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1.
Biomed Chromatogr ; : e4807, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020626

RESUMO

Periplocae Cortex, named Xiang-Jia-Pi in China, has been widely used to treat autoimmune diseases, especially rheumatoid arthritis. However, the in vivo substances of Periplocae Cortex remain unknown yet. In this study, an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used for profiling the chemical components and related metabolites of Periplocae Cortex. A total of 98 constituents were identified or tentatively characterized in Periplocae Cortex: 42 C21 steroidal glycosides, 10 cardiac glycosides, 23 organic acids, 4 aldehydes, 7 triterpenes, and 12 other types. Among them, 18 components were unambiguously identified by comparison with reference standards. In addition, 176 related xenobiotics (34 prototypes and 142 metabolites) were screened out and characterized in rats' biosamples (plasma, urine, bile, and feces) after the oral administration of Periplocae Cortex. Moreover, the metabolic fate of periplocoside S-4a, a C21 steroidal glycoside, was proposed for the first time. In summary, phase II reactions (methylation, glucuronidation, and sulfation), phase I reactions (hydrolysis reactions, oxygenation, and reduction), and their combinations were the predominant metabolic reactions of Periplocae Cortex in rat. It is the first report to reveal the in vivo substances and metabolism feature of Periplocae Cortex. This study also provided meaningful information for further pharmacodynamics study of Periplocae Cortex, as well as its quality control research.

2.
Eur J Pharmacol ; 873: 172925, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31958453

RESUMO

Osteoarthritis (OA), a degenerative arthropathy, is featured with progressive degradation of cartilage and a chondrocyte inflammatory response. Erdosteine (ER) showed the anti-oxidant properties and various anti-inflammatory effects in various diseases. However, whether it protects against OA remains unknown. In this study, we explore the potential therapeutic properties of ER on IL-1ß-stimulated rat chondrocytes and its underlying mechanism in vitro and vivo. Cell viability, pro-inflammatory cytokines and the degradation of ECM biomarkers were tested to determine the effects of ER at 10, 20, and 40 µM doses on IL-1ß-induced rat chondrocytes for 24 h in virto. In vivo, intra-articular injections of 50 µl of 100 mg/ml ER twice a week for 8 weeks. The results showed ER significantly suppressed the expressions of IL-1ß-induced the production of inflammatory factors in a dose-dependent pattern (4.30-fold decrease in COX-2, p < 0.05; 4.77-fold decrease in iNOS, p < 0.05 at 40 µM in protein levels). Moreover, ER could attenuate the degradation of ECM in IL-1ß-induced rat chondrocytes by repressing the expression of OA-related factors (2.40-fold decrease in ADAMTS-5, p < 0.05; 3.12-fold decrease in MMP1, p < 0.05; 3.97-fold decrease in MMP3, p < 0.05; and 2.62-fold decrease in MMP-13, p < 0.05 at 40 µM in protein levels). Furthermore, our study revealed that ER could inhibit the activations of IL-1ß-induced MAPK and Wnt/ß-catenin. Besides, ER could suppress the process of IL-1ß-induced P65 from the cytoplasm into the nucleus. In vivo, ER delaied the osteoarthritis progression in rat OA models. Collectively, ER might become a new therapeutic agent for OA.

3.
Gene ; 733: 144384, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31978508

RESUMO

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death. Recently, many studies have demonstrated that small nucleolar RNA (snoRNA) was closely related to HCC. OBJECTIVE: To explore whether snoRNA can be used as a molecular target for HCC. METHODS: The PubMed, Embase, and Cochrane databases were searched for the published literatures related to snoRNA and HCC until August 12, 2019. After identification, screening, and verification, this study finally included 26 studies correlating small nucleolar RNA host gene (SNHG) and HCC, and 8 studies correlating snoRNA and HCC. Based on the collation of the relevant literature, the correlation network diagram between snoRNAs and HCC was constructed. RESULTS: The SNHGs, such as SNHG1, SNHG6, SNHG16, and SNHG20 can play varied roles in HCC through different regulatory mechanisms. These SNHGs can promote and inhibit tumorigenesis. SNORD76 can promote the proliferation of tumor tissues and cells in vitro through different pathways. SnoU2_19 and SNORD76 can function through the same pathway. SNHG3, SNHG20, SNHG6, SNORD76, and snoRA47 can modulate epithelial-mesenchymal transition (EMT) to regulate the development of HCC cell or tissue. SNHG16, SNORD76, and SnoU2_19 can regulate the development of HCC through Wnt/ß-catenin signaling pathway. CONCLUSION: snoRNA can regulate the occurrence of HCC by modulating multiple molecular signaling pathways. Hence, snoRNA can be a potential molecular target for HCC.

4.
Appl Environ Microbiol ; 86(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31676481

RESUMO

Dietary fiber provides growth substrates for bacterial species that belong to the colonic microbiota of humans. The microbiota degrades and ferments substrates, producing characteristic short-chain fatty acid profiles. Dietary fiber contains plant cell wall-associated polysaccharides (hemicelluloses and pectins) that are chemically diverse in composition and structure. Thus, depending on plant sources, dietary fiber daily presents the microbiota with mixtures of plant polysaccharides of various types and complexity. We studied the extent and preferential order in which mixtures of plant polysaccharides (arabinoxylan, xyloglucan, ß-glucan, and pectin) were utilized by a coculture of five bacterial species (Bacteroides ovatus, Bifidobacterium longum subspecies longum, Megasphaera elsdenii, Ruminococcus gnavus, and Veillonella parvula). These species are members of the human gut microbiota and have the biochemical capacity, collectively, to degrade and ferment the polysaccharides and produce short-chain fatty acids (SCFAs). B. ovatus utilized glycans in the order ß-glucan, pectin, xyloglucan, and arabinoxylan, whereas B. longum subsp. longum utilization was in the order arabinoxylan, arabinan, pectin, and ß-glucan. Propionate, as a proportion of total SCFAs, was augmented when polysaccharide mixtures contained galactan, resulting in greater succinate production by B. ovatus and conversion of succinate to propionate by V. parvula Overall, we derived a synthetic ecological community that carries out SCFA production by the common pathways used by bacterial species for this purpose. Systems like this might be used to predict changes to the emergent properties of the gut ecosystem when diet is altered, with the aim of beneficially affecting human physiology.IMPORTANCE This study addresses the question as to how bacterial species, characteristic of the human gut microbiota, collectively utilize mixtures of plant polysaccharides such as are found in dietary fiber. Five bacterial species with the capacity to degrade polymers and/or produce acidic fermentation products detectable in human feces were used in the experiments. The bacteria showed preferential use of certain polysaccharides over others for growth, and this influenced their fermentation output qualitatively. These kinds of studies are essential in developing concepts of how the gut microbial community shares habitat resources, directly and indirectly, when presented with mixtures of polysaccharides that are found in human diets. The concepts are required in planning dietary interventions that might correct imbalances in the functioning of the human microbiota so as to support measures to reduce metabolic conditions such as obesity.

5.
J Pharm Biomed Anal ; 177: 112836, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31473481

RESUMO

Xian-Ling-Gu-Bao capsule (XLGB) is an effective traditional Chinese medicine prescription (TCMP) that is used for the prevention and treatment of osteoporosis in China. A rapid, simple, efficient and stable method based on UPLC-MS/MS technology was developed for simultaneous determination of multiple components of XLGB in rat plasma. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). For twenty-one selected quantitative prototypes, all calibration curves showed favourable linearity (r>0.9932) in linear ranges. The lower limits of quantification (LLOQs) were 2 ng/mL for psoralen (PL), 2.5 ng/mL for asperosaponin VI (AS), 1 ng/mL for isopsoralen (IPS) and sweroside (SW), 0.5 ng/mL for magnoflorine (MA), bavachinin (BVN), tanshinone IIA (TA), timosaponin BII (TBII) and icaritin (ICT), 0.1 ng/mL for epimedin B (EB) and epimedin C (EC), 0.05 ng/mL for icariin (IC), isobavachalcone (IBC), psoralidin (PD), bavachin (BV), bavachalcone (BC), epimedin A (EA) and isobavachin (IBV), 0.02 ng/mL for neobavaisoflavone (NEO) and icariside I (ICI) and 0.01 ng/mL for icariside II (ICII). The intra-day and inter-day (low, medium, high) precision (relative standard deviation) for all analytes was less than 8.63%, and the accuracies (as relative error) were in the range of -12.45% to 8.91%. Extraction recoveries and matrix effects of analytes and IS were acceptable. All analytes were stable during the assay and storage in plasma samples. The validated method was successfully applied to the pharmacokinetics (PK) studies of the twenty-one prototypes at pharmacodynamic doses (0.3 and 1 g/kg/day). In addition, dynamic profiles of 28 metabolites (phase II conjugates: 23 glucuronide conjugates, 2 sulfate conjugates and 3 glucuronide or sulfate conjugates) were also monitored by their area/IS area-time curves. As a result, coumarins, prenylated flavonoids from Psoraleae Fructus, alkaloids and prenylated flavonol glycosides from Epimedii Herba, and iridoid glycosides, triterpenoid saponins from Dipsaci Asperoidis Radix were considered to be the key effective substances of XLGB due to their high exposure and appropriate pharmacokinetic features. This is the first report to reveal pharmacodynamic ingredients by a reversed pharmacodynamic (PD) - pharmacokinetics (PK) study.

6.
Inflammation ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823179

RESUMO

Osteoarthritis (OA) is a common chronic inflammatory joint disease characterized by cartilage degradation. p-Coumaric acid (PCA), a dietary phenolic compound, has exerted anti-inflammatory and anti-oxidative activities in various diseases. However, the effects of PCA on OA have not been reported. In the present study, we aimed to investigate the effects of PCA on interleukin-1ß(IL-1ß)-induced inflammatory responses and cellular senescence in rat chondrocytes. Our results revealed that PCA remarkably downregulated IL-1ß-induced inflammatory factors such as COX2 and iNOS and cartilage-degrading enzymes like matrix metalloproteinases (MMP1, MMP3, and MMP13) and aggrecanases (ADAMTS4 and ADAMTS5) in chondrocytes. The IL-1ß-induced degradation of cartilage matrix (collagen II and aggrecan) could also be suppressed by PCA. Besides, PCA treatment effectively inhibited the IL-1ß-induced p16INK4a protein expression and SAß-gal activities in vitro. Mechanism analysis showed that PCA suppressed IL-1ß-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. In vivo, we also found that PCA could alleviate the development of OA in a rat model. Altogether, our findings implicate that p-coumaric acid attenuates IL-1ß-induced inflammatory responses and cellular senescence via inhibition of the MAPK and NF-κB signaling pathway in chondrocytes, and p-coumaric acid may be a promising candidate for the treatment of osteoarthritis.

7.
Front Integr Neurosci ; 13: 67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798426

RESUMO

Semantic audiovisual stimuli have a facilitatory effect on behavioral performance and influence the integration of multisensory inputs across sensory modalities. Many neuroimaging and electrophysiological studies investigated the neural mechanisms of multisensory semantic processing and reported that attention modulates the response to multisensory semantic inputs. In the present study, we designed an functional magnetic resonance imaging (fMRI) experiment of semantic discrimination using the unimodal auditory, unimodal visual and bimodal audiovisual stimuli with semantic information. By manipulating the stimuli present on attended and unattended position, we recorded the task-related fMRI data corresponding to the unimodal auditory, unimodal visual and bimodal audiovisual stimuli in attended and unattended conditions. We also recorded the fMRI data in resting state. Then the fMRI method was used together with a graph theoretical analysis to construct the functional brain networks in task-related and resting states and quantitatively characterize the topological network properties. The aim of our present study is to explore the characteristics of functional brain networks that process semantic audiovisual stimuli in attended and unattended conditions, revealing the neural mechanism of multisensory processing and the modulation of attention. The behavioral results showed that the audiovisual stimulus presented simultaneously promoted the performance of semantic discrimination task. And the analyses of network properties showed that compared with the resting-state condition, the functional networks of processing semantic audiovisual stimuli (both in attended and unattended conditions) had greater small-worldness, global efficiency, and lower clustering coefficient, characteristic path length, global efficiency and hierarchy. In addition, the hubs were concentrated in the bilateral temporal lobes, especially in the anterior temporal lobes (ATLs), which were positively correlated to reaction time (RT). Moreover, attention significantly altered the degree of small-worldness and the distribution of hubs in the functional network for processing semantic audiovisual stimuli. Our findings suggest that the topological structure of the functional brain network for processing semantic audiovisual stimulus is modulated by attention, and has the characteristics of high efficiency and low wiring cost, which maintains an optimized balance between functional segregation and integration for multisensory processing efficiently.

8.
J Leukoc Biol ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829469

RESUMO

High-fat diet (HFD) induced hepatic endoplasmic reticulum (ER) stress drives insulin resistance (IR) and steatosis. NK cells in adipose tissue play an important role in the pathogenesis of IR in obesity. Whether NK cells in the liver can induce hepatic ER stress and thus promote IR in obesity is still unknown. We demonstrate that HFD-fed mice display elevated production of proinflammatory cytokine osteopontin (OPN) in hepatic NK cells, especially in CD49a+ DX5- tissue-resident NK (trNK) cells. Obesity-induced ER stress, IR, and steatosis in the liver are ameliorated by ablating NK cells with neutralizing antibody in HFD-fed mice. OPN treatment enhances the expression of ER stress markers, including p-PERK, p-eIF2, ATF4, and CHOP in both murine liver tissues and HL-7702, a human liver cell line. Pretreatment of HL-7702 cells with OPN promotes hyperactivation of JNK and subsequent decrease of tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), resulting in impaired insulin signaling, which can be reversed by inhibiting ER stress. Collectively, we demonstrate that hepatic NK cells induce obesity-induced hepatic ER stress, and IR through OPN production.

9.
Aging (Albany NY) ; 11(24): 12532-12545, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841119

RESUMO

Osteoarthritis (OA) is a highly prevalent joint disorder blamed for pain and disability in older individuals. It's commonly accepted that inflammation, apoptosis, autophagy and cellular senescence participate in the progress of OA. Protease activated receptor 2 (PAR2), a member of the G-protein coupled receptors, is involved in the regulation of various inflammation diseases. Previous studies have identified PAR2 as a potential therapeutic target for the treatment of OA. Here, we investigated the role of PAR2 antagonist AZ3451 in inflammation response, apoptosis, autophagy and cellular senescence during OA. We confirmed that PAR2 expression was significantly up-regulated in OA articular cartilage tissues as well as in interleukin 1ß (IL-1ß) stimulated chondrocytes. We demonstrated AZ3451 could prevent the IL-1ß-induced inflammation response, cartilage degradation and premature senescence in chondrocytes. Further study showed that AZ3451 attenuated chondrocytes apoptosis by activating autophagy in vitro. The P38/MAPK, NF-κB and PI3K/AKT/mTOR pathways were involved in the protective effect of AZ3451. In vivo, we found that intra-articular injection of AZ3451 could ameliorate the surgery induced cartilage degradation in rat OA model. Our work provided a better understanding of the mechanism of PAR2 in OA, and indicated that PAR2 antagonist AZ3451 might serve as a promising strategy for OA treatment.

10.
Leukemia ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776466

RESUMO

Recurrent oncogenic mutations of MyD88 have been identified in a variety of lymphoid malignancies. Gain-of-function mutations of MyD88 constitutively activate downstream NF-κB signaling pathways, resulting in increased cellular proliferation and survival. However, whether MyD88 activity can be aberrantly regulated in MyD88-wild-type lymphoid malignancies remains poorly understood. SPOP is an adaptor protein of CUL3-based E3 ubiquitin ligase complex and frequently mutated genes in prostate and endometrial cancers. In this study, we reveal that SPOP binds to and induces the nondegradative ubiquitination of MyD88 by recognizing an atypical SPOP-binding motif in MyD88. This modification blocks Myddosome assembly and downstream NF-κB activation. SPOP is mutated in a subset of lymphoid malignancies, including diffuse large B-cell lymphoma (DLBCL). Lymphoid malignancies-associated SPOP mutants exhibited impaired binding to MyD88 and suppression of NF-κB activation. The DLBCL-associated, SPOP-binding defective mutants of MyD88 escaped from SPOP-mediated ubiquitination, and their effect on NF-κB activation is stronger than that of wild-type MyD88. Moreover, SPOP suppresses DLBCL cell growth in vitro and tumor xenograft in vivo by inhibiting the MyD88/NF-κB signaling. Therefore, SPOP acts as a tumor suppressor in DLBCL. Mutations in the SPOP-MyD88 binding interface may disrupt the SPOP-MyD88 regulatory axis and promote aberrant MyD88/NF-κB activation and cell growth in DLCBL.

11.
Med Sci Monit ; 25: 8562-8570, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721757

RESUMO

BACKGROUND This study aimed to compare femoral obturator nerve block (FONB) with fascia iliaca compartment block (FICB) in the management of acute preoperative pain in elderly patients with hip fracture. MATERIAL AND METHODS Patients ≥65 years (n=154) diagnosed with hip fracture who had surgery within 48 hours of hospital admission included two groups who received ultrasound-guided nerve block, the FONB group (n=77), and the FICB group (n=77). The visual analog scale (VAS) score for pain, requirement for analgesic drugs, nursing care requirements after hospitalization, post-operative complications, and rehabilitation were compared between the FONB and FICB patient groups. RESULTS The VAS scores after both nerve block procedures were significantly reduced compared with those before both nerve block procedures (P<0.05), but there were no differences on the second day after nerve block. The VAS scores at rest and on exercise in the FONB group were significantly lower than those in the FICB group at 30 min and one day after nerve block (P<0.05). The requirement for postoperative analgesic drugs in the FONB group was significantly lower than that in the FICB group (P=0.048). The incidence of nausea and vertigo in the FICB group were significantly higher than in the FONB group (P=0.031 and P=0.034, respectively). Patients in the FONB group experienced significantly improved quality of postoperative function (P=0.029). CONCLUSIONS Both FONB and FICB provided pain control for elderly patients with hip fracture. However, compared with FICB, FONB resulted in significantly improved analgesia with a reduced requirement for analgesic drugs.

12.
Medicine (Baltimore) ; 98(44): e17812, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689866

RESUMO

The aim of this study was to analyze the risk factors, clinical features, and antimicrobial resistance of Pseudomonas putida (P putida) isolated from Tongji Hospital in Wuhan, China.The data of 44 patients with P putida infections were retrospectively reviewed in this study. All cases of P putida strains were detected by the clinical laboratory of Tongji Hospital in the period of January 2010 to December 2017. Antimicrobial susceptibility testing was conducted using Kirby-Bauer method.Forty-four effective strains of P putida were isolated, including 32 inpatients and 12 outpatients. The 32 inpatients cases were obtained from various departments, which were urosurgery wards (n = 5, 15.6%), pediatrics wards (n = 4, 12.5%), hepatic surgery wards (n = 4, 12.5%), among others. The isolates had been discovered from urine specimens (28.2%), blood specimens (21.9%), sputum specimens (12.5%), and so on. Twenty-five patients had histories of catheterization before the isolation of P putida. Twenty-four patients were in immunocompromised states, 5 patients had undergone surgery, catheterization and were taking immunosuppressive therapy simultaneously. Polymicrobial infections were found in some P putida cases, especially Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Escherichia coli. All the patients had treated by antimicrobial before culture. Multi-drug-resistant strains were detected in 75% of P putida isolates. The P putida strains were resistant to trimethoprim/sulfamethoxazole (97.7%), aztreonam (88.6%), minocyline (74.3%), ticarcillin/clavulanic acid (72.7%), and sensitive to amikacin (86.4%), imipenem (62.8%), gentamicin (56.8%).Catheterization or other invasive procedures, immunocompromised states, and underlying diseases increased the risks of P putida infections. Moreover, the P putida strains were highly resistant to trimethoprim/sulfamethoxazole, aztreonam, minocyline, ticarcillin/clavulanic acid.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Pseudomonas/microbiologia , Pseudomonas putida/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Bioinformatics ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778157

RESUMO

MOTIVATION: Long noncoding RNA (lncRNA) has been verified to interact with other biomolecules especially protein-coding genes (PCGs), thus playing essential regulatory roles in life activities and disease development. However, the inner mechanisms of most lncRNA-PCG relationships are still unclear. Our study investigated the characteristics of true lncRNA-PCG relationships and constructed a novel predictor with machine learning algorithms. METHODS: A total of 307 true lncRNA-PCG pairs were obtained from database. Then, the different characteristics between true and random pairs were investigated using multi-omics data such as ChIP-seq, RNA-seq, microarray data and so on. These characteristics were further put into logistic regression (LR), support vector machine (SVM) and random forest (RF) algorithms to construct the models for lncRNA-PCG relationships prediction. Finally, colon cancer-associated differential expressed lncRNAs and PCGs from TCGA portal were used to perform a case study. RESULTS: There are significant differences in multiple characteristics between true and random lncRNA-PCG sets. Besides, 3-fold cross-validation and prediction results on independent test sets show the great AUC values of LR, SVM and RF, among which RF has the best performance with average AUC 0.818 for cross-validation, 0.823 and 0.853 for two independent test sets respectively. In case study, some candidate lncRNA-PCG relationships in colorectal cancer were found and HOTAIR-COMP interaction was specially exemplified. The proportion of the reported pairs in the predicted positive results was significantly higher than that in negative results (P<0.05). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

14.
Yonsei Med J ; 60(11): 1013-1020, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31637882

RESUMO

PURPOSE: Effective biomarkers and models are needed to improve the prognostic prospects of clear cell renal cell carcinoma (ccRCC). The purpose of this work was to identify DNA methylation biomarkers and to evaluate the utility of DNA methylation analysis for ccRCC prognosis. MATERIALS AND METHODS: An overview of genome-wide methylation of ccRCC tissues derived from The Cancer Genome Atlas (TCGA) database was download for analysis. DNA methylation signatures were identified using Cox regression methods. The potential clinical significance of methylation biomarkers acting as a novel prognostic markers was analyzed using the Kaplan-Meier method and receiver operating characteristic (ROC) curves. RESULTS: This study analyzed data for 215 patients with information on 23171 DNA methylation sites and identified a two-DNA methylation signature (cg18034859, cg24199834) with the help of a step-wise multivariable Cox regression model. The area under the curve of ROCs for the two-DNA methylation signature was 0.819. The study samples were stratified into low- and high-risk classifications based on an optimal threshold, and the two groups showed markedly different survival rates. Moreover, the two-DNA methylation marker was suitable for patients of varying ages, sex, stages (I and IV), and histologic grade (G2). CONCLUSION: The two-DNA methylation signature was deemed to be a potential novel prognostic biomarker of use in increasing the accuracy of predicting overall survival of ccRCC patients.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Metilação de DNA/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Bases de Dados Genéticas , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Fatores de Risco , Taxa de Sobrevida
15.
J Transl Med ; 17(1): 353, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665031

RESUMO

BACKGROUND: The colorectum includes ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Different sites of colorectal cancer (CRC) are different in many aspects, including clinical symptoms, biological behaviour, and prognosis. PURPOSE: This study aimed to analyse prognosis, genes, bacteria, fungi, and microbial metabolome in different sites of CRC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database and STAT were used to statistically describe and analyse the prognosis in different sites of CRC. RNA sequences of CRC from Broad Institute's GDAC Firehose were re-annotated and reanalysed based on different sites using weighted gene co-expression network analysis (WGCNA). The Kaplan-Meier method was used to analyse the prognosis and Cytoscape was used to construct a drug-target network based on DGIdb databases. Bacterial 16S V3-V4 and fungal ITS V3-V4 ribosomal RNA genes of stool samples were sequenced. Gas chromatography/mass spectrometry (GS/MS) was performed to detect the microbial metabolites in stool samples. Bioinformatics analysis was performed to compare distinct gut microorganisms and microbial metabolites between rectal and sigmoid cancers. RESULTS: The prognosis in CRC with different sites is significantly different. The closer to the anus predicted longer survival time. The difference between genes and co-expression pairs in CRC with different sites were constructed. The relative abundance of 112 mRNAs and 26 lncRNAs correlated with the sites of CRC were listed. Nine differentially expressed genes at different sites of CRC were correlated with prognosis. A drug-gene interaction network contained 227 drug-gene pairs were built. The relative abundance of gut bacteria and gut fungus, and the content of microbe-related metabolites were statistically different between rectal and sigmoid cancers. CONCLUSIONS: There are many differences in prognosis, genome, drug targets, gut microbiome, and microbial metabolome in different colorectal cancer sites. These findings may improve our understanding of the role of the CRC sites in personalized and precision medicine.

16.
Cancer Manag Res ; 11: 8295-8302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571987

RESUMO

Background: This study aims to compare the efficacy and adverse reactions of bortezomib for treating newly diagnosed multiple myeloma (MM) through two different administration methods: intravenous (IV) injection and subcutaneous (SC) injection. Methods: A retrospective analysis was performed in 205 patients with newly diagnosed MM, who were treated by the Department of Hematopathology, Henan Cancer Hospital, from June 2009 to December 2017. These patients were divided into two groups according to the treatment methods: IV injection group, IV injection of bortezomib; SC injection group, SC injection of bortezomib. Results: After the first course of treatment, the effect of very good partial remission (VGPR) or above (≥VGPR) in the IV injection group (IV group) and SC injection group (SC group) was 31.0% and 14.3%, respectively (P=0.004), while the overall response rate (ORR) was 72.0% and 49.5%, respectively (P=0.001). From the 2nd course to the 6th course of treatment, the ORR was not statistically different between these two groups. No significant difference was found in median progression-free survival (37 vs 45 months) and overall survival (63 vs 59 months). A lower frequency of adverse events, especially Grade 3 peripheral neuropathy, was observed in SC group compared with the IV group. Conclusion: Compared with IV administration, SC bortezomib can provide a better balance between efficacy and toxicity.

17.
Front Comput Neurosci ; 13: 59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555115

RESUMO

Previous studies have shown that task-irrelevant auditory information can provide temporal clues for the detection of visual targets and improve visual perception; such sounds are called informative sounds. The neural mechanism of the integration of informative sound and visual stimulus has been investigated extensively, using behavioral measurement or neuroimaging methods such as functional magnetic resonance imaging (fMRI) and event-related potential (ERP), but the dynamic processes of audiovisual integration cannot be characterized formally in terms of directed neuronal coupling. The present study adopts dynamic causal modeling (DCM) of fMRI data to identify changes in effective connectivity in the hierarchical brain networks that underwrite audiovisual integration and memory. This allows us to characterize context-sensitive changes in neuronal coupling and show how visual processing is contextualized by the processing of informative and uninformative sounds. Our results show that audiovisual integration with informative and uninformative sounds conforms to different optimal models in the two conditions, indicating distinct neural mechanisms of audiovisual integration. The findings also reveal that a sound is uninformative owing to low-level automatic audiovisual integration and informative owing to integration in high-level cognitive processes.

18.
World J Clin Cases ; 7(16): 2401-2405, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31531337

RESUMO

BACKGROUND: Multiple renal artery aneurysms (RAAs) involving multiple branches in a solitary kidney are rare and present a major challenge to surgeons. Ex vivo or in situ repair combined with renal artery revascularization is the classical procedure for these complicated cases, which are not suitable for endovascular repair. The choice of bypass graft remains controversial because of the risk of aneurysmal degeneration for autologous graft. CASE SUMMARY: A 39-year-old female patient presented with left lumbar pain for more than 3 mo. Computed tomography angiography showed congenital absence of the right kidney and three left RAAs involving multiple distal branches. This patient met the criteria for surgical repair due to symptoms of threatened rupture. According to the anatomy and location of multiple RAAs, ex vivo revascularization with saphenous vein graft (SVG) was performed. At the 3-year follow-up, computed tomography angiography demonstrated the aneurysmal degeneration of the Y-shaped SVG. The patient remained asymptomatic and follow-up ultrasound showed no continuous growth of SVG aneurysm. CONCLUSION: SVG aneurysm in RAA revascularization causes us to reflect on the choice of graft, especially for solitary kidney patients.

19.
J Cancer Res Clin Oncol ; 145(9): 2169-2197, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31401674

RESUMO

BACKGROUND: Recent studies have shown that the short-chain fatty acids (SCFAs) produced by the gut microbiota play a positive role in the development of colorectal cancer (CRC). AIMS: This study aims to elucidate the "food-microorganism-SCFAs" axis and to provide guidance for prevention and intervention in CRC. METHODS: The PubMed, Embase and Cochrane databases were searched from their inceptions to August 2018, and 75 articles and 25 conference abstracts were included and analysed after identification and screening. RESULTS: The concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. The protective mechanism of SCFAs against CRC has been described in three aspects: epigenetics, immunology and molecular signalling pathways. Many food and plant extracts that were fermented by microorganisms produced SCFAs that play positive roles with preventive and therapeutic effects on CRC. The "food-microorganism-SCFAs" axis was constructed by summarizing the pertinent literature. CONCLUSIONS: This study provides insight into the basic research and practical application of SCFAs by assessing the protective effect of SCFAs on CRC.


Assuntos
Neoplasias Colorretais/prevenção & controle , Ácidos Graxos Voláteis/fisiologia , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/fisiologia , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/microbiologia , Ácidos Graxos Voláteis/uso terapêutico , Alimentos , Humanos , Padrões de Prática Médica/tendências , Probióticos/uso terapêutico , Fatores de Risco , Transdução de Sinais/fisiologia
20.
PLoS One ; 14(8): e0221185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31442242

RESUMO

Many neuroimaging and electrophysiology studies have suggested that semantic integration as a high-level cognitive process involves various cortical regions and is modulated by attention. However, the cortical network specific to semantic integration and the modulatory mechanism of attention remain unclear. Here, we designed an fMRI experiment using "bimodal stimulus" to extract information regarding the cortical activation related to the effects of semantic integration with and without attention, and then analyzed the characteristics of the cortical network and the modulating effect of attention on semantic integration. To further investigate the related cortical regions, we constructed a functional brain network for processing attended AV stimuli to evaluate the nodal properties using a graph-based method. The results of the fMRI and graph-based analyses showed that the semantic integration with attention activated the anterior temporal lobe (ATL), temporoparietal junction (TPJ), and frontoparietal cortex, with the ATL showing the highest nodal degree and efficiency; in contrast, semantic integration without attention involved a relatively small cortical network, including the posterior superior temporal gyrus (STG), Heschl's gyrus (HG), and precentral gyrus. These results indicated that semantic integration is a complex cognitive process that occurs not only in the attended condition but also in the unattended condition, and that attention could modulate the distribution of cortical networks related to semantic integration. We suggest that semantic integration with attention is a conscious process and needs a wide cortical network working together, in which the ATL plays the role of a central hub; in contrast, semantic integration without attention is a pre-attentive process and involves a relatively smaller cortical network, in which the HG may play an important role. Our study will provide valuable insights into semantic integration and will be useful for investigations on multisensory integration and attention mechanism at multiple processing stages and levels within the cortical hierarchy.

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