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1.
J Ethnopharmacol ; 247: 112273, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31586692

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung, soothe the throat, restore the voice, and lubricate intestine and open the bowels. LHG has been utilized for the treatment of sore throats and hyperglycemia in folk medicine as a homology of medicine and food. The hypoglycemic pharmacology of LHG has attracted considerable attention, and mogrosides have been considered to be active ingredients against diabetes mellitus. We have found that these mogrosides could be metabolized into their secondary glycosides containing 1-3 glucose residues in type 2 diabetes mellitus (T2DM) rats in previous studies. These metabolites may be the antidiabetic components of LHG in vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides containing 1-3 glucose residues. AIMS OF THE STUDY: The aim of this study was to confirm that mogrosides containing 1-3 glucose residues were the active components of LHG for antidiabetic effects and to understand their potential mechanisms of action. MATERIALS AND METHODS: First, the special fraction of mogrosides containing 1-3 glucose residues was separated from a 50% ethanol extract of LHG, and the chemical components were identified by ultra-performance liquid chromatography (UPLC) and named low-polar Siraitia grosvenorii glycosides (L-SGgly). Second, the antidiabetic effects of L-SGgly were evaluated by HFD/STZ-induced (high-fat diet and streptozocin) obese T2DM rats by indexing fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance, and then compared with other fractions in the separation process. The changes in serum lipid levels were also detected. Finally, possible mechanisms of antidiabetic activity of L-SGgly were identified as increasing GLP-1 levels and activating liver AMPK in T2DM rats. RESULTS: The chemical analysis of L-SGgly showed that they contain 11-oxomogroside V, mogroside V, mogroside III, mogroside IIE, mogroside IIIA1, mogroside IIA1, and mogroside IA1, respectively. The total content of the mogrosides in L-SGgly was 54.4%, including 15.7% mogroside IIA1 and 12.6% mogroside IA1. L-SGgly showed excellent effects on obese T2DM rats compared with the other fractions of LHG extract, including significantly reducing the levels of FBG (p < 0.001) and modifying insulin resistance (p < 0.05). Meanwhile, they could significantly decrease the content of triglyceride (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and free fatty acid (p < 0.001) and increase the content of high-density lipoprotein cholesterol (p < 0.001) in serum of T2DM rats. Moreover, L-SGgly can significantly increase (p < 0.01) GLP-1 levels and decrease (p < 0.01) IL-6 levels in T2DM rat serum. AMPK-activating activity in T2DM rats was also upregulated by L-SGgly, but no statistical significance was shown. CONCLUSION: L-SGgly, fractions separated from LHG extract, were verified to have obvious anti-hyperglycemic and anti-hyperlipidemic effects on T2DM rats. Furthermore, L-SGgly regulated insulin secretion in T2DM rats by increasing GLP-1 levels. These findings provide an explanation for the antidiabetic role of LHG.

2.
Nat Prod Res ; : 1-7, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674849

RESUMO

A new unsaturated fatty acid (E)-7,9-diene-11-carbonyl stearic acid (1) and a new lignan 8'-acetyl olivil (2), together with 14 known compounds (3-16), were isolated from the stem of Urtica fissa E. Pritz. Their structures were elucidated by spectroscopic and mass-spectrometric analyses. 8'-Acetyl olivil (2), (6 R,9R)-roseoside (15) and urticol-7-O-ß-d-glucopyrannoside (16) exhibited significant inhibition on α-glucosidase activities, with IC50 values less than 9 µM.

3.
BMC Cancer ; 19(1): 977, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640607

RESUMO

BACKGROUND: Conventionally fractionated (CF) radiation therapy (RT) has been associated with lymphopenia, leading to compromised overall survival (OS) in cancer patients. It currently remains unknown if stereotactic body (SB) RT induces lymphopenia to the same degree. The aim of this study is to determine if SBRT with either chemotherapy (CMT) (Fluorouracil (5FU) or capecitabine) or Nelfinavir (NFV) to pancreatic adenocarcinoma induces lymphopenia to the same degree as CFRT with 5FU or capecitabine and how any associated difference affects patient survival outcomes. METHODS: Medical records of pancreatic adenocarcinoma patients treated with induction CMT followed by RT with concurrent CMT or NFV were reviewed. Patients with total lymphocyte counts (TLCs) available both prior to and following initiation of RT were included. Three groups were identified: CFRT/CMT, SBRT/CMT, and SBRT/NFV. Median delivered RT doses for CFRT and SBRT were 50.4 Gy in 1.8 Gy fractions and 35 Gy in 7 Gy fractions, respectively. TLCs from day 0 (the first day of RT) to 40 were recorded and analyzed using the Kruskal-Wallis test with p-values adjusted with Bonferroni's method. Linear regressions were utilized to estimate the slope of TLCs as it changes with time and survival analysis was performed via Kaplan-Meier plots. RESULTS: One hundred patients were identified (28 CFRT/CMT, 27 SBRT/CMT, 45 SBRT/NFV). Median pre-RT TLCs were not different among groups. Median lowest TLCs were significantly lower (p <  0.0001) and median TLCs reduction over time were significantly greater (p <  0.0001) in the CFRT group than SBRT groups. There was no difference in lowest TLCs or TLCs reduction over time between SBRT groups. Across all groups, the median time to lowest TLCs was similar. Survival analysis revealed no significant difference in median OS between SBRT and CFRT groups. However, in patients with surgery, Median OS for patients with SBRT/CMT was significantly higher than in those with SBRT/NFV (p = 0.03). CONCLUSIONS: Compared to CFRT, SBRT is associated with less lymphopenia. Further study of the effect of radiation technique on immune status is warranted.

4.
Regul Toxicol Pharmacol ; 109: 104486, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580888

RESUMO

Artemisinin-piperaquine tablet (trade name Artequick, ATQ), is a novel combination therapy for the treatment of malaria and especially for resistant P.falciparum malaria. The aim of our study was to assess the potential sub-acute toxicity profile of ATQ by oral administration route in rhesus monkeys. Monkeys were administrated once daily with doses of ATQ (39.1, 78.2, 156.4 mg/kg) for 21 days and then followed-up a 56-day recovery period. The administration of ATQ at high dose produced significant changes in the clinical signs primarily involved in gastrointestinal and nervous systems. Body weight loss, significant decrease in food consumption and body temperature were observed in monkeys at high dose. Various hematological and biochemical parameters changes, and significant pathological lesions (adrenal gland, thymus and femur epiphyseal) were observed in the middle and high dose group at the end of the treatment period. However, the toxic effects of ATQ were reversed and delayed adverse drug reaction did not occur during the recovery period. Based on the results of this study, the no-observed-adverse-effect level for ATQ was considered to be 39.1 mg/kg in rhesus monkeys.

5.
Fitoterapia ; 139: 104360, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31629869

RESUMO

Five new lignans mubiesins A - E (1-5), together with twenty-seven known compounds (6-32), were isolated from the cytotoxicity and anti-inflammation portions of Momordica cochinchinensis seeds which were widely used for various tumors and inflammations. Their structures were elucidated by extensive spectroscopic analyses (HR-MS, UV, CD, IR, 1D-NMR, and 2D-NMR). Their cytotoxic and anti-inflammatory activities were evaluated in vitro. Various lignans and saponins showed the significant activities, they could obviously inhibit the growth of tumor cells and the release of NO and TNF-α in RAW 264.7 cells induced by LPS.

6.
Endocrine ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591683

RESUMO

PURPOSE: As the treatment regimens such as metformin could confound the correlation between type 2 diabetes (T2D) and gut microbiome, we should revisit the relationship between gut microbiota and T2D patients who are not currently treated with metformin. METHODS: The study recruited 65 T2D patients: 49 with and 16 without diabetic complications, and 35 healthy controls. We sequenced the 16S rRNA V3-V4 region of gut microbiota and detected metabolites based on liquid chromatography mass spectrometry (LC/MS) and gas chromatography mass spectrometry (GC/MS) in faecal samples. RESULTS: The composition of both the gut microbiota and faecal metabolites changed significantly with T2D patients. The abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes were higher in T2D patients than healthy subjects, and the short chain fatty acids (SCFAs), bile acids and lipids of T2D patients were significantly disordered. Moreover, the abundances of certain SCFA-producing bacteria (Lachnospiraceae and Ruminococcaceae etc.) were significantly increased in T2D patients, while the faecal SCFAs concentrations were significantly decreased. It's suggested that the role of SCFA-producing bacteria was not simply to produce SCFAs. Then we identified 44 microbial modules to explore the correlations between the gut microbiota and metabolic traits. Specially, most modules including certain SCFA-producing bacteria were comprehensively correlated to body mass index, the levels of blood glucose, blood pressure, blood cholesterol and faecal bile acids and lipids. CONCLUSIONS: Our study identified the relationships between the gut microbiota and faecal metabolites, and provided a resource for future studies to understand host-gut microbiota interactions in T2D.

7.
Ophthalmic Epidemiol ; : 1-21, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640452

RESUMO

Purpose: To describe the design and methodology of the Convergence Insufficiency Neuro-mechanism in Adult Population Study (CINAPS), the first randomized clinical trial (RCT) studying young adults with symptomatic convergence insufficiency (CI) using a combination of traditional clinical tests, objective eye movement recordings, and functional brain activities as outcome measures.Methods: In this double-masked RCT, binocularly normal controls (BNC) (N = 50) and CI patients (N = 50) are randomized into office-based vergence/accommodative therapy (OBVAT) or office-based placebo therapy (OBPT). Outcome measures included clinical signs and symptoms, phoria adaptation, forced fixation disparity curves, binocular rivalry, vergence and saccadic objective eye movements, and task-induced functional brain activities. This study is registered on ClinicalTrials.gov NCT03593031.Results: No significant baseline differences are observed between the BNC (p > .4) or CI (p > .3) participants assigned to OBVAT or OBPT for age, near point of convergence (NPC), positive fusional vergence (PFV), phoria at distance and near, amplitude of accommodation, or the Convergence Insufficiency Symptom Survey (CISS). Significant differences are observed between the CI and BNC cohorts at baseline measurements for NPC, PFV, difference in phoria from far to near, amplitude of accommodation, and CISS (p < .001). For the CI patients, 26% had a comorbidity of accommodation insufficiency, and 16% self-reported ADHD.Conclusion: Features of the study design include the following: standardized diagnostic and office-based therapeutic intervention, placebo treatment arm, masked clinical outcome examinations, objective eye movement recordings, functional imaging, phoria adaptation, fixation disparity curves and binocular rivalry measurements.

8.
Brain Behav ; 9(10): e01418, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31557420

RESUMO

BACKGROUND AND PURPOSE: A higher Totaled Health Risks in Vascular Events (THRIVE) score has been shown to predict poor functional outcome in patients with acute ischemic stroke (AIS) and anterior circulation large vessel occlusions undergoing thrombectomy treatment. We attempted to evaluate the value of the THRIVE score in predicting the outcome of thrombectomy treatment in AIS patients with basilar artery occlusion (BAO). METHODS: A total of 68 AIS patients with BAO who underwent thrombectomy treatment from May 2014 to August 2018 were included in the present study. Multivariable logistic regression was performed to determine the predictive value of the THRIVE score for poor functional outcome (defined as modified Rankin Scale score ≥ 3), all-cause mortality, and hemorrhage transformation (HT) at 3 months. RESULTS: A total of 42 (61.8%) participants experienced poor functional outcomes, 25 (36.8%) patients died from all causes, and 21 (30.9%) patients had HT during the 3-month follow-up. Multivariable logistic regression showed that a higher THRIVE score was significantly associated with poor functional outcome (odds ratio [OR] 5.86, 95% confidence interval [CI], 2.28-14.91, p < .001) as well as all-cause mortality (OR 2.40, 95% CI, 1.32-4.34, p = .004) but not HT (p = .607). The C-statistic of the THRIVE score was significantly larger than that of the NIHSS score for predicting poor functional outcome (AUC = 0.913; cutoff > 5; sensitivity, 88.5%; specificity, 83.3%, p = .007) and all-cause mortality (AUC = 0.768; cutoff > 5; sensitivity, 92.0%; specificity, 65.1%, p = .018). CONCLUSIONS: A high THRIVE score was independently associated with an increased risk of poor functional outcome and all-cause mortality in AIS patients with BAO who underwent thrombectomy treatment. Moreover, the THRIVE score appeared to be a better predictor of clinical outcome than the NIHSS score.

9.
Int J Biol Sci ; 15(9): 1933-1941, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523194

RESUMO

The prognostic value of programmed death-ligand 1 (PD-L1) has been controversial in recent studies. PD-L1 is known to play a major role in suppressing the immune response, yet increasing studies have reported that PD-L1 expression has a favorable prognostic value for cancer patients. This raises the concern about how to understand PD-L1 expression: merely an immune inhibitory signal, or more likely a reactive process to T-cell response that indicates cytotoxic T lymphocyte (CTL) level in a tumor? To solve this dilemma, an integrative investigation is required. We compared the PD-L1 expression between tumor cells and immune cells, and characterized the inter- and intra-tumor correlation between CTL and PD-L1 expression. The prognostic values between PD-L1 and CTL is compared across 15 solid cancers and 11 independent cohorts of ovarian cancer. PD-L1 and PD-L1-adjusted CTL are analyzed in immunotherapy dataset receiving nivolumab. We observed unexpected high concordance between the prognostic value of PD-L1 and CTL across different cancers and cohorts. We found primarily reactive rather than constitutive PD-L1 expression in most tumors. We revealed that PD-L1-adjusted CTL level, rather than the expression of PD-L1, effectively predicts the responders to immune checkpoint inhibitors. This study highlights the importance of PD-L1 expression, as primarily a signature of reacting efficiency of pre-existing anti-tumor immunity, in balancing the tumor microenvironment. Importantly, it suggests that the reactive efficiency of PD-L1 is more useful to predict the response to immunotherapy.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31552201

RESUMO

Malaria, a mosquito-borne infectious disease, is a severe health problem worldwide. As reported, some anti-malarial drugs with anti-parasitic properties also block mast cells (MCs) activities. It is hypothesized that MCs activity may be correlated with the pathogenesis of malaria. Thus, the role of MCs on malarial pathogenesis and the involved physiological action and pathways need to be further investigated. This study aimed to investigate the effect of MCs activation on malaria disease severity using KunMing mice with Plasmodium berghei ANKA (PbANKA) infection treated with MCs degranulator (compound 48/80, C48/80) or MCs stabilizer (disodium cromoglycate, DSCG). PbANKA infection caused a dramatic increase in MCs density and level of MCs degranulation in cervical lymph node (CLN) and skin. Compared with infected control, C48/80 treatment had shortened survival time, increased parasitemia, exacerbated liver inflammation and CLN hyperplasia, accompanied with increase in vascular leakage and leukocyte number. The infected mice with C48/80 treatment also elevated the release of CCL2, CXCL1, and MMP-9 from MCs in CLN and skin, and TNF-α, IFN-γ, CCR2, and CXCR2 mRNA expression in CLN and liver. In contrast, the infected mice treated with DSCG showed longer survival time, lower parasitemia, improved liver inflammation and CLN hyperplasia, followed by a decline of vascular leakage and leukocyte number. Decreased MCs-derived CCL2, CXCL1, and MMP-9 from CLN and skin, mRNA expression in CLN and liver (TNF-α, IFN-γ, CCR2, and CXCR2) were also observed in infected mice with DSCG treatment. Our data indicated that MCs activation may facilitate the pathogenesis of PbANKA infection.

11.
JACC Cardiovasc Interv ; 12(19): 1927-1937, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521645

RESUMO

OBJECTIVES: The present study aimed to investigate the difference in target lesion failure (TLF) at 3 years after double kissing (DK) crush stenting versus provisional stenting (PS) for unprotected left main distal bifurcation (UPLMb) lesions. BACKGROUND: The multicenter and randomized DKCRUSH-V (Double Kissing Crush versus Provisional Stenting for Left Main Distal Bifurcation Lesions: The DKCRUSH-V Randomized Trial) study showed fewer 1-year TLF after DK crush for UPLMb lesions compared with PS. The study reports the 3-year clinical outcome of the DKCRUSH-V study. METHODS: A total of 482 patients with UPLMb lesions who were randomly assigned to either the DK crush group (DK group) or PS group in the DKCRUSH-V study were followed for 3 years. The primary endpoint was the occurrence of a TLF at 3 years. Stent thrombosis (ST) was the safety endpoint. Patients were classified by lesion's complexity and NERS (New Risk Stratification) II or SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) score. RESULTS: At 3 years, TLF occurred in 41 (16.9%) patients in the PS group and in 20 (8.3%) patients in the DK group (p = 0.005), mainly driven by increased target vessel myocardial infarction (5.8% vs. 1.7%; p = 0.017) and target lesion revascularization (10.3% vs. 5.0%; p = 0.029). Definite or probable ST rate at 3 years was 4.1% in the PS group and 0.4% in the DK group (p = 0.006). Notably, DK crush was associated with a significant reduction in both primary and secondary endpoints for patients with complex lesions or at high risk. CONCLUSIONS: Provisional stenting for UPLMb lesions was associated with significantly increased rates of TLF and ST over 3 years of follow-up. Further randomized study is warranted to confirm the benefits of DK crush stenting for complex UPLMb lesions. (Double Kissing and Double Crush versus Provisional T Stenting Technique for the Treatment of Unprotected Distal Left Main True Bifurcation Lesions: A Randomized, International, Multi-center Clinical Trial; ChiCTR-TRC-11001213).

12.
Adv Mater ; 31(42): e1903686, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31489725

RESUMO

Quantum confined devices of 3D topological insulators are proposed to be promising and of great importance for studies of confined topological states and for applications in low-energy-dissipative spintronics and quantum information processing. The absence of energy gap on the topological insulator surface limits the experimental realization of a quantum confined system in 3D topological insulators. Here, the successful realization of single-electron transistor devices in Bi2 Te3 nanoplates using state-of-the-art nanofabrication techniques is reported. Each device consists of a confined central island, two narrow constrictions that connect the central island to the source and drain, and surrounding gates. Low-temperature transport measurements demonstrate that the two narrow constrictions function as tunneling junctions and the device shows well-defined Coulomb current oscillations and Coulomb-diamond-shaped charge-stability diagrams. This work provides a controllable and reproducible way to form quantum confined systems in 3D topological insulators, which should greatly stimulate research toward confined topological states, low-energy-dissipative devices, and quantum information processing.

13.
DNA Cell Biol ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483163

RESUMO

Multiple studies have shown that cancer-specific alternative splicing (AS) alterations are associated with clinical outcome. In this study, we aimed to profile prognostic AS signatures for pancreatic ductal adenocarcinoma (PDAC). We integrated the percent-spliced-in (PSI) data of AS in 140 PDAC patients based on the Cancer Genome Atlas (TCGA) dataset. We identified overall survival (OS)-associated AS events using univariate Cox regression analysis. Then, prognostic AS signatures were constructed for OS and chemoresistance prediction using the least absolute shrinkage and selection operator (LASSO) method. We also analyzed splicing factors (SFs) regulatory networks by Pearson's correlation. We detected 677 OS-related AS events in 485 genes by profiling 10,354 AS events obtained from 140 PDAC patients. Gene functional enrichment analysis demonstrated the pathways enriched by survival-associated AS. The AS signatures constructed with significant survival-associated AS events revealed high performance in predicting PDAC survival and gemcitabine chemoresistance. The area under the receiver operator characteristic curve was 0.937 in training cohort and 0.748 in validation cohort at 2000 days of OS. Furthermore, we identified prognostic SFs (e.g., ESRP1 and HNRNPC) to build the AS regulatory network. We constructed AS signatures for OS and gemcitabine chemoresistance in PDAC patients, which may provide clues for further experiment-based mechanism study.

14.
Mol Med Rep ; 20(5): 4119-4124, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545435

RESUMO

Aberrant lipid metabolism contributes to the development of type 2 diabetes mellitus. The mechanisms by which hydrogen sulfide (H2S), an endogenous gasotransmitter, regulates lipid metabolism remain unclear. The aim of the present study was to investigate if the protective effects of H2S during high glucose (HG)­induced lipid accumulation in 3T3­L1 adipocytes may be mediated by AMP­activated protein kinase (AMPK). Triglyceride (TG) content and the production of H2S were determined using adipogenesis colorimetric assay kits and H2S synthesis methods. The levels of monocyte chemoattractant protein­1 and adiponectin were evaluated by ELISA. Total AMPK and phosphorylated AMPK levels were assessed by western blot analysis. HG increased the cellular level of TG and decreased H2S production in 3T3­L1 adipocytes. The H2S donor, sodium hydrosulfide (NaHS) protected against the HG­induced accumulation of TG in 3T3­L1 adipocytes. Furthermore, NaHS suppressed HG­induced TG accumulation by activating AMPK. Collectively, the findings of the present study suggested that HG induced lipid accumulation in 3T3­L1 adipocytes, and AMPK activation may underlie the lipid­lowering effects of H2S.

15.
Nat Commun ; 10(1): 3499, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375671

RESUMO

Long non-coding RNAs (lncRNAs) contribute to colorectal cancer (CRC). However, the role of lncRNAs in CRC metabolism, especially glucose metabolism remains largely unknown. In this study, we identify a lncRNA, GLCC1, which is significantly upregulated under glucose starvation in CRC cells, supporting cell survival and proliferation by enhancing glycolysis. Mechanistically, GLCC1 stabilizes c-Myc transcriptional factor from ubiquitination by direct interaction with HSP90 chaperon and further specifies the transcriptional modification pattern on c-Myc target genes, such as LDHA, consequently reprogram glycolytic metabolism for CRC proliferation. Clinically, GLCC1 is associated with tumorigenesis, tumor size and predicts poor prognosis. Thus, GLCC1 is mechanistically, functionally, and clinically oncogenic in colorectal cancer. Targeting GLCC1 and its pathway may be meaningful for treating patients with colorectal cancer.

16.
NPJ Syst Biol Appl ; 5: 28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428455

RESUMO

To study systems-level properties of the cell, it is necessary to go beyond individual regulators and target genes to study the regulatory network among transcription factors (TFs). However, it is difficult to directly dissect the TFs mediated genome-wide gene regulatory network (GRN) by experiment. Here, we proposed a hierarchical graphical model to estimate TF activity from mRNA expression by building TF complexes with protein cofactors and inferring TF's downstream regulatory network simultaneously. Then we applied our model on flower development and circadian rhythm processes in Arabidopsis thaliana. The computational results show that the sequence specific bHLH family TF HFR1 recruits the chromatin regulator HAC1 to flower development master regulator TF AG and further activates AG's expression by histone acetylation. Both independent data and experimental results supported this discovery. We also found a flower tissue specific H3K27ac ChIP-seq peak at AG gene body and a HFR1 motif in the center of this H3K27ac peak. Furthermore, we verified that HFR1 physically interacts with HAC1 by yeast two-hybrid experiment. This HFR1-HAC1-AG triplet relationship may imply that flower development and circadian rhythm are bridged by epigenetic regulation and enrich the classical ABC model in flower development. In addition, our TF activity network can serve as a general method to elucidate molecular mechanisms on other complex biological regulatory processes.

17.
Cancer Res ; 79(19): 4882-4895, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31409641

RESUMO

Immune dysregulation plays a vital role in colorectal cancer initiation and progression. Long noncoding RNAs (lncRNA) exhibit multiple functions including regulation of gene expression. Here, we identified an immune-related lncRNA, MIR17HG, whose expression was gradually upregulated in adjacent, adenoma, and colorectal cancer tissue. MIR17HG promoted tumorigenesis and metastasis in colorectal cancer cells both in vitro and in vivo. Mechanistically, MIR17HG increased the expression of NF-κB/RELA by competitively sponging the microRNA miR-375. In addition, RELA transcriptionally activated MIR17HG in a positive feedback loop by directly binding to its promoter region. Moreover, miR-17-5p, one of the transcribed miRNAs from MIR17HG, reduced the expression of the tumor suppressor B-cell linker (BLNK), resulting in increased migration and invasion of colorectal cancer cells. MIR17HG also upregulated PD-L1, indicating its potential role in immunotherapy. Overall, these findings demonstrate that MIR17HG plays an oncogenic role in colorectal cancer and may serve as a promising therapeutic target. SIGNIFICANCE: These findings provide mechanistic insight into the role of the lncRNA MIR17HG and its miRNA members in regulating colorectal cancer carcinogenesis and progression.

18.
Genes Genomics ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399846

RESUMO

BACKGROUND: Akkermansia muciniphila is an important bacterium that resides on the mucus layer of the intestinal tract. Akkermansia muciniphila has a high abundance in human feces and plays an important role in human health. OBJECTIVE: In this article, 23 whole genome sequences of the Akkermansia genus were comparatively studied. METHODS: Phylogenetic trees were constructed with three methods: All amino acid sequences of each strain were used to construct the first phylogenetic tree using the web server of Composition Vector Tree Version 3. The matrix of Genome-to-Genome Distances which were obtained from GGDC 2.0 was used to construct the second phylogenetic tree using FastME. The concatenated single-copy core gene-based phylogenetic tree was generated through MEGA. The single-copy genes were obtained using OrthoMCL. Population structure was assessed by STRUCTURE 2.3.4 using the SNPs in core genes. PROKKA and Roary were used to do pan-genome analyses. The biosynthetic gene clusters were predicted using antiSMASH 4.0. IalandViewer 4 was used to detect the genomic islands. RESULTS: The results of comparative genomic analysis revealed that: (1) The 23 Akkermansia strains formed 4 clades in phylogenetic trees. The A. muciniphila strains isolated from different geographic regions and ecological niches, formed a closely related clade. (2) The 23 Akkermansia strains were divided into 4 species based on digital DNA-DNA hybridization (dDDH) values. (3) Pan-genome of A. muciniphila is in an open state and increases with addition of new sequenced genomes. (4) SNPs were not evenly distributed throughout the A. muciniphila genomes. The genes in regions with high SNP density are related to metabolism and cell wall/membrane envelope biogenesis. (5) The thermostable outer-membrane protein, Amuc_1100, was conserved in the Akkermansia genus, except for Akkermansia glycaniphila PytT. CONCLUSION: Overall, applying comparative genomic and pan-genomic analyses, we classified and illuminated the phylogenetic relationship of the 23 Akkermansia strains. Insights of the evolutionary, population structure, gene clusters and genome islands of Akkermansia provided more information about the possible physiological and probiotic mechanisms of the Akkermansia strains, and gave some instructions for the in-depth researches about the use of Akkermansia as a gut probiotic in the future.

19.
Nanotechnology ; 30(44): 445703, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365908

RESUMO

Vertical van der Waals (vdW) heterostructures made up of two or more 2D monolayer materials provide new opportunities for 2D devices. Herein, we study the electronic transport properties of vertical integration of 2D GeSe-phosphorene(GeSe-BP) heterostructure, using the nonequilibrium Green's function formalism combined with the density-functional theory. The results reveal that the directional dependency and strain tunable transport anisotropic behavior appears in GeSe/BP-stacking vdW heterostructures. The current-voltage (I-V) characteristics indicate that the electric current propagates more easily through the perpendicular buckled direction (Y) than the linear atomic chain direction (X) in the low bias regime regardless of the GeSe-BP stacking, which is supported by the underlying electronic structures along Γ-Y and Γ-X lines. The anisotropic transmission spectra indicate an over 105 on/off ratio between the I Y and I X in GeSe-BP systems. This anisotropic transmission behavior of 2D GeSe-BP heterojunction is regardless of the considered layer distances. The similar situation can also be found in the I-V characteristics of GeSe-BP nano-device after applying a strain, and a charming behavior that the transport gap can be minished obviously when applied a compressed strain on the perpendicular y-direction or the stretched strain on the x-direction. Moreover, an intriguing semiconductor-metal transition induces by applying the in-plain strain along the y-direction. These results imply that the GeSe-BP nanojunctions may be a promising application in futuristic nano-switching materials.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31352203

RESUMO

Cistanche tubulosa, one species of Cistanches Herba, was recently confirmed to have antidepressant efficacy in chronic unpredictable stress (CUS) rats by restoring homeostasis of intestinal microbiota. In this paper, we aim to explore the metabolic profile of C. tubulosa in normal and CUS induced depressive model rats in vitro and in vivo. Using UPLC-Q-TOF-MS, the in vitro gastrointestinal metabolism of Cistanche tubulosa extract (CTE) was evaluated in both normal and CUS rats. At the same time, in vivo metabolism of CTE in normal and depressed rats were also investigated in rat urine and feces. A total of 20 and 26 metabolites were characterized from in vitro and in vivo metabolism in normal and CUS rats, respectively. CTE was metabolized to aglycones and degradation products of phenylethanoid glycosides (PhGs) and iridoid glycosides whether by normal or depressed rat intestinal microbiota in vitro. Phase II metabolites of aglycones and degradation products of PhGs and iridoid glycosides were the main metabolites in rat urine and feces. Additionally, the metabolic capability to generate secondary glycosides and aglycones in depressive rat intestinal microbiota was much weaker than that in normal rat intestinal microbiota, which was attributed to the disordered glycoside hydrolases produced by intestinal microbiota in CUS depressed rats. The results of this study laid the foundation for understanding the metabolic process and therapeutic mechanism of CTE's antidepressant property.

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