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1.
Talanta ; 207: 120285, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594625

RESUMO

Detection of microRNAs (miRNAs) in cells improves our understanding of their physiological functions and facilitates exploration of their roles diseases. The toehold-mediated strand displacement reaction initiates rolling circle amplification (RCA) to achieve signal amplification of the specific miRNA; This process is named as toehold-initiated RCA (TIRCA). The product of TIRCA was ligated to two DNA probes, which were modified with 6-carboxyfluorescein and carboxytetramethylrhodamine, respectively. Qualitative detection of miRNAs was successfully achieved by combining the fluorescence aggregation enhancement effect with fluorescence resonance energy transfer generated by the proximity of the two fluorescent dyes. Thus, this approach helps us analyze the roles of miRNAs in human disease more accurately.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31425724

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a severe mental disorder. Both environmental and genetic factors contribute to the development of SCZ. The estimated heritability of SCZ is about 80%. Previous genetic studies of SCZ mainly focused on the genetic variations associated the risk of SCZ. Limited efforts are paid to explore the roles and biological mechanism of nuclear acid methylation implicated in the pathogenesis of SCZ. METHODS: A two-stage integrative analysis of SCZ GWAS and nuclear acid methylation functional annotation data (including meQTLs and m6A) was performed in this study. First, the discovery GWAS of SCZ was aligned with genomic meQTLs and m6A annotation data to identify the candidate genes associated with SCZ. Second, another independent replication GWAS dataset of SCZ was applied to validate the discovery results. Furthermore, the functional relevance of identified candidate genes with SCZ were validated by the mRNA expression profiling of SCZ brain tissues. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes was performed by the DAVID tool. RESULTS: The two-stage integrative analysis detected 106 meQTLs related candidate genes for SCZ. After comparing with the differentially expressed genes in SCZ brain tissues, 49 overlapped genes were identified for meQTLs, such as ZSCAN12, BTN3A2 and HLA-DQA1. Besides, for meQTLs, 29 SCZ associated pathways and 56 SCZ associated GO terms were detected, such as cell adhesion molecules and asthma. For m6A, 25 candidate genes were detected by the two-stage integrative analysis for SCZ, such as ZSCAN12, HLA-DQA1 and SNX19. Furthermore, 17 of the 25 genes were detected in the mRNA expression profiling of SCZ brain tissues. CONCLUSION: This study identified multiple SCZ associated genes and pathways, supporting the implication of nuclear acid methylation in the pathogenesis of SCZ.

3.
J Mol Biol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682837

RESUMO

Alginate lyases, which are important in both basic and applied sciences, fall into ten polysaccharide lyase (PL) families. PL36 is a newly established family that includes 39 bacterial sequences and one eukaryotic sequence. Till now, the structures or catalytic mechanisms of PL36 alginate lyases have yet to be revealed. Here, we characterized a novel PL36 alginate lyase, Aly36B, from Chitinophaga sp. MD30. Aly36B is a polymannuronate specific endo-lytic alginate lyase. To probe the catalytic mechanism of Aly36B, the structures of wild-type Aly36B and its mutants (K143A/Y185A in complex with alginate tetrasaccharide and K143A/M171A with trisaccharide) were solved. The overall structure of Aly36B belongs to the ß-jelly roll scaffold, adopting a typical ß-sandwich fold. Aly36B contains a Ca2+, which is far away from the active center and plays an important role in stabilizing the structure of Aly36B. Based on structural and mutational analyses, the catalytic mechanism of Aly36B for alginate degradation was explained. During catalysis, Arg169, Tyr185, and Tyr187 are responsible for neutralizing the negative charge of the substrate, and Lys143 acts as both the catalytic base and the catalytic acid, which represents a new kind of catalytic mechanism of alginate lyases. Sequence alignment shows that these four residues involved in catalysis are highly conserved in all PL36 sequences, suggesting that PL36 alginate lyases may adopt a similar catalytic mechanism. Taken together, this study reveals the molecular structure and catalytic mechanism of a PL36 alginate lyase, broadening our knowledge on alginate lyases and facilitating future biotechnological applications of PL36 alginate lyases.

4.
Int J Mol Sci ; 20(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683503

RESUMO

Long non-coding RNAs (lncRNAs) play important roles in plant growth and stress responses. As a dominant abiotic stress factor in soil, boron (B) deficiency stress has impacted the growth and development of citrus in the red soil region of southern China. In the present work, we performed a genome-wide identification and characterization of lncRNAs in response to B deficiency stress in the leaves of trifoliate orange (Poncirus trifoliata), an important rootstock of citrus. A total of 2101 unique lncRNAs and 24,534 mRNAs were predicted. Quantitative real-time polymerase chain reaction (qRT-PCR) experiments were performed for a total of 16 random mRNAs and lncRNAs to validate their existence and expression patterns. Expression profiling of the leaves of trifoliate orange under B deficiency stress identified 729 up-regulated and 721 down-regulated lncRNAs, and 8419 up-regulated and 8395 down-regulated mRNAs. Further analysis showed that a total of 84 differentially expressed lncRNAs (DELs) were up-regulated and 31 were down-regulated, where the number of up-regulated DELs was 2.71-fold that of down-regulated. A similar trend was also observed in differentially expressed mRNAs (DEMs, 4.21-fold). Functional annotation of these DEMs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and the results demonstrated an enrichment of the categories of the biosynthesis of secondary metabolites (including phenylpropanoid biosynthesis/lignin biosynthesis), plant hormone signal transduction and the calcium signaling pathway. LncRNA target gene enrichment identified several target genes that were involved in plant hormones, and the expression of lncRNAs and their target genes was significantly influenced. Therefore, our results suggest that lncRNAs can regulate the metabolism and signal transduction of plant hormones, which play an important role in the responses of citrus plants to B deficiency stress. Co-expression network analysis indicated that 468 significantly differentially expressed genes may be potential targets of 90 lncRNAs, and a total of 838 matched lncRNA-mRNA pairs were identified. In summary, our data provides a rich resource of candidate lncRNAs and mRNAs, as well as their related pathways, thereby improving our understanding of the role of lncRNAs in response to B deficiency stress, and in symptom formation caused by B deficiency in the leaves of trifoliate orange.

5.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683670

RESUMO

Asatone and isoasatone A from Asarum ichangense Cheng were determined to be defensive compounds to some insects in a previous investigation. However, the anti-insect activity mechanisms to caterpillar are still unclear. The compounds asatone and isoasatone A from A. ichangense were induced by Spodoptera litura. The anti-insect activity of asatone and isoasatone A to S. litura was further tested by weight growth rate of the insect through a diet experiment. Isoasatone A showed a more significant inhibitory effect on S. litura than asatone on the second day. The concentration of asatone was higher than isoasatone A in the second instar larvae of S. litura after 12 h on the feeding test diet. Both compounds caused mid-gut structural deformation and tissue decay as determined by mid-gut histopathology of S. litura. Furthermore, some detoxification enzyme activity were measured by relative expression levels of genes using a qPCR detecting system. Asatone inhibited the gene expression of the cytochrome P450 monooxygenases (P450s) CYP6AB14. Isoasatone A inhibited the relative expression levels of CYP321B1, CYP321A7, CYP6B47, CYP6AB14, and CYP9A39. Asatone increased the relative gene expression of the glutathione transferases (GSTs) SIGSTe1 and SIGSTo1, in contrast, isoasatone A decreased the relative gene expression of SIGSTe1 by about 33 fold. Neither compound showed an effect on acetylcholinesterase SIAce1 and SIAce2. The mechanism of anti-insect activity by both compounds could be explained by the inhibition of enzymes P450s and GSTs. The results provide new insights into the function of unique secondary metabolites asatone and isoasatone A in genus Asarum, and a new understanding of why A. ichangense is largely free of insect pests.

6.
Psychiatry Res ; : 112639, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31685286

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, but the genetic mechanism of ADHD remains elusive now. METHODS: Tissue specific transcriptome-wide association study (TWAS) of ADHD was performed by FUSION utilizing a genome-wide association study (GWAS) dataset of ADHD (including 20,183 ADHD cases and 35,191 healthy controls) and gene expression reference from brain and blood. Furthermore, the genes identified by TWAS were compared with the differently expressed genes detected by mRNA expression profiles of ADHD rat model and autism spectrum disorders (ASD) patients. Functional enrichment and annotation analysis of the identified genes were performed by DAVID and FUMAGWAS tool. RESULTS: For brain tissue, TWAS identified 148 genes with P value < 0.05, such as TDO2 (PTWAS=4.01×10-2), CHD1L (PTWAS=9.64×10-3) and KIAA0319L (PTWAS=4.05×10-4). Further 11 common genes were examined in the mRNA expression datasets, such as ACSM5 (PTWAS=3.62×10-2, PmRNA=0.005), CCDC24 (PTWAS=1.49×10-2, PmRNA=2.35×10-3) and MVP (PTWAS=5.55×10-3, PmRNA=5.40×10-3). Pathway enrichment analysis of the genes identified by TWAS detected 3 pathways for ADHD, including Other glycan degradation (P value=0.021), Viral myocarditis (P value=0.034) and Endocytosis (P value=0.041). CONCLUSIONS: Through integrating GWAS and mRNA expression data, we identified a group of ADHD-associated genes and pathways, providing novel clues for understanding the genetic mechanism of ADHD.

7.
J Chromatogr A ; : 460630, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31677768

RESUMO

Authentication of original species is embedded in the quality control system of herbal medicines. In this work, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based untargeted metabolomics coupled with chemometric analysis was utilized for the precise authentication of the Fritillaria species for both raw materials and commercial products. First, a stepwise difference-enlarging chemometric analysis strategy was proposed to analyze eight medicinal Fritillaria species. Subsequently, 21 species-specific markers were discovered and the specificity was investigated under different sample preparation methods. Finally, the obtained species-specific markers were successfully utilized to identify the Fritillaria species in commercially relevant products. This work is the first to report robust and specific markers for authentication of Fritillaria products, showing promise for tracking the supply chain of herbal suppliers.

8.
Int J Med Mushrooms ; 21(8): 825-839, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679289

RESUMO

Grifola frondosa (hen of the woods or maitake) is a famous culinary-medicinal mushroom, and its exopolysaccharides (EPSs) have biological activities with or without supplementation with exogenous additives. In this study, a Rhizoma gastrodiae extract was added to a G. frondosa fermentation system. P-hydroxylbenzaldehyde (HBA), the main product of R. gastrodiae, had the highest utilization rate in the fermentation process (42%). In addition, the EPSs of G. frondosa after addition of R. gastrodiae extract (REPS), of HBA (HEPS), or of a standard solution according to the main component ratio of R. gastrodiae extract (CEPS) were obtained. We then determined the antioxidant and immunomodulatory activities of EPS, REPS, HEPS, and CEPS. Overall, REPS showed the highest antioxidant activities compared with EPS and HEPS (P < 0.05) but similar to that of CEPS (P > 0.05). The half-inhibitory concentration (ED50) values of REPS (< 4 mg/mL) were lower than those of EPS, HEPS, and CEPS. Moreover, REPS was better able to stimulate phagocytosis and nitric oxide production of RAW 264.7 macrophages than were the others, without a significant difference from CEPS (P > 0.05). An interesting and important finding is that a R. gastrodiae extract can increase antioxidant and immunomodulatory activities of EPS preparations from G. frondosa, and the standard solution of the main components of the R. gastrodiae extract may be better for simulating fermentation performed by G. frondosa and biological activities of its major products.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31680040

RESUMO

A novel and highly selective fluorescent 1,8-naphthalimide-based probe, 3, was designed and synthesized for rapid Cu2+ detection in a CH3CN-H2O (3:1, v/v, pH = 7.4) solution by means of a distinct hydrolysis mechanism via its Cu2+-promoting feature. Upon treatment with Cu2+, the fluorescence response of probe 3 at 550 nm abruptly decreased, which was visible to the naked eye, and this response was accompanied by a clear change of the color of the solution; the color changed from the original yellow color to colorless. This color change occurred due to the Cu2+-promoted hydrolysis of 3, which yielded a fluorescence-quenched product. It is inspiring that probe 3 exhibited excellent sensitivity, a short response time and strong anti-interference recognition. Compared with the allowable amount of Cu2+ (∼20 µM) in drinking water, the detection limit of 3 for Cu2+ is calculated to be 9.15 nM, which is much lower than the amount defined by standards. The probe can be successfully applied for the determination of Cu2+ in real aqueous samples. Furthermore, probe 3 can be used as a fluorescent sensor to detect Cu2+ in biological environments, demonstrating its low toxicity to organisms and good cell permeability in live cell imaging.

10.
Medicine (Baltimore) ; 98(44): e17682, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689788

RESUMO

Due to the various presentations of gastrointestinal tract duplications (GTD), diagnosing and management for this disease might be varied and difficult. We intend to improve the experiences for these difficult, in terms of the clinical presentations, diagnostic investigations, management.We reviewed recent literature and retrospectively analyzed 72 pediatric patients with enteric duplication. Diagnosis was confirmed by surgery and pathological examination for imaging characteristics and clinical and pathological features.The ages of patients ranged from one month to 12.5 years. The clinical presentations of the patients included 57 cases with abdominal pain, followed with nausea or vomiting, abdominal distension, etc. All of the patients were diagnosed by ultrasonography, and most of them presented as intra-abdominal cystic masses. Four cases were diagnosed with the cysts other than GTDs, like, mesenteric cyst, chledochal cyst and abscess, and so on. Computed tomography was performed on 65 patients. X-rays and barium meal showed the outline of the cyst structure, with intestinal displacement due to the pressure from the cyst. Among the 72 cases of enteric duplication, 45 were located with ileocecal area, 41 were ileal and 8 were colonic duplications.Enteric duplication is very rare in children and is prone to misdiagnosis. The preoperative diagnosis of enteric duplication can be improved through comprehensive analysis of various imaging exams and closely related clinical presentations.

11.
Cancer Med ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692291

RESUMO

The response to icotinib in advanced non-small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi-center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next-generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow-up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression-free survival (PFS) was 5.5 months (95% CI: 1.2-13.0 months). Both complex-pattern with EGFR classical mutations (EGFRcm) and single-pattern have better PFS than complex-pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65-9.75), 5.2 (95% CI: 3.24-7.16) and 3.2 (95% CI: 2.97-3.44) months, respectively, P < .05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P < .05). Diarrhea was the most frequent side effect (42.9%). Forty-eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex-pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib-resistant EGFRum NSCLC patients.

12.
BMC Cancer ; 19(1): 1048, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694573

RESUMO

BACKGROUND: Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors. METHODS: EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n = 1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n = 172) were selected as the validation set. RESULTS: In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P = 0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20 mm, submucosal invasion and undifferentiated tumor histological type (all P <  0.05); the area under the curve (AUC) was 0.694 (95% confidence interval [CI]: 0.659-0.730). Patients were divided into low-risk, intermediate-risk, high-risk and extremely high-risk groups by recursive partitioning analysis; the incidences of LNM/LVI were 5.4, 12.6, 24.2 and 37.8%, respectively (P <  0.001). The AUC of the validation set was 0.796 (95%CI, 0.662-0.851) and the predictive performance of the LNM/LVI risk in the validation set was consistent with that in the training set. CONCLUSIONS: The risk of LNM/LVI in differentiated mucosal EGC is low, which indicated that endoscopic resection is a treatment option. The risk of LNM/LVI in undifferentiated mucosal EGC and submucosa EGC are high and gastrectomy with lymph node dissection is suggested.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31694758

RESUMO

Ebola virus (EBOV) is a zoonotic pathogen, the infection often results in severe, potentially fatal, systematic disease in human and nonhuman primates. VP35, an essential viral RNA-dependent RNA polymerase cofactor, is indispensable for Ebola viral replication and host innate immune escape. In this study, VP35 was demonstrated to be phosphorylated at Serine/Threonine by immunoblotting, and the major phosphorylation sites was S187, S205, T206, S208 and S317 as revealed by LC-MS/MS. By an EBOV minigenomic system, EBOV minigenome replication was shown to be significantly inhibited by the phosphorylation-defective mutant, VP35 S187A, but was potentiated by the phosphorylation mimic mutant VP35 S187D. Together, our findings demonstrate that EBOV VP35 is phosphorylated on multiple residues in host cells, especially on S187, which may contribute to efficient viral genomic replication and viral proliferation.

14.
J Cosmet Dermatol ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697031

RESUMO

BACKGROUND/OBJECTIVES: Sjogren - Larsson syndrome (SLS) is a rare autosomal recessive disease of the mutation ALDH3A2 that identifies a part of fatty acids for fatty aldehyde dehydrogenase: NAD-oxidoreductase enzyme complex. This study aimed to access variant ALDH3A2 gene coded for FALDH and products regulating pathogenic melanogenesis owing to increased oxidative stress and reactive oxygen species resulting in DNA harm in SLS. By turning them into fatty acids, FALDH avoids the accumulation of toxic fatty aldehydes. The mutation results in the accumulation of aldehyde-modified lipids or fatty alcohols that may interfere with skin and brain function. METHODS: In Nov 2018, we performed a literature search in PubMed for clinical studies, clinical trials, case reports, controlled trials, randomized controlled trials, and systemic reviews. The search terms we used were "SJOGREN-LARSSON SYNDROME" AND "HYPERMELANNOSIS" OR "FALDH" (from 1985). The search resulted in 1,289 articles, out of these 95 articles met our inclusion exclusion criteria. Our inclusion criteria included relevant original articles relevant, critical systemic reviews, and crucial referenced articles, ex-clusion criteria included duplicates and articles not published in English language. RESULTS: Toxicity of long-chain aldehydes to FALDH-deficient cells owing to accumulation under the profound epidermis layer improves oxidative stress in the cell resulting in keratinocyte hyperproliferation. CONCLUSION: While it continues to be determined whether accumulated fatty alcohol and fatty aldehydes obtained from ether glycerolipids and sphingolipids improve the susceptibility of melanocytes and their element accountable for skin hyperpigmentation to biological colour.

15.
ACS Chem Neurosci ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697060

RESUMO

Alzheimer's disease (AD) is characterized by fibrillar deposits of amyloid-ß (Aß) peptides and neurofibrillary tangles of Tau proteins. Aß peptides are composed of 37 to 49 residues, in which the Aß42 isoform is particularly toxic and aggregation-prone and is enriched in the plaques of AD brains and thus considered central to the development of AD. Therefore, disaggregation and disruption provide potential therapeutic approaches to reduce, inhibit, and even reverse Aß aggregation. Here we capture the atomic-level details of the interactions between sigmoid Aß42 fibril 2MXU/5KK3 and either natural tanshinone compounds TS1/TS0 or negative charged ER, proposing two unprecedented disassembly mechanisms. Natural TS1/TS0 prefers to insert into the cavity together with part at the surface of the 2MXU to open up the mouth and twist the conformation, destroying the ordered growth of subsequent monomers along the fibril axis. For the more compact two-fold 5KK3, attachment of TS1/TS0 at the surface including some inserted in cavity results in the separation of the two folds. In the two sigmoid fibril systems, it is no longer applicable for the routine criterions to assess Aß42 fibril disassembly by introduction of these drugs, such as either reduced H-bond number, decreased ß-sheet contents or both. ER, like-charged to Aß42 fibril, is especially exceptional, and departs utterly from the neutral ones to disassemble Aß42 fibril. Besides of the inapplicable routine criterions, positive binding energy between ER and Aß42 fibril also deviates from the hypotheses of "ligands exhibiting greater affinity for the ß-amyloid peptide are effective at altering its aggregation and inhibiting cell toxicity" (Cairo et al, Biochemistry 2002, 41, 8620 8629), but resulting in stronger disassembly effect on the two kinds of sigmoid Aß42 fibrils than neutral TS0/TS1. The disassembly power of charged ER molecules derives from its stronger deformation ability to the conformation of Aß42 fibril than the neutral ones, twisting the one-fold 2MXU in tapered-shape and separating two-fold 5KK3 in two parts more further, that is in great agreement with experimental observations (Irwin, et al. Biomacromolecules 2013, 14 (1), 264-274). The unusual disassembly mechanisms fill the gaps and offer an alternative direction in engineering new inhibitors to treat AD.

16.
Med Sci Monit ; 25: 8422-8429, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703057

RESUMO

BACKGROUND Herein, we found that tripartite motif-containing 48 (TRIM48) was reduced in human glioblastoma (GBM) cell lines. We investigated whether and how TRIM48 functions in human GBM in vitro. MATERIAL AND METHODS Human GBM cells (U87 MG and U138 MG) were infected with lentivirus to overexpress TRIM48, and 1 human GBM cell line (T98G) was infected with siRNAs to knock down TRIM48 expression. Techniques used included cell proliferation assay, measured by CCK-8 and BrdU-ELISA method, and cell cycle assay, determined using flow cytometry. Curcumin, a specific activator of extracellular signal regulated kinases (ERK1/2), or PD98059, a specific inhibitor of ERK1/2, was used to activate or block the ERK1/2 pathway, respectively. Expression of phosphorylated (p)-ERK1/2, and its downstream targets (Cyclin D1) were measured to assess the mechanism. RESULTS Our data suggest that overexpression of TRIM48 reduces the viability of U87 MG and U138 MG and leads to cell cycle arrest (in G0-G1 phase), which is associated with blockade of the ERK1/2 pathway and reduction of Cyclin D1. In contrast, knockdown of TRIM48 resulted in the opposite effects. Interestingly, the inhibitory effect of TRIM48 overexpression on human GBM cell growth and the inactivation of ERK1/2 were significantly alleviated with additional curcumin treatment, while it the promoted the effect of siTRIM48 on human GBM cell growth, and the activation of ERK1/2 was significantly alleviated with additional PD98059 treatment. CONCLUSIONS TRIM48 suppressed the growth of human GBM cell via the prevention of ERK1/2 activation.

17.
Arch Gynecol Obstet ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667606

RESUMO

PURPOSE: To evaluate whether programmed intermittent epidural bolus (PIEB) reduces the incidence of maternal intra-partum fever compared with continuous epidural infusion (CEI) during labor. METHODS: Parturients were randomized to receive CEI (CEI group) or PIEB (PIEB group) with 10 ml per hour for epidural labor analgesia with 1500 subjects in each group. The maintaining dose of two groups is 0.08% ropivacaine with 0.4 µg/ml sufentanil, with patient-controlled epidural analgesia (PCEA) dose of 5 ml and lockout interval of 30 min. The incidence of maternal fever, pain score, epidural sensory levels, the number and proportion of PCEA demand, anesthetics consumption, satisfaction score, neonatal Apgar scale, and maternal and neonatal side effects were recorded. RESULTS: It was significantly lower of the incidence of maternal fever beginning at 4 h post-analgesia and continuing until delivery in the PIEB group than the CEI group (4 h: 2.6% vs. 4.2%; 5 h: 7.3% vs. 10.2%; delivery: 5.6% vs. 7.9%; 1 h post-delivery: 3.9% vs. 6.2%; 2 h post-delivery: 2.1 vs. 3.5%; total: 5.8% vs. 8.4% in PIEB and CEI, respectively). Compared with CEI group, pain scores at 3, 4, 5 h post-analgesia and delivery (3 h: 2 [1, 2] vs. 2 [1-3]; 4 h: 2 [2, 3] vs. 3 [2-4]; 5 h: 2 [2, 3] vs. 3 [2-4]; delivery: 3 [2-4] vs. 4 [3, 4] in PIEB and CEI, respectively), the number and proportion of PCEA demand (number: 0.7 ± 0.9 vs. 2.2 ± 1.9; proportion: 42.0% vs. 80.3% in PIEB and CEI, respectively), and anesthetics consumption significantly decreased in the PIEB group (Ropivacaine: 60 ± 13 mg vs. 76 ± 17 mg; Sufentanil: 26 ± 4 mg vs. 32 ± 6 mg in PIEB and CEI, respectively), without severe maternal and neonatal side effects and any difference in neonatal Apgar scale. The epidural sensory levels 2 h post-analgesia (2 h: 8[8, 9] vs. 9[8, 9] in PIEB and CEI) and satisfaction score (9 [9, 10] vs. 7 [6, 7] in PIEB and CEI) were significantly higher in the PIEB group compared with those in the CEI group. CONCLUSIONS: PIEB with 10 ml of 0.08% ropivacaine and 0.4 µg/ml sufentanil hourly provided a lower incidence of intra-partum fever with a better analgesic effect compared with CEI, without any severe maternal and neonatal adverse reactions.

18.
Hum Gene Ther ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31668086

RESUMO

Wilson's disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene encoding a liver active copper transport enzyme. Gene therapy with adeno-associated virus (AAV) carrying full length ATP7b, which is about 4.4 kb,, was shown to rescue copper metabolism disorder in WD mouse model. However, due to its relatively large size, the AAV vector containing full length ATP7b could be oversized for its packaging capacity, which could lead to inefficient packaging. To this purpose, we engineered a truncated ATP7b mutant (tATP7b) that is about 3.3kb in length and used for AAV gene therapy for WD mice. In vitro test showed that the excretion of copper outside the cells could be achieved with tATP7b as efficient as the full-length ATP7b. In vivo delivery of tATP7b to WD mice by AAV8 vectors corrected their copper metabolisms and significantly rescued copper accumulation related syndromes, including reduced urinary copper excretion, increased serum ceruloplasmin and improved liver damages. Thus, our work demonstrated AAV gene therapy based on truncated ATP7b is a promising strategy in the treatment of WD.

19.
Chem Biodivers ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705573

RESUMO

A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO 2 -BA) by "thiol-ene"click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γ-mercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO 2 -BA were characterized by Transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR),and Brunner-Emmet-Teller measurements  (BET). The adsorption behavior of the SiO 2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO 2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, (7.64 µmol/g) than non-glycoproteins (bovine serum albumin,BSA, 0.83 µmol/g). In addition, the practicality of the SiO 2 -BA was further assessed by selective enrichment of glycophoproteins from egg white samples.

20.
Medicine (Baltimore) ; 98(45): e17920, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702672

RESUMO

There is little information concerning the predictive ability of the preoperative platelet to albumin ratio (PAR) in hepatocellular carcinoma (HCC) patients after liver resection. In the current study, we aimed to assess the prognostic power of the PAR in HCC patients without portal hypertension (PH) following liver resection.Approximately 628 patients were included in this study. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of the PAR for both recurrence-free survival (RFS) and overall survival (OS). Univariate and multivariate analyses were used to identify the independent risk factors for both RFS and OS.During the follow-up period, 361 patients experienced recurrence, and 217 patients died. ROC curve analysis suggested that the best cut-off value of the PAR for RFS was greater than 4.8. The multivariate analysis revealed that microvascular invasion (MVI), tumor size >5 cm, high aspartate aminotransferase-to-platelet count ratio index (APRI) and high PAR were four independent risk factors for both RFS and OS. Patients with a low PAR had significantly better RFS and OS than those with a high PAR.The PAR may be a useful marker to predict the prognosis of HCC patients after liver resection. HCC patients with a high preoperative PAR had a higher recurrent risk and lower long-term survival rate than those with a low preoperative PAR.

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