF10L expression can stimulate gastric tumorigenesis by prompting RhoA-ROCK1-phospho-ERM signaling, inducing EMT and increasing HSPA6 expression.

4.
Bone ; 133: 115247, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31968281

RESUMO

Bone mineral density (BMD) is a key indicator for diagnosis and treatment for osteoporosis; the reduction of BMD could increase the risk of osteoporotic fracture. It was very recently found that Piezo1 mediated mechanically evoked responses in bone and further participated in bone formation in mice. Here, we performed cross phenotype meta-analysis for human BMD at lumbar spine (LS), femoral neck (FN), distal radius/forearm (FA) and heel and screened out 14 top SNPs for PIEZO1, these SNPs were overlapped with putative enhancers, DNase-I hypersensitive sites and active promoter flanking regions. We found that the signal of the best SNP rs62048221 was mainly from heel ultrasound estimated BMD (-0.02 SD per T allele, P = 8.50E-09), where calcaneus supported most of the mechanical force of body when standing, walking and doing physical exercises. Each copy of the effect allele T of SNP rs62048221 was associated with a decrease of 0.0035 g/cm2 BMD (P = 4.6E-27, SE = 0.0003) in UK Biobank data within 477,760 samples. SNP rs62048221 was located at the enhancer region (HEDD enhancer ID 2331049) of gene PIEZO1, site-directed ChIP assays in human mesenchymal stem cells (hMSCs) showed significant enrichment of H3K4me1 and H3K27ac in this region, luciferase assays showed that rs62048221 could significantly affect the activity of the enhancer where it resides. Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD.

5.
Int J Syst Evol Microbiol ; 69(12): 3812-3817, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31483240

RESUMO

A Gram-stain-negative, aerobic, rod-shaped, devoid of flagella, orange-yellow-coloured bacterium (strain LB2P22T) was isolated from an ice sample collected from the Laigu glacier on the Tibetan Plateau, PR China. The results of 16S rRNA gene sequence analysis indicated that strain LB2P22T belongs to the genus Flavobacterium with highest similarity to Flavobacterium laiguense LB2P30T (98.14 %), Flavobacterium glaciei CGMCC 1.5380T (98.02 %), Flavobacterium psychroterrae CCM 8827T (97.94 %) and Flavobacterium granuli CGMCC 1.10125T (97.91 %). Strain LB2P22T had 77.99-84.99 % average nucleotide identity and 22.3-29.3 % digital DNA-DNA hybridization values with its closest relatives, indicating that it represents a novel species of the genus Flavobacterium. Strain LB2P22T grew at 0-25 °C, pH 7.0-8.0 and up to 1.0 % (w/v) NaCl. The main cellular fatty acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1ω7c/C16 : 1ω6c) and anteiso-C15 : 0. The genomic DNA G+C content is 34.3 mol%. The predominant menaquinone was MK-6 and the polar lipids were phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. Based on these data, a novel species, Flavobacteriumranwuense sp. nov., is proposed, with LB2P22T (=CGMCC 1.11361T=NBRC 113777T) as the type strain.


Assuntos
Flavobacterium/classificação , Camada de Gelo/microbiologia , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacterium/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
6.
World J Gastroenterol ; 25(26): 3359-3369, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341361

RESUMO

Aptamers are a class of single oligonucleotide molecules (DNA or RNA) that are screened from random DNA or RNA oligonucleotide chain libraries by the systemic evolution of ligands by exponential enrichment technology. The selected aptamers are capable of specifically binding to different targeting molecules, which is achieved by the three-dimensional structure of aptamers. Aptamers are similar in function to monoclonal antibodies, and therefore, they are also referred to as "chemical antibodies". Due to their high affinity and specificity and low immunogenicity, aptamers are topics of intense interest in today's biological targeting research especially in tumor research. They not only have high potential for clinical advances in tumor targeting detection but also are highly promising as targeted tumor drug carriers for use in tumor therapy. Various experimental studies have shown that aptamer-based diagnostic and therapeutic methods for liver cancer have great potential for application. This paper summarizes the structure, characteristics, and screening methods of aptamers and reviews the recent research progress on nucleic acid aptamers in the targeted diagnosis and treatment of liver cancer.


Assuntos
Aptâmeros de Nucleotídeos/química , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Animais , Antineoplásicos/administração & dosagem , Aptâmeros de Nucleotídeos/administração & dosagem , Modelos Animais de Doenças , Portadores de Fármacos/química , Humanos , Microscopia Intravital/métodos , Ligantes , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Microscopia de Fluorescência/métodos , Sondas Moleculares/administração & dosagem , Sondas Moleculares/química , Estrutura Molecular , Sensibilidade e Especificidade
7.
Cardiovasc Diagn Ther ; 9(3): 239-249, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31275814

RESUMO

Background: Currently, direct comparative safety between endothelin receptor antagonists (ERAs) in pulmonary arterial hypertension (PAH) is limited. Thus, a systematic review with network analysis was conducted. Methods: An electronic search was performed for randomized controlled trials (RCTs) that reported the interested safety data (abnormal liver function, peripheral edema, and anemia) of ERAs in PAH. Risk ratios (RRs) with their confidence intervals (CIs) and the surface under the cumulative ranking curve (SUCRA) were calculated using a network analysis. Results: Ten RCTs involving 2,288 patients were included. Compared with placebo, bosentan (RR, 2.93; 95% CI, 1.78-4.84) significantly increased the risk of abnormal liver function, ambrisentan (RR, 1.62; 95% CI, 1.23-2.13) significantly increased the risk of peripheral edema, and macitentan (RR, 3.42; 95% CI, 1.65-7.07) significantly increased the risk of anemia. SUCRA analysis suggested that bosentan 125 mg twice daily had the highest risk of abnormal liver function; ambrisentan 10 mg once daily had the highest risk of peripheral edema; macitentan 10 mg once daily had the highest risk of anemia. Conclusions: Abnormal liver function (bosentan), peripheral edema (ambrisentan), and anemia (macitentan) were the safety indicators of ERAs in patients with PAH. Different monitoring parameters should be considered for individual ERA.

8.
Int J Syst Evol Microbiol ; 69(8): 2329-2334, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31135330

RESUMO

A novel Gram-stain-positive, non-motile, rod-shaped, non-spore-forming bacterium, designated HLT2-9T, was isolated from the ice tongue surface of Hailuogou Glacier in Sichuan Province, PR China. Colonies of cells were cream yellow, convex and round. Growth occurred at 0-27 °C (optimum, 20 °C), pH 7.0-10.0 (pH 7.0) and in the presence of 0-2.0 % (w/v) NaCl (0 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain HLT2-9T belonged to the genus Nocardioides. The highest level of sequence similarities were found to Nocardioides glacieisoli CGMCC1.11097T (99.24 %), Nocardioides oleivorans CGMCC 4.6882T (98.54 %) and Nocardioides ganghwensis CGMCC 4.6875T (98.54 %). However, the low average nucleotide identity (85.6-87.9 %) and digital DNA-DNA hybridization values (26.4-30.2 %) of strain HLT2-9T to its three closest relatives demonstrated that it represents a novel species of the genus Nocardioides. The major cellular fatty acids of strain HLT2-9T were C17 : 1ω8c and iso-C16 : 0. Strain HLT2-9T contained ll-2,6-diaminopimelic acid as the diamino acid in the cell-wall peptidoglycan. The predominant menaquinone is MK-8(H4). The G+C content of the genomic DNA was 70.65 mol%. Based on evidence collected from the phenotypic, genotypic and phylogenetic analyses, a novel species Nocardioideszhouii sp. nov. is proposed, with HLT2-9T (=CGMCC 1.11084T=NBRC 109783T) as the type strain.


Assuntos
Actinobacteria/classificação , Camada de Gelo/microbiologia , Filogenia , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
9.
Biomed Res Int ; 2019: 1341370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016184

RESUMO

A novel lectin (ABL) was purified from the dried fruiting bodies of Agaricus bitorquis. An efficient 3-step purification protocol involved two consecutive steps of ion exchange chromatography on Q-Sepharose and SP-Sepharose and gel filtration by FPLC on Superdex 75. ABL is a monomeric protein with the molecular mass of 27.6 kDa, which is different from other lectins from genus Agaricus. Its N-terminal amino acid sequence is EYTISIRVYQTNPKGFNRPV which is unique and sharing considerably high similarity of other mushroom lectins. The hemagglutinating activity of the lectin was inhibited by inulin. Based on hemagglutination tests, ABL prefers rabbit, human type A, and AB erythrocytes to human type B and O erythrocytes. The lectin inhibits the activity of HIV-1 reverse transcriptase and the proliferation of leukemia cell (L1210) with an IC50 value of 4.69 and 4.97 µM, respectively. Furthermore, ABL demonstrates the highest mitogenic activity with a response of 24177.7 ± 940.6 [3H-methyl] thymidine counts per minute (CPM) at a concentration of 0.91 µM.


Assuntos
Agaricales/química , Agaricus/química , Proliferação de Células/efeitos dos fármacos , Transcriptase Reversa do HIV/antagonistas & inibidores , Inulina/metabolismo , Lectinas/farmacologia , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemaglutinação/efeitos dos fármacos , Testes de Hemaglutinação/métodos , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Coelhos
10.
Exp Cell Res ; 378(1): 66-75, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30844391

RESUMO

Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed low expression of miR-194 in chemoresistant HCC cells. A remarkable decrease of miR-194 was detected in EpCAM or CD133-positive liver CSCs and CSC-enriched hepatoma spheres. Interference miR-194 facilitated liver CSCs expansion by enhancing the self-renewal of liver CSCs. While up-regulating miR-194 inhibited liver CSCs expansion by suppressing the self-renewal of liver CSCs. Furthermore, hepatoma cells with miR-194 overexpression performed more sensitivity to sorafenib treatment. Mechanistically, functional studies found that Ras-related C3 botulinum toxin substrate 1 (RAC1) was a direct target of miR-194. Overexpression of miR-194 inhibited the expression of RAC1 in liver CSCs. Special RAC1 siRNA diminished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-194 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-194-inhibited liver CSCs expansion. More importantly, downregulated expression of miR-194 was a predictor of poor prognosis of HCC patients.

11.
Sci Rep ; 9(1): 1151, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718596

RESUMO

Agaricus bisporus is in general cultivated on wheat and rice straw in China. However, millet straw is a potential alternative resource for Agaricus bisporus cultivation, but this has hardly been studied. In the present study, the feasibility of millet straw based mushroom production was analyzed by three successive trials. Mature compost demonstrated high quality with total nitrogen, pH, and C/N ratio of 2.0%, 7.5, and 18:1 respectively, which was suitable for mushroom mycelia growth. During composting, 47-50% of cellulose, 63-65% of hemicellulose, and 8-17% lignin were degraded, while 22-27% of cellulose, 14-16% of hemicellulose, and 15-21% of lignin were consumed by A. bisporus mycelia during cultivation. The highest FPUase and CMCase were observed during mushroom flushes. Endo-xylanase had the key role in hemicellulose degradation with high enzyme activity during cultivation stages. Laccase participated in lignin degradation with the highest enzyme activity in Pinning stage followed by a sharp decline at the first flush. Yield was up to 20 kg/m2, as this is similar to growth on wheat straw, this shows that millet straw is an effective resource for mushroom cultivation. Actinobacteria, Bacteroidetes, Chloroflexi, Deinococcus-Thermus, Firmicutes, and Proteobacteria were the dominant phyla, based on 16S rRNA gene sequencing during composting. The key environmental factors dominating bacterial communities of the samples were determined to be pH value, cellulose content, and hemicellulose content for prewetting and premixed phase of basic mixture (P0); moisture content for phase I (PI); and nitrogen content, lignin content, and ash content for phase II (PII), respectively.

12.
Oncologist ; 24(6): 812-819, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30181315

RESUMO

BACKGROUND: IBM Watson for Oncology (WFO), which can use natural language processing to evaluate data in structured and unstructured formats, has begun to be used in China. It provides physicians with evidence-based treatment options and ranks them in three categories for treatment decision support. This study was designed to examine the concordance between the treatment recommendation proposed by WFO and actual clinical decisions by oncologists in our cancer center, which would reflect the differences of cancer treatment between China and the U.S. PATIENTS AND METHODS: Retrospective data from 362 patients with cancer were ingested into WFO from April 2017 to October 2017. WFO recommendations were provided in three categories: recommended, for consideration, and not recommended. Concordance was analyzed by comparing the treatment decisions proposed by WFO with those of the multidisciplinary tumor board. Concordance was achieved when the oncologists' treatment decisions were in the recommended or for consideration categories in WFO. RESULTS: Ovarian cancer showed the highest concordance, which was 96%. Lung cancer and breast cancer obtained a concordance of slightly above 80%. The concordance of rectal cancer was 74%, whereas colon cancer and cervical cancer showed the same concordance of 64%. In particular, the concordance of gastric cancer was very low, only 12%, and 88% of cases were under physicians choice. CONCLUSION: Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major cause of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. ClinicalTrials.gov Identifier: NCT03400514. IMPLICATIONS FOR PRACTICE: IBM Watson for Oncology (WFO) has begun to be used in China. In this study, concordance was examined between the treatment recommendation proposed by WFO and clinical decisions for 362 patients in our cancer center, which could reflect the differences of cancer treatment between China and the U.S. Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major causes of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. This study may have a significant effect on application of artificial intelligence systems in China.

13.
BMC Pharmacol Toxicol ; 19(1): 43, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29996945

RESUMO

BACKGROUD: Cationic liposomes (CLs) can be used as non-viral vectors in gene transfer and drug delivery. However, the underlying molecular mechanism of its cytotoxicity has not been well elucidated yet. METHODS: We herein report a systems biology approach based on whole-transcriptome sequencing coupled with computational method to identify the predominant genes and pathways involved in the cytotoxicity of CLs in HepG2 cell line. RESULTS: Firstly, we validated the concentration-dependent cytotoxicity of CLs with an IC50 of 120 µg/ml in HepG2 exposed for 24 h. Subsequently, we used whole-transcriptome sequencing to identify 220 (77 up- and 143 down-regulated) differentially expressed genes (DEGs). Gene ontology (GO) and pathway analysis showed that these DEGs were mainly related to cholesterol, steroid, lipid biosynthetic and metabolic processes. Additionally, "key regulatory" genes were identified using gene act, pathway act and co-expression network analysis, and expression levels of 11 interested altered genes were confirmed by quantitative real time PCR. Interestingly, no cell cycle arrest was observed through flow cytometry. CONCLUSIONS: These data are expected to provide deep insights into the molecular mechanism of CLs cytotoxicity.


Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Lipossomos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Transcriptoma/efeitos dos fármacos
14.
J Food Drug Anal ; 26(2): 823-833, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29567254

RESUMO

Rhizoma corydalis and Radix Angelicae Dahurica (Yuanhu-Baizhi) herbal medicine pair has been used for thousands of years and has been reported to be potentially active in recent cancer therapy. But the exact active components or fractions remain unclear. In this study, a new comprehensive two-dimensional (2D) 3-aminopropyltriethoxysilane (APTES)-decorated MCF7-cell membrane chromatography (CMC)/capcell-C18 column/time-of-flight mass spectrometry system was established for screening potential active components and clarifying the active fraction of Yuanhu-Baizhi pair. APTES was modified on the surface of silica, which can provide an amino group to covalently link cell membrane fragments with the help of glutaraldehyde in order to improve the stability and column life span of the MCF7 CMC column. The comprehensive 2D MCF7-CMC system showed good separation and identification abilities. Our screen results showed that the retention components are mainly from the alkaloids in Yuanhu (12 compounds) and the coumarins (10 compounds) in Baizhi, revealing the active fractions of Yuanhu-Baizhi herbal medicine pair. Oxoglaucine, protopine, berberine, osthole, isopimpinellin and palmitic acid were selected as typical components to test the effects on cell proliferation and their IC50 were calculated as 38.17 µM, 29.45 µM, 45.42 µM, 132.7 µM, 156.8 µM and 90.5 µM respectively. Cell apoptosis assay showed that the drug efficacy was obtained mainly through inducing cell apoptosis. Furthermore, a synergistic assay results demonstrated that oxoglaucine (representative of alkaloids from Yuanhu) and isopimpinellin (representative of coumarins from Baizhi) showed significant synergistic efficacy with GFT, indicating that these components may act on other membrane receptors. The proposed 2D CMC system could also be equipped with other cells for further applications. Besides, the follow-up in-vitro experimental strategy using cell proliferation assay, cell apoptosis assay and synergistic assay proved to be a practical way to confirm the active fractions of herbal medicine.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Membrana Celular/efeitos dos fármacos , Cromatografia/métodos , Corydalis/química , Medicamentos de Ervas Chinesas/farmacologia , Antineoplásicos Fitogênicos/química , Neoplasias da Mama/fisiopatologia , Membrana Celular/química , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Células MCF-7 , Espectrometria de Massas , Plantas Medicinais/química , Propilaminas/química , Rizoma/química , Silanos/química
15.
Gene ; 657: 19-29, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29505837

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. However, the exact pathophysiology of PCOS remains largely unclear. We performed deep sequencing to investigate the mRNA and long noncoding RNA (lncRNA) expression profiles in the ovarian tissues of letrozole-induced PCOS rat model and control rats. A total of 2147 mRNAs and 158 lncRNAs were differentially expressed between the PCOS models and control. Gene ontology analysis indicated that differentially expressed mRNAs were associated with biological adhesion, reproduction, and metabolic process. Pathway analysis results indicated that these aberrantly expressed mRNAs were related to several specific signaling pathways, including insulin resistance, steroid hormone biosynthesis, PPAR signaling pathway, cell adhesion molecules, autoimmune thyroid disease, and AMPK signaling pathway. The relative expression levels of mRNAs and lncRNAs were validated through qRT-PCR. LncRNA-miRNA-mRNA network was constructed to explore ceRNAs involved in the PCOS model and were also verified by qRTPCR experiment. These findings may provide insight into the pathogenesis of PCOS and clues to find key diagnostic and therapeutic roles of lncRNA in PCOS.


Assuntos
Perfilação da Expressão Gênica/métodos , Nitrilos/efeitos adversos , Ovário/química , Síndrome do Ovário Policístico/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Triazóis/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Letrozol , Síndrome do Ovário Policístico/induzido quimicamente , Ratos , Análise de Sequência de RNA/métodos
16.
Biochimie ; 148: 46-54, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29501482

RESUMO

A novel extracellular laccase was purified from fermentation broth of the white rot fungus Trametes sp. F1635 by a three-step protocol including two consecutive ion-exchange chromatography steps on DEAE-Sepharose and SP-Sepharose, and a final gel-filtration on Superdex 75. The purified laccase (TsL) was a monomeric protein with the molecular mass of 64.8 kDa. It demonstrated high oxidation activity of 4.00 × 104 U/mg towards ABTS. Its N-terminal amino acid sequence was AIGPVADLTIINNAV which was unique and sharing high similarity of other fungal laccases. TsL was a yellow laccase based on absorption spectrum analysis. It demonstrated an acidic pH optimum of 2.6 and temperature optimum of 50 °C towards ABTS. The Km and Vmax values towards ABTS were estimated to 18.58 µM and 1.35 µmol/min, respectively. TsL manifested effective decolorization activity towards eriochrome black T (EBT), remazol brilliant blue R (RBBR), malachite green (MG), and eriochrome black T (EBT) (over 60%). Violuric acid (VA) and acetosyringone (AS) were the optimal mediators for the laccase in dye decolorization. Results suggest that TsL demonstrates great potential for dye decolorization and water treatment.


Assuntos
Corantes/metabolismo , Espaço Extracelular/enzimologia , Lacase/metabolismo , Trametes/citologia , Sequência de Aminoácidos , Cor , Fermentação , Concentração de Íons de Hidrogênio , Cinética , Lacase/química , Peso Molecular , Temperatura , Trametes/enzimologia
17.
Hepatobiliary Pancreat Dis Int ; 16(2): 139-146, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28381376

RESUMO

BACKGROUND: The benefits of the application of basiliximab induction therapy in liver transplantation are not clear. The present meta-analysis was to evaluate the pros and cons of basiliximab use in liver transplantation. DATA SOURCES: We searched the associated publications in English from July 1998 to December 2015 in the following databases: MEDLINE, PubMed, Ovid, EMBASE, Web of Science and Cochrane Library. RESULTS: Basiliximab significantly decreased the incidence of de novo diabetes mellitus after liver transplantation (RR=0.56; 95% CI: 0.34-0.91; P=0.02). Subgroup analysis showed that basiliximab in combination with steroids-free immunosuppressant significantly decreased the incidence of biopsy-proven acute rejection (RR=0.62; 95% CI: 0.39-0.97; P=0.04) and new-onset hypertension (RR=0.62; 95% CI: 0.42-0.93; P=0.02). CONCLUSIONS: Basiliximab may be effective in reducing de novo diabetes mellitus. What is more, basiliximab in combination with steroids-free immunosuppressant shows statistical benefit to reduce biopsy-proven acute rejection and de novo hypertension.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Fígado , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Basiliximab , Biópsia , Distribuição de Qui-Quadrado , Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Hipertensão/etiologia , Hipertensão/prevenção & controle , Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Proteínas Recombinantes de Fusão/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
18.
Inflammation ; 40(3): 788-797, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28194607

RESUMO

Exposure to ozone has been associated with airway inflammation and glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) to reverse ozone-induced glucocorticoid insensitivity and to detect its effects with glucocorticoids in protecting against airway inflammation. After C57/BL6 mice were exposed to ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml), dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0.1 ml, respectively, for 10 times over 5 weeks. At sacrifice, lung histology, airway inflammatory cells, levels of related cytokines in bronchoalveolar lavage fluid (BALF), and serum were analyzed, airway inflammatory cell infiltration density and mean linear intercept (Lm) were measured, the expression of IL-17A mRNA, glucocorticoid receptors (GR), NF-κB, and p38 mitogen-activated protein kinase (MAPK) phosphorylation were determined. We found that combination administration markedly reduced ozone-induced total inflammatory cells, especially neutrophils; inhibited levels of cytokines, including IL-8, IL-17A, and TNF-α in BALF; and suppressed airway inflammatory cell infiltration density and Lm. Additionally, combination administration significantly elevated levels of IFN-γ in BALF, decreased the dexamethasone-induced increase of IL-17A mRNA, and increased the expression of GR and decrement of NF-κB and p38MAPK phosphorylation, which are also related to glucocorticoids insensitivity. Collectively, combination administration shows profound efficacy in inhibiting certain cytokines, and IL-17 mAb partly improved the glucocorticoids insensitivity via modulating the enhanced production rate and improving expression of IL-17A induced by glucocorticoids administration and p38MAPK, NF-κB signaling pathway.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Glucocorticoides/farmacologia , Interleucina-17/imunologia , Ozônio/toxicidade , Animais , Anticorpos Monoclonais/farmacologia , Asma/tratamento farmacológico , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Camundongos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Neutrófilos/imunologia , Neutrófilos/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Biomed Pharmacother ; 88: 335-341, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28119235

RESUMO

The potential suppression role of cordycepin (Cor) on airway remodeling in a rat model of chronic asthma was investigated in this paper. We evaluated the anti-remodeling of Cor (50mg/kg) combined with or without budesonide (BUD) and investigated the possible underlying molecular mechanisms. We found that Cor attenuated immunoglobulin (Ig) E, alleviated the airway wall thickness, and decreased eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF). Notably, Cor reduced the up-regulation of IL-5, IL-13 and TNF-α in the BALF. Cor also regulated the increase of A2AARmRNA and the decrease of TGF-ß1 expression. Furthermore, Cor markedly blocked p38MAPK signaling pathway activation in the OVA-driven asthmatic mice. The combination treatment of Cor and BUD showed profound efficacy in regulating the levels of inflammatory cells and the expression of IL-13, TGF-ß1 and A2AARmRNA. Collectively, this study demonstrated that Cor combined with glucocorticoids treatment shows synergistically profound efficacy in inhibiting airway remodeling, and some benefits of Cor may result from the increased A2AARmRNA expression, the reduced TGF-ß1 levels and the inhibition of Th2-cytokines through the suppression of the p38MAPK signaling pathways.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/patologia , Desoxiadenosinas/uso terapêutico , Animais , Asma/induzido quimicamente , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/citologia , Budesonida/uso terapêutico , Citocinas/metabolismo , Feminino , Imunoglobulina G/metabolismo , Mediadores da Inflamação/metabolismo , Contagem de Leucócitos , Ovalbumina , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
20.
Int J Biol Macromol ; 95: 920-927, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27793681

RESUMO

A novel laccase was purified from fermentation broth of the white rot fungus Cerrena unicolor strain GSM-01 following three ion-exchange chromatography steps and one gel-filtration step. The purified enzyme was determined to be a monomeric protein of 63.2kDa and demonstrated high oxidation activity of 2.05×104U/mg towards ABTS. Its cDNA, gene, and amino acid sequences were obtained. It possessed high sequence similarity with that of other laccases but different enzymatic properties. It manifested optimal pH and temperature of 2.6 and 45°C, respectively. Fe3+ and Fe2+ were the most efficient inhibitors towards Cerrena unicolor laccase (CUL), while Mn2+ can slightly enhance the laccase activity of 3.8-10.5%. The Km and Vmax of CUL were estimated to 302.7µM and 13.6µMm-1, respectively. CUL was effective in the decolorization of bromothymol blue, evans blue, methyl orange, and malachite green with decolorization efficiencies of 50%-85%. It possesses potential application in textile and environmental industries.


Assuntos
Corantes/metabolismo , Espaço Extracelular/enzimologia , Lacase/genética , Lacase/metabolismo , Polyporaceae/citologia , Sequência de Aminoácidos , Clonagem Molecular , Cor , Espaço Extracelular/genética , Concentração de Íons de Hidrogênio , Cinética , Lacase/química , Lacase/isolamento & purificação , Peso Molecular , Polyporaceae/enzimologia , Especificidade por Substrato , Temperatura
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