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1.
Nutr Diabetes ; 9(1): 32, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685792

RESUMO

OBJECTIVE: The aim of this case-control study was to assess the efficacy of dapagliflozin combined with metformin for type-2 diabetes mellitus (T2DM) with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 36 patients with newly-diagnosed T2DM and OSAHS were randomized divided into two groups. Eighteen OSAHS patients with T2DM, who were treated with dapagliflozin and metformin, were assigned as the dapagliflozin group. These patients were given dapagliflozin and metformin for 24 weeks between February 2017 and February 2018. Another 18 OSAHS patients with T2DM, who were treated with glimepiride and metformin for 24 weeks, were assigned as the control group. Fasting plasma glucose (FPG) level, postprandial blood glucose (PPG), hemoglobin A1C (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), minimum oxygen saturation (LSpO2), and Epworth Somnolence Scale (ESS) score were measured before and at 24 weeks after the initiation of treatment. RESULTS: In the dapagliflozin group, triglyceride (TG), systolic pressure (SBP) and diastolic pressure (DBP) significantly decreased following treatment, while high-density lipoprotein cholesterol (HDL-C) significantly increased (P < 0.05). Furthermore, a reduction in AHI, an increase in LSpO2 and a decrease in ESS score were observed in the dapagliflozin group (P < 0.05), but not in the control group. Moreover, blood glucose, HbA1c, HOMA-IR, and BMI significantly decreased in these two groups, and the decrease was more significant in the dapagliflozin group. CONCLUSION: These present results indicate that dapagliflozin can significantly reduce glucose, BMI, blood pressure and AHI, and improve hypoxemia during sleep and excessive daytime sleepiness, which thereby has potential as an effective treatment approach for OSAHS.

2.
Pharmacotherapy ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742742

RESUMO

BACKGROUND: The pathogenic mechanism of antituberculous drug-induced liver injury (ATDILI) is associated with antioxidant enzymes. The objective of the present study was to investigate the associations of ATDILI susceptibility with genetic polymorphisms of antioxidant enzyme genes including nitric oxide synthase 2 (NOS2), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 2 (SOD2), BTB domain and CNC homolog 1 (BACH1), and MAF bZIP transcription factor K (MAFK). METHODS: Thirty tag single nucleotide polymorphisms (tag-SNPs) from the all candidate genes were genotyped in a 2-stage cohort study including an initial discovery stage with 461 ATDILI patients and 466 controls and a replication stage with 216 ATDILI patients and 432 controls. The frequencies and distributions of genotypes and haplotypes were compared between the case and control groups. Three different genetic models including dominant, recessive, and additive models were used to determine the associations with susceptibility to ATDILI. RESULTS: The SNPs rs9906835, rs944725, and rs3794764 of the NOS2 gene were significantly associated with an increased risk of ATDILI. The MAFK rs3735656 SNP was significantly associated with a decreased risk for ATDILI. The AAA haplotype of the NOS2 gene was associated with susceptibility to ATDILI. The treatment outcomes of patients with tuberculosis were further affected by genetic variants of the NOS2 and MAFK genes. CONCLUSIONS: Genetic polymorphisms of NOS2 and MAFK are associated with ATDILI susceptibility in Chinese patients with tuberculosis. The variants in NOS2 and MAFK affect treatment outcomes of tuberculosis patients. Further studies are needed to better understand the molecular mechanisms of ATDILI susceptibility via regulation of the expression of ATDILI-susceptibility genes and proteins.

3.
J Hazard Mater ; : 121511, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31706745

RESUMO

Black-odorous rivers and lakes are a serious environmental problem and are frequently reported in China. Despite this, there have been no comprehensive in-depth reviews of black-odorous water formation mechanisms, contributing factors and potential treatment technologies. Elements such as S, C and N play an important role in the biogeochemical cycle of black-odorous waterbodies, with water blackening caused by metal sulfides such as iron sulfide (FeS) and manganese sulfide (MnS). Volatile substances such as volatile organic sulfur compounds (VOSCs) are the main contributors of odor. Microorganisms such as sulfate reducing bacteria (SRB), Bacteroidetes and Proteobacteria play important roles in blackening and odor formation processes. Effectiveness of the commonly used treatments methods for black-odorous waterbodies, such as artificial aeration, sediment dredging, microbial enhanced technologies and constructed wetlands, varies significantly under different conditions. In contrast, bio-ecological engineering technologies exhibit comprehensive, long-lasting and economical treatment effects. The causes and mechanisms of black-odorous water formation require further investigation, as well as the optimal application conditions and mechanisms of treatment technologies. This study comprehensively reviews 1) the characteristics and current distribution of black-odorous waterbodies; 2) the compounds contributing to black-odorous phenomenon; 3) black-odorous waterbody production mechanisms; 4) treatment technologies for black-odorous waterbodies. Further studies on the mechanisms of blackening and odor formation are required, with treatment application conditions and mechanisms also requiring further clarification. In addition, the long-term ecological restoration of black-odorous rivers immediately after remediation is key issue that is easily overlooked but merits further investigation and development.

4.
PLoS One ; 14(9): e0222904, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31568536

RESUMO

PURPOSE: In 2013, the American Society for Radiation Oncology (ASTRO) issued a Choosing Wisely recommendation against the routine use of intensity modulated radiotherapy (IMRT) for whole breast irradiation. We evaluated IMRT use and subsequent impact on Medicare expenditure in the period immediately preceding this recommendation to provide a baseline measure of IMRT use and associated cost consequences. METHODS AND MATERIALS: SEER records for women ≥66 years with first primary diagnosis of Stage I/II breast cancer (2008-2011) were linked with Medicare claims (2007-2012). Eligibility criteria included lumpectomy within 6 months of diagnosis and radiotherapy within 6 months of lumpectomy. We evaluated IMRT versus conventional radiotherapy (cRT) use overall and by SEER registry (12 sites). We used generalized estimating equations logit models to explore adjusted odds ratios (OR) for associations between clinical, sociodemographic, and health services characteristics and IMRT use. Mean costs were calculated from Medicare allowable costs in the year after diagnosis. RESULTS: Among 13,037 women, mean age was 74.4, 50.5% had left-sided breast cancer, and 19.8% received IMRT. IMRT use varied from 0% to 52% across SEER registries. In multivariable analysis, left-sided breast cancer (OR 1.75), living in a big metropolitan area (OR 2.39), living in a census tract with ≤$90,000 median income (OR 1.75), neutral or favorable local coverage determination (OR 3.86, 1.72, respectively), and free-standing treatment facility (OR 3.49) were associated with receipt of IMRT (p<0.001). Mean expenditure in the year after diagnosis was $8,499 greater (p<0.001) among women receiving IMRT versus cRT. CONCLUSION: We found highly variable use of IMRT and higher expenditure in the year after diagnosis among women treated with IMRT (vs. cRT) with early-stage breast cancer and Medicare insurance. Our findings suggest a considerable opportunity to reduce treatment variation and cost of care while improving alignment between practice and clinical guidelines.

6.
Am J Med Genet A ; 179(12): 2459-2468, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520464

RESUMO

Hartnup disease is an autosomal recessive condition characterized by neutral aminoaciduria and behavioral problems. It is caused by a loss of B0 AT1, a neutral amino acid transporter in the kidney and intestine. CLTRN encodes the protein collectrin that functions in the transportation and activation of B0 AT1 in the renal apical brush bordered epithelium. Collectrin deficient mice have severe aminoaciduria. However, the phenotype associated with collectrin deficiency in humans has not been reported. Here we report two patients, an 11-year-old male who is hemizygous for a small, interstitial deletion on Xp22.2 that encompasses CLTRN and a 22-year-old male with a deletion spanning exons 1 to 3 of CLTRN. Both of them present with neuropsychiatric phenotypes including autistic features, anxiety, depression, compulsions, and motor tics, as well as neutral aminoaciduria leading to a clinical diagnosis of Hartnup disease and treatment with niacin supplementation. Plasma amino acids were normal in both patients. One patient had low 5-hydroxyindoleacetic acid levels, a serotoninergic metabolite. We explored the expression of collectrin in the murine brain and found it to be particularly abundant in the hippocampus, brainstem, and cerebellum. We propose that collectrin deficiency in humans can be associated with aminoaciduria and a clinical picture similar to that seen in Hartnup disease. Further studies are needed to explore the role of collectrin deficiency in the neurological phenotypes.

7.
Math Biosci Eng ; 16(5): 3382-3392, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31499619

RESUMO

Exploiting Modification Direction (EMD) based data hiding achieves good stego-image quality and high security level. Recently, a section-wise EMD was proposed to enhance the embedding capacity of EMD. Later, Wang et al. introduced a switch map based multi-group EMD to further improve the embedding capacity. However, by a detail observation on the switch map in Wang et al.'s scheme, we find that more codewords with longer code-length can be put into the switch map. In this paper, we build a new switch map by Huffman code, and construct an enhanced multi-group EMD using Huffman code based switch map. Our scheme has higher embedding capacity than Wang et al.'s scheme and other EMD based data hiding methods.

8.
Sci Total Environ ; 694: 133770, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31401510

RESUMO

A new method has been developed for improving the overall immobilization efficiency of phosphorus (P) in sediment. A capping agent (lanthanum modified bentonite, LMB) was sprinkled on the sediment surface to prevent the release of P in the top sediment layer. Meanwhile, an oxidizing agent (calcium nitrate, CN) was injected into the sediment layer (~5 cm) to immobilize labile P in deep sediment layers. High-resolution sampling techniques, including diffusive gradients in thin films (DGT) and high-resolution dialysis (HR-Peeper) were employed to investigate the fine-scale changes of labile and/or soluble nitrogen, P, sulfide and iron in sediments, respectively. The results showed that the combined application of LMB and CN had significant advantages over the individual treatments. The average concentrations of soluble reactive phosphorus (SRP) (0.01 mg/L) in the overlying water after a 68-day incubation were only 10%, 21% and 4% for the CK, LMB and CN treatments, respectively. Furthermore, the immobilization effect caused by the combined treatment reached from the sediment-water interface to a depth of 60 mm in the sediment, and the effective depth was much >20 mm caused by LMB treatment. The concentrations of SRP in the sediment profile were also lower than those of the other treatments. The results of this work indicate that the combined application of capping and oxidizing agents is a promising method to control water eutrophication by preventing the release of P from both the top and deep sediment layers.

9.
Mol Med Rep ; 20(4): 3065-3074, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432152

RESUMO

Human bone marrow­derived mesenchymal stromal cells (hBMSCs) have been revealed to be beneficial for the regeneration of tissues and cells in several diseases. The present study aimed to elucidate the mechanisms underlying the effect of hBMSC transplantation on neuron regeneration in a rat model of middle cerebral artery occlusion (MCAO). The hBMSCs were isolated, cultured and identified. A rat model of MCAO was induced via the modified Longa method. Neurological severity scores (NSS) were adopted for the evaluation of neuronal function in the model rats after cell transplantation. Next, the expression levels of nestin, ß­III­tubulin (ß­III­Tub), glial fibrillary acidic protein (GFAP), HNA and neuronal nuclear antigen (NeuN) were examined, as well as the positive expression rates of human neutrophil alloantigen (HNA), nestin, NeuN, ß­III­Tub and GFAP. The NSS, as well as the mRNA and protein expression of nestin, decreased at the 1st, 2nd, 4 and 8th weeks, while the mRNA and protein expression of NeuN, ß­III­Tub and GFAP increased with time. In addition, after treatment, the MCAO rats showed decreased NSS and mRNA and protein expression of nestin, but elevated mRNA and protein expression of NeuN, ß­III­Tub and GFAP at the 2nd, 4 and 8th weeks, and decreased positive expression of HNA and nestin with enhanced expression of NeuN, ß­III­Tub and GFAP. Therefore, the present findings demonstrated that hBMSC transplantation triggered the formation of nerve cells and enhanced neuronal function in a rat model of MCAO.

10.
BMC Cancer ; 19(1): 779, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391008

RESUMO

BACKGROUND: Numerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear. METHODS: The miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network. RESULTS: In total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 - AS, FOXD2 - AS1, AC105277.1, AC099850.3, STARD4 - AS1, SLC16A1 - AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR - 654, miR - 503, miR - 450a, miR - 379, miR - 369, miR - 190a, miR - 101, and let-7c) were found to be significantly associated with overall survival (log-rank p < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT. CONCLUSIONS: In this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.

11.
J Biomed Nanotechnol ; 15(10): 2045-2058, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462370

RESUMO

Combining photodynamic therapy (PDT) and chemotherapy can improve anti-cancer efficacy. In this study, a novel copolymer PTPP combining thioketal and protoporphyrin was synthesized and tested for antitumor activity. Self-assembled PTPP micelles loaded with doxorubicin (DOX) showed uniform size, narrow particle size distribution and greater antitumor activity in vivo and in vivo than DOX-loaded micelles made from the commonly used material mPEG-PCL. Under laser irradiation, the photosensitizing protoporphyrin of DOX/PTPP produces abundant reactive oxygen species (ROS) that directly kill tumor cells as well as destroy the micelles themselves, leading to drug release. The ROS and DOX then act synergistically against the tumors. These ROS-responsive, laser-sensitive polymeric micelles may be useful for combining PDT and chemotherapy.


Assuntos
Espécies Reativas de Oxigênio/química , Doxorrubicina , Liberação Controlada de Fármacos , Micelas , Fotoquimioterapia , Polímeros
12.
J Invertebr Pathol ; 166: 107228, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386829

RESUMO

As a polyphagous herbivore, the two-spotted spider mite Tetranychus urticae is engaged with various plant hosts and interacts with diverse organisms that share the same ecological niche. Thus, T. urticae faces frequent challenges from viral infections. However, the RNA viruses of T. urticae are still unknown. Here, we constructed two libraries (~8 Gb for RNA and ~10 Mb for small RNA) from a strain of T. urticae using deep sequencing, and identified three novel RNA viruses from the families Kitaviridae, Dicistroviridae, and Chuviridae. Among them, the Kitaviridae and Dicistroviridae viruses presented a possible interaction pattern with the host RNA interference pathway.

13.
Biochem Biophys Res Commun ; 518(2): 219-226, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31434611

RESUMO

Mycobacterium tuberculosis (MTB) infection could induce death of host human macrophages, promoting bacterial spread. In the current study we tested the potential role of microRNA-579 (miR-579) in the death of macrophages infected with MTB. In the primary human macrophages MTB infection induced upregulation of miR-579 but downregulation of its mRNA targets, SIRT1 and PDK1, which were accompanied by significant macrophage death and apoptosis. miR-579 inhibition, by its anti-sense sequence, restored SIRT1-PDK1 expression and significantly attenuated MTB-induced cytotoxicity and apoptosis in human macrophages. Conversely, ectopic overexpression of miR-579 further downregulated SIRT1-PDK1 expression and exacerbated MTB-induced cytotoxicity in human macrophages. Further studies showed that cPWWP2A, the miR-579's endogenous sponge circRNA, was downregulated in MTB-infected macrophages. Conversely, forced overexpression of cPWWP2A, by a recombinant adeno-associated virus construct, reversed MTB-induced miR-579 upregulation and macrophage cytotoxicity. Taken together, our results show that miR-579 upregulation mediates MTB-induced macrophage cytotoxicity. Targeting cPWWP2A-miR-579 axis could be a novel strategy to protect human macrophages from MTB infection.

14.
J Intensive Care Med ; : 885066619861580, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31284807

RESUMO

BACKGROUND: Midkine has been reported to play a crucial role in inflammatory, hypoxia, and tissue injury processes. We aimed to investigate plasma midkine in septic patients and its association with 28-day mortality and organ function. METHODS: Septic patients admitted to the Department of Critical Care Medicine, Zhongda Hospital, a tertiary hospital, from November 2017 to March 2018 were enrolled in the study. The baseline characteristics of the septic patients were recorded at admission. A peripheral blood sample was obtained at admission, and plasma midkine levels were evaluated with an immunoassay. All patients were followed up with for 28 days, with all-cause mortality being recorded. RESULTS: A total of 26 septic patients were enrolled, which included 18 survivors and 8 nonsurvivors at day 28. Plasma midkine levels were significantly elevated in the nonsurvivor group compared with the survivors (ng/L, 763.6 [404.7-1305], 268.5 [147.8-511.4]; P = .0387]. Plasma midkine levels were elevated in septic patients with moderate/severe acute respiratory distress syndrome (ARDS) compared with patients with non/mild ARDS (ng/L, 522.3 [336.6-960.1] vs 243.8 [110.3-478.9]; P = .0135) and in those with acute kidney injury compared with those without (ng/L, 489.8 [259.2-1058] vs 427.9 [129.6-510.3]; P = .0973). Changes in plasma midkine levels were also associated with extravascular lung water index (P = .063) and pulmonary vascular permeability index (P = .049). CONCLUSIONS: Plasma midkine was associated with 28-day mortality, as well as pulmonary and kidney injury, in septic patients.

15.
J Natl Compr Canc Netw ; 17(7): 813-820, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31319393

RESUMO

BACKGROUND: The purpose of this study was to assess advanced imaging (bone scan, CT, or PET/CT) and serum tumor biomarker use in asymptomatic breast cancer survivors during the surveillance period. PATIENTS AND METHODS: Cancer registry records for 2,923 women diagnosed with primary breast cancer in Washington State between January 1, 2007, and December 31, 2014, were linked with claims data from 2 regional commercial insurance plans. Clinical data including demographic and tumor characteristics were collected. Evaluation and management codes from claims data were used to determine advanced imaging and serum tumor biomarker testing during the peridiagnostic and surveillance phases of care. Multivariable logistic regression models were used to identify clinical factors and patterns of peridiagnostic imaging and biomarker testing associated with surveillance advanced imaging. RESULTS: Of 2,923 eligible women, 16.5% (n=480) underwent surveillance advanced imaging and 31.8% (n=930) received surveillance serum tumor biomarker testing. Compared with women diagnosed before the launch of the Choosing Wisely campaign in 2012, later diagnosis was associated with lower use of surveillance advanced imaging (odds ratio [OR], 0.68; 95% CI, 0.52-0.89). Factors significantly associated with use of surveillance advanced imaging included increasing disease stage (stage III: OR, 3.65; 95% CI, 2.48-5.38), peridiagnostic advanced imaging use (OR, 1.76; 95% CI, 1.33-2.31), and peridiagnostic serum tumor biomarker testing (OR, 1.35; 95% CI, 1.01-1.80). CONCLUSIONS: Although use of surveillance advanced imaging in asymptomatic breast cancer survivors has declined since the launch of the Choosing Wisely campaign, frequent use of surveillance serum tumor biomarker testing remains prevalent, representing a potential target for further efforts to reduce low-value practices.

16.
EMBO Rep ; 20(7): e47563, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31267712

RESUMO

Monoubiquitination of histone H2B on lysine 120 (H2Bub1) is an epigenetic mark generally associated with transcriptional activation, yet the global functions of H2Bub1 remain poorly understood. Ferroptosis is a form of non-apoptotic cell death characterized by the iron-dependent overproduction of lipid hydroperoxides, which can be inhibited by the antioxidant activity of the solute carrier family member 11 (SLC7A11/xCT), a component of the cystine/glutamate antiporter. Whether nuclear events participate in the regulation of ferroptosis is largely unknown. Here, we show that the levels of H2Bub1 are decreased during erastin-induced ferroptosis and that loss of H2Bub1 increases the cellular sensitivity to ferroptosis. H2Bub1 epigenetically activates the expression of SLC7A11. Additionally, we show that the tumor suppressor p53 negatively regulates H2Bub1 levels independently of p53's transcription factor activity by promoting the nuclear translocation of the deubiquitinase USP7. Moreover, our studies reveal that p53 decreases H2Bub1 occupancy on the SLC7A11 gene regulatory region and represses the expression of SLC7A11 during erastin treatment. These data not only suggest a noncanonical role of p53 in chromatin regulation but also link p53 to ferroptosis via an H2Bub1-mediated epigenetic pathway. Overall, our work uncovers a previously unappreciated epigenetic mechanism for the regulation of ferroptosis.

17.
Sci Total Environ ; 691: 969-980, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31326819

RESUMO

A good understanding of lead (Pb) mobilization in eutrophic lakes is a key to the accurate assessment of Pb pollution. In this work, dissolved and labile Pb was determined by both high resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) in sediment-water profiles of the hyper-eutrophic Meiliang Bay of Lake Taihu on a monthly basis during one year. The drinking water standards for dissolved Pb of the World Health Organization (10µg/L) and those of China were exceeded in the overlying water (20.79-118.5µg/L). Out of which, a total of five months even exceeded the fisheries water quality limitation (50µg/L) in China. The algal blooms created an anaerobic environment in the surface sediments in July. The reductive conditions led to the dissolution of Fe/Mn and this caused the release of Pb, followed by organic matter complexation. This was supported by the coincident changes of dissolved Pb with dissolved organic matter (DOM) in sediments under anaerobic incubation. Algae residue decomposition in October caused another distinct release of Pb, but this process should be considerably suppressed by increased sulfide precipitation and pyrite adsorption of Pb ion. These results indicated that Pb mobilization in sediments can be significantly enhanced by algal blooms in eutrophic lakes, indicating that further attention should be paid to Pb pollution in waters with harmful algal blooms.


Assuntos
Sedimentos Geológicos/química , Proliferação Nociva de Algas , Chumbo/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental
18.
Biomed Res Int ; 2019: 3065818, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236404

RESUMO

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related death in the world. Despite the fact that there are many methods to treat HCC, the 5-year survival rate of HCC is still at a low level. Emodin can inhibit the growth of HCC cells in vitro and in vivo. However, the gene regulation of emodin in HCC has not been well studied. In our research, RNA sequencing technology was used to identify the differentially expressed genes (DEGs) in HepG2 cells induced by emodin. A total of 859 DEGs were identified, including 712 downregulated genes and 147 upregulated genes in HepG2 cells treated with emodin. We used DAVID for function and pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING, and Cytoscape was used for module analysis. The enriched functions and pathways of the DEGs include positive regulation of apoptotic process, structural molecule activity and lipopolysaccharide binding, protein digestion and absorption, ECM-receptor interaction, complement and coagulation cascades, and MAPK signaling pathway. 25 hub genes were identified and pathway analysis revealed that these genes were mainly enriched in neuropeptide signaling pathway, inflammatory response, and positive regulation of cytosolic calcium ion concentration. Survival analysis showed that LPAR6, C5, SSTR5, GPR68, and P2RY4 may be involved in the molecular mechanisms of emodin therapy for HCC. A quantitative real-time PCR (qRT-PCR) assay showed that the mRNA levels of LPAR6, C5, SSTR5, GPR68, and P2RY4 were significantly decreased in HepG2 cells treated with emodin. In conclusion, the identified DEGs and hub genes in the present study provide new clues for further researches on the molecular mechanisms of emodin.

19.
Acta Otolaryngol ; 139(9): 769-776, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240977

RESUMO

Background: The electrophysiology of auditory nerve mature is particularly important for unilateral hearing loss. Objectives: To assess the hearing status in young children with congenital monaural malformation and evaluate their potential for practical use in the functional maturation parameters of the auditory pathway. Materials and methods: ABR (auditory brainstem responses) and ASSR (auditory steady-state responses) threshold measurements were performed in 21 young children with congenital monaural atresia. Results: The average electrophysiologic thresholds for the ABR were 65 dB nHL ± 1.20 in malformed ears and 25 dB nHL ± 0.48 in normal ones. All 21 atretic ears presented with typical conductive hearing loss. There was no statistic positive correlation in hearing-impaired ears between the methods of ABR and ASSR responses (r = 0.12, 0.20 and 0.17). The IPL (interpeak latency) of I-III, III-V and I-V of atretic ears in ABR test was decreased relative to normal ears. Furthermore, a shortening of the IPLs I-III, III-V, I-V can be observed with increasing age of the children in malformed ears. Conclusions and significance: The ABR- and ASSR-based hearing evaluation in young children with congenital monaural malformation should be viewed as complementary technologies. Besides, there was no delay of functional maturation at brainstem level although unilateral hearing was deprived during their early years of life.

20.
Pharmacol Res Perspect ; 7(3): e00488, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31149343

RESUMO

In this study, we describe a novel approach for collecting bile from dogs and cynomolgus monkeys for metabolite profiling, ultrasound-guided cholecystocentesis (UCC). Sampling bile by UCC twice within 24 hours was well tolerated by dogs and monkeys. In studies with atorvastatin (ATV) the metabolite profiles were similar in bile obtained through UCC and from bile duct-cannulated (BDC) dogs. Similar results were observed in UCC and BDC monkeys as well. In both monkey and dog, the primary metabolic pathway observed for ATV was oxidative metabolism. The 2-hydroxy- and 4-hydroxyatorvastatin metabolites were the major oxidation products, which is consistent with previously published metabolite profiles. S-cysteine and glucuronide conjugates were also observed. UCC offers a viable alternative to bile duct cannulation for collection of bile for metabolite profiling of compounds that undergo biliary excretion, given the similar metabolite profiles in bile obtained via each method. Use of UCC for metabolite profiling may reduce the need for studies using BDC animals, a resource-intensive model.

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