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1.
Artigo em Inglês | MEDLINE | ID: mdl-31674895

RESUMO

Huge numbers of bacteria reside in the digestive tract of most animals. During an investigation into the bacterial diversity of primates, strain YIM 102668T was isolated. When neighbour-joining phylogenetic analysis based on 16S rRNA gene sequences was conducted, strain YIM 102668T formed a cluster within the family Flavobacteriaceae and in a lineage not associated with any known group of previously proposed genera. Closely related genera were Algoriella (94.8 %), Chishuiella (94.8 %), Empedobacter (highest 94.6 %), Moheibacter (90.9 %) and Weeksella (90.6 %). In addition, strain YIM 102668T contained MK-6 as the predominant respiratory quinone and iso-C15 : 0 as the major fatty acid. The major polar lipid was phosphatidylethanolamine and the genomic DNA G+C content was 30.6 mol%. These chemotaxonomic characterizations confirmed that strain YIM 102668T belonged to the family Flavobacteriaceae. Supported by the results of phylogenetic, phenotypic and chemotaxonomic analyses, we propose that strain YIM 102668T represents a novel genus, for which the name Faecalibacter macacae gen. nov., sp. nov. is proposed. The type strain is YIM 102668T (=KCTC 52109T=CCTCC AB 2016016T).

2.
Chem Commun (Camb) ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675017

RESUMO

Presented here is the deep eutectic solvothermal synthesis of an open framework copper selenidogermanate, namely [NH3CH3]0.75Cu1.25GeSe3 (CuGeSe-1), which exhibits a rapid and effective Cs+ ion exchange performance (qm = 225.3 mg g-1). CuGeSe-1 shows a structural flexibility upon Cs+ exchange. The robust selenide-based framework contributes to an excellent pH stability (1-12). The Cs+-laden product could be facilely eluted.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31692185

RESUMO

Cage-type compounds offer molecule-level confined spaces with different sizes, shapes, and functional groups for various molecule guests to achieve some specific behaviors/functions, such as ultrahigh affinity of host-guest recognition, multi-tunable photophysical property, and highly-stereoselective/photo-driven catalysis. Herein, we report the synthesis and characterization of three-dimensional tetraphenylethene-based octacationic cage with fluorescent property and host-guest recognition via CH•••π, π-π, and/or electrostatic interactions for polycyclic aromatic hydrocarbons (e.g. coronene) in organic media and water-soluble dyes (e.g. sulforhodamine 101) in aqueous media, respectively. The X-ray structure of cage⸧coronene exhibits a cuboid internal cavity with the size of approximate 17.2 Å (length) × 11.0 Å (width) × 6.96 Å (height) and "hamburger"-type host-guest complexes, which are hierarchically stacked into 1D nanotube and 3D supramolecular framework. Compared to its host-guest complexes, free cage possesses a similar but empty cavity in the crystalline state, indicating that the stability and rigidity of cage itself are consistent both in the absence and presence of guest. Furthermore, as a single-molecular fluorescent platform, tetraphenylethene-based octacationic cage with dye guests (e.g. sulforhodamine 101) can form host-guest complex with higher absolute quantum yield ( Φ F = 28.5%), larger excitation-emission gap (Δλ ex-em = 211 nm), longer lifetime (τ = 7.0 ns), compared to guest ( Φ F = 10.5%; Δλ ex-em = 11 nm; τ = 4.9 ns); and purer emission with a narrow full width at half-maxima (Δλ FWHM = 38 nm), compared to host (Δλ FWHM = 111 nm), respectively. This study provides insight into construct cationic cage with both fluorescence and host-guest properties, and might facilitate further design of multifunctional cages and other fluorescent supramolecular systems based on host-guest recognition.

4.
Mol Med Rep ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31702811

RESUMO

Insulin resistance (IR) is the impaired insulin response that causes decreased glucose tolerance. Electrical stimulation (ES) can improve insulin sensitivity in the skeletal muscle. However, the underlying molecular mechanisms remain to be elucidated. In the present study, the effect of ES and diet therapy on IR and the role of the mammalian target of rapamycin (mTOR) pathway in the improvement of IR by ES were investigated. A total of 70 Sprague­Dawley male rats were divided into five groups: Normal (n=10), IR control (n=15), diet (n=15), ES (n=15) and ES + diet (n=15) groups. An IR rat model was established by high­fat and high­carbohydrate diet for 5 weeks and confirmed by measurement of fasting plasma glucose (FPG), insulin, insulin sensitivity index (ISI) and IR index. ES on the Zusanli (ST36), Sanyinjiao (SP 6) and Weiwanxiashu (EX­B3) acupoints and the low­fat and low­carbohydrate diet demonstrated protective effects. The body weight, concentrations of FPG, insulin, triglycerides (TG), free fatty acids (FFA) and total cholesterol (TC) of the rats were detected. Pathologic changes in the liver and pancreatic tissues were assessed. Western blotting and immunohistochemistry were performed to determine the role of PI3K/Akt/mTOR signaling. Results demonstrated that ES and diet therapy significantly increased ISI and reduced FPG, IR index, FFA, TG, TC and weight. Inflammatory cell infiltration in the liver and pancreatic tissues was ameliorated and lipid droplets and cavitation in hepatocyte were decreased after ES and diet therapy. The administration of ES and diet therapy also enhanced glucose transport by the upregulation of glucose transporter 4 and accelerated glycogen synthesis through the suppression of glycogen synthase kinase 3α/ß via PI3K/Akt/mTOR signaling. Hence, the present results demonstrated that ES combined with diet therapy improved IR through PI3K/Akt/mTOR signaling. The proposed therapy was superior to the method of diet alone.

5.
Emerg Microbes Infect ; 8(1): 1574-1583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682177

RESUMO

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has become an important re-emerging pathogen with its rapid spread to many non-endemic areas. The lack of effective vaccines and antiviral agents is largely attributed to the elusive infection and dissemination dynamics in vivo. In this study, we designed and developed a novel, replication-competent, CHIKV reporter virus (CHIKV-iRFP) encoding a near infrared fluorescent protein (iRFP). In vitro and in vivo characterization demonstrated that CHIKV-iRFP retained similar replication and virulence phenotypes to its parental virus. Neonatal BABL/c mice and IFNAR-/- A129 mice were highly susceptible to CHIKV-iRFP infection. Following intracranial (i.c.) inoculation, CHIKV-iRFP efficiently replicated and disseminated into whole body, resulting in rapid death in an age-dependent manner. Remarkably, upon footpad injection, CHIKV-iRFP readily disseminated from footpad to head and whole skeleton, with a specific tropism for bone marrow. Taken together, this novel reporter virus provides a powerful tool to track real time CHIKV replication and to test the in vivo efficacy of vaccines and antiviral therapeutics.

6.
Diagn Cytopathol ; 47(11): 1223-1228, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587518

RESUMO

Despite being an important differential diagnosis of bladder tumor on cystoscopy, follicular cystitis (FC) is rarely diagnosed on cytologic material. We performed a retrospective study on cases of FC diagnosed on bladder biopsy and/or urine cytology in our institution. A total of 35 cases of FC were identified with a female predominance (F:M = 2:1). Hematuria was the most common clinical presentation. Cystoscopic findings included mass lesions, yellow plaques, and surface erythema. History of urinary tract infection was reported in 48% of the patients, and majority of those patients had positive concurrent urine culture, most commonly with beta-hemolytic streptococcus, Group B. A total of 17 out of 35 patients had urine cytology specimens. When the presence of follicular dendritic cells in clusters of variously sized lymphocytes is used as the cytological diagnostic criterion, 6 out of 17 cases were diagnosed as FC and 5 out of 6 were confirmed by concurrent biopsy. This retrospective study not only analyzed the clinical characteristics of FC but also elucidated the cytological diagnostic criteria of FC and confirmed its specificity.

7.
Cancer Lett ; 469: 35-53, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31589905

RESUMO

Due to a global increase in the incidence of thyroid cancer, numerous novel mouse models were established to reveal thyroid cancer pathogenesis and test promising therapeutic strategies, necessitating a comprehensive review of translational medicine that covers (i) the role of mouse models in the research of thyroid cancer pathogenesis, and (ii) preclinical testing of potential anti-thyroid cancer therapeutics. The present review article aims to: (i) describe the current approaches for mouse modeling of thyroid cancer, (ii) provide insight into the biology and genetics of thyroid cancers, and (iii) offer guidance on the use of mouse models for testing potential therapeutics in preclinical settings. Based on research with mouse models of thyroid cancer pathogenesis involving the RTK, RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, SRC, and JAK-STAT signaling pathways, inhibitors of VEGFR, MEK, mTOR, SRC, and STAT3 have been developed as anti-thyroid cancer drugs for "bench-to-bedside" translation. In the future, mouse models of thyroid cancer will be designed to be ''humanized" and "patient-like," offering opportunities to: (i) investigate the pathogenesis of thyroid cancer through target screening based on the CRISPR/Cas system, (ii) test drugs based on new mouse models, and (iii) explore the underlying mechanisms based on multi-omics.

9.
J Chemother ; : 1-8, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631801

RESUMO

Escherichia coli is a common pathogen of bacterial biofilm infections. Sub-minimum inhibitory concentration ceftazidime (sub-MIC CAZ) could inhibit the biofilm formation of E. coli. Deletion of the ibpAB genes could increase the extracellular indole concentration of E. coli and then inhibit biofilm formation. Therefore, we speculated that sub-MIC CAZ might inhibit biofilm formation via ibpAB. In this study, the results showed that sub-MIC CAZ could significantly inhibit biofilm formation, swimming motility and the expression of the ibpA gene, while it could increase the expression of tnaA gene and extracellular indole concentration. Knockout of the ibpA gene resulted in a decrease in biofilm formation and swimming motility and an increase in the indole concentration. When treated with sub-MIC CAZ, the tnaA gene expression, indole concentration, biofilm formation and swimming motility of MG1655 ΔibpA were similar to those of the control group. The results indicated that sub-MIC CAZ might inhibit the biofilm formation of E. coli by increasing the extracellular indole concentration and downregulating the ibpA gene.

10.
Pharmacogenomics J ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636355

RESUMO

Clinical data on the relationships of cytochrome P450 (CYP2) B6 516G>T polymorphisms with efavirenz-induced central nervous system (CNS) side effects and virological response in HIV-infected adults are controversial. We sought to analyze the associations by meta-analysis. To identify eligible studies, we systematically searched PubMed, Embase, ScienceDirect, and Web of Science. The strength of the associations was measured by odds ratio (OR) and effect size (ES) with 95% confidence interval (CI). Seventeen studies comprising a total of 3598 HIV-infected adults were included. The results showed that the CYP2B6-516 GG genotype was significantly associated with a decreased risk of efavirenz-induced CNS side effects compared with the GT and TT genotypes (GG + GT vs. TT: OR = 0.60, 95% CI = 0.41-0.87, P = 0.006; GG vs. GT + TT: OR = 0.68, 95% CI = 0.51-0.91, P = 0.008; GG vs. GT: OR = 0.70, 95% CI = 0.51-0.94, P = 0.018), and there was no significant association between the genetic variants GT and TT (GT vs. TT: OR = 0.82, 95% CI = 0.54-1.26, P = 0.372). However, there was no significant association between CYP2B6-516 GG and GT + TT genotypes in virological response (GT + TT vs. GG: ES = 1.06, 95% CI = 0.95-1.18, P = 0.321; OR = 1.01, 95% CI = 0.65-1.58, P = 0.963). Taken together, our results demonstrated that compared with the normal efavirenz clearance genotype CYP2B6-516 GG, the slow and very slow efavirenz clearance genotypes GT and TT were significantly associated with an increased risk of efavirenz-induced CNS side effects but not an increased virological response. To promote the tolerance of efavirenz, it is better to adjust the dosage of efavirenz according to the polymorphisms of CYP2B6-516 in HIV-infected adults.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31584868

RESUMO

A yellow, Gram-stain-negative, aerobic, non-gliding, non-spore-forming, rod-shaped strain, designated YIM 102600T, was isolated from the faeces of Macaca mulatta dwelling in the Yunnan Wild Animal Park, Yunnan Province, South-West PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 102600T was a member of the genus Flavobacterium, and closely related to Flavobacterium qiangtangense F3T (96.9 % similarity) and Flavobacterium noncentrifugens R-HLS-17T (96.0 % similarity). Phylogenetic trees showed that strain YIM 102600T formed a clade with F. qiangtangense F3T and F. noncentrifugens R-HLS-17T. Growth occurred at 4-30 °C (optimum, 28 °C), pH 7.0-8.0 (pH 7.5) and NaCl concentration 0-2 % (w/v; 0-1 %, w/v). The major fatty acids were iso-C15:0 and summed feature 3 (comprising C16:1 ω7c and/or C16:1 ω6c). The predominant polar lipid was phosphatidylethanolamine and the sole respiratory quinone was menaquinone-6. The DNA G+C content was 36.4 mol%. The calculated digital DNA-DNA hybridization values between strain YIM 102600T and other species of Flavobacterium ranged from 70.0 to 75.0 % and average nucleotide identity values were in a range between 13.7 to 23.5 %. Based above the consensus of phenotypic and phylogenetic analyses as well as whole genome comparisons, strain YIM 102600T (=KCTC 52099T=CCTCC AB 201632T) is proposed to represent type strain of a novel species, Flavobacterium macacae sp. nov.

12.
J Nanobiotechnology ; 17(1): 103, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581948

RESUMO

BACKGROUND: Immunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs). RESULTS: MXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H2O2. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs. CONCLUSIONS: Our work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.

13.
Cancer Biomark ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31640084

RESUMO

BACKGROUND: Breast cancer is a worldwide leading cause of cancer mortality and it is associated with numerous tumor suppressor genes and oncogenes. Growing evidence exists that different KLFs play pivotal roles of in human malignancies. However, the function of KLFs in breast cancer development has remained uncovered. OBJECTIVE: To explore the potential prognostic biomarkers among KLFs in breast cancer. METHODS: In the present study, by using multiple large open databases, such as Oncomine database, Kaplan-Meier Plotter, and bc-GenExMiner online software, we deeply analyzed the expressions and clinical values about KLFs in patients with breast cancer. RESULTS: KLF4/5/8/9/10/15 were significantly down-regulated in breast cancer samples. KLF11 exerts significantly negative effect on the prognosis of patients, whereas expressions of KLF4/15 were associated with better prognosis. Moreover, the vital genes KLF4/11/15 showed significant association with clinical parameters including age, estrogen receptor, progesterone receptor, epidermal growth factor receptor-2, Scarff-Bloom-Richardson grade, and Nottingham prognostic index. CONCLUSIONS: Bioinformatics analysis suggested that KLF4/11/15, compared to other KLFs, might be potential prognostic indicators and treatment targets for breast cancer patients.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31642911

RESUMO

OBJECTIVES: The aim of this study was to establish an original transapical septal myectomy procedure that can be performed in the beating heart via a minimally invasive approach for the treatment of hypertrophic obstructive cardiomyopathy. METHODS: We designed an original intracardiac septum resection device to conduct off-pump septal myectomy in swine. A subxiphoid minithoracotomy was performed to access the apex of the heart. This resection device was inserted into the left ventricular outflow tract of the heart via the apex. The basal anteroseptal myocardium beneath the right aortic cusp was identified using a combination of transoesophageal and transthoracic echocardiography and then resected and collected by the device. RESULTS: Six consecutive operations were successfully and accurately performed using the custom-made device under echocardiographic guidance. All pigs survived and appeared to be normal until planned euthanasia 1 week after operation. A 300-700 mg portion of the septal myocardium was resected from the normal swine heart. Echocardiography and electrocardiogram revealed no abnormalities after resection. One exception was the fifth pig, in which mild annular regurgitation of the aortic valve occurred after repetitive resection. Postmortem necropsy demonstrated that all resections were correctly located at the basal anteroseptal septum beneath the right aortic cusp. CONCLUSIONS: Our study provides the first proof-of-concept evidence for a novel beating heart transapical septal myectomy procedure, which showed promising translational potential for the treatment of hypertrophic obstructive cardiomyopathy. This procedure would probably reduce operative risks and improve outcomes and reduce the demanding expertise required to perform conventional surgical myectomy.

16.
J Cell Mol Med ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578820

RESUMO

SARI (suppressor of AP-1, regulated by IFN) impaired tumour growth by promoting apoptosis and inhibiting cell proliferation and tumour angiogenesis in various cancers. However, the role of SARI in regulating tumour-associated inflammation microenvironment is still elusive. In our study, the colitis-dependent and -independent primary model were established in SARI deficiency mice and immuno-reconstructive mice to investigate the functional role of SARI in regulating tumour-associated inflammation microenvironment and primary colon cancer formation. The results have shown that SARI deficiency promotes colitis-associated cancer (CAC) development only in the presence of colon inflammation. SARI inhibited tumour-associated macrophages (TAM) infiltration in colon tissues, and SARI deficiency in bone marrow cells has no observed role in the promotion of intestinal tumorigenesis. Mechanism investigations indicated that SARI down-regulates p-STAT1 and STAT1 expression in colon cancer cells, following inhibition of MCP-1/CCR2 axis activation during CAC development. Inverse correlations between SARI expression and macrophage infiltration, MCP-1 expression and p-STAT1 expression were also demonstrated in colon malignant tissues. Collectively, our results prove the inhibition role of SARI in colon cancer formation through regulating TAM infiltration.

17.
Biol Pharm Bull ; 42(11): 1867-1876, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484847

RESUMO

Anandamide (AEA) played potent neuroprotective activities via cannabinoid type 1 (CB1) and 2 (CB2) receptor. N-Linoleyltyrosine (NITyr), as an AEA analogue, was synthesized in our laboratory and evaluated the neuroprotective effects and mechanisms for the first time. NITyr was synthesized via substitution reaction. The neuroprotective effects of NITyr were evaluated in a gerbil model of transient cerebral ischemia. Each gerbil was subjected to open field test (OFT), Rotard rod test (RRT), Morris water maze (MWM) successively and executed after animal behaviors. Part of the brain was stained with hematoxylin and eosin (HE) and Nissl staining, and the rest for biochemical analysis. NITyr could not increase spontaneous locomotor activity and ameliorate the anxiety behavior in the OFT but could improve the motor coordination in the RRT and the spatial memory impairment in the MWM. Immunohistochemically, NITyr could attenuate the ischemia-induced neural loss in the hippocampus. The Enzyme-linked immunosorbent assay (ELISA) suggested that NITyr ameliorated the inflammation and oxidative stress. Consistently, NITyr could up-regulate the expressions of p-phosphadylinositol 3-kinase (PI3K) and p-Akt but not PI3K and Akt in the hippocampus. In addition to oxidative stress, CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251 could reverse the above phenomena. However, CB1 receptor antagonist AM251 could reverse oxidative stress. Accordingly, NITyr could up-regulate the expressions of CB2 but not CB1. NITyr could improve the motor coordination, learning and memory impairments, neural loss in the hippocampus and the inflammation of the mice via CB2 receptor involvement of PI3K/Akt signaling pathway.

18.
Inorg Chem ; 58(19): 12832-12842, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31490672

RESUMO

Rational synthesis of inorganic matter remains a great challenge encountered with modern synthetic chemistry. Here we reported the stepwise solvothermal conversion from GeO2 to [MGe4S10]n3n- (M = Cu, Ag) polymer via isolatable [Ge2S6]4- and [Ge4S10]4- anions by virtue of templating technique. The facile sulfuration of GeO2 resulted in the methylammonium-templated dimeric thiogermanate [CH3NH3]4Ge2S6 (1). This was used subsequently as a precursor for the formation of adamantane-like [Ge4S10]4- cluster, which was isolated as a mixed methylammonium/ethylammonium salt [CH3CH2NH3]3[CH3NH3]Ge4S10 (2). Compound 2 was then successfully used as a precursor to react with Cu+ and Ag+ cations in the presence of tetraethylammonium, resulting in alternating copolymeric products [(CH3CH2)4N]3MGe4S10 (M = Cu (3), Ag (4)), whose anionic moieties feature a novel zigzag chainlike structure constructed by [Ge4S10]4- clusters via two-coordinate Cu+/Ag+ linkers. Mixed amine/ethanol or deep eutectic solvents were applied as media for the syntheses of 1-4, and all the products were characterized in the solid state and solution. Crystal structural analysis of the title compounds revealed significant templating roles of the alkylammonium cations as both space-filling agents and hydrogen-bonding donors, suggesting the structure-directing mechanism for the species formation and crystal growth. The design and optimization of multistep structural conversion upon templating effects would be beneficial for drawing rational, predictable pathways for inorganic synthesis.

19.
Hepatology ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31529495

RESUMO

Although knowledge regarding the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has profoundly grown in recent decade, the internal restrictive mechanisms remain largely unknown. We have recently reported that the transcription repressor interferon regulatory factor-2 binding protein 2 (IRF2BP2) is enriched in cardiomyocytes and inhibits pathological cardiac hypertrophy in mice. Notably, IRF2BP2 is abundantly expressed in hepatocytes and dramatically downregulated in steatotic livers, whereas the role of IRF2BP2 in NAFLD is unknown. Herein, using gain- and loss-of-function approaches in mice, we demonstrated that while hepatocyte-specific Irf2bp2 knockout exacerbated high-fat diet-induced hepatic steatosis, insulin resistance and inflammation, hepatic Irf2bp2 overexpression protected mice from these metabolic disorders. Moreover, the inhibitory role of IRF2BP2 on hepatosteatosis is conserved in a human hepatic cell line in vitro. Combinational analysis of digital gene expression and chromatin immunoprecipitation sequencing identified activating transcription factor 3 (ATF3) to be negatively regulated by IRF2BP2 in NAFLD. Chromatin immunoprecipitation and luciferase assay substantiated the fact that IRF2BP2 is a bona fide transcription repressor of ATF3 gene expression via binding to its promoter region. Functional studies revealed that ATF3 knockdown significantly relieved IRF2BP2 knockout-exaggerated hepatosteatosis in vitro. CONCLUSION: IRF2BP2 is an integrative restrainer in controlling hepatic steatosis, insulin resistance and inflammation in NAFLD through transcriptionally repressing ATF3 gene expression.

20.
Cell Prolif ; : e12689, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502302

RESUMO

OBJECTIVES: Osteogenesis is coupled with angiogenesis during bone remodelling. G-protein-coupled receptor (GPCR) kinase 2-interacting protein-1 (GIT1) is an important protein that participates in fracture healing by regulating angiogenesis. This study investigated whether GIT1 could affect bone mesenchymal stem cells (BMSCs) to secrete angiogenic factors to enhance fracture healing by promoting angiogenesis and its possible mechanism. MATERIALS AND METHODS: The angiogenesis of mice post-fracture was detected by micro-CT and immunofluorescence. Subsequently, vascular endothelial growth factor (VEGF) level in mouse and human BMSCs (hBMSCs) under TNF-α stimulation was detected. The hBMSCs were transfected with GIT1 shRNAs to further explore the relationship between GIT1 and VEGF and angiogenesis in vitro. Furthermore, based on previous research on GIT1, possible signal pathways were investigated. RESULTS: GIT1 knockout mice exhibited impaired angiogenesis and delayed fracture healing. And GIT1 deficiency remarkably reduced the expression of VEGF mRNA in BMSCs, which affected the proliferation and migration of human umbilical vein endothelial cells. GIT1 knockdown inhibited the activation of Notch and NF-κB signals by decreasing nuclear transportation of NICD and P65/P50, respectively. Overexpression of the canonical NF-κB subunits P65 and P50 markedly increased NICD-dependent activation of recombination signal-binding protein-jκ reporter. Finally, GIT1 enhanced the affinity of NF-κB essential modulator (NEMO) for K63-linked ubiquitin chains via interaction with NEMO coiled-coil 2 domains. CONCLUSION: These data revealed a positive role for GIT1 by modulating the Notch/NF-κB signals which promoting paracrine of BMSCs to enhance angiogenesis and fracture healing.

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